Modern Cyclophane Chemistry

Rolf Gleiter, Henning Hopf (Eds.) Modern Cyclophane Chemistry

Modern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

Further Titles of Interest: from WILEY-VCH N. Krause, A. S. K. Hashmi (Eds.)

Modern Allene Chemistry Two Volumes

2004, ISBN 3-527-30671-4 R. Mahrwald (Ed.)

Modern Aldol Reactions Two Volumes

2004, ISBN 3-527-30714-1 T. Takeda (Ed.)

Modern Carbonyl Olefination Methods and Applications

2004, ISBN 3-527-30634-X D. Astruc (Ed.)

Modern Arene Chemistry Concepts, Synthesis, and Applications

2002, ISBN 3-527-30489-4

Rolf Gleiter, Henning Hopf (Eds.)

Modern Cyclophane Chemistry

Professor Dr. Rolf Gleiter Institute of Organic Chemistry University of Heidelberg Im Neuenheimer Feld 270 69120 Heidelberg Germany Professor Dr. Henning Hopf Institute of Organic Chemistry Technical University of Braunschweig Hagenring 30 38106 Braunschweig Germany

n This book was carefully produced. Nevertheless, authors, editors and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for A catalogue record for this book is available from the British Library. Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data is available in the Internet at . © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim All rights reserved (including those of translation in other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Printed in the Federal Republic of Germany Printed on acid-free paper Cover design: The drawings for the cover were provided by Björn Hellbach Typesetting K+V Fotosatz GmbH, Beerfelden Printing betz-druck gmbh, Darmstadt Bookbinding Litges & Dopf Buchbinderei GmbH, Heppenheim ISBN

3-527-30713-3

V

Contents Preface

XV

List of Contributors

XVII

1

Cyclophynes

1.1 1.2 1.2.1 1.2.2 1.3 1.4 1.5 1.6 1.7

Yoshito Tobe and Motohiro Sonoda Introduction 1 Orthocyclophynes and Related Systems 2 Planar Dehydrobenzoannulenes 3 Nonplanar Orthocyclophynes 13 Metacyclophynes and Related Systems 17 Paracyclophynes and 1,3,5-Bridged Cyclophynes Concluding Remarks 35 Acknowledgement 36 References 36

2

Hetera (Cyclo-)phanes

2.1 2.1.1 2.1.2 2.1.3 2.2 2.2.1 2.2.1.1 2.2.1.2 2.2.1.3 2.2.1.4 2.2.1.5 2.2.1.6 2.2.1.7 2.2.2 2.2.2.1

Fritz Vögtle, Gregor Pawlitzki, and Uwe Hahn Introduction 41 Selection of Topics Presented 41 Definitions 42 Why Conduct a Survey on Heteraphanes? 49 Heteraphanes 51 Planar Chiral and Helical Chiral Phanes 51 Design of Phanes with Planar and Helical Chirality 51 Hetera [2.2]Metacyclophanes 53 Planar Chiral [2.2]Metacyclophanes 55 Planar Chiral Hetera [n]Para- and Hetera [n]Metacyclophanes 56 Dioxa [2.2]Phanes and Oxaza [2.2]Phanes 57 Enantiomer Separations 57 Strongly Helical Heteraphanes 58 Catenanes, Rotaxanes, and Knotanes of the Heteraphane Type 59 Template Synthesis of Rotaxanes Using Cyclophane Wheels 59

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Modern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

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Contents

2.2.3 2.3 2.4 2.5

Higher Order [n]Rotaxanes via Non-ionic Template Effect 60 Combination of Anionic and Non-ionic Template 61 Molecular Knots and Similar Macrocycles of the Heteraphane Type 61 Further Heteraphanes, Metallaphanes and Supramolecular Phanes Conclusions 62 Acknowledgement 74 References 74

3

Highly Strained Cyclophanes

2.2.2.2 2.2.2.3 2.2.2.4

81

3.6 3.6.1 3.6.2 3.6.3 3.7

Takashi Tsuji Introduction 81 [n]Metacyclophanes 81 Synthesis 81 Structures and Physical Properties 83 Reactions of Strained [n]Metacyclophanes 84 Thermal and Photochemical Reactions 84 Addition Reactions 85 Reactions with Electrophiles 86 Reactions with Nucleophiles 87 [n]Paracyclophanes 89 Synthesis 90 Structures and Physical Properties 91 Reactions of Strained [n]Paracyclophanes 92 Thermal and Photochemical Reactions 92 Reactions with Electrophiles 94 Diels-Alder and Other Reactions 94 Kinetic Stabilization of [4]Paracyclophane Systems 95 Aromaticity of Bent Benzene Rings 96 Cyclophanes containing Polycyclic Aromatic Rings: (2,7)Pyrenophanes 96 [1.1]Paracyclophanes 98 Synthesis 99 Kinetic Stabilization of [1.1]Paracyclophane Systems 100 Structures and Physical Properties 100 References and Notes 102

4

Superphanes 105

4.1 4.2 4.2.1 4.3 4.4 4.4.1

Rolf Gleiter and Rolf Roers Introduction 105 [n2]Cyclopropenonophanes 106 Synthesis 106 Superbridged Cyclopropenyliophanes 109 C4-Superphanes 109 Properties of Cyclobutadieno Superphanes 115

3.1 3.2 3.2.1 3.2.2 3.2.3 3.2.3.1 3.2.3.2 3.2.3.3 3.2.3.4 3.3 3.3.1 3.3.2 3.3.3 3.3.3.1 3.3.3.2 3.3.3.3 3.3.3.4 3.4 3.5

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Contents

4.4.2 4.5 4.6 4.7 4.8 4.9

Oxidative Demetallations 116 C5-Superphanes 117 Superbridged Benzene Rings 120 Concluding Remarks 126 Acknowledgement 127 References 127

5

Carbon-Bridged Ferrocenophanes

131

5.4 5.4.1 5.4.2 5.4.3 5.5 5.6

Joon-Seo Park and T. Randall Lee Introduction 131 Nomenclature 132 Mononuclear Carbon-Bridged Ferrocenophanes 133 [1]Ferrocenophanes 133 [2]Ferrocenophanes 134 [3]Ferrocenophanes 136 [4]Ferrocenophanes 140 [5]Ferrocenophanes 144 [m]Ferrocenophanes (m>5) 146 Multiply-Bridged Mononuclear Ferrocenophanes ([m]nFerrocenophanes) 147 Multinuclear Ferrocenophanes 150 [0.0]Ferrocenophanes 150 [1n]Ferrocenophanes 151 mn]Ferrocenophanes 153 Summary 154 References 154

6

Endohedral Metal Complexes of Cyclophanes

6.1 6.2 6.2.1 6.2.2 6.2.3 6.3 6.3.1 6.3.2 6.3.3 6.4 6.4.1 6.4.2 6.5 6.5.1 6.5.2 6.5.3

Rolf Gleiter, Bernhard J. Rausch, and Rolf J. Schaller Introduction 159 Singly-Bridged Group IVB Metallocenes 160 Singly-Carbon-Bridged Group IVB Metallocenes 160 Singly-Silicon-Bridged Group IVB Metallocenes 161 Singly-Boron- and Phosphorous-Bridged Group IVB Metallocenes 162 Doubly-Bridged Group IVB Metallocenes 163 Doubly-Carbon-Bridged Group IVB Metallocenes 163 Doubly-Silicon-Bridged Group IVB Metallocenes 165 Structural Features of Doubly-Bridged Group IVB Metallocenes 166 Endohedral Group VIB and VIIIB Metal p-Complexes 168 Bridged Bis[benzene]chromium Complexes 168 Bridged Metallocenophanes of Group VIIIB Metals 170 Cavities as Hosts for Cations of Group IB, IIIA and IVA Metals 176 Endohedral Silver Complexes with Cyclophanes 176 Silver Complexes with p-Prismands 180 Group IIIA and IVA Complexes of Cyclophanes 181

5.1 5.2 5.3 5.3.1 5.3.2 5.3.3 5.3.4 5.3.5 5.3.6 5.3.7

159

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6.5.4 6.6 6.7 6.8

Group IIIA Complexes with p-Prismands 182 Concluding Remarks 184 Acknowledgments 184 References 184

7

Intramolecular Reactions in Cyclophanes

189

7.5 7.5

Henning Hopf Introduction 189 Reactions between the Benzene Rings of Cyclophanes The Pseudo-gem Effect 198 Intramolecular Reaction between Functional Groups in Cyclophanes 201 Conclusions 207 References 208

8

Reactive Intermediates from Cyclophanes

8.1 8.2 8.3 8.4 8.5 8.6

Wolfram Sander Thermolysis of [2.2]Paracyclophanes 211 Photolytical Cleavage of [2.2]Paracyclophanes 217 Cleavage of [2.2]Paracyclophanes via Electron Transfer 220 Cleavage of Cyclophanes with Unsaturated Bridges 221 Cleavage of Cyclophanes with Carbonyl Groups in the Bridge 223 References 226

7.1 7.2 7.3 7.4

9

9.1 9.2 9.2.1 9.2.2 9.2.2.1 9.2.2.2 9.3 9.3.1 9.3.1.1 9.3.1.2 9.3.1.3 9.3.2 9.3.3 9.4 9.5 9.6

190

211

X-ray Crystal Structures of Porphyrinophanes as Model Compounds for Photoinduced Electron Transfer 229

Hermann Irngartinger and Thomas Oeser Introduction 229 Porphyrin–Quinone Cyclophanes 230 Double-Bridged Porphyrin–Quinone Cyclophanes 230 Single-Bridged Porphyrin–Quinone Cyclophanes 232 Phenyl-Spacered Porphyrin–Quinone Cyclophanes 232 Naphthalene-Spacered Porphyrin–Quinone Cyclophanes 235 Porphyrin-Aromatic-Ring Cyclophanes 238 Single Bridge from Opposite meso-Positions 238 Substituted Phenyl Rings as Cyclophane Components 238 Polycyclic Aromatic Ring-Systems as Cyclophane Components 243 Aromatic Heterocycles as Cyclophane Components 245 Single Bridge from Opposite non-meso-Positions 248 Capped Porphyrins 249 Porphyrinophanes with Fullerene Hosts 253 Concluding Remarks 254 References 255

Contents

10

Ultraviolet Photoelectron Spectra of Cyclophanes

10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.7.1 10.7.2 10.7.3 10.8

Heidi M. Muchall 259 Introduction 259 [2.2]Paracyclophane 263 Modified Bridges in [2.2]Paracyclophane 265 Conjugating Substituents in [2.2]Paracyclophane Donor–Acceptor Cyclophanes 268 Heterocyclophanes 270 Miscellaneous Compounds 270 [6]Phanes with Higher Aromatic Systems 270 Cyclopropenophanes 271 Metacyclophanediynes 272 References 273

11

11.1 11.2 11.3 11.4 11.4.1 11.4.2 11.4.3 11.5 11.6 11.6.1 11.6.2 11.7 11.8 11.9 11.10 11.10.1 11.10.2 11.10.3 11.10.4 11.10.5 11.11

UV/Vis Spectra of Cyclophanes

266

275

Paul Rademacher Introduction 275 Characteristic Properties of Cyclophanes with Implications for their Electronic Spectra 275 [n]Cyclophanes 277 [m.n]Paracyclophanes 279 [1.1]Paracyclophane 279 [2.2]Paracyclophane 280 [m.n]Paracyclophanes 284 Multibridged [2n]Cyclophanes and Related Compounds 285 [m.n]Arenophanes 288 [m.n]Naphthalenophanes 288 [n.n]Pyrenophanes 289 Fluorinated Cyclophanes 290 Heterocyclophanes 290 Multi-layered Cyclophanes 297 Donor–Acceptor Cyclophanes 298 Donor–Acceptor Substituted [n.n]Paracyclophanes 298 [n.n]Paracyclophane Quinhydrones 300 [n.n]Metacyclophane Quinhydrones 303 Oligooxa[m.n]paracyclophane Quinhydrones and Related Compounds 304 Donor–Acceptor Substituted [n.n]Cyclophanes with Extensive p-Electron Systems 305 References 307

12

Electronic Circular Dichroism of Cyclophanes

12.1 12.2

Stefan Grimme and Arnold Bahlmann Introduction 311 Theoretical Methods 312

311

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12.3 12.3.1 12.3.2 12.4 12.4.1 12.4.1.1 12.4.1.2 12.4.2 12.4.2.1 12.4.2.2 12.4.2.3 12.4.3 12.4.3.1 12.4.3.2 12.4.4 12.4.4.1 12.5 12.6 12.7

Excited States of Model Compounds 314 Boat-type Deformation in Benzene 314 Interacting Benzene Fragments 319 Theoretical and Experimental CD Spectra of Cyclophanes [n]Cyclophanes 323 9,12-Dimethyl-4-oxa[7]paracyclophane 323 [6]Paracyclophane-8-carboxylic Acid 324 [2.2]Paracyclophanes 325 [2.2]Paracyclophane 325 4-Fluoro-[2.2]paracyclophane 327 4-Methyl[2.2]paracyclophane 329 [2.2]Metacyclophanes 331 1-Thia[2.2]metacyclophane 331 1-Thia-10-aza[2.2]metacyclophane 332 Cyclophanes with Two Different Aromatic Rings 333 14,17-Dimethyl[2](1,3)azuleno[2]paracyclophane 333 Conclusions 334 Acknowledgement 335 References 335

13

Fully Conjugated Beltenes (Belt-Like and Tubular Aromatics)

13.1 13.2 13.3 13.4 13.5 13.6 13.7

Rainer Herges Introduction 337 Approaches Towards Fully-Conjugated Beltenes 341 Belt-like Benzoannulenes (8) 342 [0n]Paracyclophanes 7 344 Möbius Belts 354 Conjugated Belts from Fullerenes 355 References 356

14

14.1 14.1.1 14.1.2 14.1.3 14.2 14.3 14.3.1 14.3.2 14.4 14.4.1 14.4.2

Molecular Electrochemistry of Cyclophanes

323

337

359

Bernd Speiser Introduction 359 Electron Transfer and Molecular Electrochemistry 359 Molecular Electrochemistry of Cyclophanes 359 Methods of Molecular Electrochemistry 360 Molecular Electrochemistry of Hydrocarbon Cyclophanes 361 Molecular Electrochemistry of Functionalized Cyclophanes 363 Substituted Cyclophanes 363 Cyclophanes with Non-metallic Heteroatoms as Ring Members 364 Molecular Electrochemistry of Organometallic Cyclophane Derivatives 367 A Possible Classification of Organometallic Cyclophane Derivatives 367 Metallocenophanes and Metallametallocenophanes 367

Contents

14.4.3 14.4.4 14.5 14.6

Cyclophanes Cyclophanes Conclusions References

as p-Complex Ligands 370 as Supramolecular Components 374 376 376

15

NMR Spectra of Cyclophanes

15.1 15.2 15.2.1 15.2.2 15.2.3 15.3 15.4 15.5 15.6 15.7 15.8 15.9

Ludger Ernst and Kerstin Ibrom Introduction and Scope 381 [n]Phanes 382 [n]Metacyclophanes 382 [n]Paracyclophanes 385 Other [n]Phanes 387 [2.2]Phanes 389 [3.3]Phanes 396 [m.n]Phanes (m > 2, n ³ 2) 400 [mn]Phanes 406 Other Phanes 409 Conclusion 412 References 412

381

16

Strained Heteroatom-Bridged Metallocenophanes

16.1 16.2 16.2.1 16.2.1.1 16.2.1.2 16.2.1.3 16.2.1.4 16.2.2 16.2.3 16.2.4 16.3 16.3.1 16.3.2 16.3.2.1 16.3.2.2 16.3.2.3 16.3.2.4 16.4 16.4.1 16.4.2 16.5

Ian Manners and Ulf Vogel Introduction 415 Synthesis and Structure 416 [1]Ferrocenophanes 416 Group 13 Bridged [1]Ferrocenophanes 417 Group 14 Bridged [1]Ferrocenophanes 417 Group 15 Bridged [1]Ferrocenophanes 419 Group 16 Bridged [1]Ferrocenophanes 419 Other [1]Metallocenophanes 419 [2]Ferrocenophanes 420 Other [2]Metallocenophanes 422 Ring-Opening Polymerization of Strained Ferrocenophanes 422 Stoichiometric Insertion and Ring-Opening Reactions 422 Ring-Opening Polymerizations (ROP) 423 Thermal ROP 423 Living Anionic ROP of Silicon-Bridged [1]Ferrocenophanes 424 Transition Metal-Catalyzed ROP of [1]Ferrocenophanes 425 Other Initiation Methods for ROP 426 Properties and Applications of Ring-Opened Polyferrocenes 426 Polyferrocenylsilanes 426 Other Polymetallocenes via ROP 430 References 431

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17

17.1 17.2 17.3 17.4 17.5 17.5.1 17.5.2 17.5.3 17.6 17.7 17.8 17.9 18

18.1 18.2 18.3 18.4 18.4.1 18.4.2 18.4.3 18.4.4 18.5 18.6 19

19.1 19.1.1 19.2 19.3 19.3.1 19.4 19.4.1 19.5

Cyclophanes as Templates in Stereoselective Synthesis

435

Valeria Rozenberg, Elena Sergeeva, and Henning Hopf Introduction 435 Chiral [2.2]Paracyclophanes: Nomenclature and Stereochemical Assignment 435 The Resolution of Representative Mono- and Disubstituted [2.2]Paracyclophanes 437 Monosubstituted [2.2]Paracyclophanes as Chiral Inductors 437 Disubstituted [2.2]Paracyclophanes as Chiral Inductors 440 Ortho- and syn-latero-Substituted Derivatives 440 Pseudo-ortho-Derivatives 449 Pseudo-gem-Derivatives 452 Chiral Templates from Substituted [2.2]Paracyclophanes as Building Blocks 454 Stereoselective Reactions in the Side Chain of the Paracyclophanyl Moiety 457 Concluding Remarks 458 References 459 Vapor-Based Polymerization of Functionalized [2.2]Paracyclophanes: A Unique Approach towards Surface-Engineered Microenvironments

Doris Klee, Norbert Weiss, and Jörg Lahann Introduction 463 Synthesis of Functionalized [2.2]Paracyclophanes 464 CVD Polymerization of Functionalized [2.2]Paracyclophanes Immobilization of Bioactive Substances via Functionalized Poly(p-xylylenes) 472 Introduction 472 Surfaces for Blood Contact 475 Surfaces for Tissue Contact 476 Surface Engineering of Microfluidic Devices 478 Conclusions 481 References 482 From Cyclophanes to Molecular Machines

463

466

485

Amar H. Flood, Yi Liu, and J. Fraser Stoddart Introduction 485 Control over the Location and Motion of Moving Parts in Molecular Machines 485 The Creation of the Tetracationic Cyclophane 486 Host–Guest Chemistry with the Tetracationic Cyclophane 488 Location Control: Host–Guest Chemistry 488 Catenane Chemistry with the Tetracationic Cyclophane 492 Going for Gold – The Story of Olympiadane 495 Rotaxane Chemistry with the Tetracationic Cyclophane 497

Contents

19.5.1 19.6 19.6.1 19.6.2 19.6.3 19.6.4 19.6.5 19.7 19.7.1 19.7.2 19.7.3 19.7.4 19.8 19.9 19.10

Location Control – Catenanes and Rotaxanes 499 Switchable Rotaxanes, Catenanes and Pseudorotaxanes 499 Controllable Molecular Shuttles 500 Switchable Catenanes 502 Switchable Rotaxanes 503 Photochemically Switchable Pseudorotaxanes 503 Control of Motion 504 Electronic Devices Containing Molecular Switches 505 A [2]Catenane-Based Electronic Device 506 Bistable [2]Rotaxane Electronic Devices 508 Memory Devices 510 Miniaturization of the Crossbar 510 Mechanical Devices with Molecular Machines 513 Conclusions 515 References 516

20

Molecular Recognition Studies with Cyclophane Receptors in Aqueous Solutions 519

20.1 20.2 20.2.1 20.2.2 20.2.3 20.2.4

20.3 20.3.1 20.3.2 20.3.3 20.4 20.5 20.6 20.7 20.8

François Diederich Introduction 519 Complexation of Aromatic Solutes 520 Polar Effects in Cyclophane Complexation 520 Complexation of Polycyclic Aromatic Hydrocarbons (PAHs) in Water 521 The Combination of Apolar Binding and Ion Pairing Leads to Very High Substrate Selectivity 523 Solvent Dependency of Cyclophane-Arene Complexation and the Nonclassical Hydrophobic Effect: Enthalpic Driving Forces in Aqueous Solution 525 Steroid Recognition by Cyclophane Receptors 527 The Search for Cyclophanes with Larger Preorganized Cavity-Binding Sites 527 Steroid Complexation by Cyclophanes 9 and 10 529 Double-decker Cyclophanes for Efficient Steroid Complexation: Dissolution of Cholesterol in Water 533 Catalytic Cyclophanes 536 Dendritically Encapsulated Cyclophanes (Dendrophanes) 541 Conclusions 543 Acknowledgments 543 References 544

Subject Index

547

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XV

Preface [2.2]Paracyclophane, first prepared in 1949 by Brown and Farthing and then systematically investigated by Cram and his co-workers from 1951 onward, is now a molecule with a history spanning half a century. A history, however, as confirmed inter alia by this monograph, that is not only active and living, but also increasingly extending into novel fields and applications. This is rare for any organic compound and certainly rare for hydrocarbons (excluding such household chemicals such as natural gas and gasoline). So, what are the reasons for this unabated interest? The first reason was already obvious to the pioneer workers in this area: The interaction between layered p-systems combined with an unusual three-dimensional structure. Indeed, most of the early studies in cyclophane chemistry were connected to the problem of the “bent and battered benzene rings” (so the title of a classical review article by Cram) and the consequence this structural feature had on the chemical behavior of the cyclophanes. Obviously, the distance between the aromatic subunits (the “decks”) could be altered by changing the nature of the molecular bridges, and one can say that this classical period of cyclophane chemistry culminated in the preparation of superphane by Boekelheide and certainly with the preparation of [1.1]paracyclophane by Tsuji. What – secondly – had become more and more obvious during these studies was the realization of what may be called the “phane concept”. Just as benzene is the epitome of a planar (flat) aromatic molecule, [2.2]paracyclophane is the example par excellence of a three-dimensional aromatic molecule. Not only did leaving the p-plane lead to the realization that a new, widely variable class of chiral molecules had become available – with all the effects on, for example, stereoselective synthesis – but the bridged aromatic concept could be connected effortlessly to the simultaneously evolving areas of crown ether, cryptand, cavitand, and supramolecular chemistry. To put it another way: numerous supramolecular structures are cyclophanes (and it may be added in passing that – viewed from this angle – there is also a huge group of naturally occurring cyclophanes). Thirdly, the zwitter character of the cyclophanes became evident during this period. Whereas, for example, adamantane or cubane are only aliphatic molecules, and benzene or the condensed aromatic systems or even the fullerenes are only (highly) unsaturated compounds, the cyclophanes are both: aromatics and aliphatModern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

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Preface

ics (as already indicated by the euphonious name), making the use of both types of chemistries applicable. As far as the aromatic part of the cyclophanes is concerned, this not only meant the application of the typical reactions of classical aromatic chemistry to these compounds, but also the preparation of reactive intermediates derived from the aromatic rings: radical cations, radical anions, etc. Furthermore there was also the unique possibility of combining cyclophane chemistry with the archetypical layered inorganic chemistry, as exemplified by the classics ferrocene and dibenzene chromium. The cyclophanes, however, offer the additional topologically interesting and important possibility of bonding the metal to the interior or the exterior of the organic ligand. Incidentally, the chemical behavior of the molecular bridges in cyclophanes has not been studied to the same extent as the reactivity of the aromatic subunits. Finally, the crucial test for the significance of a molecular assembly is its practical application. After all, if the properties of a chemical compound are really “interesting”, there must also be practical, industrial applications. With the increased use of cyclophanes as monomers for the preparation of new polymers by CVD techniques with unusual and characteristic properties, polymers not just of importance as chemically very stable surfaces, e.g. for printed circuits, but also as new materials for medical application and drug delivery, cyclophanes are finding more and more applications in materials science. Together with their use in all kinds of optical devices, and as ligands in stereoselective synthesis, we are observing a very rich field developing here. It is our aim with this volume to show these different developments in cyclophane chemistry. That we succeeded was, of course, only possible because we found a group of excellent contributors and cyclophane specialists willing to give us their time and share their knowledge. As far as the practical side is concerned, we are very grateful to Drs. Gudrun Walter, Bettina Bems from Wiley/VCH, Mary Korndorffer for copy editing and Petra Krämer and C. Mlynek for drawing the numerous and often very complex structures. We dedicate this volume to the memory of Donald Cram and Virgil Boekelheide.

Heidelberg/Braunschweig April 2004

Rolf Gleiter Henning Hopf

XVII

List of Contributors Arnold Bahlmann Universität Münster Organisch-Chemisches Institut Corrensstraße 40 48149 Münster Germany

Rolf Gleiter Universität Heidelberg Organisch-Chemisches Institut Im Neuenheimer Feld 270 69120 Heidelberg Germany

François Diederich ETH Zürich Department of Chemistry and Applied Biosciences Wolfgang-Pauli-Straße 10 8093 Zürich Switzerland

Stefan Grimme Universität Münster Organisch-Chemisches Institut Corrensstraße 40 48149 Münster Germany

Ludger Ernst Technische Universität Braunschweig NMR-Labor der Chemischen Institute Hagenring 30 38106 Braunschweig Germany Amar H. Flood University of California, Los Angeles Department of Chemistry and Biochemistry 405 Milgard Avenue CA 90095-1569 Los Angeles USA

Uwe Hahn Rheinische Friedrich-WilhelmsUniversität Bonn Kekulé-Institut für Organische Chemie und Biochemie Gerhard-Domagk-Str. 1 53121 Bonn Germany Rainer Herges Universität Kiel Institut für Organische Chemie Otto-Hahn-Platz 4 24098 Kiel Germany

Modern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

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List of Contributors

Henning Hopf Technische Universität Braunschweig Institut für Organische Chemie Hagenring 30 38106 Braunschweig Germany Kerstin Ibrom Technische Universität Braunschweig Institut für Organische Chemie Hagenring 30 38106 Braunschweig Germany Hermann Irngartinger University of Heidelberg Institute of Organic Chemistry Im Neuenheimer Feld 270 69120 Heidelberg Germany Doris Klee RWTH Aachen Department of Textile and Macromolecular Chemistry 52074 Aachen Germany Joerg Lahann University of Michigan Departments of Chemical Engineering, Material Science and Engineering, and Macromolecular Science and Engineering 3414 G.G. Brown 2300 Hayward Ann Arbor MI – 48109-2139 USA T. Randall Lee University of Houston Department of Chemistry 4800 Calhoun Road Houston, TX 77204-5003 USA

Yi Liu University of California, Los Angeles Department of Chemistry and Biochemistry 405 Milgard Avenue CA 90095-1569 Los Angeles USA Ian Manners University of Toronto Department of Chemistry 80 St. George Street Toronto, Ontario M5S 3H6 Canada Heidi M. Muchall Concordia University Department of Chemistry and Biochemistry and Centre for Research in Molecular Modeling Montreal, Quebec H4B 1R6 Canada Thomas Oeser University of Heidelberg Institute of Organic Chemistry Im Neuenheimer Feld 270 69120 Heidelberg Germany Joon-Seo Park University of Houston Department of Chemistry 4800 Calhoun Road Houston, TX 77204-5003 USA Gregor Pawlitzki Rheinische Friedrich-WilhelmsUniversität Bonn Kekulé-Institut für Organische Chemie und Biochemie Gerhard-Domagk-Str. 1 53121 Bonn Germany

List of Contributors

Paul Rademacher Universität Duisburg-Essen Institut für Organische Chemie Universitätsstr. 5–7 45117 Essen Germany Bernhard J. Rausch Clariant BL Pharma Germany Molecules Synthesis Centre Industriepark Höchst, D 569 65926 Frankfurt/Main Germany Rolf Roers Bayer MaterialScience AG Building B 103 51368 Leverkusen Germany Valeria Rozenberg Russian Academy of Science A. N. Nesmeyanov Institute of Organoelement Compounds Vavilova str., 28 119991 Moscow Russia Wolfram Sander Ruhr University Bochum Department of Organic Chemistry II 44780 Bochum Germany Rolf J. Schaller EMS-Dottikon AG Hembrunnstr. 17 5605 Dottikon Switzerland Elena Sergeeva Russian Academy of Science A. N. Nesmeyanov Institute of Organoelement Compounds Vavilova str., 28 119991 Moscow Russia

Motohiro Sonoda Osaka University Graduate School of Engineering Science, Division of Frontier Materials Science 1-3 Machikaneyama Toyonaka 560-8531 Japan Bernd Speiser Universität Tübingen Institut für Organische Chemie Auf der Morgenstelle 18 72076 Tübingen Germany J. Fraser Stoddart University of California, Los Angeles Department of Chemistry and Biochemistry 405 Milgard Avenue CA 90095-1569 Los Angeles USA Takashi Tsuji Hokkaido University Division of Chemistry, Graduate School of Science Sapporo 060-0810 Japan Yoshito Tobe Osaka University Graduate School of Engineering Science, Division of Frontier Materials Science 1-3 Machikaneyama Toyonaka 560-8531 Japan Ulf Vogel University of Toronto Department of Chemistry 80 St. George Street Toronto, Ontario M5S 3H6 Canada

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List of Contributors

Fritz Vögtle Rheinische Friedrich-WilhelmsUniversität Bonn Kekulé-Institut für Organische Chemie und Biochemie Gerhard-Domagk-Str. 1 53121 Bonn Germany

Norbert Weiss RWTH Aachen Department of Textile and Macromolecular Chemistry 52074 Aachen Germany

1

1

Cyclophynes Yoshito Tobe and Motohiro Sonoda

1.1

Introduction

The chemistry of cyclophynes having carbon–carbon triple bond bridges has been one of the most actively investigated fields in modern cyclophane chemistry, particularly in connection with the evolving fields of carbon-rich materials and shapepersistent macrocyclic compounds. In accordance with the remarkable progress in this field over the last decade, a number of reviews has already been published based on the authors’ own perspectives [1–9]. Since, in this review, the authors wish to provide a comprehensive survey of cyclophyne chemistry, some overlaps are inevitable. The properties of cyclophynes are characterized by the geometric and electronic properties of triple bonds and the substitution pattern of the aromatic rings. With regard to the geometrical properties, the macrocyclic frameworks of cyclophynes can be expanded by incorporation of triple bonds because of their linearity. The substitution pattern of the aromatic rings, on the other hand, fixes the direction of the bridging triple bonds, defining the whole molecular shape. As a result, a variety of two- and three-dimensional architectures can be built by connecting aromatic rings with triple bond linkages. The ortho substitution pattern would lead to conjugated cyclophynes, also regarded as dehydrobenzoannulenes (DBAs), with either planar or nonplanar shape depending principally on their ring size. Although planar DBAs had been studied extensively during the late 1950s through mid-1970s in connection with the aromaticity/antiaromaticity of annulenes, these are currently being investigated with renewed interest regarding their potential as opto-electronic materials. On the other hand, nonplanar macrocycles of this type have been studied with regard to their conformation, chirality, and their potential application to liquid crystalline and sensing materials. Some highly unsaturated members of this type of compound have been shown to serve as precursors of ordered carbon materials. Since the meta substitution pattern would make the size of the cyclophynes larger than the ortho analogs, keeping the planarity of the macrocyclic rings, a number of shape-persistent metacyclophynes have been synthesized in order to investigate their supramolecular properties such as guest-binding and self-association in solution, solid state, and at solid–liqModern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

2

1 Cyclophynes

uid and air–liquid interfaces. To form cyclic structures of para substitution pattern, macrocycles adopt a cylindrical shape, and with 1,3,5-trisubstitution, a cagelike structure can be constructed. These three-dimensional molecules have been studied in view of the host–guest chemistry of curved p-systems, strain of triple bonds, and their transformation into all-carbon molecules. Concerning the electronic properties of C–C triple bonds, acetylene linkages are capable of transmitting electronic perturbation efficiently from one end of conjugated p-systems to the other because of the isotropic distribution of the p electrons along the C–C axis. This characteristic is responsible for the unique optoelectronic properties predicted for planar cyclic compounds like DBAs. Because C–C triple bonds have a high energy content, it is well known that structurally unhindered alkynes react violently, frequently with explosion. Similarly, diynes are known to undergo topochemical polymerization to form poly(butadiyne)s, potential materials with nonlinear optical properties. The high potential of the triple bonds toward spontaneous chemical reactions has been exploited to provide the transformation of some cyclophynes into all-carbon and carbon-rich materials. In addition, because triple bonds serve as good ligands for transition metals, a number of metal complexes of cyclophynes with unique structures has been readily prepared. Besides the interest from materials science, recent development of new synthetic methods, particularly those based on transition metal-catalyzed bond formation between sp–sp2 and sp–sp carbons, have been playing a crucial role in the rapid growth of this field. This chapter covers the recent development of the twoand three-dimensionally shaped cyclophynes from the above points of view. For convenience, the molecules are classified into three types: (1) orthocyclophynes with either planar or nonplanar shape; (2) metacyclophynes; and (3) paracyclophynes and 1,3,5-bridged cyclophynes, on the basis of the substitution pattern. Those compounds with mixed substitution pattern such as ortho, para and meta, para are included in one of the above three types depending on their most characteristic structural and/or functional properties.

1.2

Orthocyclophynes and Related Systems

Fully conjugated planar orthocyclophynes are regarded as dehydrobenzoannulenes (DBAs) [2, 3, 4, 6]. 12-, 14- and 18-membered macrocycles of this type are investigated intensively in connection with their opto-electronic properties, theoretical and experimental inspection of aromaticity, and as substructures of hitherto unknown two-dimensional carbon networks, graphyne and graphdiyne [9]. On the other hand, since the macrocyclic frameworks of larger orthocyclophynes are nonplanar, these molecules are investigated in view of their structure and the chirality of twisted p-systems [7]. In addition, highly unsaturated compounds of this class are studied as possible precursors to nanocarbon materials such as carbon onions and tubes.

1.2 Orthocyclophynes and Related Systems

Fig. 1.1

1.2.1

Planar Dehydrobenzoannulenes

It was predicted that the two-dimensional carbon network, graphyne, would exhibit semiconductive and nonlinear optical properties [10]. Recent calculations from first principles confirmed that graphyne should be a semiconductor with a moderate band gap and should be quite stable once synthesized [11]. It was predicted that potassium-intercalated graphyne would become metallic with a remarkably short distance (4.30 Å when each 12-membered ring holds a potassium atom) between the intercalant layers [12]. In connection with the nonlinear optical properties of graphyne, hyperpolarizabilities of ladder oligomers of dehydrobenzo[12]annulene ([12]DBA) have been estimated, based on semiempirical calculations, indicating that these can be promising third-order nonlinear optical materials [13]. Force field calculations for networks related to graphdiyne revealed that they would exhibit negative Poisson’s ratios, an unusual mechanical property caused by the rotation of triangles [14]. Most cyclophynes were synthesized by using the Stephens-Castro and Sonogashira reactions for the C(sp2)–C(sp) bond formation or copper(II)-mediated oxidative coupling for C(sp)–C(sp) bond formation. Remarkable improvements in the synthesis of cyclophynes have been achieved as exemplified by the synthesis of the known [12]DBA 1 a. These include (1) the Stephens-Castro reaction of the preformed copper(I) acetylide [15]; (2) one-step synthesis by the Sonogashira coupling using acetylene [16]; (3) selective construction of the 12-membered ring based on a masking/protection protocol for both aryl iodide using dialkyltriazene group and alkyne terminal using trialkylsilyl groups [17]; and (4) the alkyne metathesis method [18], which has been developed recently (Scheme 1.1). The first two methods were also utilized for the synthesis of thiophene analogs 2 a [16] and 3 [19]. By stepwise construction of the requisite precursor followed by intramolecular Sonogashira coupling, Haley synthesized bisDBAs 4 and 5 a [17]. An another derivative of the latter compound 5 b was also prepared by an in situ deprotection–cyclization method to prove the theoretical prediction for hyperpolarizability of this sys-

3

4

1 Cyclophynes

Fig. 1.2

Scheme 1.1

1.2 Orthocyclophynes and Related Systems

Scheme 1.2

tem (Scheme 1.2) [20]. Not only the parent hydrocarbon 1 a but also a number of its derivatives 1 b–d have been prepared by the metathesis method, except for those with substituents adjacent to the alkyne bridges. Similarly, the metathesis method was applied to the synthesis of bisDBA 4 and orthometacyclophyne 6 [18]. Since the late 1980s, Youngs and Tessier have been developing new frontiers in the chemistry of the [12]DBA system [6]. A number of transition metal complexes of 1 a were prepared such as Co(0), Cu(I), Ag(I), and Ni(0) complexes [21]. Significantly among these metal complexes, the Ni(0) complex becomes semiconductive [22]. For example, the Ni(0) complex doped with potassium [2.2.2]cryptate (1 : 2 ratio) exhibits conductivity of a moderate semiconductor regime (2 ´ 10–3 S cm–1). The hexamethoxy derivative 1 g, hexa-alkoxy derivatives 1 e–f having long alkyl chains, and their Ni(0) complexes were also prepared, as well as the quinone 7 and thiophene derivatives 2 b–c [23]. In spite of the expectation based on their structural similarities to hexasubstituted triphenylene derivatives, DBAs 1 e–f and 2 b–c with long alkyl chains did not exhibit liquid crystalline properties. A dihydro derivative of 1 a, cyclophanediyne 8, was prepared by Iyoda et al. using modified McMurry coupling conditions, followed by dehydroxylation [24]. Although the X-ray structure analysis of 8 revealed its short transannular distance (the shortest C(sp)–C(sp) distance: 2.77 Å), it was inert to photoirradiation. On the other hand, heating 8 at 250 8C in the presence of cyclohexa-1,4-diene resulted in the formation of dibenzonaphthocyclooctatetraene, a product of the Bergman cyclization. The corresponding transannular distances of the oxygen- and sulfurbridged diynes 9 a and 9 b, respectively, are longer than that of 8 (3.44 and 3.50 Å, respectively), and it is reported that these compounds are inert to thermal and photochemical cyclization [25]. Hexa-ethynyl derivatives 1 i–j were prepared as the key intermediates for the synthesis of antikekulene 12, an antiaromatic counterpart of kekulene [26]. Thus

5

6

1 Cyclophynes

the first intramolecular CpCo-catalyzed cyclotrimerization of 1 i and 1 j yielded the triphenylene-based cyclophynes 10 a and 10 b, respectively, whose second cycloisomerization furnished the corresponding pentaphenylene-based cyclophynes 11 a and 11 b (Scheme 1.3). The final cyclization to the target 12 is yet to be realized. Besides this spectacular synthetic endeavor, the parent hydrocarbon 1 h was found to form crystals with highly organized channels including tetrahydrofuran induced by multiple alkyne C–H. . .O hydrogen bonds [27]. Perethynyl-substituted dibenzodehydro[12]annulene 13 a was prepared by Rubin et al. by oxidative coupling of a differentially substituted hexa-ethynylbenzene derivative [28]. Hydrocarbon 13 a can be regarded as a constituent unit of a two-dimensional network with different topology from that of graphdiyne and as a monomer of ladder polymers constructed from the dibenzodehydro[12]annulene ring, called acynes. In this connection, Anthony prepared tetra-ethynyl-substituted [14]DBA 14 having acenaphthene units as a possible monomer unit of the related ladder polymers [29]. In connection with the topochemical polymerization of butadiynes, Komatsu et al. prepared octafluoro[12]DBA 13 c, whose reduction potential was more negative than that of the parent hydrocarbon 13 b [30]. In the two crystal forms of 13 c, the molecules are stacked in a slanted manner, while in the cocrystal of 13 b and 13 c (1 : 2), the molecules are stacked in a columnar arrangement forming a sandwich-like complex. In spite of the favorable packing geometries for topochemical polymerization, none of the crystals underwent photochemical polymerization, probably because of the high potential energy of the polymerization product. As a quantitative measure of aromaticity of DBAs, the nuclear independent chemical shift (NICS) values at the center of the macrocyclic ring of 1 a, as well as

Scheme 1.3

1.2 Orthocyclophynes and Related Systems

Fig. 1.3

those for [14]annulene 15, [16]annulene 16, and [18]annulene 17 a, were estimated by the DFT method, indicating that 1 a and 16 are moderately antiaromatic while 15 and 17 a are weakly aromatic [31]. Similarly we can predict that highly strained [10]annulene 18 is fully aromatic [31 c]. In order to investigate the effect of strain on the tropicity of DBA rings, tetrakisdehydro[12]annulene 19 was generated by photochemical [2+2] fragmentation of the propellane precursor 20 in an argon matrix at low temperature and was characterized by comparison of UV and IR spectra with those calculated by the DFT method (Scheme 1.4) [32]. Unfortunately, since the [12]annulene system 19 was too reactive to observe its tropicity in solution, the next higher homolog 21 was produced by the same method from the homologous precursor 22. The calculated 1H NMR chemical shift by the DFT method and experimental observations revealed that strained pentakisdehydro[14]annulene 21 was as diatropic as the corresponding tetrakisdehydro derivative 22. Interestingly, the 14-membered DBA ([14]DBA) 15 underwent topochemical polymerization induced by photoirradiation or by applying pressure (20 000 psi) [33]. From the packing diagram of the crystal, trans–trans geometry of the polymer chain was suggested. This represents the first example of the topochemical polymerization of a conjugated cyclic diyne derivative, although the reactions of acyclic butadiyne derivatives have been well known to form poly(butadiyne)s, which are known to exhibit interesting optical properties. In connection with the theoretical prediction regarding the tropicity of dehydrobenzo[14]annulenes, Haley prepared a number of monobenzo, dibenzo, and monothiopheno derivatives such as 23–27 and studied their diatropicities based on the 1H NMR chemical shifts [34]. As a result, fusion of a benzene ring to the dehydro[14]annulene ring induces stepwise loss of aromaticity with increasing number of the fused rings. The relative aromaticity (RA) was defined by the chemical shifts relative to those of a nonconjugated reference compound. The experimental RAexpt values are in accord with the theoretical values (RANICS) derived from the calculated NICS values. To further confirm the aromaticity of the [14]annulene system, hybrid systems 28 and 29 formed by fusion of the [14]DBA ring to dimethyldihydropyrene (DHP) unit were prepared [35]. The chemical shift of the probe methyl group in the DHP system of mono-DBA-fused compound 28 was compared with appropriate references. However, the effect of benzoannelation on aromaticity of the [14]DBA ring is not conclusive probably because of the small chemical shift change. BisDBA fused system 29 cannot be used for the examination of aromaticity because

7

8

1 Cyclophynes

Fig. 1.4

the effect of one DBA unit on the DHP probe should counteract that of the other DBA. Since Mitchell et al. developed reversible photochemical isomerization of fused DHPs with the corresponding [2.2]metacyclophane systems, the isomerization of 29 was examined, because its absorption band extended to 600–800 nm region, which may be used as “read out” without scrambling of information. However, photochemical isomerization was not successful because the cyclophane form reverts very easily to the starting material 29. A hybrid system 30 between [14]DBA 15 and [2.2]paracyclophane was synthesized in order to investigate the global transannular delocalization through the overall p system [36]. By comparison of the UV absorption with those of appropriate acyclic reference compounds, it was concluded that 30 sustained p-electron delocalization through the circuit composed of the DBA and [2.2]paracyclophane systems.

1.2 Orthocyclophynes and Related Systems

Scheme 1.4

Haley developed an in situ deprotection–Sonogashira coupling method using o(ethynylphenyl)butadiyne derivatives, which are otherwise too reactive to handle, as a butadiyne building block of DBAs, utilizing the reactivity difference between TMS and TIPS groups towards deprotection [37]. With this method, synthesis of a variety of dehydrobenzo[18]annulene ([18]DBA) derivatives was achieved, including the parent hydrocarbon 17 a (its first characterization) and derivatives such as 17 b and 17 c with electron-donating and accepting substituents at specific positions [38]. The first hyperpolarizabilities (b) of several donor–acceptor substituted derivatives of 17 a were determined in order to examine their second-order nonlinear optical properties [39]. The hyperpolarizability of some derivatives was comparable to that of the known reference compound, 4-dimethylamino-4’-nitrostilbene, while that of others was superior. This method was also applied to the synthesis of [16]DBA 16 [40], thiopheno[18]annulenes 31–33 [41], and the [18]DBAcrown ether hybrid 34 [42]. The latter compound was prepared with the intention of organizing the DBA units by formation of a supramolecular poly(rotaxane) structure by complexation with a polyammonium ion at the crown ether unit. Moreover, larger DBAs 35 and 36 with hexatriyne linkage(s) were prepared by the same protocol using an o-(ethynylphenyl)hexatriyne derivative [40]. The Haley method was also successfully adopted as the crucial step for the synthesis of a number of graphdiyne structures such as “bow tie” 37, “boomerang” 38, “diamond” 39, “half wheel” 40, and “trefoil” 41 [37, 43]. All the partial graphdiynes are stable up to ca. > 200 8C where they decomposed within a narrow range of temperatures as observed by DSC, forming black, insoluble materials which were difficult to characterize. The ultimate goal, a “perfect wheel” 42, is yet to be synthesized. Organometallic DBA derivatives have been studied extensively by Bunz et al. [3]. Ferrocene derivatives of [18]DBAs 43 a–b and [24]DBAs 44 have been synthesized by oxidative coupling of the corresponding diethynylferrocene [44]. Since 43 a and 43 b exhibited similar oxidation potentials, it was deduced that the through bond/ space interactions between the ferrocene units were small. Similarly, (CpCo)cyclobutadienyl derivatives 45 a–b and 46 a were obtained from a diethynylcyclobutadiene complex. Selective deprotection of the TMS/TIPS-protected tetraethynylcyclobutadiene complex followed by oxidative coupling furnished perethynylated [18]- and [24]annulene derivatives 45 c and 46 b, respectively, which would serve as building blocks for the organometallic graphdiynes.

9

10

1 Cyclophynes

Fig. 1.5

Ferroceno[14]annulenes 47 and 48 and (CpCo)cyclobutadieno[14]annulenes 49 and 50 were prepared to study the aromaticity/antiaromaticity of the ferrocene and (CpCo)cyclobutadiene rings, respectively [45]. Since the p electrons in the fused [14]annulene rings in 47 and 48 are more localized than the corresponding benzoannulenes, it is deduced that ferrocene is more aromatic than benzene. Moreover, according to the same ring current criterion, the (CpCo)cyclobutadiene ring is also more aromatic than benzene, even slightly so than ferrocene. The larger homologs, ferroceno[18]annulene 51 a–c and (CpCo)cyclobutadieno[18] annulene 52 a–d were prepared to explore the possible transformation of organometallic DBAs into onion- or tube-like carbon structures by their explosive decomposition [46], the observations first being reported by Vollhardt (Section 1.2.2). Among several organometallic [18]DBAs, only 51 b, 52 b, and 52 c underwent explosive decomposition. While the materials formed from the former two compounds were amorphous, that derived from 51 b exhibited distinct nanostructure as revealed by the TEM observations. In connection with the ultimate two-dimensional network, the synthesis of partial structures, cyclobutadieno “bow tie” 53, cyclobutadieno and ferroceno “half square” 54 and 55, and cyclobutadieno “three-quarters square” 56, has been accomplished [47]. The target, “perfect square” 57, has not so far been prepared.

1.2 Orthocyclophynes and Related Systems

Fig. 1.6

11

12

1 Cyclophynes

Fig. 1.7

Fig. 1.8

1.2 Orthocyclophynes and Related Systems

Fig. 1.9

1.2.2

Nonplanar Orthocyclophynes

Orthocyclophynes constructed from more than four benzene rings adopt nonplanar conformations and have been investigated in view of their structure and the chirality of twisted p-systems and of their unique properties caused by the twisted structures. Indeed, the X-ray crystal structure of [24]orthocyclophanetetrayne 58 revealed that it possessed twisted, saddle-like conformation of the macrocyclic ring [15]. Moreover, the crystal of the cyclic hexamer 59 adopts a helical conformation with the principal axis extending through the two peripheral rings and between the two eclipsed tolan moieties [15]. The solid state conformation of the even larger decamer 60 is irregular and no longer helical [48]. Butadiyne-bridged macrocycle 61 was also shown to possess a twisted macrocyclic ring [49]. The mixed ethynylene–butadiynylene macrocycles 62 a–b, 63, and 64, the latter two being prepared using Haley’s protocol, were also shown to adopt nonplanar saddle-like conformations [37, 50]. The barrier for flipping of 62 a was estimated by a variable-temperature NMR study to be 9.3 kcal mol–1. Perhaps the most exciting finding, reported by Vollhardt et al., for these highly unsaturated macrocycles is that 62 b exploded violently with a flash of orange light to yield ordered carbon materials which were shown by TEM to possess tube- and onion-like structures [50]. Moreover, not only the corresponding cobalt complex 65 but also simple acyclic complexes such as 66

13

14

1 Cyclophynes

were shown to form carbon onions with diameters of 100–800 Å and multiwalled nanotubes with diameters of 60–400 Å upon annealing at 800 8C [51]. A number of twisted macrocycles were synthesized by Fallis et al. by dimerization of terminal alkynes using copper(I)-mediated oxidative coupling. In certain cases, however, intramolecular cyclization competed with the dimerization. Thus in the case of diethynylterphenyl 67, both intramolecular cyclization and dimerization took place, yielding monomers 68 and dimers 69, respectively, whose distribution depended on substituents and reaction conditions (Scheme 1.5) [52]. The carboxy derivative of monomer 68 was shown by X-ray structural analysis to possess highly strained triple bonds with distortion angles of 16.3–16.78. In contrast, similar oxidative coupling of monomer 70 a–c, whose backbone was extended compared to that of terphenyl 67, resulted in the selective formation of cyclic dimers 71 a–c. The X-ray crystal structure of 71 a revealed that the central benzene rings

Fig. 1.10

1.2 Orthocyclophynes and Related Systems

were aligned to a slightly offset but overlapping geometry with inter-ring distance of 3.57 Å. It is noteworthy that the dialkoxy derivative 71 c exhibits liquid crystalline behavior, suggesting the occurrence of a unique liquid crystalline phase based on twisted p frameworks. Similarly, the isomeric cyclophynes 72 and 73 with meta-bridged central benzene rings were prepared by oxidative dimerization [53]. These isomers did not interconvert because of steric constraints. Large octatetrayne-bridged cyclophynes 74 [54] and 75 [55] were prepared by the in situ deprotection–oxidative coupling method without isolating unstable phenylbutadiyne intermediates. The twisted thiophenophynes 76 a–c were prepared by Marsella by intermolecular Sonogashira coupling of the terminal alkyne and iodothiophene derivatives [56]. Since the efficiency of the cyclization depends on the substituents of the central benzene ring, the mixed cyclophyne 76 b being formed most efficiently, the presence of phenyl/perfluorophenyl interactions was invoked. Baxter prepared the pyridine analog 77 of twisted cyclophyne 71 a and investigated its properties as a potential fluorescence sensor for heavy metals such as Pd(II) and Hg(I) [57]. He also prepared the macrocycle 78 and its isomer 79 having central bipyridine rings [58]. While molecular mechanics calculations for 78 suggest that it possesses a twisted conformation similar to that of 71 a, molecular modeling of 79 by semiempirical molecular orbital calculations suggests the presence of a few minimum energy conformers. The former 78 binds Co(II), Ni(II), Zn(II), and Cu(II) ions as detected by UV absorption and fluorescence, while its isomer 79 binds only Cu(II) and Ag(I). Phenanthroline-based

Fig. 1.11

15

16

1 Cyclophynes

Scheme 1.5

macrocycle 80 was prepared using Cu(II)-templated oxidative coupling of the monomer unit [59]. The initial product was a copper(II) complex from which free macrocycle 80 was liberated by treatment with KCN. The barrier for twisting of the free macrocycle 80 and its Cu(II) complex was determined by variable temperature NMR spectra to be 9.4 and 13.6 kcal mol–1, respectively. The [6]helicene-based double-helical cyclophyne 81 was prepared by Fox in enantiomerically pure form and its UV and CD spectra have been investigated [60]. Since the two helicene units are orthogonal with respect to each other, electronic delocalization through the entire p system seems to be inhibited. Double-helical binaphthyl-based cyclophynes 82 [61] (enantiomerically pure) and bithiophenebased scaffold for double-helical ladder polymers 83 [62] (racemic) were prepared by the Sonogashira reaction. Diederich prepared chiral binaphthol-based cyclophynes such as 84 and 85 by oxidative coupling of the monomer units and studied their binding properties toward pyranoside derivatives [63]. The trimeric macrocycle 84 forms 1 : 1 complexes with glucopyranoside derivatives in CDCl3 with moderate discrimination of not only the enantiomers but also the anomers. On the other hand, the tetrameric phosphate receptor 85 was capable of binding a pyranose derivative even in a protic solvent containing up to 20% v/v CD3OD in CD3CN.

1.3 Metacyclophynes and Related Systems

Fig. 1.12

1.3

Metacyclophynes and Related Systems

The general structures for phenylacetylene macrocycles 86 and diethynylbenzene macrocycles 87 may represent prototypical metacyclophynes. In general, when the number (n) of the constituent units is small (n = 3), the macrocycles must be unstable because of bond angle distortion. When n is large (n ³ 7), the macrocycles should adopt nonplanar conformations. On the other hand, medium-sized macrocycles (n = 4–6) should be stable and adopt approximate planar conformations. Metacyclophynes have been extensively studied during the last decade, because they have a persistent flat shape and can functionalize at both the interior and/or exterior of the macrocyclic framework. Aspects of their supramolecular chemistry that have been studied include guest-binding ability utilizing internal binding sites, construction of supramolecular structures using peripheral functionalities, self-as-

17

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1 Cyclophynes

Fig. 1.13

Fig. 1.14

sociation in solution, liquid crystalline phase, and solid state, and organization at various interfaces [1, 5, 7]. Most of the syntheses of this class of compounds have been achieved by the Sonogashira type C(sp2)–C(sp) bond formation and by the Hay or Eglinton methods

1.3 Metacyclophynes and Related Systems

for C(sp)–C(sp) bond formation. By using a combination of selective protection/ masking of a terminal acetylene moiety by TMS group and aryl iodide by triazene group, respectively, Moore succeeded in the size-selective synthesis of a variety of nanoscale macrocycles such as 88 [64]. An attempt at the solid phase synthesis of a derivative of the phenylacetylene macrocycle 86 (n = 6) was not successful presumably because of catenation of the macrocycle to the polymer support [65]. One-step synthesis based on alkyne metathesis was investigated by Bunz to furnish derivatives of 86 (n = 6), albeit in low yields [66]. A comprehensive survey regarding the synthetic strategy for construction of unsaturated macrocycles was reported recently by Schlüter [7]. Noncovalent template-directed, size-selective synthesis of porphyrin-containing metacyclophynes such as 89 and 90 has been developed by Saunders using coordination of pyridine derivatives of appropriate size and geometry to metalloporphyrin unit of the substrates [67]. This method was employed to prepare even larger porphyrin macrocycles such as the 108-membered 91 [68] and the 144-membered 92 [69], the largest shape-persistent macrocycle so far known. On the other hand, covalent template-directed method was employed by Höger et al. for the synthesis of ethynylene-butadiynylene macrocycles such as 108 a described later, giving the desired macrocycle more selectively than the macrocyclization without using a template [70]. A new method for oxidative coupling of a terminal acetylene was developed by Bäuerle based on efficient formation of a self-assembled platinum intermediate 93, which then furnished butadiyne-bridged terthiophenophyne 94 by oxidative elimination of the metal (Scheme 1.6) [71]. Highly strained small metacyclophynes are not accessible by these coupling reactions. Thus phenylacetylene trimer 95 and tetramer 96 a–b were prepared by bromination–dehydrobromination sequences of the corresponding cyclophenes, which were obtained by using the McMurry reaction [72]. This method was applied to the synthesis of twisted biphenyl-based cyclophanediynes 97 a–b [73]. Xray structural analysis of 95, 96 a and 97 b revealed that the triple bond of the former was deformed by 21.48, while the largest distortion of the latter two was only 12.38 and 9.58, respectively. Other methods for the synthesis of metacyclophynes include the McMurry coupling for dienetetrayne 98 [74] and the Williamson ether synthesis for oxygen- or sulfur-bridged compounds 99 a and 99 b [75]. Moore and coworkers synthesized acetylene-bridged [26]metacyclophynes 86 having substituents at the periphery of the desired benzene ring and developed pioneering works on the properties derived from their association by weak noncovalent interactions [1]. Namely, self-association behavior of 100 a–f was investigated in both apolar (chloroform) and polar solvents such as acetone, acetonitrile, and THF by 1H NMR spectroscopy and vapor pressure osmomeric (VPO) analyses [76]. In chloroform, compounds 100 a–d self-associate to form dimeric aggregate caused by a p–p stacking interaction, while in polar solvents 100 d forms higher aggregates owing to solvophobic interactions. The peripheral substituents play crucial role in the association behavior in both apolar and polar solvents. In chloroform, the ester-substituted compound 100 a exhibits the stronger tendency to self-associate than the mixed ester–alkoxy hybrid derivatives 100 b–c, presum-

19

20

1 Cyclophynes

Fig. 1.15

1.3 Metacyclophynes and Related Systems

Scheme 1.6

ably because of favorable polar–p interactions in the former which bears only electron-withdrawing groups. Similarly, in polar solvents, ester 100 d aggregates much more strongly than the ethers 100 e–f; the reason for the substituent effect on the solvophobically driven aggregation is uncertain. The imine derivatives 101 also stacked in polar solvents to form aggregates, indicating that this group does not disturb solvophobically driven p–p stacking [77]. In acetone, 101 tends to form a dimer more strongly than higher aggregates, presumably because of electrostatic interactions between the imine groups. Yamaguchi et al. synthesized chiral ana-

Fig. 1.16

21

22

1 Cyclophynes

logs 102 incorporating enantiomerically pure chiral benzo[c]phenanthrene units and investigated the stereoselectivity in their self-association in solution [78]. Enantiomerically pure macrocycles aggregate more strongly than the corresponding racemic macrocycle and the M,M,M isomers aggregate more strongly than M,P,M isomer, indicating that the macrocycles differentiate between enantiomers and diastereomers. [26]Metacyclophynes 100 g–i bearing alkoxy substituents, however, form discoid nematic liquid crystalline phases in a relatively wide range, at temperatures higher than 120 8C [79]. In solid state, phenol derivative 100 j forms channels with diameter of about 9 Å, which are filled with solvent molecules (12 ethanol, 6 methanol, and 3 water), because of the two-dimensional hydrogen bonds [80]. Each layer of 100 j stacks in ABCABC sequence. On the basis of the surface pressure-area isotherm, it was deduced that amphiphilic macrocycles such as 100 k and 100 l with segregated hydrophilic and hydrophobic groups formed Langmuir–Blodgett

Fig. 1.17

1.3 Metacyclophynes and Related Systems

Fig. 1.18

(LB) layers adopting the edge-on orientation [81]. The layer formed from 100 k was transferred onto fused silica and Si(100) surfaces, forming a well-organized two-dimensional array with slightly tilted edge-on configuration. [26]Metacyclo100 m possessing interior methoxy groups was synthesized by Kawase and Oda and was shown to bind ammonium ions selectively, in spite of the large cavity relative to the ion [82]. X-ray structural analysis of 100 m indicated that the distance between the diagonal oxygen atoms was 8.1 Å. In the crystal, it forms a displaced sheet which stacks to form open channels with internal pores of 4.5 Å. By contrast, [24]metacyclophyne 96 b with a smaller binding site binds a variety of alkali metal cations with considerably large association constants [72 c]. Association behavior of hexagonal butadiyne-bridged cyclophynes 104 a–b, “big brothers” of 100 a and 100 d, and its square analogs 103 a–b have been investigated in detail by Tobe et al. using 1H NMR and VPO in both apolar and polar solvents [83]. In polar solvents, these aggregate stronger than in chloroform due to the solvophobic interactions, with association constants for the formation of higher aggregates several times larger than those for dimerization, suggesting a nucleation mechanism. They also self-associate more strongly in aromatic solvents such as toluene and o-xylene than in chloroform. Moreover, 104 a–b tend to aggregate more readily than the corresponding acetylene-bridged cyclophynes 100 a and 100 d, owing to the withdrawal of the electron density from the aromatic rings by the butadiyne moieties. Cyano derivative 104 c and the pyridine analogs 105 and 106 were also prepared [84]. Interestingly, these form heteroaggregates with the

23

24

1 Cyclophynes

corresponding cyclophynes 103 a and 104 a due to dipole–dipole interactions, with distinct recognition of the ring size of their partners. The macrocycle 104 c, 105, and 106 bearing an interior binding group bind organic cations such as tropylium and guadinium ions to form both 1 : 1 and 2 : 1 (host : guest) complexes. The hybrids 107 a–b between 100 a and 104 a, prepared by Tour, aggregate in chloroform, albeit only weakly [85]. Since 107 b does not possess electron-withdrawing groups, the presence of hydrogen bonds between the hydroxy groups was invoked. Much larger macrocycles 108 a–f, which possess substituents not only at the corner phenyl group but also on the rotating phenyl groups placed between the corners, have been synthesized by Höger et al. [5, 86]. The characteristic feature of this system is that the amphiphilic substituents on the rotating rings can modify the properties of macrocycles in response to the external environment. Thus in the crystal of 108 b obtained from pyridine, two alkoxy groups are pointing outward and the cavity is self-occupied by the other two alkoxy groups as well as the solvent (6 pyridine molecules), two of which are hydrogen-bonded to the internal phenolic groups [87]. On the other hand, in the crystal obtained from THF, all alkoxy groups point outwards, forming distinct channels which are filled with the solvent (12 THF molecules), four of which are hydrogen bonded to the hydroxy groups of 108 b. The internal hydroxy groups of 108 b also act as the binding functionality in complexation with a tetraamine guest, which fits the cavity of 108 b to form maximum hydrogen bonds [88]. Interestingly, macrocycle 108 c bearing octadecyl groups on the rotating phenyl rings formed a nematic mesophase between 185–207 8C [89]. Since the related macrocycle 108 d having octadecyl groups on the corner did not form liquid crystals and, in the X-ray structure of 108 c, all alkyl chains self-occupied the cavity, it was deduced that such a structure, with flexible side groups pointing inwards, must be responsible for the formation of this novel thermotropic mesophase. Although most of the macrocycles of this type did not associate in solution, the heavily alkylated derivative 108 e formed solvophobically driven aggregates in dichloromethane/hexane mixture [90]. More strikingly, cyclophyne 108 f with two poly(styrene) chains of narrow dispersity, stacked with each other in cyclohexane to form long tubular aggregates up to 60 nm length [91]. With regard to the organization on surfaces, compound 108 e was reported to adsorb on the surface of highly oriented pyrolytic graphite (HOPG) in highly ordered face-on configuration, which was observed by STM [90]. Macrocycles 109 a–c having bipyridine units were prepared by Schlüter et al. [92]. X-ray structural analysis revealed that these form layered structures and channels filled mainly with solvent molecules and partly with the side chains. The stacking sequences (109 a AB, 109 b ABC, and 109 c ABCD pattern) differed and depend on the direction of the flexible side chain in the crystals. Ruthenium complexes of 109 a and 109 c were prepared, in which both metal atoms were located in the exocyclic position. Moreover, a number of terpyridine-based large macrocycles such as 110 a–c and 111 a–c were synthesized [93]. In analogy with 109 a–c, crystals of 110 a–c form layered structures and channels filled with solvent molecules and flexible side chains. Ordered monolayers of 110 c adsorbed on HOPG

1.3 Metacyclophynes and Related Systems

Fig. 1.19

were observed by STM although the resolution of the images was not high presumably because of low attraction of the substrate on the surface. With regard to the host–guest chemistry of metacyclophynes, Yoshida et al. prepared [24]metacyclophanetetrayne 112 containing two pyridine rings facing each other [94]. By complexation with SbCl5, the fluorescence of 112 was enhanced, while it did not bind SbCl3 and zinc halides. Oxygen-bridged macrocycle 113 formed a complex with C60 fullerene with a moderate binding constant [95]. In contrast, the exocyclic pyridine-containing macrocycles 114 a and 114 b were pre-

25

26

1 Cyclophynes

Fig. 1.20

pared with the aim of constructing supramolecular structures by chelating them to transition metals [96]. The related pyridinophanes 115 a–c formed complexes with ruthenium porphyrin [97]. The same macrocycle 115 c self-assembled with platinum(II) to form a double-decker complex, which in the crystal formed channels filled with two solvent molecules (ClCH2CH2Cl) [98]. From the same point of view, a phenanthrolin-based macrocycle 116 was prepared by Schmittel [99]. By self-assembly of two molecules of 116 with four copper(I) ions and two molecules of linear rod-like units, which also possessed two phenanthrolin units, a large structure called a nanobox with > 5000 Å3 void, containing about 240 molecules of acetone, was prepared. Redox active macrocycles 117 a–b were prepared and their oxidation potentials were determined [100]. Since both compounds exhibited three reversible oxidation

1.3 Metacyclophynes and Related Systems

Fig. 1.21

potentials, one of which was a 2-electron and one a 3-electron oxidations, respectively, these molecules can accommodate many holes with independent potentials. Potentially redox active cyclophynes having carbazole rings 118 [101] and oligothiophene moieties 119 a–b [102] were also prepared. Godt utilized the rigid shape of the meta phenylene-ethynylene-substituted benzene unit to prepare extremely large macrocycles such as 120 and catenane 121, which would not otherwise be easily accessible [103]. Some of the related large macrocycles exhibited thermotropic nematic and smectic mesophases.

27

28

1 Cyclophynes

Fig. 1.22

1.4

Paracyclophynes and 1,3,5-Bridged Cyclophynes

Since paracyclophynes adopt a cylindrical shape with curved p-conjugated systems, they have been studied in view of the noncovalent interactions of curved psystems and strain of the triple bonds, particularly in the small p-systems. In contrast to ortho- and metacyclophynes, since it is difficult to synthesize cyclophynes of this type by transition metal-mediated coupling reactions, a number of methodologies have been developed to construct the macrocyclic framework efficiently. [2n]Paracyclophynes (n = 6, 7, 8, 9) 122 a–d were prepared by Kawase and Oda by bromination/dehydrobromination of the corresponding olefinic paracyclophanes, which were in turn obtained by using the McMurry reaction [104]. As the ring size becomes smaller, notable downfield shifts of the sp carbon signals were observed in the 13C NMR spectra due to increasing strain. Since semiempirical mo-

1.4 Paracyclophynes and 1,3,5-Bridged Cyclophynes

Fig. 1.23

lecular orbital calculations predict that 122 a and 122 c should possess nanosize cavities with diameters of 13.1 and 17.4 Å, respectively, the formation of novel inclusion complexes with relatively large nonpolar guests was expected. Indeed, 122 a formed a 1 : 1 inclusion complex with hexamethylbenzene in which the guest molecule was situated at the center of the cavity tilted 98 from the horizontal plane of the macrocyclic ring, as revealed by X-ray analysis [105]. On the other hand, 122 c formed crystals including four molecules of toluene in the cavity which was more elliptical than that of 122 a. A pair of toluene molecules is located between two molecules of 122 c with short interatomic distances, indicating that they act as an adhesive by CH–p nteractions. Since the cavity of 122 a may fit C60 fullerene, 1 : 1 complex formation of 122 a with C60 was investigated [106]. Indeed, 122 a binds C60 strongly even in benzene with a binding constant of 1.6 ´ 104 L mol–1. X-ray crystal structural analysis of the inclusion complex of 122 a

29

30

1 Cyclophynes

with a C60 derivative revealed that the C60 cage was not deeply embedded in the cavity but floating on the bowl-shaped conformation of 122 a, because the cavity is a little too small for C60 to be fully embedded. Oxygen-bridged paracyclophyne 123 also binds C60 in toluene but with less strength [95]. Butadiyne-bridged [46]cyclophyne 124 was synthesized by the group of Tsuji using photochemical valence isomerization of the corresponding Dewar benzene valence isomer 125 [107]. Semiempirical molecular orbital calculations predict that it has a cylindrical cavity with a diameter of about 15 Å. Although the individual triple bonds were not much deformed (bending angle: about 98), compound 124 was air-sensitive and decomposed gradually within several days. Related metaparacyclophyne 126 and orthoparacyclophyne 127 were also successfully prepared by photochemical valence isomerization of the corresponding Dewar benzene isomers 128 and 129 [108]. While both diastereomers of 128 underwent smooth isomerization to 126, only the dl-isomer of 129 was converted into 127 and meso-129 decomposed on photolysis. In view of the lability of 124, hexatriyne-bridged [63]paracyclophyne 130 would not be stable enough for isolation. Accordingly, its formation was detected by la-

Fig. 1.24

1.4 Paracyclophynes and 1,3,5-Bridged Cyclophynes

ser-desorption time-of-flight mass spectroscopy (LDTOF MS) of its precursor 131 having propellane units by [2+2] cycloreversion of the cyclobutene rings [109]. Conversion of the ions of 130 into the carbon cluster C36 has been investigated in connection with the related study for paracyclophanepolyynes 136 a–b described below. Cyclophynes of [n.n]paracyclophane type would become more reactive as the number of triple bonds in the bridge increases, because of the enhanced reactivity of conjugated polyynes and of the bond angle strain. [6.6]Paracyclophanetetrayne 132, prepared by novel dimerization of a quinodimethane type intermediate, possesses relatively strained triple bonds with bending angles of 8–118 but it is stable enough for full characterization [110]. Dithia[7.7]cyclophanetetrayne 133 is much less strained [75 b]. On the other hand, fully unsaturated [8.8]paracyclopha-

Fig. 1.25

31

32

1 Cyclophynes

neoctayne 134 eluded isolation in oxidative decomplexation of its precursor, the cobalt complex 135 [111]. The formation of the higher analog, [12.12]paracyclophanedodecayne 136 a, was only indicated in the negative mode LDTOF MS of its precursor 137 a, from which stepwise loss of indan fragments took place by [2+2] cycloreversion [112]. Interestingly, the corresponding chloro derivative 136 b, generated similarly from 137 b, lost chlorine atoms to form ultimately the C36 anion, a carbon cluster attracting particular interest. These observations suggest possible use of reactive polyynes for size-selective, and hopefully geometry-selective, formation of carbon clusters in connection with the formation of C60 from highly unsaturated 1,3,5-bridged cyclophynes described below, even though the structure of the above C36 anion has not yet been confirmed. To construct the three-dimensional structure of 1,3,5-bridged cyclophynes, the length of the bridge and proper choice of precursor turned out to be critical owing to competing intra- versus intermolecular reactions. For example, while trithia[7.7.7](1,3,5)cyclophanehexayne 138 was obtained in a good yield by intramolecular cyclization of dimeric precursor 139, attempted coupling from monomeric units 140 and 141 failed (Scheme 1.7) [113]. Similarly, Cu(II)-mediated oxidative coupling of tris(ethynylphenyl) compounds 142 and 144 afforded highly strained metacyclophynes 143 [114] and 145 [115], respectively, by intramolecular coupling, rather than giving the respective cage-shaped dimers (Scheme 1.8). On the other hand, large three-dimensional macrocycles were readily obtained by oxidative dimerization of the corresponding monomer units. The first member of this class, [16.16.16](1,3,5)cyclophanehexa-eneoctadecayne 146 was synthesized

Fig. 1.26

1.4 Paracyclophynes and 1,3,5-Bridged Cyclophynes

Scheme 1.7

Scheme 1.8

by Rubin et al. [116]. Interestingly, in the ion cyclotron resonance mass spectrum of 146, dehydrogenation down to C60H–14 formed by the loss of four hydrogen atoms was observed. Moreover, Rubin and Tobe prepared independently the precursors 147 [117] and 148 a–b [118] to generate C60H6 (149 a) or C60Cl6 (149 b), which would form C60 fullerene efficiently by cyclization of reactive polyyne chain with loss of six hydrogen or chlorine atoms. Indeed, in the LDTOF MS of 147 and 148 a–b, not only the formation of 149 a–b by extrusion of carbon monoxide and indan, respectively, but also their further transformation into C60 ion were observed, indicating a possible method for size- and shape-selective synthesis of carbon clusters of the fullerene family from highly unsaturated cage-like cyclophynes (Scheme 1.9). This method was also applied to the generation of diazafullerene C58N2, albeit in low efficiency of dehydrogenation from the precursor 150 [119]

33

34

1 Cyclophynes

Fig. 1.27

Scheme 1.9

1.5 Concluding Remarks

Fig. 1.28

and the formation of C78H18 (151), a possible precursor to higher fullerene like C78 [120]. Extremely large, three-dimensional, phenylacetylene macrocycles 152 and 153 were successfully prepared by Moore et al. [121]. The final step of the synthesis proceeded in high yields were intramolecular Sonogashira coupling of bis-seco intermediates, which were manipulated using the same masking/protention protocol employed for the synthesis of planar macrocycles such as 88.

1.5

Concluding Remarks

In connection with the concurrent growth of chemistry of carbon-rich materials with opto-electronic functions, triggered by the discovery of fullerenes and nanotubes, and the emerging supramolecular chemistry of nano-size materials, enormous progress, which is much more than that envisaged as a revival of annulene chemistry, has been achieved during the last decade. The unique structural and electronic properties of cyclophynes, and their facility for manipulation, ensure that their potential to provide new materials will continue.

35

36

1 Cyclophynes

1.6

Acknowledgement

This work was supported by CREST, Japan Science and Technology Agency (JST).

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1999, 5, 1728–1733; (b) A. Godt, S. Duda, Ö. Ünsal, J. Thiel, A. Härter, M. Roos, C. Tschierske, S. Diele, Chem. Eur. J. 2002, 8, 5094–5106; (c) M. R. Shah, S. Duda, B. Müller, A. Godt, A. Malik, J. Am. Chem. Soc. 2003, 125, 5408–5414. (a) T. Kawase, H. R. Darabi, M. Oda, Angew. Chem. 1996, 108, 2803–2805; Angew. Chem. Int. Ed. Engl. 1996, 35, 2664–2666; (b) T. Kawase, N. Ueda, K. Tanaka, Y. Seirai, M. Oda, Tetrahedron Lett. 2001, 42, 5509–5511. T. Kawase, Y. Seirai, H. R. Darabi, M. Oda, Y. Sarakai, K. Tashiro, Angew. Chem. 2003, 115, 1659–1662; Angew. Chem. Int. Ed. 2003, 42, 1621–1624. T. Kawase, K. Tanaka, N. Fujiwara, H. R. Darabi, M. Oda, Angew. Chem. 2003, 115, 1662–1666; Angew. Chem. Int. Ed. 2003, 42, 1624–1628. M. Ohkita, K. Ando, T. Suzuki, T. Tsuji, Chem. Commun. 2001, 2570–2571. (a) M. Ohkita, K. Ando, K. Yamamoto, T. Suzuki, T. Tsuji, Chem. Commun. 2000, 83–84; (b) M. Ohkita, K. Ando, T. Suzuki, T. Tsuji, J. Org. Chem. 2000, 65, 4385–4390. Y. Tobe, T. Morinaka, M. Sonoda, unpublished results. H. Hopf, P. G. Jones, P. Bubenitschek, C. Werner, Angew. Chem. 1995, 107, 2592–2594; Angew. Chem. Int. Ed. Engl. 1995, 34, 2367–2368. M. M. Haley, B. L. Langsdorf, Chem. Commun. 1997, 1121–1122.

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2

Hetera (Cyclo-)phanes Fritz Vögtle, Gregor Pawlitzki, and Uwe Hahn

2.1

Introduction 2.1.1

Selection of Topics Presented

In this survey we first sum up achievements made in the author’s group during the past few years in the field of rigid cyclophane propellers. These comprise chiral [2.2]metacyclophanes, the chirality of which is mostly due to a heteroatom in the bridge part of the molecule. “Tailoring” and “tuning” of the chirality of cyclophanes was successfully approached in this way. [n]Para- and [n]metacyclophanes (n = bridge length) and phanes containing characteristic aliphatic parts, such as adamantane (“aliphanes”, see below), are also described. Macrobi- and tri-cyclic phanes as well as larger ring phanes up to gigantocyclic ones are likewise compared. Catenanes and rotaxanes of various types including the amide-based cyclophane family have been made accessible in preparative yields by new template syntheses. New phane-type molecular knots with amide bridging units were developed exhibiting topological chirality. No doubt the emergence and rational design and synthesis of new (cyclo-)phane scaffolds – and the easier and quicker availability of their building blocks – during the past few years has accelerated and facilitated the development of new supramolecular architectures. It seems difficult in the framework of such a volume to supplement the author’s own research results with all the other international work on hetera(cyclo-)phanes, with the same rigour. However, as we wanted to set our own results in the context of other’s work, we decided to present other contributions in the form of tables of the various families of characteristic compound structures with corresponding references indicated there. In such a way, the reader gains a fascinating graphical survey of what has been achieved during the past years. As (cyclo-)phanes “live” with their formulae which immediately reveal ring size, as well as their hetero-, hetera-, carbo-, carba-character, the reader can access the literature of compound families he is interested in.

Modern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

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Much progress has been made recently particularly in the development of metalla and supramolecular phanes, where some formulae given in the last part of this contribution also disclose the principles and the possibilities for future. 2.1.2

Definitions

Heteraphanes are (cyclic) molecules that are composed of one (or more) arene unit(s) (“aromatic” ring like benzene, pyridine, thiophene) that is bridged by an aliphatic unit (of bridge length 0–? atoms) in which at least one atom is a heteroatom [1–3]. Fig. 2.1 shows examples of a heteraphane, a heterophane and a mixed hetero/heteraphane in order to demonstrate the difference. “Phane” is used as the stem name for such ring compounds. In Fig. 2.2 we use the prefix “cyclo” (or “benzeno”) if a benzene ring is the arene core. “Carbaphane” is used for those (carbo- or hetero-)phanes with bridges lacking heteroatoms (Fig. 2.3). Some other definitions have been formed and accepted during the recent years: in “aliphanes” [1], the arene part of the (areno-)phanes is replaced by a characteristic aliphatic ring. Fig. 2.4 shows characteristic examples. In the following, we will exclude the more trivially ortho-bridged benzenes, even if they can be viewed as “orthocyclophanes” [1]. Whereas overviews on cyclophanes and heterophanes have already been published, heteraphanes to our knowledge seem never to have been collected and compared [4].

a Thiophenophane a Oxaphane a [n+3]Phane

Concrete phane name: 2-Thia[n+2](1,3)benzenophane

Fig. 2.1

Some “heteraphanes” and related phane-species

2.1 Introduction

Fig. 2.2

Some heterophanes

43

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2 Hetera (Cyclo-)phanes

Fig. 2.2

(cont.)

2.1 Introduction

Some carbaphanes (benzenophanes, cyclophanes) bearing no heteroatom in the bridges. At the same time these compounds are carbophanes (no heteroatom in the arene core)

Fig. 2.3

45

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2 Hetera (Cyclo-)phanes

Fig. 2.3

(cont.)

2.1 Introduction

Fig. 2.3

(cont.)

Fig. 2.4

Some “aliphanes”

47

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2 Hetera (Cyclo-)phanes

Fig. 2.4

(cont.)

2.1 Introduction

2.1.3

Why Conduct a Survey on Heteraphanes?

1) It is difficult to find these scattered compounds in the literature. Many are not named as phanes and even less characterized as heteraphanes. 2) There is a large variety of compounds described in different contexts. Unless they are collected in one article, they cannot be compared properly. 3) The synthetic methods leading to heteraphanes are usually C–X-bond formations (X = heteroatom), which means that there is a rich knowledge available in carrying through and optimizing macrocyclization reactions of this type [5]. 4) Many crown ethers, cryptands and macrocyclic ligand systems related to natural products [1] belong to this family of phane compounds (Fig. 2.5). 5) The chemistry of “metallaphanes” as well as of “supramolecular phanes” has recently developed impressively quickly. In “metallaphanes” (list see below, Fig. 2.18), a metal center forms one or several of the bridge’s hetero atoms. Also by means of hydrogen bond formation, macrocyclization can be done through supramolecular forces, which leads to “supramolecular phanes” (list see below, Fig. 2.19). 6) Wheels for rotaxanes and macrocyclic rings for catenanes and knots mainly consist of heteraphanes (and heterophanes), as their template syntheses rely on heteroatoms in the bridges (or/and in the core) [5–7]. 7) Heteroatoms in the bridges often lead to lower symmetry of the molecules and that is why they can be chiral provided that conformational rigidity/mobility of the molecule is properly designed. 8) Solubility can be influenced to some extent by implementation of heteroatoms. 9) ”Nanocycles” of nm-size, “gigantocycles” (³ 50) and “ultracycles” (> 100 ring members) [8] can often be made easier than defined macrocyclic hydrocarbons of same ring member number (Fig. 2.6). 10) It is impressive how manifold the research areas are, in the context of which heteraphanes have been synthesized. To sum up, even if heteraphanes may be less eye-catching than the corresponding hydrocarbons (like e.g. “Kekuléne” [1]) or heterophanes (e.g. “sexipyridine” [1]) they offer advantages that justify putting them together here for the first time as a family of compounds. In such a way, they can help to design new phane compounds and help to easier find new synthetic strategies for such macrocycles. Of course, in this rather short article not every synthesized heteraphane can be put forward; this contribution therefore contains a selection of newer and more recent work around the years 2000–2002 and in such a way should help to find literature that is otherwise difficult to scan.

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MeO

Fig. 2.5

A selection of heteraphanes related to natural products [1].

2.2 Heteraphanes

Fig. 2.5

(cont.)

Fig. 2.6

A representative of giganto-/ultracyclic heteraphane [8].

2.2

Heteraphanes 2.2.1

Planar Chiral and Helical Chiral Phanes 2.2.1.1 Design of Phanes with Planar and Helical Chirality

Helical molecules are well known in nucleic acid, peptide, and sugar chemistry. The different interaction of left- and right-handed screw-shaped molecules with left- and right-circularly polarized light, respectively, is a fundamental process that can be studied by electronic circular dichroism (CD) measurements. An advantage of small helical molecules compared with biological ones is that their usually rigid structure (cf. hexahelicene) permits more precise calculations and conclusions compared to flexible aliphatic molecules containing stereogenic centers [66, 67].

51

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2 Hetera (Cyclo-)phanes

The design of new planar chiral or helical chiral molecules with property differences that although small can be tailored, is a permanent challenge in organic chemistry. The spectroscopic and chiroptic examination of a series of related molecules should lead to a deeper knowledge about structure and strain and the CD and electronic properties. Structure–chiroptics relationships are important for the qualitative and quantitative understanding of chirality and the interaction of circularly polarized light with chiral molecules. The examination of model substances may in future allow the prediction of (chir-)optical properties and the determination of the absolute configuration. As far as synthesis is concerned, such knowledge allows the design of novel helical molecules with tailored chiral properties. The formulae 62–66 (Fig. 2.7) show our concept to reduce the size and complexity of screw molecules while preserving the propeller sense. By replacing benzene rings through aliphatic bridges one finally ends up with the dinucleic planar chiral [2.2]metacyclophane 65 skeleton and with the mononucleic [n]meta- or [n]paracyclophanes 66. We therefore used the rigid [2.2]metacyclophane skeleton (65, Fig. 2.7), which leads to small planar chiral compounds by suitable substitution and to small helical chiral molecules by insertion of heteroatoms into the cyclophane bridges (see 67 b, 68–71, Fig. 2.8), in such a way ending up with hetera [2.2]phanes. An advantage of this choice is the limited number of atoms, that made a reliable calculation of the CD spectra possible, and the good solubility and high crystallization tendency of [2.2]metacyclophanes allowing X-ray crystallographic examination of torsion effects and absolute configurations.

Evolution of more and more simple helical and planar chiral molecules starting from the quaterphenylophane 62 by continuous formal distraction of benzene rings; these molecules are chiral without having stereogenic centers (if n in 66 is small) [67]

Fig. 2.7

2.2 Heteraphanes

2.2.1.2 Hetera [2.2]Metacyclophanes

Introduction of heteroatoms into the [2.2]metacyclophane’s bridges (Fig. 2.8), thus leading to symmetry breaking and to heteraphanes, allows a controlled increase of the twisting of the connected benzene rings against each other. In addition the internal deformation of the two-bladed propellers should be the more pronounced the closer the two benzene rings are pressed together by short cyclophane bridges -CH2-X- and -CH2-Y- in 67 (Fig. 2.8). Therefore we synthesized a number of monohetera- and dihetera [2.2]metacyclophanes [68] in which the carbon–heteroatom distance determines the molecular strain. Fig. 2.8 shows [2.2]metacyclophanes 68–70 in the order of increasing strain. The C-X bond length decreases from X=S to X=O, so that the 1-oxa [2.2]metacyclophane 70 [69] is the sterically most strained monohetera [2.2]metacyclophane with the highest boat-shaped deformation in the benzene rings. The thiazacyclophanes of type 71 are comparatively easy to synthesize in one (cyclization) step [68], so that we were able to prepare a range of differently substituted representatives that allowed us to study the influence of intra-annular substituents R on the CD and other properties [70].

Fig. 2.8

Two-wing propeller molecules

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2 Hetera (Cyclo-)phanes

The chirality-inducing step is the formal substitution of one or more carbon atoms in the bridge of the [2.2]metacyclophane hydrocarbon 67 b to yield the heterocycles 67 a (X =/ Y, Fig. 2.8). The length of the bridges and consequently helicity and strain can be influenced within wide limits. The first member of the [2.2]metacyclophane family to be synthesized was the achiral hydrocarbon 67 b itself [71]; the first molecule with heteroatoms in the bridge was 1,10-dithia [2.2]metacyclophane 67 c [72]. 1-Thia- 68 and 1-oxa [2.2]metacyclophane 70 were prepared many years later [69] by intramolecular ring closure methods. Considering that these cyclophanes are ring-strained, the syntheses of 67 c and 71 and most cyclophanes mentioned in the following were carried out under high-dilution conditions [73], by the use of selected bases and by taking advantage of the cesium effect [74]. All chiral representatives 68–71 could be separated into their enantiomers using chiral column materials. Comparisons of experimental and theoretical CD spectra allowed the assignment of the absolute configuration of 68 and 71 [75]. A slight shortening of the cyclophane bridges was also achieved by the synthesis of the N-tosylazacyclophane 69 b [76]. In this case the tosyl group affected the chiroptical studies adversely, caused by the additional (tosyl) chromophore. Subsequent removal of the tosyl group in order to yield the free amine 69 a failed because of special reactivity due to the clamped molecule’s geometry and strain. This problem was circumvented by using a different protection-group strategy. Introduction of the N-activating trifluoroacetyl group allowed cyclization and subsequent cleavage of the activating group and yielded the free amine 69 a [77].

The N-activating effect of the trifluoroacetyl group also allowed for the first time two-component cyclizations of suitable building blocks yielding 1,10-diazacyclophane 72 a [78] and 1-thia-10-aza [2.2]metacyclophanes 71 a, b. The 1,10-diazacyclophane 72 b is, according to calculations and NMR studies, one of the most strained compounds in the [2.2]metacyclophane series. The close proximity of the arene rings is indicated by a strongly highfield-shifted inner proton signal [d(Hi) = 3.81] compared to the [2.2]metacyclophane hydrocarbon 67 b [d(Hi) = 4.25]. The even higher strained (because the C-O is shorter than the C-N bond length) 1-oxa-10-aza [2.2]metacyclophane 73 a was detected by mass spectrometry after comparable synthetic procedures, but isolation has failed so far. We tried to improve the synthetic processes for such highly strained molecules (repulsive steric

2.2 Heteraphanes

Hetera[2.2]metacyclophanes: representatives 73 a–d are helical chiral. Dioxa[2.2]metacyclophane does not yet exist

Fig. 2.9

Fig. 2.10 Planar chiral carba[2.2]metacyclophanes

interactions between the intra-annular positions 8 and 16, see Fig. 2.10) combined with new N-activating group strategies. Nevertheless, all efforts to synthesize the highest strained 1,10-dioxa [2.2]metacyclophane 74 in preparative amounts failed.

2.2.1.3 Planar Chiral [2.2]Metacyclophanes

[2.2]Metacyclophanes 65, substituted in one or more of the positions 4, 14 or 6, 12 (cf. Fig. 2.10) are planar chiral and were used by Lehner, Schlögl, Ugi, Ruch, and Derflinger for studies towards quantitative correlations with regard to chirality functions [79]. Thus, 75 b should exhibit a double Cotton effect intensity compared to 65 b, provided that R is the same. Spectroscopic and theoretical results were published in detail [80]. Attempts to introduce substituents into the carbon skeleton of diaza [2.2]metacyclophanes 72 to render it chiral were unsuccessful. Because of the higher steric strain the synthetic yields are lower than for 71 a [78].

55

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2 Hetera (Cyclo-)phanes

Fig. 2.11 The achiral 1,10-dihetera[2.2]metacyclophanes 67 and 72

2.2.1.4 Planar Chiral Hetera [n]Para- and Hetera [n]Metacyclophanes

We synthesized a number of dithiabridged paracyclophanes [81] with aliphatic and partly unsaturated bridges. These were obtained under dilution conditions by the use of suitably functionalized cyclization substrates (dibromides [82], dithiols [83]). The introduction of unsaturated elements (76 a, b) enabled the examination of the influence of etheno and ethyno bridges towards the deformation of the aromatic parts and chiroptical properties. NMR- and X-ray crystallographic studies revealed C2-symmetry of the dithia[8]paracyclophanes 76 a, d and C1-symmetry of the oxa[7]paracyclophane 77 a and its carbocyclic analog 77 b in the solid state and in solution.

These cyclophanes were separated into their enantiomers and showed similar CD spectra with typical Cotton effects for electron transitions of the aromatic rings with significant contributions of the sulfur atoms. According to calculations the first oxa[7]paracyclophane 77 a [84] showed a remarkably short oxygen–benzene distance compared with the carbocyclic analog 77 b [85] which is indicated by a strong charge transfer band in the CD spectrum (see also Chapter 12). The chiral cyclophane 77 a was synthesized [86] via the dithia-route and sulfone pyrolysis [87] developed earlier by us.

2.2 Heteraphanes

The pathway to dithia[n]metacyclophanes 78 by thiol/bromide cyclizations [86] and subsequent sulfone pyrolysis allowed the first systematic studies of the previously poorly examined planar chiral [n]metacyclophanes. The motion of the cyclophane bridges was examined by dynamic NMR methods. It turned out that the cyclophane bridges undergo rather complex pseudorotation motions which can be frozen at low temperatures whereas a flip-process [87] is prevented by the intra-annular substituents. The distances between bridge and benzene ring obtained from Xray crystal structures correlate well with the observed NMR shifts [78 b].

2.2.1.5 Dioxa [2.2]Phanes and Oxaza [2.2]Phanes

These types of very narrowly bridged and therefore highly strained [2.2]cyclophanes were addressed several times through the past 20 years, but could so far not be synthesized in preparative amounts [78 a]. This goal remains a challenge for future.

2.2.1.6 Enantiomer Separations

The separation of enantiomers was carried out by HPLC on cellulose-tris(3,5-dimethylphenylcarbamate) columns on analytical scale, and repeated several times to yield enough material for CD measurements. Successful use of Okamoto’s separation resins [88] led to base-line separation of nearly all the chiral cyclophanes described above. For separation on a preparative scale we used semipreparative columns to get up to gram amounts of pure enantiomers for further examinations like gas phase CD measurements. Calculations of CD spectra with the AM1/MRD-CI and DFT/RPA methods were carried out on 1-thia- 68 and 1-oxa [2.2]metacyclophane 70 [89]. The spectra of

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both compounds are remarkably similar showing three lowest lying negative bands followed by an intense positive peak at 200 nm and a negative band around 180 nm. These experimental features are well reproduced by the calculations. The corresponding thia [2.2]metacyclophane 68 shows a higher calculated CD intensity (by a factor of two) than the oxa-cyclophane 70 due to the stronger deviation of the geometry from C2h-symmetry.

Calculations of the CD spectra of [n]cyclophanes on first sight seem to be more difficult due to the inherent flexibility of the relatively long aliphatic chains (n ³ 6). In favorable cases, however the conformers which result from chain rotation are identical, as shown for the recently resynthesized 9,12-dimethyl-4-oxa[7]paracyclophane 77 a [86, 90] so that only one conformation has to be considered. Shortening of the aliphatic bridge in [n]paracyclophanes results in stronger deformations of the benzene ring towards a boat-shaped conformation. Strong interactions of the energetically high-lying lone-pair orbital at the oxygen atom with benzene ring orbitals can be expected from geometrical considerations. In the case of dithia [n]metacyclophanes 78 c, d [86 a] two energetically close lying conformers for each enantiomer must be taken into account to explain the experimental CD spectra. The best AM1/MRD-CI CD data were obtained for a 70 : 30% mixture of two conformers of 8,12-dimethyl-2,5-dithia[6]metacyclophane. This value is in good agreement with the ratio 70% derived from NMR data. Gas phase CD-measurements [91] and the extension of these measurements into the VUV i.e. to higher excited electronic states proved to be important for a better understanding of circular dichroism and for a reliable comparison with theoretical calculations.

2.2.1.7 Strongly Helical Heteraphanes

Owing to the elongated screw shape, the heteracyclophanes 83, 85 and the naphthalenophane 84 are expected to reveal high chirality comparable to the helicenes. Indeed, elongation of the screw (from biphenylo- to terphenylophanes) leads to an increased optical rotation [92].

2.2 Heteraphanes

This new helix type even surpasses some helicenes known for high rotatory strength and molar rotation. 2.2.2

Catenanes, Rotaxanes, and Knotanes of the Heteraphane Type 2.2.2.1 Template Synthesis of Rotaxanes Using Cyclophane Wheels

Some years ago, we reported on an efficient strategy with near to quantitative yields for the synthesis of a phenyl ether [2]rotaxane 90 based on the action of a preorganized supramolecular nucleophile 88, which is formed from the molecular

Fig. 2.12 Synthesis of ether rotaxanes with ether axles by the trapping method. The wheel is a heteraphane and it is only due to the hydrogen bonding abilities of its heteroatom that it is able to form the concave template for the trapping (threading) of the axle part

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recognition of a phenolate anion stopper 86 by the tetralactam wheel 87 [93] which is a hetera-cyclophane. We termed this synthetic step “trapping” because the nucleophilic blocking group is caught by the wheel like a mouse in a trap. This supramolecular nucleophile 88 can now generate a rotaxane by an SN reaction with an electrophilic axle centre piece 89 as shown in Fig. 2.12. We have demonstrated that a variety of other anionic nucleophiles can be used as axle building blocks alternatively. New families of rotaxanes were synthesized upon formation of acetal, thioacetal, ester, thioester, sulfide, N-tosylamide, and phosphate bonds in their axles. The yields are high (23–81%) which underlines the versatility of this synthetic interlocking concept which makes use of the heteraphane 87 acting as concave template for anions [93].

2.2.2.2 Higher Order [n]Rotaxanes via Non-ionic Template Effect

We also developed a method for the synthesis of monodisperse higher order rotaxanes of the amide type based advantageously on an iterative reaction sequence [94]. Up to five heteraphane-type tetralactam wheels (87) could be threaded on one axle yielding the [6]rotaxane 93 (wheels and stoppers like in Fig. 2.12). To build up higher order rotaxanes in this way, semiaxles have to be synthesized that contain more amide groups, one for each wheel to be bound and then threaded. Therefore we elongated a bulky stopper group in a repetitive reaction sequence that led to the diamide 91, which is a semiaxle. Reaction of bis-wheeled 91 with the diacid dichloride 92 enables to bind one more wheel 87 on the axle on account of the additional amide group. Condensation with the second bis-wheeled 91 leads to the penta-wheeled [6]rotaxane 93 carrying five heteraphane units 87 topologically bound.

Fig. 2.13 Synthesis of oligo[n]rotaxanes 93 with heteracyclophane

wheels (87 in Fig. 2.12)

2.2 Heteraphanes

2.2.2.3 Combination of Anionic and Non-ionic Template

Applying the trapping (anionic template) synthesis in combination with the threading method (non-ionic template) for rotaxanes, we reacted an axle precursor with the phenolate 86 (Fig. 2.12) in presence of the heteraphane wheels 87 [95]. Besides small amounts of the free axle and the corresponding [2]rotaxanes (up to 10%) the [3]rotaxanes 94–96 were obtained in yields up to 29%. In all cases the isolation of the [3]rotaxanes 94–96 could easily be carried out by column chromatography.

2.2.2.4 Molecular Knots and Similar Macrocycles of the Heteraphane Type

A “molecular eight” type topologically chiral molecule 97 was described [96]. [1]Rotaxanes of the type 98 were obtained, too, which are also topologically chiral [97]. An analogous reaction of a double sulfonamide-substituted catenane [98] yielded “pretzelanes” [98]. A most simple synthesis of a molecular trefoil knot of the heteraphane type was achieved, in up to 20% yield, which proceeds under self-organization without any added auxiliary component [99] (Fig. 2.16).

Fig. 2.14 “Supramolecular eight” 97

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Fig. 2.15 Sulfonamide-based [1]rotaxanes 98

As byproducts monocyclic heteraphanes like 101, 102 and in some cases higher oligomers including catenanes have been isolated as well [99]. 2.2.3

Further Heteraphanes, Metallaphanes and Supramolecular Phanes

In order to allow a more general view and comparison of heteraphane structures, more recent phanes with heteroatoms in the bridges are put together in the following Figs 2.17 – 2.19. These comprise usual heteroatoms like oxygen, nitrogen, but also boron, metal-carbonyl-complexed multiple bonds (Fig. 2.17), but also metal atoms (Fig. 2.18) and finally non-covalently connected bridges (Fig. 2.19).

2.3

Conclusions

This survey of cyclophanes and phanes (heteraphanes) substituted by heteroatoms in the bridge sets them in the context of aliphanes, heterophanes, metallo- and supramolecular phanes and certainly shows that a surprising variety of fascinating macrocyclic structures and even architectures have been synthesized and investigated during the past few years. All in all, this is a chapter of heteromacrocyclic chemistry, even if the heterophanes, the pyridinophanes, thiophenophanes etc. had to be more or less neglected. Heteraphanes are interesting because their preparation in many cases is easier than that of the corresponding hydrocarbons. On the other hand, hydrocarbons

2.3 Conclusions

Fig. 2.16 Synthesis of trefoil knot 103, a heteracyclic paracyclo(2,6)pyridinophane

cannot easily offer hydrogen bonding or p–p interactions or charges for host– guest interactions, whereas the heteraphanes can form supramolecular complexes and therewith can be considered as supramolecular phanes. The synthetic methods used to form C–X bonds (X = heteroatom) are additionally valuable. It is not surprising that gigantocyclic compounds, molecular knots, catenanes, rotaxanes have been tried with C–heteroatom connection rather than C–C-bond connection and so the chemistry of molecular ribbons and tubes has developed, too. The implementation of heteroatoms in the bridges of cyclophanes and phanes leads to many more possibilities than with the hydrocarbons, not only for intramolecular interactions, but also for host–guest interactions and with regard to symmetry breaking leading to chirality.

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Fig. 2.17 Some selected further heteraphanes from more recent literature

2.3 Conclusions

Fig. 2.17 (cont.)

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Fig. 2.17 (cont.)

2.3 Conclusions

Fig. 2.17 (cont.)

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Fig. 2.17 (cont.)

2.3 Conclusions

Fig. 2.18 Some selected metalla-

phanes

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Fig. 2.18 (cont.)

2.3 Conclusions

Fig. 2.18 (cont.)

As this area of research will grow with higher speed during the next years due to better synthetic and analytical methods, it will increase in importance and produce new complicated structures beyond molecular knots and beyond molecular tubes, which are of interest for applications. For the first time, the term supramolecular phanes is used here to collect and put together this new family of compounds under this topic. The fact that heteroatom containing macrocycles have at least presently some advantages compared to carbocyclic compounds, is demonstrated easily by the existence of heterocyclic knot molecules of the Sauvage and Vögtle type and nucleic acid type. So far, no carbocyclic knot molecule is known at all as the synthesis cannot be easily done via template synthesis. The authors hope that this collection of heteraphanes leads the reader to new ideas and the design of novel skeletons with implemented heteroatoms and also to new carbocyclic architectures.

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Fig. 2.19 Selected su-

pramolecular phanes

2.3 Conclusions

Fig. 2.19 (cont.)

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2.4

Acknowledgement

We are grateful to CERC3 (“Topological Stereochemistry, Topological Chirality”) and for the continuing collaboration in connection with the joint project entitled, “Topological chiral and cycloenantiomeric catenanes, rotaxanes and pretzelanes” (cooperation partners: Prof. Dr. A. v. Zelewsky (Fribourg), Prof. Dr. J.-P. Sauvage (Strasbourg), Dr. A. M. Brouwer (Amsterdam) including our group (F. Schelhase, R. Henkel).

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81

3

Highly Strained Cyclophanes Takashi Tsuji

3.1

Introduction

When bridged with a side chain at the meta or para positions, the planarity-preferring benzene ring is forced to bend into a boat form, unless the bridging chain is sufficiently long. In the past 30 years, research on the preparation of bridged benzene derivatives, that is, metacyclophanes and paracyclophanes, with ever shorter bridges has made remarkable progress, driven by the interest in the properties of strained molecules as well as the challenges inherent in their synthesis and also in the pursuit of improved understanding of aromaticity [1, 2]. In this review, recent developments in the chemistry of strained cyclophanes including pyrenophanes are described. The reactivity of strained [n]meta- and [n]paracyclophanes (n £ 6) is greatly enhanced as the number of methylene groups in the bridging chain is decreased from six to five and then to four. Their enhanced reactivity is a consequence of the high steric strain present both in the bent benzene rings and in the distorted bridges, which is released in transition states upon reaction with a variety of reagents. Bending of benzene rings causes a rise of HOMO as well as a fall of LUMO in energy as a consequence of the torsion of p–bonds in the aromatic p–electron system. This also leads to activation of the benzene ring of strained cyclophane. The electron distribution in the benzene ring and the orbital coefficients of frontier orbitals are also perturbed. For the same bridge length a metacyclophane is less strained and, thus, significantly more stable in general than is its para analog.

3.2

[n]Metacyclophanes 3.2.1

Synthesis

As expected, the thermal stability of [n]metacyclophanes decreases with decreasing bridge length. Compared with shelf-stable [6]metacyclophanes 1 and the higher homologs, [5]metacyclophanes 2 exhibit markedly enhanced reactivity and the parModern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

82

3 Highly Strained Cyclophanes

Scheme 3.1

ent compound slowly polymerizes on standing at room temperature. Highly strained [4]metacyclophane 3 a has so far defied direct observation, but its generation as a fleeting intermediate has been demonstrated by interception reactions. Synthesis of 2,6-bridged p-nitrophenols 4 b, that is, substituted [n]metacyclophane derivatives (n = 6, 7, 9, 10 . . .), by base-catalyzed condensation of cycloalkanones with nitromalonaldehyde was reported as early as 1947 by Prelog et al. [3] (Scheme 3.1). Several useful routes to [6]metacyclophane and its derivatives have subsequently been devised [1]. They include (1) thermal rearrangement-aromatization of substituted [6.2.1]propellanes; (2) acid-catalyzed rearrangement of [6]paracyclophanes; (3) intramolecular diene-yne Diels-Alder reaction followed by dehydrogenation; and (4) cycloaddition of an m-xylylene diradical with 1,3-dienes. Of those methodologies, only the thermal rearrangement of propellanes has been successfully extended to the preparation of [5]metacyclophanes by Bickelhaupt et al., who developed a novel synthetic route which required relatively mild reaction conditions that sensitive [5]paracyclophanes could tolerate (Scheme 3.2). In a related approach, Reese et al. have accomplished the preparation of [5](1,3)naphthalenophane [4]. Condensation of cyclooctanone with nitromalonaldehyde by Prelog et al. did furnish a bridged compound, but the product was found to be 5 a (n = 5), a tautomer of substituted [5]metacyclophane 4 a (n = 5). Apparently, the relief of steric strain on going from 4 a to 5 a overcompensated the loss of aromatic stabilization energy. Bickelhaupt et al. found that, while treatment of syn-6 with t-BuOK in DMSO in an attempt to generate [4]metacyclophane 3 a only led to the formation of polymeric material, the corresponding reaction of anti-6 yielded 7, the Dewar isomer of 3 a (Scheme 3.3) [5]. Upon thermolysis at about 150 8C, 7 underwent rearrangement to give 3 a which was too unstable to be isolated, but instead was intercepted as Diels-Alder adducts as described later. Upon photolysis, however, 7 was quantitatively converted to the corresponding prismane, dampening the prospect of generating 3 a at low temperature [5 b].

Scheme 3.2

3.2 [n]Metacyclophanes

Scheme 3.3

3.2.2

Structures and Physical Properties

The most prominent geometrical feature of a strained metacyclophane is the outof-plane bending of the aromatic ring into an unsymmetrical boat conformation, represented by the projected deviation angles a and c (Scheme 3.4). The deformation of the aromatic ring is also recognized in the projected angle b of the benzylic carbon–carbon bonds, which reflects the degree of out-of-plane bending of the latter with respect to the aromatic ring and pyramidalization at the bridgehead carbon atoms. As expected, those deformation angles increase in the order of [4]- > [5]- > [6]metacyclophane (Tab. 3.1). Tab. 3.2 lists the strain energy (SE) evaluated for 1 a and 2 a using homodesmotic reactions and the results of their partitioning into the components, that is, the strain energies due to the distortion of benzene ring SE(C6H6), the distorted bridge SE(bridge), and the repulsive interactions between them SE(rep) [6]. The hexamethylene chain of 1 a resides at one side of the aromatic ring as illustrated in Scheme 3.4. Ring flip to the other side is slow at room temperature, but readily takes place at higher temperatures (DG{ = 17.4 kcal mol–1 at 76.5 8C). In 2 a, the bridge is too short to swing around to the other side. [6]Metacyclophanes un-

Scheme 3.4

Tab. 3.1 Deformation angles for strained [n]meta- and [n]paracyclophanes

Compound

Method

a (8)

b (8)

c (8)

(a + c)

(a + b)

1d 2d 3a 30 31 a 32 a 38 a

experimental experimental MNDO experimental SCF/DZ SCF/TZ2P B3LYP/6-31G*

19.4 26.8 40.6 19–21 23.7 29.7 28.0

39.7 48.0 46.1 18–21 28.6 38.0 46.4

8.4 12.0 12.0 – – – –

27.8 38.8 52.6 – – – –

– – – 39–40 52.3 67.7 74.5

83

84

3 Highly Strained Cyclophanes Tab. 3.2 Partition of the strain energy in strained [n]meta- and [n]paracyclophanes (kcal mol–1)

Compound

Method

SE(C6H6)

SE(bridge)

SE(sum)

SE(rep) a)

1a 2a 32 a 38 a

DFT DFT MP2/DZP MP2/6-31G*

12.1 28.4 78.2 90.5

12.8 10.7 12.2 9.1

24.9 39.2 90.4 99.6

8.4 12.0

a) SE(rep) = SE(HD)–SE(sum). SE(HD) is the strain energy obtained from a homodesmotic reaction. SE(rep) is ascribed to the repulsion between the bridge and the benzene ring.

dergo a second conformational movement, a pseudorotation of the hexamethylene bridge on the same side of the ring, with an activation barrier of DG{ = 11–13 kcal mol–1. A related conformational motion, the exo–endo equilibration, occurs in 2 with comparable ease (Scheme 3.4). The position of equilibrium depends on the structure of the bridge as well as on the substituents on the aromatic ring. The parent [5]metacyclophane exclusively exists in the exo conformer. The chlorine substituents at C2 and C5 tend to stabilize the endo conformer more than the exo conformer and the endo conformer is observed in a minor quantity in 2 d. 3.2.3

Reactions of Strained [n]Metacyclophanes

Bickelhaupt and coworkers investigated the chemistry of [5]metacyclophane and its derivatives, the smallest metacyclophane viable at room temperature, in great detail [7]. They have revealed not only the remarkable enhancement of reactivity, but also several reaction patterns that do not find an analogy in conventional aromatic behavior. They have also found that the reactivity of substituted [5]metacyclophanes is affected by some subtle factors including substituent effects and the hybridization state of the atoms in the bridge.

3.2.3.1 Thermal and Photochemical Reactions

Under flash vacuum thermolysis (FVT) conditions [5]metacyclophane 2 a undergoes homolytic cleavage at one of the benzylic bonds to generate a diradical, which cyclizes again, ultimately giving a mixture of 5- and 6-methyltetralins. FVT of 7, in contrast, mainly provided tetralin, together with lesser amounts of methylindans. The generation of [4]metacyclophane 3 a from 7 followed by rearrangement via a benzvalene intermediate has been proposed [5 d]. The preferred process on irradiation of 2 is rearrangement to the ortho isomers by way of benzvalenes, whose intermediacy is supported by labeling experiments [7 b]. It is noteworthy that higher homologs of [5]metacyclophane do not undergo an analogous rearrangement. Thus, the benzvalene formation seems to be facilitated by the distorted geometry of the benzene ring.

3.2 [n]Metacyclophanes

3.2.3.2 Addition Reactions

Simple alkylbenzenes resist the addition of dienophiles unless highly reactive dienophiles and forcing reaction conditions are employed. Strained metacyclophanes, however, react with dienophiles in Diels-Alder reactions with a rate that approaches and sometimes surpasses that of ordinary 1,3-dienes. The addition occurs across the aromatic ring at C2 and C5, because only this regiochemistry effectively removes the steric strain in the metacyclophanes. While 3 a has defied direct observation so far, it was intercepted by its Dewar benzene precursor under the condition of its generation at about 150 8C to furnish 8 a and 8 b as the primary products (Scheme 3.5). Note that these dimers resulted from the Diels-Alder reactions of 3 a as diene with the unactivated double bond of 7 as dienophile [5 e, 7 c]. In the presence of maleic anhydride or hexafluoro-2-butyne, the corresponding adduct has been obtained instead. Compared with 3 a, 2 a exhibits significantly reduced Diels-Alder reactivity, but in comparison with simple alkylbenzenes its reactivity is still spectacular [7 b, d]. With reactive dienophiles such as dimethyl acetylenedicarboxylate (DMAD) and acrylonitrile, it readily reacts at room temperature to give the corresponding adducts, respectively (Scheme 3.6). As anticipated, the reactivity of 1 is strongly reduced compared with that of 2. The parent compound 1 a still forms adducts with strong dienophiles, but chlorine substitution at the aromatic ring blocks the Diels-Alder reactions. Dichlorocarbene does not react with benzene itself. It does, however, react with aromatics in which the benzene ring is incorporated in a strained cyclophane system. Upon reaction with 2 a, dichlorocarbene preferentially adds in a 1,2-fashion to the formal “anti-Bredt” type double bond of the benzene ring of 2 a to afford the norcaradiene 9, which immediately rearranges to 11 via electrocyclic ring opening followed by a [1,5]sigmatropic chlorine migration (Scheme 3.7). A com-

Scheme 3.5

Scheme 3.6

85

86

3 Highly Strained Cyclophanes

Scheme 3.7

Scheme 3.8

putational study supports that the [1,5]chlorine migration in the rearrangement of 10 to 11 is essentially concerned with minor charge separation [8]. Reaction of 2 a with the precursor 12 of the phosphinidene complex 13 with CuCl as catalyst gave the adduct 14 as the only product (Scheme 3.8) [9]. This is the first addition of a phosphinidene complex to a benzene ring. Contrary to the 1,2-addition of dichlorocarbene, 13 adds to 2 a in a 1,4-fashion. The difference in behavior between these divalent species is rationalized in terms of a difference in size of the central atoms. As the C(sp3)–C(sp3) bond (1.54 Å) is considerably shorter than the analogous C–P bond (1.87 Å), the carbon atom is apparently too small to achieve sufficient overlap between the frontier orbitals of 2 a and dichlorocarbene in the transition state for the 1,4-addition. Theoretical calculations also support the mechanism of the reaction of 13 with 2 a as being a direct 1,4-addition. In sharp contrast to 12, 14 remains unchanged even under prolonged heating in the presence of CuCl. The decomplexation of 14 with iodine and methylimidazole afforded 15, the first uncoordinated 7k3-phosphanorbornadiene, which is moderately stable at room temperature toward loss of the phosphinidene bridge. Previous attempts to obtain a simple, unbridged 7k3-phosphanorbornadiene had failed, presumably because it rapidly excluded the phosphorus bridge. Compounds 14 and 15 undoubtedly owe their kinetic stabilization to the overall increase in strain that results on dissociation into highly strained 2 a and the phosphorus species.

3.2.3.3 Reactions with Electrophiles

A characteristic reaction of short-bridged metacyclophanes is the acid-catalyzed rearrangement to their corresponding ortho isomers. While 1 a is relatively stable towards acids, [5]metacyclophanes are particularly sensitive and undergo the rear-

3.2 [n]Metacyclophanes

Scheme 3.9

rangement under surprisingly mild conditions [7 b–d]. The mechanism illustrated in Scheme 3.9 is supported by labeling experiments and product analysis. The key step is protonation of one of the bridgehead positions, which is followed by a 1,2-alkyl shift. It should be noted that each step is facilitated by a significant reduction in steric strain. In the reaction of 2 d, a 1,2-chloride shift precedes the final deprotonation to afford 16 a. The replacement of the chlorine atom at C2 in 2 d with a methoxyl group as in 2 e leads to the formation of 19. Owing to the low migratory aptitude of the methoxyl group, 17 undergoes a further 1,2shift of the alkyl bridge followed by loss of the methyl group via attack by a nucleophile, eventually to furnish 19. The bromination of 2 a occurs without a catalyst at –75 8C, but again proceeds with rearrangement to afford 16 b.

3.2.3.4 Reactions with Nucleophiles

Haloaromatics are normally unreactive towards nucleophilic substitution unless the aromatic ring is activated by strongly electron-withdrawing groups [7 a]. Here, [5]metacyclophanes again constitute an exception, as they are unusually reactive in nucleophilic substitutions without the need for activation by electron-withdrawing groups. Thus, 2 c, d readily undergo attack by alkoxide ions at the ipso carbon atom to give 2 f via the Meisenheimer complex 20 (the SN2Ar mechanism: Scheme 3.10). The reaction is slower when the chlorine at C5 is missing, in line

Scheme 3.10

87

88

3 Highly Strained Cyclophanes

Scheme 3.11

with the SN2Ar mechanism. The reaction of 2 b with alkoxide ions similarly occurs at the ipso position, but the subsequent course of the reaction is different and the intermediate adds a proton to give 21 (Scheme 3.11). Fluorobenzenes are normally better substrates than the corresponding chlorides for substitution by the SN2Ar mechanism. The distinctive behavior of 2 b compared with that of 2 c, d has been ascribed to the shift of the rate-determining step from the initial addition of the nucleophile, which is normally rate-determining, to the next step, the extrusion of the halide ion, in the reaction of 2 b. In the reactions of 2, the attack by the nucleophile is accompanied by the release of a considerable amount of strain because the intermediates, such as 20, do not have “antiBredt” double bonds involving C2 whereas the extrusion of the halide ion is counteracted by the reintroduction of the strain. Under these specific circumstances, the poor nucleofugality of the fluorine substituent retards the fluoride ion extrusion to the extent that the alternative pathway of protonation can prevail, resulting in the formation of 21. When 2 b is treated with a large excess of MeONa, cyclohexadienone 22 is formed via the SN2 substitution with concomitant fluoride extrusion. Intuitively, one would have expected that the reaction of 2 c, d with the hydroxide ion should proceed by the SN2Ar mechanism similar to the attack by alkoxides. However, the reaction takes a completely different course, giving 24 instead of the substitution products [7 d]. This has been interpreted as outlined in Scheme 3.12. Nucleophilic attack at the bridgehead position is in general the kinetically preferred primary mode of attack, even in the alkoxide reactions. In these reactions, however,

Scheme 3.12

3.3 [n]Paracyclophanes

Scheme 3.13

the primary intermediates analogous to 23 do not have a rapid follow-up reaction available, but an unproductive reversion to the reactants, and the alternative, kinetically less favorable attack at C2 eventually opens the pathway leading to 2 f. In its reaction with hydroxide ion, 2 b again exhibits behavior quite different from that of 2 c, d, giving 22 instead of 24 (X = H). The kinetically preferred adduct, corresponding to 23, being incapable of undergoing a ring contraction because of the poor nucleofugality of the fluorine substituent, the attack at C2 provides a chance to furnish 25, from which 22 is derived. Treatment of 26 with t-BuOK in DMSO, in an attempt to synthesize dichloro[1.1]metacyclophane 27, led to the formation of 28 and 29 in 9 and 10% yield, respectively (Scheme 3.13) [10]. The formation of 28 has been rationalized in terms of the attack on 27 by an adventitious hydroxide ion at one of the bridgehead positions followed by ring opening. The yield of 28 increased to 40% when 4 equivalents of water were purposely added: in this case 29 was absent.

3.3

[n]Paracyclophanes

In the [n]paracyclophane series, the borderline for stability at ambient temperature has been found between [6]paracyclophane 30, which is an isolable, chemically fairly stable compound, and [5]paracyclophane 31, which has so far been observed only in solution below room temperature [1, 2]. [4]Paracyclophane 32 is observable only under matrix isolation at low temperature and rapidly disappears in fluid solution even below –100 8C. The instability of 31 and 32 most probably arises from their high propensity for undergoing addition at the bridgehead positions, whereby the steric strain inherent in the ring systems is largely released: their half-lives in solution are concentration-dependent, indicating a bimolecular or chain mechanism of polymerization. Thus, the kinetic stability of 32 is markedly ameliorated by introducing substituents that sterically hinder access to the bridgehead carbon atoms by other reagents. [4]Paracyclophane is so strained that its energy is comparable to or slightly higher than that of the Dewar isomer 36

89

90

3 Highly Strained Cyclophanes

and its kinetic stability is also limited by the intrinsic reactivity to rearrange thermally to the latter. 3.3.1

Synthesis

The first synthesis of [6]paracyclophane was accomplished by Jones and coworkers in 1974, using an ingenious methodology, a rearrangement of highly energetic carbene intermediate 33 (Scheme 3.14) [11]. This reaction, however, provided 30 a only in low yield and more efficient routes to [6]paracyclophane and its derivatives have subsequently been explored, that is, the thermal, photochemical or silver-ion-catalyzed aromatization of corresponding 1,4-bridged Dewar benzenes by Jones, Bickelhaupt, Tobe, and Gleiter, and the ring contraction of 3,6-bridged oxepin derivative by Tochtermann [1 c]. The preparation of 1,4-bridged Dewar benzenes has been achieved in turn by the methods including (1) silver-ion-catalyzed isomerization of 3,3'-hexamethylene bicyclopropenyl; (2) ring contraction of [6.3.2]propellane derivatives; and (3) AlCl3-catalyzed intramolecular dimerization of 1,10-dodecadiyne followed by cycloaddition of a third alkyne. [6]Paracyclophane is stable enough to permit structural modification and, by annelating benzene ring(s) to its aromatic core, [6](1,4)naphthalenophanes as well as [6](1,4)- and [6](9,10)anthracenophanes have been prepared [12]. Of these strategies, only the photochemical Dewar benzene route has successfully been applied for the generation of [5]- and [4]paracyclophanes (Schemes 3.15 and 3.16). While 30 is obtained in high yield by mildly heating the corresponding Dewar isomer, the lower homologs have been prepared solely by photolysis of their Dewar isomers. The thermal aromatization of 1,4-bridged Dewar benzene requires increasingly high temperature as the length of bridging chain is shortened. Strained 31 cannot survive the thermolysis conditions required to generate it from relatively stable 35. Photolysis, however, can be carried out regardless of the reaction temperature, allowing the preparation of sensitive 31 [13] and 32 [14, 15] at low temperature. Since both 31 and 32 possess more intense, far-reaching (in wavelength) chromophores than the Dewar precursors and are susceptible to the photochemical reversion to give the latter, the isomerization of the latter into the former by irradiation can not be brought to completion, but reaches a photostationary state usually consisting mainly of the Dewar isomer. The photochemical aromatization of the Dewar benzenes seems to take place in their singlet excited

Scheme 3.14

3.3 [n]Paracyclophanes

Scheme 3.15

Scheme 3.16

states and appears to be hindered by substituents which facilitate intersystem crossing to the triplet excited states [16 c]. 3.3.2

Structures and Physical Properties

The most prominent feature in the structure of strained paracyclophane is the bending of its aromatic ring into a boat form, accompanied by the out-of-plane bending of the benzylic carbon–carbon bonds. The degrees of these distortions are given by the critical angles a and b, defined respectively as in Scheme 3.15. Tab. 3.1 displays experimental geometrical parameters for 30, together with those calculated for 31 a, 32 a, and 38 a. The good agreement between the experimental and calculated values for 30 suggests that the values computed for the smaller analogs will also be sufficiently reliable. The calculated structure of 38 a, the most highly strained paracyclophane ever experimentally accessed, is instructive; 38 a has C2v symmetry and the bridge bisects the bent benzene ring [15 b]. The extent of bond alternation in the benzene ring is surprisingly small for the severe deformation of the ring, less than 0.02 Å, irrespective of the methods employed (SCF and MP2/6-31G*, B3LYP/6-31G*). Thus, the severely twisted bonds between the bridgehead and the adjoining carbon atoms are only slightly longer than the neighboring non-twisted bonds, suggesting the sustenance of cyclic delocalization of p-electrons in the benzene ring. The predicted deformation angles a and b are in the ranges of 27–29 8 and 45–48 8, respectively, and the sum (a + b) amounts to 74–75 8. As a result, the bridgehead carbon atoms are markedly pyramidalized, decreasing the sum of the bond angles around each of them to 339.3 8 (B3LYP/631G*) from 360 8 for a planar trivalent carbon atom. The residual aromatic carbon atoms are also pyramidalized (the sum of the bond angles is 355.6 8) as illustrated

91

92

3 Highly Strained Cyclophanes Tab. 3.3 Longest wavelength absorption bands of strained [n]paracyclophanes

kmax (nm)

30 a

30 b

31 a

31 b

32 a

32 b

296

329

330

360

370–380

425

in Scheme 3.16, so as better to maintain p-orbital overlap with adjacent bridgehead carbon atom. The strain energy due to the distortion of the benzene ring and that due to the distorted bridge are evaluated separately for 32 a and 38 a, and listed in Tab. 3.2 [2 b, 17]. The strain is evidently localized largely in the bent benzene moiety in the [4]paracyclophanes. The strain energies of 30 a and 31 a have been estimated to be 40 and 63 kcal mol–1, respectively. It is of interest that 38 is a fully unsaturated species and the p-bond isomerism in 38 gives rise to bicyclo[4.2.2]decapentaene 39 as an alternative structure. All the available data support the adoption of the former structure in preference to that of the latter; namely, the similarity in shape of the UV/Vis absorption spectra of 38 a, b to those of 32 a, b, respectively, and the structures of chemically intercepted products (see below), in addition to computational analysis. According to the theoretical calculations, however, the latter is only slightly less stable, by 3.9 kcal mol–1 at the B3LYP/6-31G* level, than the former, suggesting that the structural preference may be reversed by introducing suitable substituents [15]. The 1H NMR spectra of [5]- and [6]paracyclophanes exhibit temperature-dependent NMR behavior caused by flipping of the oligomethylene bridge. The barrier of flipping is in the range of 10–15 kcal mol–1. Protons in the central portion of the bridge of 31 are upfield shifted in their spectra and resonate at high field up to d –0.62, indicating that, despite the severe distortion, the benzene ring retains its aromatic character with remarkable tenacity [13]. This notion is further strengthened by the examination of the magnetic property of [4]paracyclophane as described below. Absorption bands in the UV/Vis spectra of paracyclophanes are increasingly shifted bathochromically with decreasing length of the bridging chain, in agreement with the predicted narrowing of the HOMO–LUMO energy gap in a bent benzene ring. The representative results are listed in Tab. 3.3. 3.3.3

Reactions of Strained [n]Paracyclophanes 3.3.3.1 Thermal and Photochemical Reactions

When heated, [6]paracyclophane undergoes homolysis at one of the benzylic carbon-carbon bonds to generate diradical 41 b, which then collapses to afford the spiro derivative 42 b (Scheme 3.17) [18 a]. This type of thermal transformation is reversible for 40 a/42 a, suggesting that 40 a and 42 a are nearly balanced in energy while the interconversion is in favor of the spiro form in the more strained [6]paracyclophane system. The strain of paracyclo-

3.3 [n]Paracyclophanes

Scheme 3.17

Scheme 3.18

phane is rapidly accumulated as the number of bridging carbon atoms decreases from eight to four, whereas the strain of the corresponding Dewar isomers remain virtually unaffected. Thus, the relative energy of a paracyclophane to its Dewar isomer is expected to reverse at a certain chain length. Theoretical calculations suggest that, when the bridging chain is shortened to tetramethylene, the Dewar form becomes isoenergetic to or slightly lower in energy than the cyclophane form [17 a, c]. This reversal of stability order has been corroborated for the pair of 43 and 44 : 44 thermally reverts to 43 with a half-life 15 ± 5 min at –20 8C (DG{ = 18.3 ± 0.3 kcal mol–1: Scheme 3.18) [16 b, c]. The efficient valence isomerization of benzene ring into the Dewar form upon irradiation is a characteristic reactivity common to strained [n]paracyclophanes (n £ 6). Although photochemical conversions of aromatic compounds into Dewar isomers have been well documented, they are inefficient, minor processes in most of the cases. This type of transformation is thus greatly facilitated by the enforced distortion of benzene ring into the boat form by a short bridge in the strained paracyclophanes. The activation of [7]- and [8]paracyclophanes toward the analogous isomerization appears to be insufficient and their photolysis merely produces polymeric material. While [6](1,4)- and [5](1,4)naphthalenophanes photochemically behave similarly, giving corresponding 1,4-bridged benzo Dewar isomers upon irradiation, [6](1,4)anthracenophane preferentially undergoes photo-dimerization to give a mixture of [2 + 2] stereoisomers conjoined at C1 and C2 [18 c]. Irradiation of a mixture of 32 a and 36 a in a quasi-photoequilibrium, in a glass matrix at 77 K, leads to the formation of p-quinodimethane 45, presumably via photochemical extrusion of ethylene from 32 a in competition with the cycloreversion to give 36 a (Scheme 3.19) [14].

93

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3 Highly Strained Cyclophanes

Scheme 3.19

3.3.3.2 Reactions with Electrophiles

As is the case with strained metacyclophanes, 30 a is sensitive to acid and readily undergoes rearrangement, upon exposure to trifluoroacetric acid, to give a mixture of less strained 1 a and the ortho isomer. Since the reaction proceeds under the conditions under which 1 a is inert, the latter is formed directly from 30 a via sequential Wagner-Meerwein shifts in the protonated intermediate. In contrast, 32 a undergoes 1,4-addition at the bridgehead positions in preference to the rearrangement leading to tetralin in the reactions with protic solvent molecules (Scheme 3.20) [14, 19]. Due to the extreme steric strain, 32 a behaves as an unusually basic hydrocarbon and reacts with methanol even under neutral conditions. [5]Paracyclophane shows an intermediate behavior and affords both 1,4-adducts and the rearranged product. The observed distinctive behaviors of the strained paracyclophanes in the reaction with electrophiles are presumably dictated by factors including the charge distribution in the cation intermediate 47, the degree of strain release in the transition state leading to each product from 47, and the nucleophilicity of the reactant which adds to 47. When exposed to bromine, 30 a suffers addition reaction rather than substitution reaction to give the 1,4-adduct almost quantitatively [18 b]. The benzo-annelated analogs of 30 a undergo acid-induced oligomerization in preference to the rearrangement to the less strained isomers. Their dimers and trimers were isolated and their structures were elucidated by X-ray crystallography [18 b, d]. [6](9,10)Anthracenophanes are highly sensitive to acid and readily isomerize to the 9-methylene-10-dihydro derivatives, as is predicted by theoretical calculations [20].

3.3.3.3 Diels-Alder and Other Reactions

[6]Paracyclophane 30 a exhibits enhanced reactivity in the reaction with dienophiles, compared with the less strained homologs, and affords adducts at the non-

Scheme 3.20

3.3 [n]Paracyclophanes

Scheme 3.21

Scheme 3.22

bridgehead positions. The reactions of the benzo-annelated analogs of 30 a with dienophiles take different courses which are initiated by the addition to the bridgehead position and proceed stepwise via zwitterion and/or diradical intermediates depending on the dienophile and the polarity of the solvent [18 d]. The extremely bent benzene ring of [4]paracyclophadiene 38 a behaves as an activated alkene in the reaction with cyclopentadiene and the transient 38 a has been efficiently intercepted by the latter to afford a mixture of twofold adducts 48 a and 48 b; a rare, if not unprecedented, case in which an aromatic ring participates as a dienophile in a Diels-Alder reaction (Scheme 3.21) [15]. This result provided strong support for the preference of structure 38 over the p–bond shifted structure 39. A bridged cyclooctatetraene derivative has been obtained in the reaction of a substituted [6]paracyclophane with dichlorocarbene, while the major product in the reaction with dibromocarbene is a bridged cycloheptatriene [21]. Oxidation of 30 a with mCPBA leads to the dimeric oxidation product 50, for which epoxidation followed by rearrangement to give 49 has been proposed as a mechanism (Scheme 3.22) [18 a, d]. Butyllithium and s-BuLi add to 30 a in 1,2- or 1,4-fashion, while with t-BuLi or tBuOK/BuLi its aromatic ring is metalated, allowing the functionalization of the aromatic ring by subsequent treatment with electrophiles [22].

3.3.3.4 Kinetic Stabilization of [4]Paracyclophane Systems

The high lability of [4]paracyclophane evidently arises from its propensity for undergoing addition at the bridgehead positions, as exemplified by the formation of adducts such as 46 and 48. Thus, it is suggested that the ring system may be kinetically stabilized by introducing substituents that specifically shield the bridgehead sites from access by attacking reagents. Among a number of derivatives designed and prepared on the basis of such consideration, the best result has so far been obtained with 44 whose lifetime in solution was successfully extended to 12 min at –20 8C [16 a, c]. The measurement of the 1H NMR spectrum of [4]paracyclophane ought to provide not only definitive evidence for its formation

95

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3 Highly Strained Cyclophanes

but also valuable information concerning the aromaticity of its severely bent benzene ring, but has been thwarted because of the thermal instability. The improved thermal stability of 44 is high enough to permit the measurement of the 1H NMR spectrum, which revealed the sustenance of a substantial diamagnetic current in the benzene ring, despite its extreme bending (a + b = 72.5 8). Thus, the isomerization of 43 to 44 is attended by the pronounced upfield shift of the Ha signal and the marked downfield shift of the Hb signal as depicted in Scheme 3.18. Theoretical calculations also support the retention of substantial aromaticity in the bent benzene moiety of 44 as judged by the magnetic criteria of aromaticity, namely diamagnetic susceptibility exaltation and nucleus-independent chemical shift (NICS).

3.4

Aromaticity of Bent Benzene Rings

The strain energy of [4]paracyclophane (90–100 kcal mol–1), which mainly arises from the distortion of the benzene ring as described above, far exceeds the resonance stabilization energy of benzene (20–30 kcal mol–1). Thus, its aromatic stabilization energy compensates only a fraction of the strain energy at best. Moreover, [4]paracyclophane and its derivatives behave chemically like activated alkenes and readily undergo addition reactions rather than substitution reactions. Accordingly, they cannot be regarded as aromatics so far as their chemical reactivities are concerned. How can the energy of [4]paracyclophane and its chemical properties be reconciled with the observed diatropicity, which is indicative of the sustenance of cyclic delocalization of p-electrons in the benzene ring? In benzene, distortion into a nonplanar geometry unavoidably gives rise to torsion of p-bonds, which is not suppressible by localization of p-bonds. Thus, the carbon atoms of a benzene ring undergo extensive pyramidalization–rehybridization upon severe bending, as theoretical calculations reveal, to avoid the rupture of the p-bonds leading to degeneration into a biradical(oid), at the expense of energy even greater than its aromatic stabilization energy, and, consequently, the cyclic conjugation seems to be retained. The sustenance of aromatic conjugation in the severely bent benzene rings, as found in [4]paracyclophane, is a consequence of accommodation of the geometrical constraint imposed on the ring and basically not attributable to the aromatic stabilization effect. Accordingly, strained cyclophanes such as [5]metaand [4]paracyclophanes are kinetically highly reactive, high energy species, yet they seem to sustain rather strong diatropicity and only a small degree of bond alternation [2, 16 c, 23].

3.5

Cyclophanes containing Polycyclic Aromatic Rings: (2,7)Pyrenophanes

Aiming at the construction of bowl-shaped molecules, Bodwell and coworkers have developed a new synthetic route to strained 2,7-bridged pyrenes in which the

3.5 Cyclophanes containing Polycyclic Aromatic Rings: (2,7)Pyrenophanes

Scheme 3.23

polycyclic aromatic hydrocarbon framework is bent over its entire aromatic surface [24]. Pyrene is a repeating subunit around the equator of D5h C70, D5d C80, and D6h C84. The synthetic approach is based upon the valence isomerization of [2.2]metacyclophane-1,9-dienes to 10b,10c-dihydropyrenes followed by dehydrogenation, and severe nonplanarity is imparted to the pyrene system by the incorporation of a tether between the 2 and 7 positions as outlined in Scheme 3.23. Among the known pyrenophanes including those prepared in this way, the pyrene moiety of 1,7-dioxa[7](2,7)pyrenophane 53 a suffers the highest degree of the overall bend (h = 109.1 8), as measured by the angle h between the C1-C2-C3 and C6-C7-C8 planes. It is even slightly more bent than the pyrene subunit in C70, though the local curvature is less as evaluated by the p-orbital axis vector (POAV) analysis [24 a]. The bending in 53 a is quite evenly distributed over the surface of the pyrene unit. Attempted synthesis of [6]- and 1,6-dioxa[6](2,7)pyrenophanes from the corresponding metacyclophane-1,9-dienes has resulted in the almost quantitative recovery of the latter. The way in which the distortion from planarity of the pyrene system influences its p-electron delocalization was investigated by using two quantitative measures of aromaticity based on geometry and magnetism. Both methods suggest that the p-electron structure of the pyrene moiety is almost untouched and its aromaticity is diminished only slightly upon increasing the bend angle h from 0 8 to 109.2 8 [24 e]. The [n](2,7)pyrenophanes exhibit enhanced reactivity with decreasing length of the bridging chain [24 b]. Thus, 53 a reacts with TCNE in benzene at room temperature to give 55, while 53 b does not react even at reflux (Scheme 3.24). Addition of PTAD to 53 a rapidly proceeds at room temperature to afford a 2 : 1 PTADpyrenophane adduct 56 a. In contrast to TCNE, PTAD did react with 53 b to furnish an analogous 2 : 1 adduct, but the reaction was clearly slower than that of

Scheme 3.24

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3 Highly Strained Cyclophanes

Scheme 3.25

53 a. The higher homolog 53 c showed only traces of reaction with PTAD even after prolonged reaction time. AM1 calculations predict that the difference in strain energy between 53 a and 53 b is of the order of 15 kcal mol–1. Attempted bromination of 54 a and 54 b, and Friedel-Crafts acetylation of the former all met with difficulty and have failed so far to furnish the functionalized pyrenophanes. Treatment of 53 a or 53 b with t-BuLi, in an attempt to metalate the pyrenophane regioselectively, has resulted in the cleavage of the aryl-oxygen bond. Reduction of 54 a, d with lithium metal gives dimeric dianions 57 a, b, respectively, via the coupling of their radical anion intermediates at C6 (Scheme 3.25). Upon further reduction with lithium metal, these species undergo concomitant bond cleavage/intramolecular bond formation to afford monomeric dianions 58 a, b [25]. In contrast, the two electron reduction of pyrene with alkali metals converts it into an antiaromatic dianion (pyrene)2–. In the two-electron reduction of the strained pyrenophanes 54 a, d, the system dodges getting into an unfavorable strained antiaromatic state by undergoing the intramolecular bond formation which introduces a pronounced fold into what was a pyrene moiety.

3.6

[1.1]Paracyclophanes

The construction of [1.1]paracyclophane 61, that is the connection of two benzene rings at the para positions with two methylene bridges in a cyclic array, apparently requires severe bending of the rings and bonds. Despite its fascinating structure, to our knowledge, no report concerning 61 had been published when we embarked on its preparation. The successful generation of [4]paracyclophanes from the corresponding Dewar benzene precursors, however, suggested that 61 might well be accessible via valence isomerization of the bis(Dewar benzene) isomers 59. The first step of this isomerization from 59 to 60 is nothing else but the generation of a [4]paracyclophane skeleton, if a stepwise mechanism is assumed, and the second step corresponds to the formation of much less strained, six-carbonbridged paracyclophane from the respective Dewar benzene precursors (Scheme 3.26). Thus, the second step should be much easier than the first. This expectation is supported by computational analysis on 59 a–61 a which reveals, as described later, that the initial step is a slightly endothermic process whereas the second step is highly exothermic. The degree of ring deformation in 61 a is comparable to that calculated for [5]paracyclophane and much less than that for

3.6 [1.1]Paracyclophanes

Scheme 3.26

[4]paracyclophane. Although the parent [1.1]paracyclophane lacks the stability to persist in solution at ambient temperature, the ring system has been stabilized kinetically by introducing suitable substituents to such an extent that isolation as crystals is allowed. 3.6.1

Synthesis

Bis(Dewar benzene) precursor 59 is obtained via a synthetic pathway including twofold cycloaddition of acetylene to bis(enone) 62 as a key step (Scheme 3.27) [26]. The subsequent transformation of 63 to 59 was carried out in essentially the same manner as reported for the preparation of [4.2.2]propellatetraene 37 [27]. Compound 62 is in turn prepared in five steps from diethyl dihydroterephthalate. The photocycloaddition of acetylene to 62 occurs stereoselectively to furnish the anti-bis(acetylene) adduct 63 a. The observed stereoselectivity probably results from the preferential bending of the central six-membered ring toward the cyclobutene ring in the mono-adduct as suggested by force field calculations. Irradiation of 59 a, b gives rise to 61 a, b, respectively, which are both photochemically labile and subsequently converted into the transannular addition products 62. Neither the less symmetrical products resulting from the aromatization in only one of the Dewar benzene moieties nor prismane derivatives have been detected in the photolysate. The secondary transannular addition within 61 to give 64, to our knowledge, represents the first direct formation of a benzene p,p'-dimer and is certainly a consequence of the face-to-face arrangement of the bent benzene rings in close proximity (Scheme 3.28). The thermal stabilities of 61 a, b are comparable to that reported for [5]paracyclophane and their UV/Vis absorption spectra remain unchanged for several hours at –20 8C but decay within 4 h at room temperature, suggesting that the reactivity of [1.1]paracyclophane is primarily determined by the extent of bending of

Scheme 3.27

99

100

3 Highly Strained Cyclophanes

Scheme 3.28

the aromatic rings and the ring system is neither particularly stabilized nor particularly destabilized by the close stacking of the benzene rings. 3.6.2

Kinetic Stabilization of [1.1]Paracyclophane Systems

The known reactivity of strained paracyclophanes suggests that the kinetic stabilization of [1.1]paracyclophane systems requires the protection of all four bridgehead carbon atoms from access by other reagents. Such consideration led to the design of a number of substituted derivatives, among which 61 c gave the best result [28]. The substituents in 61 c are conformationally flexible and the effective bulkiness is very much dependent on their adopted conformations, yet they are expected to protect all the bridgehead carbon atoms in the most preferred conformation. The UV/Vis absorption due to 61 c decays only by 8% after a solution in n-decane is heated at 100 8C for 2 h, demonstrating the greatly improved stability. Irradiation of 59 tends to afford mainly 64 rather than 61, except at very low conversion, because 61 is efficiently transformed into 64 upon excitation and, moreover, the chromophore of 61 is more intense and far-reaching in wavelength than that of 59. The transannular adduct 64 c, however, undergoes thermal cycloreversion to regenerate 61 c, rendering the preparation of fairly air-sensitive 61 c in pure form rather simple. Thus, air-stable 64 c is readily isolated as colorless crystals and it can be quantitatively converted to 61 c by mildly heating its solution in a de-aerated solvent. 3.6.3

Structures and Physical Properties

The geometrical as well as electronic structures of [1.1]paracyclophane, its strain energy, and thermodynamic stability relative to related compounds are of special interest. To gain insights into these points, theoretical analyses were carried out by ab initio and DFT quantum mechanical methods [26 b]. The geometry-optimized structure of 61 a is D2h symmetric and the nonbonding interatomic distance between the opposing bridgehead carbon atoms is in a range of 2.36– 2.40 Å, compared with 2.778 Å in [2.2]paracyclophane, suggesting strong electronic interactions between the p-bonds of the aromatic rings. The bending angles a and b are about 23 8 and 27 8, respectively. Relative energies calculated for 61 a and relevant related compounds are collected in Tab. 3.4.

3.6 [1.1]Paracyclophanes

Inspection of Tab. 3.4 reveals that 61 a is certainly the most stable of the isomers and that the isomerization of 59 a to 60 a is endothermic whereas that of 60 a to 61 a is strongly exothermic. Accordingly, it is not unreasonable that 60 is not detected during the photolysis of 59, though a stepwise mechanism is likely in operation. Although 61 a is the most stable of the calculated isomers, it is still a highly strained molecule. For the evaluation of strain energy in 61 a, 9,10-dihydroanthracene serves as an ideal reference compound. The total strain energy of 61 a thus evaluated is 128.1, 93.6, and 106.5 kcal mol–1 at the RHF/6-31G*, MP2/ 6-31G*, and B3LYP/6-31G* levels, respectively. The calculations confirm that the HOMO and LUMO of 61 a are significantly raised and lowered in energy, respectively, compared with those of p-xylene as a consequence of bending of the benzene rings and of their mutual electronic coupling. The reduced HOMO–LUMO energy gap in 61 a (8.83 eV), compared with that in p-xylene (12.33 eV) manifests itself in the UV/Vis absorption spectrum. [1.1]Paracyclophane 61 a exhibits pronounced bathochromic shifts of absorption bands (kmax 290, 377 nm), compared with [2.2]paracyclophane (kmax 284, 302 nm), reflecting the severer distortion and the stronger transannular electronic interactions in the former than in the latter. A broad, relatively weak band (kmax 377 nm) in the range of 330–450 nm in the spectrum of 61 a is a characteristic feature common to the spectra of [1.1]paracyclophanes: 370–480 nm (kmax 405 nm) for 61 b and 400–530 nm (kmax 461 nm) for 61 c. The molecular structure of 61 c in the crystalline state has Ci symmetry and the polycyclic core is slightly distorted from ideal D2h symmetry (Fig. 3.1) [28]. The transannular interatomic distance between the opposing bridgehead carbon atoms is 2.376(5) Å, less than the sum of the van der Waals radii (3.5–3.6 Å) by more than 1.0 Å. The averaged total bending angle (a + b ) is 49.8 8, which is the largest value ever observed for a paracyclophane and only slightly less than that calculated for [5]paracyclophane. Thus, the geometrical parameters of 61 a given by the theoretical calculations are in good agreement with the experimental data. The bridgehead carbon atoms are effectively protected by the aromatic substituents, also in good agreement with the results of molecular modeling: this is certainly the reason for its remarkable stability. The thermal isomerization of 64 c to 61 c follows first-order kinetics and activation parameters for the process are: DH{ = 21.1 ± 0.8 kcal mol–1 and DS{ = –10.5 ± 2.6 cal mol–1 K. The half-life of 64 c at 40 8C is 191 ± 2 min. The thermal instability of 64 a, b might be due to their intrinsic reactivity to revert thermally to 61 a, b, respectively, which would be rapidly consumed under the conditions.

Tab. 3.4 Calculated energies of 59 a, 60 a, and 64 a relative to [1.1]paracyclophane 61 a (kcal mol–1)

Method

59 a

60 a

61 a

64 a

SCF/6-31G* B3LYP/6-31G*

51.5 70.7

62.3 –

0 0

8.7 25.6

101

102

3 Highly Strained Cyclophanes

Fig. 3.1

Crystal structure of 61 c

3.7

References and Notes (a) F. Bickelhaupt, W. H. de Wolf, in Advances in Strain in Organic Chemistry, ed. by B. Halton, JAI Press, Greenwich, Ct. 1993, 3, 185–227; (b) Y. Tobe, in Topics in Current Chemistry, ed E. Weber, Springer, Berlin 1994, 172, 1–40; (c) V. V. Kane, W. H. de Wolf, F. Bickelhaupt, Tetrahedron, 1994, 50, 4575–4622; (d) H. Hopf, Classics in Hydrocarbon Chemistry, Wiley-VCH, Weinheim, 2000, 321–378. 2 (a) T. Tsuji, in Advances in Strained and Interesting Organic Molecules, ed. B. Halton, JAI Press, Stamford, Ct., 1999, 7, 103–152; (b) T. Tsuji, M. Ohkita, H. Kawai, Bull. Chem. Soc. Jpn., 2002, 57, 415– 433. 3 (a) V. Prelog, K. Wiesner, Helv. Chim. Acta 1947, 30, 1465–1471; (b) V. Prelog, K. Wiesner, W. Ingold, O. Häfliger, Helv. Chim. Acta, 1948, 31, 1325–1341. 4 P. Grice, C. B. Reese, J. Chem. Soc., Chem. Commun., 1980, 424–425. 1

(a) L. A. M. Turkenburg, J. W. van Straten, W. H. de Wolf, F. Bickelhaupt, J. Am. Chem. Soc., 1980, 102, 3256–3257; (b) G. B. M. Kostermans, M. Hogenbirk, L. A. M. Turkenburg, W. H. de Wolf, F. Bickelhaupt, J. Am. Chem. Soc., 1987, 109, 2855–2857; (c) G. B. M. Kostermans, P. van Dansik, W. H. de Wolf, F. Bickelhaupt, J. Am. Chem. Soc., 1987, 109, 7887– 7888; (d) G. B. M. Kostermans, P. van Dansik, W. H. de Wolf, F. Bickelhaupt, J. Org. Chem., 1988, 53, 4531–4534. 6 M. J. van Eis, W. H. de Wolf, F. Bickelhaupt, R. Boese, J. Chem. Soc., Perkin Trans. 2, 2000, 793–801. 7 (a) P. A. Kraakman, J.-M. Valk, H. A. G. Niederländer, D. B. E. Brouwer, F. M. Bickelhaupt, W. H. de Wolf, F. Bickelhaupt, C. H. Stam, J. Am. Chem. Soc., 1990, 112, 6638–6646; (b) L. W. Jenneskens, H. J. R. de Boer, W. H. de Wolf, F. Bickelhaupt, J. Am. Chem. Soc., 1990, 112, 8941–8949; (c) F. Bickelhaupt, 5

3.7 References and Notes

8

9

10

11 12

13

14

15

16

W. H. de Wolf, J. Phys. Org. Chem., 1998, 11, 362–376; (d) G. W. Wijsman, W. M. Boesveld, M. C. Beekman, M. S. Goedheijt, B. L. M. van Baar, F. J. J. de Kanter, W. H. de Wolf, F. Bickelhaupt, Eur. J. Org. Chem., 2002, 614– 629. M. J. van Eis, B. S. E. van der Linde, F. J. J. de Kanter, et al., J. Org. Chem., 2000, 65, 4348–4354. (a) M. J. van Eis, C. M. D. Komen, F. J. J. de Kanter, et al., Angew. Chem., 1998, 110, 1656–1658; Angew. Chem. Int. Ed., 1998, 37, 1547–1550; (b) M. J. van Eis, H. Zappey, F. J. J. de Kanter, W. H. de Wolf, F. Bickelhaupt, J. Am. Chem. Soc., 2000, 122, 3386–3390. M. J. van Eis, F. J. J. de Kanter, W. H. de Wolf, F. Bickelhaupt, J. Org. Chem., 1997, 62, 7090–7091. V. V. Kane, A. D. Wolf, M. Jones, Jr., J. Am. Chem. Soc., 1974, 96, 2643–2644. (a) Y. Tobe, S. Saiki, N. Utsumi, T. Kusumoto, H. Ishii, K. Kakiuchi, K. Kobiro, K. Naemura, J. Am. Chem. Soc., 1996, 118, 9488–9497; (b) Y. Tobe, S. Saiki, H. Minami, K. Naemura, Bull. Chem. Soc. Jpn., 1997, 70, 1935–1942. (a) L. W. Jenneskens, F. J. J. de Kanter, P. A. Kraakman, L. A. M. Turkenburg, W. E. Koolhaas, W. H. de Wolf, F. Bickelhaupt, Y. Tobe, K. Kakiuchi, Y. Odaira, et al., J. Am. Chem. Soc., 1985, 107, 3716–3717; (b) Y. Tobe, T. Kaneda, K. Kakiuchi, Y. Odaira, Chem. Lett., 1985, 1301–1304; (c) G. B. M. Kostermans, W. H. de Wolf, F. Bickelhaupt, Tetrahedron, 1987, 43, 2955–2966; (d) D. S. van Es, F. J. J. de Kanter, W. H. de Wolf, F. Bickelhaupt, Angew. Chem., 1995, 107, 2728–2730; Angew. Chem. Int. Ed., 1995, 34, 2553–2555. (a) T. Tsuji, S. Nishida, J. Chem. Soc., Chem. Commun., 1987, 1189–1190; (b) T. Tsuji, S. Nishida, J. Am. Chem. Soc., 1988, 110, 2157–2164. (a) T. Tsuji, S. Nishida, J. Am. Chem. Soc., 1989, 111, 368–369; (b) T. Tsuji, S. Nishida, M. Okuyama, E. Osawa, J. Am. Chem. Soc., 1995, 117, 9804–9813. (a) M. Okuyama, T. Tsuji, Angew. Chem., 1997, 109, 1157–1158; Angew. Chem. Int. Ed., 1997, 36, 1085–1087; (b) M. Okuya-

17

18

19

20 21

22

23

24

ma, M. Ohkita, T. Tsuji, J. Chem. Soc., Chem. Commun., 1997, 1277–1278; (c) T. Tsuji, M. Okuyama, M. Ohkita, H. Kawai, T. Suzuki, J. Am. Chem. Soc., 2003, 125, 951–961. (a) S. Grimme, J. Am. Chem. Soc., 1992, 114, 10542–10547; (b) I. Frank, S. Grimme, S. D. Peyerimhoff, J. Am. Chem. Soc., 1994, 116, 5949–5953; (c) B. Ma, H. M. Sulzbach, R. B. Remington, H. F. Schaefer III, J. Am. Chem. Soc., 1995, 117, 8392–8400. (a) Y. Tobe, K. Ueda, K. Kakiuchi, Y. Odaira, Y. Kai, N. Kasai, Tetrahedron, 1986, 42, 1851–1858; (b) Y. Tobe, M. Jimbo, K. Kobiro, K. Kakiuchi, J. Org. Chem., 1991, 56, 5241–5243; (c) Y. Tobe, T. Takahashi, K. Kobiro, K. Kakiuchi, J. Am. Chem. Soc., 1991, 113, 5804–5808; (d) Y. Tobe, A. Takemura, M. Jimbo, T. Takahashi, K. Kobiro, K. Kakiuchi, J. Am. Chem. Soc., 1992, 114, 3479–3491. G. B. M. Kostermans, M. Bobeldijk, W. H. de Wolf, F. Bickelhaupt, J. Am. Chem. Soc., 1987, 109, 2471–2475. S. Rosenfeld, J. Org. Chem., 1993, 58, 7572–7575. (a) V. Königstein, W. Tochtermann, Tetrahedron Lett., 1986, 27, 2961–2964; (b) V. Königstein, W. Tochtermann, E.-M. Peters, K. Peters, H. G. von Schnering, Tetrahedron Lett., 1987, 28, 3483– 3486. (a) Y. Tobe, M. Jimbo, S. Saiki, K. Kakiuchi, K. Naemura, J. Org. Chem., 1993, 58, 5883–5885; (b) Y. Tobe, M. Jimbo, H. Ishii, S. Saiki, K. Kakiuchi, K. Naemura, Tetrahedron Lett., 1993, 34, 4969–4970. By applying their newly proposed procedure for the evaluation of aromatic stabilization energy (ASE), Schleyer and Puhlhofer have shown that the ASE of 31 a is estimated to be 19.5 kcal mol–1, thus, the distortion in 31 a reduces the ASE of the benzene moiety by 12 kcal mol–1 P. von R. Schleyer, F. Puhlhofer, Org. Lett., 2002, 4, 2873–2876. The ASE of 38 a, evaluated by applying the same procedure, is 13–17 kcal mol–1: T. Tsuji, unpublished results. (a) G. J. Bodwell, J. N. Bridson, T. J. Houghton, J. W. J. Kennedy, M. R. Man-

103

104

3 Highly Strained Cyclophanes nion, Chem. Eur. J., 1999, 5, 1823–2827; (b) G. J. Bodwell, J. J. Fleming, M. R. Mannion, D. O. Miller, J. Org. Chem., 2000, 65, 5360–5370; (c) G. J. Bodwell, J. J. Fleming, D. O. Miller, Tetrahedron, 2001, 57, 3577–3585; (d) G. J. Bodwell, D. O. Miller, R. J. Vermeij, Org. Lett., 2001, 3, 2093–2096; (e) G. J. Bodwell, J. N. Bridson, M. K. Cyranski, J. W. J. Kennedy, T. M. Krygowski, M. R. Mannion, D. O. Miller, J. Org. Chem., 2003, 68, 2089–2098. 25 (a) I. Aprahamian, G. J. Bodwell, J. J. Fleming, G. P. Manning, M. R. Mannion, T. Sheradsky, R. J. Vermeij, M. Rabinovitz, J. Am. Chem. Soc., 2003, 125, 1720–1721; (b) I. Aprahamian, G. J. Bodwell, J. J. Fleming, G. P. Manning,

M. R. Mannion, T. Sheradsky, R. J. Vermeij, M. Rabinovitz, Angew. Chem., 2003, 115, 2651–2654; Angew. Chem. Int. Ed., 2003, 42, 2547–2550. 26 (a) T. Tsuji, M. Ohkita, S. Nishida, J. Am. Chem. Soc., 1993, 115, 5284–5285; (b) T. Tsuji, M. Ohkita, T. Konno, S. Nishida, J. Am. Chem. Soc., 1997, 119, 8425–8431. 27 (a) T. Tsuji, Z. Komiya, S. Nishida, Tetrahedron Lett., 1980, 21, 3583–3586; (b) T. Tsuji, S. Nishida, Tetrahedron Lett., 1983, 24, 3361–3364. 28 (a) H. Kawai, T. Suzuki, M. Ohkita, T. Tsuji, Angew. Chem., 1998, 110, 827–829; Angew. Chem. Int. Ed., 1998, 37, 817–819; (b) H. Kawai, T. Suzuki, M. Ohkita, T. Tsuji, Chem. Eur. J., 2000, 6, 4177–4187.

105

4

Superphanes Rolf Gleiter and Rolf Roers

4.1

Introduction

Chemists, especially those who are dealing with polycyclic hydrocarbons, prefer descriptive names for their highly symmetrical molecules [1] such as cubane and adamantane. The name cyclophane was coined by Cram and Steinberg [2] from cyclo, phenyl and alkane in 1951 for tricyclo[8.2.2.24,7]hexadeca-4,6,10,12(1),13,15hexane (1). With cyclophane chemistry becoming more popular a systematic set of rules for the cyclophanes was proposed [3]. The suffix “phane” thereby defines a compound containing at least one aromatic (or cyclic conjugated) moiety and at least one bridge. Since the synthesis of [2.2]paracyclophane various kinds of phanes have been prepared [4]. In connection with this review we mention the multibridged species [5] and the first superphane [26](1,2,3,4,5,6)cyclophane (2) which was prepared by Boekelheide et al. [6] and paved the way for superphane chemistry [5, 7]. The attribute “super” was suggested by Hopf [6 a] for 2. The structure of 2 can be described as two benzene rings clamped parallel on top of each other by six ethano bridges. The superphane terminology can easily be extended to various other cyclic conjugated p-systems [7]. In the following we will discuss the syntheses, structures and properties of various superphanes, ordered according to the ring size of the cyclic conjugated p-system.

Chart 4.1

Modern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

106

4 Superphanes

4.2

[n2]Cyclopropenonophanes 4.2.1

Synthesis

The first cyclopropenono superphanes were synthesized by a stepwise process [8]. The treatment of cyclodeca-1,6-diyne (3(3)), cyclododeca-1,7-diyne (3(4)) and cyclotetradeca-1,8-diyne (3(5)) with an equimolar amount of LiCCl3 in THF at –78 8C to –10 8C yielded the dichlorobicycloalkenynes (4(n)) [9]. Subsequent hydrolysis yielded the [32]-, [42]- and [52]cyclopropenonoacetylenophanes (5(n)) but also the ring-enlarged cyclic diynes 6(n) (Scheme 4.1) [9]. The efforts to prepare [n2]cyclopropenonophanes directly from the cycloalkadiynes 3(n) failed even with a large excess of LiCCl3. More successful was the cyclopropanation of the triple bond in 5(n) with one equivalent of sodium trichloroacetate followed by hydrolysis. This treatment afforded the desired [n2]cyclopropenonophanes 7(n) in low yields (3–5%) (Scheme 4.2). Higher yields were obtained by an alternative protocol which is outlined in Schemes 4.3 and 4.4 [8]. The key compounds for this reaction were the dichlorotricyclodienes 8(n) and 9(n). These species were converted into the corresponding dichloro[n2]cyclopropenyliophanes 10(n) (Scheme 4.3) by hydride abstraction. The cations were then converted without isolation into [n2]cyclopropenonophanes 7(n) by hydrolysis.

Scheme 4.1

4.2 [n2]Cyclopropenonophanes

Scheme 4.2

Scheme 4.3

The starting materials, the isomeric mixture of 8(n) and 9(n), were prepared in a four-step sequence (Scheme 4.4) by applying a modified form of methods developed in the chemistry of monofunctional dichlorocyclopropenes (Scheme 4.4) [9]. The cyclodiynes 3(n) (n = 3–5) were treated with Schwartz’s reagent and N-bromosuccinimide (NBS) to yield 11(n) and 12(n), respectively. Treating 11(n) or 12(n) with a large excess of sodium trichloroacetate provided the dibromotetrachlorotricycloalkanes 13(n) and 14(n) in about 50% yield. Dehalogenation of 13(n) and 14(n) with methyl lithium gave 8(n) and 9(n) in yields of 90%.

Scheme 4.4

107

108

4 Superphanes

Molecular structure of 7(3); top view (above), side view (bottom).

Fig. 4.1

The [n2]cyclopropenonophanes 7(n)(n = 3–5) proved to be fairly stable crystalline compounds. X-ray structure analysis of 7(3) revealed that there is an interplanar angle between the cyclopropenone moieties of 95.58. The ten-membered ring adopts a boat conformation (Fig. 4.1). Further cyclopropenonophanes were obtained from the tetrathiacyclodiynes 15(m,n = 3–6) (Scheme 4.5) [10]. The reaction of 15(m,n) with sodium trichloroacetate yielded the bicyclic and tricyclic tetrathiacyclopropenonophanes 16(m,n) and 17(m,n). The superphanes 17(3,5), 17(4,6), 17(5,5), 17(5,6) and 17(6,6) were isolated. For 17(3,5), 17(4,6) and 17(5,5) [11] structural details were obtained from X-ray studies on single crystals. These studies revealed a conjugation between the sulfur substituents and the cyclopropenone rings. The protocol for preparing tetrathiacyclopropenonophanes shown in Scheme 4.5 can be extended to the corresponding tetraselena congeners. This has been demonstrated by preparing 1,1',7,7' tetraselena[7,7']cyclopropenonophane [12] from 1,4,10,13-tetraselenacyclooctadeca-2,11diyne [13].

4.4 C4-Superphanes

a, b

+

Scheme 4.5

4.3

Superbridged Cyclopropenyliophanes

So far there is only one example, 20, known of a superbridged cyclopropenyliophane [14]. It was generated by the superbridged [52]cyclopropenonophane 18 (Scheme 4.6), a congener of 7(5) [9]. The geminal dimethyl groups were used to avoid side reactions when the O-alkylated cyclopropenone derivative 19 was reacted with 1,5-diaminopentane [14]. Xray investigations on 20 revealed that the two cyclopropenylium rings are nearly parallel to each other. In contrast, in the twofold bridged [52]cyclopropenyliophane 19 the interplanar angle between the two rings amounts to 418. The bond lengths within the cyclopropenylium rings vary between 1.34 Å and 1.38 Å [14].

Scheme 4.6

4.4

C4-Superphanes

In 1988, a new pathway for cyclobutadieno superphanes was established, which was based on cyclic precursors [15, 16]. The reaction of 1,6-cyclodecadiyne (3(3)) with dicarbonyl(g5-cyclopentadienyl)cobalt, (CpCo(CO)2) gave superphane 26 in

109

110

4 Superphanes

12% yield (Scheme 4.7). A second low molecular mass product isolated with 6% yield was the intramolecular complex 23. The product distribution can be rationalized as an interplay of steric and electronic factors. Key intermediates were cobaltacyclopentadienyl species such as 22 and the tricyclic cyclobutadiene complex 25, which could not be isolated under these reaction conditions [7, 17]. The X-ray structure of 26 is shown in Fig. 4.2. The central carbon backbone has a C4h symmetry and the distance between the cyclobutadiene moieties is 2.9 Å. Fig. 4.2 shows a projection from the top and indicates a pinwheel conformation of the four propane chains [15]. Obviously, the intermolecular pathway with the intermediates 24 and 25 is preferred to the intramolecular route (intermediate 21, cobaltacycle 22). We ascribe this partly to the relative low first ionization energy of 3 which was assigned to the ionization from the highest occupied molecular orbital, the “in-plane” p-orbital of 3(3). This favours a side attack of electrophilic metal fragments on the triple bonds. Furthermore, the formation of the highly strained 22 needs higher activation energy than that of its intermolecular analogue [16].

Scheme 4.7

4.4 C4-Superphanes

Fig. 4.2

Molecular structure of 26; side view (left), top view (right). The distances are given in Å.

The higher activation energy can be explained with the anti-Bredt structure of 22. This concept prompted the question, whether the ratio of intermolecular and intramolecular products is a function of the diyne ring size. The investigation of symmetric cycloalkadiynes 3(3–6) in reaction with CpCo complexes showed that diynes with an odd number of chain atoms yield superphanes whereas an even number of chain atoms lead to intramolecular complexes preferably [16, 18]. Strong steric effects of bulky a-alkylsilyl substituents of unsymmetric monoalkynes are well known to be the key of transition metal-induced [2+2]cycloadditions which lead to C2v symmetric main products [19]. We found that diynes 27 and 28 [20] can be reacted to form superphanes 29 and 30 in high yields (40–60%) (Scheme 4.8) [21]. Obviously, silyl bridges have strong directing effects in so far as they block intramolecular pathways and repress oligomerizations in favor of the dimerization as well [17]. In our search for higher oligomers we reasoned that small chains on both sides of the triple bonds or small chains on one side and a chain with bulky groups on the other might favor higher oligomers. Indeed, we found that 1,1,2,2-tetramethyl1,2-disilacycloocta-3,7-diyne can be reacted to the belt-like phanes 31 and 32 (Chart 4.2) [22]. The one-pot concept of cyclodiyne dimerization gave access to fairly simple syntheses of cyclobutadieno superphanes. However, a stepwise synthesis, i.e. the di-

111

112

4 Superphanes

a) CpCo(COD), 120 8C Scheme 4.8

Chart 4.2

rected synthesis of the tricyclic diyne 25, was targeted for three reasons: 1) the exclusion of competing oligomerizations; 2) the incorporation of different chain lengths in one superphane; 3) the combination of different metal fragments. Our successful stepwise pathway to superphane 26 started from a masked cyclodecadiyne, 1,6-cyclodecynol (33) which was dimerized with CpCo(COD) and oxidized to the tricyclic diketone 34 (Scheme 4.9) [23]. The Lalezari procedure leads to the tricyclic diyne 25 in good yields [24].

4.4 C4-Superphanes

a) CpCo(COD); b) acetone, Al(O-/Pr)3; c) H3N2CONH2HOAc; d) SeO2/CH3CO2H; e) 180 8C–2008C/Cu Scheme 4.9

Scheme 4.10 summarizes four reactions of 25. Refluxing of 25 with CpCo(CO)2 yielded 26 in high yields after only 2 h reaction time [23]. This explains why 25 could never be isolated during the one-pot reaction of 3(3) to 26. When 25 was refluxed with CpCo(CO)2 together with an excess of DMAD, the mixed superphane 35 could be isolated in poor yields. Nevertheless, this finding supports the idea of an intramolecular cobaltacyclopentadiene intermediate. This species might undergo not only a straight forward rearrangement to 26, but a “trimerization” is also possible by incorporating a third alkyne unit. The potential of a stepwise superphane synthesis was further demonstrated in the reaction of 25 with Fe(CO)5 in refluxing toluene. The mixed superphane 36 was isolated with 8% yield and combines different metals in one superphane. Finally, the reaction with (Me5Cp)Co(CO)2 yielded 37, the first superphane of this family, which displayed different substitution patterns on the CpCo units. 37 was subsequently used as starting point for a series of donor–acceptor-substituted superphanes [25]. Chart 4.3 lists the other superphanes 38–40 which were accessible by stepwise syntheses [26]. A systematic extension of the stepwise superphane synthesis led to belt-like macrocycles with four (46) and eight (47) CpCo-cyclobutadienyl-building blocks [27] respectively. The synthesis of these species starts with 41 (Scheme 4.11) which can be obtained by reacting 33 with CpCo(COD). Selective oxidation of one alcohol function of 41 yields 42. Using the Lalezari protocol (cf. Scheme 4.9) allows the introduction of one alkyne unit (43). The CpCo(COD)-supported dimerization of 43 and subsequent oxidation of the alcohol functions led to 44 which was converted into 45, the key species for the synthesis of the belt-like species 46 and 47.

113

114

4 Superphanes

Scheme 4.10

Chart 4.3

4.4 C4-Superphanes

Scheme 4.11

4.4.1

Properties of Cyclobutadieno Superphanes

Biscyclobutadieno superphanes turned out to be ideal model compounds for the study of interactions between two CpCo cyclobutadiene units with varying distances and varying electronic environments, respectively [17, 28]. Cyclic voltammetry of 26 and 23 a (Fig. 4.3) showed that the oxidation potential of 26 is significantly smaller than that of the intramolecular reference complex 23 a. This lower value corresponds to a higher HOMO of 26 as compared to 23 a. The second potential of 26, which is higher relative to that of 23 a, indicates that the positive charge generated during the first oxidation is partially delocalized. By increasing the chain lengths (48 and 49) the CpCo units get more independent. Through the

115

116

4 Superphanes

CV oxidation potentials of 26, 48, 49, and 23 a. The data are referred to the ferrocene/ferrocenium couple.

Fig. 4.3

investigation of a series of donor–acceptor-substituted superphanes a ground state p/p interaction was detectable [25] (see also chapter 14). 4.4.2

Oxidative Demetallations

When 26 is reacted with (NH4)2[Ce(NO3)6], the CpCo fragments are removed [29]. As main product (80%) the [34]-bridged syn-tricyclo[4.2.0.02.5]octa-3,7-diene (50) was isolated (Scheme 4.12). Irradiation of 50 yielded the propella [34]cubane (51). Scheme 4.12 summarizes the pathway from the cyclic alkyne to the bridged cubane. This sequence corresponds to a fourfold dimerization of two fixed alkyne units.

4.5 C5-Superphanes

3(3)

Scheme 4.13

4.5

C5-Superphanes

For the sake of completeness we mention only briefly the superphanes which are derived from ferrocene, because Chapter 5 in this book is devoted to bridged ferrocenes. In the early 1980s, Hisatome et al. achieved the synthesis of a pentabridged ferrocenophane [30]. In Scheme 4.13 we show an abbreviated way how the first C5-superphane was achieved [31]. Following the earlier work of Schlögl et al. [32] ferrocene was bridged via Friedel-Crafts acylation and alkylation in a stepwise manner. The synthesis of [24](2,3,4,5)thiophenophane (59), which was seen as the first “ultimate” heterophane, was achieved in a five-step synthesis starting from 3,4bis(chloromethyl)-2,5-dimethylthiophene (55) (Scheme 4.14) [33]. It turned out, that the superthiophenophane shows remarkable bathochromic shifts when the UV spectrum was compared with those of doubly bridged thiophenophanes and tetramethylthiophene. This shift was considered as evidence for either a transannular interaction [34] of the two thiophene rings in 59, an increased distortion of the planes of the two rings, or both [35]. Analogous to the stepwise synthesis of 26, we developed a sequence for superphanes with CpCo-stabilized cyclopentadienone units, in which a [2+2+1]cycloaddition of two alkynes and one CO group is accomplished (Scheme 4.15) [35, 36]. 5-cyclodecynone (60) was refluxed with CpCo(CO)2 to yield the isomeric triketones 61. The Lalezari procedure led to tricyclic diyne 62.

Scheme 4.12

117

118

4 Superphanes

Scheme 4.14

a) CpCo(CO)2, 190 8C; b)H3N2CONH2HOAC; c)SeO2/CH3CO2H; d) 180 8C–2008C/Cu Scheme 4.15

Scheme 4.16

4.5 C5-Superphanes

Scheme 4.17

Starting from 62, both the mixed superphane 63 as well as the biscyclopentadienono superphane 64 could be synthesized (Scheme 4.16). The chemoselectivity of tricyclic diyne 62 was controlled by the reaction conditions. At 190 8C, the mixed superphane 63 was the main low molecular weight product, whereas irradiation of 62 led to 64 in which the CO units are exclusively syn oriented [36]. Oxidation of CpCo-stabilized cyclopentadienono superphanes turned out to be irreversible under CV standard conditions [35]. Protonation [37 a, b, c], alkylation [37 d, e] and acylation [37 f ] of cyclopentadienone metal complexes are well-known reactions. Treatment of CpCo cyclopentadienone complexes with an excess of triethyloxonium tetrafluoroborate yields yellow colored O-ethylcobalticinium salts. In the case of 64 the same reaction afforded the mono- and bis-O-ethylcobalticinium salts [38]. Protonation of 64 yields the diprotonated superphane [38]. Recently, a stepwise synthesis of a mixed thiopheno-cyclobutadieno superphane was accomplished, based on the zirconocene dichloride mediated thiophene formation [39]. Starting from a silaprotected 1,6-cyclodecynol 65 the tricyclic thiophene derivative 66 was prepared by applying a protocol suggested by Negishi et al. [39 a] and Nugent et al. [39 b]. The silyl-protected diol 66 was transferred in two steps into the dione 67. The synthesis of the tricyclic diyne 68 was accomplished via the Lalezari protocol (Scheme 4.17). The intramolecular ring closure to the mixed superphane 69 was achieved by heating 68 with CpCo(COD).

119

120

4 Superphanes

4.6

Superbridged Benzene Rings

The first superphane was synthesized by Boekelheide et al. via the application of an ingenious and efficient protocol [6]. The synthesis of 2 was based on the o-xylylene dimerization reaction [40] which was applied three times [6]. Gas phase pyrolysis of 2,4,5-trimethylbenzyl chloride (70) at 710 8C and 10–2 torr gave 71 (Scheme 4.18). Heating of 71 at 300 8C yielded the dimer 72. For the next dimerization step 72 was transformed to the chloride 75 by conventional means. Repeating the dimerization step a second time yielded the tetrabridged cyclophane 76. After conversion to 79 the stage was set to generate 2 (Scheme 4.18). A second route to 2 was published by Hopf et al. [41]. This six-step route commences with a modified Rieche formylation of 80 to afford a mixture of the dialdehydes 81 and 82 (Scheme 4.19). The next step, the transannular bond formation, was accomplished by a Bamford-Stevens reaction. In the cases of 81 and 82 two new transannular C–C bonds were formed to yield the fourfold bridged isomers 83 and 84. Repeating the

710 Scheme 4.18

4.6 Superbridged Benzene Rings

Scheme 4.19

Rieche formylation and Bamford-Stevens procedure yields the fivefold bridged cyclophane 87 which was converted via 88 to 2. The bottleneck of this elegant procedure is the low yield of 81 and 82 (16%). The molecular geometry of superphane 2 determined by X-ray crystallographic analysis [6 b, 42] is shown schematically in Fig. 4.4. As anticipated, the molecule adopts D6h symmetry with the ethano bridges in an eclipsed conformation. The benzene rings are separated by 2.624 Å. The most surprising feature is the distortion of the bond angle of the sp2–sp3 carbon–carbon bonds out of planarity with the benzene ring by 20.38. Calculations by Lindner predict [43] a strain energy for 2 between 60 and 79 kcal mol–1. The photoelectron spectroscopic investigation of 2 reveals an ionization energy of 7.55 eV [44]. This energy seems rather low, however due to symmetry reasons

121

122

4 Superphanes

Fig. 4.4

Perspective view of 2. The distances are given

in Å.

the HOMO of [2n]cyclophanes is effected only weakly by the ethano bridges and thus its electron donor capability is less than expected [45]. This behavior is also found in the UV/Vis absorption spectrum of the charge transfer complex of 2 with TCNQ [6 b]. The value recorded for the maximum of the long wavelength band (kmax = 572 nm) is considerably shorter than expected if the shortening of the distance between the decks and the alkyl effect of the bridges were independent and additive [6 b]. With respect to its high strain energy, the superphane 2 is relatively stable. Heating of 2 in the presence of trapping agents for benzylic radicals (diisopropyl benzene) at 350 8C for 24 h or dimethyl maleate at 200 8C (for 24 h) led only to the complete recovery of unchanged 2. Birch reduction of superphane 2 gave the expected dihydro product in only poor yield [6 b] whereas [2,2]paracyclophane and [24](1,2,4,5)cyclophane were reduced easily. A better way to achieve a dihydro derivative was found by treating 2 with the strong electrophile dimethoxycarbonium tetrafluoroborate [6 b]. This treatment gave a deep red solution whose 1H NMR spectrum is in accord with structure 89 (Scheme 4.20). The reduction of the red solution with NaBH4 led to the dihydro derivative 90. Reaction of 2 with an excess of NBS and a small amount of benzoyl peroxide yielded a monobromide, accompanied by traces of dibromides. Treatment of the resulting monobromide with DBN yielded [26](1,2,3,4,5,6)cyclophan-1-ene (91) (Scheme 4.20) [6 b]. The reaction of 2 with ethyl diazoacetate in presence of CuSO4 led to an enlargement of one ring in 2 (Scheme 4.21) [6 b] to yield a mixed phane with one cycloheptatriene ring 92. This product was transferred to the corresponding tropylium phane 94 by reduction and treatment with BF3. It is interesting to note that 94, when exposed to water, was transferred back to superphane 2 [6 b]. When a solution of 2 in dichloromethane was treated with an excess of dicyanoacetylene in the presence of aluminum trichloride the adduct 96 (X-ray analysis) was isolated after aqueous work-up (Scheme 4.22). A logical interpretation of structure 96 is that to each deck of 2 one equivalent of dicyanoacetylene was added to yield the intermediate 95 which leads via HCl addition and intramolecu-

4.6 Superbridged Benzene Rings

Scheme 4.20

; Scheme 4.21

lar Diels-Alder addition to 96. The unusual structure of 2 is matched by its unusual chemistry. A strong motivation for the synthesis of [36](1,2,3,4,5,6)cyclophane 97 was the prediction that it can be isomerized by photochemical means to the sixfold bridged hexaprismane 98 [46]. Shinmyozu et al. [47, 48] described two closely related routes to 97 in which the propano bridges between the benzene rings were introduced step by step via a transannular aldol condensation reaction between an acetyl group and a formyl group. The difference between the routes results from the starting material. The first route is summarized in Scheme 4.24. It commences with [33](1,3,5)cyclophane (99) [49] which was obtained by reaction of 1,3,5-tris(bromomethyl)benzene and (p-tolylsulfonyl)methyl isocyanide (TosMIC) [50]. Acylation of 99, followed by formylation produces 100. Intramolecular aldol type condensation between an acetyl group and a pseudogeminally sub-

123

124

4 Superphanes

Scheme 4.22

Scheme 4.23

Scheme 4.24

4.6 Superbridged Benzene Rings

Scheme 4.25

stituted formyl group and subsequent hydrogenation leads to the ketone 101 which was reduced to the fourfold bridged cyclophane 102 [47]. Twofold repetition of the five steps just described leads to 97 via the fivefold cyclophane 103 [51]. In a preceding variant of this synthesis [47] the key ring-closing step was carried out between an acetyl group and a pseudogeminally substituted CH2Cl group (100 in which CHO was replaced by CH2Cl). This was continued until 97 was obtained. A second, more efficient way started from [32](1,3)cyclophane (104) [52] which was converted into the tetrakis(bromomethyl)[32]cyclophane 105. Twofold ring closure between 105 and TosMIC (Scheme 4.25) in the presence of NaH in DMF yielded 106. The fourfold bridged cyclophane 107 was obtained from 106 by reduction with Li/NH3 in the presence of ethanol. By a sequence of acetylation/formylation, 107 was transferred to 103 and finally to 97 [48]. The multibridged cyclophanes with propano bridges such as 97, 99, 102, 103 and 107 are flexible in solution. The energy barrier (DG=) for the flipping of the propano bridges of one pinwheel conformation into the other (see Scheme 4.26) was estimated by NMR spectroscopy to be 10.9 kcal mol–1 (Tc = –40 8C) [48]. Ab initio calculations suggest a stepwise mechanism for this process. X-ray investigations were carried out on 97 and various complexes such as the complex 97 · TCNQ · C6H6 (1 : 1 : 1) at –190 8C, and 97 · TCNQF4 (1 : 1) [53]. In the first two crystals the cyclophane moiety is observed in a D6h conformation due to severe disorder of the bridges. No structural differences were observed in the cyclophane moieties of 97 and its TCNQ complex. Contrastly, in the complex of 97 · TCNQF4 the

Scheme 4.26

125

126

4 Superphanes Fig. 4.5 Perspective view of 97. The distances are given in Å.

cyclophane moiety shows approximately C6h symmetry in the solid state (Fig. 4.5). The distance between the two benzene rings in both 97 · TCNQ · C6H6 and 97 · TCNQF4 was found to be 2.94 Å. This value is larger than that reported for 2 by 0.32 Å, indicating that much less strain energy is present in 97. In line with the larger distance of the p-systems is the smaller angle (4.58) found for the bending of the C(sp2)–C(sp3) bond out of the plane of the benzene ring of 97 compared with 2 (208). The interplanar angles within the propano bridges vary between 1408 and 1428 (Fig. 4.5). A comparison between the longest wavelength band in the UV/Vis spectrum of the TCNE complexes of 2 (kmax = 572 nm) [6 b] and 97 (kmax = 728 nm) shows a considerable difference. This is in agreement with the observation that propano bridges influence the antisymmetric HOMO whereas ethano bridges influence a symmetric lower lying occupied MO [54].

4.7

Concluding Remarks

Since the first synthesis of 2, the superphane concept has been extended to cyclic p-systems of ring size three to five. Larger ring systems, e.g. tropylium have not been reported. A further extension, e.g. the replacement of all ethano bridges in 2 by double bonds (108) or even benzene rings to “hyperphanes” (109) is also missing. However, the latter case is not far away in view of the recent synthesis of a tetrabenzoannelated 1,2,4,5-cyclophane [55]. Although the superphanes provide excellent models for studying the interactions of rigid and sterically fixed p-systems by means of spectroscopy and electrochemistry, not many studies are known to date. This is mainly because the multistep syntheses required to prepare the various superphanes deter chemists from further investigations. Therefore more simple pathways are desired. By looking at the known superphanes one notices that most examples contain two p-systems of the same kind. However, donor–acceptor superphanes should also be of interest with respect to their properties.

4.9 References

Scheme 4.27

4.8

Acknowledgement

We are grateful to the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie and the BASF Aktiengesellschaft, Ludwigshafen, for financial support.

4.9

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4

5

6

7

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Carbon-Bridged Ferrocenophanes Joon-Seo Park and T. Randall Lee

5.1

Introduction

In the early 1950s, ferrocene was discovered independently by two research teams [1, 2]. Although Kealy and Pauson proposed a r-bonded structure in their report to Nature [1], Woodward soon afterward suggested the ‘sandwich structure’ for this new iron compound [3], which was quickly confirmed by X-ray diffraction studies [4, 5]. Despite intense study for more than 50 years, ferrocene is still attracting the interest of scientists working in a wide variety of disciplines. Ferrocene is the first known ‘sandwich complex’, in which two cyclopentadienyl (Cp) ligands lie in parallel planes with a separation of * 3.32 Å [6–8]. The distance between the two Cp rings is comparable to the van der Waals distance between two aromatic rings, which is * 3.40 Å. The Cp ligands in ferrocene are covalently bonded to the iron center, but they are almost free to rotate with respect to each other; the activation barrier to the rotation is about 4–8 kJ mol–1 [9– 12]. The staggered conformation of the rings with approximately 368 of ring twist angle is slightly preferred over the eclipsed conformation [13]. Ferrocene is a diamagnetic, 18-electron, d6 complex, and the aromatic character of ferrocene was demonstrated in 1952 [6]. Ferrocene acts as a weak base, and thus the Cp rings in ferrocene can undergo various electrophilic substitution reactions. Although the mechanism is still controversial, the reactions might start from the attack of the electrophile on the lone pairs of the metal center to give the bent intermediate followed by migration of the electrophile to the Cp ligand and then deprotonation. Ferrocene undergoes various aromatic reactions including Friedel-Crafts acylation and alkylation, Vilsmeier formylation, and mercuration [14, 15]. Ferrocene is 106 times more reactive than benzene in Friedel-Crafts acylation. Several useful reviews provide comprehensive summaries of the chemistry of ferrocene [16, 17]. Ferrocene and its derivatives have certain desirable characteristics that render them useful in a variety of applications. Unlike most organometallic compounds, ferrocene is soluble in most organic solvents and stable in air and at elevated temperatures [18]. Ferrocene, therefore, can be easily handled without decomposition. Ferrocene is reversibly oxidized by mild one-electron oxidizing agents to the more reactive deep green ferrocenium radical cation, which is an excellent radical trap Modern Cyclophane Chemistry. Edited by Rolf Gleiter, Henning Hopf Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30713-3

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5 Carbon-Bridged Ferrocenophanes

[15]. This property renders ferrocene attractive for use in chemical sensing and other technologies [19]. The p-electrons of the Cp rings of ferrocene are delocalized through the d-electrons of iron, which makes ferrocene and its derivatives useful for constructing conducting and optoelectronic materials [20–22]. Ferrocenophanes are ferrocene derivatives in which the two Cp rings are connected by an atomic or molecular bridge. Ferrocenophanes also possess most of the desirable properties mentioned above for ferrocene. In ferrocenophane, however, the rotation of Cp rings can be restricted, and the dihedral angle of two Cp rings can be varied depending on the length, position, and structure of the bridges. The structural variation can affect the properties and thus the reactivities of ferrocenophanes. For example, the tilt of Cp rings can facilitate electrophilic attack on the metal center. Investigation of ferrocenophanes, therefore, includes synthesis and structural characterization of ferrocenophane derivatives and the study of their properties as a function of structure. Several useful reviews for this area of research have been published [23–25]. Recent development of various kinds of ferrocenophanes suggest that an updated review is timely. To this end, the focus of the present review is the synthesis and structure of ferrocenophanes having all carbon bridges. Descriptions of other ferrocenophanes and related metallocenes can be found in chapters 4, 6, and 16.

5.2

Nomenclature

In ferrocenophanes, the Cp rings of ferrocene are connected by either an atomic or a molecular bridge. The carbon-bridged ferrocenophanes can be categorized into two major groups depending on the number of ferrocene units in the compound. The first class consists of mononuclear ferrocenophanes in which the Cp rings of one ferrocene moiety are connected by one or more bridges. The mononuclear ferrocenophanes can be further divided into two subgroups depending on the number of bridges: singly-bridged ([m]) and multiply-bridged ferrocenophanes ([m]n). The second class can be described as multinuclear ferrocenophanes ([mn]) in which two or more ferrocene units are linked by one or more bridges (Fig. 5.1). This review adopts the most widely accepted nomenclature, which was proposed by Smith [26] and Vögtle and Neumann [27] for bridged organic aromatic cyclophanes and metallocenophanes. The mononuclear ferrocenophanes are denoted as [m][n][o][p][q]ferrocenophanes, where the number in square brackets indi-

Fig. 5.1

Structures of ferrocenophanes

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

cates the length of the bridge. For multiply-bridged homonuclear ferrocenophanes, the relative location of the bridge is provided by the number in round brackets. The numbering of atoms begins at the end of the longest bridge. If multiple bridges have the same length, the substituted bridge is numbered first. According to this system of nomenclature, compound 1 is denoted as 1-hydroxy-2methyl[5]ferrocenophane, and the name of the multiply-bridged ferrocenophane 2 is 2,2-dimethyl[3](1,1')[3](3,3')ferrocenophane. Multinuclear ferrocenophanes are denoted as [m.n.o.p.q]ferrocenophanes. The ferrocenophane 3 is named as 1methyl[1.1](1,1'';1',1''')ferrocenophane, where the placement of the bridges is also provided by the number in round brackets. Because ferrocenophane structures are diverse, a different nomenclature can sometimes be more convenient to denote the structure.

5.3

Mononuclear Carbon-Bridged Ferrocenophanes 5.3.1

[1]Ferrocenophanes

[1]Ferrocenophane, with a single carbon atom in the bridge, is too strained to exist due to the extreme tilt of the Cp rings. A number of heteroatom-bridged [1]ferrocenophanes, however, have been reported; apparently, the larger atomic radii of the heteroatoms afford less tilted and thus more stable structures than the mono-carbon-bridged [1]ferrocenophane. The relative strain in heteroatom-bridged [1]ferrocenophanes is related to the ring tilt angle, which varies from 18 to 278 in known derivatives. The strain in these ferrocenophanes leads to thermal ringopening polymerization (ROP) to give ferrocene-containing polymers (Scheme 5.1). Since the first report by Manners and co-workers of the successful synthesis of poly(ferrocenylsilanes) by a thermal ROP [28], various heteroatom-bridged [1]ferrocenophanes, including those with Group 13 through Group 16 elements in their bridges, have been found to undergo ROP reactions [29–40]. Because heteroatom-bridged ferrocenophanes are beyond the scope of this chapter, we refrain from more detailed discussions and direct the reviewer to recent reviews on the topic [41, 42] as well as chapter 16.

133

134

5 Carbon-Bridged Ferrocenophanes

Scheme 5.1

5.3.2

[2]Ferrocenophanes

Analyses of ferrocenophanes bridged by two carbon atoms have shown that these compounds are highly strained because the length of the bridge is relatively short [43–45]. As mentioned in the previous section, the tilt angle of the Cp rings can be used to estimate the ring strain in ferrocenophanes. Regardless of their high strain, a number of interesting [2]ferrocenophanes have been reported. The reaction of 6,6-dimethylfulvene 6 with sodium followed by treatment with ferrous chloride gave the first carbon-bridged [2]ferrocenophane, 1,1,2,2-tetramethyl[2]ferrocenophane 8 (Scheme 5.2 and see chapter 6, section 6.4.2 for the analogous ruthenocenophane) [46]. Normally, the Cp rings of a [2]ferrocenophane are more tilted than those of ferrocene itself, and thus the [2]ferrocenophane is protonated more easily than ferrocene. The single crystal X-ray data for 8 showed a ring twist angle of 268 and a ring tilt angle of 238 [45]. The distance between carbon 1 of a Cp ring and carbon 1' of another Cp ring was found to be 2.70 Å, whereas the distance between the centers of two Cp rings was 3.32 Å. The nonsubstituted hydrocarbon-bridged analog exhibited a slightly smaller ring tilt angle of 21.68 [47]. The [2]ferrocenophanes bridged by two carbon atoms possess ring tilt angles comparable with those of highly strained silicon-bridged [1]ferrocenophanes (i.e. 20.88). Several interesting [2]ferrocenophanes having unsaturated bridges have been reported. In 1976, Yasufuku and coworkers described the reaction of transition metal ethynyl complexes with p-cyclopentadienyl(triphenylphosphine)dialkylacetylenecobalt [48]. The reaction of 1,1'-bis(phenylethynyl)ferrocene 9 with the diphenylacetylene cobalt complex afforded 1,2-(1,1'-ferrocenylene)-3,4,5,6-tetraphenylbenzene 10, which was the first ferrocenophane bridged with an aromatic ring [49]. When 9 was treated with p-cyclopentadienylbis(triphenylphosphine) cobalt, compound 11 was obtained in 10% yield [49]. The single crystal X-ray structure of 10

Scheme 5.2

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.3

exhibited a Cp ring tilt angle of 23.78 [50]. The dihedral angles between the central benzene ring and the Cp rings were found to be 90.68 and 94.98, and the two Cp rings were in a nearly eclipsed conformation. In compound 10, the length of bridging carbon–carbon bond (Csp2–Csp2) was found to be 1.388 Å, which is similar to the carbon–carbon length in benzene itself (1.397 Å). The trinuclear ruthenacycle [2]ferrocenophane 12 was prepared by the reaction of 1,1'-bis(phenylethynyl)ferrocene 9 with Ru3(CO)12 [51]. In the reaction, the dinuclear ruthenacycle complex 13 was also obtained as a minor product. The single crystal X-ray structure of 12 showed a ring tilt angle of 21.8; which is comparable to those of normal [2]ferrocenophanes even though two ruthenium atoms coordinate to the diene part of the complex.

The phosphorous-containing ferrocenophane, 1,1'-diphospha[2]ferrocenophane 14, was prepared by a four-step synthesis starting from 1-phenyl-3,4-dimethylphosphole-2-carboxaldehyde [52]. The aldehyde group of the 1-phenyl-3,4-dimethylphosphole-2-carboxaldehyde was converted to a bromomethyl group and then intermolecularly coupled via a Grignard reaction. After reduction and cleavage of the two Pphenyl bonds by lithium, treatment with ferrous chloride afforded the targeted compound 14. Because stabilized sp2 phosphorous derivatives are known as p-acceptor ligands rather than classical r-donor phosphines, the resulting compound promises an access to polymers containing unique sp2 phosphorous centers. The phosphorous-containing derivative 14 exhibited a Cp ring tilt angle of 208, which is similar to that of its all-carbon analog [52].

135

136

5 Carbon-Bridged Ferrocenophanes

Scheme 5.4

The structural data highlighted above indicate that [2]ferrocenophanes bridged by two saturated carbon atoms are highly strained. Like heteroatom-bridged ferrocenophanes, these highly strained ferrocenophanes can be used as monomers for ROP. As mentioned in the previous section, [1]ferrocenophanes bridged by single heteroatoms form organometallic polymers with high molecular weights due to their highly strained structures. The polymerization of a [2]ferrocenophane with two silicon atoms in the bridge, however, failed due to its minimal ring strain derived from a small tilt angle of 4.198 [53]. In contrast, the more strained carbonbridged [2]ferrocenophane with a tilt angle of 21.68 successfully polymerized to give poly(ferrocenylethylenes) [54]. Highly strained unsaturated [2]ferrocenophanes can also be utilized for polymerization. The intramolecular McMurry coupling of 1,1'-ferrocenedicarbaldehyde 15 afforded the vinylene-bridged ansa-ferrocene complex 16 (Scheme 5.4) [55]. The Xray crystallographic data of the complex, ansa-(vinylene)[2]ferrocenophane 16, showed a bent structure with a ring tilt angle of 238, which is comparable to those of saturated analogs. The ring-opening metathesis polymerization (ROMP) of this highly strained ferrocenophane with a molybdenum-based ROMP initiator [56] afforded insoluble poly(ferrocenylene vinylene) 17 (Scheme 5.4). The fully conjugated organometallic polymer is expected to facilitate electronic interactions between the metal centers due to its inherent electron delocalization. A pressed pellet of this polymer, however, exhibited weak conductivity after doping with I2. To overcome the poor solubility, block copolymers of ansa-(vinylene)[2]ferrocenophane with norbornene were prepared [55]. 5.3.3

[3]Ferrocenophanes

[3]Ferrocenophanes are the most readily accessible of all carbon-bridged ferrocenophanes because bridges that consist of three carbon atoms introduce relatively little structural strain in the system. The first [3]ferrocenophane was synthesized by Lüttringhaus and Kullick in the late 1950s. The reaction of sodium cyclopentadienide 18 with 1,3-dibromopropane gave the bis-cyclopentadienyl hydrocarbon 19, which was doubly deprotonated with sodium. Treatment of the disodium salt with ferrous chloride gave polymeric ferrocenes from which [3]ferrocenophane 20 was isolated in low yield (Scheme 5.5) [57]. A number of [3]ferrocenophanes have been prepared by intramolecular acylation reactions. The compound [3]ferrocenophane-1-one 22 was prepared by hetero-

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.5

annular Friedel-Crafts cyclization of b-ferrocenylpropionic acid 21 [58, 59]. Three reagents, trifluoroacetic anhydride, polyphosphoric acid, and aluminum chloride, were investigated for the self-condensation of b-ferrocenylpropionic acid 21, where trifluoroacetic anhydride afforded the desired product in the highest yield (87%). The starting propionic acid 21 was prepared by various methods, such as Willgerodt reaction of ferrocenyl ketones, carbethoxylation of acetylferrocene, and Friedel-Crafts acylation of ferrocene [60]. In the Friedel–Crafts acylation, the expected heteroannular cyclization might compete with the homoannular cyclization of acids. A systematic study of the effect of aliphatic chain length of x-ferrocenylaliphatic acids on cyclization showed that b-ferrocenylpropionic acid gave the heteroannularly-bridged [3]ferrocenophane-1-one 22, while x-ferrocenylaliphatic acids with longer chains afforded the homoannularly cyclized products or polymers [58]. The single crystal X-ray structure of [3]ferrocenophane-1-one 22 showed a tilt angle for the Cp rings of 8.88, which is smaller than those observed for [2]ferrocenophanes (> 20 8) [61]. The distance between carbon 1 of Cp and carbon 1' of Cp’ was found to be 3.10 Å, which is larger than those of [2]ferrocenophanes. These observations provide strong evidence that [3]ferrocenophanes possess less structural strain than [2]ferrocenophanes. Starting from 22, various derivatives of [3]ferrocenophane can be produced. Reduction of 22 by lithium aluminum hydride (LAH) afforded the corresponding alcohol 23. On the other hand, reduction with LAH-aluminum chloride gave the unsubstituted [3]ferrocenophane 20 in a nearly quantitative yield [58]. Furthermore, the modified McMurry coupling of [3]ferrocenophane-1-one 22 gave E,Zbis([3]ferrocenophane-1-ylidenes) 24 and 25 in 70% overall yield, in which the two [3]ferrocenophanes are separated by a rigid carbon–carbon double bond (Scheme 5.6) [62].

The intramolecular Friedel-Crafts cyclization can be extended to the asymmetric synthesis of ferrocenophanes [63]. A series of ferrocenyl ketones 26 underwent conversion to the corresponding alcohols 27 in high enantiomeric excesses via oxazaborolidine-catalyzed reduction. Subsequent methanolysis of the (R)-a-ferrocenyl

137

138

5 Carbon-Bridged Ferrocenophanes

Scheme 5.6

Scheme 5.7

alcohols 27 gave the corresponding methyl ethers 28, which were in turn converted to ethyl 3-ferrocenopropanoates 29 with retention of configuration on treatment with 1-ethoxy-1-(trimethylsilyloxy)ethene and BF3 · OEt2. After ester hydrolysis, heteroannular Friedel-Crafts cyclization of the resulting acids 30 afforded the enantiomerically enriched [3]ferrocenophanes 31. A number of [3]ferrocenophanes have been prepared by various condensation reactions. The [3]ferrocenophanes with functional groups at the 2-position of the bridge can be prepared by Dieckmann condensation of the dimethyl ester of ferrocene-1,1'-diacetic acid 32 followed by saponification and decarboxylation (Scheme 5.8) [64]. Like [3]ferrocenophane-1-one 22, [3]ferrocenophane-2-one 34 also can be reduced to the unsubstituted [3]ferrocenophane 20 and converted to the unsaturated [3]ferrocenophan-1-ene. Similarly, the intramolecular Claisen condensation of methyl 1'-acetylferrocenecarboxylate with potassium triphenylmethoxide in refluxing xylene afforded [3]ferrocenophane-1,3-dione 35 in high yield (78%) [65]. The single crystal X-ray structure of 35 showed that two Cp rings are tilted 9.88 with respect to each other [66]. The 2-substituted [3]ferrocenophane-1,3-dione 36 was prepared similarly. An alternative route to the 2-substituted compound, the alkylation of the carbanion

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.8

generated from [3]ferrocenophane-1,3-dione, however, afforded mainly the O-alkylation product 37, which was rationalized on the basis of steric hindrance of the 2-position by a-hydrogens of the Cp rings. On the other hand, condensation of [3]ferrocenophane-1,3-dione with benzaldehyde using triethylamine as catalyst gave 2-benzal[3]ferrocenophane-1,3-dione 38 [65]. The X-ray crystallographic data of 38 showed a little larger ring tilt angle (13.578) compared to that of 35 [67].

The compound 1-oxo-3-phenacyl[3]ferrocenophane 40 was prepared via internal Michael addition of 1-acetyl-1'-(3-oxo-3-phenyl-1-propenyl)ferrocene 39 using potassium hydroxide in boiling ethanol, where 1,14-dioxo[3.3]ferrocenophane-2,15-diene 41 was found as a co-product arising from the retro-Claisen-Schmidt reaction (Scheme 5.9) [68]. Subsequently, reaction with sodium methoxide in dimethylformamide was found to give only 40 in a slightly improved yield (21%). A series of 1,1'-dicinnamoylferrocenes 42 were converted to the corresponding [3]ferrocenophanes 43 by samarium diiodide-promoted reductive cyclization in a stereoselective manner (Scheme 5.10) [69]. In the single crystal X-ray structure, the Cp rings are in an eclipsed conformation with a ring twist angle of 2.78 and a ring tilt angle of 9.638. Unsaturated amino-substituted [3]ferrocenophanes 45 were prepared by an acidcatalyzed Mannich-type condensation of the corresponding enamines 44 [70, 71]. Catalytic hydrogenation of the resulting unsaturated [3]ferrocenophanes 45 in

Scheme 5.9

139

140

5 Carbon-Bridged Ferrocenophanes

Scheme 5.10

Scheme 5.11

THF at ambient temperature and pressure afforded the 1,3-trans-disubstituted [3]ferrocenophanes 46 (Scheme 5.11) [72]. 5.3.4

[4]Ferrocenophanes

[4]Ferrocenophanes can be prepared using many of the synthetic routes employed in the synthesis of [3]ferrocenophanes. The reaction of sodium cyclopentadienide 18 with 1,4-dibromobutane afforded the bis-cyclopentadienyl butane, which was then doubly deprotonated and treated with ferrous chloride to give [4]ferrocenophane 47 (Scheme 5.5) [57]. Another pathway to [4]ferrocenophanes involves the co-condensation of iron atoms with spirocyclic precursors. The co-condensation of iron atoms with a doubly vinylic cyclophane, [2.4]hepta-4,6-diene, yielded [4]ferrocenophane 47 as one of four different ferrocene derivatives [73]. 1-Methyl[4]ferrocenophane-4-one 48 was prepared by the treatment of methylenetriphenylphosphorane with 1,1'-diacetylferrocene and excess dimethylsulfinyl anion [74]. However, in contrast to the previous section, [4]ferrocenophane-1-one derivatives could not be prepared directly by intramolecular Friedel-Crafts cyclization of b-ferrocenylbutyric acid, which afforded the homoannularly cyclized compound 49 [58]. The alternative route, therefore, involves ring expansion of the trimethylene bridge of 22, which was prepared by heteroannular cyclization of b-ferrocenylpropionic acid. The bridge enlargement of 22 was achieved by the reaction with diazomethane to give two isomers, [4]ferrocenophane-1-one 50 and [4]ferrocenophane-2-one 51 [75]. When methanol was used as a catalyst, the formation of b-ketone 51 was exclusively dominant; in the reaction with BF3·OEt2 in benzene, however, the proportion of a-ketone 50 increased. In the latter case, bridge elonga-

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

tion occurred even though the adjacent bridges sterically hindered the carbonyl group.

As mentioned in Section 5.3.2, ferrocenophanes possessing unsaturated carbon bridges are attractive for use as monomers in ROMP to generate conjugated organometallic polymers. Furthermore, heteroatom-bridged [1]ferrocenophanes can also be used to prepare conjugated organometallic polymers [28–42]. These latter materials, however, routinely exhibit lower conductivities than well-known p-conjugated organic polymers; the diminished conductivities have been attributed to the lack of p-overlap at the heteroatoms. On the other hand, ROMP of ferrocenophanes having unsaturated carbon bridges are expected to show enhanced conductivity because the unsaturated bonds are retained in the resulting polymers (Scheme 5.12). Several [4]ferrocenophanes having unsaturated carbon bridges have been prepared. The base-catalyzed heteroannular cyclization of 1,1'-bis((trimethylsilyl)ethynyl)ferrocene 54 afforded the fully conjugated 1,1'-(1-methoxy-1,3-butadienylene)ferrocene 55, where 54 was prepared by the coupling reaction of 1,1'-diiodoferrocene with two equivalents of (trimethylsilyl)acetylene catalyzed by (Ph3P)2PdCl2 and Cu(OAc)2· H2O [76, 77]. A variety of [4]ferrocenophanes can be produced from the 1,1'-(1-methoxy-1,3-butadienylene)ferrocene 55. Hydrolysis of 55 with aqueous acetic acid afforded the 1,1'-(4-oxo-1-butenylene)ferrocene 56 in 76% yield. The carbonyl group of 56 was reduced to the corresponding methylene group giving the [4]ferrocenophane 57 having a mono–olefinic bridge. On the other hand, the reduction of the 1,1'-(4-oxo-1-butenylene)ferrocene 56 with sodium borohydride gave the corresponding alcohol, 1,1'-(4-hydroxy-1-butenylene)ferrocene 58, which could be further converted to the diolefinic [4]ferrocenophane 52 by dehydration on activated alumina [77]. Analysis by single crystal X-ray crystallography showed that the ring tilt angles of the two Cp rings of 1,1'-(1-methoxy-1,3-butadienylene)ferrocene 55 were 7.168 and 11.078 for two independent molecules in the unit cell, which are comparable to that

Scheme 5.12

141

142

5 Carbon-Bridged Ferrocenophanes

Scheme 5.13

observed for [3]ferrocenophane-1-one 22 (8.88) [61] but significantly smaller than that of 1,1,2,2-tetramethyl[2]ferrocenophane 8 (23.28) [45]. The ring tilt angles suggest that the strain in 55 is comparable to that of [3]ferrocenophane-1-one 22; however, the longer bridge of the former complex allows a staggered conformation of the Cp rings [77]. The unsaturated butadiene-bridged ferrocenophanes 52 can also be prepared via reduction of the corresponding diketone 59 [78]. The starting compound, [4]ferrocenophane-1,4-dione 59, was prepared by the intramolecular coupling of commercially available 1,1'-diacetylferrocene [79]. Reduction of 59 with sodium borohydride in methanol gave a diastereomeric mixture of the corresponding diol 60, which upon treatment with p-toluenesulfonic acid in benzene afforded 1,1'(1,3-butadienylene)ferrocene 52. The single crystal X-ray structure of 52 exhibited a ring tilt angle of 10.28, which is slightly larger than that of [4]ferrocenophane1,4-dione 59 (6.78). Surprisingly, the sp2 carbons in the bridge of 52 showed bond angle distortions of * 108 (i.e., an average bond angle of 129.88 rather than 1208); these distortions were not observed in the diketone 59. The relief of strain is probably the major driving force for the ROMP of 52 [78]. In the early 1970s, Hisatome and his coworkers reported the preparation of various [4]ferrocenophanes by the acid-catalyzed reaction of 1,1'-bis(a-hydroxy-aphenylethyl)ferrocene 61. The mixture of products obtained from the reaction of a benzene solution of 61 with HCl included an insoluble peroxide derivative 62 and a soluble unsaturated derivative of [4]ferrocenophane 63 [80]. These compounds were also prepared by the oxidative reaction of 1,1'-bis(1-phenylvinyl)ferrocene

Scheme 5.14

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.15

with molecular oxygen in the presence of various diamagnetic or paramagnetic Lewis acids as two components of the product mixture [81]. As mentioned above, unsaturated butadiene-bridged ferrocenophanes are attractive candidates for the preparation of conjugated organometallic polymers via ROMP. Interest in ferrocene-based conjugated polymers arises from an expectation that the extended conjugation promises electrically conductive polymers. The development of processable high molecular weight polymers is desired for most microelectronics applications. It is anticipated that the ferrocene groups in ferrocene-containing polymers would be able to rotate, making the polymer soluble and thus processable. Several attempts to prepare such conjugated polymers, however, have led to materials having poor solubility, low conductivity, and low molecular weights. For example, the ROMP of [4]ferrocenophane-1,3-butadiene 52 afforded only low molecular weight oligomers/polymers that exhibited poor solubilities in common organic solvents (Scheme 5.12) [82]. The conductivity of the resulting low molecular weight materials after doping was ~10–4 X–1 cm–1, and interchain hopping was found to be the dominant mechanism for charge transport. In related work, the polymerization of 1,1'-(1-methoxy-1,3-butadienylene)ferrocene 55 afforded a soluble polymer in benzene [82]. The vinyl ether group in the resulting polymer, however, is known to undergo facile hydrolysis [76, 77]. To synthesize a soluble and thus processable polymer, 1,1'-(1-tert-butyl-1,3-butadienylene)ferrocene 65 was prepared [83]. ROMP of 65 with a tungsten-based metathesis catalyst afforded the deep red high molecular weight polymer 66, which was soluble in common organic solvents, including benzene, methylene chloride, and tetrahydrofuran. The UV/Vis spectrum of the resulting conjugated polymer 66 showed a bathochromic shift when compared with its monomer 65, suggesting extended conjugation for this new material [83].

Scheme 5.16

143

144

5 Carbon-Bridged Ferrocenophanes

Scheme 5.17

Scheme 5.18

Another example of an unsaturated [4]ferrocenophane having a benzoquinonelike structure 68 was prepared in 30% yield by the reaction of 1,1'-bis(a-bromoacetyl)ferrocene 67 with an excess of potassium butoxide in tetrahydrofuran [84]. Ring closing metathesis (RCM) of 1,1'-diallylferrocenes 69 and 70 with Grubbs’ catalyst afforded [4]ferrocenophane-2-enes 71 and 72, respectively. Starting with asubstituted derivatives (R = Ph, 4-MeOC6H4), RCM proceeded on the meso-diastereoisomers 69 and 70 to afford cis-disubstituted ferrocenophanes 71. For the methyl-substituted derivatives (R = Me), however, the trans-disubstituted ferrocenophanes 72 were also obtained. According to the results, large R groups appear to prevent RCM cyclization to the trans-disubstituted [4]ferrocenophane-2-ene 72 [85]. 5.3.5

[5]Ferrocenophanes

Like [3]ferrocenophanes and [4]ferrocenophanes, the most direct route to [5]ferrocenophanes involves treatment of the corresponding disodium salt of the bis-cyclopentadienyl hydrocarbon with ferrous chloride (Scheme 5.5) [59]. In 1960, Hauser and coworkers reported the base-catalyzed condensation of the readily available 1,1'-diacetylferrocene 73 with benzaldehyde, which afforded an unknown complex as well as the expected 1,1'-dicinnamoylferrocene 75 [86]. Later, Furdik suggested the 3-phenyl[5]ferrocenophane-1,5-dione 76 (R = Ph) structure for the unknown complex, and extended the reaction to the condensation with other aromatic [87–89] and aliphatic aldehydes [90]. Barr and Watts reported that the condensation of 73 with formaldehyde afforded the 2-ethoxymethyl[5]ferrocenophane1,5-dione 77 along with the [5]ferrocenophane-1,5-dione 76 (R = H) [91]. The mechanism for the formation of the [5]ferrocenophane-1,5-dione 76 (R = H) was proposed to consist of a Claisen-Schmidt reaction followed by internal Michael addi-

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.19

tion. Starting with these complexes, various [5]ferrocenophane derivatives could be prepared. The reduction of the diketone 76 by LAH–AlCl3 afforded the corresponding [5]ferrocenophane 78, which in turn was oxidized to the monoketone 79 by manganese dioxide. The resulting monoketone 79 was reduced by LAH to the alcohol 80, the dehydration of which introduced unsaturation into the bridge to give 81. On the other hand, the reduction of the diketone 76 by LAH afforded the tetrahydropyran derivative 83 instead of the expected diol 82. In addition to the preceding examples, a wide variety of [5]ferrocenophanes have been prepared using condensation reactions [91, 92].

The UV/Vis spectrum of [5]ferrocenophane-1-one 79 (R = H) exhibited a bathochromic shift of all absorption maxima, while the [3]ferrocenophane-1-one 22 failed to show such shifts. Furthermore, unlike the saturated analog 78, the unsaturated derivatives of [5]ferrocenophane-1-ene 81 showed well-defined maxima at 275 nm, indicating extended conjugation between the Cp rings and the adjacent double bonds. These observations indicate that overlap of the Cp p-electrons with those of adjacent double bonds in ferrocenophanes having bridges with five or more carbon atoms is conformationally possible due to their enhanced flexibility when compared to analogs bridged with shorter chains [91]. The compound 3-phenyl[5]ferrocenophane-1,5-dione 76 (R = Ph) can be utilized as a monomer for the preparation of nonconjugated conducting polymers. As shown in

145

146

5 Carbon-Bridged Ferrocenophanes

Scheme 5.20

the previous section, electronic interactions between ferrocenyl moieties can be facilitated by the preparation of conjugated polymers. Enhanced electronic communication also can be achieved by close co-facial alignment of the Cp rings of ferrocenyl moieties. From the dione 76 (R = Ph), 3-phenyl[5]ferrocenophane-1,5-dimethylene 84 was prepared via Wittig reaction in 72% yield. The resulting diene 84 was further radically cyclopolymerized to give the corresponding poly(ferrocenophane) 85, which allows close co-facial stacking of the Cp ligands [93]. 5.3.6

[m]Ferrocenophanes (m > 5)

Ferrocenophanes having bridges of more than five carbon atoms are expected to contain less strain than those having shorter bridges. The heteroannular cyclization of diester 86 can provide ferrocenophanes bridged by more than 5 carbon atoms 87 [94, 95]. By this condensation, [6]-, [8]-, [9]-, and [10]ferrocenophanes have been prepared in relatively good yields (50–75%), while [4]ferrocenophane was synthesized in 20% yield. An interesting class of ferrocenophanes having more than five carbon atoms in the bridge consists of ferrocenophanes having extended transannular p-electronic interactions between aromatic rings and double bonds. The compound [2]paracyclo[2]paracyclo[2]ferrocenophane-1,9,17-triene 89 was obtained as part of the product mixture from the intramolecular titanium-induced reductive coupling of dialdehyde 88, which was prepared by the palladium-catalyzed substitution of 1,1'diiodoferrocene with 4-vinylbenzaldehyde [96]. A similar intramolecular titaniuminduced reductive coupling of 1,1'-bis(p-formylphenylethynyl)ferrocene afforded [2]paracyclo[2]paracyclo[2]ferrocenophane-9-ene-1,17-diyne, which exhibited a bathochromic shift compared with 1-(p-methylphenylethynyl)ferrocene, indicating

Scheme 5.21

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.22

Scheme 5.23

a transannular p-electron interaction between the two benzene rings and the two triple bonds [96]. Various mononuclear and multinuclear ferrocenophanes having a conjugated chain of double bonds and para-substituted benzene rings in the bridge have been prepared by one-pot multiple Wittig reactions [97]. A method was developed for preparing macrocyclic ferrocenophanes via the cyclization of 1,1'-bis(x-cyanoalkyl)ferrocenes 90 promoted by methyl magnesium iodide or sodium N-methylanilide [98]. The solubilities of the ferrocenophanes 91 were found to increase with increasing bridge length. 5.3.7

Multiply-Bridged Mononuclear Ferrocenophanes ([m]nFerrocenophanes)

Schlögl and coworkers reported the synthesis of a di-bridged ferrocenophane via heteroannular Friedel-Crafts cyclization of b-ferrocenophanylpropionic acid 92 (see chapter 6, section 6.4.2 for the analogous ruthenocenophane) [99, 100]. The propionic acid 92 was prepared by formylation of [3]ferrocenophane 20 followed by condensation of the resulting aldehyde with malonic acid and then catalytic hydrogenation of the b-ferrcenophanylacrylic acid. Rinehart’s group also synthesized the multiply-bridged ferrocenophanes by Friedel-Crafts acylation [101]. They employed, however, a different synthetic strategy to prepare the propionic acid 92, which was synthesized by acetylation of [3]ferrocenophane 20, carboethoxylation of the acetyl derivative, catalytic hydrogenation of the b-carbonyl group, and saponification of the resulting ester. In both methods, [3]-a-oxo-[3]ferrocenophane 93 was reduced by LAH to afford the fully saturated [3][3]ferrocenophane 94. Rinehart’s method produced isomeric acetyl derivatives and thus [3][3]ferrocenophane isomers, [3][3](1,1';2,2')ferrocenophane, and [3][3](1,1';3,3')ferrocenophane. In contrast, Schlögl’s formylation method afforded only the (1,3) isomer. The tri-bridged ferrocenophane isomers 95 were prepared using Rinehart’s method, starting from [3][3]ferrocenophane [101].

147

148

5 Carbon-Bridged Ferrocenophanes

Scheme 5.24

Analysis of the multiply-bridged [3][3](1,1';3,3')ferrocenophane 94 by single crystal X-ray diffraction found that the average distance between the two cyclopentadienyl rings is 3.18 Å, which is smaller than that of unbridged ferrocene (3.32 Å) [102]. The reduced distance implies that the second trimethylene bridge introduces additional strain. The single crystal X-ray structure of [3][3][3]ferrocenophane 95 showed a shorter Cp–Cp' distance (3.15 Å) than that of [3][3]ferrocenophane 94 as well as that of ferrocene itself [103]. The ring tilt angle of 95 was 2.48, which is smaller than that of the di-bridged analog (98) [102]. Studies examining the effect of the number of trimethylene bridges on the structure of the corresponding ferrocenophanes found that the added bridges shorten the Cp–Cp’ distances and increase the electron density of the metal center [104]. The synthesis of [4]ferrocenophanes bridged with five tetramethylene groups has been reported (see chapter 4, section 4.5) [105, 106]. In contrast, the pentabridged [3]ferrocenophane has yet to be prepared due to its highly strained structure. Nevertheless, several tri-bridged [3]ferrocenophanes have been prepared [100, 101, 107, 108]; apparently, the structural strain introduced by an additional short trimethylene chain disturbs the preparation of [3]ferrocenophanes linked with more than three trimethylene bridges. In an effort to prepare the tetra-bridged [3][3][3][3]ferrocenophane 96, Schlögl and Peterlik applied their formylation method to [3][3]ferrocenophane [100]. Reinhart’s group, however, showed that the resulting compound was actually the di-bridged ferrocenophane 97 produced by homoannular cyclization [109]. Similarly, the attempt to prepare [3][3][3][3][3]ferrocenophane 98 yielded the [3][3][3]ferrocenophane derivative 99 [110]. In the single crystal X-ray structures of both 97 and 99, the Cp ligands reside in an eclipsed conformation.

Hisatome and coworkers assumed that the failure to prepare tetra- or pentabridged [3]ferrocenophanes from the propionic acid derivatives of [3][3][3]ferrocenophane 95 was due to the considerably reduced distance between the two Cp rings in the starting materials (3.15 Å), which prevents the acylium ion of a tribridged [3]ferrocenophane from attacking the corresponding carbon of the facing Cp ring [111]. Elongation of the distance between the two Cp rings and thus the

5.3 Mononuclear Carbon-Bridged Ferrocenophanes

Scheme 5.25

two carbon atoms to be linked was expected to facilitate heteroannular cyclization rather than homoannular cyclization (Scheme 5.25). According to structural studies, a distance longer than 3.20 Å between the two carbon atoms to be bridged to each other is required to form the expected tetra-bridged [3]ferrocenophane [112]. The elongation could be achieved by replacing one of the trimethylene groups of [3][3][3]ferrocenophane-3-propionic acid with a longer tetramethylene group. The introduction of a tetramethylene bridge into the position adjacent to that targeted for bridging was expected to give a distance of 3.35 Å between the Cp and Cp' carbons (e.g., the 2- and 2'-carbons adjacent to the tetramethylene bridge in the [4][3][3](1,1';3,3';4,4')ferrocenophane 101). Using this strategy, Hisatome and coworkers successfully prepared the tetra-bridged [4][3][3][3]ferrocenophane 103 and the penta-bridged [4][3][3][3][3]ferrocenophane 104 [109, 110]. The single crystal Xray structure of 104 showed that the two Cp rings reside in a nearly perfectly eclipsed conformation, almost parallel to each other, with a ring tilt angle of only 1.98. Recently, the heteroannular Friedel-Crafts cyclization of ferrocenylpropanoic acids was applied to the asymmetric synthesis of [3][3](1,1';3,3')ferrocenophane [63, 113]. The SnCl4-promoted intramolecular Friedel–Crafts cyclization of (R,R)1,1'-bis(2-chloroformyl-1-phenylethyl)ferrocene prepared from 105 afforded a

Scheme 5.26

149

150

5 Carbon-Bridged Ferrocenophanes

7 : 37 : 56 ratio of singly-bridged [3]ferrocenophane isomers. The major diastereomer was isolated after the mixture was converted to the corresponding methyl esters 106, 107, 108 due to the poor stabilities of the acids. After reduction and ester hydrolysis, TFAA-mediated intramolecular Friedel–Crafts cyclization of the acid 109 gave a ferrocenyl ketone, which was further reduced to a di-bridged C2-symmetric ferrocenophane 110. The single crystal X-ray structure of the ferrocenophane revealed a ring tilt angle of 6.58.

5.4

Multinuclear Ferrocenophanes

Multinuclear ferrocenophanes consist of more than two ferrocene units linked together. In these complexes, electronic communication between the metals may be transmitted “through bond” and/or “through space”. Multinuclear ferrocenophanes, therefore, have attracted many researchers due to their potential technical applications. The properties of multinuclear ferrocenophanes vary with the structure and the nature of the bridge. Depending on the degree of intramolecular interaction, multinuclear ferrocenophanes can exhibit properties of the individual components or something altogether different. 5.4.1

[0.0]Ferrocenophanes

The first example of a simple multinuclear ferrocenophane, [0.0]ferrocenophane 112, has been prepared via several synthetic strategies, including pyrolysis of polymercury ferrocenophane [114], modified Ullmann coupling of 1,1'-diiodoferrocene [115], coupling of 1,1'-dilithioferrocene using organocuprates [116], and the reaction of fulvalene dianion 111 with ferrous chloride [117]. The yields of these reactions are typically low due to the high probability of oligomerization and polymerization. The direct synthesis via the reaction of fulvalene dianion with FeCl2 gave the highest yield (40%) of all of these reactions (Scheme 5.27) [118]. The observed poor solubility of 112 in organic solvents was attributed to the rigidity of the molecule, which prevents adequate solvation. According to the single crystal X-ray structure, the two iron atoms of 112 are located in the center of the ferrocene units at a metal–metal distance of 3.98 Å [119]. The iron(II)-iron(III) mixed valence system of the 112 was obtained by benzoquinone oxidation. These complexes showed a broad near-infrared absorption, which can be assigned to intramolecular electron transfer. Com-

Scheme 5.27

5.4 Multinuclear Ferrocenophanes

pound 112 underwent facile oxidation by tetracyanobenzoquinodimethane (TCNQ) to give a mixed valence TCNQ salt, which was expected to show high conductivity. The room temperature bulk conductivity of compressed disks of the TCNQ salt was measured to be consistently above 10 X–1 cm–1, which indicates an unusually high conductivity along the main crystal axis [117]. Another known example of a [0.0]ferrocenophane is bis(indacenyl)diiron [120, 121]. This compound was prepared by the reaction of dilithium indacenide with ferrous chloride. The molecule exists as a mixture of syn 113 and anti 114 isomers.

5.4.2

[1n]Ferrocenophanes

Reduction of the bisfulvene 115 with lithium aluminum hydride or methyl lithium afforded the dianion 116, which in turn was treated with ferrous chloride to give [1.1]ferrocenophane 117 in yields ranging from 14 to 20% (Scheme 5.28) [122, 123]. The 1H NMR analysis of 117 suggested that the two methyl groups possess an exo configuration. Although a twisted anti conformer of the compound was proposed due to the steric strain in the syn conformer, the single crystal X-ray structure of the compound showed that the bridges exist in a syn conformation with the methyl groups in the exo position. The Cp rings of each ferrocene unit lie in a staggered conformation at an angle of 22.48 and with a ring tilt angle of 2.78 [124]. The exo,exo,anti-1,12-dimethyl[1.1]ferrocenophane, however, was later identified. The anti conformer showed large twist (36.18 and 34.08), rotation (3.48 and 53.98), and tilt angles (4.18 and 22.78), which suggests a high flexibility of the molecule, unlike the initial expectation [125, 126]. Through the intermediacy of 1,1'-bis(6-fulvenyl)ferrocene 119, the unsubstituted [1.1]ferrocenophane 118 was also prepared [127]. The reaction of 1,1'-dilithioferro-

Scheme 5.28

151

152

5 Carbon-Bridged Ferrocenophanes

cene with 6-dimethylaminofulvene followed by hydrolysis afforded 119 in better than 80% yield. Similarly, a mixed [1.1]metallocenophane was prepared [128] and its electrochemical properties were investigated by cyclovoltammetry [129]. The hetero-binuclear iron/ruthenium system 120 exhibited a reversible one-electron oxidation associated with ferrocene and an irreversible two-electron oxidation associated with ruthenocenophane, indicating a lack of interaction between the two metallocenophane units.

In related work, the aluminum chloride-catalyzed Friedel-Crafts reaction between ferrocene and 1,1'-bis(chlorocarbonyl)ferrocene 121 afforded the dinuclear [1.1]ferrocenophane-1,12-dione 122