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!
"
!# $
% # $ & # $
%% " '!# % &
$ #
$ # $ % " % " % " %% " % "&" " &
! ! % % ! # $" % "# "
% ( ) %" " " * +
,-./%" " 0" " %" , % ,/(
." " % %% %" % ,/+,,0 !" #
$% &% &'
( ) * + ) * ) *+* ,)) #$ " # 1 23 $ " & 4#$ 5 " 67 ---------------------------------------------------------------------------------------------8* 9 :% 8* ;
< ' % = 8 > & && 9 2 ? (0/+-- @ ?... 7 @+,,, ...,-??A..A-+?-+B?(..C?...44 1
-+
2 % - " ! ?( 4#$ . 2 %% / " 7 77& 1 0"' R1 N
R4
ClPR2R3 2
PR6R7
+
R
N
X 1
3
R5
N H
Y
R
4
1 & " * %% 1 /" ? #$ 1 0 1" >+/" "/ - 01 ! " #$ " #2$ " & 1 " ! % 4#$ 0 426; 3%
" ?0 -' 1a
5 NEt3
6
Z
N H
N H
7
Z = O, S
9 4#$ 3 % 4 " # $ 2 &
- # $ 5" !* 4#D$ %% 6 * Z
O P O
N
P
Z
P O
Ar 8
Ar O
[O]
N O
O
P
Ar
O
O Ar 9
0 2 " - ! -#- $? #7$ !* .<
. " ? / " % 72#'$" !
' -+?
O OP
OH
N H
O
N
N H
Ar O
3 (5)
O
N
Ar
P
O
10
P O
2EtOH O
N
Ar
O P
O O P O
N H
O Ar
O
N H 13
O
12
Ar O
OO OP Ar O
Ar O
N
O
11
O O OP
O2
426; *?- ?- " 2 2 #.? % $ > E -# $ #0$ E %% " % 6 , " " -#@ $# ! $#2$" ?. -? 1 2 " 3 " 4&" 4' CH2NMe2
CH2NMe2 ClP(OEt)2 N H 14
N
(EtO)2PO(Me)C= CHC(O)Me
P(OEt)2 15
CH2NMe2
N (S)P(OEt)2 16
CH2NMe2
N (O)P(OEt)OCH=CCl2 17
" ?
% 2 ? ?-( " &
& & ???-
%
? 4#$ " " % 2 ! ? " 5.7 ? -+-
1a, 1c
+
Cl2PR'
R' P N
PR'
+
R N H
+
N H 19
R 18
R
R'P
N 2
R
2
20
5.7 ! "
" # " $ - "
426; ,,? " " # $ " . # -(F ( $,?( 4 . % % " / 4#D$...0' HNEt2 + NEt3
3d
ROH + NEt3
3a
N 21
N
S Cl3 CCHO
RI
(S)P(OR)2 22
PCl2 N
N
(O)PR(OR) 24
23
(O)P(OR)OCH=CCl2
9 4E2 /
(/
" / #;GH?+ $ #.(.I1$" !
#'-$ , #. $" ! " ?/ 4E2# $ " % .2" ' OR
CH2X
O P CH2X
N O P
ROH
OH O
OH O O O
+
O
O
N H
O
O
25
?@ .3 -#? $ .4 " " ! %% .5?0 -+
PBrn N
P(O)R2 N
Me
Me
Me
Me
3–n
3–n
28a,b 28 a R = NEt2, b R = Ph
26
. #
" $ #? $ " ! ! " #$ " 3"% ? 1 26; #2 $ #.6$ ' +PCl3 _ 3KCl
3
P 3
29
.6 " D %% #/7 $ " -.-? ?- ?-? #/7 /71$ " %' PBr2 PBr3 N
N
Me
Me 30a
PBr2
N Me 30b
PBr2
Ph2P
N
PPh2
R2(X)P
N
Me
Me
30c
30d
Ph2P
N
CH
O
Me 30e
@ 2 %% % ?, ? - */ %%/. -.' CH N Me 31
N
PPh2
P(X)Ph
32
. ( ) * + ) * 89 *+* ,)) -@ " ..?.I1 " + - " " ! #//$ % #/0$---(' -+(
Me
Me PCl3
2EtOH
AlCl3
N
N
Cl2P
Me
Me Me
Me S N
(EtO)2P
Me
33
N
(EtO)2P(S) 34
Me
?- " # ..?.I1 + $ " !" "% -(F ?- + #/2$ " & " --( E -+-/ 6 - ..?.I1 #- $3( /3 1 ! " % # " &$ --(J ?-- /3" %
-+ /3
#/4$#/5$
#/6$4 /5 /6% 070 *%#0.$+.' R' R'' N
R'
Cl2P N
R
N
R
38, 39
R
Me
Me 36a–c a R = R' = R'' = H; b R = R'= H, R'' = Me; c R = R'= R'' = Me
Z ( O, S)
R'
R''
PCl3
Me
R''
X2P
37 X = OH 38 X = NR2 39 X = OR
R''
X2(Z)P
R' N
R Me 40 X = NR2, Z = S; 41 X = OR, Z = O 41 R = R'= R'' = H
Cu2Cl2
(RO)2P(O)
C5H5N N 41a
RX 39 R = R'= R'' = H
R(RO)(O)P
Cu2Cl2 N Me 42
C5H5N
Me
R(RO)(O)P N Me 42a
00. 0 0. -- -( " .F (# ! $ #0/$ (# ! $ #0/ $ ( #($ & *% * & -(' -++
(EtO)2(O)P
(EtO)2(O)P N H
N H 43a
43
" % -0 + (+ & # $
(+ #00$ (#+$ ** -, 00 (+ 00 %" ! O2N
O2N MnO2 N H
(EtO)2(O)P
(EtO)2(O)P
44
N H 44a
-. % * / ( ) * +/:, (* ) - #02$" 4#$ 9 2 < " 9%% 02 1 2 03 1 " .' SPRR'
SH
N H 45
ClPRR' NEt3
SH
+ N H 45a,b
N
PRR' 46a,b a R = R' = OAlk, b R = R' = NAlk2
- " & % 9323 % % 0 ( ) * +* % 1)& * + ) " 4#$ "
" %"? %% @ " - 04 23 - - % #05 $'
-+/
CH
CH(Cl)P(O)Ph2 ClPPh2
N
N
R 47a,b a R = H; b R = Ac
R 48a–c a R = PPh2; b R = Ac; c R = H
06 %% 061 " ? 27 1' Cl P(O)Ph2
O ClPPh2 N
O
N
R 49a,b
O
R 50a,b a R = PPh2; b R = Ac
a R = H; b R = Ac
% " 2" ( & 23 " # 4 26;
$ 2 " % ! 21 " & -
- - ? #2. $ !* 2.1 J 2. " * E - - ?#2.$" ' O 49a
O
5 NEt3
[O] N
O
O
N
R 51a R = PO2Ar
R 51b R = P(O)O2Ar O OP(O)2Ar
OP(O)2Ar 49a
5
Cl N H 52a
O2
Cl N H 52b
O
80oC
O
O P(O)2Ar Cl N H 52c
O
6 & " , * %% # ?&! -+?!* + $ #2/$"'
-+0
Cl2POR
N
N CH2CH2OH
CH2N
CH2CH2O
CH2N 53
CH2CH2OH
POR CH2CH2O
, ( ! * # $-2#?&! + !* -?!* - $ #20$' N
Br
N H
N
Br
.HCl
P O EtO O
Cl2POEt N H
O HO
O
3NEt3
N
N H
O
54
. !" ''!&, &';#
$% &!& !'
. ( ) * + ) * ); <=*+* ,)) :0" /,& 23 ! -(.I1
"
0 # $ 4 26; # $ #/: $ ..( R' N H
R''
R' (R2N)3P _ R NH 2
N
R''
P(NR2)2 3d–i
!!!"#!!! !!! !!! !!!
# ?(.$ & 23# /$ ( / < .0F & "& 4
K4'E'2L & "
" 1 " -.F % " 2 ! " " < & / 0 #; G 2 &< ; G 7 &$ 0 " - " % -+,
%%
(((+ * * &
%% * % (/ " # '-$ ! #-..I1 -( $ 22 4 26; "
.# $,0 # $ % PNEt2
H N
N
3P(NEt2)3 N
N H
PNEt2
55
" % 2 #,, $
/ " " & " - #23$ " !
",
/" " & 426;
24% (( *
24 % ,- #23$ P(O)(OH)2 H2O(H+)
3d R'Hal
N H
N
+ _ 56 P(NR2)2Hal 57a–c 57a–c a R = R' = Et; b R = Et, R' = Pr; c R = R' = Bu R'
.. ( ) * + ) * * 89; <=*+* ,)) ( " -( (M? " !
" % & % ( ! ? #25$ (M? " #
& $ " ( ! ? #26$' Br P(OEt)3_ N H
Me
Br
-/.
NiCl2
P(OEt)3_ N H
Me
(EtO)2(O)P
NiCl2
N H 58
Me
(EtO)2(O)P N H 59
Me
(+ " & + " " (0(2+ #37$ !(+ #3$-(' O2N
O2N
O2N P(OEt)3 O2N
MnO2 N H
(EtO)2(O)P
N H
(EtO)2(O)P
N H
61
60
% " 4E7E1 ! " (,+.(0(3 ! 2* +. + # .I1$ ( 3. #-?? $" 3/#+?+ $(,' COOEt
HO
COOEt
R2PO
S
Et2NPR2 N H
N H 62
Me
Me
COOEt
R2PO N H 63
Me
%% " -( J - ! ? # $ ( ! +?+- " !
& + #+.+(I1 -. $ - ! ? (#?!?&! ?! ($ 32 #---+ $ - ! ( ! ? #77& $ #30$' + CH2NMe3I HO
CH2P(O)(OR)2 HO
COOEt
COOEt
P(OR)3 N H
N H 64
Me
OR P
O
Me
ROH
CH2 COOEt
N H 65
Me
+? %% ? " ( " %" 33?-- " *%# 34$'
-/
O
Br
HP(O)(OEt)2 N H
O
OH
Br
P(O)(OEt)2
EtONa
O
N H 66 OH
(EtO)2(O)P
P(O)(OEt)2
P(OEt)3 NiBr2
N H
O
67
& " * & % &" %% ?35'
X
N H
"$
N H
%+- !& * ./ ** + ( :* < 1* ** * * % + ) ) & * ,(/ + +( " " & *%" - 36' %
N H
N H
-#4 $ " ++ " 47 " +/' %
%
N H
N H
9 % " ! %% +0 " % " 4 -/?
%
N H
N H
%
! % & +, 0" & #- $ 4.' N H
" -# $/. 4/'
%
N H
N H
M *% / * ?#&! $ - ! ( ! 40'
! N
"$
R
!
4 * " %% -(# $? ! /? " & ? ! ?(#77& $ 42.' "$
"$
J ? 77 ? 43/-'
2#4 $ * 44" * " /' -/-
" * # ! $? /( #45$ #46$%% *" " /+ " ' ! %
!
!
!
!
%
!
!
!
" ! 57 % 2 #57$ 7 #5$ // (I1 57 #0.0(F$< 0.I1 +(/.F" 7 5 -.-(FJ " !
%% - #5.$ " #575.$ !* " #5/52$'
CH2OH (Me2N)2POR N H 80a
80a
+
N Me2NPOR 80
N H 81 CH2OX
CH2OP(OR)NMe2
2(Me2N)2POR 2Me2NH
CH2OP(OR)NMe2
CH2OH
N
N Me2NPOR 82
Y 83–85
83 X = H, Y = Me2NP(O)(OR); 84 X = P(O)(OR)NMe2, Y = H; 85 X = Y = P(O)(OR)NMe2
-/
.0 ( ) * +% 1)( & * + ) ) 4 " & " /0 " " & ?'" -?! 6 " " /, " " 0. ( " & " -&! - ! ? " " & /0 " + " % " -&! ? % & " 0
53" !' O P(OR)3 O
N H 86
/0/,0- "% % 0?& 4#$ 06 061 ( 06 " & " -?! 54" " * 55' RP(OR')2 X 49a–c
O
O
X
RP(OR')2
N R''
N R''
87 P(O)(OR')R
87
EtOH
OR'
O
X
N R''
X
N R''
88
/00. 06 " *
#*$-&! - ! ? 56 0?" ' 56 ! " ! ?
* 0 56 " % N
" ..(.#-$ O 1G7
*
56 "& 2–3PPP7#A?Q#A?– A?Q$$7–3PPP7 #–#– ?– $$ " '2PPP7?0?#-$2–3.//#-$3PPP7?.+#-$O2–3PPP7 /?#-$I<7PPP7?/+,#-$7–3.0(#-$3PPP7?..#-$O7–3PPP7(.#-$I -/(
R R'
OH P(O)RR'
P(O)H
49a
N O H 89a–d 89a–d a R = R'= OMe; b R = R' = OEt; c R = OH, R' = p-C6H4Me; d R = OH, R' = -naphthyl
! " 0? 0- " & ?' &!-& -R ! --R#?$67 " ! 56" 67! E *
0 0?" " 56" # &!$ 67 OH
OP(O)(OR)2 49a
(RO)2P(O)H RONa
N H
O
O
N H
90
67" N
-) 04 - 041 " & 0( 0+ " -# ! $ #6$" # $ #*$ " ! OH CHP(O)(OR')2
H(O)P(OR')2
47a,b
91
R
%% 6. 0/ 2 6/ % % 00 "
*? '
R'
N H 92
CH(OH)P(O)(OR)2
N
CH(OH)P(O)(OR)2
X 93
J " ?.
06 %/-F 60 !#,?F$/-0,' PPh3 49a
-/+
2PPh3 CH2Cl2
+ N H 94
O
O PPh3
* " ,. " 9 " %", ,? 1G2 & " 1 " ,- 2 " " 1G2 ) # $- *( " 2 " "& E2G1E1G7
, ,(7 * "
% S ! %" 2 22 * 62 #-- $ 22 *" ,+ N
N(Me)2Et
+
H(O)P(OEt)O N H
O
95
* " ,/ & & * " " " ,0 * " & ,. 1 " 63#;RG9723 G .< ;R G 3 G $ # 4 26; $ ) * ! 12 " ,. " * ? 1 #63$ 2 #64$ %% ? % 3"% 0- ? 6364 * " " ' (O)P(OR)2
N(CH2)nC6H4R'
NNa
(RO)2P(O)H
N H
RONa
Na
N H 96a–f
(CH2)nC6H4R' N (O)P(OR)2
N H
(O)P(OR)2 NH(CH2)nC6H4R'
(O)P(OR)2 N
(CH2)nC6H4R'
(CH2)nC6H4R'
N H
96
N H 97a–e !&!'&!'&!'( !(!)& $*# *#
-//
&! % 1 #63$2 #64$%% " ! 2 2& +'" " 2 .? 4 65 " - 64 1 ,,. 8 &E) ?--?-( " @ -# ! $ " & & CH(NR2')P(O)(OR'')2 R 98a–e
! !!! !! !"#!!$ +!"#!!"#+! ,-* ,.!!
- " 06 " " ! ,-- ? 66 77.- NR2 P(OR')R''
49
R2NP(OR')R''
N H 99
(R2N)3P
P(NR2)2
100
-3 ! -#?! $? * " 8 &E) % % - ! -#?& ? &! $ ? 7 -#?& ? ! $- ! ? 7. " 7/ % 70..( OH
NR2
OH
OH
P(O)(OR')2
P(O)(OR')2
Me N H 101
Me N H 102
OR O
P
OR
O
O
P S O
P(O)(OR')2
P(O)(OR')2
Me N H 103
-/0
Me N H 104
.2 ( ) * +.:) & * ! & ? " .+ 72" % 73' O
O
N(CH2)nOH
RPR'R''
O
N(CH2)nOPR'R''
S
105a–d
N(CH2)nOP(S)R'R'' 106a–d
!!!(!!! !!!!!!/
@ % & ? 74 " 4#$ " " " " ./ .0 1 ? 74 " & *% " #&! $? 75 ! " & ., O
O
N(CH2)nCl
P(OR)3
NCH2P(O)(OR)2
n=1
107a–c
108
#? $ #- $? #741>$ 4 26;
% !
& 721 #-0-, $ 1 % % 4#$ 721 % 76 1 *%' 105b,d
+
N (CH2)nOP(O)R'(OR)
RI
109a,b !!!!/
& % & .0&& ." % 4#$ #?+-? $ &! & # $ " & & & ? ! " ! % 7 " < " 4#$" 107b
EtOPRR'
NCH2CH2P(O)RR' 110a–c
110 a R = R' = NAlk2; b R = NAlk2, R' = Et; c R = NAlk2, R' = Ph
-/,
. % " & " " 2# $? # $ 2#- $? #1$ 2# $? #$2#? $?( #.$.I1 / :0' N C(O)(CH2)n P(O)(OEt)2
113a–c
P(OEt)3
NC(O)(CH2)n Cl
O
111a–c N
115 P(O)(OEt)2 111, 113 a n = 1, b n = 2, c n = 3 O
O
NCH2CH2Cl
P(OEt)3
NCH2CH2P(O)(OEt)2
O
O
112
114
J " (.I1 ! 2" / M ! +./(I1
! %! 2!* 34' (EtO)2P(O) O 111a
P(OEt)3
N O 116
O
P(OR)3
P(O)(OR)2
NCH2CH2Cl O
N
O
O 117
6 %% ? " * / &' ' ; ?,
!&' !& ' %! ! ! '%& !'&
/ ( ) * * & * +# $ ? ! " " #$ #- $ !5' -0.
P
POCl3
O
1d N H
3
118
>#$" #6$- #.7$ -'
1d
P(Z)R'R''
ClP(Z)RR'''
ClP(Z)R'R''
N H
(Z)PRR''' 119a,b
120a–e
!!!0)!!!0) !!! 0 ! !! 0!!! 0)! !! 0 !!!0)
%% 4#$
% " " " .(.I1
# $ & #6;G;RRRG131TG7<6;G;RRRG7HTG7<6 ;G;RRRG4 TG7$ " " & %% " 4#D$ " " & # .I1$ ! #.$ '
1a
Cl2P(Z)R
N
P(Z)R
2NEt3 2 121a–c 00) 0
@ ! 0 , ( + " & - " , 2D 2 * %
% " ! 2#% $ #..$ 2#% $* #./$+,'
-0
1. PCl5, 2. SO2
3. H2O
R
CH=CH2 R = H, C(O)CF3
R
CH= CHP(O)(OH)2 122 1. PCl5, 2. SO2
C(O)Me
ClC= CHP(O)Cl2 123
- 02" ? & #*$ " %% 4#$ 426;; & " .0 SP(Z)RR' ClP(Z)RR'
45
NEt3
N H 124 Z = O, S, R,R' = Alk, OAlk
4#D$ # $3"% .2
%" !
% * P(O)CH
S 45
Cl2P(O)CH=CHOEt NEt3
N H
2
125
" - 02 1 # $ .3 - 03 1 " 4#$ !* .4" " ! - ?. SPRR' 45a,b
S
46a,b
S
S
S
N H
) ! 127
126
2
2% " !.5 #.6$ #/7$ ?'
NCH=CH2
2PCl5
SO2
129
-0?
+ – NCH=CHPCl3PCl6
128 Et4NI
NCH=CHP(O)Cl2
NCH=CHPCl2 130
@ ! "
2 ?? 22 !#/$'
2
NK
+Cl2P(O)Ph
N P(O)Ph 2 131
- ? " /.?-& -13 " //?' CH2
PPh3 Cl2PPh3
N
O
N
Et
O
Et 132
CH =PPh3
Me Cl2PPh3
R
Me
R
Me 133
2 %% /0?(?+? ! /2?/ ? ! /3?0 " ' R
R ClP(Z)R'R'' NH
NP(Z)R'R''
:B
134–136 0)!!!$ 0 !!!'1.$$* - ,. 0 !!!
? " . (I1 ?, #? $ #/4$ #? $ #/5$"' O 3
NH
O
O O
3Cl2P(O)Me
NP(O)MeCl
:B
+
NP Me
137 138
O 2
2#3 ! & $ ! " /6-. 07--?0--' -0-
ClP(Z)R'R''
NCHROH
NCHROP(Z)R'R''
:B 139, 140 139 Z = S, R = H, R', R'' = OAlk, Alk; 140 Z = O, R = CCl3, R',R'' = OAlk, Alk HP(O)(OR)2
NCH2CH2OH
NCH2CH2OP(O)(OR)2
CCl4, NEt3
141 R = Alk
2 %% & ? " 0. - 0/ -( % " %% ? 00-+' P(R'n)F4–n NH
R NSiMe3
P(R'n)F4–n
R=H R
142
R
R = Me
R
NP(R'n)F4–n 143 O
O NSiMe3
R
ClP(O)R2
NP(O)(OR)2 144
02 -/' C(O)Cl
COOH (ClCO)2
NBz
NBz
NBz
HP(O)(OR)2
–CO, –HCl (O)P(OH)2
(O)P(OR)2 NBz
1. H2/Pd NH
2. H2O 145
-0 %% /. ( :* < )<+,* 9 % E %% E * # - *$" !% -,6 " 03 %% "% ?' -0
NNHR'
O
R 146 !))2 3
% " - * - 04 3 * ! "
% " CH=NNHC(O)(CH2)nP(O)R2 47a
H2NNHC(O)(CH2)nP(O)R2 N H 147
// * + ( :* < ) ? < < ( ( %=( * * ,* )( %- 04 1 06 1 " % " (/ " * 2 ?# $** ?# $* * - #041$ " % " - " " %% 05 06 47 0,' CHC(O)R'
49a,b
R'C(O)CH2P(O)R''
– R''2P(O)O
+
O
R
C(O)R' C
P(O)R''2
O
R 149 CH=CHC(O)R' R'C(O)CH2P(O)R''2 47a,b
+
N R
– R''2P(O)O
C(O)R' CH=C P(O)R''2
N 148 R +4 '5+.1,* 56 , '7,6 8 -56*.'7,6* 56*. "#
-0(
" - ? 06 -+-0F" "
+0F
" 47 27 " ! % " (.' C(O)OMe
CH2 47b
P(O)(OMe)
P(O)(OMe)
1. TiCl4 2. O
1. NaBH4
C(O)OMe
2. Et3N, t
N Me
Ac P(O)(OMe) C(O)OH
1. Ph2P(O)N3 2. PhCH2OH *$
P(O)(OH)O
_
+
Ac 150
NH3
Ac
/0* + ( @# $A:* < )8 %=( * #
$
-4 2" *- 0 *%(?(' P 4a
R''Cl
151
N H
OR R''
R'
$'$"#!!!
6 %% %% 2.(?' _ + PPhRR'X
N H 152 "$ '$!/' ,-
! 2/%%4#$ 0 /' P(OR)2Cu2Cl2 N H 153
-0+
/2 += * * % + ( :* < )
> %
* -# &! % $ 20 " & %% 22 * 23/' ClP(O)(OR)CH=CHOR 1d
(O)P(OR)CH=CHOR
Cl2P(O)CH=CHOR ROH
154
N H
H 0" 20 3
" " !
" @6)
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(O)P(OR)CH2CH=
NO2
N 156 H
20 # . (I1$ 24' (O)P(OR)CHBrCHBrOEt
N H 157a,b a R = Et, b R = Pr
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(CH2)n–1P(O)R(OR')
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