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Reactions Involve Sulfur Ylides
陈殿峰2012.05.12陈殿峰
2012.05.12
22
• 1. Introduction• 2. Corey-Chaykovsky Reaction• 3. Cyclization• 4. Tandem Reaction• 5. Conclusion
2
Contents
33
1.Introduction
3
Reference: Dai, L-X; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341 Aggarwal, V. K. Acc. Chem. Res. 2004, 37, 611 Aggarwal, V. K. Chem. Rev. 2007, 107, 5841
Sulfur YlideCommonly used formethylene transfer
R1≠ R2≠ Me :chiral sulfur ylide
S
O
Type 1
R1
R2
R2SR'
Type 2
More versatile
44
PhCHO + BnBr
Surlfide
Base,solvent, rt
O
Ph Ph
RCHO+ PPh3R'XBase
R R'
[O]
R R'
O
2.1 Epoxidation
4
Method 1:
Method 2:
S
Johnson, A.W.1958
Si S
O
Corey, E. J.Chaykovsky, M. J.
1965
R1S
R2
BnBr
R1SR2
Ph
Br
Base
R1SR2
Ph
RCHO
O
R Phsub or stoichiometric
Furukawa, N1987
2. Corey-Chaykovsky Reaction
55
PhCHO + BnBr
Surlfide
Base,solvent, rt
O
Ph Ph
Limitation:1. Aryl aldehyde only2.Strong nuclephility of sulfide only3. High active halides only
2.1 Epoxidation
2. Corey-Chaykovsky Reaction
666
Aggarwal, V. K. J. Am. Chem. Soc. 1994, 116, 5973-5974.
SO
PhCHN2
0.2eq
+ RCHOCu(acac)2 O
R Ryield : 32%~ 73% d.r. : 70:30 ~>98:2ee : 68%~93%~
Aggarwal, V. K. J. Am. Chem. Soc. 1996, 118, 7004-7005.
Slow addition for 24h
2.1 Epoxidation
2. Corey-Chaykovsky Reaction
777
Aggarwal, V. K. J. Am. Chem. Soc. 1994, 116, 5973-5974.
O
R1 RRCHO R1 N
NR3
M+
R2
0-20% BnEt3N+Cl-
1.0 mol% Rh(OAc)220% tetrahydrothiophene
Solvent, ToC
R2
R3=EWG Yield : 15%~98% d.r. : 58:42~>98:2
Yield : 21%~99% d.r. : >98:2 ee : 20%~94%
S
O
R1 NN
R3
MR2 PTC
25~45 oC R1 N2
R2
Mechanism:
2.1 Epoxidation
2. Corey-Chaykovsky Reaction
88
First example
8L-X, Dai. J. Chem. Soc., Perkin Trans. 1996, 867
OH
S
racemic
2.2 Aziridination
2. Corey-Chaykovsky Reaction
99
First Asymmetric example
9
2.2 Aziridination
2. Corey-Chaykovsky Reaction
Saito, T. Tetrahedron Lett. 2001, 42, 5451
101010Aggarwal, V. K. J. Chem. Soc., Perkin Trans. 2001, 1635
NR2
R1
N2
Ph
+
sulfide 1 (20~100 mol%)Rh(OAc)2(1 mol%)
DCM, rt
N
R2
R1 Ph
yield : 47%~91%trans/cis : 1:1~ > 10:1 ee : 88%~93%
R3= EWG
NTs
R1
N2
+
(100 mol%)Rh(OAc)2(1 mol%)
DCM, rt
N
R2
R1 COX
yield : 47%~91%trans/cis. : 1:1~ 1:12 ee : 30%~58%
X
O
X= OEt, NEt2
S
2.2 Aziridination
2. Corey-Chaykovsky Reaction
111111
Si S
O
O
SES
Aggarwal, V. K. Angew. Chem. Int. Ed. 2001, 40, 1433
2.2 Aziridination
2. Corey-Chaykovsky Reaction
121212
When using stoichiometric sulfonium salts:
Yield up to 99%d.r. Up to >99:1
Ee up to 99%
Yong, Tang. J. Am. Chem. Soc. 2006, 128, 9730-9740.
2. Corey-Chaykovsky Reaction
2.3 Cyclopropanation
131313
Aggarwal, V. K. J. Chem. Soc., Perkin Trans. 2000, 3267Aggarwal, V. K. Chem. Eur. J. 2006, 12, 568
2. Corey-Chaykovsky Reaction
2.3 Cyclopropanation
141414
Aggarwal, V. K. J. Chem. Soc., Perkin Trans. 2000, 3267Aggarwal, V. K. Angew. Chem. Int. Ed. 2001, 40, 1433
2. Corey-Chaykovsky Reaction
2.3 Cyclopropanation
151515
NH
COOH
CatalystR1
O
S R2+
20 mol % Cat
CHCl3, -10oCCHO
R2R1 yield : 63%~85% d.r. : 6:1~72:1 ee : 89%~96%
NH
COOH
72% conversion46% ee
2. Corey-Chaykovsky Reaction
2.3 Cyclopropanation
yield : 35%~86% d.r. : 2:1~16:1 ee : 42%~80%
R1 OMe
O
R2S
O+
cat (10 mol%)
Toluene, -40oC3 days
R1
O
R2
O
OMeNH
NH HNHN
Ph PhO OF3C
F3C
CF3
CF3
MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 3240-3241.
W-J, Xiao. J. Org. Chem. 2011, 76, 281-284
1616
S
X NuS
Nubase
E
Nu
Nu
ENu
Doerring, W. v.; Schreiber, K. J. Am. Chem. Soc. 1955, 77, 514-520
NH
CHONaH
THF, 0oC
SN
CHO
S
N
O
SN O
NaN3 acetone/water72%
N
N3
OH
NO
NH
OH
O
O NH2
OH
R
R=CHOR=CH2OH
O
O
H2N
N
OMe
NH
O NH2
O
+
Mitomycin
Jimenez, L. S. J. Am. Chem. Soc. 1994, 116, 4977-497816
3. Cyclization
3.1 Vinylsulfur ylide
171717
R
HN
R'
O
n
n=1,2R=Ts, CO2MeR'=H, Me
PhS
Ph+
DBU(2.0 eq)
1.2 eq
CH2Cl2,0oC0.09M
N
R
n
O
yield 50%~96%
OTf
O
S
yield: 30%~80% ee : 86%~99%
OTf
N NH
Ts SO
NH N
Ts SO
NaH,1.2eq
DMF, 0oC68%
PhS
Ph+
OTf
N
N
Ts
S
O
HCl/dioxane,20min
aq NH3, 42h80%
N
NH
Ts
4 steps, 20%
HN
O
NH
O OH
O
HO
OH
O
HO
CO2H
(-)-balanol
Aggarwal, V. K. Angew. Chem. Int. Ed. 2006, 45, 7066-7069
3. Cyclization
3.1 Vinylsulfur ylide
181818
NH
R1
R2
XH
R
BrS
Ph
Ph+
1.2 eq
X=O, N, SR1=H. PhR2=H, alkyl, CO2MeR=Ts, Ph, SES
NaH (3.5 eq)
CH2Cl2, 0oC - rtN
X
R
R2
R1
yield: 68~99%
XH
YH BrS
Ph
Ph+
1.2 eq
OTf
NaH (3.5 eq)
CH2Cl2, 0oC - rt
YH= OH, NHTsXH= NHTs, OH
X
Y
yield: 64%~ 99%
OTf
Aggarwal, V. K. Org. Lett. 2009, 11, 257-260
NH
R1
R2
XH
R
BrS
Ph
Ph
N
X
R
R2
R1S
Ph
Ph OTf
S
H Ph
Ph
N
X
R
R2
R1 S
Ph
Ph
N
X
R
R2
R1
PhSPh
NaH
OTf
Proposed Mechanism:
3. Cyclization
3.1 Vinylsulfur ylide
191919
W-J, Xiao. Chem. Commun. 2011, 47, 1869-1871
SPh
Ph OTfNH
OH
R2
R1
R3
+KOH (2.5 eq)
CH2Cl2, 0oC-rt, 10hC=0.01M
NR3
R2
R1
O
yield: 60%~ 93%
SPh
Ph
NH
OH
KOH
NOH
NOH
SPh Ph
NO
SPh Ph
TM
OTf
3. Cyclization
3.1 Vinylsulfur ylide
202020
SPh
Ph OTf+
R1
HN N
R2
Br
1.25 eq
i-Pr2NEt(2.5 eq)
MeCN.reflux
NNR1 R2
OTf
R1,R2=aromatic, aliphatic
yield: 71%~91%
SPh
Ph OTf
R1
HN N
R2
Br
NNR1 R2
OTf
SPh
Ph OTf
base
R1N N
R2
SPh Ph
H
R1N N
R2
SPh Ph
OTf
PhSPh
Aggarwal, V. K. Org. Lett. 2011, 13, 3060-3063
Proposed Mechanism:
3. Cyclization
3.1 Vinylsulfur ylide
212121
R X12
3
4
X=O, NR'
Type A
Type B
Type C
R X
R X
XRFormal 4+1
Formal 2+1
Yong Tang. J. Org. Chem. 2008, 73, 6909-6912
OH
S CO2Et
R
CO2Me
CO2Me+
Br
R= armatic, aliphatic 1.3 eq
Cs2CO3
DMF. -40oCO
R
EtO2C
CO2Me
yield: 80%~99% dr : 6.5/1~15/1 ee : 81%~95%
1.3 eq
OEtO2C
CO2Me yield: 89% dr : 14/1 ee : 94%
Ph
CTMS
R1
R2
O
+ S
R4R3
TMS O
R4
R3
R1
R2
Solvent, ToCyield :43%~96%
Danheiser, R. L. J. Am. Chem. Soc. 1998, 120, 9690-9691
3. Cyclization
3.2 Fomal 4+1
222222
S
COR1
+ R2 CO2R4
NSO2R3 toluene/CH2Cl2(9:1)
0.01M, -80oC-rtN
SO2R3
CO2R4
R2
R1OC
yield :83%~99% dr > 95:5 ee : 82%~98%
Wen-Jing Xiao. Angew. Chem. Int. Ed. 2010, 49, 4495-4498
S CO2EtBr CO2R2
NO2R1
+
K2CO3
MeCN, -20oC
ONEtO2C
R1 CO2R2
O
yield: 79%~99%
OH
S CO2Et
Br
yield > 89% ee < 40%
NMeO
N
H CO2Et
Br
yield : 30%~79% ee : 96%~99%
Yong Tang. Tetrahedron. 2008, 64 , 5583-5589
Gaunt. M. J. Chem Rev. 2007, 107, 5596-5605
3. Cyclization
3.2 Fomal 4+1
232323
R2Cl
NNH
O R1
R3 S
O
+
Cu(OTf)2(10mol%)
L(11mol%)
N N
R2
O
R1
R3
ONa2CO3,THF
yield : 76%~97% er : 71:29~ 98:2
Proposed Mechanism:
Bolm, C. J. Am. Chem. Soc. 2012, 134, 6924-6927
3. Cyclization
3.2 Fomal 4+1
242424
SBr CO2Me + COR2R1
K2CO3
MeCN
MeO2C
R1 COR2
O
yield: 60%~93%R1=H, Me, aromatic
Yong Tang. J. Am. Chem. Soc. 2008, 130, 5408-5409
Yong Tang. J. Org. Chem. 2010, 75, 3454-3457
CO2Me + COR2R1
Cs2CO3,10ul H2O
BTF
MeO2C
R1 COR2
O
yield: 45%~91% ee : 54%~88%
R1=H, Me, aromatic
S
Br
OH
CO2Me BaseS
Br
OH
CO2MeS
OH
CO2MeS
OH
CO2MeS
OO
R2
H
H
R1
proton transfer
CO2MeS
OO
R2
H
R1H
CO2MeS
OO
R2
H
R1H
COR2R1
MeO2C
R1 COR2
O
Proposed Mechanism:
4. Tandem Reactions
252525
R1
R3 O
R2
S CO2Me
Br
Et3N
S CO2Me S CO2Me
CO2Me
O
R2S
R3
R1
CO2Me
O
R2S
R1
R3
CO2Me
R3
R2
O
R1
R1
R3 O
R2S CO2Me
Br
+EtOH, 0oC
CO2Me
R3
R2
OEt3N
yield : 30%~85%
R1
Junliang Zhang. Chem. Asian. J. 2009, 4, 1527-1529
Proposed Mechanism:
4. Tandem Reactions
262626
R1S
O+
R3 NO2
X
CO2Et
R2
CHCl3 (0.02M)
0oC- rt, 24hX
R2
NO
O
HCO2Et
H
H
R3
R1
OH
yield: 75%~99% dr > 95:5
yield :80%d.r. > 95:5 e.r. 90:10
Proposed Mechanism:
Wen-Jing Xiao. Angew. Chem. Int. Ed. 2009, 48, 9542-9545W-J, Xaio. J. Org. Chem. 2012, 77, 1072-1080.
4. Tandem Reactions
272727W-J, Xiao. J. Am. Chem. Soc. 2008, 130, 6946-6948.W-J, Xiao. Chem. Eur. J. 2012, 18, 4073-4079.
PhN
D
N OO
Ph
Ph
OD
N O
Ph
Ph
OD
OO
O
H
HN
NH
S
PhS
Ph
O
N
D
O
OH
HN
NH
S
Ar
Ar
PhS
O H2N NH
S
Ar
PhNO2
DH2N N
H
S
Ar
O
Ph
Ph
OO
N
N O
Ph
Ph
OO
DMAP
DMAPD
N O
Ph
Ph
OO
N
O
Ph
Ph
O
CO
N
O
Ph
Ph
O
O
N
O
Ph
Ph
O
O
D
DMAPD
DMAP
Proposed Mechanism:
4. Tandem Reactions
SR2
OR1
ArNO2
Thiourea(10 mol%)DMAP (10 mol%)
CHCl3, rt, 24h+ HN O
O
Ar R2R1
O
yield : 15%~ 95% d.r. : 91:9~>99:1 ee : 76%~94%
282828
O
R2
R1
SR+
[Rh(OAc)2]2 (2.5 mol%)
CH2Cl2, reflux
R=Me, Ph
O
R1
SR
R2
yield : 60%~98%
O
R2
R1
+
[Rh(OAc)2]2 (2.5 mol%)
CH2Cl2, refluxS
SR1
H
R2
Oyield : 43%~92%
d.r. ~3:1
Kouichi Ohe; Sakae Uemura. Org. Lett. 2003, 5, 2619-2621
O
R2
R1Rh
O
RhR1
R2
O
RhR1
R2
SR
O
Rh R1
R2
SR
[2,3] WittigO
R1
SR
R2
+ SO
RhR1
R2
[2,3] WittigO
R1
S
R2
D-A
SR1
H
R2
O
Proposed Mechanism:
4. Tandem Reactions
292929
R1+
SPh
O
R2
2.0 eq
PPh3AuNTf2 (5 mol%)
DCE, 60oC, 22h, 0.4M
O
R1
R2
yield: 30%~82%
Skrydstrup, T. Angew. Chem. Int. Ed. 2012, 51, 1-5
Proposed Mechanism:
4. Tandem Reactions
30
5. Conclusion
PPh3
O
R+NR1
PG
R R1
O
PPh3
NHPG
HCHO
R R1
O NHPG
chiralcatalyst
NHNH HN
HN
Ph PhS SF3C
F3C
CF3
CF3
R1
Br
O
+ R2
R3
O20 mol % cat1.3 eq Cs2CO3
MeCN, 80oC, 24h
R3
R2
OR1
Oyield : 60%~96%d.r. >99:1 ee : 80%~97%
Y-C, Chen. J. Am. Chem. Soc. 2008, 130, 2456-2457
N
OMe
N
OMe
Nitrogen
Phophorus:
Gaunt, M. J. Angew. Chem. Int. Ed. 2004, 43, 4641-4644
1). Sulfur ylides are important synthon in organic synthesis;2). New type ylide with unconventional properties need to be developed;3). Sulfide/metal-carbenoid system could be used in more kinds of reactions;4). Asymmetric proceeds using unchiral sulfide are potentially prospective.
Other Ylides:
3131