reactions involve sulfur ylides 陈殿峰 2012.05.12 陈殿峰 2012.05.12

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


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%~


Slow addition for 24h

2.1 Epoxidation


777


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


88

First example

8L-X, Dai. J. Chem. Soc., Perkin Trans. 1996, 867

OH

S

racemic

2.2 Aziridination


99

First Asymmetric example

9

2.2 Aziridination


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


111111

Si S

O

O

SES

Aggarwal, V. K. Angew. Chem. Int. Ed. 2001, 40, 1433

2.2 Aziridination


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.


2.3 Cyclopropanation

131313

Aggarwal, V. K. J. Chem. Soc., Perkin Trans. 2000, 3267Aggarwal, V. K. Chem. Eur. J. 2006, 12, 568



141414

Aggarwal, V. K. J. Chem. Soc., Perkin Trans. 2000, 3267Aggarwal, V. K. Angew. Chem. Int. Ed. 2001, 40, 1433



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



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


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


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


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


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:

reactions involve sulfur ylides 陈殿峰 2012.05.12 陈殿峰 2012.05.12

Documents