Preparation of Allyl Sulfoxides by Palladium-Catalyzed Allylic Alkylation of Sulf

enate Anions

Guillaume Maitro, Guillaume Prestat,

David Madec, ＊ and Giovanni Poli ＊

J. Org. Chem. 2006, 71, 7449-7454

演講者：化生四 張永宏

2

Allyl Sulfoxides

• Allyl sulfoxides are versatile and valuable building blocks in organic synthesis .

S

R

Ph O S

Ph

O

R [T]

1. BuLi2. PhSCl

R OH

Acc. Chem. Res. 1974, 7, 147.• It is proved by their use in the preparation of various functionalized compounds and natural products.

SO

PhR Bu2SnH, AIBN OR

Angew. Chem. Int. Ed. 2002, 41, 4323.

azobisisobutyronitrile

NN

N

N

S

R

Ph O S

Ph

O

R

PPh

Ph

Ph

O

R

H2O

OH

R

SOPh

[2,3]-sigma. O SPh

O

O O Bu3SnH

- Bu3Sn

O

RR R

R

R R

Bu3Sn

3

Palladium-Catalyzed Allylic Alkylation of Sulfur Nucleophiles

4

Generations of Carbon-Heteroatom Bonds by Palladium Complex

OAc+ TsNa + 4H2O

Pd(PPh3)4

(5 mol %)

rt, THF-MeOHTs

Ts

(Ts = p-CH3C6H4SO2)

+

Chem. Lett. 1981, 1357-1360.

R-Z O

OPdLn

CO2

PdL

L+ Z

NuH

PdLn

PdLn

RZH + Nu

R-Z

a

b

Synlett 1993, 680-682.

(Nu = sulfur nucleophiles)

R-Z O

O

+ [Pd]Z-R

O

O

[Pd][Pd]

CO2

SR

SR

[Pd]

OAc[Pd]

AcO

[Pd]

+

[Pd]

[Pd]

Ts

TsTs

+

[Pd]

5

Synthesis of Allyl Sulfoxides

6

Mechanism of The Synthesis of Sulfenate

7

Methods of Generation of Sulfenate Anions

• Sulfur oxidation

• Addition-elimination reaction

• Ring-opening reaction

• Ring manipulation route

• Sigmatropic rearrangement

• Metal insertion reaction

• Retro-Michael reaction

8

Generation of Sulfenate Anions by Sulfur Oxidation

• Sulfenate anions are of limited stability.• A competitive oxidative pathway leading to symmetri

cal disulfides may occur.• The oxidizing agents employed up to now, m-CPBA a

nd hydrogen peroxide, were not particularly well suited to this task.

SH

R1

R2

R3

1) MeLi, -78oC, THF

2) 1, -78oC3) R4X, -78oC to rt X = Br, I

S(O)R4

R1

R2

R3

NO

Me

t-Bu SO2Ph

1

J. Org. Chem. 1997, 62, 8626-8627

S

R1

R2

R3

NO

Me

t-Bu SO2PhS

R3

R2

R1

OMe

N

t-Bu

SO2Ph SO

R1

R2

R3

9

Generation of Sulfenate Anions by Metal Insertion Reaction

n-Bu S(O)Tol

1) PdCl2(dppf) (2 mol%) Et2Zn (2 eq) THF (0.1 M) -78oC to rt

2) H+

n-Bu

TolS(O)

S(O)Tol+

n-Bu

Et

S(O)Tol

Org. Lett. 2001, 3, 3627-3629

dppf = diphenylphosphinoferrocene Fe

Ph2P

PPh2

10

Generation of Sulfenate Anions by Ring-Opening Reaction

S

OLDA

THF, -78oC

S

OLi

RX S RO

Synlett, 1996, 1996, 247

S

O LDA

H S

O

S

O

11

Methods of Generation of Sulfenate Anions

• Sulfur oxidation

• Addition-elimination reaction

• Ring-opening reaction

• Ring manipulation route

• Sigmatropic rearrangement

• Metal insertion reaction

• Retro-Michael reaction

12

Generation of Sulfenate Anions by retro-Michael reaction

SR1 CO2R2

O1. Base 2. R3X S

R1 R3

O

*

R1 = aryl, alkylR2 = Me, Et

ee up to 29%with n-BuLi/(-)-sparteine as base

J. Org. Chem. 2005, 70, 2812-2815

R1SO

13

The Catalytic Cycle for Transition Metal-Catalyzed Allylic Alkylations

14

Preparation of β-Sulfinylesters

a:

b:

c:H3C

CH3

CH3

15

Mechanism of The Preparation of The β-Sulfinylesters

O

OH

HO

SO

O

K

OHO

O

OH

HO

SO

K

OH

OS

R

CO2t-BuSR

CO2t-Bu

O

R S

CO2t-BuBase

H SR SRCO2t-Bu

SRCO2t-Bu

H2O

16

Mechanism of The Formation of Sulfenate Anions

retro-Michael reaction

RS O

Ot-Bu

O

RS O

Ot-Bu

O

Base

HSO

R + O

Ot-Bu

17

Optimization of Reaction Conditions

( dppe = cis-Ph2PCH=CHPPh2 )

18

Allylic Acetates

OAc Ph OAc

Ph

OAc

OAcOAc

1-phenylallyl acetate

allyl acetate cinnamyl acetate

cyclopent-2-enyl acetate cyclohex-2-enyl acetate

19

Palladium-Catalyzed Allylic Alkylation of Sulfenate Anions

20

The Interconversion Equilibrium between The Two Diastereomers

Sp-Tol

O

OS p-Tol

Sp-Tol O

Synlett, 2004, 995-998

(R,R/S,S) (S,R/R,S)

21

Palladium-Catalyzed Allylic Alkylation of Sulfenate Anions

22

Palladium-Catalyzed Allylic Alkylation of Sulfenate Anions

23

Allylic Alkylations in Biphasic Conditions

24

Conclusions

We have reported the first palladium-catalyzed allylation of sulfenate anions.

This new, smooth, and operationally very simple method further extends the set of sulfur-based nucleophiles that can be successfully allylated under palladium catalysis.

The stereogenic nature of the sulfur atom in the generated allyl sulfoxides, and the potential sulfoxide-sulfenate rearrangement associated to these compounds are expected to make of this reaction a synthetically interesting transformation.

25

S

O LDA

H S

O

S

O

n-BuLi/(-)-sparteine