An efficient asymmetric oxidation of sulfides to sulfoxides

Tetrahedron Letters,Vol.25,No.lO,pp Printed in Great Britain

oo40-4039/84 $3.00 + .OO 01984 Pergamon Press Ltd.

1049-1052,1984

AN EFFICIENT ASYi+iETRIC OXIDATIONOF SULFIDES TO SULFOXIUES

Philippe

PITCHEN

and Henri B. KAGANX

Laboratoire de Synthese Asymetrique (Associe au CNRS, LA n"255) Universite Paris-Sud, 91405 Orsay France

Abstract The Sharpless addition

reagent

t 1 mol eq. diethyl

(Ti(OiPr)4

of one mol eq. H20 gives a new homogeneous

to sulfoxides H20/J-BuOOH

in dichloromethane.

sulfoxide.

Chiral

sulfoxides

considerable

metric

C-C bond formation

tion of intermediate chiral

sulfides

nantiomeric

for the oxidation

importance

diastereomeric

menthyl method

in synthesis

have been observed

of some sulfides

in some cases

into optically

sulfoxides

9-13

active

reagent

with a modified

procedure.

(I) as a model

substrate.

methyl p-tolyl

epoxidation

of allylic

in CH2C12,

sulfide

alcohols

and it is critical

Precipitation always

l:(l or 2):1:2,

(84 or 91% e.e. respectively,

conditions

(R,R)-diethyl

- 2O'C) leads to racemic methyl p-tolyl

Ti(OiPr),/(R,R)-llET/H20/TBHP, sition

(Ti(OiPr)4,

(presumably

Ti02).

Ti/DET/

beeing observed

synthonsforasym-

oxidationofpro-

moderate

to hign e-

a simple method

eve. up to 93% inone. 14 can of allylic alcohols

The standard

tartrate

gives a dramatic

yield

aithough

epoxidation

at - 20°C). A perfectly

The chemical

asymmetric

Sharpless

(DET),t-Bu@DH

sulfoxide(2). - However,

to avoid an excess of water

sulfidesin-

sulfoxides,w?+h

be used for the sulfide We selected

for asymmetric

by

is based on the separa-

. We wish to present

case. We found that the Sharpless oxidation

oxidizes

as chiral

sulfinates 5-8.Chemical for chiral

modified

for the stoichiometry

. The main synthesis of chiral sulfoxides

is not a preparative

excesses

reagent which cleanly

ranged from 4 to 93% with the highest

in the case of methyl -p-tolyl

1-4

(DET) t 2 J-BuOOH)

The best results were obtained

= 1:2:1:2. The e.e. observed

are gaining

tartrate

change

soluble

for

(TBHP), I:I:2

the combination

in the enantiomer species

compo-

is formedinthese

(> 4-5 equivalents),

is satisfactory

method

which

and sulfone

leads to

formation

is

negligible.

The procedure

for sulfide

and (R,R)-DET

(1.71 mL, 10 mmol)

90 ~1, 5 mmol)

oxidation

is introduced

is exemplified

are d&solved

through

in the case of -1.Ti(OiPr)4

(1.49mL,5mmol)

at 25'C in 50 mL CH2C12 under nitrogen.

a septum via microsyringe.

1049

Stirring

is maintained

H20 until

1050

the yellow

solution

becomes

homogeneous

(15-20 min) and 1 (0.7 g, 5 mmol)

tion is cooled to - 20°C, and 5 mL (10 mmol) of a CH2C12 is kept at - 20°C for 4 h. Introduction

ted. The solution tion gives a white

gel which

well washed with CH2C12.

is stirred

The combined

dried over Na2S04 and concentrated

dicated

in Table

oxidation

to see that a substrate

such asl, which

most enantiomerically combination sulfoxide

the optimum

synthesis

2 by the reagent

that the system

giving two tartrate

units acting as bridges

copy shows two ester-bands tion after the controlled

combination

addition

superimposable

It appears

(Ti(OiPr)4

(in the conditions

of Table

free

between

that in the se-

when alkyl = Me. It is interesting

that the sulfoxide


is not obtained

(of sulfoxide).

Treatment

albya

ofracemic

the two metal centers 16.1nfra-redspectros-

; 1635 cm-l chelated). We found the followingsituaof water to (Ti(OiPr)4 transformed

on the one obtained species

has been obtained

(R)-methyl

p-tolyl

e.e.). Finally,

we got the best result with a reagent

ter equivalent.

The water molecule

presumably

promotes

t DET

; 1:l) : the

into a new one (1740 cm-l,

with two equivalents

is almost as stereoselective

1, - 2O"C,

It appears

t DET, 1:l) is a dimer with alcohol interchanges

of 1 equivalent

that a similar

2 DET t 1 Ti(OiPr)4

temperature.

arein-

sulfone.

(1735 cm -l, 1635 cm-') immediately

1670 cm-'), almost Ti(DiPr)4.

(1735 cm

(lit.

The results

is not able to form a chelate on titanium,

It has been assumed

two band system

reaction

and kinetic resolution

-1

(AcOEt, cyclohexane

types of sulfides.

e.e. is obtained

does not produce

is

; mp 73-74.5°C)6.

pure sulfoxide -2. We established

of asymmetric

The filtrate

+ 132.5' (c=2, acetone),mp67-69°C

of several

1, taking - 20°C as standard sulfide

is introdu-

of 10 mL of H20 to this cooled solu-

paste. Chromatography

; Icd~=

: Ecx}~~= t 145.5" (acetone)

ries of S-alkyl e-tolyl

(2M)14a

layers are then washed with NaOH (1N) and brine,

organic

to give a white

The reagent was used for asymmetric

of TBHP

1 h (- 20°C + + 20°C) and filtered.

1:l) on silica gel gives 0.7 g (90%) of (R)-2 data for pure (R)-2

solution

is added. The solu-

of DET versus

and indeed we observed

as the reagent

sulfoxide

containing

incorporating.water

was thus obtained

2 diethyl

the formation

that the

tartrate

with 70%

and 1 wa-

of an 0x0 bridge between

two titaniums. We are currently new asymmetric metric

investigating

synthesis

oxidation

the scope and various mechanistic

of sulfoxides,

of sulfides

where

and synthetic

the highest enantiomeric

by a purely chemical

system were obtained.

excesses

aspects

of this

known forasym-

1051

Table 1 Asymmetric oxidation of various sulfides

Reactions conditionsa

Sulfide Methyl e-tolyl sulfide 1

- 2ooc

II

4h

- 40 -+ - 24°C

Sulfoxide configuration

e.e.(%)b

Yield(%)c'd

91

(R)

90

12 h

93

(R)

95

II

+

1°C

1.5 h

75

(R)

90

II

+ 21oc

20 min

47

(R)

90

II

+ 41oc

10 min

21

(R)

90

Ethyl p-tolyl sulfide

- 20.X

3h

74

(R)

71

-i-propyl ptolyl sulfide

- 2ooc

3h

63

(R)

56

-n-butyl ptolyl sulfide

- 2ooc

3h

20

(R)

28

Benzyl -p-tolyl sulfide

- 2ooc

12 h

7

(R)

41

Mesityl e-tolyl sulfide

- 2ooc

24 h

t-butyl (ptoluene-thio) acetate

t 2OOC

lh

4

(R)

66

hethy phenyl sulfide

- 2ooc

12 h

09

(R)

81

Eulfidg

0

= 2x10-l M in CH2C12, under nitrogen atmosphere. Reagent :Ti(OiPr)4

= Eeageng

t (R,R)-diethyltartrate + H20 + TBHP (1:2:1:2). Measured by the specific rotation of isolated sulfoxides using for the maximum specific rotations the values given in ref236. Isolatedyields for reactions at the 5 mnol scale and expressed with respecttoTi('liPr)4 The starting material accounts for the remainder, sulfone was not detected.

Acknowledgements We thank CNRS for its financial We thank Professor

K.B.Sharpless

support.

One of us (P.P.) acknowledges

for useful discussions

DGRST for a fellowship.

and communication

of unpublished

data.

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