A chiral amination reagent and an efficient synthesis of (S)-methyl p -tolyl sulphoxide

Tetrahedron Printed in

Letters,Vo1.23,No.?6,pp Great Britain

A CHIRAL

2687-2690,1982

AMINATION

SYNTHESIS

OF

Department

REAGENT

(S)-METHYL

Anders

Kjaer*

of Organic

(+)-O--

bromocamphor-n

salts,

of enantiomerically

difficulties.

produced

nation

It occurred

from

* salts into individual Hence,

homogeneous

SULPHOXIDE

Malver

The Technical

Univer-

Denmark

- sulphonyl)-hydroxylamine,

(1 ), a chiral

into diastereomeric

reaction

forms

the basis

(S)-methyl-p-tolyl

amina-

aminosulphonium of a convenient

sulphoxide,

asynthesis

a key compound

in sul-

stereochemistry.

Synthesis siderable

and Olaf

sulphides This

-sulphonates.

of enantiomerically phur

prochiral

AN EFFICIENT

p-TOLYL

2800 Lyngby,

(a- Bromocamphor-n

converts

tion reagent,

AND

Chemistry,

sity of Denmark,

Summary

0040-4039/82/262687-04$03.00/o 01982 Pergamon Press Ltd.

prochiral sulphoxide

we synthesized’ reagent

modelled

homogeneous

to us that resolution sulphides

by chiral

enantiomers,

might

Tamura’s

is a task

of diastereomeric

amination,

followed

be a useful

adjunct

- sulphonyl)-hydroxylamine

(+)-(a-bromocamphor-n. after

sulphoxides

reagent,

g-me

often beset

with con-

aminosulphonium by conversion to existing

of the

methods.

(1 ), a chiral

sitylene sulphonylhydroxylamine,

amiwide n

ly adopted

for the amination

of various

nucleophiles

including

sulphides

and sulphoxides.

‘

n

The reagent action

(1) proved

with acetone,

quite

stable

and identical

and was

characterized

with a specimen

2687

produced

as the oxime by treating

(2). ’ formed acetoneoxime

upon rewith

2688

(+)- a-bromocamphor-n-sulphonyl

chloride.

R-O-NH2

R-O-N<

11)

(2)

soz-!

R=O

6%. -+-0

&

S

A1

Br

Optically

active methyl p-tolyl

lations within the series a starting

material

enantiomers.

5

of tri-

we treated

agent (1) in ether.

A quantitative

a-bromocamphor-n

-sulphonates.

the extent of asymmetric fractionated compared

tolyl sulphimide,

[a] i” = +267’

useful,

because the less

zations from prepared

water.

8

Alternative

ders the salt (4) equally

accompanied sulphimides oximide

amount of the resulphonium

In order to assess

were set free from the non-

The rotation

[a] ;5 = +10.2O (Me2CO),

(R)-N-p-toluenesulphonyl -_

methyl p-

of the (R)-enantiomer -

homogeneous

of the enantiomeric

of only a

is preparatively

after only three recrystalliamination reagent,

(-)-a-bromocamphor

of the salt (3) to methyl -p-tolyl racemization.

on deprotonation.

(5), ’ followed

instantaneously.

an excess

as

alkyl methyl sulphoxide

induction thus is low the reaction

ammonium

corre-

similarly

-71-sulphonate,

ren-

available.

by extensive formed

6

homogeneous

utilization

available

available

the sulphimides

soluble salt (3) becomes

from commercially

Acid hydrolysis

separated

(Me2CO), 7 reveals

few per cent. Even when the asymmetric

B=Me

of the two amino methyl p-tolyl

and subjected to tosylation.

with that of the enantiomerically

B=p-Tolyl

sulphide with an equimolar

induction in the reaction,

salt mixture

A= p-Tolyl;

difficultly

yield of a mixture (3) and (4),

A=Me:

IhI:

sulphur compounds, 4 but also serves

of otherwise

methyl E-tolyl

(31:

is a key compound in stereochemical

and tetra-coordinate

for the synthesis

Hence,

sulphoxide

, R-O-

‘NH2

by quantitative

whereas Hence,

proceeded

readily,

alkali caused rapid decomposition

recourse

deimination

sulphoxide

11

was taken to oxidation

of the latter to (S)-methyl

but was of the free

of (3) to the sulphp-tolyl

sulph-

2689

P-W.

p-To],_

//O

0

SP u

'S

Me’

Me.

‘NH I51

oxide

(6). both reactions

74.5-75.5’C

rically

known to proceed

and [a] :” = -145.3’

[al E5= +145.3O tiomer.

16)

(c _ 0.795,

lo We believe homogeneous

with retention.

(c - 0. 8, Me2CO),

Me2CO)

p-tolyl

Unfortunately,

methyl

the method

of salts of type (3) and (4) from

matching

for the supposedly

that the here described

The sulphoxide the values,

enantiomerically

method

(6) obtained

provides

had m. p.

m. p. 74. 5 - 75. 5’C, homogeneous

(R)-enan-

the easiest

access

to enantiome-

Quantitative

yields

were obtained

sulphoxides. is not generally

applicable.

(1) and butyl methyl

IL-tolyl sulphide,

and o-methoxyphenyl

recrystallization

proved

unsuccessful

sulphide,

phenyl sulphide,

methyl

but efficient

phenyl sulphide, separation

phenyl

by fractional

in all the cases.

Acknowledgement The authors

are grateful

to Miss

Lone Biitow for her assistance

during the initial

phase of this work.

References 1.

I

The sulphonyl camphor-n iminoacetate

chloride

-sulphonate

(46 mM),

and Notes

produced

from

was added to a cooled

commercial

and stirred

(+)-ammonium

solution

a-bromo-

of ethyl -N-hydroxy-

(46 mM) and TEA (46 mM) in DMF (15 ml) to give ethyl -N-(a-bromocam-

phor-n -sulphonyloxy)-acetite one stereoisomer

according

(88%)) m. p. 130-131°C, to ‘H NMR.

The protected

[a] z5 = + 57. 2O (21.

hydroxylamine

ester

CHC13);

(10 mM)

2690

was kept in 80% H2S04 (40ml) water

(150ml),

solution

for 30 set,

was used as such;

2.

Y. Tamura,

3.

Produced acetone

from

ethyl

(2 ml),

extraction.

and M. Ikeda,

dissolved

in dioxane

It was recrystallized

nyl chloride

A specimen,

Synthesis,

(4x 50 ml).

1977,

iodometrically.

1.

by dilution

from EtOAc:hexane,

in benzene,

(2. 5 ml) and

by adding 80% H2S04

(85 %) was isolated

produced

into ice-

The dried ether

-sulphonyloxy)-acetimidate’

alternatively

and acetoneoxime

with ether

(0. 5 ml) at O’C,

The oxime

was then poured

of (1) were determined

(a-bromocamphor-a

of 10 min.

CHC13).

and extracted

the contents

J. Minamikawa

in the course

(21,

stirred

at O°C for 4 h. The solution

with water and ether

m. p. 81°C,

from

containing

(0. 25 ml)

[a] “,5 = +90.3O

(+)-a-bromocamphor

TEA,

possessed

-n -sulpho-

identical

physi-

cal data. 4.

For a review,

see D. J. Cram and J. M. Cram,

5.

J. P. Lockard,

C. W. Schroeck

6.

The salt mixture

dried,

concentrated

ene sulphonyl graphy

was quickly

to 3 ml,

chloride.

(EtOAc).

The product

After

(previously

to tosylation

filtration

1973,

at O°C.

1972,

purified

31,l.

485.

1 N NaOH (1.2 ml) was The extract

by adding pyridine

was oxidized

of Mn02,

10

-Chem. Commun.,

a 40% yield

was

and -p-tolu-

by flash chromato-

solid,

m. p. 59-61°C,

784.

of the pure salt (3) was ob-

produced

with KMn04

the sulphoximide

1975,

H20).

in dichloromethane,

as a hygroscopic

reported:

water,

[a] i5 = +57. 4O (21,

of the sulphimide

chloromethane

(10ml)

was non-fractionally

from

at O°C and rapid extraction, tion.

Synthesis,

with CHC13 (3 x 10ml).

and A. Kjaer, --J. Chem. Sot.,

m. p. 203-204°C,

A solution

extracted

and subjected

three recrystallizations

tained,

in water

Chem. Forsch.,

Yield 42 %.

B. W. Christensen After

and C. R. Johnson,

(1 mM) was suspended

added and the mixture

Fortschr.

from

at 20°C in aqueous

(5) was isolated

m. p. 58-60 ‘C, [a] z5 = -32.4’(2

(3) by alkali

0.885,

dioxane

by extraction

[ a] i5 = +32.6O

(~0.9,

Me2CO)

addition solu-

with diMe2CO)

for the

(R)-enantiomer). 10.

D. J. Cram, J.Am.

11.

J. Day,

Chem. Sot.,

The deimidation

D. R. Rayner, 1970,

The resulting

(96 % yield). in

D. J. Duchamp

and D. C. Garwood,

92, 7369.

of (5) was performed

water was added at ZO’C.

(Received

D. M. vonSchriltz,

UK 27 April

1982)

in 4 N H2S04 to which 2 mol. equiv. of NaN02 in sulphoxide

(6) was extracted

with CHC13