Stereochemistry of the sulfinylnitrene - sulfoxide reaction. Nucleophilic substitution at sulfur with retention of configuration.

Tetrahedron Lettera

NUCLEOPHILIC

SUBSTITUTION

AT SULFUR

Tom J. Maricich Department

Fargo,

ThB stereochemical compounds ceptions

generally

course

occurs

which occur with retention

eulfoxide

((t)-(R)-&) -

ionine eulfimide, 3 awl the reaction methyl

butyl eulfoxide

in benzene. 5

p-toluenesulfinyloitrene in the eulfimide Treatment toluenesulfinyl

product

sulfoxide,’

(Ib)

a four-membered sulfoxide

in acetonitrile

isolated absence

acetone).6

e-Toluenesulfonamide

of added eulfoxlde.

The formation action of benaeneand diphenyl

1972)

Novembe.~

with eulfoxidee 1

at sulfur.

Three

(15.2%)

material

and related

reported

ex-

active methyl E-tolyl

of methionine

sulfoxide

with (t)-(R)-&ald

to meth-

(-)-@)-

on the etereochemirrtry

of the reaction

((t)-(R)-2~). --

of configuration

Retention

eulfurane

((t)-(_R)-&)

intermediate.

of 99 % optical

purity with E-

of 92. 1% optical purity

and methyl B-tolyl

and other minor

of

sulfide

components

cryetalliaed

(by:

(2.8%)

normally

t 247.6. were

aleo

found in the

5b

of sulfimide

may be considered

or p-toluenelrulfinyl

sulfoxide.

30

of optically

cyclic

((t)-(_R)-&)

in addition to polymeric

University

at 50’ gave a 42% yield of nonfractionally

(t)-@)-N-(E-toeyl)ethyl-E-tolylaulfimide c 1.68,

sulfoxlde

REACTION.

OF CONFIGURATION.

reactions

the conversion

We wish to report

with methyl p-tolyl

aupports

exchange

8rit&r.

USA

of 5, r-ditosyl-sulfodiimide 4

of (t)-(_R)-methylp-tolyl azide

of configuration

are the “0

with dimethyl

58102

substitution

in &eat

Hoffman

in UK for publication

of nucleophilic

with inversion

L.

North Dakota Sate

North Dakota

in USA 24 July 1972; received

- SULFOXIDE

WITH RETENTION

and Virgil

of Chemistry.

Printed

Preae.

OF THE SULFINYLNITRENE

STEREOCHEMISTRY

(iieoeived

Per-n

Ao. 52, pp 5309 - 5312, 1972.

Reaction

of &

general.

axlde with dimethyl with diphenyl

5309

having

been produced

sulfoxide,

nulfoxide

5a

from the re-

methyl p-tolyl

gave N-(benaeneeulfonyl)-

sulfoxide,

diphenylsulfimide

(26%),

9

RiRI

t

A&N,

benzenesulfonamide

‘R’

Ar -

EL.

R’ -

C6H5

CH3

CY CH3

p-C&W-L

CH3

c

g-CH3WG

CH3

with a dipolar

of sulfoxide

cycloaddition

reaction

charged

to suifimide

negative leaving

are assumed

(equatorial).

orientation

pseudo-rotation

9

a and -7 are labeled _a if formed if the pseudo-rotational

expulsion

directly.

Regardless

would be expected.

(~mechanism

followed

I).

by S-O

atoms

the cyclic

reasons.

or vice versa,

of the actual mechanism

(aa,

4 E,

7a to be --

of 6 and 1 are interchanged).

are rate determining,

of the

Such an%

structures

from 2 by axial attack and 2 if formed processes

electro-

nitrogen and axial expulsion

for electronic

inter-

having the four-

pair in the most

of -6a to 72 or of equivalent

where the ring oxygen and nitrogen

1,g

geometry,

and the electron

would be favored

(structures

equatorial

(Scheme

oxygen on the

S-N cyclization

bipyramidal

Axial attack by the entering

would require

However,

is consistent

(4b) with sulfoxide

and other sulfuranes,

trigonal

mechanism

attack.

of configuration

(t)-(_R)-&.

to possess

oxygen group (aa mechanism) -

mediates

adduct 2.

of phosphoranes7

ring in the axial-equatorial orbital

with retention

to be an attack of the sulfoxide

sulfur of -4b to give a dipolar

ring opening would lead to the sulfimide

(a and a

C&5

;, of p-toluenesulfinylnitrene -

is proposed

By analogy to the chemistry

p-cH3c6K

c6H5

c6H5

step of the reaction

membered

-_NsS’

2

d_

mediates

Ar

a

The transformation

(7%).

R

-N2

a

positively

and diphenyl sulfide

2

1

The first

(27%),

The inter -

by equatorial

axial attack and

could occur lo to form (t)-(IX)-& or 4

the same product,

(t)-(R)-&,

No. 52

5311

Scheme

I

-

Failure

to obtain complete

age from the dipolar

retention

adduct 2 through deoxygenation

give p-toluenesulfonylnitrene

@) and methyl

most likely produce the racemic of a sulfide

from this reaction

Furthermore,

tion.

Scheme

sulfimide

p-tolyl

may be explained

of the sulfoxide

from direct

of sulfonamides

with the sulfide,

suggests

crosses

by sulfinyl

attack of the nitrene reaction

II) by leak-

nitrene 5

to

of the latter would 11 on sulfur. Isolation

supports

that the singlet

over to the triplet

\

(Scheme

Recombination

sulfide.

and from the diphenyl sulfoxide

the formation

which does not recombine hydrogen

of configuration

P-chc6&’

this explana-

sulfonyl

state (9

nitrene g,

and abstracts

from the medium. II 2

__c

p-cI-LJ61-14so,-~:

tJ

t

p-CH,C&,SCH, -

-

(f)-&

s I

1 (+)-(_R)-3c -

-p-cH,c&&-~;

t

-

R-H

p-CH,C&,SO,NH,

9 The development a convenient

of the sulfinyl

route for the preparation

purity through other methods. tion with methanolic sion),

aside reaction

provides

potassium

a two-step

l-4

of chiral

In particular,

hydroxide

converting

(t)-(g)-&

sulfimides

not readily

employing

this reaction

hydrolysis

of the optically

method for inverting the configuration

to (t)-(B)-& available

in high optical

(retention)

active

of chiral

provides

in conjunc-

sulfixnide ’ (inversulfoxides.

NO. 52

5312

Acknowledgements: Cancer

This investigation

in part by a grant from the National

We also wish to thank Jill Armbrust

Institute.

samples

was supported

of the optically

active

and Victor

Munson for preparing

stifoxide. REFERENCES

(1)

(a)

T. R. Williams, 4684 (1972).

A. Nudelman,

(b)

D. J.Cram, J.Day. D.R.Rayner, Garwood. c., 92, 7369 (1970) M. Kise,

S. Oae,

(3)

B. W. Christensen

(4)

B. W.Ghristensen,

c.,

(5)

(a)

T. J. Maricich

and V. L. Hoffman.

(b)

T. J. Maricich,

J. Am. Chem. a., _--

(7)

(8)

have been determined,

and B.M.

Martin and E. F. Perozzi,

(9)

R.S.

(IO)

K.Mislow,

(11)

A referee

J.Chem.P&. _Accounts

of configuration

(9

s.,

hindrance

rotations

L. &

C&.

Accounts

%.,

s -

6674 (1971);

2,

2,

active

by

compounds

have been shown to be lb

634 (1970);

&

Chem. Res.,

J. Am. Chem. Sot.,

identified

for optically

like those used in our experiments.

D. Gorenstein,

&, 70 (1968).

6077 (1971);

N. C. Baensiger,

I. C. Paul,

R. E. Buckles,

J. C. R. J.

5749 (1969).

2, 321 (1972).

that all of &

could be produced

and sulfide in a solvent

cage.

to prevent that rotation.

from rapid recombination

While possible,

obtained is too high to be explained

exists

729 (1971).

and the compoutxis

slight rotation of the sulfide would be necessary steric

Letters,

, 3&, 933 (1960).

Chem.Res.,

has suggested

sulfonylnitrene

Trost, g,

and T. D. Simpson,

Berry,

Tetrahedron

The maximum

data.

and F. H. Westheimer.

R. W. LaRochelle

&

4131 (1968).

9&, 7179 (1968).

644 (1970); F. Westheimer,

2,

Maner,

934 (1969).

stable to mild conditions

D. Gorenstein L, ibid

J. Chem. Sot.

and D.C.

Letters,

in this study is known and was satisfactorily

with reported

(or their enantiomers) optically

Tetrahedron

9&

597 (1971).

Each compound involved comparison

a nd N. Furukawa,

aad A. Kjaer,

J. Am. Chem. Sot.,

D.M. vonSchrilts, D. J.Duchamp, cited therein. and references

(2)

(6)

hf. Yokoyama,

R. E. Booms and D. J. Cram.

of the

the extent of retention

soley by that mechanism.

to invert the configuration

Only a and little