Rearrangements of cyclic sulfoxides

Tetrahedron Letters No.11, PP_ 849-852, 1969. Pergsmon Press.

REARRANGEMENTS

Robert

B.

Morin,

OF

Douglas

The

CYCLIC

0.

Spry,

Lilly Research Eli Lilly and Indianapolis,

Printed in Great Britain.

SULFOXIDES

and

Richard

A.

Mueller

Laboratories Company Indiana

(Received in USA 25 November 1968; received in UK for publication 29 January 1969)

It has can

undergo

the

sulfur

this

an

an

The

found

that

internal

becomes

appears

possess

been

phenoxymethyl

oxidative-reductive

oxidized.1

to be

penicillin

We

a general

have

reaction

reaction

found

in the

of cyclic

sulfoxide

methyl

in which

a carbon

work

reported

sulfoxides

which

ester B to

here

that

do not

a-hydrogen.

2,2_dimethylthiachroman

l-oxide

1,

mp

c / cn

60-61°, on treatment

with

S

S

c CXA CHZ

CH3

4

freshly 80%

distilled

yield.

The

acetic

anhydride

structural

assignment

1733 cm-l; nmr (CHC13) 6 1.40 AB pattern

4.20

and

4.05

chemical

transformations

of water

to

formation

the

of olefinic

(m, of

anhydride

at

(s,

reflux is based

3), 2.03

caused

compounds

substance.

2

a decrease and

the

two

849

gave

on physical

(s,

2, J = 11 Hz), the

temperature

31,

7.01

1.93

(s,

k)]

compound

data

(m,

2),

and

on

[ir 2.83

2 in

(CHC13) (m,

further

Addition

of small

quantities

in yield

of g with

concomitant

products

resulting

from

2),

No,11

850

With

disproportionation. only

disproportionation

nature

of Two

1

[nmr

(m, 4.82

product olefinic

(CHC13)

l),

7.2

was

Ac,O.

materials

were

(br.

s,

2),

but

in

a different

yield

s,

7.2-7.5

small

(m,

3.37

ratio

by

by

(br.

(CHC13)

same

of

acetate

VPC s,

6 2.4

The

4)].

quantities

Sodium

isolated

3),

4)l and 4 [nmr

(br.

of

observed.

of 1 with

6 1.68

(m,

addition

did

and

2),

(m,

not

shown

3.58

2),

olefins

cone

(br.

3.0

of 1 with

of a carbonyl

group

to Ac20

affect

the

have d,

(m,

were

treatment

to

HCl

Z),

2),

in

5.67

3.28

produced

pTsOH

structures

(s,

Z),

in higher

refluxing

xylene. The studied

effect with

on the

the

reaction

keto-sulfoxide

2,

mp

6 to In

92.5-93.5'.

the

this

sulfoxide

case

only

was the

ring

0-

Ac20

>

[mp

103-5O;

dcH3

+

afcH3

0

contracted 7.36

(m,

(br.

s,

Cm,

l)I,

obtained acid

which

products 4)1 3),

and 2.35

but

not

from

6

I. [mp (s,

31,

those

Ac20

38-40'; 5.20

In the

Ac20

treatment

a hydrogen

(CHC13)

(CHC13)

(br.

treatment.

disproportionation

possess

ir

arising

caused

nmr

s,

from

11,

to of the

on the

1772

cm-l;

5.45

(s,

oxidation

As with

the

6 2.01

of

3),

nmr

(CHC13)

11,

the

earlier

(s,

7.53

methyl

2.50

(m,

6 2.16 3),

6.50 were

groups,

sulfoxide,

addition

76-8O,

a,

of

occur. sulfoxides

n-carbon

and

4.

mp

in which

the

and

AC

0 2

mp

carbon-sulfur

CR3 cH3

3),

(s,

74-94O, bond

NO.11

851 G-H CH3

CH3 Ac,O

11

lo is not

subject

reaction (m,

was

yields, were

(m,

and

no

group

The

411

in penicillin

2

and

resulting

[nmr

-114

from

-10 was

isomer-,

in

penicillin

by

sulfoxide,

(CHC13)

are

6 1.98

formed

oxidation

a mixture

probably

a Pummerer

(s,

in nearly

31,

two

in which

3.30

quantitative

of a carbon

of the

that

reaction

Some

reaction

direction

of the

esters

can

be

B to

the

sulfur

diastereomers;

the

oxygen

and

methyl

sulfenyl

of 1 and

and

the

in the

that

of 2

The

sulfoxides

be

described

derivative

suggested

elimination.

reagent

a reaction.

is needed

Sulfoxides

rearrangements

on photolysis

products

were

which

was

2 can

the

penicillin

can

results of g2

to

as an

then of

work.

be

the

indicate

generated

due

to

work

on

that

The a

the

stereospecific.

electrophilic

cause

1

of I and

of the

mechanism

between

sulfoxide

reactions

addition

A similar

course

difference

not

(s,

reported

followed

different

did

products

sulfoxide

a single

presently

bond.

overall

The

as

-cis.5

elimination double

3 7.08

The

8 was

are

11,

constraints

substances

obtained.

whereas,

steric

observed.

5.63

21,

to

formed

6 at by

as heating

1 and

room

heating

2 will

temperature with

I, at undergo

to

the

electrophilic

reflux

in xylene

dehydrative same

or

similar

agents.

REFERENCES

1.

R. B. and

Morin,

S.

B.

L. Andrews,

2.

D.

0. Spry

3.

C. R. Johnson, 5299

G. Jackson,

(1967).

and

J. Amer.

R.

B.

Morin,

J.

C. Sharp,

R. A.

Mueller,

Chem.

Sot.,

unpublished

and

W.

G.

E.

R.

Lavagnino,

W.

B.

Scanlon,

in press.

results.

Phillips,

Tetrahedron

Letters,

852

4.

No.11

Farbenfabriken a,

5.

6.

11413d

Bayer

Akt.-Ges.,

conclusion

resulted

work

from

laboratories

and

these

A. Archer R.

Patent

804,689;

Chem.

Abstr.,

data,

unpublished

(1959).

This

R.

British

and

A. Archer,

B.

from

consideration and

S. Kitchell,

personal

C. R.

Johnson,

J. Amer.

communication.

of physical

Chem.

personal

Sot.,

88,

communication.

3462

(1966),