Synthesis of the coumarin, sesibiricin

Tetrahedron

Letters

No.

36,

pp.3317

-

SYNTHESIS R.D.H.

Murray,

Department

ally1

substituents,

from

the

readily

0-prenyiation

available

to C-8,

5-oxygen

is the more

hydroxyl,

step,

preferably

insertion

since

such

at low temperature selective

The sequence,

reaction

bisether the only

synthesis

(10, 52%) other

from

diphenol.

alkylated.

Thus

question

arises

of the isoprenyl are

group

unstable5

2

the synthesis of the bis-ether achieved

but fortuitously

at C-8,

might

product

and its

ether

on Lindlar

stepwise

(23%). conversion

hydrogenation,

the desired

(vide

infra)

furnished

3317

selective

-

function-

3, 4

that the

protection

is the

of the

substituent would

the Claisen

the facile

survive

the

rearrangement

rearrangement

(4 ) led us to anticipate

In the more

bromide,

21. was

l-dimethyl)

of 8 to 3 that a

be possible.

by two routes.

That

the 7-(1,

function

in particular

However,

rearrangement

is necessarily

this

2, 3

demonstrated

it is known

this

synthesis

regioselective

(7),

since

since

of coumurrayin (9)

provided

contain

step

ether,

a projected

Claisen

diacetate

the first

two 3, 3-dimethyl-

previously

undergo

as to whether

of 3 with 3, 3-dimethylallyl

major

we have

be expected

at 19U”.

Thus

necessitate

of 1 would

not however

1971)

in that it possesses

would

Since

precursor

Britain.

W.2.

28 July

to carbon. (6)

Great

McCabe,

Glasgow,

publication

6 or the corresponding

would

of 9 was

behaviour’ (12),

the other

and P.H.

of Glasgow,

for

as the 3, 3-dimethylallyl

during

rearrangement

University

(1) is unusual

to oxygen,

The

ethers

Ballantyne

accepted

1971;

synthetic

readily

in sesibiricin.

three-step

The

of this

at C-7

2

M.M.

in

SESIBIRICIN

of 7-hydroxy-5-methoxycoumarin

Starting

of the oxygen

COUMARIN,

Hogg,

sesibiricin’

a suitable

.

THE

Printed

Pergamon Press.

1971.

5, 7-dihydroxycoumarin

ethers

grouping

present

July

9

coumarin,

alisation

C-5

in UK

and C-prenylation

exclusively allyloxy

T.C.

one attached

that dimethylallyl

OF

of Chemistry,

(Received

The natural

331%

K2C03

direct

in acetone

monoether

to 4 .

9 which

was

efficient

mainly

the

143.5-145O,

followed

The derived2

significantly

gave

(11) , m.p.

a 7-hydroxycoumarin

but less

from

as its

dimethylpropargyl found

from

TLC

UV

NO. 36

dR

R2= CH2CH=CMe2

2

Rl= CMe2CH=CH2,

R2=Me

Rl= CMe2CH=CH2,

R2= CH2CH=CMe2

Rl=R2=

1:

Rl=Me,

2:

Rl=H,

R2= CH2CH=CMe2

11: Rl=H,

3:

Rl=H,

R2=Me

12:

Rl= CMe2CnCH,

4:

Rl=R2=Me

13:

Rl= CH2CH=Ch4e2,

5:

Rl=Me,

10.

14:

R2=H

and NMR to contain a small percentage of the 1, 1-dimethylallyl

rearrangement at 130’ for 1 hr. acetone) sesibiricin

and therefore

coumurrayin synthesis

respectively

Direct from

gave,

after hydrolysis

dimethylpropargylation

T.R.

Seshadri

and Vishwapaul,

2.

R.D.H.

Murray,

3.

R.D.H.

Murray

4.

V.K.

5.

M.M.

Ahluwalia, Ballantyne,

M.M.

and M.M. T.R. P.H.

Ballantyne,

Seshadri McCabe

separated

andK.P.

(MeI,

K2C03

in

of the synthetic

efficient

of 1 into six-step

route to the key

3, 3-dimethylallyl

bromide.

monoethers

of 12 and 14, 50% and 14%

by TLC.

4, 202 (1970).

Mathai,

Tetrahedron,

and P. Venkateswarlu, and R.D.H.

by heating

10 (8%) and the two isomeric

Indian J. Chem.,

Ballantyne

converted

the synthetic

(7) with excess

Claisen

accomplished

by conversion

A more

gave a mixture

7, which were conveniently

1.

(11) was verified

of the diacetate

R2= CMe2CXH

The structure

from 7) was achieved by improving

in L 2-dimethoxyethane

(ll and 13).

product (2) was readily

to 5 and methylation.

Thus treatment

(12).

R2=H

The selective

ether of 9 was quantitatively

that of the monoether

of 1 (25% overall

R2= CH2CH=CMe2

phenol (2).

m. p. 121-122O, in high yield.

(4) via acid hydrolysis

intermediate K2C03

(I),

R2= CH2CH=CMe2

Rl= CH2GH=CMe2,

of the desired

The sole rearrangement

into seeibiricin

CH2CH=CMe2

Murray,

Tetrahedron, 26,

G,

1247 (1971).

4667 (1970). Indian J. Chem.,

Tetrahedron,

3,

2. 115 (1969). 871 (1971).