Diastereocontrol of the claisen rearrangement by substituents external to the pericyclic array: Synthetic studies on betaenone B and stemphyloxin I

Tetrahedron Letters,Vo1.28,No.27,pp Printed in Great Britain

DIASTEREOCONTROL

0040-4039187 $3.00 + .oo Pergamon Journals Ltd.

3065-3068,1987

OF THE CLAISEN REARRANGEMENT BY SUBSTITUENTS EXTERNAL TO THE PERICYCLIC ARRAY: STUDIES ON BETAENONE B AND STEMPHYLOXIN I

SYNTHETIC

Daniel Department

V. Pratt

of Chemistry.

*1

and Paul B. Hopkins

University

of Washington.

Seattle.

WA

98195

Summary:

Thermal Claisen rearrangement of substrates 5 and 6. each prepared in seven steps from the Diels-Alder adduct of methoxybenzoquinone and 1.3.butadiene. affords products 7 and 8. respectively. These disparate results demonstrate that the stereochemical outcome of Claisen rearrangements of this type may be controlled by the spatial requirements of substituents external to the pericyclic array.

Despite

years

rearrangement derivatives case, was, We

exists

however. report

found

to

the

study

and would

an example

of

synthetically

variant

is the

has indicated

formed

appendage

external

that

bond

respond to

pericyclic

to

readily

The

rearrangements

of the

of interest tricyclic

Diels-Alder

N-bromosuccinimide

in turn treatment

treated

with

of organic

steric via

biased preference influence.

the

reversed

resulting

Claisen

by altering

products

origin,

to

are

of

betaenone

B

I (2).5b6

intermediate.

reduction7’8 equiv

to external

of fungal

Y

X

common

This

The

array.

Claisen

appendage

conformationally

quantitatively

of phytotoxins

of the

be axial.4

a cyclohexanone

be essentially

of a family

variations of an allylic

in a suitably

attachment may

to the

in the synthesis

to

useful

attachment

carbon-carbon

be expected

outcome

of substituents

as intermediates

remain

such

newly

the stereochemical

requirements interest

for

be slight,

letter

in which

and stemphyloxin

(1)5a

A previous

a preference

in this

spatial

potential

there

investigation.* 3.4 One

are little-studied.

of cyclohexanone.

there

rearrangement, the

of extensive

which

equiv

extract),

the The

tricyclic

4.

adduct

of methoxybenzoquinone

(25”.

1 h) to afford

methyllithium

providing

in THF

the tricyclic

-H

-CH2CH20H

2

-OH

-CH=CHOH

decalins

functionalized

enone

in THF 1.4

involve

1

5 and 6. which

decalin and

1.3.butadiene.

the corresponding (0’)

followed

enone 4 (m.p.

3065

3. prepared

tricyclic by

188189’)

were by 8

prepared

sodium

was treated

bromoether.

acidic in 62%

from

work-up overall

the

borohydride with which

1.8 was

(PTSA*H20 yield

from

3.

3066

c

4

3

,.Br _.H

6

The

enone

equiv

4 was

converted

(C6H5)2CuLi.

Dean-Stark

3) neat

sequence:

2) excess

C6H5.

reflux.

analysis)

face

X-ray

crystallized

appendage The

latter

the synthesis

result

despite

system.

We believe

severe

steric clearly

phenyl

ring

blocks

result

of avoiding

X-ray

structure

newly

establish

The

several

Thermolysis single

the structure

with The

contact 7.

product

excess

sequence:

PTSA*H20.

6 was

prepared

5 equiv

3)

to

1)

C6H6.

from

1.3

reflux.

enone 4 by the

(C6H5)3P.

THF.

trans-2-buten-l-01,

with

convex

for

(lH

-78”+

-

PTSA*H20.

of 8 to be as shown.

the

mechanism

this

the

interest

(v/v)

of the

for

axial

(lH

NMR

in 86% yield. A single 10 the product of concave

Claisen

rearrangement

concave

face

formation,

Specifically.

but

This

of the

orientation

is found

of 5)

I (2)

8. in 70%

yield.

the product

of convex

face carbon-carbon

Single

the CPK

of the ring

observed

(the in the

of thermolysis

precursor:

of 6

Epimerization

position

would

potentially

160’1

cleanly

afforded

n-C10H22:N.N-dimethylaniline.

analysis),

of

phenyl

is also

in the outcome

to an equatorial

tricyclic

rather

inspection

ortho-hydrogens

and

appendage

of the

of 5. one of the

as a stemphyloxin pseudoaxial

product

the rule of axial

bond

at the ring fusion

explanation

7.

follows

molecule.

formation.

atoms

to 25”

on the crowded

preference of

a single

state.

conformation

bond

from its 5b in 2.

6 [99:1

NMR 10

on cooling

of 5 to 7 formally

face

state

the hydrogen

appendage

substrate

both

afforded

it to be ketone

bond formation

carbon-carbon

Support

mixture

transition

not an inherent

ground

210”]

established

pericyclic

7 is of synthetic

of Claisen

reaction

regard

on the

in the

face

pentenyl

Substrate

steps)‘:

rearrangement

key stereorelationships

rearrangement

the

carbon-carbon

present

ketone

two

unequivocally

reflects

that

convex steric

attached

I.

this

of ketone

(see below).

from

product

requiring

suggests

(71%.

via a chair-type

that

congestion

models

the

directly

is interesting

this

25’

three-step

trans.2-penten-l-01.

steps).

n-C10H22:N.N-dimethylaniline.

of stemphyloxin

delivery.4

2) excess

two

5 by the

(50%).

of this

attachment

substrate

n-C5HllC~CCuCH=CHSn(n-C4H9)3Li.

of 5 [96:4(v/v)

analysis

(58%.

CH3CN. trap

rearrangement (60%):

105”

1) 2 equiv

Dean-Stark

which

crystal

-40”

DBU.

Pb(OAc)4.

Thermolysis

Claisen

THF/Et20.

trap;

analogous 40’:

to

crystal

X-ray

analysis

bond formation.

of

revealed

a

306 7

5

= -

8 The conversion diminished convex The

spatial

face carbon-carbon

energetic

significantly

Claisen

Ketone

this

equiv

samarium(ll)iod

end.

of the

of diastereoisomers.

less hindered it

periphery.

interest

tn THF

by treatment

convex

face).

possesses

all of the

as well

as sufficient

concave-face 6+8

an allylic

unit

(-78’)

resulting

enone isomer

Intermediate stereochemistry functionality

with

at the sterically formation

relative

effects

to

group

congested

(210’). the

face.

reflected

This

example

stereochemical

the

of 5)

concave

is qualitatively

5+7

in determining

B (1). and

betaenone

neat

allylic

DBU

(90”).13

alcohol

lithium

of which

permit 11.12

in

the

is a clear outcome

9.

is believed

Oxidation

and functionality elaboration

to

has been carried

followed

dimethylcuprate

10 is a promising

to allow

to

Apparently,

to the phenyl

of

to a cyclohexanone.

excess

afforded

and synthetically.

of 6 (relative

bond

(160”)

as a precursor

of 8 with

the major

mechanistically

reaction

role of steric

append

Treatment

both

substituent

avoiding

at which

dominant

which

8 is of synthetic

toward

mixture

avoiding

of the potentially

steps

followed

of

temperature

rearrangements

of interest

of the acetylene

bond formation,

advantage diminished

illustration

since

of 6 to 8 is again requirements

of 9 (PCC. (Et20.

-78’)

be 10 (delivery

intermediate required

for for

50% afforded

of methyl

betaenone construction

of the southern

several

by reduction

periphery.

with

1.5

from

8).

a 4:l

from

the

B (1) synthesis. of 15

the

northern

3068

References

1. Searle Scholar,

and Endnotes

1984-1987 Raulins. N.R. Org. React. 1975. 22, 1: (b) B ennett. G.B. Synthesis 1977. Chem. Res. 1977. 10. 227: (d) Bartlett. P.A. Tetrahedron 1980. 36. 1.

589: (c)

2.

(a) Rhoads. S.J.: Ziegler. F.E. Act.

3.

(a) Parker, K.A.: Farmar, J.G. Tetrahedron Lett. 1985, 26, 3655: (b) F raser-Reid. B.: Tulshian. D.B.: Tsang. R.: Lowe, D.: Box, V.G.S. Tetrahedron Lett. 1984. 25. 4579: (c) Tulshian. D.B.; Tsang. R.; Fraser-Reid, B. J. Org. Chem. 1984. 49. 2347; (d) Ireland. R.E.: Varney. M.D. J. Org. Chem. 1983.

48. 1829. Ponaras.

5.

(a)Ichihara. A.; Oikawa. Ii.: Hayashi. K.: Sakamura. S.: Furusaki. A.: Matsumoto. T. 1. Am. Chem. Sot. 1983. 105. 2907; (b) Barash. I.; Manulis. S.; Kashman. Y.: Springer, J.P.: Chen. M.H.M.: Clardy. J.; Strobel. G.A. Science 1983. 220. 1065.

6.

For the synthesis of a less substituted member of this family, Tokugawa. N.: Sakamura. S. Tetrahedron Lett. 1986. 27. 1347.

7.

Satisfactory

8.

Birnbaum. G.I. J. Org. Chem. 1960. the full account of this work.

9.

Corey,

10.

Tables atomic

11.

We cannot at this time rule out the unlikely possibility that face (axial) appendage attachment via a boat-type transition to the ketone.

12.

While it is also true that the concave face of 6 is more congested than the concave face of 5. this synthetic precursor of effect alone cannot be responsible for thf observed results, since the immediate 5 also appears (2D NOESY and COSY H NMR) to undergo Claisen rearrangement with concave face carbon-carbon bond formation.

13.

The possibility of side chain epimerization during the DBU-promoted by the observation that treatment of 8 with i) NaBH4: ii) DBU; product.

14.

(a) Molander. G.A.: J. Am. Chem. Sot.

15.

A.A.

E.J.:

Tetrahedron

‘H

NMR.

Lett.

1983. 24. 3.

4.

IR. and MS were obtained

Wollenberg.

R.H.

J. Am.

25. 1660.

for

Ichihara.

all of the compounds

Improvements

Chem. Sot.

see:

1974.

in this

A.:

described

preparation

Kawagishi.

H.:

herein will

be reported

in

96. 5581.

of final atomic coordinates, bond lengths and angles along with a computer generated plot with labels are available as supplementary data. See Announcement to Authors Tetrahedron Lett. 1983. 24. 5154. Discussion of the conformational details of 7 and 8 is deferred to a later publication, but we note that both structures possess a twist boat cyclohexanone.

Hahn.

1980.

G. J. Org. 102. 2693.

Chem. 1986,

the product 8 results from initial state followed by epimerization

HBr elimination iii) PCC also

51. 1135: (b) Girard.

P.:

Namy.

concave adjacent

is argued against affords the same

J.L.:

Kagan.

H.B.

This work was supported by the Dreyfus Foundation. Research Corporation, and the Petroleum We thank Professor Gary Drobny for Research Fund Administered by the American Chemical Society. assistance in 2D NMR measurements, Mr. Jeff Bryan and Dr. Bernard Santarsiero for determining the X-ray structure of 8. and Mr. Regan Shea for assistance in the preparation of the figures.

(Received in USA 18 February 1987)