Intramolecular photochemical [2+2] cycloadditions. Regiochemistry of the photocyclizations of some oxygen-substituted 6-allylcyclohexenones.

Tetrahedron Letters,Vol.23,No.l,pp 23-26,1982 Printed in Great Britain

INTRAMOLECULAR

PHOTOCHEMICAL

PHOTOCYCLIZATIONS

[2+2] CYCLOAODITIONS.

OF SOME OXYGEN-SUBSTITUTED

Stephen F. Martin*'

Department

0040-4039/82/010023-04$03.00/O 01982 Pergamon Press Ltd.

of Chemistry,

and

REGIOCHEMISTRY

OF THE

6-ALLYLCYCLOHEXENONES.

James B. White

The University

of Texas, Austin,

Texas

78712

Abstract: The regioselectivity of the intramolecular [2+2] photocycloadditions of certain 6-allylcyclohexenones appears to be largely independent of the substituent (H,ORl on the distal terminus of the isolated double bond.

During

the course of an investigation of unconjugated

cy~loadditions~ cyclizations placing

of several

various

preferred

dienones,

functionalized

substituents

of the intramolecular we examined

6-allylcyclohexenones

on the isolated

photochemical

the regioselectivity to determine

carbon-carbon

double bond.

[2+2]

of the photothe effect.of Based upon the

orientation

observed in the bimolecular photoadditions of cyclic enones to enol 3 ethers and enol esters, we expected that the regiochemistry of the photocyclization

of 6-allylcyclohexenones remote terminus

the intramolecular sense opposite

might be inverted when an oxygen

of the isolated

carbon-carbon

photocycloadditions

to that generally

now wish to report the preliminary

The requisite prepared lithium

enolates

and then methyl

and erythro-aldols

,

Hanovia

reactions

with either

proceeded

the threo-isomers

lamp with a uranium

in this investigation

by the sequential

acrolein

or

aldol -5b was photolyzed,

and we

4a-c

photoproducts

an approximately

with a moderate

(0.1-0.2X

reaction

protected

(Table ll.5

threo-

As antici-

to high degree of stereo-

the major or exclusive

products.*

in cyclohexane

good yields (Table 11.12

2:1 mixture

23

were readily

--l-3 with

B-pivaloyloxyacrolein4

of the corresponding

4a-f as either

filter) afforded

6a-c as the only identifiable

processes,

of the cyclohexenones

THF, -78'Cl followed

gave variable mixtures

of the threo-aldols

at the

that

in a regiochemical

intermolecular

4a-f and 5b, d-f in very good overall yields

producing

Irradiation

Thus, treatment

(1.2 equiv.,

these crossed-aldol -

selectivity

for the photocyclizations

thus generated

chlorofotmate

enol esters proceed

in the related

was introduced

However we discovered

results of some of these studies.

aldol reactions.

diisopropylamide

of the kinetic

pate7

substrates

by directed

of certain

observed

substituent

double bond.

using a 450W medium pressure 11 of the expected cycloadducts Interestingly,

of photoadducts

when the erythro-

was obtained

(42%).

24

SCHEME

1

0

5b,d-f

,:R1=R2=H 2:R1=Me;R2=H 3:R1=H; R2=Me

hv 0 Me02CO H R2 R’ !

Z

Series

a-c: Z=H d-f:

The major product characterized

appears

although

Unfortunately, and 5d-f

;rb,d-f

60-f

Bb,e

Z=02c-1-6~

to be 7&, but the minor component

it is probably

all efforts

have been singularly

the regioisomeric

to separate

unsuccessful,

has not yet been fully

cycloadduct

-8b.

the threo- and erythro-aldols and it was therefore

4d-f

necessary

to

Surprisingly, the principal photoproducts formed photolyze the -~ threo/erythro- mixtures. upon irradiation of the aldols -__ 4d-f/5d-f were the cycloadducts 6d-f which were obtained as mixtures

of -exo-and endo-diastereoisomers epimeric at C(8).'* The introduction of group on the terminus of the isolated olefinic moiety did not affect the

a pivaloyloxy orientation

of the intramolecular

Since any other photoproducts exiguous

quantities

components

[2+2]

photocycloaddition

from the irradiation

(<5X), none have been isolated.

(ca. 10%) have been isolated

as originally

anticipated.

of -4d/5d and -4f/5f are formed in only On the other hand, three minor

from the photolysis

of -4e/5e, two of which appear Although the other has not been fully characterized, it is probably to be exo- and -endo-7e. the rezisomeric photocycloadduct -8e.

25

Table

Preparation

1.

R'

Entry

and Photocyclizations

R2

2

of Oxygenated

Yield (%la

H

H

H

Yield (%)

threo/erythro -___

4+5 --

a

6-Allyl-Z-Cyclohexenones

6 -

ratio (4:5) --

74

>95:5

74

b

Me

H

H

71

4.7:l

77

C

H

Me

H

72

>95:5

80

d

H

H

02C-t-Bu

e

Me

H

f

H

Me

81

6:lb

60'

02C-J-Bu

69

3:lb

73c

02C-J-Bu

76

5:lb

61'

aCombined yield of threo- and erythro- diastereoisomers. b Obtained as an inseparable mixture, and the ratio was determined 'Based upon relative

amount of _ 4 in the mixture

There are several aspects (1) Owing isolated

photocycloadditions

processes; chiral

of these photocyclizations

double bond of an unconjugated

molecular

(2) The outcome

of photocyclizations

carbon atoms in the chain linking

double bond in the starting exo- and -endo-6d-f. unlikely,

biradical

Further the factors additions,

materials

may be affected

cis-/trans --

are doubtless

studies of related photocyclizations involved

in determining

We wish to thank the National

and the Robert A. Welch Foundation

Cancer

nature

retained

in the photoproducts

of the enol ester seems

in these reactions.

to define more completely

course of intramolecular

and the results of these studies will be reported

Acknowledgment.

(3) The stepwise

of

about the carbon-carbon

are in progress

the regiochemical

of intra-

by the configuration

isomerization

involved

on the

in the related bimolecular

moieties;

as the geometry

4d-f is not completely

Since photoinduced intermediates

that merit attention: an oxygen substituent

as is observed

the two olefinic

is evident

2:1 1:2.7b

C NMR

dienone may not direct the orientation

in the same manner

of some of these photocyclizations

13

by

2.7:l

of aldols -4/5

steric and/or other factors,

to conformational,

exo/endo -Z

in due course.

Institute,

for support of this work.

photocyclo-

DHEW (Grant CA 21860)

26

References

1.

Recipient Career

2.

of a National

Development

Institute

Chemie,"

-Cf. (a) Corey, 86, 5570.

see (a) Meier,

Cancer

Institute)

H. in "Houben-Weyl,

3. Pure Appl. Chem. E,

E.J.; Bass, J.D.; LeMahieu,

lb) Yamada,

423. (c) Cantrell,

(National

Research

Methoden

Vol 4/5b, Miiller, E., Ed., Georg Thieme Verlag,

1975, p. 898 ff. (b) Kossanyi, 3.

of Health

Award, 1980-1985.

For a review of photocycloadditions der Organischen

and Notes

R.; Mitra,

Y.; Uda, H.; Nakanishi,

T.S.; Haller,

Stuttgart,

5l_, 181. R.B. J. Am. Chem. Sot. 1964,

K. J. Chem. Sot. Chem. Commun.

U.S.; Williams,

1966,

J.C. J. Org. Chem. 1969, 34, 509.

(d) Singh, P. --Ibid. 1971, 36, 3334. (e) Liu, H.J.; Ogino, T. Tetrahzn Lett. 1973 -' 4937. (f) Mori, K.; Susaki, M. Tetrahedron 1980, 36, 2197. (g) Shih, C; Fritzen, E.L.; Swenton, J.S. J. Org. Chem. 1980, 5, 4.

Prepared

according

to procedure

4462.-

-

of Protopopova

T.V.; Skoldinov,

A.P. J. Gen. Chem.

USSR. 1958, 28, 241. 5.

The spectral

data ('H NMR, l3C NMR, IR,

are in accord with the proposed analytical

low resolution

structures,

data (high resolution

mass) for all compounds

and all new compounds

mass spectra and/or combustion

gave satisfactory analysis).

The

structure

6.

of -exo-6e has been confirmed by X-ray crystallography.b We wish to thank Professor S.H. Simonsen and Dr. M. Kimura for this determination.

7.

-Cf. Torii,

8.

Since the aldols are isolated

S.; Inokuchi,

stereochemistry 13C NMR"

i whereas relative 9.

downfield

the methine

employed.

carbons

carbons

from the carbinol

of the threo-aldols

and

of the threo- aldols

carbons

are slightly

of the erythro-aldols upfield

(.l-.3ppm)

L. 3. Am. Chem. Sot. 1964, 86, 3337. C.H.; Pirrung, M.C.; Sohn, J.E. J. Org. Chem. 1979, 44, 4294,

Stiles, M.; Winkler, Heathcock,

11.

Cf. (a) Frostl, Margaretha,

R.R.; Chang, Y.; Traynor,

W.; Margaretha,

in 7b,e

as a doublet

in the cycloadducts

(J=7 Hz), and as a broadened

exo-6d-f appears as a broadened -endo-6e as a doublet (J=7 Hz). --

(Received

P. Helv. Chim. Acta 1976, 59, 2244.

(b) Altmeyer,

I;

P. Ibid. 1977, 60, 874.

The proton at C(9) appears doublet

by 'H NMR is problematic,'

The carbinol

(2-2.5ppm)

of the

to those of the erythro-aldols.

10.

12.

H. Bull Chem. Sot. Jap. 1979, 52, 1233.

as their carbonate.s, the analysis

of the aldol reactions

was therefore

4 are observed

T.; Ogawa,

in USA 13 July

singlet,

1981)

singlet

in -& endo-6d

6a-f (J=5 Hz), as a broadened

in 8b,e.

The proton at C(8) in

f as a triplet

(J=7 Hz), and in