Photooxidation of 1-acetoxy-3,5-cycloheptadiene

Tetrahedron Letters No. 43, pp 4129 - 4132. @Yergamon Press Ltd. 1979. Printed in Great Britain.

PHOTOOXIDATION

0040-4039/79/1(X2-4129#02.00/0

OF 1-ACETOXY-3,5_CYCLOHEPTADIENE

David M. Floyd* and Christopher M. Cimarusti The Squibb Institute for Medical Research P.O. Box 4000, Princeton, New Jersey 08540

Summary: A method for the preparation

of cis oxygenated cycloheptyl systems has been Photooxidation of 3 gives mainr$, resulting from attack syn to the acetoxy developed. The acetate funccon of both 4 and 5, the minor anti-product, appears to affect substituent the rate of"endoperoxide to diepoxide rearrZngement. We have been concerned genated

polyacetate

propionate

systems,

systems

epoxyphosphate

1 to the diepoxide

acetyl

derivative

diepoxide

"phosphate

of photo-generated

method

alternative

z5 and the facile

rearrangement

and thermal

poly-

from acyclic

for -cis 1,3-induction

Our inability

singlet

of -cis oxy-

the analogous

could be expected

to readily

convert

to 3,5_cycloheptadiene-

the photooxidation

of the minor endoperoxide

of the

product 5 to

conditions. 0

A0

nv>

o&o

1

2

65% The reaction forded three major

tained 65% of endoperoxide 5 combined. prophyrin

5 + 5 = 35%

of 3, under standard products.

Analysis

conditions6,

4 (40% isolated

(Hem*HCl)

Trace in 4.5 to 5 hours and af-

by l3 C and 'H nmr demonstrated

The ratio of 5 to 6 varied,

hydrochloride

was complete

by crystallization

perhaps

4129

that the mixture con1 from ether)' and 35% of 2 and

due to variations

used in individual

experiments'.

in the

approaches.

oxygen

At this time, we wish to describe

5 under both photolytic

preparation

Unlike

stereoselective

extension".'

z3 led us to consider

the addition

l-01 (11) and its derivatives.4 -

for the facile

elaboration.

of stereochemistry

the only highly

is Bartlett's

We have examined

methods

for further

very little control

To our knowledge

precursors.' unbranched

with developing

units suitable

in the amount of hemato-

4130

No. 43

Structural endoperoxide

cycloheptatriol comparison toluene,

assignments

were

initially

isomers 3 and 5_, confirmed 8 obtained

by hydrogenation

of its l3C spectrum

3.25 hours;

chromatography

on silica of the mother

in the Table. in related

We were the reaction

and that 5was Hem*HCl.

surprised

by stirring

Similar

rearranged

photolysis

results

Under

identical

for 6 hours showed

facilitating of 4 to 1. pendant mation

on 5_

literature

of the cycloheptene

Rl

endoperoxide

l2 (2) to

diepoxides

1, 5 and E

toluene

to be 11%, ~100%

group of 5 is definitely

of 2 is retarding

the rearrangement

to differentiate between the interaction of the 8,13 and the effects on the confor-

intermediate

Toluene,

substituent

imparts.

Reflux

rR1 i

dr 0

1.11%

5 %lOO%

H

3 in toluene

of 4, 5 and 2 in refluxing

5 Rl = OAc; R2 = H R2=

twill

d in less than 5 hours.

3 Rl = H; R2 = OAc

zRl=

of the

of 1. and some minor pro-

R

R2

effected

are employed,

to diepoxide

the anti-acetate

o-o

e

in the absence

of 2-cycloheptene-1,4-endoperoxide

that while

ring that the acetoxy

4

Heating

conversion

of reaction

of 2 to 6, the syn-acetate

I

of 3 and

temperature

13C nmr analysis of crude 5 obtained

rearranged

to the corresponding

with some diradical

of 4 and 6_,

at ambient

to the light source

conditions.

complete

the extent

At this time, it is not possible

by r-e-subjecting a

that the mixture

of Hem*HCl

under

for weeks

3-4% of z.

rearrangement

Thus, it appears

demonstrated

under an argon atmosphere

In fact,

5 completely

Comparing

arising

to be stable

10 hours a clean mixture

large amounts 1.

under thermal

the thermal

conversions

function

of Hem'HCl

it to contain

conditions,

the rearrangement

acetoxy

with

added Hem*HCl)

to 5 when subjected

96 hours to effect

-10 was examined.

and 71% respectively.

studies

of 2 and column

of a diepoxide

appeared

study showed

(with and without

diepoxide

were obtained

As a point of reference, diepoxide

by

13C and 'H nmr data

consistent

amounts

After

Further

If relatively

showed

at reflux took approximately ducts.

conditions6.

in the presence

of 5 to 5. 8

reactions

significant

was isolated.

to the corresponding

from preparative

obtained

of j_ (160°C,

and chemical

All relevant

of the rearrangementwas

in methanol

only slowly

also rearrange

dwas

after crystallization

since both endoperoxides

The selectivity

rapid isomerization

Structural

shifts of H, andC4are

to observe

especially

of 5 remaining,

However,

of structure

2 formed by thermolysis

liquor to remove 5.

of 4 and 5 to the reaction

5 was unchanged

of 1-O-acetyl-1,3,6-

systems.'

initially

at room temperature. 1:l mixture

Confirmation

of 3 and 5, obtained

The chemical

conditions",

with only traces

of 4.

50% as an oil from plc on silica).

on a ~a. 1:l mixture

assignments

crystal X-ray analysis"

to that of the diepoxide

were performed

are listed

made by 13C and 'H nmrg and, in the case of the

by single

-10 71%

(By 'H nmr analysis)

4131

No. 43

In terms of our synthetic goal, we have observed a highly stereoselective oxygen

addition

89:ll mixture on silica.

to the parent

of the desired

exo-isomer

Only trace amounts

Formation

mixture.

and recrystallization

from ether afforded

102\

products

of chemical

effects

by 13C and 'H nmr analysis

derivatives

4

(AcCl, pyr., CH2C12,

O'C)

from 11.

s

6f

overall

13

12

The results

of an

13 after column chromatography

pure 4 in 60% overall yield

(i%)

(89%)

the substituent

singlet

gave an 80% yield

were observed

of the acetoxy

koH

-11

conditions

11 to the endo-isomer

of bis-epoxide

of the crude reaction

6

Thus standard

alcohol fi.

transformation

on the endoperoxide

of 4 and its analogs to diepoxide

as well as further work on

rearrangement

will be reported

in due

course. NMR Data in CDC13

(Ppm)

OAc 1 OH

Assignment C-l ;I; c-4 H-l

4 67.9 36.9 72.9 128.5 ca. 4.956 (quintet)

5

5

68.8 38.4 74.4 130.4 5.436 (quintet)

67.8 32.4 51.3 52.9

7 67.7 31.3 51.5 52.7

8 69.5 44.8 68.8 31.8

References 1)

(a) P.A. Bartlett, and J. Myerson, J. Am. Chem. Sot., 100, 3950 (1978) and references. (b) E.J. Corey, and T. Case, Tetrahedron Letters, 335 (1979).

2)

P.A. Bartlett,

3)

lwas homogeneous by l3 C nmr; upon reaction with tained in very low yield.

4)

Singlet oxygen additions to these systems are unreported. (a) K. Gollnick, and G.O. Schenek in 1,4-Cycloaddition Reactions, Ch. 10, pp 255 (1968) Academic Press New York. (b) Y. Ito, M. Oda, and Y. Kitahara, Tetrahedron Letters, 239 (1975). Diels-Alder additions are known; (c) O.L. Chapman, D.J. Pasto, and A.A. Griswold, J. Am. Chem. SOC., 84, 1213 (1962); (d) M.J. Bishop, and I. Fleming, J. Chem. Sot. (C); 2524 (1970); (e) A.F. Cameron, and G. Ferguson, J. Chem. Sot. (B), 943 (1970).

and K.K. Jernstedt,

J. Am. Chem. Sot., j9_, 4829

(1977).

12 in CH3CN a complex mixture

was ob-

No. 43

41%

5)

(a) Y. Kashman, and 0. Awerbouch, Tetrahedron, 2&, 4213 (1970). (b) D.I. Sehuster, J.M. Palmer, and S.C. Dickerman,.J. Org. Chem., 3l_4281 (1966). (c) P. Radlick, J. Org. Chem., 29, 960 (1964).

6)

Preparative reactions were conducted by irradiation in methanol (lg/50 ml) with a 650W tungsten-halogen lamp (water cooled immersion well) under a stream of oxygen using HemaHCl as the sensitizer.

7)

All crystalline compounds gave satisfactory C and H analyses. The uncorrected melting points of &hese compounds are as follows6 _, 4 93.5-950C (ether); 6, 81-82OC (ether-hexane); 8, 126-127 C (ethyl acetate); 2, 110-115 C (ether); and l& 44-45.5'C (ether).

8)

Photochemical rearrangementsof endoperoxides to diepoxides are accelerated by triplet sensitizers, K.K. Macheshwari, P. DeMayo, and D. Wiegand, Can. J. Chem., 48, 3265 (1970).

9)

See Ref. 1 d,e. For related systems see Y. Hawakawa, Y. Baba, S. Makino, and R. Noyori, J. Am. Chem. Sot., 100, 1786 (1978); A.P. Cowling and J. Mann, J. Chem. Sot., Perkin I, 1564 (1978).

10)

We thank Dr. J. Z. Gougoutas and Ms. B. Toeplitz for performing this analysis.

11)

Usually much more vigorous conditions are associated with this rearrangement. See Refs. 4a and 8.

12)

A.C. Cope, T.A. Liss, and G.W. Wood, J. Am. Chem. Sot., 79_, 6287 (1957).

13)

W. Herz, R.C. Ligon, J.A. Turner, and J.F. references.

(Received

in USA 20 June 1979)

Blount, J. Org. Chem., 42 1885 (1977) and