Syntheses of macrocyclic terpenoids by intramolecular cyclization III. model reactions for the synthesis of cembrene and thunbergol derivatives

TetrahedronLettersNo. 32, pp 2763 - 2764, 1977, PergsmonPress. Printedin Great Britain.

SYNTHESES MODEL

OF

MACROCYCLIC

REACTIONS

TERPENOIDS

FOR THE SYNTHESIS Mitsuaki

OF CEMBRENE

Kodama,

Department

Kazuaki

(Receivedin Japan 18 May 1977;

epoxy sulfide ,l_ leading

to the fourteen-membered

describe

the facile

combined

with the intramolecular

cyclization

route for the synthesis of cembrene Nephthenylphenyl Although

Na104. are rather

at room temperature. ms: m/e 3425,

1662,

C7-Me), 5.2 H2).

288 (M+),

1.77

(lH,

The physical 59 (base peak),

965 cm-‘, (3H,

m, H6),

5.13

(lH,

3.04

dd, J=15.4,

These reactions although

not isolated,

is highly

selective

indicated

H,),

C3-Me

In this paper,

8.

These reactions,

a convenient

with

by thin-layer in 70%

yield

ddd, J=l4, (lH,

246 (c 12900),

s),

1.50

and useful

(4).

1 molar equivalent

chromatography,

and establish

of

both of them

during the isolation

to those of cembrene 2

(3H,

5.52

methanol

process

its structure:

256 nm (sh, E 7800),

ir (neat):

(3H,

br.s,

C, ‘-Me),

1.59

(3H, br.s,

11, 6, H5),

4.82

(lH,

J=6,

Hlo),

dd, J=9.0,

and H4 (10%)

6.2,

and C3-Me

H4),

br.d, 6.11

we

(lH,

and H2 (14%)

4.95-

d, J=l5.4,

indicating

an S-

part. that the initial

and sulfenic

providing

colorless oil,

240 (E 12700),

(lH,

constitute

of the

our study starting

(3) and 4,8,13_duvatriene-1,3-dial

at O°C in dilute

1.09

cyclizatian

cembrenes.

carbanion,

s),

9.7,

occurring

of the sulfenyl

uv (MeOH):

C3-Me),

of the diene

in the naturally

data of 4_ are similar

(3H,

intramolecular

systems via the sulfoxide -

to the diene A,

Two NOES were observed between

-cis conformation

anion-induced

ring compound ,2_. We have extended

and thunbergol

nmr (CC14): 1.08

t, Jc1.2,

in UK for publication20 June 1977)

of two products were detected

and changed

DERIVATIVES

and Sh6 ItS*

and I-ene-3-al

sulfide 2 (1) was oxidized

the formation

unstable,

(2),

THUNBERGOL

Ill.

Japan

an efficient

incorporated

formation of the 1,3-diene

AND

CYCLIZATION

Tohoku University

980,

received

we have reported

from 2 to induce the other functionalities

Shimada

of Chemistry, Sendai

ln the previous paper (l),

BY INTRAMOLECULAR

product was the mixture

acid was eliminated

during the isolation.

a new and useful sequence for the specific

a?63

of diastereomeric

sulfoxides

The direction

&

of deprotanatian

synthesis of cembrene 2.

2764

Ma. 32

3 0

PM

;

2_

R=SPh

3

R=SOPh

6

5 Since directly

(KBr):

The

isolation

treated

obtained

s),

the

with

92%

3325,

972

cm-l,

(lH,

m),

relative

at Cl

cyclization, retention

yield.

A: nmr

the

Synthesis

1.04

natural

(3H,

s),

5.11

have

Kodama,

2)

Kobayashi

H.

Y.

Dauben,

D.H.

Templeton

S.

W.E.

diterpenes

and

using

S.

Akiyoshi,

It6,

and

J.P.

Springer,

5)

Although

the

configuration Details 6)

Zaekin,

D.A.

Clardy

and

configuration

reaction

be reported

Evans,

G. C.

Evans

and

Chem.

R.H.

s),

Hl),

94

1.48

(3H, (lH,

diol

s),

to

&

was

d,

1.53

since of

proceed

in

ir

(3H,

Jz15.1,

stereochemistry

is known

was

(base peak),

to be z,

the

of sulfoxide

oxidation

the

(M+),

5.71

is assumed

considering

H2). the

the the

Andrews G. C.

our

943

Cox,

can not

and C. L. Andrews,

Org.

825,

261

current

investigation.

(1975).

35, 1044 (1962); aem . , 30, 1693 (1969).

Khim.

ibid., m5).

g,

823 (1963). M. G. B. Drew,

-

Prir.

Soedin.,

2,

52 (1968).

B.

Kimlcmd

(1968).

Tetrahedron

non-bonded

forthcoming

3065

Japan,

be deduced

the

is under

Footnotes

J.

Pentegova,

22,

sequences

Letters,

Sot.

Cryst.,

V.A.

considering in

and

Resnick,

Acta

of 2

is suggested

will

see D.A.

J.

306

(3H,

9.1,

at Cl4

configuration

Tetrahedron

P.R.

A. I. Lisina and 3) N. K. Kashtonova, and T. Norin, Acta Chem. Scrod., 4)

1.28

J=15.1,

rearrangement

these

Bull.

Thiessen

and A.

dd,

s),

above

(6).

Matsuki

and

W.G.

(3H,

the

separation,

ms: rnb

12’C,

substituent

trans

l2,3lsigmatropic

1.15

of

mixture

chromatographic

111-l

(lH,

and the

reaction

After

m. p.

References 1) M.

the

1 day).

m),

(lH,

in 2_ should

configumtion

unsuccessful,

prisms,

of C3-hydroxyl

and Cl4

of

was (O’C,

(CC14):

,l_ to ,2_ (5) and the of

3

colorless

5.05-5.25

configuration

substituents

sulfoxide

trimethylphosphite

in

4.85-5.0

of

Letters, from

2737

the

(1975).

coupling

interaction

in

the

constant, transition

Jl,

14’6.5

state

of

Hz,

trans

cycliza=

paper.

Sims, Accounts

J.

Am. Chem.

Chem. Res.,

Sot., z,

147

3,

4956

(1974).

(1971).

For

the

review,