A facile synthesis of bicyclic α-methylene-γ-lactones by intramolecular cyclization of allylsilylated aldehydes

Tetrahedron Letters,Vol.28,No.6,pp Printed in Great Britain

A

FACILE

SYNTHESIS

OF

BICYCLIC

CYCLIZATION

a-METHYLENE-y-LACTONES

OF ALLYLSILYLATED

Kiyoshi Faculty

Nishitani

of Pharmaceutical

Bicyclic

molecular function

of an aldehyde

by the action

of TiC14

The a-methylene-y-lactone natural

products

activities.2)

The

chemists.3)

with

of

and

these of

method

synthesized

employing

partial

possesses

structure

remarkable

lactones

was

yields.

Now,

lactones

by

we

wish

the

to report

strategy

carbonylallylsilane

but

with

a facile

involves

moiety

with

less

Semmelhack

satisfactory

synthesis

many by

et _. al 4, and a-methylene-ywith

results

of bicyclic

intramolecular

an aldehyde

by

a-methylene-y-lactones

developed.

et al ') reported the synthesis of bi- or tricyclic --. lactones by an intramolecular reaction of an aldehyde unit moiety,

of many

biological

reported

Okuda

(bromomethyl)acrylate

intra-

yield.

polycyclic

were

of Tokyo,

162, Japan

a 8-ethoxycarbonylallylsilane

is an important

terpenes

syntheses

cyclization

University

Tokyo

in an excellent

synthesis

Recently,

intramolecular

Science

were

unit

ring

especially

INTRAMOLECULAR

ALDEHYDES"

Shinjuku-ku,

a-methylene-y-lactones

reaction

BY

and Koji Yamakawa*

Sciences,

Ichigaya-Funagawara,

Summary:

0040-4039/87 $3.00 + .OO Pergamon Journals Ltd.

655-658,1987

an

a-

in their

a-methylene-y-

reaction

of

a 8-ethoxy-

unit.

MesSi

EtOOC A synthesis

of allylsilylated

w-Tetrahydropyranyloxy trimethylsilylpropionate7) give

CH2C12

esters giving

stereomers

(3) were

mixture treated

a quantitative

of the mesylates

with

(4) was

(DBU) to afford

The configuration

of the double

triplet

(lH,J=7)

hydropyranyl toluene alcohol

in its 'H-NMR

protecting

sulfonate (6) gave

lithium

of hydroxy

spectrum

at

(PPTS)

at

the desired

chloride/triethylamine

60-C. aldehyde

The

Swern

deduced

6 6.64.')

group of 5 was performed

655

with ester

yield.

to The in

l,B-diazabicyclo(5) in good

Removal

oxidation")

8-

of the dia-

to be Z isomer

in ethanol

(7a) in good

follows. ethyl

at -78'C

(4). The mixture

in benzene

of 5 was

as

with

(3) in 74% yield.8)

an a,8-unsaturated bond

out

coupled

dicyclohexylamide esters

of mesylates refluxed

carried

was

methanesulfonyl

yield

[5,4,01undec-7-ene

(7) was

(l;n=3)

(2) using

a diastereoisomeric

hydroxy

aldehydes

valeraldehyde6)

with

yield. by the

of the tetrapyridinium

of the

p-

resulting

656

The other aldehyde

(7b) was synthesized

from w-tetrahydropyranyloxy

hexana16) (l;n=4) and ethyl (3-trimethylsilylpropionate by a similar method as described for the synthesis of 7a in good yield. THPO(CH2)n+l

CHO

1

Me3Si a,

b

t

+

(CH2),+,-OTHP

EtOOC Me3 Si (CH2)2

COOEt

2

Me3Si

c,d

t

R=H

4;

R=Ms

Me3Si

e

\

3;

\

-EtOOC&(CH2)nCH0

Etooc 5;

R=THP

7a;

n=3

6;

R=H

7b;

n=4

Scheme 1") a) dicyclohexylamine,n-BuLi/THF,-78OC (quant.).

c) DBU/benzene,

reflux

(74-82%). b) MsCl,Et3N/CH2C12,0°C

(a9-98%). d) PPTS/EtOH,60 'C (73-83%).

e) (COCl) 2,DMS0,Et3N/CH2C12,-600C,(91%). Hosomi et -* al 12) reported that an intermolecular coupling of B-alkoxycarbonylallyltrimethylsilane with aldehydes using a Lewis acid gave unsatisfactory results because of polymerization and aldol condensation of the starting material or the products. An intramolecular

reaction of the allylsilane moiety with the aldehyde

unit in 7a was performed as follows. The aldehyde (7a)(0.78 mmol) was treated with

Tic14

hydroxy

(3.9 mmol)

ester

in CH2C12

(5 ml) at -2OOC. Work-up

(8) [IR; 3400, 1710, 1625 cm-',

6.23(1H,t,J=l)l quantitatively.

'H-NMR;

as usual gave

a

5.64(1H,dd,J=1,0.5),

The hydroxy ester was heated at reflux tem-

perature with p-TsOH in benzene for 1 hr giving a bicyclic a-methylene-ybutyrolactone (9)13) [IR; 1755, 1655 cm-', 'H-NMR; 3.47(1H,m,w/2=20), 5.02(1H,br t,J=5), 5.70,6.28(1H each,d,J=3)1 in 83% yield. Intramolecular cyclization of 7b was also achieved by the action of TiC14 in CH2C12 at -5 - 0°C giving a cis hydroxyl ester

(11) in respective

evidenced s,w/2=5), were

yields of 57% and

by the following

39%. Their stereochemistry was 'H-NMR data; 10: 2.76(1H,br d,J=l2), 4.0l(lH,br

11: 2.50(1H,td,J=10,3),

treated

lactone

with

p-TsOH

ester (IO) and a trans hydroxyl

3.57(1H,td,J=70,4). These

in benzene

hydroxy

esters

at 60°C for 1 - 1.5 hr to give a cis

(12) [IR; 1760,167O cm-', 'H-NMR; 3.04(1H,m,w/2=12),

4.57(7H,q,J=6),

657

5.55,6.22(1H cm

-1

good

,

each,d,J=3)1

'H-NMR;

These

yields.

authentic

la&ones

spectral reported

(13) ,mp 35-37OC,[IR;

lactone

5.42,6.10(18

data

were

by Grieco

each,d,J=3)1

in good

1760,167O

respectively

agreement

with

those

of the

b

EtOOC

d

10

12

EtOOC

d

13

11

Scheme

2")

a) TiC14/CH2C12,-20°C c) TiC14/CH2C12,

(quant.).

-5

- 0 "C(96%).

Studies Part

2)

on the Terpenoids

XXXVI,

d) p-TsOH/benzene,60

Pharm. AI Bull -J.M. Cassady Models"

34, 1319

J.M.

1980, pp 201-267, 3)

H.M.R.

C.H.

White,

"The Total

5)

Compounds

Iida

llAnticancer Agents

and

and references J.

Heathcok,

New

M.

and

XXXVII.

A. Mikami,

Chem. --

cited

Based

Synthesis

on Natural

Academic

Press,

Product

New

York,

therein.

Rabe,

S.L.

York,

J.D. Douros,

Anqew. Chem Int --_---Z ---L Graham, M.C. Pirrung, of Natural

Products",

Ed, F.

Enql.

,24,

Plavac

and

Ed. J. ApSimon,

1983, Vol. 5, and references

cited

94 C.T.

John

therein.

98, 3384 (1976). and E.S.C. Wu, J. Am. -Chem. &, S. Nakatsukasa, K. Oshima and H. Nozaki, -Chemistry Letters,

M.F. Semmelhack Y. Okuda, 1985,

6)

& Sons,

Alicyclic

(1986).

Cassady

and

(1985);

Wiley 4)

Hoffmann

(83%).

'C (91-94%).

Notes

K. Nishitani,

and M. Suffness,

Ed.

and

and Related

K. Yamakawa,

1h

b) p-TsOH/benzene,reflux

References

1)

in

et al. 14) --

EtOOC

2

7a

and a trans

3.73(lH,td,J=11,4),

The

481.

w-tetrahydropyranyloxy

Pentamethylene mole

hexamethylene

of 2,3-dihydropyran

of PPTS [n=3;

or

bp

to give

aldehydes

in

(I) were

glycol

CH2C12

mono-tetrahydropyranyloxy

120-130°C/0.9

torr,41%

was

at room

synthesized

treated

with

temperature derivatives

(52% conversion),

n=4;

as follows. an

equivalent

in the

presence

[THPO(CH2)n+20Hl, bp 150-155°C/0.5

658

The mono-ols

torr, 38% (76% conversion)].

[n=3; bp 115-120 'C/O.2 torr,

aldehydes(1)

were oxidized 93%, n=4;

to yield the

13O'C/O.l

torr,

88%1. 7)

L.H. Sommer, &,

8)

G.M.

G.H. Barnes and L.S. Stone,Jr., _---J. Am. Chem.

Goldberg,

76, 1609 (1954).

This mixture should consist of at least two isomers evidenced by TLC or the 'H-NMR spectrum signals

at

of the mesylates

6 3.00 and 3.05.

(4) exhibiting

The stereochemistry

two singlet methyl of the condensation

reaction is not clarified yet, but is now under investigation. 9)

H.M.R. Hoffmann and R. Henning, Helv. Chim. Acta., 66, 828 (1983).

IO)

A.J. Mancuso, S-L. Huang and D. Swern, J. Org. Chem., 43, 2480 (1978).

‘1)

In each case purified

products

were characterized

by IR, 'H-NMR and MS

spectral analysis, the results of which are fully in accord with assigned structures. 12)

A. Hosomi,

H. Hashimoto

and

H.Sakurai,

Tetrahedron

Letters,

21, 951

(1980). 13)

T.F. Murray,

E.G. Samsel,

V. Varm

and J.R. Norton,

J. Am. Chem. G, -----

103, 7520 (1980). 14)

P.A. Grieco and M. Miyashita, J. Org. Chem., 39, 120 (1974). (Received in Japan 2 September 1986)