Regiocontrol in the intramolecular silyl modified sakurai (ISMS) reaction. An efficient synthesis of a Dacus oleae fruit fly pheromone.

0040-4039/92

Tctmhcdron Letters, Vol. 33, No. 13, pp. 1799-1802. 1992 Ptiitcd in Great Britain

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Regiocontrol in the Intramolecular Silyl Modified Sakurai USMS) Reaction. An Efficient Synthesis of a Dacus oleae Fruit Fly Pheromone. Istvan Department

: The ISMS reaction,

Abstract

be controlled

to produce

efficient synthesis

avermectin

family

and

numerous

molecules

requires

we report

some of our results

Silyl-Modified

the efficient

(ISMS) reaction, The power

in a variety

1 Any

approach

towards

and spiroketals.

of a new methodology

of the ISMS annelation

active

is further

and these

In this letter,

: the Intramolecular

which allows the rapid and high yielding

of a Dacus oieae Fruit Fly pheromone

synthesis

of biologically

agents of the milbemycin

synthetic

of tetrahydropyrans

on the development

Sakurai

short and convergent

present

the antiparasitic

pheromones.

these important-subunits.

olefins, can now

was used in a highly

8.

antibiotics,

preparation

of regioisomeric

The ISMS methodology

are key-subunits

such as the polyether

Mekhalfia

Sheffield 53 7HF, England

afforded a mixture

which initially

only the exocyclic alkene.

and spiroketals

products

and Abdelaziz

The University,

of a Dacus oleae pheromone

Tetrahydropyrans natural

E Mark?

of Chemistry,

construction

demonstrated

of

by the

8.2

X OSi Me,

1

2

Figure 1

During

some recent

aldehydes

and ketones

annellating

reagents

efficiently.5

Unfortunately,

formed

2a and 2b,

with little control

these isomers generated

might

on neutral,

tetrahydropyrans

in our original

under

This study resulted

radical-mediated

into homoallylic procedure,

of the C-C double

be triggered

by its hydrolysis

basic additives.

studies

could be converted

by traces the reaction

oxidations,3

and

spiroethers

a mixture

bond position.

in only marginal 1799

could

that

alkenes

4 were

that the formation

in trimethylsilyl

and investigated

success6

also be prepared

of regioisomeric

We reasoned

of triflic acid present conditions

we discovered

ethers in a single step.4 By using the

triflate

of or

the effect of various

1800

Table 1.

Modified ISMS Anneilations of Carbonyl Derivatives with 2b

Entry

Substrate

Product

Vield(a)

, (4

85%

CHO

2cb’

78%

0

3(C)

0” X

84%

OMe

88%

OMe

5(@

83%

(a) All yields refer to pure, chromatographically homogeneous, material; (b) EtOSiMe, (200 mol %) was added to the reaction mixture; (c) C,H,,OTMS (10 - 15 mol %) was added to the reaction mixture; (d) No trimethylsilyl ether other than 2b was added.

Remarkably,

of a simple trimethylsilyl

the addition

to the reaction dramatically

mixture modified

exocyclic isomer.

- containing

the carbonyl

the product

ratio,

Some example

of this modified

As can be seen from Entries exo-methylene

oxocene

case of aldehydes isomerisation. necessary?,

8

ISMS condensation

The reaction

and ketones

conditions

1 and 2), 200 mol % of C2H50SiMe3 with cyclohexanone

or C2HsOSiMe3

and the annellating

to the almost

1-3, both aldehydes

in high yield.

(entries

However,

leading

ether, such as QH130SiMe3 compound

exclusive

reagent

formation

2b -

of the

are shown in Table 1. afford smoothly

are substrate are required

the desired

dependent.

In the

to stop the exo-endo

(entry 3), only IO-15 mol % of C&13OSiMe3

is

1801

Interestingly, cases,

these

no external

ortholactone (Entry

ketals

10 derived

5), the basic

exomethylene

9 (entry 4) prove to be excellent trimethylsilyl

skeleton

spiroketal

ether

from 6-valerolactone of numerous

subunit

9

substrates

is required. produces

Furthermore,

the important 1 The efficient

pheromones.

5 into a Dacus oleae pheromone

annellation

i

system

transformation

of this

8 is summarised

in Figure 2.

J6

ii

4

(87%)

(77%)

5

of the

1.5,51-spiroketal

0

0

In

for the ISMS reaction.

7

6

i

iii

= Os04 cat / NM0 / acetone Hz0 / 20°C / 17 hrs; ii = Na104 / H,O / MeOH / 20°C; iii = NaBH, / EtOH / 20°C then HCI / H,O / THF

-

(80%)

Figure 2 Catalytic affording

quantitatively, borohydride catalysed

11 proceeded,

osmylation

predominantly using

the

sodium

leading

isomer periodate,

finally

produced

from the least hindered

Cleavage

of the vicinal

and the resulting

to a 1:1.2 mixture

equilibration

as expected, 6.

ketone

pheromone

8 (eq/axial

5,

accomplished

7 was reduced

(at Cd) of the axial and equatorial the desired

face of bicycle

diol 6 was

with sodium

alcohols

8.

Acid-

ratio - 19:l) in 54%

overall yield from 5.

Figure 3 The structure analysis ISMS

of this pheromone

of the derived

annellation

spiroketals.14 high-yielding

p-bromobenzoate

is a powerful

The synthetic synthesis

was unambiguously (Fig 3).12,13

methodology

established In conclusion,

for the preparation

utility of this condensation

of the Olive Fruit Fly pheromone

by X-ray crystallographic we have shown of tetrahydropyrans

has been exemplified 8.

Further

that the and

by the rapid and

work from this laboratory

1802

on synthetic

applications

of this novel methodology

is currently

underway

and will be reported

in due course. Acknowledgements: Education Council

(SERC),

References 1.

Financial

is gratefully

support

acknowledged.

the Nuffield

for this work Awards

Foundation

by the Algerian

from the Science

Ministry

of Higher

and Engineering

Research

and the Royal Society are highly appreciated.

and Notes

a. Perron,

K. M. Chem. Rev., 1989,89,

F.; Albizati,

1617. b. Boivin, T. L. B. Tetrahedron,

1987,43,3309. 2.

P.; Yeates, C. Tetrahedron Lett., 1983,24, 3905. b. Kay, T. I.; Williams,

a. Kocienski,

Tetrahedron Letf., 1983,24,5915. Francke, 3.

W.; Reith,

W. J. Chem. Sot. Chem. Commun., 1980, 52. A. Tetrahedron Left., 1990,31, 7237. b. Mark6, I. E.;

a. Markb, I. E.; Mekhalfia,

A.; Ollis, D. A. Synlett., 1990, 347. c. Mark& I. E.; Mekhalfia,

Mekhalfia,

E. G.

c. Baker, R.; Herbert, R.; House, P. E.; Jones, 0. T.;

A.; Ollis, D. A.

Synleff., 1990, 345. 4.

Mekhalfia,

A.; Mark6,

I. E.; Tetrahedron Lett., 1991,32,4779.

5.

Mekhalfia,

A.; Mark6,

I. E.; Adams, H. Tetrahedron Lett., 1991,32,

6.

Among other bases, pyridine, showing

the highest

purification

triethylamine

exo-endo ratio (8:l). However,

EtOSiMe3

8.

The role of the extra trimethylsilyl

can also be used instead of C6H130SiMe3 it is tempting

are capricious.

The

rapid and reversible

for

formation

effect on the reaction

with equally good results.

ether is not clearly understood

to speculate

any traces of triflic acid, generating

illustrated

these reactions

ratio.

7.

beneficial

4783.

were used, with the latter one

of the final product is also far from trivial and proved to be deleterious

the exo-endo product

However,

and collidine

that the trimethylsilyl

at this early stage.

ether will react readily with

the alcohol and the catalyst (TMSOTf).

of the corresponding

acetal/ketal

Furthermore,

might also have a

rate and the exo-endo selectivity.

This effect is further

by the absence of endo isomer in the ISMS annellation

of acetals, ketals and

ortholactones. 9. 10.

Acetals are also excellent Kocienski,

substrates

for the ISMS reaction.

P. J.; Street, S. D. A.; Yates, C.; Campbell,

S. F. I. Chem. Sot. Perkin Trans I, 1987,

2171. V.; Kelly, R. C.; Cha, D. F. Tetrahedron Left., 1976,1973.

11.

VanRheenen,

12.

We are grateful

13.

Prepared from 8 in 77% yield (pBrCfl4COBr/Et3N/4-DMAP/CH2C12/20°C/17hrs).

14.

to Mr H. Adams for performing

For other approaches

to tetrahydropyrans

Taddei, M. I. Org. Chem. , 1988,53,

Tetrahedron Lett., 1987,28,3441. Chem. , 1984,49,2808.

(Received in UK 20 January 1992)

this X-ray analysis.

using allylsilanes,

see:

a. Coppi, L.; Ricci, A.;

911 b. Wei, Z. Y.; Li, J. S.; Wang, D.; Chan, T. H.

c. Sakurai, H.; Sasaki, K.; Hayashi,

J.; Hosomi,

A. J. Org.