Lewis-acid-promoted additions of carbonyl compounds to donor-acceptor substituted cyclopropanes: a new synthesis of 2,3-dihydrofurane derivatives

Tetrahedron Letters, Vo1.22, Printed in Great Britain

pp 2981 - 2984,

N0.31,

LEWIS-ACID-PROMOTED ADDITIONS OF CARBONYL CYCLOPROPANES:

A NEW SYNTHESIS

COMPOUNDS

fiir Organische

Am Hubland,

Summary: propaneesters

During

of carbon

the presence

intermediates

skeletons

in organic

2

synthesis

from siloxycyclo-

have attained

remarkable

importance

for the

(l_) - (3_) are very useful

. To our knowledge, there is only one publication

(4) smoothly

inherent

in a compound

to KUWAJIMA

adds to aldehydes

(5). Therefore

the r-lactones

are synthesized

of Tic14 with good yields.

of a C-C bond; according

methylsiloxycyclopropane affording

Chemie der Universitat

'. The "oxycyclopropanes"

the use of the strain energy

for the formation

DERIVATIVES

Reissig

2,3-dihydrofurane-3-carboxylates

and ketonesin

SUBSTITUTED

D-8700 Wiirzburg, Germany

the last decade cyclopropanes

construction

describing

Methyl

TO DONOR-ACCEPTOR

OF 2,3_DIHYDROFURANE

By Hans-Ulrich Institut

0040-4039/81/312981-04$02,00/O 01981 Pergamon Press Ltd.

1981

of type (1) - (3)

and NAKAMURA

3 l-ethoxy-l-tri-

R-CHO under Tic14 activation

(4) - can be regarded

as homoenolate

anion

equivalent.

R3 R’O

Me3Si0

II)

R2, R3= Alkyl,

Rl = SiMe,

;

(ZJ

RI = Alkyl

;

RZ,

(3)

R’ =

j

R2 = CO,C,H,

Alkyl

R3 =

Alkyl,

H H , COAlkyl

-P

C2H50 (4)

Currently propanes enolethers

we are investigating

the reactivity

(c), which are conveniently and methyl diazoacetate

4

accessible

of donor-acceptor-substituted in good yields

from trimethylsilyl-

. These siloxycyclopropaneesters 2981

cyclo-

(_S_)feature

very

2982

high reactivity first results

concerning

Cyclopropane hydelTiCl4, 4-oxoester

towards electrophilic

@),

In this communication

the lewis-acid-promoted

treated

after aqueous

is stopped

additions

in dichloromethane

5. Alcohol

distillation

although

our

compounds.

amounts

provides

(l), the likely precursor

at -78'C after 20 minutes,

we present

to carbonyl

with equimolar

workup and bulb-to-bulb

(8) in 76 % yield

if the reaction

species.

of benzaldethe chlorinated

of (8_), is obtained

only in low quantitiy

(16 %).

From (@)

and benzophenone

affords

crystalline

mixture

with methanol

olefin

@).

(6a)-o(lla):

procedure

(lOa) in 95 % yield, -

and stirring

With methanol

which can be further by pyrolysis

y-lactol

the analogous

transformed

whereas

at room temperature

(BF3-Et20

catalysis)

into the methyl

followed

by aqueous

quenching

workup

of the reaction

for 6 hours gives 82 % of the

r-lactol

is converted

to the ketal

2,3-dihydrofurane-3-carboxylate

(2 h, 150°C, 0.1 mm). Both steps are almost

quantitative

(lla) -

(overall yield

88 %).

H (@I I I I I BF, x Et*0

(12a) -

(@),

- cat.

2983

Table: Methyl

2,3-dihydrofurane-3-carboxylate

0 &R4

+

synthesis

-

(6)

UL)

RI

Entry

R2

R3

a

t-C4Hg

H

H

b

t-C4Hg

H

H

R4, R4

Methoda

'gH5' 'gH5 C6H4-C6H4

Yieldb %

mp./bp.

A

88

73-75 Oc

B

61

125-126.5

C

88

60-70 'C/O.01 mm

B

58

85-86 'C

C

88

150 OC/O.Ol mm

B

51

117-119

'C

(fluorenone) C

t-C4Hg

H

H

-(CH2)5(cyclohexanone)

d

t-C4Hg

H

H

e

t-C4Hg

H

CH3

f

-(CH2)4-

Footnotes:

C6H5CH2,

'gH5' 'gH5 C6H5, C6H5

H

aA: as described

is thermolyzed purification

for (G);

for 1 h at 150°C/0.1

pure compound

combustion

analysis

This three step procedure (methods

B, C; see table).

quarternary be applied

centres.

Enolizable

goes the same transformation potential

precursor

gave

spectra.

derivatives

as further

cyclopropane

reactions

(6e) ' is transformed -

why this reaction

(a) with R'=H. However in satisfying

difficulties 6. With

into (lie) in -

that the ketone can also be connected

to be clarified

yield

lactones

the bicyclic

sequence

compound

(entry f). The product of medium

show

(lla-q) are thus obtained -

the case with TiCl4-controlled

for functionalized

examples

ketones can also be used without

demonstrates

It remains

to cyclopropanes

yield

(method A) can be simplified,

the l-methyl-substituted

88 % (entry e); this example

(IJ)

(Il_); all new compounds

and characteristic

(entries c and d) as is frequently

Oc

mm; C: as A but without

The 2,3-dihydrofurane

in good to very good yield.

benzophenone

B: crude r-lactot

at the stage of (10) and (12). bisolated -

of spectroscopically satisfactory

C6H5CH2

to

could not

(6f) under(12f) is a -

ring size, as is suggested

2984

by the known oxidative Whereas t-C4H9,

cleavage

of bicyclic

enolethers

(4) adds only to aldehydes

but not to ketones

due to the 1-2-arrangement

of donor and acceptor

Studies

sluggish

concerning

unsymmetrical

References

.

we found that l-t-butyl-1-trimethylsiloxycyclopropane

R'= H) does not react even with benzaldehyde

relatively

8

ketones are readily the reaction

ketones

3, activation

the bisdonor-substituted

of our cyclopropanes

substituents

attacked

mechanism

and while

(1) (R1= SiMe3, R*= -

is so strong

under the influence

and the stereoselectivity

are involved as carbonyl

component

9

(6)

that even

of lewis acids. if aldehydes

are under way

10

or

.

and Notes

1. Reviews:

R. V. Stevens,

D. Seebach,

Act. Chem. Res. 1977,

Angew. Chem.

A$, 193; S. Danishefsky

ibid.,

Int. Ed. Engl. -1979, 18, -- 239; A. de Meijere,

12, 66; -1979, --

ibid., 1979

,

ig, 809. 2. Reviews:

U. Schtillkopf,

Angew. Chem. Int. Ed. Engl. 1968, z, 588; J. M. Conia, Pure

Appl. Chem. 1975, 43, 317; E. Wenkert, Heterocycles

Act. Chem. Res. 1980, 13, 27; E. Wenkert,

-1980, 14, __ 1703; see also Nachr. Chem. Techn.

3. E. Nakamura,

I. Kuwajima,

4. H.-U. Reissig,

zg, 450.

J. Am. Chem. Sot. 1977, 22, 7360.

E. Hirsch, Angew. Chem.

5. A 65:35 mixture

Lab. 1980,

of diastereomers

Int.

is obtained

Ed. Engl. 1980, 22, 813. when starting

with the two stereoisomers

of (6a) (cis:transw60:40). 6. T. Mukaiyama, 7. Synthesized

Angew.

Chem.

by deprotonation

with methyliodide

of (6a) with lithiumdiisopropylamidaand -

in 92 % yield;

Ed. Engl.,

in press.

8. I. J. Borowitz,

G. Gonis,

Int.

Int. Ed. Engl. -1977, 16, _- 807. I. Boehm, E. Hirsch,

R. Kelsey,

H.-U. Reissig,

R. Rapp, G. 3. Williams,

alkylation Angew.

Chem.

J. Org. Chem.

1966,

31, 3032. 9. Model MNDO calculations substituted Erlangen, lO.The

carbon

Industrie

a longer distance

between

the donor and acceptor

to Dr. E. U. Wuerthwein,

Universitat

for these calculations.

technical

gratefully

indicate

atoms; we are very grateful

assistance

acknowledged.

of I. Boehm in synthesizing This work was supported

and the Deutsche

Forschungsgemeinschaft.

(Received in Germany 21 April

1981)

the cyclopropanes

(5) is

by the Fonds der Chemischen