Reactivity enhancement through strain and electronic effects: α-heterocyclopropylidenacetates as powerful Michael acceptors

Tetrahedron Letters,Vol.27,No.51,pp Printed in Great Britain

Institut fur Organische Martin-Luther-King-Platz

6185-6188,1986

Chemie der Universitat 6, D-2000 Hamburg 13,

+Chlorocyclopropylidenacetates

which

2a,

blocks

for

engaged and

the

construction

ci-chlorosubstituent in

tested

a search their

modify

for

relative

3,3_dimethylacrylate To

may

2a,

of

various

be

undesirable

I.

bi-

and

reactivity

in

Hamburg, W.-Germany

readily proven

accessible from to

be

tricyclic

in certain

cyclopropylidenacetates

with

comparison

to

useful

l-

building

skeletons.2*394 applications,

other that

As

we

have

3c-substituents of

2a1 and

methyl

(senecioester). a three-step

sequence

was

envisaqed

(see

2c,d

lc,d

Sahenne

are have

chloro-l-(trichlorovinyl)cyclopropanes,'

the

0040-4039/86 $3.00 + -00 Pergamon Journals Ltd.

Transformations

of

2a

scheme

1).

3c,d

to

2b,a,aU

6185

(for

conditions

see

table

1 1.

6186

Sodium

phenylseienide

titative tion

yield

at

under

the

with

the

acid

very

good

2ia in

overall

a two-phase

catalysis with to

to

give

3b,c,ail.

yield

solid-liquid

methylene

droxide,

in

2b,c,d table

I).

Table

1.

this

Reaction

Reaction

known

under was

phenyl-

TEBA

aqueous

by

quan-

substitu-

methylmercaptan caused

sodium

conditions.5

parent

compound

and

were

formal Ib,c,

carbonate

work-up

The

c<-thio-

new

2il~ were

thus

to

benzenesulfenate

ob-

with

PhS-

best

achieved

quite

as

and

MeS-

good

powdered The

as

the

or

ones

compounds

yields

via

Ultn,a~, (see

characterization 2b,(c,ah'. Yield

M.p.

IRb

[%I

[“Cl

[cm-‘] 1740

I: NaSePh,EtOH,-78'C,3h

Ia

95-100

la

IV: t-BuSH,t-BuSNa(trace),DMSO,RT,lOmin

Ib

83

29

1730

IUD

VIIa:

21to

93

127d

1700 1720

2)Na2COS

_C

la

Va: PhSH/PhSNa(lO:l.5),OMSO,RT,l5min

1C

95-100

_c

la:

VIIIb:

2c

89- 95

_c

1700

1P

Via: MeSH,MeSNa(30:2),HMPA,RT,lOmin

adl

86

_c

1720

2a

II: PhS02Na,H20/CH2C12,TEBA,5'C,24h

3a

54

51

1750

2a

III: MePhS02Na,H20/CH2C12,TEBA,5"C,4h

3a(Me)

62

78

1760

3a(Me)

l)m-CPBA,CHCl ~,-15°C,10min;2)Na2CO~

VII: Zn-Cu,THF/H20(99:l),RT,U.S.,20min

3Ib(Me)

94

_c 127d

1735 1700

%(Me)

IXa: KOH,CH2C12,DB-18-C-6,U.S.,2Omin

2b

73

3a

Va: PhSH/PhSNa(lO:l),OMSO,RT,lOmin

3c

90

1730

3a(Me)

Vb: PhSH/PhSNa(lO:l),HMPA,RT,lOmin

3ar(Me)

66

1725

3a:

IXa: KOH,CH2C12,DB-l8-C-6(tr.),RT,lJ.S.,30min

2c

81

3c(Me)

IXb: KOH,CH2C12,OB-18-C-6(tr.),RT,U.S.,55min

2c

81

3a(Me)

Vlb: MeSH,MeSNa(100:1),DMS0,14-180C,30min

3d(Me)

62

63

1730

2aU

65

49

1700

3dI(Me) IXa: KOH,CH2CL2,OB-l8-C-6(tr.),RT,U.S.,l5min a 2%

was purified

b All new compounds tal analysis

by distillation,

all others by column

were fully characterized

or molecular

mass determination

chromatography

also by 'H NMR, (high resolution

of

in the

2a

l)m-CPBA,CHClS,-5-O'C;

a

hy-

overall

product

Prod.a

7

with

potassium

cyclopropylidenacetates

conditions

reduced

ultrasonification

in these

of

added

chloride)

and

under

dibenzo-[181crown-6.8

not

was

(triethylbenzylammonium

consisting

yields

conditions,

or

tetrahydrofuran

was

chloride

21

and

mild

substituted

system

of

Iha in practically nucleophilic

t-butylmercaptan

followed

under

transfer

conversion Educt

in

sequence

gave

(phenylselenocyclopropyl)acetates

the

F-Elimination

phase

with

e-toluenesulfenate

which

couple

and

underwent

yields.6

system

3a,

zinc-copper

the

(m-CPBA)

and

sodium

-78OC

laz,dI, but

products 2~

Alternatively, to

of

p-elimination

at

readily

yield

lltp. Oxidation

cyclopropylidenacetate in

2a

la

position

to

m-chloroperbenzoic

tained

1).

catalysis

to

yielded

to

table

cyclopropylcarbinyl

thiolate

reduction

added

(see

1700 _C

1700

over silica gel.

13C NMR, MS as well as elemenMS). c Oil. d B.p..

6187

R*

R* =

PhSH,

,111w X

cqrne

\

THF,

PhSNa * 27’C SPh

R4

2

(R’

-

R4 = H)

5

4

(R’

-

R4 + H)

6

me-

H

,,.6

co,me

2-(

me

a

The well by

as

relative their

letting

dilution of

the

reactivities

substituted

pairs

of

strained

increase

the

ring

carbon Table

more

or

and 2.

7. less

decrease

Y

in

Methyl

(see

to

R1

table

the

hindrance relative

factors

were

at

under

the

show

the

5160

the

+27'C that

both

ring,

that

up

Michael

to

however,

4a

in

high presence Za,~c,d)

methyl

3,3-

apparently

attack

215

at

the

/3-

fold.

additions

2a,b,c,ti,

of

as

determined

the

(as

over

nucleophilic

reactivity

for

nucleophiles

2)

of on

to

2a,b,c,afl

heterosubstituents

a factor

substituents

steric

toward

thiophenolate

and

2b) up

cyclopropylidenacetates

4a1 for

results

by

the

these

cyclopropylidenacetates

acrylate Compd.

(as

Competition to

compete

The

reactivity

dimethylacrylate cause

them

conditions.'

of

analogues

of

and

thiophenolate

3,3-dimethyl-

7. R2

R3

R4

Prod.

Compet. 4a5 2a

2a

Cl

H

H

H

H

5a

2b

H

H

H

H

H

51b

with

Compet.

factors

86

215 18

0.08

2c

SPh

H

H

H

H

5c

2a

24

5160

2d

SMe

H

H

H

H

5d

2a

9

1930

H

H

H

H

8

4a5

0. 4

4=5

7

1.0

41

4a1

Cl

Me

H

H

H

6al

4a2

Cl

H

Me

Me

H

6a2

4a5

2P

4a3

Cl

H

Me

H

Me

6a3

4a5

2a

4a4

Cl

Me

Me

Me

H

6a4

4a5

4a5

Cl

Me

Me

Me

Me

6a5

4"5

103

42

2.5

17

2.1

10 1.0

105 43 25 2.5

/

x SPh

+ CQ,Me

CO,Me

10

9a 9b

X=H

9c

X=SPh

X=CI

The

reactivity

of

the

dienophile

is

about

cycloadded

to

cyclopentadiene

=

91%

1.4)

and

unsubstituted (endo/exo -The strated the

ga

utility with

12

new &-phenylthiocyclopropylidenacetate

same

as

that

at

(endo/exo --

of

three of

of

room

the

d-chloro

temperature

= 2.8)2.4

2lb required

Za: in

d to

to

react

(2~)

derivative

respectively

~4

Similarly,

diethyl

C,C-bond

different

potassium

gave

42%

11

give

Za.*

81%

within

a

$a: (endo/exo _____

4 h,

completely

as Both

while

the

yieldinq

81%

98lfn

= 3.3).

presence

References

the

compound

crown-6,10

and

CO, Me

a 96%

forminq

carbon

malonate

II2 respectively

and

additions

yield

of

ethyl

ll(iDafter

and 16

cyanoacetate

(non-optimized)

after

was

Nitromethane

diisopropylamine

fluoride,

isolated

Michael

nucleophiles,

h at

added

demon-

in benzene

in

dibenzo[l81room to

temperature.

yield

69%

Ill

1 - 3 h.

and footnotes.

This work was supported by the Deutsche Fonds der Chemischen Industrie, Hoechst

Forschungsqemeinschaft (Grant Me 405/14-l), AG and Chemische Werke tiijlsAI;.

the

1

lh. Liese, G. Splettstosser, A. de Meijere, Angew. Int. Ed. Engl. 1, 790 (1982); Angew. Chem. Suppl.

2

D. Spitzner, A. Engler, Th. Liese, G. Splettstosser, A. de Meijere, Angew. Chem. 3, 799 (1982); Angew. Chem. Int. Ed. Engl. 21, 791 (1982); Angew. Chem. Suppl. 12, 1722.

3

See also: A. de Meijere,

4

D. Spitzner,

5

Cf. H.J. Reich, J.M. Renga, I.L. Reich, J. Am. Chem. Sot. 97, 5434 (1975); H.J. Reich, S.K. Shah, ibid. 2, 3250 (1975); K.B. Sharpless, K.M. Gorxn, R.F. Lauer, D.W. Patrick, S.P. Singer, M.W. Younq, Chem. Ser. g, 9 (1975).

6

The ethyl ester corresponding to 1$ has previously been prepared only with poor yield: J. Salaiin, F. Bennani, J.-C. Compain, A. Fadel, J. Ollivier, J. Orq. Chem. 45, 4129 (1980). More recently, however, its preparation has beer1 drastically improvs: D. Spitzner, Ft. Swoboda, Tetrahedron Lett. g, 1281 (1986).

/

For other examples of ultrasound 47, 751, 5030 (1982).

8

Cf. S. Keyaniyan, M. Apel, J.P. Richmond, A. de Meijere, Angew. Chem. Int. Ed. Engl. 24, 770 (1985).

9

Cf. T.S. Lee in S.L. Friess, A. Weissberger: Technique science, New York 1953, Vol. III, p. 100-130.

lo

Conditions (Received

Germany

Angew. Chem.

Bull. Sot. Chim. Beiges 93, 241 (1984).

G. Bengtson,

as employed in

Chem., 2, 799 (1982); 1982, 1715.

A. de Meijere,

to be published.

activation

by: I. Belsky, 6 February

cf. B.-H. Han, P. Boudjoak,

J. Orn. Chem.

-Anqew. Chen. 97, 763 (1985);

in Orqanic Chemistry,

J. Chem. Sot., Chem. Commun. 1977,

1986;

accepted

30 September

237.

1986)

inter-