Organic reactions at high pressure. Michael addition of activated acyclic donors with β,⨿-disubstituted enone acceptors.

Tetrahedron Letters,Vo1.24,No736,pp Prlnted In Great Brltau

ORGANIC ACTIVATED

REACTIONS

ACYCLIC

3841-3844,1983

AT HIGH PRESSURE.

0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd

MICHAEL

DONORS WITH B,8-DISUBSTITUTED

W1111am Department

G. Dauben*

ADDITION

OF

ENONE ACCEPTORS?

and John M. Gerdes

of Chemistry, Umvers1ty of California, Berkeley, California 94720

Abstract High pressure, 15 kbar (1.5 GPa), Michael additions of doubly activated donors to stencally hindered enone acceptors with 1,5-d1azab1cyclo[4.3.0]non-5-ene acetonitnle affords Michael adducts in 42-82% yield.

Formation 1s

limited

of molecules

densat10n.2'3

Michael

and directing

groups5

protic

solvent

stenc

hindrance

1s achieved

which

either

mes1tyl

in aprotic

success

Recently,

oxide

donors,

work

as base 1n acetonltnle

1n this laboratory

react via Michael

solvent

,/K C02C2H5 R1 = H or CH

3 R2 = CH3 or 0C2H5

X, Y = CH3

X,

Y =-(CH2)3-

3841

catalysts,4

in overcoming

pressure

condensatlve

con-

Michael-type

has revealed

condensations has shown undergo that sterically

diones,

and enone

cyclizations

O]non-5-ene

7

,COR2

bases,

Michael

0 R:

X = CH3, Y = H

initiated

reaction

to undergo

Matsumoto6

or 1,3-cyclic

or 1,5-diazabicycloC4.3

0

X = H, Y = CH3

limited

conditions.

1 e., B-keto esters

tnethylamlne

weak

to classical

are inefficacious

of stencally

reaction

by the Michael

and acceptors

employing

inherent

these modifications

and aprotrc

centers

donors

media

side-reactions

routine

cycloalkanone

when either

quaternary

congested

fail to react or react slowly at ambient

at 1Q kbar.

including

15 kbar pressure ut111zed

however,

Nevertheless,

activated

acceptors

conducted

by using high pressure

additions

hindered

additions

contiguous

of stencally

avoid undesirable

cond1t10ns,2a

that substrates Michael

possessing

due to the inability

acyclic in

(DBN) 1s

at

3842

We report donors,

in this commumcatlon

diethylmalonate,

stencally Michael

demanding

summarized

(1.0 mmol)

(MgS04), x-x.

concentrated

Under

optimal

and donors

for the formation either

obtained

control

donor

(3 5 mL/mmol)

by concentration,

to yield

&,

dependent &,

experiments

(1.0 mmol) little

pressure

in this study are the primary

and &&

for entries

demonstrate to effect

Michael

crude mixtures

addltlon

adducts

two contiguous of acceptors

at 15 kbar, 25 "C, for materials

by 'H NMR analysis.

l-6 performed ln refluxlng of Michael

condensation.

product:.

were dried

reaction

by reaction

of

acetonltnle adducts

that the mild aprotlc

Michael

(1.0 mmol)

Michael

with

involving

of starting

(~10%) or no formation

These experiments

the use of elevated

acceptor

afforded

products

the

at the temperatures

the corresponding

and DBN (1.5 mnol)

with

(1.5 GPa),

The ether portions

studies

&!&, &Q,

activated

15 kbar

out by treating

with water.

(520%) or no reaction

for 24 h indicated

GC and IH NMR analyses. necessitate

of products

incomplete

(1.0 mmol),

(3.5 mL/mmol)

Temperature

of acycllc

2_methylacetoacetate,

45 'C and 15 kbar pressure,

were formed.

(1 bar) pressure

the acceptor

I were carried

followed

addltlons

The high pressure,

ln acetonltnle

ether and washed

conditions,

centers

Ambient

and ethyl

and then chromatographed"

quaternary

48 h revealed

in Table

Depressurizatlon,

with dlethyl

Michael

,J,-,!J (Table I).

and DBN' (1.5 mmol)

and times indicated. which were diluted

methylmalonate,

enone acceptors

condensations8

with donor

dlethyl

high pressure

I-,$,$by

condltlons

All the ketones

In contrast,

when

the

C02C2H5

a HD

0

H

0

C02C2H5

CH2C02C2H5

C02C2H5

starting

materials

react with

used for the preparation

sodium

ethoxlde

respectively.2a*11 of the reaction Ethoxlde

control

to react with

donor

and acceptor

expected

Michael

ethanol,

reaction

&I, and ,J.& are allowed

only the cyclic

condltlons

ketones

Q-8

used under high pressure

to

are isolated, permit

control

sequence.

lowed

diethylmalonate

ln refluxlng

Thus, the mild

of ketones ,&, &,

experiments

at 1 bar pressure

sodium dlethylmalonate starting

initiated were

materials. cycloalkanones

allowed

ln which

in ethanol

Heating G

enones 2"'

these mixtures

at reflux,

and ,@,, respectively.

to react in ethanol

and tlld were

at 25 OC, 24 h, afforded

al-

only recovered

24 h, produced

the

When enone $, and sodium

at 15 kbar, 25 "C, 48 h, condensation

I

Michael

I

I

0

2

4

are Isolated.

0

cl 0

0

Acceptor

I.

d15 kbar, 45 'C, 48 h.

aYields

6

Entry

Table

eStarting

materials

Iz

acyclic

donors

recovered.

z"

C H 225

/%O

R(71jb

&$44)dse

jj$73F

/C02C2H5

upon chromatographic

mlxtured

mlxturec

&(0)d'e

complex

(55jd C02C2H5

I

&(O?

complex

Q

0

at 15 kbar.a

'15 kbar, 45 "C, 36 h.

&

R=

purification.

b15 kbar, 25 "C, 48 h.

R=

k

ketone acceptors

31

CH

Donors

to a,B-unsaturated

data. fDecomposes

spectral

C02C2H5

R = H\C/CoZC2H5

activated

gave satisfactory

Product

of doubly

All products

addition

I

w

00 4

w

3844

products

,I& and a

methylmalonate also falled logues ducts

were not observed.

when allowed

to afford

of & (Table

The lnablllty

I) further

In conclusion, creased

Michael

of ethoxlde

the notion

of the Michael

high pressure

substitution products

produces

those adducts

in the yields

condltlons

effectively

with

Requisite

of product

References This study was supported

2.

(a) Bergman,

E. D.; Ginsburg,

pp. 187-188;

p. 247.

3.

(a) Martin,

4.

For a recent Slnsterra,

example,

Fang, J.-M. J_. m.

6.

(a) Matsumoto, 1013,

W. G.; Bunce,

8.

For a descnptlon H. 0. 2. w.

9.

Michael afford

additions

IO.

Short

11.

(a) Steiner, 3_. e. Khuda,

Michael

1s discussed

path column U

*.

w,

79,

USA

imposed

affording

by lnMichael

Furthermore, subsequent

these

cycllzatlons

&.

Foundation, React.

m,

Grant CHE-810-2938. l&

179; (b) Ref. 2a,

(b) Ref. 3a, p. 435. J., Campaner,

B., Mestres,

R.,

cited therein.

@,@,I, 20,

T. Chem. Lett. -----I.

770; (b) Matsumoto,

K. m

w,

1981, 1673.

(submitted).

methodology

used, see:

Dauben,

W. G., Krabbenhoft,

The increased

effective

as base failed

base strength

to

of DBN at

in Ref. 7. slllca

30-200 mesh;

B. Helv. Chum. Acta

138, Proc. Chem

Sot. &'j$$, 3071,

21

are required

substrates.

at 45 "C, 15 kbar pressure,

centers

mild to lnhlblt

Science

m

Chem

adducts.

2358. m

pro-

282

chromatography,

, Wlllholm,

M. J. -Chem.

(Received

hindrance thereby

ana-

and Notes

419,

3

R. A. 2. m.

42,

24 h,

Michael

media

demanding

at 15 kbar (25 "C and 45 "C) using tnethylamlne

the desired

high pressure

Chem. m.

Qfl,

dlethyl

47_, 3464.

of the high pressure

3.

centers

heating

A., Garcia-Raso,

K., Uchlda,

(c) Matsumoto,

Dauben,

and aprotlc

the stenc

1037, and references

Q&Z,

Chem. m,

K. Angew.

7.

Q,,@, 3,

sodium

reflux,

the simple

stencally

quaternary

D., Pappo, R. m.

Garcia-Raso,

J. V. Synthesis

5.

I&

by the National

S. F. Tetrahedron

to yield

reacting

are sufflclently

the exception

1.

with

overcomes

two contiguous

at high pressure

and rearrangements

hindered

8,Q and ID& or the methyl

that high pressure

condensation

of 42-82%.

contalnlng

adducts,

conditions

near the donor and acceptor

addition

aprotic

supports

success

the increasingly

to react with enones 2 and 2 at 1 bar pressure,

any of the respective

and a.

for the routine

Furthermore,

June 1983)

a.

m, m,

(d) Farmer,

dlethyl

ether/hexane

35_, 1752, I&

elution.

(b) Crossley,

90, (c) Kon, G.A.R.,

E. H., Ross, J. J

%.

Sot.

A. W. Qudrat-Im,

127,