1.3-diketones by 1:1-reactions of Li-enolates with acid chlorides generation of kinetic enolates with mesityl lithium

Tetrahedron Letters

No. 13, PP 1187 - llgo,

1.3-DIKETONES

BY

l:l-REACTIONS

GENERATION

OF KINETIC

Albert Institut

Pergamon Press.

OF Li-ENOLATES ENOLATES

Marvin

in Great Britain.

WITH ACID

WITH

S.Hoekstra,

Printed

MESITYL

and Dieter

CHLORIDES

LITHIUM

Seebach*

fiir Organische Chemie des Fachbereichs 14 Chemie, Justus-Liebig-Universittit GieI3en, Heinrich-Buff-Ring 58, D- 6300 Lahn-Gie8en (Received in UK 10 February 1977; accepted for publication 21 February 1977) quoted 1) that the reaction

It is generally gents

K.Beck,

1977.

is not a practical

peting

(e. g.

0-acylation)

method

of alkali

of preparing

and subsequent

enolates

such

1.3-dicarbonyl

reactions

as i with acylating

compounds

(e.g.

2+1+_3). -_ _

p because

Addition

reaof com-

of one equiva-

01 Li

1,

=1 lent of an acid calculated

from

theoretical tage

=2 chloride

to a twofold

the acylating

yield

of only

kinetically

present by LDA

We would

like

ly from

compounds

extremely

in acylations

(i) a simple

procedure

l:l-reactions

method

1-2

reasonable

1 3) ; this

included,

is a serious Furthermore,

with acid which

these

free

to obtain

Li-enolates

enolates

free

disadvan-

generated

385) .

chlorides

allows

a

the diiso-

useful 4) - Li- enolates

of amine

of generating

to high yields

is deliberately

and not the reagent.

the - otherwise

from

step

to the enolate

the substrate

problems

since

gives

R

high yields and acid

of amines

direct-

ketones. of enolates above

the thiolating -aldehydes

here

and (ii) a convenient

In reactions mentioned

can cause

to report

of 1.3-dicarbonyl chlorides

besides

of the enolate

reagent 3) , but,

50% with respect

if i is to be considered

propylamine

exess

’

i L-

6) .

with sulfenylchlorides

can be envisaged,

reagent This

stirred

same

we had found

in THF

technique

RSCl,

at -lOO°C

was

problems

that addition gave

now applied

1187

where

similar

of the enolate

high yields to the present

even

to those solution

of sensitive

reaction.

to

a-R%

A -78’C

1188

cold

No. 13

solution

methyl

of a Li-enolate,

lithium

in THF

-run) 7) to a THF -dicarbonyl after cyclic

ketones

To

avoid

the presence

Li- enolate lene

step

generation,

lithium

(2)

6

as well from

could

4

as dimethyl

only

formed

enol

ethers

be employed

for

-Q-U

this

-z

)

analysis

arailable

of the (CH3)Si-derivatives

high yield

in a ratio generated

of ca.

were

(b. p.

165OC) can be seperated column.

described

here

in this

The IR, were

fully

that ,5~ (kinetic

9:l.

which

silicagel

4

9) Li-compound

The

way

(method

from

NMR,

results

low boiling

and MS spectral

compatible

can be from

are

ketones

used

for

and to

kinetic

derivative

mesity-

2-methyl-cyclohexanone

(5

4

mcsitylcnc

5b = (ratio SO:101

(-78’C)

and determined

enolate)

of acylations

B) are

chloride

the starting

amides

&

Sa =

readily

as electrophiles.

table).

We added

purpose.

-

of aliphatic

temperature

the hindered 8) hydrocarbon

2

of this

from

when LDA or other

whether

chloride

(see

1.3-

efficiently

chlorides

the reaction

The

in good yields

and - more

and acid

and

a 20 mmole-

temperature.

isolated

carbamoyl

Lowering

ether

for

and 13-nitro-propionyl

=

to a solution

chain

by a few percent

silyl

of preparing

we tested

of open

are

enol

min.

at the same

nucleophiles,

reaction.

silyl

15-40

table,

cycloheptanone

the yields

of amine

(within

stirred

enolates

as reactand

1 :1-stoichiometric

the extra

slowly

in the accompanying

acids

improves

the corresponding

chloride

As one can see,

1. 3-diketone

by this

from

is added

of an acid

P shown

carboxylic

to -1OO’C save

A),

can be employed

the 5-nitro-

prepared -78’

solution

workup.

and aromatic Even

(method

compounds

aqueous

generated

also

products

and $5 had been accomplished

listed

by filtration

given

from

formed

in

with enolates

in the table.

data obtained

with the structures

by GC

The mesitylene

through

a short

the products

in the table.

No. 13

1189

Table 1.3-Dicarbonyl derivatives from 1:1-reactions of Li-enolates with acid chlorides. Method A refers to enolate generation from silyl enol ethers and CH3Li, method -B to enolate formation from ketones and 1 -lithio-2.4. 6- trimethyl benzene Li-enolate i of carbonyl compound (method of generation), acid chloride

seaction temp.

l-

r OC3

3-pentanone (B), 2-methyl-prosony chloride

- 78

3-methyl-2-pentanone (B), benzoyl chloride

- 78

cyclohexanone (g), butyryl chloride

- 78

1. I-dicarbonvl

compound

Taq--

formulab)

b. popC!/I’orr]

2 a) lield of distilled, :hromatographed, )r recrystallized )roduct [o/o

ioa-ii3120

55

57c)

Qa-

i30-138120

65

cyclohexanone, benzoyl chloride -100 - 78

(A) (A_) (El

cycloheptanone, 6-nitro-propionyl (A) (A) (B)

properties

92155

80

-100 - 78

a9-

97-100145

a0 78

-100 - 78 - 78

707066-

65 73 67

- 78 -100

R= CH(CH3)2 R = N(CH3)2

-100

of known derivatives

b) The 1.3-dicarbonyl form is shown and enol form (by NMR analysis). c) Adding (calcd.

a3 ai 71

chloride

cycloheptanone (A), 2- methyl-propionyl chloride carbamoyl chloride cyclooctanone (A), 2-methyl-propionyl chloride

a9

ao- a4

- 78

cyclohexanone (A), pivaloyl chloride

a) The

a7-

are

identical

although

most

73 73 69

.27-132120 66- 69/10

76 a4

i20-i2a/io

74

with literature products

l/2 equivalent of benzoyl chloride to 1 equivalent from acid chloride) or 25% (calcd. from enolate)

are

data. mixtures

of carbonyl

of the enolate ave 49% of 1. 3-diketone g!Za).

No. 13

1190

References

1)

and Footnotes

Reviews:

C. R. Hauser, “Modern

H. 0. House, nia 1972,

2nd edition,

(Edit.),

Academic

recent

papers

see

instance:

H.O. House,

J.Org.

Chem.

2,

(1975);

2114

514 (1973);

T.Tanaka

Lett.

T. J. Brocksom,

2757.

New York

1975,

Lett.

1975,

1535;

1:1-Acylations

N. Petragnani,

59 (1954);

Park,

pg.

Califor-

Vol. 5,

372.

M. Gall,

and M. F. Salomon,

-

8,

Menlo

Chimicum”

R.A.Auerbach,

Tetrahedron

1976,

Inc.

“Methodicum

Press

R. G. Salomon

et al.,

Tetrahedron

- For

and N. P. Peet,

J. Org. Chem.

40,

S. L.Hartzell

of ester

and R. Rodrigues,

and M. W.

enolates

with ethyl

J. Org. Chem.

2,

(1974).

a) D.Seebach 2,

and V. Ehrig,

127 (1972);

1357. Ester

enolates

exess

of lithium 1971,

have been

“Modern

of Li-enolates

M. Arai,

amide:

pg.

1973,

1495.

by using

M. W.Rathke

an equivalent

and J.Deitch,

Tetrahedron

1976,

and M. Teschner,

7)

The

solution

Chem. Ber.

or with a dropping

vessel

from

the flask

through

a short

1976,

reported 109,

is either funnel

hindered

Lett.

not been

of the enolate

the solution

the reaction

with highly

Tetrahedron

117) have

D. Seebach

W. A. Benjamin,

Inc.

Menlo

Park,

Califor-

568/569.

generated

6)

jacket

reactions”,

and N. Minami,

Synthesis

pressing

Lett.

with 1:1-stoichiometry

isopropyl

synthetic

Acylation

cooling

Tetrahedron

acylated

cyclohexyl

2nd edition,

-78’C

V. Ehrig,

and R.Ruden,

nia 1972,

mann,

-84, 107 (1972); Angew. Chem. Intern. Edit. and M.Teschner, Liebigs Ann. Chem. 1976,

2953.

H. 0. House,

Sato,

Angew. Chem.

D. Seebach,

- b) E. J. Corey

Lett.

5)

11; F.Korte

Stuttgart,

for

Org.Reactions

W. A. Benjamin,

Verlag

chloroformate:

4)

chapt.

and J.T.Adams.

reactions”,

Thieme

1488

3)

synthetic

Georg

Rathke,

2)

F. W. Swamer,

1601

1817;

(I,Kuwajima,

H. Quast

in which

and M. Heusch-

(1976).

or

the enolate

tube (0.7

T.

yet.

added with a syringe

with jacket

teflon

alkoxides

mm

- most

inserted conveniently

had been inner

into a - by

generated

diameter)

into

with inert

gas pressure. 8)

The

use of 2.4. d-tri-sec.-butyl-

purpose 9)

From

is currently 1 equivalent

equivalents (1974);

investigated

in our

of the commercial

of t -butyllithium,

Tetrahedron

and 2.4. 6-tri-t

Lett.

cf.

1976,

for

this

laboratory.

1-bromo-2.4.6-tri-methyl-benzene

D.Seebach 4839.

-butyl-phenyllithium

and H.Neumann,

Chem.Ber.

and 2 107,

847