Page 51 - Advanced Organic Chemistry Part B - Reactions & Synthesis

of ketones and carboxylic acids. Both -keto acids and malonic acids undergo facile 23
decarboxylation.
SECTION 1.2
H Alkylation of Enolates
O O OH O
–CO 2
C C C R C
X C O X C X CH R
R R'
R' R'
β-keto acid: X = alkyl or aryl = ketone
substituted malonic acid: X = OH = substituted acetic acid

Examples of this approach to the synthesis of ketones and carboxylic acids are presented
in Scheme 1.4. In these procedures, an ester group is removed by hydrolysis and decar-
boxylation after the alkylation step. The malonate and acetoacetate carbanions are the
synthetic equivalents of the simpler carbanions that lack the additional ester substituent.
In the preparation of 2-heptanone (Entry 1), for example, ethyl acetoacetate functions

Scheme 1.4. Synthesis by Decarboxylation of Malonates and other -Dicarbonyl
Compounds

1 a H O, OH – H +
–
CH COCHCO C H 2 CH COCHCO 2 CH CO(CH ) CH 3
3
2 4
3
3
2 2 5
(CH ) CH (CH ) CH 52 – 61%
2 3 3 2 3 3
(prepared as in Scheme 1.3)
2 b NaOBu
CH (CO C H ) + C H Br C H CH(CO C H )
7 15
2 2 5 2
7 15
2
2 2 5 2
–

C H CH(CO C H ) H 2 O, OH H + C H CH(CO H) 2
7 15
2
7 15
2 2 5 2
Δ
C H CH(CO H) 2 C H CO H + CO 2
2
7 15
2
8 17
66 – 75%
3 c O, OH
–
C H
CO 2 2 5 H 2 H + CO H Δ
2
2
CO H + CO 2
CO C H CO 2 H
2 2 5
(prepared as in Scheme 1.3)
4 d
–
1) H O, OH
2
NCCH CO C H + CH Cl NaOEt CH 2 CHCN 2) H + CH 2 CH CN
2 2 5
2
2
2
C H
Cl Cl CO 2 2 5 3) Δ, –CO 2 Cl
5 e
O O
CO 2 CH 3 Na CO 2 CH 3
+ PhCH Cl CH 2 Ph
2
O O
CO CH CH Ph
2 3 2
CH Ph + LiI + CH 3 I + CO 2 72 – 76%
2
a. J. R. Johnson and F. D. Hager, Org. Synth., I, 351 (1941).
b. E. E. Reid and J. R. Ruhoff, Org. Synth., II, 474 (1943).
c. G. B. Heisig and F. H. Stodola, Org. Synth., III, 213 (1955).
d. J. A. Skorcz and F. E. Kaminski, Org. Synth., 48, 53 (1968).
e. F. Elsinger, Org. Synth., V, 76 (1973).