Page 177 - Advanced Organic Chemistry Part B - Reactions & Synthesis

transformation results in the acylation of the carbon nucleophile. This transformation 149
corresponds to the general reaction Path B, as specified at the beginning of this chapter
(p. 64). SECTION 2.3
Acylation of Carbon
O O – O Nucleophiles
–
RC X + R′ C EWG RC CR′ 2 RCCR′ 2
2
X EWG EWG
The reaction pattern can be used for the synthesis of 1,3-dicarbonyl compounds and
other systems in which an acyl group is to an anion-stabilizing group.
O
O
2
+ R CH EWG R 1 EWG
R 1 X 2
R 2

2.3.1. Claisen and Dieckmann Condensation Reactions

An important group of acylation reactions involves esters, in which case the
leaving group is alkoxy or aryloxy. The self-condensation of esters is known as
the Claisen condensation. 216 Ethyl acetoacetate, for example, is prepared by Claisen
condensation of ethyl acetate. All of the steps in the mechanism are reversible, and a
full equivalent of base is needed to bring the reaction to completion. Ethyl acetoacetate
is more acidic than any of the other species present and is converted to its conjugate
base in the final step. The -ketoester product is obtained after neutralization.

CH CO CH CH 3 + CH CH O – – CH CO CH CH 3 + CH CH OH
2
2
2
3
2
2
2
2
3
3
O O –
CH COCH CH 3 + – CH CO CH CH 3 CH COCH CH 3
3
2
2
2
2
3
2
CH CO CH CH 3
2
2
2
O – O
CH C OCH CH 3 CH CCH CO CH CH 3 + CH CH O –
2
3
2
3
2
2
3
2
CH CO CH CH 3
2
2
2
O O
CH CCH CO CH CH 3 +CH CH O – CH CCHCO CH CH 3 +CH CH OH
3
2
2
2
3
2
3
2
2
3
2
–
As a practical matter, the alkoxide used as the base must be the same as the alcohol
portion of the ester to prevent product mixtures resulting from ester interchange.
Sodium hydride with a small amount of alcohol is frequently used as the base for ester
condensation. The reactive base is the sodium alkoxide formed by reaction of sodium
hydride with the alcohol released in the condensation.
R′OH + NaH R′ONa + H 2
As the final proton transfer cannot occur when -substituted esters are used, such
compounds do not condense under the normal reaction conditions, but this limitation
216
C. R. Hauser and B. E. Hudson, Jr., Org. React., 1, 266 (1942).