Homophthalate Claisen condensation

The conversion of the substituted 1,3-dicarbonyl compound into homophthalic acid is remarkably facile loss of the acetyl group by a retro-Claisen condensation and hydrolysis of the ester group are complete in a few minutes in aqueous sodium hydroxide. The overall synthesis of homophthalic acids from o-bromobenzoic acids occurs in high yield and provides an attractive route. 

A vigorous Claisen condensation ensues when a homophthalic ester and methyl formate are treated with sodium ethoxide and the active methylene group is formylated. Cyclization takes place with ease in acidic media to produce a methyl isocoumarin-4-carboxylate (50JCS3375). Hydrolysis under acid conditions is sometimes accompanied by polymerization, but the use of boron trifluoride in acetic acid overcomes this problem. Decarboxylation may be effected in the conventional manner with copper bronze, though it sometimes accompanies the hydrolysis. 

The construction of isocoumarin natural products offers another instructive comparison between DoM and more conventional methodologies. Thus, in the synthesis of hydrangenol 37 (Scheme 12), [31a] a five-step, one-pot process directly furnishes the heteroannelated product 36, a sequence involving a low-temperature DoM of a dimethyl amide, an LDA-induced chain extension, and a base-mediated cyclization. BBr3 treatment leads to the natural product 37 in good overall yield. The chosen classical alternative, [31b] involving Claisen condensation of 39 with 40 to give 38, is achieved in low over l yield due to the an inefficient preparation of the homophthalic ester 39 (from 3-nitrophthalic anhydride), a memento of an earlier DoM- classical route comparison (Scheme 3). 

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See also in sourсe #XX -- [ , ]

See also in sourсe #XX -- [ , ]

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