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20.2.4.1.6.1 Variation 1: Cross Coupling with Lithium α-Halocarboxylates

DOI: 10.1055/sos-SD-020-00280

Masse, C. E.Science of Synthesis, (200720345.

An attractive approach to the synthesis of succinic acid derivatives would seemingly be the α-alkylation of carboxylate enolates with 2-bromocarboxylate derivatives. However, attempts at this approach using ester enolates and 2-haloacetates have met with disappointing results due to either the decomposition of the ester enolates at the higher temperatures required for the formation of the alkylation product or formation of nucleophilic acyl substitution products (e.g., β-oxo ester derivatives). These limitations have necessitated the use of the malonic ester route, which requires an additional decarboxylation step. However, it has been established that the analogous alkylation reaction with carboxylic acid dianions and 2-halocarboxylic acids proceeds smoothly to afford the substituted succinic acids in good conversions.[‌15‌] In particular, treatment of the dilithium salt of 2-methylpropanoic acid (16) with a variety of 2-bromocarboxylates 17 affords, after acidic workup, the substituted succinic acids 18 in good yields (Scheme 10).

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