Syntheses of Enantiomerically Pure Cyclopent-2-ene-1-carboxylic Acid and (Cyclopent-2-enyl) acetic Acid by Enantioselective Palladium-Catalyzed Allylic Alkylations - Synthesis of Enantiomerically Pure (-)-Chaulmoogric Acid

摘要

Asymmetric Pd-catalyzed allylic alkylations of dimethyl malonate and diethyl 2-acetoxymalonate with 3-chlorocyclopentene, using phosphanyloxazolines 1 and ent-1 as chiral ligands, gave products (-1)-2 and (+)-3b with 95 and 99.5% e, respectively. Oxidative degradation of (+)-3b furnished (+)-(R)-cyclopent-2-carboxylic acid [(+)-4] with > 99% ee. Alkylation product (-)-2 was transformed into enantiomerically pure (-)-(R)-(cyclopent-2-enyl)acetic acid [(-)-5] by three simple steps. Availability of (-)-5 enabled the first synthesis of enantiomerically pure (-)-chaulmoogric acid [(-)-9] in three steps.