合成路线1

A further procedure employed the chiral keto acid (XXII) as the key intermediate. The cyclohexenone carboxylic acid (XXI) was synthesized via aldol condensation between 3-benzoylacrylic acid (XIX) and ethyl acetoacetate (XX), followed by cyclization and decarboxylation under Robinson annulation reaction conditions. Resolution of (XXI) to furnish the desired (S)-enantiomer (XXII) was accomplished either via formation of the diastereomeric salts with cinchonidine or, alternatively, by esterification of (XXI) with n-butanol --yielding the isomeric mixture (XXIII)--, followed by enantioselective hydrolysis of the (S)-butyl ester from in the presence of alpha-chymotrypsin. Coupling of keto acid (XXII) with tetrahydropyridine (V) provided keto amide (XXIV). The keto group of (XXIV) was then reduced with NaBH4 to form a diastereomeric mixture of allylic alcohols (XXV), which were further reduced employing NaBH3CN in the presence of ZnCl2 to furnish the target (R)-cyclohexenecarboxamide (XXVI). The amide function of (XXVI) was finally reduced to the title amine by means of LiAlH4 in methyl tert-butyl ether.