Synthesis of (+)-Febrifugine and a Formal Synthesis of (+)-Halofuginone Employing an Organocatalytic Direct Vinylogous Aldol Reaction

Dedicated to Professor Scott E. Denmark on the occasion of his 60^th birthday

Abstract

The enantioselective organocatalytic direct vinylogous aldol reaction of γ-crotonolactone and a suitable aldehyde was utilized in the synthesis of a functionalized γ-butenolide. The γ-butenolide (aldol product) was stereoselectively converted into a 5-aminoalkyl butyrolactone, which isomerized to the key 2,3-disubstituted piperidinone, a common intermediate to (+)-febrifugine and (+)-halofuginone.

Key words

asymmetric catalysis - aldol reaction - stereoselective synthesis - piperidines - total synthesis

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