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

The enantioselective organocatalytic direct vinylogous aldol reaction of gamma-crotonolactone and a suitable aldehyde was utilized in the synthesis of a functionalized gamma-butenolide. The gamma-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.