A Versatile Strategy for Divergent and Diastereoselective Synthesis of Natural Product-Like Polyhydroxylated Indolizidines

A general and versatile method for the divergent and
diastereoselective synthesis of polyhydroxylated indolizidines
has been established. The annulation reactions of a readily
available enantiopure dihydroxylated cyclic secondary enamine with α,β-unsaturated carboxylates including methyl
acrylate, methyl crotonate, methyl 2-hexenoate, allenoate,
and dimethyl acetylenedicarboxylate and with malonyl
chloride produced hexahydro- or tetrahydro-5-indolizinone-8-carboxylates in high yields. The resulting 5-indolizinone
derivatives were converted into diverse polyhydroxylated
indolizidines in good yields through practical hydrogenation
and reduction reactions.