Enantioselective Total Synthesis of (+)-Neostenine

A chirality transfer approach using acyclic polyol intermediates for the synthesis of (+)‐neostenine (1) has been developed. The sequential Overman/Claisen rearrangement of an allylic 1,2‐diol was especially useful, installing two contiguous stereocenters with complete diastereoselectivity in a one‐pot sequence. The SmI2‐mediated cyclization and the subsequent chemoselective reduction of a lactam moiety accomplished the first enantioselective total synthesis of (+)‐neostenine (1). 18 steps to alkaloid! The first enantioselective total synthesis of (+)‐neostenine by a chirality transfer approach using three sigmatropic rearrangements of acyclic polyol intermediates has been reported (see scheme). The sequential Overman/Claisen rearrangement was especially useful to introduce two contiguous stereocenters, including a carbon–nitrogen bond. The reaction took place in a completely stereoselective fashion in a one‐pot sequence.