Efficient Total Synthesis of (+)-Dihydropinidine, (−)-Epidihydropinidine, and (−)-Pinidinone

The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (1), (−)-epidihydropinidine (2) (as HCl salts), and (−)-pinidinone (3) were efficiently synthesized from (S)-epichlorohydrin (7) as common substrate using regioselective Wacker−Tsuji oxidation of alkenylazides 10 and 14 as well as a highly diastereoselective reduction of cyclic imine 11 as key steps. The protecting group free total syntheses represent the up to date shortest routes with highest overall yields for all three naturally occurring alkaloids (1−3). The first single-crystal X-ray analysis of (−)-epidihydropinidine hydrochloride (2·HCl) confirmed its proposed absolute configuration to be (2S,6S), corresponding to that of the isolated natural product.