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

The 2,6-disubstituted piperidine alkaloids (+)-dihydropinidine (<b>1</b>), (−)-epidihydropinidine (<b>2</b>) (as HCl salts), and (−)-pinidinone (<b>3</b>) were efficiently synthesized from (<i>S</i>)-epichlorohydrin (<b>7</b>) as common substrate using regioselective Wacker−Tsuji oxidation of alkenylazides <b>10</b> and <b>14</b> as well as a highly diastereoselective reduction of cyclic imine <b>11</b> 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 (<b>1</b>−<b>3</b>). The first single-crystal X-ray analysis of (−)-epidihydropinidine hydrochloride (<b>2</b>·HCl) confirmed its proposed absolute configuration to be (2<i>S</i>,6<i>S</i>), corresponding to that of the isolated natural product.