A Novel Asymmetric Route to Chiral, Nonracemic cis-2,6-Disubstituted Piperidines. Synthesis of (+)-Pinidinone and (+)-Monomorine

摘要

The abundance of biologically active alkaloids containing the 2,6-disubstituted piperidine ring 4 has resulted in considerable synthetic efforts to reach these systems. During our continuing studies on chiral bicyclic lactams 1, we recently studied the thiolactam version 2 and found that a number of highly stereoselective thio-Claisen rearrangements produced quaternary substituted systems 3, which ultimately led to highly substituted cyclohexenones. We now describe, in preliminary form, our findings that the thiolactams 2 are readily transformed in three steps to chiral nonracemic 2,6-cis substituted piperidines 4 with very high stereoselectivity, and we are pleased to demonstrate this process by the asymmetric synthesis of two piperidine alkaloids, (+)-pinidinotie (9) and (+)-monomorine (14).