Diastereoselective synthesis of new zwitterionic bicyclic lactams, scaffolds for construction of 2-substituted-4-hydroxy piperidine and its pipecolic acid derivatives

RSC Adv. 2022 Feb 2;12(7):4187-4190. doi: 10.1039/d1ra09298g. eCollection 2022 Jan 28.

Abstract

The synthesis of new chiral highly functionalized zwitterionic bicyclic lactams starting from acyclic β-enaminoesters derived from (R)-(-)-2-phenylglycinol is described. The key step involved an intramolecular non-classical Corey-Chaykovsky ring-closing reaction of the corresponding sulfonium salts derived from β-enaminoesters. This methodology permits the generation of two or three new stereogenic centers with high diastereoselectivity. The utility of these intermediates was demonstrated by the stereocontrolled total synthesis of cis-4-hydroxy-2-methyl piperidine and its corresponding pipecolic acid derivative.