Lewis acid-mediated S N2 type displacement by grignard reagents on chiral perhydropyrido[2,1- b]pyrrolo[1,2- d][1,3,4]oxadiazine. Chirality induction in asymmetric synthesis of 2-substituted piperidines

Abstract

Et 2AlCl-mediated nucleophilic alkylation with Grignard reagents on chiral perhydropyrido[2,1- b]pyrrolo[1,2- d][1,3,4]oxadiazine has proved to proceed via an S N2 mechanism at low temperatures (below −80 °C) with high to excellent inversive stereoselection, while, at an elevated temperature, hydrazonium ions are formed preferentially leading to retentive stereoselection. This methodology provides useful access to enantioselective preparation of 2-substituted piperidines and is used for asymmetric synthesis of (+)-coniine.