Lewis acid-mediated S(N)2 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

Et2AlCl-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(N)2 mechanism at low temperatures (below -80 degrees 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. (C) 1997 Elsevier Science Ltd.