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

Article abstract of DOI:10.1016/S0040-4039(97)00991-X

Et₂AlCl-mediated nucleophilic alkylation with Grignard reagents on chiral perhydropyrido[2,1-b]pyrrolo[l,2-d][1,3,4]oxadiazine has proved to proceed via an S(N)2 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.