Asymmetric synthesis of (1R,5S)‐2‐methyl‐6,7‐benzomorphan via Aza‐Prins reaction

Abstract

1R,5S)-2-Methyl-6,7-benzomorphan has been synthesised from (R)-(benzyloxy) (phenyl)acetaldehyde. On a 2-mmol scale Bi (OTf) 3 promoted Aza-Prins reaction with N-tosylhomoallylamine afforded an 88/12 mixture of 6-oxa-2-azabicyclo[3.2.1]octanes. Major diastereoisomer was converted to enantiomerically pure (2S,4S)-2-benzyl-1-methylpiperidin-4-ol via a highyielding sequence hydrogenolysis/N-detosylation/N-methylation. Acid-catalysed intramolecular FriedelÀCrafts cyclisation of the piperidinol afforded (1R,5S)-2-methyl-6,7-benzomorphan in five steps with a yield of 25%.