A Domino Aza-Prins/Friedel–Crafts Reaction for the Synthesis of Benzomorphans

Abstract

A new domino sequence involving an aza-Prins cyclization and a Friedel–Crafts reaction is reported. The starting materials are N-tosylimines prepared in situ from N-tosylated homoallylamines and derivatives of phenylacetaldehyde. The domino reactions are mediated by Brønsted and Lewis acids and give benzoannelated azabicyclononanes. Many derivatives thereof contain the benzomorphan scaffold and are thus of pharmaceutical interest as analgesics. The method provides a one-step access to substituted benzomorphans from readily available starting materials. The yields are generally good and various substituents are tolerated.

Key words

arylation - cyclization - imines - aza-Prins reaction - Friedel–Crafts reaction - morphine - pentazocine - domino reaction

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