Synthesis 2017; 49(03): 693-703
DOI: 10.1055/s-0036-1588071
paper
© Georg Thieme Verlag Stuttgart · New York

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

Jasper Ploog
University of Hamburg, Department of Chemistry, Pharmaceutical and Medicinal Chemistry, Bundesstraße 45, 20146 Hamburg, Germany   Email: maison@chemie.uni-hamburg.de
,
Juliane Pongs
University of Hamburg, Department of Chemistry, Pharmaceutical and Medicinal Chemistry, Bundesstraße 45, 20146 Hamburg, Germany   Email: maison@chemie.uni-hamburg.de
,
Stefan Weber
University of Hamburg, Department of Chemistry, Pharmaceutical and Medicinal Chemistry, Bundesstraße 45, 20146 Hamburg, Germany   Email: maison@chemie.uni-hamburg.de
,
Wolfgang Maison*
University of Hamburg, Department of Chemistry, Pharmaceutical and Medicinal Chemistry, Bundesstraße 45, 20146 Hamburg, Germany   Email: maison@chemie.uni-hamburg.de
› Author Affiliations
Further Information

Publication History

Received: 11 August 2016

Accepted: 18 August 2016

Publication Date:
14 September 2016 (online)


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.

Supporting Information