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Updated: Jul 12, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
First asymmetric synthesis of trans-3,4-dimethyl-4-arylpiperidines
Daniel P Furkert1, Stephen M Husbands
1Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. df218@bath.ac.uk
Abstract:
The first asymmetric synthesis of the trans-3,4-dimethyl-4-arylpiperidine opioid antagonist scaffold is reported. C-3 stereochemistry was established via CBS reduction and stereoselective anti-SN2' cuprate displacement of the derived allylic phosphonate. The resultant vinyl bromide was then elaborated to the target compound by Suzuki coupling and trans-selective 4-methylation. Extension of this methodology should allow general enantioselective access to highly substituted piperidine ring systems.
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