title: First asymmetric synthesis of trans-3,4-dimethyl-4-arylpiperidines.
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.
authors: Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. df218@bath.ac.uk
authors: Daniel P
authors: DP
authors: Furkert
authors: Stephen M
authors: SM
authors: Husbands
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D015394:Molecular Structure; D009292:Narcotic Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; C032727:piperidine