First asymmetric synthesis of trans-3,4-dimethyl-4-arylpiperidines.
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.
Furkert
Daniel P
DP
Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. df218@bath.ac.uk
Husbands
Stephen M
SM
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
D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; C032727:piperidine