A diastereoselective intramolecular hydroamination approach to the syntheses of (+)-, (+/-)-, and (-)-pinidinol.
A diastereoselective, lanthanocene-catalyzed, intramolecular hydroamination reaction was applied to the preparation of 2,6-disubstituted piperidines. Various metal/ligand arrays in the catalysts were examined using a model substrate to allow optimization of the diastereoselectivity. It was determined that the relationship between metal size and ligand bulk plays an integral role in the transformation. The complex Cp2NdCH(TMS)2 converted 2-substituted 8-nonen-4-amines to 2,6-disubsituted piperidines with greater than 100:1 selectivity for the formation of the cis isomer. A short synthesis of pinidinol, an alkaloid isolated from various pine and spruce species, was then carried out to exploit this stereoselective reaction.
Molander
G A
GA
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA. gmolandr@sas.upenn.edu
Dowdy
E D
ED
Pack
S K
SK
D000588:Amines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000588:Amines; D010880:Piperidines; C431206:pinidinol