Stereoselective Syntheses of (+)-2-epi-Deoxoprosopinine, (−)-Deoxoprosophylline, (+)-cis-195A, and 2,5-Di-epi-cis-195A from a Common Chiral Nonracemic Building Block

Approaches toward the syntheses of alkaloids belonging to the 2,6-disubstituted 3-hydroxypiperidine and cis-decahydroquinoline (cis-DHQ) classes of alkaloids are developed, starting from a common chiral nonracemic bicyclic lactam lactone (BLL). Two key δ-lactam intermediates, (5S,6S)-5-hydroxy-6-hydroxymethyl- and (5S,6S)-5-hydroxy-6-methylpiperidin-2-ones, are prepared; the latter δ-lactam is obtained via a direct decarbonylation of a bicyclic lactam lactol. The BLL is also used to prepare (4aR,5R,8aS)- and (4aR,5S,8aS)-5-methyloctahydroquinolin-2-ones, which involved a 6-exo-trig free-radical conjugate addition reaction. The stereoselectivity observed in the free-radical cyclization step is found to be governed by allylic 1,2-strain arising from the interaction of the N-(p-methoxybenzyl) group and the C6 substituent in the lactam ring of the free-radical intermediate. The effectiveness of the developed approaches is demonstrated by the asymmetric syntheses of (+)-2-epi-deoxoprosopinine, (−)-deoxoprosoph...