A flexible enantioselective approach to 3,4-dihydroxyprolinol derivatives by SmI2-mediated reductive coupling of chiral nitrone with ketones/aldehydes

Abstract

A flexible enantioselective approach to polyhydroxylated prolinol derivatives was described, which is based on the samarium diiodide-mediated reductive coupling of the chiral nitrone (3S,4R)-8, derived from D-isoascorbic acid with aldehydes/ketones. Thereby, polyhydroxyprolinol derivatives 9a-e and 9h-j were obtained from aromatic ketones and aliphatic aldehydes in good to excellent yields of 65-91%. These reductive hydroxyalkylations are highly diastereoselective in establishing the C-4 stereogenic center. By this way, the asymmetric syntheses of (-)-8a-epi-swainsonine (4) and (-)-8,8a-di-epi-swainsonine (5) have been achieved. (c) 2012 Elsevier Ltd. All rights reserved.