Synthesis of Indolizidines from Optically Pure α-Amino Acids via Stereocontrolled Rhodium-Catalyzed Hydroformylation of N-Allylpyrroles

Indolizidine alkaloids have attracted considerable attention because of their vast array of structural diversity and varied biological activity. This article relates the results that we obtained in the field of the total synthesis of indolizidines from a-amino acids, based on the rhodium-catalyzed hydroformylation of N-allylpyrroles intermediates. The formed pyrrolylbutanals undergo an intramolecular cyclodehydration to 5,6-dihydroindolizines, which are fully hydrogenated to indolizidines. All reaction sequences are stereocontrolled: indeed, the chiral center in the starting amino acid is transferred into 5,6-dihydroindolizine moiety with complete stereochemical integrity and the new stereogenic center at C9 carbon atom in the final indolizidines is generated in only one configuration. Chirality 23: 730-735, 2011. (C) 2011 Wiley-Liss, Inc.