Synthetic studies on d-biotin.: Part 7:: A practical asymmetric total synthesis of d-biotin via enantioselective reduction of meso-cyclic imide catalyzed by oxazborolidine

A novel and convenient method for the stereoselective synthesis of d-biotin I starting from the commercially available cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 has been developed. The key features of this synthesis include the enantioselective reduction of a meso-cyclic imide, mediated by a chiral oxazborolidine catalyst, derived from (1S,2S)-(+)-threo-l(4-nitrophenyl)-2-amino-1,3-propanediol and the direct introduction of a C-5 side chain to the (3aS,6aR)-thiolactone through a modified di-Grignard reaction. Eriantioselectivities of 98% in the oxazborolidine-catalyzed asymmetric reduction process have been achieved. (C) 2003 Elsevier Ltd. All rights reserved.