Synthetic Studies on (+)‐Biotin, Part 11: Application of Cinchona Alkaloid‐Mediated Asymmetric Alcoholysis of meso‐Cyclic Anhydride in the Total Synthesis of (+)‐Biotin

A practical and asymmetric process for the total synthesis of (+)‐biotin (1) has been accomplished starting from cis‐1,3‐dibenzyl‐2‐oxoimidazolidine‐4,5‐dicarboxylic acid (2). This approach features a highly enantioselective alcoholysis of meso‐cyclic anhydride 3 into (4S,5R)‐cinnamyl hemiester 4 mediated by Cinchona alkaloids. Another attractive feature of this synthesis involves the use of recyclable palladium nanoparticles‐catalyzed assembly of the 4‐carboxybutyl chain at C‐4 in (3aS,6aR)‐thiolactone 7 employing an improved Fukuyama‐type cross‐coupling reaction