A Practical Synthesis of (+)‐Biotin from L ‐Cysteine

α‐Amino aldehyde 4 , which is readily derived from L ‐cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16 , afforded α‐amino nitrile 5 with high diastereoselectivity ( syn / anti =11:1) and in high yield. Amide 6 , derived from 5 , was converted to thiolactone 8 , a key intermediate in the synthesis of (+)‐biotin ( 1 ), by a novel S , N ‐carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21 , which has an ester group, in the presence of a heterogeneous Pd/C catalyst allowed the efficient installation of the 4‐carboxybutyl chain to provide 9 . Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L ‐cysteine.