A Stereospecific Synthesis of Biotin from an Aromatic Precursor. Preliminary Communication

The total synthesis of the important natural product biotin 1 from the readily available keto diester 3 is described. This approach features the stereospecific hydrogenation of the thiophene intermediate 19 as the key synthetic step. The required differentiation of the diacid functionality of compound 7 is achieved by selective lactam formation with the terminal acid to yield the 8‐membered lactam 8 . A modified Curtius reaction then affords the rearranged diurethane 18 through a series of acyl transfers. Finally, a novel conversion of the 3, 4‐diurethane moiety to the imidazolidone portion of biotin is utilized to complete the synthesis.