Studies on the Asymmetric Total Synthesis of d-Biotin ( V )

An efficient, high-yielding and stereoselective synthesis of d-biotin(6) is described. The stereoselective reduction of the known (3aS, 6aR)-1, 3-dibenzyl-tetrahydro-4H-thieno-[3, 4-d] imidazol-2, 4 (1H)-dione(1) with diisobutylaluminum hydride(DIBAL-H) in toluene gave(3aS, 4S, 6aR)-1, 3-dibenzyl-4-hydroxy-tetrahydro-1H-thieno-[3, 4-d]imidazol-2(3H)-one(2) in 91% yield with 99.7% e.e.. Alcohol 2 was directly converted into (3aS, 4S, 6aR)-phosphonium salt 3 upon reaction with triphenylphosphine hydrogen tetrafluoroborate. Condensation of the corresponding ylide with 4-formylbutric acid afforded unsaturated acid 4. Catalytic hydrogen transfer hydrogenation of compound 4 with Pd-D297 resin/ammonium formate system led stereoselectively to (3aS, 4S, 6aS)-dibenzylbiotion(5), which was debenzylated by treatment with orthophospaoric acid in the presence of phenol to yield d-biotin(6). The overall yield of d-biotin was 42% from thiolactone 1.