Novel Enantioselective Syntheses of (+)-Biotin

Article abstract of DOI:10.1021/jo00107a009

Two conceptually attractive enantioselective syntheses of (+)-biotin from L-cysteine are reported based upon an intramolecular 1,3-dipolar cycloaddition of a carbamoyl azide.The first approach (12 steps) involves the following as key-steps: (i) the macrothiolactonization of acid 10b to Z-olefin 14, (ii) the thermolysis of the ene carbamoyl azide 15 in water with direct formation of a mixture of the benzylated derivatives of (+)-biotin 16a and 17a.The second approach (14 steps) involves the following: (i) elimination of bromide 29 to the endocyclic thioenol ether 30, (ii) thermolysis of the ene carbamoyl azide 30 to the exocyclic thioenol ethers 31a and 31b.Both the synthesis of 29 and the final transformation of 31a and 31b into (+)-biotin are based upon literature precedents.