Enhancing the AsymmetricHydrogenation/Desymmetrizationof an Achiral Lactone in the Synthesis of (+)-Biotin

(+)-Biotin plays an essential role as a cofactor in many biological systems and is used to supplement the diets of humans and animals. One of the most elegant chemical production processes involves the asymmetric hydrogenation/desymmetrization of a <i>meso</i>-anhydride to yield the key lactone intermediate. However, relatively high catalyst loadings limit the attractiveness of this route. A number of strategies have been investigated to improve the efficiency of the hydrogenation process, and an improved two-step process has been developed, which significantly reduces the amount of expensive chiral catalyst required and pairs this with a cheap, readily available nickel catalyst, producing the key chiral lactone without a reduction in the enantioselectivity.