Improved Chiral Synthesis of Ravuconazole

Abstract

A short, elegant, and high yielding synthesis of ravoconazole is presented. The key step of this synthesis is an enantioselective palladium-catalyzed chiral zinc-allene addition reaction. The starting materials are 2-chloro-1-(2,4-difluorophenyl)-ethanone and (R)-4-phenylbutyn-2-ol obtained from enzymatic resolution of its racemate.

Keywords:

• Azoles
• enantioselective addition reaction
• enzymatic resolution
• Pd catalysis
• propargylic alcohol
• zinc-allene derivative

ACKNOWLEDGMENTS

We are grateful for the important contribution of the analytical services of Basilea China, especially to Xianzheng Liang and Jianxia Zhou for the determinations of the ee of the produced compounds. Skillful technical assistance by other analytic chemists in Basilea China is greatly acknowledged.