An Enantioselective Synthesis of an 11-β-HSD-1 Inhibitor via an Asymmetric Methallylation Catalyzed by (S)-3,3'-F2-BINOL.

An efficient asymmetric synthesis of 11-beta-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-l-phenylpropan-l-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3 '-F-2-BINOL under solvent-free and metal-free conditions.