Divergent and Stereoselective Synthesis of β-Silyl-α-Amino Acids through Palladium-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C-H Bonds

A general and practical PdII-catalyzed intermolecular silylation of primary and secondary C-H bonds of alpha-amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure beta-silyl-alpha-amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration. The synthetic importance of this method is further demonstrated by the late-stage functionalization of biological small molecules, such as (-)-santonin and b-cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this beta-C(sp(3))-H silylation process.