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

Abstract

A general and practical Pd^II -catalyzed intermolecular silylation of primary and secondary C-H bonds of α-amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure β-silyl-α-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 β-cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this β-C(sp³ )-H silylation process.