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

• Published in: Angewandte Chemie International Edition 2016-10, Vol.55 (44), p.13859-13862
• Main Authors: Liu, Yue-Jin, Liu, Yan-Hua, Zhang, Zhuo-Zhuo, Yan, Sheng-Yi, Chen, Kai, Shi, Bing-Feng
• Format: Article
• Language: English
• Subjects: amino acids; Amino Acids - chemical synthesis; Amino Acids - chemistry; asymmetric transformations; Catalysis; chiral auxiliaries; C−H activation; Molecular Conformation; Palladium - chemistry; Silanes - chemical synthesis; Silanes - chemistry; silylation; Stereoisomerism
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201607766

A general and practical PdII‐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. Good to Si you: A general and practical PdII‐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. Furthermore, the late‐stage functionalization of biological small molecules such as (−)‐santonin and β‐cholic acid is demonstrated.