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 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.
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
Yue-Jin
YJ
Liu
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
Yan-Hua
YH
Liu
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
Zhuo-Zhuo
ZZ
Zhang
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
Sheng-Yi
SY
Yan
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, 91125, USA.
Kai
K
Chen
Department of Chemistry, Zhejiang University, Hangzhou, 310027, China. bfshi@zju.edu.cn.
Bing-Feng
BF
Shi
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*; D012821:Silanes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D012821:Silanes; D010165:Palladium
C−H activation; amino acids; asymmetric transformations; chiral auxiliaries; silylation