Catalytic Asymmetric Synthesis of Cα-tetrasubstituted α-Amino Acids

Abstract

A review. The ever-increasing demand for better life requires the development of more effective drugs to cope with diseases and to prolong the life span. Today, the creation of new drugs is not only by high-throughput screenings, but also by rational design. It is now believed that the screening of synthetic libraries that derived from various types of privileged scaffolds, rather than com. ones, is more promising to discover new small mol. drugs. Therefore, in recent years, the need for efficient and diverse synthesis of optically active compds. with privileged scaffolds stimulated the catalytic asym. synthesis of 3,3-disubstituted oxindoles, trifluoromethylated compds. and difluoroalkylated compds. The four distinct strategies for the synthesis of tetrasubstituted α-amino acids are: (1) the enantioselective Strecker reaction between cyanide and ketimine, (2) catalytic asym. addn. of nucleophiles to ketimines derived from α-keto esters, (3) catalytic asym. allylation and arylation of nitrogen substituted esters by various types of electrophilies and (4) the direct catalytic enantioselective amination of a,a-disubstituted carbonyl compds. However, due to the challenge in the construction of tetrasubstituted carbon stereogenic centers, there still have much room for further improvement in terms of substrate cope, catalyst loading, enantioselectivity and practicability. [on SciFinder(R)]