Cross-Dehydrogenative Coupling Reactions by Transition-Metal and Amihocatalysis for the Synthesis of Amino Acid Derivatives

摘要

The direct cross-dehydrogenative coupling (CDC) of C—H bonds has become a potent strategy for C-C bond formation. As CDC reactions avoid prefunctionalization of the substrates, they are more atom-economical and environmentally friendly than other cross-coupling reactions. Several research groups have reported CDC reactions of various sp~3 C—H bonds, such as benzylic and allylic C—H bonds, a-C— H bonds of tertiary amines and ethers, and C—H bonds of alkanes, with other C—H bonds. As far as we know, there are only two successful examples of CDC reactions for the synthesis of amino acid derivatives, although these compounds are so important in terms of their biological activity. Li and co-workers developed CDC reactions of N-acetylgly-cine esters and N-aryl glycine amides with malonates and alkynes in the presence of Cu(OAc)2 (2.0 equiv) and catalyzed by CuBr, respectively. However, they reported that N-aryl glycine esters, unlike N-aryl glycine amides, could not undergo a CDC reaction. Owing to the importance of amino acid derivatives and the lack of successful CDC reactions of glycine derivatives with ketones, we embarked on a study of CDC reactions of N-substituted glycine esters with unmodified ketones for the synthesis of amino acid derivatives.