Copper‐catalyzed enantioselective Michael reaction of α‐substituted cyanoacetates with acrylates was developed as the first highly enantioselective cyanoacetate Michael reaction with acrylate‐class substrates, providing a new method for constructing quaternary stereogenic carbon centers in acyclic systems. The reaction was efficiently promoted by a Cu‐prolinol‐phosphine‐ sec ‐amine chiral ligand L1 system, achieving both high reactivity and enantioselectivity. The α‐substituents of the cyanoacetates were not restricted to a methyl group; ethyl, butyl, isobutyl, and others were also tolerated. Moreover, the catalysis was applicable to reactions with acrylamides, which had not been employed in asymmetric cyanoester Michael reaction. Selective transformations of both ester and nitrile groups in the multifunctional Michael addition products were demonstrated.
Onizawa et al. (Wed,) studied this question.