Stereodivergent access to non-natural α-amino acids via enantio- and Z / E -selective catalysis

Abstract

The precise control of Z and E configurations of the carbon-carbon double bond in alkene synthesis has long been a fundamental challenge in synthetic chemistry, even more pronounced when simultaneously striving to achieve enantioselectivity [( Z , R ), ( Z , S ), ( E , R ), ( E , S )]. Moreover, enantiopure non-natural α-amino acids are highly sought after in organic and medicinal chemistry. In this study, we report a ligand-controlled stereodivergent synthesis of non-natural α-quaternary amino acids bearing trisubstituted alkene moieties in high yields with excellent enantioselectivity and Z / E selectivities. This success is achieved through a palladium/copper–cocatalyzed three-component assembly of readily available aryl iodides, allenes, and aldimine esters by simply tuning the chiral ligands of the palladium and copper catalysts.