Asymmetric α‐Allylation of Glycinate with Switched Chemoselectivity Enabled by Customized Bifunctional Pyridoxal Catalysts

Abstract Owing to the strong nucleophilicity of the NH 2 group, free‐NH 2 glycinates react with MBH acetates to usually deliver N‐allylated products even in the absence of catalysts. Without protection of the NH 2 group, chiral pyridoxal catalysts bearing an amide side chain at the C3 position of the naphthyl ring switched the chemoselectivity of the glycinates from intrinsic N‐allylation to α‐C allylation. The reaction formed chiral multisubstituted glutamic acid esters as S N 2′–S N 2′ products in good yields with excellent stereoselectivity (up to 86 % yield, >20 : 1 dr, 97 % ee). As compared to pyridoxal catalysts bearing an amide side arm at the C2 position, the pyridoxals in this study have a bigger catalytic cavity to enable effective activation of larger electrophiles, such as MBH acetates and related intermediates. The reaction is proposed to proceed via a cooperative bifunctional catalysis pathway, which accounts for the high level of diastereo‐ and enantiocontrol of the pyridoxal catalysts.