Catalytic Asymmetric Synthesis of β-Amino α-Tertiary Alcohol through Borrowing Hydrogen Amination

Abstract

The first enantioconvergent transition-metal-catalyzed amination of racemic α-tertiary 1,2-diols providing access to vicinal β-amino α-tertiary alcohols is disclosed. The iridium-catalyzed amination reaction proceeds through a chiral phosphoric acid-mediated borrowing hydrogen pathway with excellent yields and enantioselectivities for a range of amine nucleophiles and α-tertiary 1,2-diols. An array of β-amino α-tertiary alcohols were obtained with high yields and enantioselectivities (50 examples with up to 91% yield and up to 99% ee). These important chiral amino alcohol products can be easily converted into chiral ligands and bioactive skeletons. Mechanistic investigations proposed a dynamic kinetic resolution pathway involving imine formation and then imine reduction as the enantiodetermining step.