Facile Preparation of Chiral 1,2-Amino Alcohols Containing Unsymmetrical N-α-Secondary Alkyl Substituents

Abstract To address the lack of general synthetic methods for accessing chiral 1,2-amino alcohols bearing unsymmetrical N-α-secondary-alkyl groups (CAUAs), we developed an efficient protocol based on diastereoselective addition of alkyl Grignard and MeLi reagents to (S)-3,3-dimethyl-1,7a-dihydro-3H,5H-pyrrolo [1,2-c]oxazol-5-one (2). Careful methanolysis of the resulting adducts provided diverse CAUAs featuring a terminal ester functionality. Notably, intermediate 11 served as a key precursor for the synthesis of BiOx ligand 12, which exhibited exceptional performance in catalyzing the Ni-catalyzed enantioselective coupling of α-iodoacetals with aryl bromides.