Chiral Phosphoric Acid Catalyzed Kinetic Resolution of 2-Amido Benzyl Alcohols: Asymmetric Synthesis of 4H-3,1-Benzoxazines

An efficient method for the asymmetric synthesis of 4H-3,1-benzoxazines was developed by kinetic resolution of 2-amido benzyl alcohols using chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) were kinetically resolved with high selectivities, with an s factor of up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, wherein the amide moieties reacted as the electrophiles. Gram-scale reaction and facile transformations of the chiral products demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles.