Chiral Benzimidazole Manganese Catalysts for Asymmetric Transfer Hydrogenation of 3-Substituted 2H-1,4-Benzoxazines.

The efficient synthesis of chiral 3,4-dihydro-2H-1,4-benzoxazines is of considerable interest to both academia and the pharmaceutical industry. Current catalytic methods predominantly rely on precious metals and air-sensitive chiral phosphine ligands. As a cost-effective alternative, the asymmetric reduction of benzoxazine frameworks using earth-abundant metals remains underexplored. Herein, we report manganese catalysts bearing chiral benzimidazole ligands derived from (1S,2S)-1,2-diphenylethylenediamine for the asymmetric transfer hydrogenation (ATH) of 2H-1,4-benzoxazines. This protocol affords chiral 3,4-dihydro-2H-1,4-benzoxazines in excellent yields (up to 99%) with good enantioselectivities (up to 82% ee). The catalytic system retained its enantioselectivity in a gram-scale reaction, underscoring its potential for the practical synthesis of pharmaceutical intermediates containing the 3,4-dihydro-2H-1,4-benzoxazine scaffold.