Chiral Phosphoric Acid-Catalyzed Hydrolysis of 4H-Oxazines for Diverse Syntheses

The use of water as a nucleophile in catalytic asymmetric reactions remains a significant challenge, primarily due to its intrinsically low nucleophilicity and small size, which make precise control over both reactivity and stereoselectivity particularly difficult. To address this issue, we developed a CPA-catalyzed asymmetric hydrolysis system, successfully achieving the efficient and highly stereoselective transformation of 4H-oxazines with water. Under this catalytic system, the initial formation of chiral α-bromo ketones is followed by their in situ conversion through reduction and intramolecular SN2 reactions, directly affording valuable chiral bromo alcohols and chiral oxazolone derivatives in high yields with excellent enantioselectivity.