Kinetic resolution of indolines by asymmetric hydroxylamine formation

Catalytic kinetic resolution of amines represents a longstanding challenge in chemical synthesis. Here, we described a kinetic resolution of secondary amines through oxygenation to produce enantiopure hydroxylamines involving N-O bond formation. The economic and practical titanium-catalyzed asymmetric oxygenation with environmentally benign hydrogen peroxide as oxidant is applicable to a range of racemic indolines with multiple stereocenters and diverse substituent patterns in high efficiency with efficient chemoselectivity and enantio-discrimination. Late-stage asymmetric oxygenation of bioactive molecules that are otherwise difficult to synthesize was also explored. Catalytic kinetic resolution of amines is a longstanding challenge in chemical synthesis. Here, the authors report on titanium-catalysed asymmetric oxygenation with hydrogen peroxide for kinetic resolution of secondary amines through oxygenation to produce enantiopure hydroxylamines involving N-O bond formation.

Automated summary

The study discusses the challenges and methods of catalytic kinetic resolution of amines, specifically focusing on the titanium-catalyzed asymmetric oxygenation with hydrogen peroxide. This approach allows for the efficient production of enantiopure hydroxylamines from secondary amines, demonstrating high chemoselectivity and enantio-discrimination. Late-stage asymmetric oxygenation of bioactive molecules is also explored in this research.