Gang Wang1, Ran Lu2, Chuangchuang He2, Lei Liu3,4. 1. School of Chemistry and Chemical Engineering, Shandong University, Jinan, China. 2. School of Pharmaceutical Sciences, Jinan, China. 3. School of Chemistry and Chemical Engineering, Shandong University, Jinan, China. leiliu@sdu.edu.cn. 4. School of Pharmaceutical Sciences, Jinan, China. leiliu@sdu.edu.cn.
Abstract
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 represents a longstanding challenge in chemical synthesis. Here, we described a kinetic resolution of secondary n class="Chemical">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.