Ana Xu, Lanxing Ren, Junrong Huang, Yuxiang Zhu, Gang Wang, Chaoyi Li, Yongqiang Sun, Lijuan Song, Hengzhi You and Fen-Er Chen
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引用次数: 0
Abstract
A novel Ir-catalyzed asymmetric hydrogenation protocol for the synthesis of chiral tetrahydroquinoxaline (THQ) derivatives has been developed. By simply adjusting the reaction solvent, both enantiomers of mono-substituted chiral THQs could be selectively obtained in high yields with excellent enantioselectivities (toluene/dioxane: up to 93% yield and 98% ee (R); EtOH: up to 83% yield and 93% ee (S)). For 2,3-disubstituted chiral THQs, the cis-hydrogenation products were obtained with up to 95% yield, 20 : 1 dr, and 94% ee. Remarkably, this methodology was also applicable under continuous flow conditions, yielding gram-scale products with comparable yields and enantioselectivities (dioxane: 91% yield and 93% ee (R); EtOH: 90% yield and 87% ee (S)). Unlike previously reported Ir-catalyzed asymmetric hydrogenation protocols, this system exhibited a significant improvement as it required no additional additives. Furthermore, comprehensive mechanistic studies including deuterium-labeling experiments, control experiments, kinetic studies, and density functional theory (DFT) calculations were conducted to reveal the underlying mechanism of enantioselectivities for both enantiomers.
期刊介绍:
Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.