Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinones via Rh-thiourea catalyzed asymmetric hydrogenation

Xu, Ana1; Li, Chaoyi1; Huang, Junrong1; Pang, Heng1; Zhao, Chengyao1; Song, Lijuan1; You, Hengzhi1,2; Zhang, Xumu3; Chen, Fen-Er1,2,4

2023-07-01

10.1039/d3sc00803g

CHEMICAL SCIENCE   影响因子和分区

2041-6520

2041-6539

Chiral tetrahydroquinoxalines and dihydroquinoxalinones represent the core structure of many bioactive molecules. Herein, a simple and efficient Rh-thiourea-catalyzed asymmetric hydrogenation for enantiopure tetrahydroquinoxalines and dihydroquinoxalinones was developed under 1 MPa H-2 pressure at room temperature. The reaction was magnified to the gram scale furnishing the desired products with undamaged yield and enantioselectivity. Application of this methodology was also conducted successfully under continuous flow conditions. In addition, H-1 NMR experiments revealed that the introduction of a strong Bronsted acid, HCl, not only activated the substrate but also established anion binding between the substrate and the ligand. More importantly, the chloride ion facilitated heterolytic cleavage of dihydrogen to regenerate the active dihydride species and HCl, which was computed to be the rate-determining step. Further deuterium labeling experiments and density functional theory (DFT) calculations demonstrated that this reaction underwent a plausible outer-sphere mechanism in this new catalytic transformation.

SCI ; EI

英语

NI论文

其他

Shenzhen Science and Technology Research Fund["JCYJ20190806142203709","JSGG20191129114029286","JSGG20201103153807021","GXWD20220811173736002"] ; Guangdong Basic, Applied Basic Research Foundation[2021A1515110366]

Chemistry

Chemistry, Multidisciplinary

WOS:001035597000001

ROYAL SOC CHEMISTRY

20233214519761

Catalysis ; Chlorine compounds ; Density functional theory ; Enantioselectivity ; Hydrogenation ; Nuclear magnetic resonance spectroscopy ; Stereochemistry

Chemistry:801 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Organic Compounds:804.1 ; Probability Theory:922.1 ; Atomic and Molecular Physics:931.3 ; Quantum Theory; Quantum Mechanics:931.4

Web of Science

1.Harbin Inst Technol Shenzhen, Sch Sci, Taoyuan St, Shenzhen 518055, Peoples R China
2.Harbin Inst Technol Shenzhen, Green Pharmaceut Engn Res Ctr, Taoyuan St, Shenzhen 518055, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Dept Chem, Shenzhen 518055, Peoples R China
4.Fudan Univ, Engn Ctr Catalysis & Synth Chiral Mol, Dept Chem, Shanghai 200433, Peoples R China

Xu, Ana,Li, Chaoyi,Huang, Junrong,et al. Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinones via Rh-thiourea catalyzed asymmetric hydrogenation[J]. CHEMICAL SCIENCE,2023,14:9024-9032.

Xu, Ana.,Li, Chaoyi.,Huang, Junrong.,Pang, Heng.,Zhao, Chengyao.,...&Chen, Fen-Er.(2023).Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinones via Rh-thiourea catalyzed asymmetric hydrogenation.CHEMICAL SCIENCE,14,9024-9032.

Xu, Ana,et al."Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinones via Rh-thiourea catalyzed asymmetric hydrogenation".CHEMICAL SCIENCE 14(2023):9024-9032.