Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted Exocyclic Olefins: An Efficient Access to Dexmethylphenidate

Tian, Yingying1; Zhu, Yu-Yi2,3; Yu, Jianchao1; Liu, Dong-Huang1; Yin, Qin4; Ni, Shao-Fei2,3; Bai, Shao-Tao1,5,6; Zhang, Xumu1

2023-07-01

10.31635/ccschem.023.202202601

CCS CHEMISTRY   Impact Factor & Quartile

2096-5745

An Ir-catalyzed enantioselective hydrogenation of challenging tetrasubstituted exocyclic olefins is dis-closed. This new catalytic system tolerates a broad substrate scope and affords valuable chiral cyclic & beta;- amino esters possessing two vicinal stereocenters in high yields and excellent enantioselectivities and dia-stereoselectivities (up to 94% yield, 96% ee, 99:1 dr). Control experiments and deuterium-labeling reac-tions reveal an iminium hydrogenation mechanism upon Bronsted acid-promoted tautomerization of the C=C double bond to cycliciminium intermediates. Density functional theory calculations showcase that the excellent selectivities are derived from C-H & BULL;& BULL;& BULL;& pi; interaction between the substrate and the chiral ligand. Application in gram-scale preparation of dexmethylphenidate with up to 1500 turnover num-ber is also demonstrated, showing the promising potential of Ir-catalyzed enantioselective hydrogena-tion in drug synthesis.

asymmetric hydrogenation tetrasubsti-tuted olefins iridium Bronsted acids dexmethy-lphenidate

ESCI

English

First ; Corresponding

National Natural Science Foundation of China[21991113] ; Stable Support Plan Program of Shenzhen Natural Science Fund[20200925161222002] ; Guangdong Basic and Applied Basic Research Foundation["2021A1515110808","2021B1515020062"] ; Guangdong Provincial Key Laboratory of Catalysis[2020B121201002]

Chemistry

Chemistry, Multidisciplinary

WOS:001029683600001

CHINESE CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Dept Chem, Shenzhen, Peoples R China
2.Shantou Univ, Dept Chem, Shantou, Peoples R China
3.Shantou Univ, Key Lab Preparat & Applicat Ordered Struct Mat Gua, Shantou, Peoples R China
4.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China
5.Shenzhen Polytech Univ, Inst Carbon Neutral Technol, Shenzhen, Peoples R China
6.Shenzhen Polytech Univ, Ctr Carbon Neutral Catalysis & Engn, Shenzhen, Peoples R China

Tian, Yingying,Zhu, Yu-Yi,Yu, Jianchao,et al. Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted Exocyclic Olefins: An Efficient Access to Dexmethylphenidate[J]. CCS CHEMISTRY,2023.

Tian, Yingying.,Zhu, Yu-Yi.,Yu, Jianchao.,Liu, Dong-Huang.,Yin, Qin.,...&Zhang, Xumu.(2023).Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted Exocyclic Olefins: An Efficient Access to Dexmethylphenidate.CCS CHEMISTRY.

Tian, Yingying,et al."Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted Exocyclic Olefins: An Efficient Access to Dexmethylphenidate".CCS CHEMISTRY (2023).