Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes

Yan, Qiaolin1; Duan, Meng2,6,7; Chen, Cien3,4; Deng, Zhiqing4,5; Wu, Mandi3,4; Yu, Peiyuan6,7; He, Ming-Liang3,4; Zhu, Guangyu4,5; Houk, K. N.2; Sun, Jianwei1,8

2022-04-01

10.1039/d2sc00636g

Chemical Science   影响因子和分区

2041-6520

2041-6539

Despite the enormous developments in asymmetric catalysis, the basis for asymmetric induction is largely limited to the spatial interaction between the substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between two aryl groups without a directing group or electronic manipulation. Here we address this challenge by using a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With versatile 2-indole imine methide as the platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly pi-pi stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.

SCI ; EI

英语

NI论文

其他

National Natural Science Foundation of China[91956114,22077108] ; Research Grants Council of Hong Kong[16303420,11303320,11104020,16309321] ; Science and Technology Innovation Committee of Shenzhen["JCYJ20180507181627057","JCYJ20200109141408054"] ; Guangdong Provincial Key Laboratory of Catalysis[2020B121201002] ; National Science Foundation["CHE-1764328","OCI-1053575"]

Chemistry

Chemistry, Multidisciplinary

WOS:000787851800001

ROYAL SOC CHEMISTRY

20222012106933

Enantioselectivity ; Hydrogen bonds

Physical Chemistry:801.4 ; Organic Compounds:804.1

Web of Science

1.Hong Kong Univ Sci & Technol HKUST, Chinese Natl Engn Res Ctr Tissue Restorat & Recon, Hong Kong Branch, Dept Chem,Kowloon, Clear Water Bay, Hong Kong, Peoples R China
2.Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
3.City Univ Hong Kong, Dept Biomed Sci, Kowloon Tong, Hong Kong, Peoples R China
4.CityU Shenzhen Res Inst, Shenzhen, Peoples R China
5.City Univ Hong Kong, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
6.Southern Univ Sci & Technol, Guangdong Prov Key Lab Catalysis, Dept Chem, Shenzhen 518055, Peoples R China
7.Southern Univ Sci & Technol, Guangdong Prov Key Lab Catalysis, Shenzhen Grubbs Inst, Shenzhen 518055, Peoples R China
8.HKUST, Shenzhen Res Inst, 9 Yuexing 1st Rd, Shenzhen 518057, Peoples R China

Yan, Qiaolin,Duan, Meng,Chen, Cien,et al. Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes[J]. Chemical Science,2022.

Yan, Qiaolin.,Duan, Meng.,Chen, Cien.,Deng, Zhiqing.,Wu, Mandi.,...&Sun, Jianwei.(2022).Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes.Chemical Science.

Yan, Qiaolin,et al."Organocatalytic discrimination of non-directing aryl and heteroaryl groups: enantioselective synthesis of bioactive indole-containing triarylmethanes".Chemical Science (2022).