Organocatalytic enantioselective synthesis of C_sp2-N atropisomers via formal C_sp2-O bond amination

Qian, Chenxiao1,2,3; Huang, Jing2,3; Huang, Tingting1; Song, Lijuan4; Sun, Jianwei2,3; Li, Pengfei1

2024-03-13

10.1039/d3sc06707f

CHEMICAL SCIENCE   影响因子和分区

2041-6520

2041-6539

Compared with well-developed construction of C-sp2-C-sp2 atropisomers, the synthesis of C-sp2-N atropisomers remains in its infancy, which is recognized as both appealing and challenging. Herein, we achieved the first organocatalyzed asymmetric synthesis of C-sp2-N atropisomers by formal C-sp2-O amination. With the aid of a suitable acid, 3-alkynyl-3-hydroxyisoindolinones reacted smoothly with 1-methylnaphthalen-2-ols to afford a wide range of atropisomers by selective formation of the C-sp2-N axis. Particularly, both the kinetic (Z)-products and the thermodynamic (E)-products could be selectively formed. Furthermore, the rarely used combination of two chiral Br & oslash;nsted acid catalysts achieved excellent enantiocontrol, which is intriguing and unusual in organocatalysis. Based on control experiments and DFT calculations, a cascade dehydration/addition/rearrangement process was proposed. More importantly, this work provided a new plat-form for direct atroposelective construction of the chiral C-sp2-N axis.

SCI ; IC ; CCR ; EI

英语

第一 ; 通讯

Guangdong Provincial Key Laboratory Of Catalysis[20200925151614002] ; Shenzhen Innovation of Science and Technology Commission[2019BT02Y335] ; Guangdong Innovative Program[2020B121201002]

Chemistry

Chemistry, Multidisciplinary

WOS:001160954300001

ROYAL SOC CHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Southern Univ Sci & Technol SUSTech, Guangming Adv Res Inst, Dept Chem,Guangdong Prov Key Lab Catalysis,Coll Sc, Shenzhen 518055, Peoples R China
2.Hong Kong Univ Sci & Technol, Chinese Natl Engn Res Ctr Tissue Restorat & Recons, Dept Chem, Kowloon, Clear Water Bay, Hong Kong, Peoples R China
3.Hong Kong Univ Sci & Technol, Chinese Natl Engn Res Ctr Tissue Restorat & Recons, Hong Kong Branch, Kowloon, Clear Water Bay, Hong Kong, Peoples R China
4.Harbin Inst Technol Shenzhen, Sch Sci, Shenzhen 518055, Peoples R China

Qian, Chenxiao,Huang, Jing,Huang, Tingting,et al. Organocatalytic enantioselective synthesis of C_sp2-N atropisomers via formal C_sp2-O bond amination[J]. CHEMICAL SCIENCE,2024,15(11).

Qian, Chenxiao,Huang, Jing,Huang, Tingting,Song, Lijuan,Sun, Jianwei,&Li, Pengfei.(2024).Organocatalytic enantioselective synthesis of C_sp2-N atropisomers via formal C_sp2-O bond amination.CHEMICAL SCIENCE,15(11).

Qian, Chenxiao,et al."Organocatalytic enantioselective synthesis of C_sp2-N atropisomers via formal C_sp2-O bond amination".CHEMICAL SCIENCE 15.11(2024).