Enantioselective Cross-Coupling for Axially Chiral Tetra-ortho-Substituted Biaryls and Asymmetric Synthesis of Gossypol

Yang, He1,3; Sun, Jiawei1; Gu, Wei1; Tang, Wenjun1,2

2020-04-29

10.1021/jacs.0c02686

Journal of the American Chemical Society   影响因子和分区

0002-7863

1520-5126

The axially chiral tetra-ortho-substituted biaryl skeleton exists in numerous biologically important natural products, pharmaceutical molecules, chiral catalysts, and ligands. The efficient synthesis of chiral tetra-ortho-substituted biaryl structures remains a challenging but unsolved problem. Among various asymmetric synthetic protocols, enantioselective Suzuki-Miyaura cross-coupling represents one of the most straightforward and versatile approaches. Herein we describe a powerful Suzuki-Miyaura coupling enabled by a P-chiral monophosphorus ligand BaryPhos, providing a broad range of synthetically challenging chiral tetra-ortho-substituted biaryls in excellent enantioselectivities and yields. In addition to the enhanced reactivity for sterically hindered cross-coupling, the rational design of BaryPhos also enabled a new catalysis mode of asymmetric cross-coupling involving noncovalent interactions between the ligand and two coupling partners to effect efficient stereoinduction. This protocol is robust and practical, allowing for a concise enantioselective synthesis of therapeutically valuable male contraceptive and antitumor agent gossypol.

SCI ; IC ; CCR ; EI

英语

NI论文

其他

Strategic Priority Research Program of the Chinese Academy of Sciences[XDB20000000] ; CAS[QYZDY-SSW-SLH029] ; NSFC[21725205][21432007][21572246]

Chemistry

Chemistry, Multidisciplinary

WOS:000529959000037

AMER CHEMICAL SOC

20202108701941

Enantioselectivity ; Stereochemistry ; Chelation ; Ions ; Drug products

Chemistry:801 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2

Web of Science

1.Univ Chinese Acad Sci, Ctr Excellence Mol Synth, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China
2.Univ Chinese Acad Sci, Sch Chem & Mat Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Shenzhen 518055, Peoples R China

Yang, He,Sun, Jiawei,Gu, Wei,et al. Enantioselective Cross-Coupling for Axially Chiral Tetra-ortho-Substituted Biaryls and Asymmetric Synthesis of Gossypol[J]. Journal of the American Chemical Society,2020,142(17):8036-8043.

Yang, He,Sun, Jiawei,Gu, Wei,&Tang, Wenjun.(2020).Enantioselective Cross-Coupling for Axially Chiral Tetra-ortho-Substituted Biaryls and Asymmetric Synthesis of Gossypol.Journal of the American Chemical Society,142(17),8036-8043.

Yang, He,et al."Enantioselective Cross-Coupling for Axially Chiral Tetra-ortho-Substituted Biaryls and Asymmetric Synthesis of Gossypol".Journal of the American Chemical Society 142.17(2020):8036-8043.