Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Bronsted Acid-Catalyzed Isomerization of BCBs

Lin, Si-Li1; Chen, Ye-Hui1; Liu, Huan-Huan1; Xiang, Shao-Hua1,2; Tan, Bin1

2023-09-21

10.1021/jacs.3c06525

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   Impact Factor & Quartile

0002-7863

1520-5126

Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used in asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes are involved in enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- and enantiocontrol. The utilization of N-triflyl phosphoramide as a chiral Bronsted acid promoter enables this isomerization process to proceed under mild conditions with low catalyst loading as well as good functional group compatibility. The resulting chiral cyclobutenes could serve as platform molecules for downstream manipulations with excellent reservation of stereochemical integrity, demonstrating the synthetic practicality of the developed method. Control experiments have also been performed to verify the formation of a key carbocation intermediate at the benzylic position.

SCI

English

NI Journal Papers

First ; Corresponding

National Key R&D Program of China["2022YFA1503703","2021YFF0701604"] ; National Natural Science Foundation of China["21825105","22231004","22271135"] ; Guangdong Innovative Program[2019BT02Y335] ; Shenzhen Science and Technology Program["KQTD20210811090112004","JCYJ20210324120205016","JCYJ20210324105005015"]

Chemistry

Chemistry, Multidisciplinary

WOS:001070269700001

AMER CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Dept Chem, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Shenzhen 518055, Peoples R China

Lin, Si-Li,Chen, Ye-Hui,Liu, Huan-Huan,et al. Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Bronsted Acid-Catalyzed Isomerization of BCBs[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2023,145(39).

Lin, Si-Li,Chen, Ye-Hui,Liu, Huan-Huan,Xiang, Shao-Hua,&Tan, Bin.(2023).Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Bronsted Acid-Catalyzed Isomerization of BCBs.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,145(39).

Lin, Si-Li,et al."Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Bronsted Acid-Catalyzed Isomerization of BCBs".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 145.39(2023).