Copper-Catalyzed Enantioselective Skeletal Editing through a Formal Nitrogen Insertion into Indoles to Synthesize Atropisomeric Aminoaryl Quinoxalines
Xu Zhang
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
These authors contributed equally to this work.
Search for more papers by this authorJin-Qi Zhang
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
These authors contributed equally to this work.
Search for more papers by this authorZe-Hua Sun
School of Chemistry and Chemical Engineering, Shandong University
These authors contributed equally to this work.
Search for more papers by this authorHui-Mei Shan
School of Chemistry and Chemical Engineering, Shandong University
School of Chemistry and Chemical Engineering, Shandong University of Technology
Search for more papers by this authorCorresponding Author
Prof. Jun-Cheng Su
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
Search for more papers by this authorProf. Xiao-Pan Ma
Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, College of Pharmacy, Guilin Medical University, 1 Zhi Yuan Road, Guilin, 541199 China
Search for more papers by this authorProf. Gui-Fa Su
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
Search for more papers by this authorCorresponding Author
Prof. Li-Ping Xu
School of Chemistry and Chemical Engineering, Shandong University
Search for more papers by this authorCorresponding Author
Prof. Dong-Liang Mo
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
Search for more papers by this authorXu Zhang
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
These authors contributed equally to this work.
Search for more papers by this authorJin-Qi Zhang
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
These authors contributed equally to this work.
Search for more papers by this authorZe-Hua Sun
School of Chemistry and Chemical Engineering, Shandong University
These authors contributed equally to this work.
Search for more papers by this authorHui-Mei Shan
School of Chemistry and Chemical Engineering, Shandong University
School of Chemistry and Chemical Engineering, Shandong University of Technology
Search for more papers by this authorCorresponding Author
Prof. Jun-Cheng Su
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
Search for more papers by this authorProf. Xiao-Pan Ma
Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, College of Pharmacy, Guilin Medical University, 1 Zhi Yuan Road, Guilin, 541199 China
Search for more papers by this authorProf. Gui-Fa Su
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
Search for more papers by this authorCorresponding Author
Prof. Li-Ping Xu
School of Chemistry and Chemical Engineering, Shandong University
Search for more papers by this authorCorresponding Author
Prof. Dong-Liang Mo
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004 China
Search for more papers by this authorAbstract
Skeletal editing represents an attractive strategy for adding complexity to a given molecular scaffold in chemical synthesis. Isodesmic reactions provide a complementary skeletal editing approach for the redistribution of chemical bonds in chemical synthesis. However, catalytic enantioselective isodesmic reaction is extremely scarce and enantioselective isodesmic reaction to synthesize atropisomeric compounds is unknown. Herein, we report a facile method to synthesize axially chiral aminoaryl quinoxalines through Cu(I)-catalyzed dearomatization and sequential chiral phosphoric acid (CPA) catalyzed enantioselective isodesmic C−N bond formation and cleavage from indoles and 1,2-diaminoarenes under mild reaction conditions. In this process, the five-membered ring of the indole scaffold was broken and a novel quinoxaline skeleton was constructed. This method allows the practical and atom-economical synthesis of valuable axially chiral aminoaryl quinoxalines in high yields (up to 95 %) and generally excellent enantioselectivities (up to 99 % ee). Notably, this novel type of quinoxaline atropisomers has promising applications in developing axially chiral ligand in asymmetric catalysis. This strategy represents the first example of CPA-catalyzed enantioselective isodesmic reaction to form axially chiral compounds.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
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