Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N-N Axis†
Fang-Bei Ge
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
These authors contributed equally to this work.
Search for more papers by this authorQi-Kun Yin
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, 264005 China
These authors contributed equally to this work.
Search for more papers by this authorChuan-Jun Lu
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
These authors contributed equally to this work.
Search for more papers by this authorXuan Xuan
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, 264005 China
Search for more papers by this authorJia Feng
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
Search for more papers by this authorCorresponding Author
Ren-Rong Liu
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
E-mail: [email protected]Search for more papers by this authorFang-Bei Ge
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
These authors contributed equally to this work.
Search for more papers by this authorQi-Kun Yin
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, 264005 China
These authors contributed equally to this work.
Search for more papers by this authorChuan-Jun Lu
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
These authors contributed equally to this work.
Search for more papers by this authorXuan Xuan
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, Shandong, 264005 China
Search for more papers by this authorJia Feng
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
Search for more papers by this authorCorresponding Author
Ren-Rong Liu
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071 China
E-mail: [email protected]Search for more papers by this authorDedicated to the Special Issue of Emerging Investigators in 2024.
Comprehensive Summary
Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored; in particular, the synthesis of N-N benzimidazole atropisomers is still unprecedented. Herein, the first enantioselective synthesis of N-N benzimidazole atropisomers via the palladium-catalyzed de novo construction of benzimidazole skeleton is presented. With readily available palladium catalyst and biphosphine ligand, a broad range of nonbiaryl benzimidazole and indole-benzimidazole atropisomers were conveniently accessed in high yields and with excellent enantioselectivities. Significantly, these N-N benzimidazole atropisomers showed great antitumor activity and selectivity to breast cancer MCF-7 cells. The simple catalytic system, broad substrate scope, high enantioselectivity, and good bioactivity make this approach highly attractive.
Supporting Information
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| Cell lines | IC50 values of compound 4/(μmol·L–1) | |||
|---|---|---|---|---|
| 4t | 4s | (S)-4s | (S)-4t | |
| MCF-7 | 2.1 | 0.09 | 18.2 | 23.6 |
| B16 | > 50 | > 50 | > 50 | > 50 |
| A549 | > 50 | > 50 | > 50 | > 50 |
| HepG2 | > 50 | > 50 | > 50 | > 50 |
| HL7702 | > 50 | > 50 | > 50 | > 50 |
