Rhodium(I) Carbene-Promoted Enantioselective C−H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights
Tian-Yi Wang
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and School of Pharmacy, University of Chinese Academy of Sciences, Shanghai, 201203 China
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
These authors contributed equally to this work.
Search for more papers by this authorXiao-Xuan Chen
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Dong-Xing Zhu
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and School of Pharmacy, University of Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorProf. Dr. Lung Wa Chung
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Ming-Hua Xu
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and School of Pharmacy, University of Chinese Academy of Sciences, Shanghai, 201203 China
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007 China
Search for more papers by this authorTian-Yi Wang
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and School of Pharmacy, University of Chinese Academy of Sciences, Shanghai, 201203 China
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
These authors contributed equally to this work.
Search for more papers by this authorXiao-Xuan Chen
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Dong-Xing Zhu
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and School of Pharmacy, University of Chinese Academy of Sciences, Shanghai, 201203 China
Search for more papers by this authorProf. Dr. Lung Wa Chung
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Ming-Hua Xu
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and School of Pharmacy, University of Chinese Academy of Sciences, Shanghai, 201203 China
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, 518055 China
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007 China
Search for more papers by this authorGraphical Abstract
A highly enantioselective C(sp2)−H functionalization of simple unprotected indoles, pyrroles, and their common analogues such as furans, thiophenes, and benzofurans by arylvinylcarbene insertion to access unique heteroarene-containing chiral diarylmethine derivatives has been developed for the first time. Mechanistic and DFT calculation studies revealed that the reductive elimination is the rate-determining step.
Abstract
A rhodium(I)-diene catalyzed highly enantioselective C(sp2)−H functionalization of simple unprotected indoles, pyrroles, and their common analogues such as furans, thiophenes, and benzofurans with arylvinyldiazoesters has been developed for the first time. This transformation features unusual site-selectivity exclusively at the vinyl terminus of arylvinylcarbene and enables a reliable and rapid synthetic protocol to access a distinctive class of diarylmethine-bearing α,β-unsaturated esters containing a one or two heteroarene-attached tertiary carbon stereocenter in high yields and excellent enantioselectivities under mild reaction conditions. Mechanistic studies and DFT calculations suggest that, compared to the aniline substrate, the more electron-rich indole substrate lowers the C−C addition barrier and alters the rate-determining step to the reductive elimination, leading to different isotope effect.
Conflict of interest
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 Supporting Information of this article.
Supporting Information
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| anie202207008-sup-0001-3af.cif275 KB | Supporting Information |
| anie202207008-sup-0001-5n.cif352.8 KB | Supporting Information |
| anie202207008-sup-0001-6b.cif459.1 KB | Supporting Information |
| anie202207008-sup-0001-misc_information.pdf11.7 MB | Supporting Information |
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