Direct Catalytic Asymmetric and Regiodivergent N1- and C3-Allenylic Alkylation of Indoles
Taochun Zha
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorJiehui Rui
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorZhihan Zhang
Department of Chemistry and Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 China
Search for more papers by this authorDongqiang Zhang
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorZhirong Yang
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorCorresponding Author
Peiyuan Yu
Department of Chemistry and Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 China
Search for more papers by this authorYingcheng Wang
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorFangzhi Peng
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorCorresponding Author
Prof. Zhihui Shao
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorTaochun Zha
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorJiehui Rui
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorZhihan Zhang
Department of Chemistry and Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 China
Search for more papers by this authorDongqiang Zhang
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorZhirong Yang
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorCorresponding Author
Peiyuan Yu
Department of Chemistry and Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 China
Search for more papers by this authorYingcheng Wang
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorFangzhi Peng
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorCorresponding Author
Prof. Zhihui Shao
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091 China
Search for more papers by this authorGraphical Abstract
We report the first direct catalytic asymmetric N1-functionalization of 1H-indoles via an allenylic alkylation strategy. This transformation produces N-alkylated indoles bearing axial chirality with a stereocenter non-adjacent (β) to the nitrogen. The regioselectivity (N1/C3) of this process can be switched efficiently. We also introduce a new class of tri-substituted allenylic electrophiles.
Abstract
Herein we report a Pd-catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H-indoles by employing P-chiral BIBOP-type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs2CO3 at elevated temperatures in MeCN, N1-alkylated indoles bearing axial chirality with a stereocenter non-adjacent (β) to the nitrogen are produced in good yields with high enantioselectivity and complete N1-regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K2CO3 at room temperature in CH2Cl2, chiral C3-alkylated indoles can also be obtained. Notably, we introduce a new class of tri-substituted allenylic electrophiles that proceeded through different pathways from di-substituted allenylic electrophiles.
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 from the corresponding author upon reasonable request.
Supporting Information
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| anie202300844-sup-0001-4j.cif769.8 KB | Supporting Information |
| anie202300844-sup-0001-7a.cif501.6 KB | Supporting Information |
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