Direct Catalytic Asymmetric and Regiodivergent N1- and C3-Allenylic Alkylation of Indoles |
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| Authors: | Taochun Zha Jiehui Rui Zhihan Zhang Dongqiang Zhang Zhirong Yang Peiyuan Yu Yingcheng Wang Fangzhi Peng Prof Zhihui Shao |
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| Institution: | 1. 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;2. Department of Chemistry and Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 China |
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| 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. |
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| Keywords: | Allenylic Alkylation Asymmetric Synthesis Indoles Kinetic Resolution Regiodivergence |
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