Rhodium(I)-Catalyzed Enantioselective C(sp3)—H Functionalization via Carbene-Induced Asymmetric Intermolecular C—H Insertion†
Bo Liu
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong, 518055 China
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203 China
Search for more papers by this authorCorresponding Author
Ming-Hua Xu
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong, 518055 China
E-mail: [email protected]Search for more papers by this authorBo Liu
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong, 518055 China
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203 China
Search for more papers by this authorCorresponding Author
Ming-Hua Xu
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Shenzhen, Guangdong, 518055 China
E-mail: [email protected]Search for more papers by this author† Dedicated to Department of Chemistry, SUSTech, on the Occasion of Her 10th Anniversary.
Main observation and conclusion
Transition-metal-catalyzed C—H insertion of metal-carbene represents an excellent and powerful approach for C—H functionalization. However, despite remarkable advances in metal-carbene chemistry, transition metal catalysts that are capable of enantioselective intermolecular carbene C—H insertion are mainly constrained to dirhodium(II) and iridium(III)-based complexes. Herein, we disclose a new version of asymmetric carbene C—H insertion reaction with rhodium(I) catalyst. A highly enantioselective rhodium(I) complex-catalyzed C(sp3)—H functionalization of 1,4-cyclohexadienes with α-aryl-α-diazoacetates was successfully developed. By using chiral bicyclo[2.2.2]-octadiene as ligand, rhodium(I)-carbene-induced asymmetric intermolecular C—H insertion proceeds smoothly at room temperature, allowing access to a diverse variety of α-aryl-α-cyclohexadienyl acetates and gem-diaryl-containing acetates in good yields with good to excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the reaction was highlighted by facile synthesis of a novel cannabinoid CB1 receptor ligand. This method may offer a new opportunity for the development of therapeutically exploitable cannabinoid receptor type ligands in medicinal chemistry. 
Supporting Information
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Appendix S1: Supporting Information |
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