Pd-catalyzed asymmetric oxidative C-H/C-H cross-coupling reaction between dialkylaminomethylferrocenes and indolizines

• Published in: Chem catalysis Vol. 2; no. 1; pp. 102 - 113
• Main Authors: Liu, Chen-Xu, Zhang, Wen-Wen, Yang, Pusu, Zhao, Fangnuo, Feng, Zuolijun, Wang, Quannan, Zhang, Su-Zhen, Gu, Qing, You, Shu-Li
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.01.2022
• Subjects: asymmetric catalysis; C-H/C-H cross-coupling; ferrocene; indolizine; planar chirality; regioselectivity; planar chirality; regioselectivity; C-H/C-H cross-coupling; asymmetric catalysis; ferrocene; SDG9: Industry innovation and infrastructure; indolizine
• ISSN: 2667-1093; 2667-1093
• DOI: 10.1016/j.checat.2021.11.001

Oxidative C-H/C-H cross-coupling reactions between two (hetero)arenes through 2-fold C-H activation offer rapid assembly of diverse bi(hetero)aryls. Herein, a Pd-catalyzed asymmetric oxidative C-H/C-H cross-coupling reaction of ferrocenes with indolizines was disclosed. A palladium(II)/monoprotected amino acid (MPAA) catalytic system exhibited excellent reactivity, regioselectivity, and enantioselectivity for the coupling reaction. This approach marks the first example of direct arylation of indolizines in an enantioselective oxidative C-H/C-H cross-coupling process and offers a powerful strategy for the synthesis of highly enantioenriched planar chiral ferrocenes. [Display omitted] •Asymmetric oxidative C-H/C-H cross-coupling reaction of indolizines•Readily available Pd catalysts•Broad substrate scope and excellent functional group tolerance Over the past decades, various strategies have emerged to achieve C-H functionalization of indolizines. Despite challenges in reactivity, regioselectivity (C1/C3), and homodimerization of indolizines, our work discovered the first enantioselective C-H/C-H cross-coupling reaction involving ferrocenes and indolizines with high regio- and enantio-selectivities, and broad substrate scope. The current method was also compatible with substrates derived from complex natural products and pharmaceuticals. Mechanistically, detailed deuteration experiments were conducted for the understanding of the regioselectivity of this reaction. We anticipate that this asymmetric C-H activation protocol will have important implications for the functionalization of indolizines. Indolizine is an important N-fused heterocycle widely distributed in natural products, agrochemicals, pharmaceuticals, and organic functional materials. We developed the first enantioselective C-H/C-H cross-coupling reactions involving ferrocenes and indolizines with excellent functional group tolerance. This method is compatible with substrates derived from complex natural products and pharmaceuticals.