Pd(II)/Cu(I) Co-catalyzed Dual C-H Functionalization of Indoles at C2 and C3 Positions Using Bifunctional
Jiahui Huang1, Xiujuan Ai1, Shuai Zhou1
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
Abstract:
A Pd(II)/Cu(I) co-catalyzed dual C-H functionalization strategy enables the one-pot synthesis of C2/C3-difunctionalized indoles using arylsulfonyl reagents. In this method, Cu(I) reduces S(VI) reagents to generate arylsulfonyl radicals, which react with Pd(II) to form electrophilic Ar-Pd(III) intermediates. These intermediates regioselectively arylate indoles at the C2 position, followed by Cu(II)-mediated C-H functionalization at the C3 position, to deliver the final products. This synergistic method enhances efficiency, reduces waste, and streamlines complex indole functionalization.
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