Year: 2026
Type: preprint
Abstract: Direct C(sp3)–H functionalization of methylpyridines is intrinsically challenging. Herein, we report a transition-metal-free, silylboronate-mediated heterobenzylation of methylpyridines with aryl fluorides. The combination of a silylboronate and KOtBu enables direct C(sp3)–H/C(sp2)–F coupling under mild conditions, providing efficient access to structurally diverse azaarylmethanes. The reaction accommodates π-extended aryl fluorides, polyfluoroarenes, and various 4-alkylpyridines, including substrates bearing multiple potentially reactive C–H or C–F bonds, with useful levels of chemo- and regioselectivity. The method is also applicable to the late-stage functionalization of structurally complex molecules. Alkyl fluorides are also compatible via the C(sp3)–H/C(sp3)–F coupling reaction. Mechanistic studies, including aryl-halide comparison, radical-trapping, investigation of pronucleophile, Hammett plot, competition experiments, and DFT calculation support an ionic pathway involving generation of a heterobenzylic nucleophile followed by nucleophilic substitution of the C–F bond. For electronically neutral and electron-rich aryl fluorides, the observed reactivity is consistent with a concerted SNAr pathway. This strategy provides a complementary approach to conventional transition-metal-catalyzed heterobenzylic arylation and expands the synthetic utility of organofluorine compounds as coupling partners for C–C bond formation.
Source: ChemRxiv
Authors: Seishu Ochiai, Zhengyu Zhao, Norio Shibata
Institution: Nagoya Institute of Technology
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223168248