Convenient and efficient access to tri- and tetra-substituted 4-fluoropyridines via a [3 + 2]/[2 + 1] cyclization reaction

• Published in: Chinese chemical letters 2022-06, Vol.33 (6), p.2982-2986
• Main Authors: Tang, Xuejiao, Liu, Kun, Qu, Zeming, Zhan, Junyan, Zhu, Rukui, Teng, Fan, Meng, Lili, Huang, Yanmin, Huang, Chusheng, He, Yimiao, Zhu, Qiang
• Format: Article
• Language: English
• Subjects: 4-Fluoropyridine; [3 + 2]/[2 + 1] cyclization reaction; DMSO as an oxidant; gem-Difluorocyclopropene; PKM2 modulator; Regioselectivity
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2022.02.031

A [3 + 2]/[2 + 1] cycloaddition reaction of gem‑difluorocyclopropenes is presented, offering a mild and efficient approach to accessing tri- and tetra-substituted 4-fluoropyridines in moderate to good yields with excellent regioselectivity. Multiple synthetic applications, including process-scale reactions, modification of bioactive molecules, derivatization reactions and synthesis of the analogue of the PKM2 modulator, are subsequently described. An [3 + 2]/[2 + 1] cycloaddition reaction of gem‑difluorocyclopropenes is presented, offering a mild and efficient approach to accessing tri- and tetra-substituted 4-fluoropyridines in moderate to good yields with excellent regioselectivity. Multiple synthetic applications, including process-scale reactions, modification of bioactive molecules, derivatization reactions and synthesis of the analogue of the PKM2 modulator, are subsequently described [Display omitted] .