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

Abstract

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 .