Decarboxylative C-4 Alkylation of Pyridines Enabled by Ground-state Hantzsch Ester

Abstract

Herein, we report a metal- and light-free C-4 alkylation of pyridines through a decarboxylative Minisci-type reaction between fumarate-derived pyridinium salts and aryliodine(III) dicarboxylates. In this protocol, an NADH analogue serves as the sole reductant for alkyl radical generation under ambient aerobic conditions, without photoexcitation or electrochemical input. A key feature of this design is the dual role of aryliodine(III) dicarboxylates, which function both as alkyl radical precursors and as oxidants for rearomatization, thereby eliminating the need for any external oxidant. The reaction proceeds in a simple “dump-and-stir” manner under mild conditions and provides an efficient and practical platform for the regioselective C-4 alkylation of pyridines from inexpensive and readily available starting materials.