biostudies-literatureSun GQNIGMS NIH HHS67-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC10036166biostudies-literatureUnknown615(7950)Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds^1,2. Site-selective C-H functionalization would provide a direct way of making these medicinally active products^3-5. For example, nicotinic acid derivatives could be made by C-H carboxylation, but this remains an elusive transformation^6-8. Here we describe the development of an electrochemical strategy for the direct carboxylation of pyridines using CO₂. The choice of the electrolysis setup gives rise to divergent site selectivity: a divided electrochemical cell leads to C5 carboxylation, whereas an undivided cell promotes C4 carboxylation. The undivided-cell reaction is proposed to operate through a paired-electrolysisNatureElectrochemical reactor dictates site selectivity in N-heteroarene carboxylations.PMC10036166R24 GM146107P41 GM103521R01 GM130928Zhang WLin SLiao LLZhang ZYu PLu ZSun GQWang YYu DGLi LfalseElectrochemical reactor dictates site selectivity in N-heteroarene carboxylations.Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds^1,2. Site-selective C-H functionalization would provide a direct way of making these medicinally active products^3-5. For example, nicotinic acid derivatives could be made by C-H carboxylation, but this remains an elusive transformation^6-8. Here we describe the development of an electrochemical strategy for the direct carboxylation of pyridines using CO₂. The choice of the electrolysis setup gives rise to divergent site selectivity: a divided electrochemical cell leads to C5 carboxylation, whereas an undivided cell promotes C4 carboxylation. The undivided-cell reaction is proposed to operate through a paired-electrolysis2023-01-01T00:00:00Z2023 Mar2025-04-22T15:05:37.547Z2025-04-06T01:18:31.113ZS-EPMC100361663660381110.1038/s41586-022-05667-0