A Strategic Advance from Pincer Complexes to Hexadentate‐Co(III) Catalyst for Metal–Ligand Cooperative Activation of Primary Alcohols to Access Highly Functionalized Pyrimidines

In this report, we present a sustainable, eco-friendly, practical, and cost-effective one-pot three-component reaction for the synthesis of a diverse library of highly substituted pyrimidines from amidines, primary alcohols, and aromatic ketones, catalyzed by a cobalt(III) complex. The well-defined cobalt(III) complex [Co(III)BPMAP-O]ClO₄ is derived from a redox-active phosphine-free, pentadentate mono-carboxamide ligand (BPMAP-H), and is formed in situ from various cobalt(II) sources, including CoCl₂·6H₂O, CoBr₂, Co(NO₃)₂·6H₂O, Co(OAc)₂·4H₂O via oxygen activation. Using aromatic ketones and benzyl alcohols, a wide range of 2,4,6-trisubstituted pyrimidines (TriPym) and 2,4,5,6-tetrasubstituted pyrimidines (TetraPym) were synthesized (119 examples) in isolated yields of up to 93%. The catalytic system is also applicable to aliphatic ketones and aliphatic primary alcohols, affording 31 additional examples with yields of up to 92%. Control experiments and DFT calculations support a plausible mechanism involving dehydrogenation of the alcohols through a metal-ligand cooperative pathway.