Alkoxide−Bridged Dicobalt(II) Compounds as Precatalysts for C−H Borylation and Application to Late-Stage Functionalization

Treatment of K₂[Co₂(O^tBu)₆] with a series of imidazolium salts, ^RACNC-(HBr)₂, provided a route to sterically modified t-butoxide-bridged cobalt compounds, (^RACNC)Co₂(O^tBu)₄ (^RACNC = N-alkyl-substituted pyridine dicarbene). Characterization by X-ray diffraction and SQUID magnetometry established non-interacting and high-spin dicobalt structures with bridging and terminal alkoxide ligands where the ACNC pincer spans both idealized tetrahedral cobalt atoms. In the presence of excess tert-butyl ethylene (TBE) and B₂Pin₂, the (^RACNC)Co₂(O^tBu)_4, derivatives served as precatalysts for the borylation of electron-rich arenes. Side-by-side comparison enabled the identification of a second-generation pre-catalyst, (^EtACNC)Co₂(O^tBu)₄, which displayed improved activity for the borylation of substrates bearing large R groups and aryl-CH₃ groups and improved meta selectivity for phenol, aniline, and alkyl benzene derivatives. When applied to biologically active molecules, 11 late-stage functionalizations were achieved, followed by a series of hydroxylations and deuterations, highlighting the application of the developed precatalysts for pharmaceutical research and development. In operando monitoring of the catalytic borylation and the observed site selectivities support formation of monomeric, pincer-supported cobalt(I) complexes as the active catalyst.