Selective activation of the ortho C?F bond in pentafluoropyridine by zerovalent nickel: Reaction via a metallophosphorane intermediate stabilized by neighboring group assistance from the pyridyl nitrogen

Density functional theory is used to explore the origins of the chemoselectivity and regioselectivity of activation of C?F bonds in pentafluoropyridine with [Ni(PR₃)₂] species. Experimentally, Ni-fluoride species are observed and activation occurs preferentially at the 2-position (i.e., the C?F bond ortho to the pyridyl nitrogen). This is in marked contrast to related platinum reagents, which form Pt-alkyl species featuring fluorophosphine ligands with activation occurring exclusively at the 4-position. Using a model nickel complex, [Ni(PMe ₃)₂], computed potential energy surfaces reveal two distinct types of reaction pathways: conventional oxidative addition and phosphine-assisted C?F bond activation. In the latter, the activated fluorine is transferred first to the phosphine ligand before migrating to the metal center. The phosphine-assisted routes lie substantially above their oxidative addition counterparts unless activation occurs at the 2-position, where coordination of the pyridyl nitrogen stabilizes both the metallophosphorane intermediate and the preceding transition state. The result is a lowering of the barrier such that the phosphine-assisted route becomes competitive with conventional oxidative addition. This "neighboring group acceleration" is unique to the phosphine-assisted pathway and, moreover, is unique to activation at the 2-position because it depends on the ability of the nitrogen to participate in a benzyne-like, pyridin-1,2-diyl coordination mode. © 2010 American Chemical Society.