Ortho Derivatization of Phenols through C–H Nickelation: Synthesis, Characterization, and Reactivities of Ortho-Nickelated Phosphinite Complexes

Reported here are the synthesis and characterization of ortho-nickelated complexes derived from phosphinite ligands and investigated as model compounds in the development of C–H functionalization strategies for arenol substrates. Reaction of i-Pr2POPh with 0.6 equiv of [(i-PrCN)­NiBr2]n and 0.8 equiv of NEt3 in toluene (100 °C, 36 h) gave the yellow, monomeric cyclometalated complex trans-{κ2P,C-C6H4OP­(i-Pr)2}­Ni­(i-Pr2POPh)Br (3a) in 93% yield. The closely related yellow-orange dimeric species [{κ2P,C-C6H4OP­(i-Pr)2}­Ni­(μ-Br)]2 (4a) was obtained in 70% yield when i-Pr2POPh was treated with 2 equiv each of the Ni precursor and NEt3. These complexes have been characterized fully and shown to interconvert in the presence of excess ligand (4a3a) or excess Ni precursor (3a4a). Treatment of 3a or 4a with benzyl bromide at 90 °C over extended periods led to benzylation of the Ni–aryl moiety in these complexes. Examination of the cyclometalation pathway for i-Pr2POPh has shown that the first species formed from its ambient-temperature reaction with [(i-PrCN)­NiBr2]n is trans-(i-Pr2POPh)2NiBr2 (2a). NMR studies showed that 2a undergoes a rapid ligand exchange at room temperature, which can be slowed down at −68 °C; this fluxional process shifts in the presence of NEt3, implying the partial formation of an amine adduct. Heating toluene mixtures of 2a and NEt3 at 90 °C for 38 h led to the formation of 3a via C–H nickelation. That phosphinite dissociation from 2a precedes the C–H nickelation step is implied by the observation that the formation of 3a is hindered in the presence of excess i-Pr2POPh. The impact of phenol ring substituents on the C–H nickelation rate was probed by preparing substituted derivatives of 2a, trans-(4-R-C6H4OP­(i-Pr2)}2NiBr2 (R = OMe (2b), Me (2c), COOMe (2d)), and measuring their relative rates of C–H nickelation. These studies showed that the formation of cyclonickelated products is favored in the order COOMe < Me < OMe, which is consistent with an electrophilic nickelation mechanism. Studying the C–H nickelation of 3-F-C6H4OP­(i-Pr2) allowed us to establish that metalation is favored at the para position with respect to F (85:15).