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>i</i>-Pr<sub>2</sub>POPh with 0.6 equiv of [(<i>i</i>-PrCN)­NiBr<sub>2</sub>]<sub><i>n</i></sub> and 0.8 equiv of NEt<sub>3</sub> in toluene (100 °C, 36 h) gave the yellow, monomeric cyclometalated complex <i>trans</i>-{κ<sup>2</sup><i>P</i>,<i>C</i>-C<sub>6</sub>H<sub>4</sub>OP­(<i>i</i>-Pr)<sub>2</sub>}­Ni­(i-Pr<sub>2</sub>POPh)Br (<b>3a</b>) in 93% yield. The closely related yellow-orange dimeric species [{κ<sup>2</sup><i>P</i>,<i>C</i>-C<sub>6</sub>H<sub>4</sub>OP­(<i>i</i>-Pr)<sub>2</sub>}­Ni­(μ-Br)]<sub>2</sub> (<b>4a</b>) was obtained in 70% yield when <i>i</i>-Pr<sub>2</sub>POPh was treated with 2 equiv each of the Ni precursor and NEt<sub>3</sub>. These complexes have been characterized fully and shown to interconvert in the presence of excess ligand (<b>4a</b> → <b>3a</b>) or excess Ni precursor (<b>3a</b> → <b>4a</b>). Treatment of <b>3a</b> or <b>4a</b> 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>i</i>-Pr<sub>2</sub>POPh has shown that the first species formed from its ambient-temperature reaction with [(<i>i</i>-PrCN)­NiBr<sub>2</sub>]<sub><i>n</i></sub> is <i>trans</i>-(<i>i</i>-Pr<sub>2</sub>POPh)<sub>2</sub>NiBr<sub>2</sub> (<b>2a</b>). NMR studies showed that <b>2a</b> undergoes a rapid ligand exchange at room temperature, which can be slowed down at −68 °C; this fluxional process shifts in the presence of NEt<sub>3</sub>, implying the partial formation of an amine adduct. Heating toluene mixtures of <b>2a</b> and NEt<sub>3</sub> at 90 °C for 38 h led to the formation of <b>3a</b> via C–H nickelation. That phosphinite dissociation from <b>2a</b> precedes the C–H nickelation step is implied by the observation that the formation of <b>3a</b> is hindered in the presence of excess <i>i</i>-Pr<sub>2</sub>POPh. The impact of phenol ring substituents on the C–H nickelation rate was probed by preparing substituted derivatives of <b>2a</b>, <i>trans</i>-(4-R-C<sub>6</sub>H<sub>4</sub>OP­(<i>i</i>-Pr<sub>2</sub>)}<sub>2</sub>NiBr<sub>2</sub> (R = OMe (<b>2b</b>), Me (<b>2c</b>), COOMe (<b>2d</b>)), 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-C<sub>6</sub>H<sub>4</sub>OP­(<i>i</i>-Pr<sub>2</sub>) allowed us to establish that metalation is favored at the para position with respect to F (85:15).