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

Abstract

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-Pr 2 POPh with 0.6 equiv of [(i-PrCN)NiBr 2 ] n and 0.8 equiv of NEt 3 in toluene (100°C, 36 h) gave the yellow, monomeric cyclometalated complex trans-{κ 2 P,C-C 6 H 4 OP(iPr) 2 }Ni(i-Pr 2 POPh)Br (3a) in 93% yield. The closely related yellow-orange dimeric species [{κ 2 P,C-C 6 H 4 OP(i-Pr) 2 }Ni(μ-Br)] 2 (4a) was obtained in 70% yield when i-Pr 2 POPh was treated with 2 equiv each of the Ni precursor and NEt 3 . These complexes have been characterized fully and shown to interconvert in the presence of excess ligand (4a → 3a) or excess Ni precursor (3a → 4a). 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-Pr 2 POPh has shown that the first species formed from its ambient-temperature reaction with [(iPrCN)NiBr 2 ] n is trans-(i-Pr 2 POPh) 2 NiBr 2 (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 NEt 3 , implying the partial formation of an amine adduct. Heating toluene mixtures of 2a and NEt 3 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-Pr 2 POPh. The impact of phenol ring substituents on the C−H nickelation rate was probed by preparing substituted derivatives of 2a, trans-(4-R-C 6 H 4 OP(i-Pr 2 )} 2 NiBr 2 (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-C 6 H 4 OP(i-Pr 2 ) allowed us to establish that metalation is favored at the para position with respect to F (85:15).

C–H Nickelation of Aryl Phosphinites: Mechanistic Aspects

“…Thus, we succeeded in accessing the isolable and thermally stable ortho-metalated complexes {(κ P ,κ C -ArOPR 2 )Ni(μ-Br)} 2 and (κ P ,κ C -ArOPR 2 )Ni(L)Br (Chart 1; R = i-Pr) and then studied their structures, stabilities, and reactivities with electrophiles. 8 In addition to the aforementioned promising reactivities of aryl phosphinites, we should also note that these substrates present many advantages in the context of the proposed studies: they are derived from phenols, which are inexpensive and ubiquitous in organic synthesis; the PR 2 directing group is easily grafted onto phenols by reaction with ClPR 2 ; 31 P NMR spectroscopy provides a convenient and powerful method for monitoring reactions and detecting intermediates. These advantages compelled us to undertake detailed mechanistic studies on C−H cyclonickelation of aryl phosphinites.…”

NBO Orbital Interaction Analysis for the Ambiphilic Metal–Ligand Activation/Concerted Metalation Deprotonation (AMLA/CMD) Mechanism Involved in the Cyclopalladation Reaction ofN,N-Dimethylbenzylamine with Palladium Acetate

“…The cyclopalladation reaction involves C–H bond activation and knowledge gained on this process can help develop efficient methodology . In this regard, the mechanism of cyclopalladation has undergone scrutiny by NMR and is believed to involve an anagostic intermediate where the C–H bond lies above the palladium square plane without activation and then moves on to an agostic stage in the square plane of palladium where activation takes place .…”

Chasing the agostic interaction in ligand assisted cyclometallation reactions of palladium(ii)

“…Any knowledge gained from such studies should improve understanding of the important steps involved in catalytic C−H functionalization processes and help develop more efficient methodologies. 6 The key activation step in these ligand-directed C-H bond functionalizations is the weakening of the C-H bond and this is achieved by forming an agostic interaction 7 which lengthens the bond by donation of σ-bond electron density to the metal. Removal of the hydrogen can then be assisted by the presence of a proton accepting ligand such as in the case of Pd(OAc)2 8 or having a base present such as NaOAc.…”