Synthesis and Structure of Intermediates in Copper-Catalyzed Alkylation of Diphenylphosphine

Cu(I) catalysts for alkylation of diphenylphosphine were developed. Treatment of [Cu(NCMe)₄][PF₆] (1) with chelating ligands gave [CuL(NCMe)][PF₆] (2; L = MeC(CH₂PPh₂)₃ (triphos), 3; L = 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (XantPhos)). These complexes catalyzed the alkylation of PHPh₂ with PhCH₂Br in the presence of the base NaOSiMe₃ to yield PPh₂CH₂Ph (4). The precursors Cu(dtbp)(X) (dtbp =2,9-di-t-butylphenanthroline, X = Cl (5) or OTf (6)), CuCl, and 1 also catalyzed this reaction, but dtbp dissociated from 5 and 6 during catalysis. Both 2 and 3 also catalyzed alkylation of PHPh₂ with PhCH₂Cl/NaOSiMe₃, but XantPhos dissociation was observed when 3 was used. When CH₂Cl₂ was used as the solvent for alkylation of PhCH₂Cl with precursors 2 or 3, or of PhCH(Me)Br with 2, it was competitively alkylated to yield PPh₂CH₂Cl (7), which was formed exclusively using 2 in the absence of a benzyl halide. Cu(triphos)-catalyzed alkylation of PhCH(Me)Br gave mostly PPh₂CHMePh (8), along with some Ph₂P-PPh₂ (9), which was also formed in attempted alkylation of dibromoethane with this catalyst. The phosphine complexes [Cu(triphos)(L′)][PF₆] (L′ = PH₂Ph (10), PH₂CH₂Fc (Fc = C₅H₄FeC₅H₅, 11), PHPh₂ (12), PHEt₂ (13), PHCy₂ (Cy = cyclo-C₆H₁₁, 14), PHMe(Is) (Is = 2,4,6-(i-Pr)₃C₆H₂, 15), PPh₂CH₂Ph (16), PPh₂CH₂Cl (17)), and [Cu(XantPhos)(L′)][PF₆] (L′ = PHPh₂ (18), PPh₂CH₂Ph (19)) were prepared by treatment of 2 and 3 with appropriate ligands. Similarly, treatment of dtbp complexes 5 or 6 with PHPh₂ gave [Cu(dtbp)(PHPh₂)(X)] (X = OTf (20a) or Cl (20b)), and reaction of PPh₂CH₂Ph (4) with 1 formed [Cu(PPh₂CH₂Ph)₃][PF₆] (21). Complexes 2, 3, 11−14, 16, 17, 19, and 21 were structurally characterized by X-ray crystallography. Deprotonation of diphenylphosphine complex 12 in the presence of benzyl bromide gave diphenylbenzylphosphine complex 16, while deprotonation of 12 in CD₂Cl₂ gave 17 containing a PPh₂CD₂Cl ligand. Low-temperature deprotonation of the soluble salt 12-[B(Ar_F)₄] (Ar_F = 3,5-(CF₃)₂C₆H₃) in THF-d₈ gave the phosphido complex Cu(triphos)(PPh₂) (22). Thermally unstable 22 was characterized by NMR spectroscopy and, in comparison to 12, by density functional theory (DFT) calculations, which showed it contained a polarized Cu−P bond. The ligand substitution step required for catalytic turnover was observed on treatment of 16 or 17 with PHPh₂ to yield equilibrium mixtures containing 12 and the tertiary phosphines 4 or 7; equilibrium constants for these reactions were 8(2) and 7(2), favoring complexation of the smaller secondary phosphine in both cases. These observations are consistent with a proposed mechanism for catalytic P−C bond formation involving deprotonation of the cationic diphenylphosphine complex [Cu(triphos)(PHPh₂)][PF₆] (12) by NaOSiMe₃ to yield the phosphido complex Cu(triphos)(PPh₂) (22). Nucleophilic attack on the substrate (benzyl halide or CH₂Cl₂) then yields the tertiary phosphine complex [Cu(triphos)(PPh₂CH₂X)][PF₆] (X = Ph (16) or Cl (17)), and ligand substitution with PHPh₂ regenerates 12.