Phosphinoferrocene Ureas: Synthesis, Structural Characterization, and Catalytic Use in Palladium-Catalyzed Cyanation of Aryl Bromides
Abstrakt
Phosphinoferrocene ureas Ph2PfcCH2NHCONR2, where NR2 = NH2 (1a), NHMe (1b), NMe2 (1c), NHCy (1d), and NHPh (le); the analogous thiourea Ph2PfcCH2NHCSNHPh (1f); and the acetamido derivative Ph2PfcCH2NHCOMe (1g) (Cy = cyclohexyl, fc = ferrocene-1,1'-diyl) were prepared via three different approaches starting from Ph2PfcCH2NH2*HCl (3*HCl) or Ph2PfcCHO (4). The reactions of the representative ligand le with [PdCl2(cod)] (cod = cycloocta-1,5-diene) afforded [PdCl(mu-Cl)(1e-kappa P)2]2 or [PdCl2(1e-kappa P)2] depending on the metal-to-ligand stoichiometry, whereas those with [PdCl(eta(3)-C3H5)]2 and [PdCl(L-NC)]2 produced the respective bridge cleavage products, [PdCl(eta(3)-C3H5)(1e-kappa P)] and [PdCl(L-NC)(1e-kappa P)] (L-NC = [(2-dimethylamino-kappa N)methyl]phenyl-kappa C-1).
Attempts to involve the polar pendant in coordination to the Pd(II) center were unsuccessful, indicating that the phosphinoferrocene ureas 1 bind Pd(II) preferentially as modified phosphines rather than bifunctional donors. When combined with palladium(II) acetate, the ligands give rise to active catalysts for Pd-catalyzed cyanation of aryl bromides with potassium hexacyanoferrate(II).
Optimization experiments revealed that the best results are obtained in 50% aqueous dioxane with a catalyst generated from 1 mol % of palladium(II) acetate and 2 mol % of le in the presence of 1 equiv of Na2CO3 as the base and half molar equivalent of K4[Fe(CN)6]*3H2O. Under such optimized conditions, bromobenzenes bearing electron-donating substituents are cyanated cleanly and rapidly, affording the nitriles in very good to excellent yields.
In the case of substrates bearing electron-withdrawing groups, however, the cyanation is complicated by the hydrolysis of the formed nitriles to the respective amides, which reduces the yield of the desired primary product. Amine- and nitro-substituted substrates are cyanated only to a negligible extent, the former due to their metal-scavenging ability.