Phosphinoferrocene Ureas: Synthesis, Structural Characterization, and Catalytic Use in Palladium-Catalyzed Cyanation of Aryl Bromides

Phosphinoferrocene ureas Ph2PfcCH2NHCONR2, where NR2 = NH2 (1a), NHMe (1b), NMe2 (1c), NHCy (1d), and NHPh (1e); 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 1e with [PdCl2(cod)] (cod = cycloocta-1,5-diene) afforded [PdCl­(μ-Cl)­(1eP)2]2 or [PdCl2(1eP)2]2 depending on the metal-to-ligand stoichiometry, whereas those with [PdCl­(η3-C3H5)]2 and [PdCl­(LNC)]2 produced the respective bridge cleavage products, [PdCl­(η3-C3H5)­(1eP)] and [PdCl­(LNC)­(1eP)] (LNC = [(2-dimethylamino-κN)­methyl]­phenyl-κC1). 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 1e 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.