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

Phosphinoferrocene ureas Ph<sub>2</sub>PfcCH<sub>2</sub>NHCONR<sub>2</sub>, where NR<sub>2</sub> = NH<sub>2</sub> (<b>1a</b>), NHMe (<b>1b</b>), NMe<sub>2</sub> (<b>1c</b>), NHCy (<b>1d</b>), and NHPh (<b>1e</b>); the analogous thiourea Ph<sub>2</sub>PfcCH<sub>2</sub>NHCSNHPh (<b>1f</b>); and the acetamido derivative Ph<sub>2</sub>PfcCH<sub>2</sub>NHCOMe (<b>1g</b>) (Cy = cyclohexyl, fc = ferrocene-1,1′-diyl) were prepared via three different approaches starting from Ph<sub>2</sub>PfcCH<sub>2</sub>NH<sub>2</sub>·HCl (<b>3</b>·HCl) or Ph<sub>2</sub>PfcCHO (<b>4</b>). The reactions of the representative ligand <b>1e</b> with [PdCl<sub>2</sub>(cod)] (cod = cycloocta-1,5-diene) afforded [PdCl­(μ-Cl)­(<b>1e</b>-κ<i>P</i>)<sub>2</sub>]<sub>2</sub> or [PdCl<sub>2</sub>(<b>1e</b>-κ<i>P</i>)<sub>2</sub>]<sub>2</sub> depending on the metal-to-ligand stoichiometry, whereas those with [PdCl­(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)]<sub>2</sub> and [PdCl­(L<sup>NC</sup>)]<sub>2</sub> produced the respective bridge cleavage products, [PdCl­(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)­(<b>1e</b>-κ<i>P</i>)] and [PdCl­(L<sup>NC</sup>)­(<b>1e</b>-κ<i>P</i>)] (L<sup>NC</sup> = [(2-dimethylamino-κ<i>N</i>)­methyl]­phenyl-κ<i>C</i><sup>1</sup>). Attempts to involve the polar pendant in coordination to the Pd­(II) center were unsuccessful, indicating that the phosphinoferrocene ureas <b>1</b> 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 <b>1e</b> in the presence of 1 equiv of Na<sub>2</sub>CO<sub>3</sub> as the base and half molar equivalent of K<sub>4</sub>[Fe­(CN)<sub>6</sub>]·3H<sub>2</sub>O. 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.