Synthesis of a Polar Phosphinoferrocene Amidosulfonate Ligand and Its Application in Pd-Catalyzed Cross-Coupling Reactions of Aromatic Boronic Acids and Acyl Chlorides in an Aqueous Medium
Abstrakt
The reaction of [1'-(diphenylphosphino)ferrocenyl]methylamine (1), generated in situ from its hydrochloride and triethylamine, with 2-sulfobenzoic anhydride afforded an anionic phosphino-amide, which was isolated as a triethylammonium salt, Ph2PfcCH2NHCOC6H4SO3(HNEt3) (2; fc = ferrocene-1,1'-diyl). A similar reaction of 1 with phthalic anhydride only furnished the salt (Ph2PfcCH2NH3)[C6H4CO2H(CO2)].
When it was reacted with [PdCl2(MeCN)(2)] and [(LPd)-Pd-NC(mu-Cl)](2) (L(NC) = 2-[(dimethylamino-kappaN)methyl]phenyl-kappaC-1), compound 2 gave rise to the bisphosphine complex [PdCl2(2-kappa P)2] and the bridge-cleavage product [L(NC)PdCl(2-kappa P)], respectively. An analogue of the latter complex containing 2'-amino-[1,1'-biphenyl]-2-yl-kappaN-2,C-2 as the auxiliary chelating ligand, compound 8, was prepared in a similar manner from 2 and the respective Pd precursor.
Finally, the reaction of 2 with [L(NC)Pd(acac)] proceeded with the replacement of the acetylacetonate ligand (acac), affording a dipalladium complex featuring two phosphinosulfonate anions as the O,P-bridges, [L(NC)Pd(mu(P,O)-Ph2PfcCH2NHCOC6H4SO3)](2), which was structurally characterized by single-crystal X-ray diffraction analysis. All of these Pd(II) complexes, especially compound 8, formed active catalysts for Pd-mediated cross-coupling of aromatic boronic acids with benzoyl chlorides to produce substituted benzophenones in toluene (benzene) water biphasic mixtures.
This particular coupling reaction was employed during the preparation of 4'-chloro-4-hydroxybenzophenone, which was in turn converted to fenofibrate, a generic drug widely used to reduce cholesterol levels in blood.