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.

The reaction of [1′-(diphenylphosphino)ferrocenyl]methylamine (<bold>1</bold>), 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) (<bold>2</bold>; fc = ferrocene-1,1′-diyl). A similar reaction of <bold>1</bold> with phthalic anhydride only furnished the salt (Ph2PfcCH2NH3)[C6H4CO2H(CO2)]. When it was reacted with [PdCl2(MeCN)2] and [LNCPd(μ-Cl)]2 (LNC = 2-[(dimethylamino-κ<italic>N</italic>)methyl]phenyl-κ<italic>C</italic>1), compound <bold>2</bold> gave rise to the bis-phosphine complex [PdCl2(<bold>2</bold>-κ<italic>P</italic>)2] and the bridge-cleavage product [LNCPdCl(<bold>2</bold>-κ<italic>P</italic>)], respectively. An analogue of the latter complex containing 2′-amino-[1,1′-biphenyl]-2-yl-κ2<italic>N</italic>,<italic>C</italic>2 as the auxiliary chelating ligand, compound <bold>8</bold>, was prepared in a similar manner from <bold>2</bold> and the respective Pd precursor. Finally, the reaction of <bold>2</bold> with [LNCPd(acac)] proceeded with the replacement of the acetylacetonate ligand (acac), affording a dipalladium complex featuring two phosphinosulfonate anions as the O,P-bridges, [LNCPd(μ(P,O)-Ph2PfcCH2NHCOC6H4SO3)]2, which was structurally characterized by single-crystal X-ray diffraction analysis. All of these Pd(II) complexes, especially compound <bold>8</bold>, 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. [ABSTRACT FROM AUTHOR]