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
(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 [LNCPd­(μ-Cl)]2 (LNC = 2-[(dimethylamino-κN)­methyl]­phenyl-κC1), compound 2 gave rise to the
bis-phosphine complex [PdCl2(2-κP)2] and the bridge-cleavage product [LNCPdCl­(2-κP)], respectively. An
analogue of the latter complex containing 2′-amino-[1,1′-biphenyl]-2-yl-κ2N,C2 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 [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 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.