High-Activity Catalysts for Suzuki Coupling and Amination Reactions with Deactivated Aryl Chloride Substrates: Importance of the Palladium Source

A range of ortho-metalated catalysts with alkylphosphine ligands of the general formula
[Pd(X)(κ2N,C-C6H4CH2NMe2)(PR3)] have been synthesized, and the crystal structures of five
examples (R = Cy, X = TFA, OTf, Cl, I; PR3 = PCy2(o-biphenyl), X = TFA) have been
determined. The crystal structures of two dimeric precursor complexes, [{Pd(μ-TFA)(κ2N,C-C6H4CH2NMe2)}2] and [{Pd(TFA)(κ2N,C-C6H4CHNiPr)}2], have also been determined. The
application of the phosphine adducts to both Suzuki coupling and Buchwald−Hartwig
amination reactions with aryl chloride substrates was examined, and the performance of
these catalysts versus conventional palladium sources was evaluated. In general the
palladacyclic complexes show considerably enhanced activity. Typically, the best activity is
seen with tricyclohexylphosphine adducts in Suzuki coupling and tri-tert-butylphosphine
analogues in amination reactions. In nearly all the amination reactions performed, small
amounts of a second product species were observed, namely 4,6-bis(aryl)-3,4-dihydro-2H-[1,4]oxazines. The crystal structure of one example, 4,6-bis(4-methoxyphenyl)-3,4-dihydro-2H-[1,4]oxazine, was determined. Studies on the activation of palladacyclic precatalysts in
the coupling of morpholine led to the isolation of a morpholine adduct, [Pd(TFA)(κ2N,C-C6H5CH2NMe2){NH(CH2CH2)O}], which was structurally characterized by X-ray analysis.