Studies on the Optimization of Buchwald-Hartwig Amination of Aryl Halides

Abstract

Developing new catalyst systems for cross-coupling reactions such as Buchwald-Hartwig aminations has been one of the remarkable topics in the palladium-catalyzed, cross-coupling reaction research area. In this thesis, the use of the easily synthesized and handled Pd(η3-1-Ph-C3H4)(η5-C5H5) (I) as a catalyst precursor for Buchwald-Hartwig amination of aryl halides was investigated utilizing various phosphines (PtBu3, Xphos and Mor-Dalphos), different phosphine (L) to Pd ratios (L:Pd = 2:1 and 1:1) and different procedures; in situ generation of PdLn prior to addition of other reactants (Method A) and in situ generation of PdLn in the presence of aryl halide but prior to the addition of other reactants (Method B). The reaction profiles are monitored by gas chromatography (GC) and the effect of each of the mentioned parameters on the reaction rate is determined. The reaction profiles of I with various phosphines are also compared with those of other precursors, Pd2(dba)3, Pd(OAc)2 and [Pd(η3-1-Ph-C3H4)Cl]2 (IV). In spite of a large number of studies involving modification of Buchwald-Hartwig amination reactions by developing new precursors and phosphines, fewer studies have been carried out on catalytic mechanisms and there is still ambiguity about the catalytically active species in these palladium-catalyzed reactions. This study on a representative Buchwald-Hartwig amination finds that, in Buchwald-Hartwig aminations, various species might be participating as the catalytically active species via various mechanisms, utilizing different catalyst systems. This finding is contrary to the observations for other cross-coupling reactions such as Suzuki-Miyaura and Mizoroki-Heck in which the efficient formation of putative PdL2 from Pd(η3-1-Ph-C3H4)(η5-C5H5) (I) resulted in higher initial rates and higher conversions under mild reaction conditions, than other common precatalysts (Pd(OAc)2, Pd(PPh3)4, Pd2dba3, etc.) containing a variety of phosphine ligands. Therefore, to further our studies, the solution chemistry of I and IV with PtBu3, XPhos and Mor-DalPhos has been studied by 1H NMR and 31P NMR spectroscopy. All intermediates observed were characterized by NMR spectroscopy.