Bromophenyl-Diphenylphosphine Oxides as Novel Starting Materials in the Suzuki–Miyaura and the Hirao Cross-Couplings, as well as in the Michaelis–Arbuzov Reaction

High Resolution Image Download MS PowerPoint Slide 4- and 3-Bromophenyl-diphenylphosphine oxides prepared by us in a selective P–C coupling reaction offered themselves as excellent new starting materials in the Suzuki–Miyaura C–C and in the Hirao P–C cross-coupling reactions, as well as in the Michaelis–Arbuzov reaction. Novel bis (>P(O))-functionalized aromatics are the valuable products of the two latter phosphinoylations. The three transformations outlined were performed by applying metal catalysts (mainly Pd, but Ni may also be suitable) under microwave irradiation. Twenty-three, mostly new, P-functionalized aromatics were made available and fully characterized. On the other hand, the effect of the substituents in the aromatic ring on the reactivity, as well as the mechanism and energetics of the reactions, was studied by density functional theory calculations at the B3LYP/6-31G(d,p) level of theory. As regards the C–C cross-coupling, the 4- and 3-Ph 2 P(O)-substitution had only a minor effect on the value of the activation energy. In the transition metal-catalyzed Arbuzov reaction, the initial oxidative addition step shows comparable activation barriers for all investigated systems. However, in the subsequent steps, including the elimination of MeBr and the reductive elimination step, both the intermediates and transition states exhibit much larger differences in relative Gibbs free energy, which probably causes the observed differences in reactivity of the 4- and 3-Ph 2 P(O)-substituted models, as compared to the unsubstituted case. The elimination of MeBr has the highest Gibbs free energy requirement during the process. This high energy barrier may be overcome by the beneficial effects of microwave irradiation. In the Hirao cross-coupling, the 4-Ph 2 P(O)-substitution resulted in a decrease in the barrier of the oxidative addition step, whereas both the 3-Ph 2 P(O)-substitution and the electron-sending 4-Me- and 4-MeO-substituents led to a slight increase in the barrier. The theoretical data were in accord with the experimental findings.