It was proved by our experiments that on microwave irradiation, the mono‐ or bidentate phosphorus ligands generally applied in the palladium(II)‐catalyzed P–C coupling reaction of aryl bromides and dialkyl phosphites or secondary phosphine oxides may be substituted by the excess of the >P(O)H reagent that exists under a tautomeric equilibrium. Taking into account that the reduction of the palladium(II) salt and the ligation of the palladium(0) so formed requires 3 equivalents of the P‐species for the catalyst applied in a quantity of 5–10%, all together, 15–30% of the P‐reagent is necessary beyond its stoichiometric quantity. In the coupling reaction of diphenylphosphine oxide, it was possible to apply diethyl phosphite as the reducing agent and as the P‐ligand. The reactivities of the diethyl phosphite and diphenylphosphine oxide reagents were compared in a competitive reaction. The mechanism and the energetics of this new variation of the Hirao reaction of bromobenzene with Y2P(O)H reagents (Y=EtO and Ph) was explored by quantum chemical calculations. The first detailed study on simple reaction models justified our assumption that, under the conditions of the reaction, the trivalent form of the >P(O)H reagent may serve as the P‐ligand in the palladium(0) catalyst, and shed light on the fine mechanism of the reaction sequence. The existence of the earlier described bis(palladium complex) {[H(OPh2P)2PdOAc]2} was refuted by high level theoretical calculations. This kind of complex may be formed only with chloride anions instead of the acetate anion. The interaction of palladium acetate and Y2P(O)H may result in only the formation of the [(HO)Y2P]2Pd complex that is the active catalyst in the Hirao reaction. The new variation of the Hirao reaction is of a more general value, and represents the greenest protocol, as there is no need for the usual P‐ligands. Instead, the >P(O)H reagent should be used in an excess of up to 30%. Hence, the costs and environmental burdens may be decreased.

Background: The Hirao reaction discovered ca. 35 years ago is an important P–C coupling protocol between dialkyl phosphites and aryl halides in the presence of Pd(PPh3)4 as the catalyst and a base to provide aryl phosphonates. Then, the reaction was extended to other Preagents, such as secondary phosphine oxides and H-phosphinates and to other aryl and hetaryl derivatives to afford also phosphinic esters and tertiary phosphine oxides. Instead of the Pd(PPh3)4 catalyst, Pd(OAc)2 and Ni-salts were also applied as catalyst precursors together with a number of mono- and bidentate P-ligands. Objective: In our review, we undertook to summarize the target reaction with a special stress on the developments attained in the last 6 years, hence this paper is an update of our earlier reviews in a similar topic. Conclusion: “Greener” syntheses aimed at utilizing phase transfer catalytic and microwave-assisted approaches, even under “P-ligand-free. or even solvent-free conditions are the up-to date versions of the classical Hirao reaction. The mechanism of the reaction is also in the focus these days.

The microwave-assisted Hirao reaction of bromobenzene and diarylphosphine oxides was performed at 120 °C using triethylamine as the base, and 5% of palladium acetate as the catalyst in ethanol. 5% Excess of the >P(O)H reagent served as the reducing agent, while another 10% as the preligand (in the >POH tautomeric form). It was found that the P–C coupling reaction was significantly faster with (2-MeC6H4)2P(O)H (A) and (3,5-diMeC6H3)2P(O)H (B), than with Ph2P(O)H (C) and (4-MeC6H4)2P(O)H (D). Moreover, species A and B could be applied as selective P-ligands in the reaction of bromobenzene with C or D. Dependence of the effectiveness of “PdP2” catalysts with diarylphosphine oxide preligands on the methyl substituents followed a reversed order as the reactivity of the diarylphosphine oxide species in the P–C coupling itself. Formation of the “PdP2” catalyst from palladium acetate and diarylphosphine oxide has never been studied, but now it was evaluated by us at the B3LYP level of theory applying 6-31G(d,p) for C,H,P,O and SDD/MW28 for Pd including the explicit-implicit solvent model. The novel mechanism requiring three equivalents of the >P(O)H species for each of the palladium acetate molecule was in agreement with the preparative experiments. The ligation of palladium(0) with different P(III) species comprising the >POH form of the >P(O)H reagent was also studied, and the critical role of the steric hindrance on the ligation, and hence on the activity of the “PdP2” catalyst was substantiated. Last but not least, the influence of the Me substituents in the aromatic ring of the P-reagents on the energetics of the elemental steps of the Hirao reaction itself was also evaluated.

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The Hirao reaction, i.e. the P–C coupling between a bromoarene and a >P(O)H reagent performed in most cases in the presence of a Pd(0) complex incorporating a P-ligand may also be carried out applying a Ni(II) catalyst precursor with or without Zn or Mg as the reducing agent. The Ni catalysts may include P- or N-ligands. B3LYP/6-31G(d,p)//PCM(MeCN) quantum chemical calculations suggested that the mechanism of the NiX2 catalyzed (X=Cl or Br) P–C couplings performed in the absence of a reducing agent, and in the excess of the >P(O)H reagent serving as the P-ligand (via its tautomeric >POH form) is completely different from that of the Pd(OAc)2 promoted version, as no reduction of the Ni(II) occurs. In the two variations mentioned, the active catalyst is the dehydrobrominated species derived from primary complex [(HO)Y2P]2Ni(II)Br2, and the [(HO)Y2P]2Pd(0) complex itself, respectively. Both species undergo temporary oxidation (to “Ni(IV)” and “Pd(II)”, respectively) in the catalytic cycle. During the catalysis with “P2Ni(II)X2”, one of the P-ligands serves the >P(O)H function of the ArP(O)H <  product. The consequence of this difference is that in the Ni(II)-catalyzed case, somewhat less >P(O)H-species is needed than in the Pd(0)-promoted instance. Applying 10 % of the Pd(OAc)2 or NiX2 precursor, the optimum quantity of the P-reagent is 1.3 equivalent and, in the first approach, 1.1 equivalent, respectively. Preparative experiments justified the new mechanism explored. The ligation of Ni(II) was also investigated by theoretical calculations. It was proved that the bis-complexation is the most favorable energetically as compared to the mono-, tri- and tetra-ligation.