New Developments on the Hirao Reactions, Especially from “Green” Point of View

Abstract

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.

Microwaves as “Co-Catalysts” or as Substitute for Catalysts in Organophosphorus Chemistry

“…The Hirao reaction of aryl, heteroaryl, and vinyl halogenides (or other derivatives) with dialkyl phosphites, alkyl H -phosphinates, and secondary phosphine oxides is an important method for the synthesis of phosphonates, phosphinates, and phosphine oxides, respectively [ 117 , 118 , 119 ]. The original Hirao P–C coupling aimed at the synthesis of arylphosphonates reacting aryl- and vinyl halogenides with dialkyl phosphites in the presence of tetrakis(triphenylphosphine)palladium ( Scheme 12 ) [ 120 , 121 , 122 ].…”

Focusing on the Catalysts of the Pd- and Ni-Catalyzed Hirao Reactions

“…Let us survey the possible Pd complexes that were considered as catalysts in the Hirao reaction ( Figure 2 ). All agreed on that regarding the palladium salt precursors, Pd(OAc) 2 is the best choice due to its lipophilicity [ 10 , 12 ]. Although this salt consists of trimers or even polymers, its structure is generally represented as Pd(OAc) 2 .…”

“…To date, a number of variations of the P–C couplings were developed comprising in situ formed catalysts from suitable precursors, such as Pd(OAc) 2 and PdCl 2 , and different added mono- or bidentate P-ligands. The protocol was extended to H -phosphinates, as well as secondary phosphine oxides applying a wide range of arenes [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Later on, Ni- and Cu complexes were also used as catalysts [ 10 , 11 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

Denitrative Cross-Couplings of Nitrostyrenes

“…In parallel with the development of the cross-coupling yielding conjugated sulphones, analogous fruitful research on conjugated phosphonates was ongoing ( Scheme 24 and Scheme 25 ). These can be traditionally accessed by various well-established methods, such as Wittig reaction or the Hirao reaction [ 62 , 63 , 64 ]. Nevertheless, the direct coupling of nitrostyrene with dialkyl phosphites certainly enhanced the existing portfolio of the method, due to its unconventional and straightforward approach.…”