A Study on the Reactivity of Monosubstituted Benzenes in the MW-Assisted Pd(OAc)2-catalyzed Hirao Reaction with Ph2P(O)H and (EtO)2P(O)H Reagents

The reactivity order of “iodobenzene > bromobenzene > phenyl trifluoromethanesulfonate” was established in microwave (MW)-assisted Pd(OAc)2-catalyzed P–C coupling reactions with diphenylphosphine oxide and diethyl phosphite, where the excess of the these >P(O)H reagents served as the reducing agent, and, via its tautomeric >P-OH form, also as the P-ligand. The P–C coupling of Ph2P(O)H with PhBr at 120 °C took place via an induction period, during which the active “P-Pd-P” catalyst was formed from the Pd(II) salt and the >P(O)H species. The lower reactivity of PhBr towards Ph2P(O)H could be promoted by the addition of 20% of KI to the reaction mixture at 120 °C, or utilizing 1 equivalent of KI after a pre-reaction with PhBr at 120-150 °C followed by the P–C coupling at 100 °C. The reactivity of PhOTf and a bromo analogue was compared in competitive couplings with Ph2P(O)H. Beyond this, the reactivity of Ph2P(O)H and (EtO)2P(O)H towards PhOTf was evaluated in another competitive experiment. Increasing the scale of the P–C coupling reaction of (EtO)2P(O)H with PhBr, the quantity for the components of the catalyst could be decreased.