Competitive and selective Csp3-Br versus Csp2-Br bond activation in palladium-catalysed Suzuki cross-coupling: An experimental and theoretical study of the role of phosphine ligands

Phosphine ligands have been demonstrated to have an effect on reactivity and selectivity in the competitive intramolecular palladium-catalysed Suzuki-Miyaura coupling of dibromo sulfoxide 1 a possessing two different hybridised electrophilic carbons. It was found that the bromine bond to the sp³-hybridised carbon is selectively replaced in the presence of unhindered phosphines such as PPh₃ or xantphos. The use of hindered phosphine ligands such as P(o-tol)₃ and P(1-naphthyl)₃ reversed the selectivity, conducting the cross-coupling at the Csp²-Br. Identical trends were observed in external competition experiments carried out with bromomethyl sulfoxide and different substituted bromoarenes. DFT and DFT/MM calculations showed that the selectivity observed is mainly due to the different facility of the ligands to dissociate. Bisphosphine catalysts favour coupling at the sp³ carbon, whereas monophosphine catalysts prefer the sp² carbon.