Competitive and Selective Csp3Br versus Csp2Br Bond Activation in Palladium-Catalysed Suzuki Cross-Coupling: An Experimental and Theoretical Study of the Role of Phosphine Ligands

摘要

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.