Switching Catalyst Selectivity

Palladium-catalysed reactions are of key importance in synthetic chemistry, being widely applied in pharmaceutical and agrochemical sectors of industry. In particular, cross-coupling reactions offer a straightforward way of converting carbon-halogen bonds into new carbon-carbon bonds, building-up the complexity of molecular frameworks. However, achieving the desired selectivity in systems that have multiple halogen atoms, each of which can be a potential reaction site, can be extremely challenging.

In recent work published in Journal of the American Chemical Society, Professor Ian Fairlamb, working in collaboration with Dr Charlotte Willans from University of Leeds and Dr Mark Ford from Bayer AG has explored innovative ways in which the selectivity of such reactions can be controlled.

In particular, the researchers discovered that the selectivity of very well-established catalyst systems could be completely changed by making very small changes to the reaction conditions. Specifically, they found that for reactions of 2,4-dibromopyridine, the reactive site could be switched from the 2-position to the 4-position by decreasing the amount of triphenylphosphine ligand and adding a simple tetraalkylammonium salt.

Careful studies by the team led them to conclude that the small change in reaction conditions converted the catalyst from a mononuclear species with a single palladium centre (red, see Figure), to a palladium cluster (blue, see Figure). This change in catalyst speciation led to the resulting switch in reaction selectivity.

Professor Ian Fairlamb explains: “I think that in general, researchers in this area should be screening a range of palladium catalysts with different speciation – something that is rarely considered. As we show here, the results can be very interesting and potentially widen the scope of what can be achieved in this important class of reaction, generating different, unexpected products from the same starting material in a controllable way.”

He goes on to add: “General rules about palladium catalyst speciation are not so easy to develop, but we are working hard towards that goal. Furthermore, future research in Pd-catalyzed cross-coupling chemistry needs to focus on using very low palladium loadings, particularly with sustainability and cost in mind – we therefore need to do everything we can to enable catalyst systems to do more using less.”

The research is published in Journal of the American Chemical Society and has recently been featured in Nature Reviews Chemistry.