Photoinduced C–N coupling provides more information on mechanistic pathways in widely used reaction

Ullmann C–N coupling – a copper mediated carbon–nitrogen coupling reaction used to create arylamines – is one of the most widely used reactions in the pharmaceutical industry. But while extensive work has been done on the chemistry of the reaction, until now it has generally been thought that the mechanism proceeds via a concerted oxidative addition to cleave off the aryl group. And there has been no evidence to contradict this, until Greg Fu and Jonas Peters at the California Institute of Technology, US, started collaborating that is.

Peters’ group had previously been working on photoluminescent copper complexes. ‘We made those compounds originally for another reason altogether and they happened to be extraordinarily luminescent, which you wouldn’t have expected at the time.’ Conversation between Peters and his students turned to whether these complexes could be used for photoinduced C–N coupling and led to the collaboration with Fu.

After tweaking the complexes to improve the solubility the team had a copper carbazolide complex, Cu(Pm-Tol 3 ) 3 , ready to test. Irradiating an acetonitrile solution of that complex with iodobenzene gave the coupling product, even at temperatures as low as -40°C.

Peters’ and Fu’s work, in showing that the reaction can also occur at low temperatures after irradiation, is the first evidence that the Ullmann reaction can, under some circumstances, proceed instead by a radical route.

However, whether this finding will lead to more or remain an intellectual curiosity is unclear. ‘It suggests that there’s more than one mechanism possible,’ says Stephen Buchwald from the Massachusetts Institute of Technology, US, explaining the relevance of the paper. Current Ullmann chemistry is extensively used and efficient, adds Buchwald, ‘but anytime anyone looks at a reaction in a different way there’s a possibility that it will open up better or different ways of doing things … I think this is a very interesting finding and could lead to very important additional things but we call it research because we don’t know.’

‘We have a very specific system,’ admits Peters, ‘but what one would like to know and pursue is can you use light to drive Ullmann C–N coupling of a wider substrate scope and are there other molecules that might lend themselves to this kind of approach?’ Unsurprisingly, that’s what Peters and Fu are now working on, expanding their findings and looking at triggering reactions using the excited states of copper complexes.