Shining new light on the Ullmann reaction


 

ullmann

The proposed single electron transfer pathway for Ullmann C-N coupling © Science/AAAS

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-Tol3)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.


Related Content

Carbon–carbon couplings go 3D

8 June 2014 Research

news image

Reaction extends 2010 Nobel prize winning Suzuki coupling and can be used to modify natural products

Recruiting electrophiles for organic cross-coupling

12 April 2012 News Archive

news image

Cross-coupling with two electrophiles provides chemists with new ways to make carbon-carbon bonds

Most Read

UC Davis chemist sentenced to four years over explosion

19 November 2014 News and Analysis

news image

Postdoc sentenced over attempt to make explosive device and reckless disposal of hazardous waste

Spanish fly

10 October 2013 Podcast | Compounds

news image

Helen Scales looks at cantharidin, the active ingredient in this famous aphrodisiac

Most Commented

Beetle behind breath test for bank notes

17 November 2014 Research

news image

Photonic crystal inks inspired by longhorn beetle could help to fight counterfeiting

Toxicologists enter the fray on endocrine disruptors

29 July 2013 News and Analysis

news image

Open letter urges the European commission to consult with the scientific community before enacting any regulation