If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.



A Marriage Of Catalysts

Organic Synthesis: Photoredox, nickel catalyses merge in cross-coupling

by Bethany Halford
June 6, 2014 | A version of this story appeared in Volume 92, Issue 23

Two coupling reaction schemes.

By combining photoredox catalysis with nickel catalysis, chemists have managed to broaden the scope of cross-coupling reactions. The new method, developed independently by two different research teams, will allow molecule makers to readily form carbon-carbon bonds that were tough to forge with previously developed cross-coupling reactions.

Cross-coupling reactions have been transformational in their ability to construct carbon-carbon and carbon-heteroatom bonds, notes the University of Pennsylvania’s Gary A. Molander, one of the researchers who came up with the marriage of catalysis methods. “However, there are several well-known limitations of these reactions that are inextricably linked to the mechanism by which these reactions proceed,” he says.

Molander and his coworkers reasoned that by shifting the traditional two-electron cross-coupling mechanism to a one-electron process, they might be able to expand the scope of the reaction to include substrates such as sp3-hybridized carbons. These substrates typically undergo transmetalation too slowly to be reliable partners in cross-coupling.

The Penn chemists found that by combining an iridium photoredox catalyst with a nickel catalyst, they could cross-couple potassium alkoxyalkyl- and benzyltrifluoroborates with an array of aryl bromides under exceptionally mild conditions (Science 2014, DOI: 10.1126/science.1253647). They were also able to do the reactions asymmetrically in certain cases.

Princeton chemists led by David W. C. MacMillan and Abigail G. Doyle were thinking along the same lines. They similarly discovered that by combining an iridium photoredox catalyst with a nickel catalyst, they could couple amino acids, as well as α-oxygen- or phenyl-substituted carboxylic acids, with aryl halides. The reaction also works to directly cross-couple dimethylaniline with aryl halides via C–H functionalization (Science 2014, DOI: 10.1126/science.1255525).

“What photoredox catalysis allows us to do is to take a feedstock chemical, such as carboxylic acids on sp3-hybridized carbons, and bring it into the realm of a cross-coupling reaction,” Doyle explains.

“The outgrowth of this for the future is just enormous,” MacMillan adds. “There’s a litany of things to think about in terms of using nickel insertion chemistry and merging it with the massive range of photoredox processes.”

“I think both papers are very important contributions toward the goal of turning photoredox catalysis into a standard part of the synthetic chemistry toolbox,” comments Tehshik P. Yoon, an expert in organic synthesis at the University of Wisconsin, Madison. “There have already been some really great contributions in which transition-metal catalysis was combined with photoredox catalysis, but I think what makes these results striking is their generality. MacMillan and Doyle provide us with a new way to think about assembling essentially any benzylic amine; Molander similarly provides us with a new approach toward diarylmethanes. I think the potential impact of these methods on synthesis is exceptionally high.”



This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.