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.



Green Cross-Coupling Affordably Sized Up

Aryldiazonium salts provide an alternative to aryl halides and use milder conditions in cost-effective process-scale Suzuki-Miyaura reactions

by Stephen K. Ritter
September 1, 2014 | A version of this story appeared in Volume 92, Issue 35

As cross-coupling reactions have become more central to organic synthesis, chemists have been refining methods to make them greener and less costly on a large scale. In one of these efforts, an industry-academic collaboration between the University of Strathclyde, in Scotland, and GlaxoSmithKline led by doctoral student Aymeric P. Colleville has developed aryldiazonium salts as efficient coupling partners for the Suzuki-Miyaura reaction (Org. Process Res. Dev. 2014, DOI: 10.1021/op5002353). Researchers typically use aryl halides as coupling partners. But these reagents are only modestly activated and require rigorous reaction conditions and more active homogeneous catalysts that depend on expensive ligands. One method for preparing aryl halides for cross-couplings is with aryldiazonium salts via the Sandmeyer reaction. Previous lab-scale research has shown that direct cross-coupling of aryldiazonium species—avoiding aryl halides altogether—can shorten reaction sequences. The more reactive aryldiazonium reagents also allow chemists to use less active and lower cost heterogeneous catalysts in many cases. Colleville and coworkers optimized the conditions and established a safety protocol for scaling up these reactions so they might be carried out on a practical level for pharmaceutical production. To demonstrate the new process capabilities, they prepared mole quantities of a biaryl intermediate used to prepare angiotensin II inhibitors.

Reaction scheme showing diazonium-boronic acid cross-coupling


This article has been sent to the following recipient:

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