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.



Methylene activation reached new heights

Methylene activation reached new heights

by Stu Borman
December 13, 2016 | A version of this story appeared in Volume 94, Issue 49

A reaction scheme shows functionalization of a β C–H bond.
In the new reaction, a palladium catalyst with a chiral ligand activates a β-methylene C–H bond in an amide starting material to enantioselectively form an aryl product.

An organic synthesis method that took flight this year could prove to have an unusually wide wingspan. Developed by Jin-Quan Yu and coworkers at Scripps Research Institute California after a 14-year effort, the reaction advances a long-standing goal: activating specific C–H bonds in organic compounds and converting them catalytically and enantioselectively into C–C bonds or other derivatives.

Since there’s no shortage of C–H bonds in organic compounds, the technique has lots of potential for widespread applicability. Specifically, the new reaction uses a palladium catalyst and quinoline-based ligand to convert β-methylenes—CH2 groups two carbon atoms away from amides or carboxylic acids—into chiral centers (Science 2016, DOI: 10.1126/science.aaf4434).

Synthetic organic chemists had previously developed ways to activate several types of C–H bonds, such as by preinstalling activating groups in substrates. But the ability to target C–H bonds of unactivated methylene groups and then derivatize them catalytically and enantioselectively had been largely unsolved.

“Yu’s trailblazing group has managed to bring to reality what might have been considered seemingly impossible,” commented Erick M. Carreira, an expert on asymmetric synthesis at the Swiss Federal Institute of Technology (ETH), Zurich.

Since the paper came out, Yu and his coworkers have been developing their approach further by extending it to create chiral centers near other functional groups, such as alkyl amines. A number of applications for the β-methylene reaction have already been identified at Bristol-Myers Squibb and another pharmaceutical company, “but optimization is needed to improve the yield for the complex substrates at hand,” Yu says. “We are negotiating to license this technology to a chemical development company.”


Top Headlines of 2016

Top Research of 2016

Revisiting Research of 2006


This article has been sent to the following recipient:

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