The reactivity of vinyl cations is the focus of a new Journal of the American Chemical Society article co-authored by Chemistry Professor Matthias Brewer and an international group of researchers.

The article, titled Reactivity Profiles of Diazo Amides, Esters and Ketones in Transition Metal Free C-H Insertion Reactions, compares the reactivity of vinyl cations in C-H insertion reactions in systems that are all-carbon, to systems that contain a nitrogen or oxygen atom. This research explains why all-carbon systems undergo an efficient rearrangement and C-H insertion sequence, while incorporating a nitrogen diminishes the efficiency of this sequence and incorporating an oxygen changes the course of the reaction completely.

“With this understanding in hand, we not only have a better fundamental understanding of the reactivity of vinyl cations, but we are now in a better position to develop strategies that will allow us to change the course of the heteroatom-containing reactions to give the butenolide and γ-lactam products we want,” Brewer says. “We hope that this research will peak other people’s interests in vinyl cations, and will help to make them more main-stream reactive intermediates that people take advantage of.”

Brewer explains that one branch of organic chemistry involves developing new chemical reactions that can be used to make molecules in new ways. Reactions that create new carbon-carbon (C-C) bonds are particularly important because these bonds are the structural framework of organic molecules. Forming these bonds allows synthetic chemists to create more complicated and useful structures.

Over the past decade, C-H insertion reactions have become important ways to make new C-C bonds, Brewer says. These reactions take advantage of a highly reactive carbon atom that can insert itself into a C-H bond, thus forming a new C-C bond.  

Brewer and an international team of researchers from UCLA and Zhejiang University have been studying the reactivity of vinyl cations over the past few years. Early work by other researchers had shown that, in the right situation, vinyl cations could insert into C-H bonds. However, the methods that had been used to generate the vinyl cations were impractical and severely limited the utility of those reactions, he says.

The approach Brewer and the research team used to generate vinyl cations in this study is milder. This has provided a more general way to take advantage of vinyl cations to make 5-membered rings, which are very common in biologically active compounds and medicines.

The paper’s co-authors are UVM alumna Sarah Cleary, now a post-doc at Oxford University, K.N. Houk of UCLA, and Xin Li, Li-Cheng Yang, and Xin Hong of Zhejiang University.

Brewer and Cleary conducted the wet lab work—developing the insertion reaction to make carbocycles and gathering the experimental results for the heteroatom systems. Hong and Houk carried out the computational modeling, and the team worked together to understand how the results fit and to write the manuscript.

Read the paper on the Journal of American Chemical Society website.





Erica Houskeeper
Professor Matthias Brewer