Chemists Innovate a Fresh Method for Introducing Single Carbon Atoms into Rings

Chemists, led by Prof. Frank Glorius (University of Münster) and Prof. Osvaldo Gutierrez (Texas A&M University, U.S.), have introduced a precise and efficient tool for “single atom skeletal editing,” allowing the insertion of a single carbon atom into the carbon skeleton of cyclic compounds. This innovative approach facilitates the adjustment of ring sizes from five- to six-membered rings, a crucial factor in the efficient production of desired pharmaceutical products.

Published in the journal Nature Catalysis, the researchers assert that their method paves the way for designing and modifying complex molecular structures, with potential applications not only in research but also in pharmaceutical syntheses and materials science on an industrial scale. Skeletal editing, a technique used by chemists to replace atoms within a ring system, traditionally focused on nitrogen atom insertion.

In contrast, the current challenge lies in inserting a single carbon atom into an all-carbon ring. Dr. Fu-Peng Wu from the University of Münster notes, “The carbon reagent needs to be compatible with various functional groups that determine the chemical properties of the molecule. Additionally, the compound should be stable, easy to handle, and susceptible to uncomplicated activation.” Over the past few decades, only a limited number of such reagents have been developed.

The Glorius-led group employed photoredox catalysis, harnessing light energy to drive the reaction. Using specialized reactive carbon fragments (radical carbynes), they successfully inserted single carbon atoms with various functional groups into indene, a common starting material in organic compound production, as well as the product naphthalene. Gutierrez and his team conducted mechanistic computations to uncover the underlying reaction mechanism, suggesting that the reaction initiates through the initial addition of a diazomethyl radical to indene, according to postdoc Dr. Remy Lalisse.

This article is republished from PhysORG under a Creative Commons license. Read the original article.