In the quest for active ingredients in pharmaceutical research, molecules featuring a central ring system are pivotal, and the precise size of these rings is crucial for efficient manufacturing of desired products. Addressing this challenge, an international team of chemists, led by Prof. Frank Glorius (University of Münster) and Prof. Osvaldo Gutierrez (Texas A&M University, U.S.), has introduced an innovative technique known as “single atom skeletal editing.”
Published in the journal Nature Catalysis, their approach involves the strategic insertion of a single carbon atom into the carbon skeleton of cyclic compounds, allowing adjustment of the ring size from five- to six-membered rings. This breakthrough, the researchers contend, not only facilitates the design and modification of complex molecular structures but also holds promise for applications in pharmaceutical syntheses and materials science.
Skeletal editing, a method employed by chemists for atom substitution within a ring system, has traditionally focused on nitrogen atom insertion. Dr. Fu-Peng Wu from the University of Münster explains, “By contrast, inserting a single carbon atom into an all-carbon ring is an enormous challenge.” The carbon reagent must be compatible with various functional groups dictating the molecule’s chemical properties, necessitating stability, ease of handling, and susceptibility to straightforward activation—criteria met by only a limited number of developed reagents in recent decades.
The team, under Glorius’s leadership, utilized photoredox catalysis, harnessing light energy to propel the reaction forward. Employing specialized reactive carbon fragments, known as radical carbynes, the researchers successfully inserted single carbon atoms with diverse functional groups into indene—an essential starting material in organic compound production, along with the resulting product, naphthalene.
Concurrently, Gutierrez and his team conducted mechanistic computations to unveil the underlying reaction mechanism in the radical chain. Postdoc Dr. Remy Lalisse notes, “Our calculations suggest that the reaction initiates through the initial addition of a diazomethyl radical to indene.”
This groundbreaking methodology not only expands the repertoire of tools available to chemists but also enhances the efficiency and precision of molecular manipulation, holding significant implications for advancing pharmaceutical and materials science research.
Source: University of Münster