Chemists will use cheap, abundant onium salts—molecules already common in labs—as chemical linchpins to snap together complex organic building blocks in ways that were previously difficult or impossible. The problem is that many valuable molecules, from pharmaceuticals to agrochemicals, require precise control over which atoms connect where. Current methods often demand pre-functionalised starting materials or harsh conditions. This project fills that gap by developing a radical-based strategy that works directly with naturally abundant functional groups—carboxylic acids, alcohols, and amines—found in many complex molecules. The team will also design a new photocatalytic system to selectively activate carbon-hydrogen bonds, a notoriously stubborn target. If successful, the approach could streamline the late-stage modification of drug candidates, allowing chemists to tweak a molecule’s properties without rebuilding it from scratch. It could also enable the asymmetric synthesis of chiral molecules—mirror-image compounds that often have very different biological effects—using simple, readily available starting materials. This is fundamental science: it creates a new toolkit for molecular construction. Past work on similar radical and onium chemistry has already transformed how industry makes fine chemicals, and this strategy could open equally unexpected routes to new materials, catalysts, and medicines.
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Advances in chemistry require scientists to design molecular entities with specific structures and properties. This proposal will therefore develop and implement an innovative strategy to assemble molecules with broad application in high-impact areas of synthesis, from late-stage functionalisation chemistry to asymmetric catalysis. Our strategy uses readily available onium salts as linchpins to achieve the union of pairs of coupling partners bearing naturally abundant functional groups, thus unlocking access to new chemical structures. We will first introduce the use of sulfonium salts as chemical linchpins in radical chemistry, allowing the selective cross-coupling between complex molecules carrying naturally abundant functional groups (carboxylic acids, alcohols, amines) and a variety of partners. Thus, we will extend our onium-coupling strategy to the selective sp3 C-H functionalisation of complex molecules by designing a novel photocatalytic strategy (dual hydrogen atom transfer catalysis) with general applicability for radical C-H activation chemistry. We will then broaden the applicability of our strategy to the selective late-stage functionalisation of olefins and heteroaromatics, which are recurrent motifs in biomolecules. To achieve this ambitious goal, we will introduce the use of novel reactive intermediates in synthesis (onium radicals). Finally, we will demonstrate the strategy's broader synthetic application by creating a new approach to forge enantioenriched small chiral molecules, which are valuable materials in synthesis. Namely, we will introduce the use of onium salts in asymmetric catalysis to connect elemental building blocks through chiral conjunctive centres by designing appropriate catalytic strategies. In conclusion, this proposal presents a fundamentally new way to assemble chemical structures that is expected to promote dramatical long-term advances in various fields of Science and Technology.
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