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New Catalytic C-H Activation and Decarboxylation Chemistry

Final Report Summary - CATCHCHEM (New Catalytic C-H Activation and Decarboxylation Chemistry)

The Fellow (Sohel) has established a new way of making biaryl molecules that is free from transition metal catalysis and organometallic intermediates. The biaryl structure contains two benzene rings joined by a single carbon-carbon bond, and is a fundamental building block across all sectors of the fine chemical industry: pharmaceuticals, agrochemicals, polymers, and functional organic materials frequently display this motif. As a result, synthetic routes to biaryls are of utmost importance in synthetic chemistry. The conventional approach is to use transition metal catalysis and organometallic starting materials, a tremendously successful field of research that was recognised with the award of the Nobel prize in 2010. However, the requirement for precious and scarce metal catalysts and the waste associated with generating and using stoichiometric organometallics, drives research into alternative routes that are more sustainable going forward into the next decade of chemistry. Our research has uncovered a new reaction that takes aryl sulfonamides (containing one benzene ring of the putative biaryl) and reacts them with benzyne, a highly reactive intermediate that can be generated in situ. A molecular rearrangement that takes place, ejecting a molecule of sulfur dioxide, and creating a carbon-carbon biaryl bond (the second benzene ring coming from benzyne). Sohel has developed this reaction in partnership with a PhD student in our laboratory to thoroughly explore the substrate scope and applicability of this new reaction. The reaction conditions were quite mild, involving simple fluoride treatment of the benzyne precursor in an organic solvent at 50 degrees – no metal catalysis is required as the benzyne intermediate immediately reacts with the sulfonamide. The reaction works better for more sterically hindered substrates, an unusual finding that is likely connected to the sulfur dioxide extrusion reaction. This makes the method very complimentary to conventional transition metal catalysed approaches, which often struggle with this class of substrate. The complete findings of the reaction were communicated to the general chemistry journal Angew. Chem. Int. Ed. and published in 2016.
In a second line of research the MC Fellow developed some tandem reactions in arylation chemistry, whereby a single reagent effects multiple arylations in a single step, in contrast to multiple operations that would normally be required. The bulk of this chemistry is complete, and is undergoing some refinements in our laboratory prior to publication in the near future.

The MC Fellowship has enabled the development of some novel chemistry in a fundamental area of synthesis. The ability to make molecules in a more sustainable and economic way is essential to the economic development of the EU, given the structural role played by these entities in our society. In moving away from metal catalysis and demonstrating metal-free processes for biaryl synthesis, the Fellow has built a platform for further exploitation in functional molecule synthesis.