Final Report Summary - ARYLATOR (New Catalytic Reactions and Exchange Pathways: Delivering Versatile and Reliable Arylation)
We have conducted detailed investigations into the mechanism (the detailed steps by which a chemical reaction takes place) of the coupling of aryl-trimethylsilanes with simple electron rich arenes. This is a trace side reaction that we discovered in 2012, and developed into a synthetic process of considerable potential. Based on these investigations we have developed new arysilane reagents and carefully tuned iodine (III) oxidants. This has facilitated the arylation of a wide range of arenes and heterocycles with very high regio-selectivity, and without the requirement for high reaction temperatures. We have also conducted detailed studies on the stability of organoboron and organosilane reagents, aiding us in the above developments; these studies provided major advances on mechanistic understanding of the fundamental processes involved in protodeboronation of heteroaromatic systems and aryl systems. We have also investigated the hydrolysis of MIDA boronates, the synthesis and stability of silylated diazo species, the generation of arylsilanes under rhodium catalysed ‘Chatani’ conditions, elucidating a number of interactive and major inhibition processes, the cleavage of C-Si reagents for nucleophilic CF3 transfer and competing difluorocarbene generation, the kinetics of Cu/Fe catalysed oxidation, rhodium catalysed aminoborane dehydrocoupling, organocatalytic rearrangements, and gold-catalysed C-X and C-C bond activations for the release of active species in cellular environments. To assist these investigations we have developed enabling methodologies for the direct interface of high performance spectrometers with synthetic chemistry. These novel techniques offer considerable advantages over current methodologies for nuclear magnetic resonance and infra-red analysis, and have been licenced for commercialisation to an instrument manufacturer. Eight postdoctoral researchers have engaged in these research goals. Four of the postdoctoral researchers have subsequently secured academic positions, four have secured positions in the chemical industries. Four PhD students have benefited from the training and contributions to the research programme. Two have graduated and are now employed in the chemical industries. The remaining two will graduate in 2019 and 2020. This work has been reported in over 17 publications, with more to follow, and aided in the securing of a number of other funding streams, including ERC and industry.