University of Cambridge
Harnessing Non-Covalent Interactions to Address Selectivity Challenges in Catalysis
Non-covalent interactions play a crucial in all manner of chemical and biological processes. Relatively recently, the incorporation of non-covalent interactions into the design of small molecule catalysts has revolutionised the field of enantioselective catalysis. Our research is centred around applying non-covalent catalysis to tackle outstanding selectivity challenges in synthetic chemistry.
The use of non-covalent interactions to direct reactive transition metals in order to tackle issues of regioselectivity or site-selectivity in synthetic chemistry is relatively underexplored. Advances in metal-catalysed C-H functionalisation have provided many methods to functionalise arenes but an outstanding challenge in this area is control of selectivity. The first part of the talk will describe the development of a multifunctional, anionic bipyridine ligand able to control regioselectivity in the iridium-catalysed C-H borylation of arenes. This single ligand is able to operate in several modes – ion pairing mode and hydrogen bonding mode and we have now modified the structure to enable enantioseletive desymmetrization. We have subsequently applied the same strategy to the site selective cross coupling of molecules bearing multiple chloridesm, achieved by repurposing sulfonylated phosphine ligands which are more typically used to impart water solubility to transition metal complexes.
In the area of enantioselective catalysis, non-covalent catalysis has most commonly been applied to two-electron processes. The recent surge of development of single electron processes, largely due to the popularisation of photoredox catalysis, has highlighted the continuing challenge of controlling enantioselectivity in radical reactions. The second part of the talk will describe studies in applying non-covalent catalysis to the control of enantioselectivity in radical processes, specifically the Minisci-type addition of prochiral radicals to pyridines and quinolines as well as the expansion of this methodology to diazine heterocycles, aided by multivariate statistical analysis in collaboration with the Sigman group.