N-Heterocyclic Carbenes for Sustainable Organo- and Biocatalysis

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Organocatalysis offers significant advantages for sustainable chemistry, providing unique modes of chemical reactivity. Despite many advantages, the organocatalysis community has been slow to adopt 'greener' solvents, including water. The move to (asymmetric) organocatalysis in water requires careful consideration of organocatalyst pKa, kinetic activation pathways and molecular recognition. N-Heterocyclic carbenes (NHCs) are the most versatile class of organocatalyst, allowing access to a variety of catalytic intermediates for the construction of complex targets from simple starting materials under mild conditions. There has been limited exploration of NHC organocatalysis in water, which will be essential for progress towards more sustainable reaction environments.We will target NHC catalysts with pKas within the conventional pH range, which is one key criterion for successful organocatalysis in aqueous solution. Of the range of NHC catalysts employed in contemporary organocatalysis in traditional solvents, triazolium-derived NHCs are the most acidic and offer excellent potential in aqueous solution. We will explore NHC mimics of co-factor thiamine pyrophosphate (TPP) for bio- and organocatalysis of challenging transformations in aqueous solution. Biocatalysis will be explored in conjunction with TPP-dependent enzymes. To inform catalyst exploration and application, we will perform parallel mechanistic and binding studies including both computational and experimental methods.