N-Heterocyclic Carbenes for Sustainable Organo- and Biocatalysis

有机催化为可持续化学提供了显着的优势，提供了独特的化学反应模式。尽管有许多优点，但有机催化界在采用包括水在内的“绿色”溶剂方面进展缓慢。在水中（不对称）有机催化的移动需要仔细考虑有机催化剂的pKa，动力学活化途径和分子识别。N-杂环卡宾（NHC）是用途最广的一类有机催化剂，允许在温和条件下从简单的起始原料获得用于构建复杂目标的各种催化中间体。水溶液中的NHC有机催化剂的探索有限，这对于实现更可持续的反应环境至关重要。我们将针对pKas在常规pH范围内的NHC催化剂，这是水溶液中成功有机催化的关键标准之一。在传统溶剂中用于当代有机催化的NHC催化剂的范围中，三唑衍生的NHC是最酸性的，并且在水溶液中提供优异的潜力。我们将探索辅助因子焦磷酸硫胺素（TPP）的NHC模拟物，用于水溶液中具有挑战性的转化的生物和有机催化。生物催化将与TPP依赖性酶一起探索。为了告知催化剂的探索和应用，我们将进行并行的机理和约束研究，包括计算和实验方法。

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.