N-Heterocyclic Carbenes for Sustainable Organo- and Biocatalysis

有机催化为可持续化学提供了显著的优势，提供了独特的化学反应模式。尽管有很多优点，有机催化领域在采用包括水在内的“更环保”溶剂方面进展缓慢。在水中向(不对称)有机催化转移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(NHCs)是用途最广的一类有机催化剂，可以在温和的条件下从简单的起始原料中获得各种催化中间体来构建复杂的目标。NHC在水中的有机催化作用的探索一直很有限，这将是迈向更可持续的反应环境所必需的。我们将在常规pH范围内使用pKas作为NHC催化剂的目标，这是在水溶液中成功进行有机催化的关键标准之一。在传统溶剂中用于现代有机催化的NHC催化剂中，三唑衍生的NHC是酸性最强的，在水溶液中具有很好的潜力。我们将探索辅因子硫胺素焦磷酸(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。将结合TPP依赖的酶来探索生物催化。为了给催化剂的探索和应用提供信息，我们将进行并行的机理和结合研究，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.