NOHCs - 3-Alkoxyimidazolylidenes (NOHCs): A new class of highly nucleophilic carbenes. Preparation, structural and reactivity studies, and new applications in asymmetric catalysis

本项目描述了一种新型n -杂环碳烯的合成，即3-烷氧基咪唑酰基（nohc），它有望比高度通用和普遍使用的n -杂环碳烯（NHCs）更具亲核性。nohc将由相应的烷氧咪唑盐制备，亚胺和肟作为现成的起始材料，只需两个步骤就可以获得种类繁多的烷氧咪唑盐。拟议的路线将提供具有相同替代模式的nohc和NHCs，从而允许快速比较。首先，将研究nohc的固有性质，包括其前体盐的pKa测定，光谱，二聚化，以及与NHCs比较其固有反应性的计算评估。理想情况下，我们还将能够结晶“Arduengo-NOHC”，以直接确定结构的相似性和差异性。在第二步，这些新的nohc，包括一系列基于金鸡纳衍生物和手性胺的手性衍生物，将被应用于催化测试反应，以概述它们与NHCs的性能，然后将它们应用于新的和具有挑战性的催化，对映选择性转化，包括三氟甲基化，thia-Diels-Alder和Kinugasa反应。两个参与小组具有互补的专业知识，Mloston小组在含杂原子化合物的合成方面有丰富的经验，特别是咪唑- n -氧化物，而Schreiner小组精通碳化学和对映选择性有机催化。

This project describes the synthesis of a novel class of N-heterocyclic carbenes, namely 3- alkoxyimidazolylidenes (NOHCs) that are expected to be even more nucleophilic than the highly versatile and ubiquitously employed N-heterocyclic carbenes (NHCs). NOHCs will be prepared from their corresponding alkoxyimidazolium salts, which are accessible in a large variety in just two steps from imines and oximes as readily available starting materials. The proposed route will deliver NOHCs and NHCs with the same substitution patterns, thereby allowing swift comparison. First, the intrinsic properties of NOHCs will be studied including pKa determinations of their precursor salts, spectroscopy, dimerization, and computational assessments of their intrinsic reactivity in comparison with NHCs. Ideally, we will also be able to crystallize the 'Arduengo-NOHC' to directly determine structural analogies and differences. In a second step, these novel NOHCs, including a large series of chiral derivatives based on cinchona derivatives and chiral amines, will be applied to catalytic test reactions to outline their performance vs. NHCs, followed by their application to new and challenging catalytic, enantioselective transformations including trifluoromethylations, thia-Diels-Alder, and Kinugasa reactions. The two participating groups have complementary expertise with the Mloston group having ample experience in the synthesis of heteroatom-containing compounds, in particular, imidazole-N-oxides, and the Schreiner group being well versed in carbene chemistry and in enantioselective organocatalysis.