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

本项目描述了一类新的N-杂环卡宾的合成，即3-烷氧基咪唑烷(NOHS)，它们有望比用途广泛且用途广泛的N-杂环卡宾(NHCs)具有更强的亲核性。它们将由相应的烷氧基咪唑盐制备而成，从亚胺和肟作为容易获得的起始原料，只需两个步骤就可以获得大量的烷氧基咪唑盐。建议的路线将提供具有相同替代模式的非集中化中心和非集中化中心，从而实现快速比较。首先，我们将研究NOHS的内在性质，包括其前体盐的pKA测定、光谱、二聚化以及与NHCS相比其固有反应性的计算评估。理想情况下，我们还将能够将‘Arduengo-NOHC’具体化，以直接确定结构类比和差异。在第二步中，这些新颖的NOHC，包括一大系列基于金鸡纳衍生物和手性胺的手性衍生物，将被用于催化测试反应，以概述它们与NHC的性能，随后它们将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小组在合成含杂原子化合物，特别是咪唑-N-氧化物方面拥有丰富的经验，而Schiner小组精通卡宾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.