Development of asymmetric methods using an experimental-computational strategy

拟议研究的目标是开发简单、高效、广泛使用的不对称方法，作为促进学术界和工业界合成化学家工作的工具。实现这一壮举是一个持续的挑战，因为反应性和立体选择性必须同时优化。这项工作是非常重要的，因为手性分子可以具有有用的性质和许多应用。例如，大量的现代药物是手性对映体化合物。效率和成本是研究过程中与之相关的重要方面，必须利用所有可用的工具来精简和提高生产率。我的方法将侧重于实验研究和计算研究之间的强烈互动，以更低的成本和更少的时间取得进展。分子模拟特别适合于理解立体选择性和使手性诱导部分的设计合理化。我的第一个研究主题是基于N-亚氨基咪唑叶立德基团衍生的一类新型阴离子卡宾配体的催化剂的合成和研究。这些化合物将通过简单和模块化的合成路线获得，这将迅速导致创建有助于研究其潜力的络合物文库。这种多样性对于微调特定方法的金属络合物反应性也是至关重要的。第一代手性催化剂将被合成并在模型反应中进行评价(例如，烯丙烷基化、1，4-共轭加成)。我的第二个研究主题是开发新型手性碘(III)试剂，这些试剂将用于不对称碘(III)介导的反应，如酮的α-对甲苯磺酰氧基化和苯乙烯的双对甲苯磺酰氧基化。我的最后一个主题是研究路易斯碱介导的对映选择性碘环化反应。计算化学将被用来理解这些反应的机理，并帮助设计新的手性碱。

The goal of the proposed research is to develop simple and efficient asymmetric methodologies of broad use that will serve as tools to facilitate the work of synthetic chemists in both academia and industry. Achieving this feat is a continuing challenge since both reactivity and stereoselectivity must be optimized concurrently. This work is of the utmost importance since chiral molecules can possess useful properties and have numerous applications. For example, a large number of modern drugs are chiral enantiopure compounds. Efficiency and cost are important related aspects of the research process, and it is critical to employ all the tools available to streamline and enhance its productivity. My approach will focus on a strong interaction between experimental and computational studies to achieve progress at lower cost and in reduced time. Molecular modelling is particularly well suited to understand the stereoselectivity and rationalize the design of the chirality-inducing moiety. My first research theme focuses on the synthesis and investigation of catalysts based on a new class of anionic carbene ligands derived from the N-iminoimidazolium ylide motif. These compounds will be obtained through a simple and modular synthetic route, which will rapidly lead to the creation of libraries of complexes that will facilitate the investigation of their potential. This diversity is also crucial to enable the fine tuning of the metal complexes reactivity for specific methodologies. A first generation of chiral catalysts will be synthesized and evaluated in model reactions (e.g. allylic alkylations, 1,4-conjugate additions). My second research theme consists of the development of novel chiral iodine(III) reagents that will be used in enantioselective iodine(III) mediated reactions, such as the alpha-tosyloxylation of ketones and ditosyloxylation of styrene. My last theme targets the study of Lewis base-mediated enantioselective iodocyclization reactions. Computational chemistry will be used to understand the mechanism of these reactions, and help design new chiral bases.