Development of asymmetric methods using an experimental-computational strategy

使用实验计算策略开发不对称方法

• 批准号: 371568-2009
• 负责人: Legault, Claude
• 金额: $ 2.55万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528275
• 关键词: Development; asymmetric; methods; using; experimental

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.

拟议研究的目标是发展简单而有效的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。这项工作是至关重要的，因为手性分子可以拥有有用的性质，并有许多应用。例如，大量的现代药物是手性对映纯化合物。效率和成本是研究过程中重要的相关方面，使用所有可用的工具来简化和提高其生产力是至关重要的。我的方法将集中在实验和计算研究之间的强烈互动，以更低的成本和更短的时间取得进展。分子模型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 -亚胺咪唑基序衍生的一类新型阴离子碳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，这将迅速导致化合物库的创建，这将有助于研究它们的潜力。这种多样性对于特定方法的金属配合物反应性的微调也是至关重要的。第一代手性催化剂将被合成并在模型反应（如烯丙基烷基化，1,4-共轭加成）中进行评价。我的第二个研究主题是开发新的手性碘（III）试剂，这些试剂将用于对映选择性碘（III）介导的反应，如酮的α -甲氧基化和苯乙烯的二氧基化。最后一个主题是路易斯碱介导的对映选择性碘环化反应的研究。计算化学将用于了解这些反应的机理，并帮助设计新的手性碱。