Experimental-Computational Synergy to Create and Understand New Synthetic Methodologies

实验-计算协同作用以创建和理解新的合成方法

• 批准号: RGPIN-2019-05819
• 负责人: Legault, Claude
• 金额: $ 3.5万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748693
• 关键词: Experimental; Computational; Synergy; Create; Understand

Modern societies are facing a number of challenges and some can only be tackled by the development of new and innovative organic synthetic processes. Accessing new molecules of biological interest is essential to the development of new therapeutic treatments eagerly needed to support the wellbeing of the aging populations. For example, the synthesis of new antibiotic drugs is of the utmost importance to stem the emergence of drug-resistant pathogens. In the context of global energy crisis and environmental challenges, the development of synthetic methods with lower environmental impact is crucial to meet our goals of sustainable development. My research program proposes to develop new synthetic methods to access organic molecules of interest at reduced environmental cost. My group has a unique expertise in both experimental and computational chemistry. My group is thus able to accelerate the research process by exploiting molecular modeling to guide the more costly experimental work. I identified two areas of research that will contribute to develop new synthetic methods meeting our goals: 1) Iodine(III)-mediated Chemistry; 2) Organometallic Catalysis. Iodine(III)-mediated Chemistry. Oxidative transformations are key synthetic methods as they enable rapid increase in molecular complexity. The development of iodine(III)-mediated processes has been particularly interesting in this regard. Iodine(III) reagents tend to be eco-friendly, being carbon-based and usually biodegradable, and have been found to be in numerous cases a good alternative to toxic heavy metal-based reagents. One challenging area of research in iodine(III) chemistry is the development of stereoselective methods. We will capitalize on our unique experimental/computational expertise to unearth the key requirements to obtain high stereoinduction in these reactions. We will also investigate new oxidative ring contraction transformations to access chiral non racemic polysubstituted butyrolactones. Finally, we will extend our work to understand and exploit the Lewis acidity of iodine(III) reagents. Organometallic Catalysis. The field has revolutionized synthetic chemistry in the past 50 years. To create an efficient catalyst, a balance between its stability and reactivity must be achieved. These properties are largely controlled by the ligands on the complex. The synthesis of new types of ligands thus enables the creation of catalysts having new properties. I will capitalize on our recent development of new families of ylide-based ligands to improve useful synthetic methodologies. In particular, we will assess their potential as functional ligands in cooperative catalysis. In this context, we will investigate borrowing hydrogen catalysis to perform C-N and C-C coupling reactions. The unique nature of the ligands we developed are expected to yield improved reactivity profiles in these transformations.

现代社会正面临着许多挑战，有些只能通过开发新的和创新的有机合成工艺来解决。具有生物学意义的新分子对于开发新的治疗方法至关重要，这些治疗方法迫切需要支持老龄人口的健康。例如，合成新的抗生素药物对于阻止抗药性病原体的出现至关重要。在全球能源危机和环境挑战的背景下，开发对环境影响较小的合成方法对于实现我们的可持续发展目标至关重要。 我的研究计划提出开发新的合成方法，以降低环境成本获得感兴趣的有机分子。我的团队在实验和计算化学方面都有独特的专业知识。因此，我的团队能够通过利用分子建模来指导更昂贵的实验工作来加速研究过程。我确定了两个研究领域，这将有助于开发新的合成方法，满足我们的目标：1）碘（III）介导的化学; 2）有机物催化。 碘（III）介导的化学。氧化转化是关键的合成方法，因为它们能够快速增加分子的复杂性。在这方面，碘（III）介导的过程的发展特别令人感兴趣。碘（III）试剂往往是生态友好的，是碳基的，通常是可生物降解的，并已被发现在许多情况下是一个很好的替代有毒的重金属基试剂。碘（III）化学研究的一个具有挑战性的领域是立体选择性方法的发展。我们将利用我们独特的实验/计算专业知识来挖掘在这些反应中获得高立体诱导的关键要求。我们还将研究新的氧化环收缩转化，以获得手性非外消旋多取代丁内酯。最后，我们将扩展我们的工作，以了解和利用碘（III）试剂的刘易斯酸性。有机物催化。在过去的50年里，该领域已经彻底改变了合成化学。为了产生有效的催化剂，必须实现其稳定性和反应性之间的平衡。这些性质很大程度上受配合物上的配体控制。因此，新型配体的合成使得能够产生具有新性质的催化剂。我将利用我们最近开发的叶立德基配体的新家族来改进有用的合成方法。特别是，我们将评估它们作为功能配体在协同催化中的潜力。在这方面，我们将研究借用氢催化进行C-N和C-C偶联反应。我们开发的配体的独特性质，预计在这些转换中产生改进的反应性曲线。