Novel Synthetic Methodologies Exploiting Nitrogen-Containing Molecules

利用含氮分子的新合成方法

• 批准号: RGPIN-2022-04168
• 负责人: Lebel, Hélène
• 金额: $ 3.5万
• 依托单位: Université de Montréal
• 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=748692
• 关键词: Novel; Synthetic; Methodologies; Exploiting; Nitrogen

Advances in the pharmaceutical or energy sectors are inherently linked to molecular synthesis. Consequently, it is critical to develop new tools to maximize efficiency and safety, while minimizing waste and environmental impact. Nitrogen (N) and nitrogen-based functionality play a key role in function, but are challenging with regards to synthesis and catalysis. Their basicity, natural nucleophilicity and reactive promiscuity are significant hurdles for any new synthetic method to jump. The overall goal of the research program is to address the challenges by developing novel, "outside of the box" synthetic methods, many of which flip nitrogen on its head and investigate its underexplored reactivity as an electrophile. C-H functionalization is an ideal synthetic strategy for incorporating nitrogen-based functionality (C-H?C-N). We will study complexes of sustainable first row transition metals for catalytic stereoselective amination reactions using novel chiral carbamate sulfilimine ligands. Such ligands having S-N bonds have yet to be explored in catalysis. As a new solution to stereoselective C-H functionalization, novel hypervalent iodine reagents will be developed that transfer a highly desired hydroxylamine (NH-OH) unit. The incorporation of hydroxylamine functionality is highly limited using current methods. We will explore new diazotization reactions that permit the synthesis of highly reactive diazonium electrophiles from aliphatic nitrogen compounds. The proposed method makes use of highly available amines derived from biosources, and represents a more sustainable route to synthesis. Importantly, the electrophiles can be applied toward the synthesis of compounds of interest in medicinal chemistry and energy storage. Furthermore, our proposal aims to exploit nitric oxide (NO), a toxic gas and pollutant, as a new reagent in both the synthesis of hydroxylamine-containing molecules and diazotisation that produces benign nitrogen (N2) as the sole waste. Finally, the reactivity of sulfilimines (S-N) and tetrazoles will be explored for applications in the deconvolution of therapeutic targets, where an electrophilic nitrogen will selectively trap protein nucleophiles. The proposed research takes advantage of modern techniques involving organometallic catalysis, continuous flow chemistry, photocatalysis, and electrochemistry to overcome challenges in molecular synthesis that are of paramount importance in the fields of pharmaceutical and energy sciences.

制药或能源部门的进步与分子合成有着内在的联系。因此，开发新的工具以最大限度地提高效率和安全性，同时最大限度地减少浪费和环境影响至关重要。氮（N）和氮基官能团在功能中起着关键作用，但在合成和催化方面具有挑战性。它们的碱性、天然亲核性和反应混杂性是任何新合成方法跨越的重大障碍。该研究计划的总体目标是通过开发新的“盒子外”合成方法来应对挑战，其中许多方法将氮翻转到其头部并研究其作为亲电试剂的未充分探索的反应性。C-H官能化是将氮基官能团（C-H？C-N）。我们将研究可持续的第一行过渡金属配合物的催化立体选择性胺化反应使用新的手性氨基甲酸酯硫亚胺配体。这种具有S-N键的配体还有待于在催化中探索。作为立体选择性C-H官能化的新解决方案，将开发新型高价碘试剂，其转移高度期望的羟胺（NH-OH）单元。使用目前的方法，羟胺官能团的引入是高度受限的。我们将探索新的重氮化反应，使高活性重氮亲电试剂的合成脂肪族氮化合物。所提出的方法利用了来自生物糖的高度可用的胺，并且代表了更可持续的合成路线。重要的是，亲电试剂可以应用于药物化学和能量储存中感兴趣的化合物的合成。此外，我们的建议旨在利用一氧化氮（NO），一种有毒气体和污染物，作为含羟胺分子合成和重氮化的新试剂，产生良性氮（N2）作为唯一的废物。最后，将探讨磺酰亚胺（S-N）和四唑的反应性在治疗靶点的去卷积中的应用，其中亲电氮将选择性地捕获蛋白质亲核试剂。拟议的研究利用现代技术，包括有机金属催化，连续流化学，电化学和电化学，以克服在制药和能源科学领域至关重要的分子合成的挑战。