Novel Synthetic Methodologies Exploiting Nitrogen-Containing Molecules

制药或能源领域的进步与分子合成有着内在的联系。因此，开发新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对环境的影响至关重要。氮(N)和氮基功能在功能中起着关键作用，但在合成和催化方面具有挑战性。它们的碱度、天然亲核性和反应性混杂性是任何新合成方法发展的重大障碍。该研究计划的总体目标是通过开发新颖的、“开箱即用”的合成方法来解决这些挑战，其中许多方法将氮颠倒过来，并研究其作为亲电试剂的未被开发的反应性。碳氢官能化是氮基官能化（C-H?C-N）的理想合成策略。我们将研究利用新型手性氨基甲酸酯亚胺配体催化立体选择性胺化反应的可持续第一行过渡金属配合物。这种具有S-N键的配体在催化方面还有待探索。作为一种立体选择性C-H功能化的新解决方案，新型高价碘试剂将被开发出来，转移一个非常需要的羟胺（NH-OH）单元。羟胺功能的结合是高度限制使用目前的方法。我们将探索新的重氮化反应，允许从脂肪族氮化合物合成高活性的重氮亲电试剂。所提出的方法利用了来自生物来源的高可利用性胺，代表了一种更可持续的合成途径。重要的是，亲电试剂可以应用于药物化学和储能领域的化合物合成。此外，我们的提案旨在利用一氧化氮（NO），一种有毒气体和污染物，作为合成含羟胺分子和重氮化的新试剂，产生良性氮（N2）作为唯一的废物。最后，将探讨亚砜亚胺（S-N）和四唑的反应性，以便在治疗靶点的反褶积中应用，其中亲电氮将选择性地捕获蛋白质亲核试剂。该研究将利用有机金属催化、连续流化学、光催化和电化学等现代技术来克服分子合成方面的挑战，这些挑战在制药和能源科学领域至关重要。

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.