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对环境的影响，是至关重要的。氮(N)和氮基官能团在功能上起着关键作用，但在合成和催化方面具有挑战性。它们的碱性、天然的亲核性和反应性的混杂是任何新的合成方法要跨越的重大障碍。该研究计划的总体目标是通过开发新颖的“开箱即用”的合成方法来应对挑战，其中许多方法将氮气颠倒在头上，并研究其作为电泳剂的未被探索的反应性。C-H官能化是结合氮基官能团(C-H？C-N)的理想合成策略。我们将使用新型手性氨基甲酸酯磺胺配体来研究可持续的第一排过渡金属配合物，用于催化立体选择性胺化反应。这类具有S-N键的配体还有待于在催化方面进行探索。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，它可以转移一个非常理想的羟胺(NH-OH)单元。用目前的方法，羟胺官能团的结合是非常有限的。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电性化合物。建议的方法利用了从生物资源中提取的高度可用的胺，代表了一种更可持续的合成路线。重要的是，亲电性可以应用于合成药物化学和能量存储中感兴趣的化合物。此外，我们的建议旨在利用有毒气体和污染物一氧化氮(NO)作为一种新的试剂，用于合成含有羟胺的分子和作为唯一废物的重氮化反应产生无害的氮气(N2)。最后，将探索磺胺(S-N)和四氮唑的反应性在治疗靶点的去卷积中的应用，其中亲电氮会选择性地捕获蛋白质亲核试剂。这项拟议的研究利用现代技术，包括有机金属催化、连续流动化学、光催化和电化学，以克服分子合成中的挑战，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.