Anion-Gated Dual Catalysis: Alkene Difunctionalization Accelerated by High Throughput Experimentation

阴离子门控双重催化：高通量实验加速烯烃双官能化

• 批准号: EP/X015262/1
• 负责人: Matthew Gaunt
• 金额: $ 34.47万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX015262%2F1
• 关键词: Anion; Gated; Dual; Catalysis; Alkene

Catalytic multicomponent reactions that transform the C=C bonds of alkene feedstocks into complex molecules for the interrogation of biological systems are a cornerstone of modern synthesis. The intrinsic multifaceted reactivity of C=C bonds can be unlocked by many catalytic activation modes. When combined with the structural & functional diversity inherent to the ubiquitous classes of alkene feedstock, these activation modes offer remarkable flexibility for programmable synthesis of complex architectures.1 Among many classes of these reactions, transformations that form new C-C & C-N bonds are an attractive starting point for new methodologies involving transition metal-catalyzed aminoarylation. Recently, we reported a distinct catalysis platform that enables a multicomponent coupling of alkenes, aryl-electrophiles & NaN3, providing single-step access to synthetically versatile & functionally diverse beta-arylethylamine derivatives. Driven by visible-light, two discrete Cu-catalysts orchestrate Ar-radical formation & azido-group transfer steps, which underpin an alkene azido-arylation (AAA) process. The reaction exhibits broad scope in alkene & Ar-components & the azide-anion performs a multifaceted role as both nitrogen source & in mediating the redox-neutral dual-catalysis platform via inner-sphere electron transfer. The synthetic capabilities of this anion-mediated AAA & development of its related reactions is likely to be of utility in a variety of pharmaceutically relevant & wider synthetic applications.Despite several notable advances, the vast majority of synthetic chemistry is conducted in 'one-at-a-time' batch fashion using equipment that has not, essentially, changed since urea was first synthesized by Wöhler in 1828. Most synthetic chemistry is still based on a work flow that often involves routine operations and is labour-intensive & time consuming. Over the last four years, the PI & team have established a ns-HTE platform, such that we can execute & analyse 1000s of parallel & discretely programmable reactions across a wide range of chemical reaction space. The platform is facilitated by liquid handling robots (LHRs), which enables reactions to be set up on a micro or nanomolar scale. To analyse reaction mixtures from 384 or 1536-well plates, we can choose from quantitative & semi-quantitative LC-MS, high-throughput (HT) qNMR & parallel HT-TLC. Together these techniques allow unparalleled quantification & structure determination of products on a short timescale. Together we aim to use HTE to epxlore a new type a catalysis for the synthesis of complex molecules from alkenes. The 'anion-gated dual catalysis' platform brings together three readily available building blocks in a process controlled, ultimately, by a simple anion. The products can be advnaced to functional molecules that have unexplored properties in biologial systems, providing a means to explore new chemical and biology space.

将烯烃原料的C = C键变成复杂分子以询问生物系统的催化多组分反应是现代合成的基石。 C = C键的固有多面反应性可以通过许多催化激活模式解锁。当与烯烃原料无处不在类固有的结构和功能多样性结合使用时，这些激活模式为复杂体系结构的可编程合成提供了显着的灵活性。1这些反应的许多类别中，形成新的C-c＆c-c-n键的转换是涉及新方法的新方法，涉及涉及过渡金属金属 - 催化型的新方法。最近，我们报道了一个独特的催化平台，该平台可以实现烯烃，芳基电噬细胞和NAN3的多组分耦合，从而提供了单步访问合成的β-氨基甲胺衍生物的多样性且功能多样的β-苯胺衍生物。在可见光的驱动下，两个离散的Cu催化剂编排了AR-RADICAL形成和偶氮组的转移步骤，这是基于烯烃氮化液（AAA）过程的基础。该反应在烯烃和AR-Component中表现出广泛的范围，而叠氮化物大区域在氮源和通过内球电子转移中介导氧化还原的双催化平台方面既是氮源的角色又是多方面的作用。该阴离阴离子介导的AAA和其相关反应的发展的合成能力可能在各种药物相关且更广泛的合成应用中具有实用性。尽管取得了一些显着的进步，绝大多数合成化学反应是在一次性'at-at-at-At-At-At-At-At-At-aT-At-aT批次使用设备中都无法进行的，这是18岁以来的8次合成，最初是综合的。化学仍然基于通常涉及常规操作的工作流程，并且是劳动密集型且耗时的。在过去的四年中，PI＆Team建立了一个NS-HTE平台，因此我们可以在广泛的化学反应空间中执行和分析1000秒的平行和可离散的可编程反应。该平台是由液体处理机器人（LHR）制备的，该机器人可以在微或纳摩尔尺度上设置反应。为了分析来自384或1536孔板的反应混合物，我们可以从定量和半定量LC-MS，高通量（HT）QNMR和并行HT-TLC中进行选择。这些技术共同允许在短时间内对产品的无与伦比的定量确定。我们共同使用HTE来将一种新型的催化剂用于烯烃的复杂分子。 “阴离子门控的双催化剂”平台在最终由简单的阴离子控制的过程中汇集了三个随时可用的构建块。这些产品可以归纳为在生物系统中具有意外特性的功能分子，从而提供了一种探索新化学和生物学空间的方法。