New precursors for diverse radical reactions enabled by potent photoreductants

项目摘要/摘要 通过化学选择性单电子还原生成的自由基中间体在反应中具有广泛的用途。 开发有价值的合成变换。因此，光氧化还原催化，这诱导了 单一选举转移具有对激进途径的特殊选择性，已显示出作为一种 生物医学研究中的使能技术。然而，支撑当前光氧化还原催化剂的设计 限制了可获得的减排潜力，并排除了大量丰富的原料。精挑细选 从底物惰性到传统的光氧化还原催化生成自由基中间体是一个长期的过程. 没有一般解决方案的长期挑战。 这一建议是基于电化学可以产生新的自由基阴离子光催化剂这一发现 它们是非常有效的激发态还原剂，但保留了典型光氧化还原催化剂的选择性。 我们将研究如何利用这些新催化剂来开发不可行的自由基偶联反应 现代综合战术。这项研究的三个具体目标是探索截然不同但相互交织的 这一新的催化平台的各个方面。 目标1.我们正在探索从芳基氯化物中产生和利用芳基自由基的反应性的能力 目的2.我们正在探索在还原自由基偶联反应中进行羰基化合物的能力 目标3.我们正在探索获得自由基阴离子光催化剂的操作简单的策略 这些方法解决了有机反应的一个基本类别-还原-中的长期挑战。 这些新的催化系统将提供一个扩大和多样化的原料池， 下一代药物和分子探测器将被发现。

PROJECT SUMMARY/ABSTRACT Radical intermediates generated through chemoselective single electron reduction have broad utility in the development of valuable synthetic transformations. As a consequence, photoredox catalysis, which induces single election transfer with exceptional selectivity for radical pathways, has shown great promise as an enabling technology in biomedical research. However, the design underpinning current photoredox catalysts limits the accessible reduction potentials and excludes numerous abundant feedstocks. The selective generation of radical intermediates from substrates inert towards conventional photoredox catalysis is a long- standing challenge with no general solutions. This proposal is based on the discovery that electrochemistry can generate new radical anion photocatalysts that are exceptionally potent excited state reductants but retain the selectivity of typical photoredox catalysts. We will study how these new catalysts can be exploited to develop radical coupling reactions infeasible with modern synthetic tactics. The three specific aims of this research center on exploring distinct but interwoven aspects of this new catalytic platform. Aim 1. We are exploring the ability to generate and exploit the reactivity of aryl radicals from aryl chlorides Aim 2. We are exploring the ability to engage carbonyl compounds in reductive radical coupling reactions Aim 3. We are exploring operationally simple strategies to access radical anion photocatalysts These methods address long-standing challenges in a fundamental class of organic reactions, reductions. These new catalytic systems will offer an expanded and diversified pool of starting materials from which the next generation of drugs and molecular probes will be discovered.