Novel Radical Reactions for C-C Bond Formation

C-C 键形成的新颖自由基反应

• 批准号: 10371873
• 负责人: Simon B. Blakey
• 金额: $ 30.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-10 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371873
• 关键词: Acids; Agrochemicals; Alkenes; Anions; Catalysis; Chemicals; Chemistry; Complex; Consumption; Coupling; Cysteine; Development; Disease; Drug Compounding; Electrons; Event; Family; Food production; Goals; Health; Human; Lead; Light; Medicine; Metals; Methods; Modification; Molecular; Mutagenesis; Pathway interactions; Pattern; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Preparation; Process; Reaction; Reagent; Reducing Agents; Research; Temperature; Vinyl Carbamate; base; catalyst; design; functional group; improved; invention; novel; novel strategies; pharmacophore; scaffold; small molecule; tool

Abstract. The construction of valuable complex molecules from readily available chemical precursors is a central goal in synthesis. Bioactive small molecules (including pharmaceuticals and agrochemicals) are especially valuable because they influence human health and global food production. Our overall research goal is to develop new patterns in chemical reactivity that can be utilized in the solution of many diverse and impactful problems. Our lab has developed a family of radical anion-based processes that selectively activate heteroaromatic substrates for selective coupling with a range of different olefin types. Here we seek to extend this mechanistic strategy to the construction of many different valuable compound classes. In Aim 1, we propose a new strategy for the preparation of valuable fluorinated compounds through the cleavage of very strong C–F bonds (in aryl trifluoromethyl groups). We present a number of different ways that activation of these substrates by radical-anion formation could be utilized in bond-forming processes. Aim 2 seeks to utilize aryl and heteroaryl radical anions in the formation of privileged pharmacophores. In Aim 3, we describe a novel strategy for the synthesis of unnatural peptides.

抽象的。 从容易获得的化学前体构建有价值的复杂分子是该领域的核心目标 生物活性小分子（包括药物和农用化学品）尤其有价值。 因为它们影响人类健康和全球粮食生产。我们的总体研究目标是开发新的。 化学反应模式可用于解决许多不同且有影响力的问题。 我们的实验室开发了一系列基于自由基阴离子的工艺，可以选择性地激活杂芳族化合物 与一系列不同烯烃类型选择性偶联的底物在这里我们寻求扩展这种机制。 在目标 1 中，我们提出了一种新的策略来构建许多不同的有价值的化合物类别。 通过断裂非常强的 C-F 键来制备有价值的氟化化合物的策略 （在芳基三氟甲基中）我们提出了许多不同的方式来激活这些底物。 自由基-阴离子形成可用于成键过程，目标 2 寻求利用芳基和杂芳基。 在目标 3 中，我们描述了一种新颖的策略：自由基阴离子在特殊药效基团的形成中的作用。 非天然肽的合成。

项目成果

Selective C-F Functionalization of Unactivated Trifluoromethylarenes.

未活化三氟甲基芳烃的选择性 C-F 官能化。

• DOI: 10.1021/jacs.9b06004
• 发表时间: 2019-08-01
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: D. Vogt;Ciaran P. Seath;Hengbin Wang;N. Jui
• 通讯作者: N. Jui

Radical α-C-H Cyclobutylation of Aniline Derivatives.

苯胺衍生物的自由基α-C-H环丁基化。

• 发表时间: 2020-01
• 作者: Pratt, Cameron J;Aycock, R Adam;King, Max D;Jui, Nathan T
• 通讯作者: Jui, Nathan T

Catalytic Strategy for Regioselective Arylethylamine Synthesis.

区域选择性芳基乙胺合成的催化策略。

• DOI: 10.1021/jacs.9b01077
• 发表时间: 2019-02-13
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Allyson J Boyington;Ciaran P. Seath;Avery M Zearfoss;Zihao Xu;N. Jui
• 通讯作者: N. Jui

Synthesis of Spirocyclic Piperidines by Radical Hydroarylation.

通过自由基氢芳基化合成螺环哌啶。

• 发表时间: 2021
• 作者: Spurlin, Racheal M;Harris, Amber L;Pratt, Cameron J;Jui, Nathan T
• 通讯作者: Jui, Nathan T

Radical Chain Reduction via Carbon Dioxide Radical Anion (CO2•-).

通过二氧化碳自由基阴离子 (CO2™-) 进行自由基链还原。

• DOI: 10.1021/jacs.1c04427
• 发表时间: 2021-06-23
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Hendy CM;Smith GC;Xu Z;Lian T;Jui NT
• 通讯作者: Jui NT