Catalytic Methods for Rapid Aromatic Derivatization

快速芳香衍生化的催化方法

• 批准号: 9750737
• 负责人: David A Nicewicz
• 金额: $ 27.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750737
• 关键词: Alcohols; Aromatic Compounds; Boronic Acids; Chemicals; Complex; Coupling; Development; Dyes; Evaluation; Fluorides; Goals; Lead; Libraries; Metabolic; Methods; Molecular; Nitrogen; Oxidants; Oxides; Oxygen; Pharmaceutical Chemistry; Pharmacologic Substance; Play; Protocols documentation; Reaction; Reagent; Reporting; Research; Research Personnel; Research Proposals; Role; Source; Structure; System; Therapeutic; Transition Elements; Visible Radiation; aryl halide; base; catalyst; chemical reaction; design; drug candidate; flexibility; functional group; halogenation; lipophilicity; novel strategies; programs; rapid technique; scaffold; small molecule libraries; small molecule therapeutics; tool

Project Summary The objective of this research proposal is to develop new catalytic protocols for the direct C–H functionalization of aromatic compounds. Aromatic compounds are central motifs in the vast majority of therapeutics and simple methods for their further elaboration are always in demand. The goal of this research program is to generate new synthetic tools for biomedical researchers to be able to derivatize lead aromatic-containing therapeutics in order to assemble libraries of drug candidates for further evaluation. This proposal describes the use of organic dyes as catalysts to enable over a dozen new chemical transformations. The value of the proposed synthetic methods is the ability to utilize aromatics that are not pre-oxidized, allowing for greater flexibility in the types of aromatic structures that can be employed. We predict that this research program will enhance the synthetic capabilities of medicinal chemists to explore greater chemical space in the development of small molecule therapeutics.

项目摘要 该研究建议的目的是为直接C – H制定新的催化方案 芳族化合物的功能化。芳香化合物是疫苗的中心基序 始终需要大多数治疗学和进一步阐述的简单方法。 该研究计划的目的是为生物医学研究人员生成新的合成工具 能够衍生含铅芳香族疗法以组装库 候选药物进行进一步评估。该建议将有机染料的使用描述为 催化剂可以实现十几个新的化学转化。提议的价值 合成方法是利用未预氧化的芳香族剂的能力，从而使得更大 可以进行的芳族结构类型的灵活性。我们预测这项研究 计划将增强药物化学家的合成能力，以探索更大 小分子疗法发展中的化学空间。

项目成果

Predictive Model for Site-Selective Aryl and Heteroaryl C-H Functionalization via Organic Photoredox Catalysis.

• DOI: 10.1021/jacs.7b06715
• 发表时间: 2017-08-16
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Margrey KA;McManus JB;Bonazzi S;Zecri F;Nicewicz DA
• 通讯作者: Nicewicz DA

Direct C-H Cyanation of Arenes via Organic Photoredox Catalysis.

• DOI: 10.1021/jacs.6b12708
• 发表时间: 2017-03-01
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: McManus JB;Nicewicz DA
• 通讯作者: Nicewicz DA

Nucleophilic Aromatic Substitution of Unactivated Fluoroarenes Enabled by Organic Photoredox Catalysis.

• DOI: 10.1021/jacs.0c09296
• 发表时间: 2020-10-07
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Pistritto VA;Schutzbach-Horton ME;Nicewicz DA
• 通讯作者: Nicewicz DA

Cation Radical-Accelerated Nucleophilic Aromatic Substitution for Amination of Alkoxyarenes.

• DOI: 10.1021/acs.orglett.0c01621
• 发表时间: 2020-06
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: N. Venditto;David A. Nicewicz