Selective Functionalization of Aliphatic Amines

脂肪胺的选择性官能化

• 批准号: 10298573
• 负责人: Tomislav Rovis
• 金额: $ 30.94万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298573
• 关键词: Alkenes; Alkylation; Amides; Amines; Automobile Driving; Carboxylic Acids; Catalysis; Chemistry; Cobalt; Complex; Copper; Coupling; Distal; Drug Design; FDA approved; Funding; Goals; Health; Hydrogen Bonding; Imines; Metals; Methods; Nickel; Nitrogen; Oxidation-Reduction; Pharmaceutical Preparations; Pharmacologic Substance; Planet Earth; Positioning Attribute; Principal Investigator; Protocols documentation; Reaction; Research; Salts; Site; Sodium Chloride; Structure; Sulfhydryl Compounds; System; Therapeutic Agents; Uncertainty; Work; aryl halide; catalyst; chlorination; dehydrogenation; design; drug discovery; efficacious treatment; functional group; human disease; interest; programs; scaffold; small molecule; success; tertiary amine

Principal Investigator/Program Director (Last, First, Middle): Rovis, Tomislav Selective Functionalization of Aliphatic Amines and Derivatives Aliphatic amines are ubiquitous among pharmaceutical compounds, driving significant research into the synthesis and functionalization of molecules bearing nitrogen atoms. Traditional strategies use functional group handles to synthesize amines. We have been engaged in a research program that uses resident C-H bonds and transforms them directly into the functionality of interest. The central challenge to derivatizing amines, thus, was one of positional selectivity. A number of strategies were advanced in the previous funding period with broad success. In the next funding period, we will expand the repertoire of reactions, the positions of activation and the complementarity to existing methods. We will develop methods to arylate C-H bonds in aliphatic amines, to difunctionalize vicinal C-H bonds in analogy to olefin difunctionalization, again with complete positional selectivity and to use earth abundant metal salts to activate distal C-H bonds of amines. Complementary approaches will be aimed at providing a method to functionalize inaccessible C-H bonds on tertiary amines, common components of many FDA approved drugs. These will allow structural diversification of complex molecules as well as a structural editing approach to provide homologous scaffolds to bioactive molecules. Lastly, primary amines are surprisingly widely available, far more so than alkyl halides or even carboxylic acids, no doubt due to the ubiquity and importance of amide bond constructions. We will develop a complementary strategy that will use the C-N bond as a functional group handle in cross-coupling chemistry. All of these methods are designed to facilitate drug design and discovery in the pursuit of more efficacious treatments for human diseases. The specific goals of this research are as follows: 1) Site-Selective Remote Functionalization of Aliphatic Amines 2) Selective α-Functionalization of Tertiary Alkylamines 3) Deaminative Functionalization of Primary Amines PHS 398/2590 (Rev. 09/04) Page Continuation Format Page

主要研究者/项目负责人（最后，第一，中间）：Rovis，Tomislav 脂肪胺及其衍生物的选择性官能化 脂肪族胺在药物化合物中普遍存在，这推动了对脂肪族胺的重要研究。 合成和官能化带有氮原子的分子。传统策略使用功能组 合成胺。我们一直在进行一项研究计划， 并将它们直接转换为感兴趣的功能。胺衍生化的主要挑战是， 所以是一个位置选择性。在上一个供资期间提出了一些战略 广泛的成功。 在下一个资助期，我们将扩大反应的剧目，激活的位置和 对现有方法的补充。我们将开发使脂肪胺中的C-H键芳基化的方法， 类似于烯烃双官能化，双官能化邻位C-H键，同样具有完全位置 选择性和使用富含稀土的金属盐来活化胺的远端C-H键。互补 这些方法旨在提供一种官能化叔胺上不可接近的C-H键的方法， 许多FDA批准的药物的共同成分。这将使复杂的结构多样化 分子以及结构编辑方法以提供生物活性分子的同源支架。 最后，伯胺令人惊讶地广泛可得，远远超过烷基卤化物或甚至羧酸。 酸，毫无疑问是由于酰胺键结构的普遍性和重要性。我们将开发一个 这是一种互补策略，其将使用C-N键作为交叉偶联化学中的官能团手柄。 所有这些方法都旨在促进药物设计和发现，以追求更有效的治疗。 治疗人类疾病。 本研究的具体目标如下： 1)脂肪胺的定点远位功能化 2)叔烷基胺的选择性α-官能化 3)伯胺的脱氨基官能化 PHS 398/2590（Rev.09/04）