Catalytic activation and derivatization of methyl esters

甲酯的催化活化和衍生化

• 批准号: 528386-2018
• 负责人: Newman, Stephen
• 金额: $ 8.09万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=692973
• 关键词: Catalytic; activation; derivatization; methyl; esters

The world's most important agrochemicals, pharmaceuticals, and polymers are organic molecules, the vast majority of which are prepared by chemical synthesis. The diverse properties of these molecules derives from the nature and spatial relationship of the functional groups embedded within the carbon-based scaffold. The amide bond is undoubtedly one of the most important functional groups, providing molecules such as peptides and polymers with structural rigidity and the ability to interact with other organic matter. It has been estimated that up to 20% of all chemical reactions done in the world involve the synthesis of an amide. Despite the great importance of amides, the most common methods to synthesize this functional group are surprisingly archaic and wasteful. The Newman lab has recently developed a new catalytic method to form amide bonds from simple and abundant ester and amine precursors. This new method has the potential to provide a more cost effective means for preparing important agrochemicals and pharmaceuticals. However, the current catalyst system suffers from a number of limitations such as the requirement for large amounts of the catalyst, long reaction times, and high temperatures. These problems will need to be solved before potential industrial implementation. Furthermore, the underlying mechanistic discovery that metal catalysts can activate ester starting materials towards substitution chemistry has immense potential to improve the way that we access many other important functional groups. Ketones, aryl amines, aldehydes, AND aryl boronates may be readily accessible using cross-coupling of methyl esters. This research project will seek to accomplish two goals. (1) To gain mechanistic understanding of the newly discovered amide bond formation and use that knowledge to improve the catalyst to the point of industrial viability. (2) To exploit the catalytic activation of esters to make other important organic molecules. Success in these areas will decrease the cost of currently utilized agrochemicals, expand the pipeline of newly developed agrochemicals and pharmaceuticals, and reduce waste generated in chemical manufacturing plants.

世界上最重要的农用化学品、药物和聚合物是有机分子，其中绝大多数是通过化学合成制备的。这些分子的不同性质源于碳基支架中嵌入的官能团的性质和空间关系。酰胺键无疑是最重要的官能团之一，它为多肽和聚合物等分子提供了结构刚性和与其他有机物相互作用的能力。据估计，全世界高达20%的化学反应都涉及到酰胺的合成。尽管酰胺类化合物非常重要，但最常见的合成这种官能团的方法却令人惊讶地陈旧和浪费。纽曼实验室最近开发了一种新的催化方法，可以从简单而丰富的酯和胺前体中形成酰胺键。这种新方法有可能为制备重要的农用化学品和药物提供更具成本效益的手段。然而，目前的催化体系存在着催化剂用量大、反应时间长、反应温度高等诸多局限性。这些问题需要在潜在的工业化实施之前得到解决。此外，金属催化剂可以将酯类起始材料活化为取代化学的潜在机理发现，具有巨大的潜力来改进我们获得许多其他重要官能团的方式。酮、芳胺、醛和芳基硼酸盐可以通过甲酯的交叉偶联很容易地获得。这项研究项目将寻求实现两个目标。(1)从机理上了解新发现的酰胺键的形成，并利用这些知识将催化剂改进到工业可行性的程度。(2)开发酯的催化活性来合成其他重要的有机分子。这些领域的成功将降低目前使用的农用化学品的成本，扩大新开发的农用化学品和药品的管道，并减少化学制造厂产生的废物。