Catalytic activation of oxygen-containing functional groups

含氧官能团的催化活化

• 批准号: RGPIN-2020-05065
• 负责人: Newman, Stephen
• 金额: $ 3.5万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748197
• 关键词: Catalytic; activation; oxygen; containing; functional

Chemical synthesis is a laborious practice but is invaluable in providing access to molecules that provide benefits to society and help answer scientific questions. While any molecule can be prepared with existing technology, the demand of time and resources is often unreasonable. Chemical reactions that build complexity or introduce important functionality into an organic molecule are most desirable. In contrast, non-constructive redox manipulation, functional group interconversion, and protection/deprotection steps serve only to prepare a molecule for key bond formations. To make synthesis a more efficient and environmentally friendly practice, we need new chemical reactions that are able to directly harness the unprotected functional groups that are prevalent in abundant feedstock molecules in their native oxidation state. Transition metal catalysis, and cross-coupling reactions in particular, has proven itself to be powerful tool for building molecular complexity that is orthogonal to more traditional nucleophile/electrophile reactions. Thus, while Grignard reactions are the single most common non-catalytic method used to form C-C bonds, their use is now dwarfed by Pd & Ni-catalyzed couplings. Given the abundance of oxygen-containing functional groups like alcohols, phenols, ketones, and carboxylic acids, there are surprisingly few strategies for using these substrates in catalytic coupling reactions. The overarching goal of this research proposal is to change this by implementing activation strategies that exploit the natural behaviour of these functional groups. In particular, 'shortcut' reactions are sought. These direct, single step reactions are designed to replace commonly employed multi-step synthetic procedures that require non-complexity building pre-activation steps. This research goal will be achieved by exploiting the dynamic behaviour of carbon-oxygen bond containing molecules. Six graduate students and ten undergraduate HQP will tackle this problem across three objectives. Activation pathways that weaken C-O bonds in situ are sought to enable alcohols, enols, and carboxylic acids to participate in coupling chemistry as readily as alkyl halides, vinyl triflates, and acid chlorides. Mild methods to manipulate the alcohol/ketone oxidation state (`borrowing hydrogen') will be exploited in the development of Grignard-like 1,2 additions without the requirement of stoichiometric metals. Lastly, strategies to render enones and non-oxygenated pi-systems transiently nucleophilic will be explored, providing a unique approach to formal C-H functionalizations. In solving these problems, HQP will receive world-class training in organic synthesis, catalysis, and modern chemistry technologies. Insights gained along the path to discovery will be generalized to arm chemists with new tools to better access the current and future medicines, materials, and performance chemicals Canadians rely on for their quality of life.

化学合成是一项费力的实践，但在提供为社会造福并帮助回答科学问题的分子方面具有无价的价值。虽然任何分子都可以用现有技术制备，但时间和资源的需求往往是不合理的。构建复杂性或将重要功能引入有机分子的化学反应是最理想的。相比之下，非结构性氧化还原操作、官能团相互转化和保护/脱保护步骤仅用于制备用于关键键形成的分子。为了使合成成为一种更高效、更环保的实践，我们需要新的化学反应，能够直接利用在其天然氧化态的丰富原料分子中普遍存在的未受保护的官能团。过渡金属催化，特别是交叉偶联反应，已被证明是构建与更传统的亲核/亲电子反应正交的分子复杂性的强大工具。因此，虽然格氏反应是用于形成 C-C 键的最常见的非催化方法，但它们的使用现在与 Pd 和 Ni 催化的偶联相比相形见绌。考虑到醇、酚、酮和羧酸等含氧官能团的丰富性，令人惊讶的是在催化偶联反应中使用这些底物的策略很少。本研究提案的总体目标是通过实施利用这些功能组自然行为的激活策略来改变这一现状。特别是寻求“捷径”反应。这些直接的单步反应旨在取代常用的需要不复杂的预激活步骤的多步合成程序。 该研究目标将通过利用含碳氧键的分子的动态行为来实现。六名研究生和十名本科生 HQP 将通过三个目标解决这个问题。人们寻求原位削弱C-O键的活化途径，以使醇、烯醇和羧酸能够像卤代烷、三氟甲磺酸乙烯酯和酰氯一样容易地参与偶联化学。控制醇/酮氧化态（“借氢”）的温和方法将被用于开发类格氏1,2加成物，而不需要化学计量的金属。最后，将探索使烯酮和非氧化的 pi 系统瞬时亲核的策略，为正式的 C-H 官能化提供独特的方法。为了解决这些问题，HQP 将接受有机合成、催化和现代化学技术方面的世界一流培训。在发现过程中获得的见解将被推广，为化学家提供新工具，以更好地获取加拿大人赖以提高生活质量的当前和未来的药物、材料和高性能化学品。