Novel Catalysis for Macrocyclization Processes

大环化过程的新型催化

• 批准号: RGPIN-2020-05006
• 负责人: Collins, Shawn
• 金额: $ 5.76万
• 依托单位: Université de Montréal
• 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=748664
• 关键词: Novel; Catalysis; Macrocyclization; Processes

Macrocycles are a unique chemotype in chemistry that impact the fields of pharmaceuticals, agrochemicals, aromachemicals and materials science, affecting the technological and economic welfare of society. The interest in complex macrocycles in biology, medicine and energy-related fields, has highlighted the need for new catalytic strategies. The proposed program will address these state-of-the-art challenges through innovative solutions in catalysis. The program recognizes the potential of unique chiral architectures in macrocycles, and describes the development of catalytic routes towards planar chiral macrocycles as short term goals. Importantly, atropisomerism is a recognized challenge in many fields, including drug discovery, where planar chiral macrocyclic scaffolds are essentially unexplored. Specifically, the proposal describes using asymmetric organo- and Bronsted acid catalysis to prepare planar chiral macrocycles from common, readily available building blocks. A common theme is the design of processes that include versatile "handles" that can be used to tailor the macrocycles for applications in various fields. The proposal describes long-term goals to address the critical need for chemoselectivity in macrocyclization via photocatalysis. The preparation of novel chemotypes of essential macrocyclic disulfides is described via a photochemical deprotection/macrocyclization sequence. Also, photocatalysis will enable new chemistry using ubiquitous functionality found in macrocycles employed by the pharmaceutical and aromachemical industries. Transformations involving nitroindoline amides will facilitate macrocyclizations to form acyl functionality, permit the synthesis of challenging macrocyclic ketones, or enable SNAr reactions that are problematic under thermally-mediated processes. In addition, the preparation of enantioenriched macrocyclic amides and esters via dynamic kinetic resolution (DKR) would exploit photocatalysis to chemoselectively racemize key secondary amines and alcohols during the DKR process. The research goals create new tools for photomacrocyclization that will be more energy efficient and generate less waste. Lastly, the development of copper-based complexes as photocatalysts for macrocyclization is proposed. Elucidating key structural features of the catalysts for application in energy transfer or for reductive quenching processes, which remain a challenge in the area of copper-based photocatalysis, is described. The development of base metal photocatalysis has considerable potential impact for sustainable molecular synthesis, particularly when developed in parallel with continuous flow methods that are compatible with industrial scale applications. In sum, the proposed research should have a significant impact and form HQP that are trained in state-of-the-art synthetic techniques.

大环是化学中一种独特的化学类型，影响着制药、农用化学品、芳香化学品和材料科学等领域，影响着社会的技术和经济福利。生物、医学和能源相关领域对复杂大环的兴趣突出了对新的催化策略的需求。拟议的项目将通过创新的催化解决方案来应对这些最先进的挑战。该计划认识到在大环中独特的手性结构的潜力，并描述了朝向平面手性大环的催化路线的发展作为短期目标。重要的是，收缩异构在许多领域都是一个公认的挑战，包括药物发现，其中平面手性大环支架基本上未被探索。具体来说，该提案描述了使用不对称有机和Bronsted酸催化从常见的，现成的构建块制备平面手性大环。一个共同的主题是进程的设计，其中包括可用于为不同领域的应用程序定制宏循环的通用“句柄”。该提案描述了通过光催化解决大环化中化学选择性的关键需求的长期目标。通过光化学脱保护/大环化序列描述了新型必需大环二硫化物化学型的制备。此外，光催化将利用在制药和芳香化工行业使用的大环中发现的普遍功能实现新的化学。涉及硝基吲哚酰胺的转化将促进大环化形成酰基官能团，允许合成具有挑战性的大环酮，或使在热介导过程中存在问题的SNAr反应成为可能。此外，通过动态动力学分解（DKR）法制备对映体富集的大环酰胺和酯，在DKR过程中利用光催化对关键仲胺和醇进行化学选择性外消旋。研究目标是为光大环化创造新的工具，这将更节能，产生更少的废物。最后，对铜基配合物作为大环化光催化剂的发展进行了展望。阐明了用于能量转移或还原猝灭过程的催化剂的关键结构特征，这仍然是铜基光催化领域的一个挑战。贱金属光催化的发展对可持续分子合成具有相当大的潜在影响，特别是当与与工业规模应用兼容的连续流方法并行开发时。总而言之，拟议的研究应具有重大影响，并形成在最先进的合成技术训练的HQP。