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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740341
• 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.

大环化合物是化学中的一种独特化学类型，其影响药物、农用化学品、芳香化学品和材料科学领域，影响社会的技术和经济福利。在生物学，医学和能源相关领域的复杂大环化合物的兴趣，突出了新的催化策略的需要。拟议的计划将通过催化的创新解决方案来解决这些最先进的挑战。该计划认识到大环化合物独特的手性结构的潜力，并描述了作为短期目标的平面手性大环化合物的催化路线的发展。重要的是，阻转异构现象是许多领域中公认的挑战，包括药物发现，其中平面手性大环支架基本上未被探索。具体而言，该提案描述了使用不对称有机酸和布朗斯台德酸催化剂从常见的、容易获得的结构单元制备平面手性大环。一个共同的主题是设计的过程，包括多功能的“处理”，可用于定制的大环化合物在各种领域的应用。该提案描述了长期目标，以解决通过环化大环化的化学选择性的关键需求。通过光化学脱保护/大环化序列描述了必需的大环二硫化物的新化学型的制备。此外，该化合物还将利用制药和芳香化学工业所用大环化合物中普遍存在的功能性来实现新的化学。涉及硝基二氢吲哚酰胺的转化将促进大环化以形成酰基官能团，允许合成具有挑战性的大环酮，或使在热介导的过程下有问题的SNAr反应成为可能。此外，通过动态动力学拆分（DKR）制备对映体富集的大环酰胺和酯将利用手性在DKR过程中化学选择性地外消旋关键仲胺和醇。该研究目标为光大环化创造了新的工具，这将更节能，产生更少的废物。最后，展望了铜基配合物作为大环化反应光催化剂的发展前景。阐述了用于能量传递或还原淬灭过程的催化剂的关键结构特征，这在铜基催化剂领域仍然是一个挑战。贱金属催化剂的开发对可持续的分子合成具有相当大的潜在影响，特别是当与工业规模应用兼容的连续流方法并行开发时。总而言之，拟议的研究应该产生重大影响，并形成HQP，他们接受了最先进的合成技术的培训。