Generation of Z-Olefins via formic acid-mediated, metal-catalyzed additions to dienes

通过甲酸介导、金属催化的二烯加成生成 Z-烯烃

• 批准号: 531905-2018
• 负责人: Lundgren, Rylan
• 金额: $ 9.11万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658098
• 关键词: Generation; Olefins; via; formic; acid

The pharmaceutical, agrochemical, and fine-chemical sectors are under increasing pressure to prepare complex small molecules in an efficient manner while minimizing associated costs and waste outputs. The Z-olefin unit is a key structural feature found in drug molecules, fragrances and perfumes, and insecticides, while also serving as a linchpin unit in chemical synthesis. As Z-olefins are generally less thermodynamically stable than the corresponding E-isomers, their construction in the context of functional molecule synthesis remains challenging. ****We have developed a new method for the preparation of Z-olefins from dienes via the selective transfer of hydrogen from formic acid. The Rh-catalyzed process provides access to products with high chemo-, stereo-, and regioselectivity. The reduction pathway can be interrupted in the presence of electrophiles to form coupled products that contain the Z-olefin fragment. The use of formic acid as the hydride source is key to the methodology and provides significant advantages over protocols that use high pressures of hydrogen gas or inorganic/organometallic reducing agents. In order to ensure uptake of the process by commercial partners and to expand our IP landscape we aim to: 1) expand the scope of targets that can undergo Z-selective reduction and reductive coupling to strengthen the platform of reactivity; 2) identify new metal/ligand combinations that promote improved reactivity and scope at reduced metal-loadings for each class of reaction; 3) further develop collaboration and licensing relationships with partners in the pharmaceutical/custom synthesis/chemical manufacturing sectors. These studies will enable the generation of a suite of synthetic manifolds and catalysts to prepare both simple and complex molecules bearing Z-olefin units under conditions that are attractive to employ in both discovery and production contexts.******************

制药、农化和精细化工行业面临着越来越大的压力，需要以有效的方式制备复杂的小分子，同时最大限度地减少相关成本和废物产生。 Z-烯烃单元是药物分子、香料和杀虫剂中的关键结构特征，同时也是化学合成中的关键单元。由于 Z-烯烃的热力学稳定性通常不如相应的 E-异构体，因此它们在功能分子合成中的构建仍然具有挑战性。 ****我们开发了一种通过甲酸选择性转移氢从二烯制备 Z-烯烃的新方法。 Rh 催化过程提供了具有高化学选择性、立体选择性和区域选择性的产品。在亲电子试剂存在的情况下，还原途径可以被中断，形成含有 Z-烯烃片段的偶联产物。使用甲酸作为氢化物源是该方法的关键，并且比使用高压氢气或无机/有机金属还原剂的方案具有显着的优势。为了确保商业合作伙伴采用该工艺并扩大我们的知识产权版图，我们的目标是：1）扩大可以进行Z选择性还原和还原偶联的目标范围，以加强反应平台； 2) 确定新的金属/配体组合，以提高每类反应的反应性和减少金属负载量的范围； 3) 进一步发展与制药/定制合成/化学品制造领域合作伙伴的合作和许可关系。这些研究将能够生成一套合成歧管和催化剂，以在对发现和生产环境具有吸引力的条件下制备带有 Z-烯烃单元的简单和复杂分子。 ********** ******