New Catalytic Methodologies for the Synthesis of Organofluorine Compounds

合成有机氟化合物的新催化方法

• 批准号: RGPIN-2022-04290
• 负责人: Hamel, JeanDenys
• 金额: $ 1.82万
• 依托单位: University of Lethbridge
• 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=748462
• 关键词: New; Catalytic; Methodologies; Synthesis; Organofluorine

Fluorine incorporation into organic compounds poses minimal steric constraints, but its strong electron-withdrawing ability can cause a modulation of the pKa of neighbouring functional groups or the energy of frontier orbitals. Fluorine can also strengthen or participate in key intra- and intermolecular electrostatic interactions. As a result of the effects caused by fluorine incorporation, it has become key to the design of drugs, agrochemical agents, and advanced materials among other areas. This is remarkable as fluorine is virtually absent from naturally occurring organic compounds, and there is now a growing need for robust methods to access and build complexity into organofluorine compounds. Furthermore, sustainable syntheses are highly desirable and may come from improved reaction conditions minimizing chemical wastes, and from novel disconnections enabling short syntheses. Transition-metal catalysis may be a key tool to engage organic compounds into new reactivity patterns, streamlining the synthesis of fluorinated molecules via reliable and step-efficient processes. Thus, the overarching goals of this research program will be (1) to manipulate C-H and C-C bonds to better access and derivatize organofluorine compounds; (2) to establish processes for preparing strained or fused, fluorinated cyclic compounds, and investigate their novel applications towards new fluorinated motifs; and (3) to explore the bioisosterism of new fluorinated motifs and their potential as molecular probes. Over the next five years, under this Discovery Grant, graduate and undergraduate students involved in my research activities will develop new synthetic routes to fluorinated molecules by exploiting C-H and C-C bonds as handles for functionalization, and will expand on the reactivity, installation, and applications of strained fluorinated carbocycles, particularly bicyclo[1.1.1]pentanyl derivatives and gem-difluorocyclopropanes. The overall research program will result in major advances that will influence how we construct and manipulate organofluorine compound, benefiting academia, the Canadian industry (e.g. pharmaceutical, agrochemical), and efforts in R&D at large.

氟掺入到有机化合物中造成最小的空间限制，但其强的吸电子能力可以引起邻近官能团的pKa或前线轨道的能量的调制。氟还可以加强或参与关键的分子内和分子间静电相互作用。由于氟掺入所引起的影响，它已成为药物、农用化学品和先进材料等领域设计的关键。这是值得注意的，因为氟实际上不存在于天然存在的有机化合物中，并且现在越来越需要稳健的方法来获取和构建有机氟化合物的复杂性。此外，可持续的合成是高度期望的，并且可以来自最小化化学废物的改进的反应条件，以及来自能够实现短合成的新型断开。过渡金属催化可能是使有机化合物进入新的反应模式的关键工具，通过可靠和分步高效的过程简化氟化分子的合成。因此，本研究计划的总体目标将是（1）操纵C-H和C-C键，以更好地获得和衍生有机氟化合物;（2）建立制备应变或稠合的氟化环状化合物的方法，并研究其在新氟化基序中的新应用;（3）探索新氟化基序的生物电子等排性及其作为分子探针的潜力。在接下来的五年里，在这项发现资助下，参与我研究活动的研究生和本科生将通过利用C-H和C-C键作为官能化的把手来开发氟化分子的新合成路线，并将扩大应变氟化碳环的反应性，安装和应用，特别是双环[1.1.1]戊烷基衍生物和偕-二氟环丙烷。整个研究计划将导致重大进展，这将影响我们如何构建和操作有机氟化合物，使学术界，加拿大工业（例如制药，农用化学品）以及整个研发工作受益。