Low-Valent Cobalt-Catalyzed C-H Activation: Mechanistic Insight for Synthetic Applications

低价钴催化的 C-H 活化：合成应用的机理洞察

• 批准号: 289205672
• 负责人: Professor Dr. Lutz Ackermann
• 金额: --
• 依托单位: Institut für Organische und Biomolekulare Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/289205672?language=en
• 关键词: Low; Valent; Cobalt; Catalyzed; Activation

The advent of practical transition metal-catalyzed C-H activation reactions is currently revolutionizing organic synthesis. Thanks to their ubiquity in organic molecules, C-H bonds represent ideal targets for a direct functionalization approach. The resulting synthetic routes are short and efficient, thus saving resources and generating less waste. At the same time, C-H functionalizations are inherently challenging due to the low intrinsic reactivity of the C-H bond and the difficulty to control the site-selectivity. Most current methods rely on 4d transition metals as catalysts, whose high prices severely compromise the sustainability of the approach, however. Therefore, practical C-H functionalizations employing naturally abundant 3d transition metals as catalysts are in high demand. Very recent work points to low-valent cobalt complexes as particularly active and promising catalysts. As the molecular mode of action of these catalysts is almost completely unknown, their rational and systematic improvement today is impossible. The present proposal seeks to change this situation. In the first step, it aims at the full mechanistic elucidation of cobalt-catalyzed C-H functionalizations. To this end, it will characterize the in situ-formed reaction intermediates by electrospray-ionization mass spectrometry. This analytical method is particularly well-suited for this purpose because it selectively detects charged species, which supposedly play a crucial role in cobalt-catalyzed C-H functionalizations. Preliminary results fully confirm this notion. Additional experiments will probe the microscopic reactivity of mass-selected cobalt complexes in the gas phase as well as the reaction kinetics in solution. In the second step, the project will build upon the gained mechanistic insight to develop novel methods for cobalt-catalyzed C-H functionalizations. The careful design of ligands shall make possible the functionalization of unactivated C(sp3)-H bonds. Moreover, it will be attempted to replace the currently required Grignard reagents for milder bases, thereby boosting the functional-group tolerance of the reactions. Thus, the newly developed methods will greatly enhance the utility of C-H functionalization reactions for organic synthesis.

实际过渡金属催化的C-H激活反应的出现目前正在革新有机合成。由于它们在有机分子中的普遍性，C-H键代表了直接功能化方法的理想目标。由此产生的合成路线效率短而有效，从而节省了资源并减少了浪费。同时，由于C-H键的固有反应性低以及控制位点选择性的困难，C-H功能化本质上是具有挑战性的。当前的大多数方法都依赖于4D过渡金属作为催化剂，但是，高价严重损害了该方法的可持续性。因此，用自然丰富的3D过渡金属作为催化剂的实用C-H功能化量很高。最近的工作表明，低价值的钴络合物是特别活跃和有希望的催化剂。由于这些催化剂的分子作用方式几乎是完全未知的，因此它们的理性和系统的改进是不可能的。本提案试图改变这种情况。在第一步中，它旨在全面阐明钴催化的C-H功能化。为此，它将通过电喷雾质谱法来表征原位形成的反应中间体。这种分析方法特别适合此目的，因为它有选择地检测到带电物种，据说这在钴催化的C-H功能化中起着至关重要的作用。初步结果充分证实了这一概念。其他实验将探测气相中质量选择的钴复合物以及溶液中的反应动力学的显微反应性。在第二步中，该项目将建立在获得的机械洞察力的基础上，以开发用于钴催化的C-H功能化的新方法。配体的仔细设计应使未激活C（SP3）-h键的功能化。此外，它将尝试替换当前所需的Grignard试剂，以提高反应的功能组公差。因此，新开发的方法将大大增强C-H功能化反应对有机合成的实用性。