Yang Cheng, Farmer Luke A, Pratt Derek A, Maldonado Stephen, Stephenson Corey R J
Willard Henry Dow Laboratory, Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
J Am Chem Soc. 2024 May 8;146(18):12511-12518. doi: 10.1021/jacs.4c00688. Epub 2024 Apr 26.
Phthalimide--oxyl (PINO) and related radicals are promising catalysts for C-H functionalization reactions. To date, only a small number of -oxyl derivatives have demonstrated improved activities over PINO. We postulate that the lack of success in identifying superior catalysts is associated not only with challenges in the design and synthesis of new structures, but also the way catalysts are evaluated and utilized. Catalyst evaluation typically relies on the use of chemical oxidants to generate -oxyl radicals from their parent -hydroxy compounds. Herein we provide an example where a potential-controlled electrochemical analysis reveals that succinimide--oxyl (SINO) compares favorably to PINO as a hydrogen atom transfer (HAT) catalyst-in contrast to previous claims based on other approaches. Our efforts to understand the basis for the greater reactivity of SINO relative to PINO have underscored that the HAT kinetics are significantly influenced by factors beyond changes in thermodynamics. This is perhaps best illustrated by the similar reactivity of tetrachloro-PINO and SINO despite the latter engaging in substantially more exergonic reactions. The key role of HAT transition state (TS) polarization prompted the design and initial characterization of a chlorinated SINO derivative, which we found to be the most reactive -oxyl HAT catalyst reported to date.
邻苯二甲酰亚胺氧基（PINO）及相关自由基是用于C-H官能化反应的有前景的催化剂。迄今为止，只有少数氧基衍生物表现出比PINO更高的活性。我们推测，在寻找更优异催化剂方面缺乏成功不仅与新结构的设计和合成面临的挑战有关，还与催化剂的评估和使用方式有关。催化剂评估通常依赖于使用化学氧化剂从其母体羟基化合物生成氧基自由基。在此，我们给出一个例子，电位控制的电化学分析表明，琥珀酰亚胺氧基（SINO）作为氢原子转移（HAT）催化剂与PINO相比具有优势——这与基于其他方法的先前说法相反。我们为理解SINO相对于PINO具有更高反应活性的基础所做的努力强调，HAT动力学受到热力学变化之外的因素的显著影响。这或许可以通过四氯-PINO和SINO的相似反应活性得到最好的说明，尽管后者参与的反应放能更多。HAT过渡态（TS）极化的关键作用促使我们设计并初步表征了一种氯化SINO衍生物，我们发现它是迄今为止报道的反应活性最高的氧基HAT催化剂。
