Li Jianbin, Zhang Ding, Tan Lida, Li Chao-Jun
School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Road, Longgang District, Shenzhen, Guangdong, 518172, China.
Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montréal, Québec, H3 A 0B8, Canada.
Angew Chem Int Ed Engl. 2024 Oct 14;63(42):e202410363. doi: 10.1002/anie.202410363. Epub 2024 Sep 12.
The homolysis of chemical bonds represents one of the most fundamental reactivities of excited molecules. Historically, it has been exploited to generate radicals under ultraviolet (UV) light irradiation. However, unlike most contemporary radical-generating mechanisms, the direct excitation to homolyze chemical bonds and produce aliphatic carbon-centered radicals under visible light remains rare, especially in metallaphotoredox cross couplings. Herein, we present our design of the dihydropyrimidoquinolinone (DHPQ) reagents derived from ketones, which can undergo formal deacylation and homolytic C-C bond cleavage to release alkyl radicals without external photocatalysts. Spectroscopic and computational analysis reveal unique optical and structural features of DHPQs, rationalizing their faster kinetics in alkyl radical generation than a structurally similar but visible-light transparent radical precursor. Such a capability allows DHPQ to facilitate a wide range of Ni-metallaphotoredox cross couplings with aryl, alkynyl and acyl halides. Other catalytic and non-catalyzed alkylative transformations of DHPQs are also feasible with various radical acceptors. We believe this work would be of broad interest, aiding the synthetic planning with simplified operation and expanding the synthetic reach of photocatalyst-free approaches in cutting-edge research.
化学键的均裂是激发态分子最基本的反应活性之一。从历史上看，它已被用于在紫外（UV）光照射下产生自由基。然而，与大多数当代自由基生成机制不同，在可见光下直接激发以均裂化学键并产生脂肪族碳中心自由基的情况仍然很少见，尤其是在金属光氧化还原交叉偶联反应中。在此，我们展示了我们从酮类衍生而来的二氢嘧啶并喹啉酮（DHPQ）试剂的设计，该试剂可进行形式上的脱酰基反应和均裂C-C键裂解，从而在无需外部光催化剂的情况下释放烷基自由基。光谱和计算分析揭示了DHPQ独特的光学和结构特征，解释了它们在生成烷基自由基方面比结构相似但可见光透明的自由基前体具有更快的动力学。这种能力使DHPQ能够促进与芳基、炔基和酰卤的多种镍金属光氧化还原交叉偶联反应。DHPQ的其他催化和非催化烷基化转化与各种自由基受体也是可行的。我们相信这项工作将引起广泛关注，有助于简化操作的合成规划，并在前沿研究中扩大无光催化剂方法的合成范围。
