Organocatalytic C−H Functionalization of Simple Alkanes

• Published in: Angewandte Chemie 2023-11, Vol.135 (45)
• Main Authors: Su, Fen, Lu, Fengfei, Tang, Kun, Lv, Xiaokang, Luo, Zhongfu, Che, Fengrui, Long, Hongyan, Wu, Xingxing, Chi, Yonggui Robin
• Format: Article
• Language: English
• Subjects: Acylation; Alkanes; Carbon; Carbonyl compounds; Carbonyls; Catalysts; Chemical synthesis; Chemistry; Electrochemistry; Fossil fuels; Hydrogen atoms; Intermediates; Natural products; Polymers; Radicals; Reagents
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202310072

The direct functionalization of inert C(sp 3 )‐H bonds to form carbon‐carbon and carbon‐heteroatom bonds offers vast potential for chemical synthesis and therefore receives increasing attention. At present, most successes come from strategies using metal catalysts/reagents or photo/electrochemical processes. The use of organocatalysis for this purpose remains scarce, especially when dealing with challenging C−H bonds such as those from simple alkanes. Here we disclose the first organocatalytic direct functionalization/acylation of inert C(sp 3 )‐H bonds of completely unfunctionalized alkanes. Our approach involves N‐heterocyclic carbene catalyst‐mediated carbonyl radical intermediate generation and coupling with simple alkanes (through the corresponding alkyl radical intermediates generated via a hydrogen atom transfer process). Unreactive C−H bonds are widely present in fossil fuel feedstocks, commercially important organic polymers, and complex molecules such as natural products. Our present study shall inspire a new avenue for quick functionalization of these molecules under the light‐ and metal‐free catalytic conditions.