Practical and Selective sp3 C−H Bond Chlorination via Aminium Radicals

• Published in: Angewandte Chemie International Edition 2021-03, Vol.60 (13), p.7132-7139
• Main Authors: McMillan, Alastair J., Sieńkowska, Martyna, Di Lorenzo, Piero, Gransbury, Gemma K., Chilton, Nicholas F., Salamone, Michela, Ruffoni, Alessandro, Bietti, Massimo, Leonori, Daniele
• Format: Article
• Language: English
• Subjects: Agrochemicals; aminium radical; Biological properties; Chlorination; Chlorine; C−H functionalization; H-atom transfer; Intermediates; late-stage functionalization; Organic chemistry; Photochemicals; Polymers; Selectivity; Steric effects; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202100030

The introduction of chlorine atoms into organic molecules is fundamental to the manufacture of industrial chemicals, the elaboration of advanced synthetic intermediates and also the fine‐tuning of physicochemical and biological properties of drugs, agrochemicals and polymers. We report here a general and practical photochemical strategy enabling the site‐selective chlorination of sp3 C−H bonds. This process exploits the ability of protonated N‐chloroamines to serve as aminium radical precursors and also radical chlorinating agents. Upon photochemical initiation, an efficient radical‐chain propagation is established allowing the functionalization of a broad range of substrates due to the large number of compatible functionalities. The ability to synergistically maximize both polar and steric effects in the H‐atom transfer transition state through appropriate selection of the aminium radical has provided the highest known selectivity in radical sp3 C−H chlorination. Direct and selective sp3 C−H chlorination has been achieved using a photoinduced strategy. This approach is based on a radical‐chain propagation that exploits the ability of aminium radicals to undergo site‐selective H‐atom transfer (HAT).