Acid-Catalyzed Oxidative Radical Addition of Ketones to Olefins

• Published in: Angewandte Chemie (International ed.) Vol. 53; no. 33; pp. 8737 - 8740
• Main Authors: Schweitzer-Chaput, Bertrand, Demaerel, Joachim, Engler, Hauke, Klussmann, Martin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 11.08.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Catalysis; Chemistry; Chemistry, Multidisciplinary; Formations; Ketones; multicomponent reactions; Olefins; organocatalysis; Peroxides; Physical Sciences; Pyrroles; Radicals; Science & Technology; Styrenes; organocatalysis; FUNCTIONALIZATION; multicomponent reactions; ALKENES; radicals; N-HYDROXYPHTHALIMIDE NHPI; ALKYLATION; ALDEHYDES; STYRENE; ketones; peroxides
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201401062

Based on a mechanistic study, we have discovered a Brønsted acid catalyzed formation of ketone radicals. This is believed to proceed via thermally labile alkenyl peroxides formed in situ from ketones and hydroperoxides. The discovery could be utilized to develop a multicomponent radical addition of unactivated ketones and tert‐butyl hydroperoxide to olefins. The resulting γ‐peroxyketones are synthetically useful intermediates that can be further transformed into 1,4‐diketones, homoaldol products, and alkyl ketones. A one‐pot reaction yielding a pharmaceutically active pyrrole is also described. A radical combination: A multicomponent radical addition of unactivated ketones and hydroperoxide to styrenes under Brønsted acid catalysis provides a range of γ‐peroxyketones. The products can be further transformed into 1,4‐diketones, homoaldol compounds, and alkyl ketones. The formation of radicals is believed to proceed via thermally labile alkenylperoxides, which are generated in situ.