Photochemical C−H Hydroxyalkylation of Quinolines and Isoquinolines

• Published in: Angewandte Chemie International Edition Vol. 58; no. 47; pp. 16878 - 16883
• Main Authors: Bieszczad, Bartosz, Perego, Luca Alessandro, Melchiorre, Paolo
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 18.11.2019; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Chemistry; Chemistry, Multidisciplinary; Communication; Communications; dihydropyridines; Electromagnetic absorption; Functional groups; Minisci reaction; Natural products; Organic compounds; Oxidants; Oxidizing agents; Photochemicals; photochemistry; Physical Sciences; Quinolines; radical chemistry; Science & Technology; synthetic methods; HOMOLYTIC ACYLATION; ALKYLATION; ARYLATION; FUNCTIONALIZATION; NUCLEOPHILIC CHARACTER; HETEROARENES; HETEROCYCLES; photochemistry; dihydropyridines; SUBSTITUTIONS; Minisci reaction; RADICALS; radical chemistry; synthetic methods; ALKALOIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201910641

We report herein a visible light‐mediated C−H hydroxyalkylation of quinolines and isoquinolines that proceeds via a radical path. The process exploits the excited‐state reactivity of 4‐acyl‐1,4‐dihydropyridines, which can readily generate acyl radicals upon blue light absorption. By avoiding the need for external oxidants, this radical‐generating strategy enables a departure from the classical, oxidative Minisci‐type pattern and unlocks a unique reactivity, leading to hydroxyalkylated heteroarenes. Mechanistic investigations provide evidence that a radical‐mediated spin‐center shift is the key step of the process. The method's mild reaction conditions and high functional group tolerance accounted for the late‐stage functionalization of active pharmaceutical ingredients and natural products. In a different light. A visible light‐mediated C−H hydroxyalkylation of quinolines and isoquinolines that proceeds via a radical path exploits the excited‐state reactivity of 4‐acyl‐1,4‐dihydropyridines 1, which can readily generate acyl radicals upon blue light absorption. By avoiding the need for external oxidants, this strategy enables a departure from the classical, oxidative Minisci‐type pattern and unlocks a unique reactivity, leading to hydroxyalkylated heteroarenes.