Photochemical C−H Hydroxyalkylation of Quinolines and Isoquinolines. Issue 47 (11th October 2019)

• Record Type: Journal Article
• Authors: Bieszczad, Bartosz; Perego, Luca Alessandro; Melchiorre, Paolo
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 47(2019)
• Page Start: 16878
• Page End: 16883
• Publication Date: 2019-10-11
• Subjects: dihydropyridines -- Minisci reaction -- photochemistry -- radical chemistry -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201910641
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : 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.