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.
Photochemical C-H Hydroxyalkylation of Quinolines and Isoquinolines / Bieszczad, Bartosz; Perego, Luca Alessandro; Melchiorre, Paolo. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - ELETTRONICO. - 58:47(2019), pp. 16878-16883. [10.1002/anie.201910641]
Photochemical C-H Hydroxyalkylation of Quinolines and Isoquinolines
Melchiorre, Paolo
Ultimo
Supervision
2019
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.