Premium
Photochemical C−H Hydroxyalkylation of Quinolines and Isoquinolines
Author(s) -
Bieszczad Bartosz,
Perego Luca Alessandro,
Melchiorre Paolo
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201910641
Subject(s) - chemistry , reactivity (psychology) , radical , photochemistry , combinatorial chemistry , absorption (acoustics) , organic chemistry , materials science , medicine , alternative medicine , pathology , composite material
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.