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Photochemical C-H Hydroxyalkylation of Quinolines and Isoquinolines.

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.

SUBMITTER: Bieszczad B

PROVIDER: S-EPMC6900123 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Photochemical C-H Hydroxyalkylation of Quinolines and Isoquinolines.

Bieszczad Bartosz B Perego Luca Alessandro LA Melchiorre Paolo P

Angewandte Chemie (International ed. in English) 20191011 47

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 heteroaren ...[more]

PMID: 31529788

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