Selective skeletal editing of polycyclic arenes using organophotoredox dearomative functionalization

Abstract

Reactions that lead to destruction of aromatic ring systems often require harsh conditions and, thus, take place with poor selectivities. Selective partial dearomatization of fused arenes is even more challenging but can be a strategic approach to creating versatile, complex polycyclic frameworks. Herein we describe a general organophotoredox approach for the chemo- and regioselective dearomatization of structurally diverse polycyclic aromatics, including quinolines, isoquinolines, quinoxalines, naphthalenes, anthracenes and phenanthrenes. The success of the method for chemoselective oxidative rupture of aromatic moieties relies on precise manipulation of the electronic nature of the fused polycyclic arenes. Mechanistic studies show that the addition of a hydrogen atom transfer (HAT) agent helps favor the dearomatization pathway over the more thermodynamically downhill aromatization pathway. We show that this strategy can be applied to rapid synthesis of biologically valued targets and late-stage skeletal remodeling en route to complex structures.

Publisher

Nature Research

Publication Date

8-5-2022

Publication Title

Nature Communications

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://dx.doi.org/10.1038/s41467-022-32201-7

Language

English

Format

text

Link to Full Text

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