Deacylation-aided C-H alkylative annulation through C-C cleavage of unstrained ketones

Arene- and heteroarene-fused rings are pervasive in biologically active molecules. Direct annulation between a C-H bond on the aromatic core and a tethered alkyl moiety provides a straightforward approach to access these scaffolds; however, such a strategy is often hampered by the need of special reactive groups and/or less compatible cyclization conditions. It would be synthetically appealing if a common native functional group can be used as a handle to enable a general C-H annulation with diverse aromatic rings. Here, we show a deacylative annulation strategy for preparing a large variety of aromatic-fused rings from linear simple ketone precursors. The reaction starts with homolytic cleavage of the ketone alpha C-C bond via a pre-aromatic intermediate, followed by a radical-mediated dehydrogenative cyclization. Using widely available ketones as the robust radical precursors, this deconstructive approach allows streamlined assembly of complex polycyclic structures with broad functional group tolerance.

Automated summary

The study demonstrates a deacylative annulation strategy for preparing various aromatic-fused rings from linear simple ketone precursors. This strategy involves homolytic cleavage of the ketone alpha C-C bond via a pre-aromatic intermediate and a radical-mediated dehydrogenative cyclization. The approach allows streamlined assembly of complex polycyclic structures with broad functional group tolerance using widely available ketones as robust radical precursors.