Late-stage diversification of indole skeletons through nitrogen atom insertion

Julia C. Reisenbauer, Ori Green, Allegra Franchino, Patrick Finkelstein, Bill Morandi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Compared with peripheral late-stage transformations mainly focusing on carbon-hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite the recent flurry of activity in this area. Herein, we report the skeletal editing of indoles through nitrogen atom insertion, accessing the corresponding quinazoline or quinoxaline bioisosteres by trapping of an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This reactivity relies on the strategic use of a silyl group as a labile protecting group that can facilitate subsequent product release. The utility of this highly functional group-compatible methodology in the context of late-stage skeletal editing of several commercial drugs is demonstrated.

Original languageEnglish
Article numbereadd1383
Issue number6610
StatePublished - 2 Sep 2022
Externally publishedYes


Dive into the research topics of 'Late-stage diversification of indole skeletons through nitrogen atom insertion'. Together they form a unique fingerprint.

Cite this