Skeletal Editing of Indoles and Pyrroles Enabled by a Novel, Atomic Carbon Equivalent

Key words

atomic carbon equivalent - Cl-DADO - skeletal editing - late-stage diversification

Significance

Indoles and pyrroles are common structural motifs in drug discovery. As such, any chemical tool that allows for the late-stage diversification of these heterocycles would be of high ­value to the medicinal chemistry community. The ­Glorius group has developed an atomic carbon equivalent called Cl-DAD^FO that allows for the skeletal editing of indoles and pyrroles to their corresponding ring-expanded quinoline and pyridine derivatives, respectively. The photosensitive oxime ester group provides a handle for subsequent structural diversification.

Comment

The ring expansion product was reliably generated for pyrroles and indoles with substituents at all positions, including C2. Following ring-expansion, radical reaction of the oxime ester allowed for further diversification. This skeletal editing sequence was applied to several drug molecules and natural products, including the anti-migrane medication sumatripan and the anti-fungal natural product brevianamide F.