Skeletal metalation of lactams through a carbonyl-to-nickel-exchange logic.

Classical metalation reactions such as the metal-halogen exchange have had a transformative impact on organic synthesis owing to their broad applicability in building carbon-carbon bonds from carbon-halogen bonds. Extending the metal-halogen exchange logic to a metal-carbon exchange would enable the direct modification of carbon frameworks with new implications in retrosynthetic analysis. However, such a transformation requires the selective cleavage of highly inert chemical bonds and formation of stable intermediates amenable to further synthetic elaborations, hence its development has remained considerably challenging.

The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines.

Electrophilic aminating reagents have seen a renaissance in recent years as effective nitrogen sources for the synthesis of unprotected amino functionalities. Based on their reactivity, several noble and non-noble transition metal catalysed amination reactions have been developed. These include the aziridination and difunctionalisation of alkenes, the amination of arenes as well as the synthesis of aminated sulfur compounds.

Synthesis of -Alkyl Anilines from Arenes via Iron-Promoted Aromatic C-H Amination.

We report both an intermolecular C-H amination of arenes to access -methylanilines and an intramolecular variant for the synthesis of tetrahydroquinolines. A newly developed, highly electrophilic aminating reagent was key for the direct synthesis of unprotected -methylanilines from simple arenes. The reactions display a broad functional group tolerance and employ catalytic amounts of a benign iron salt under mild reaction conditions.