A simple method for N-arylation of secondary amides/amines through a NaH-initiated aryne generation strategy

A very simple and practical method has been uncovered for N-arylation of many sets of secondary amides/amines. The reaction could be easily conducted in a vial without the use of strictly anhydrous reagents and/or an inert atmosphere. This transition metal-free coupling reaction was based on the use of our previously reported novel aryne generation system: a combination of o-diiodoarene and sodium hydride. In our protocol, sodium hydride acts as an iodophile by forming a neighboring-group-assisted transition state with o-diiodoarene, which greatly enhances the metal-halogen exchange process. o-Diiodoarene has two roles in the reaction: (i) as an aryne precursor to produce an aryne at near room temperature and (ii) as an electrophilic iodine donor to support the generation of the final o-iodoaryl product. The generality of the method is demonstrated by 99 examples containing almost all kinds of amides and amines.