Radical
chain reactions leading to C–C bond formation are
widely used in organic synthesis, and initiation of the radical chain
process usually requires thermolabile radical initiators. Recent studies
on transition-metal-free cross-coupling reactions between aryl halides
and arenes have demonstrated an unprecedented initiation system for
radical chain reactions, where the combination of simple organic additives
and a base was used in place of conventional radical initiators. Among
them, the combination of <i>N</i>,<i>N</i>′-dimethylethylenediamine
(DMEDA) and <i>t</i>-BuOK is one of the most efficient and
representative reaction systems, and the radical initiation mechanism
of this system has attracted considerable research interest. In this
study, through the combination of kinetic studies, deuterium labeling
experiments, and DFT calculations, the radical initiation mechanism
of the diamine-promoted cross-coupling reaction was carefully reinvestigated.
In light of the present study, a mechanistic network of radical initiation
in the DMEDA/<i>t</i>-BuOK system was revealed, which differs
dramatically from the previously realized single radical initiation
pathway. In this mechanism, the diamine acts as a hydrogen atom donor
and plays a dual role as both “radical amplifier” and
“radical regulator” to initiate the radical chain process
as well as to control the concentration of reactive radical species.
This represents a rare example of a structurally simple molecule playing
such a subtle role in the radical chain reaction system. The present
study sheds some light on the novel radical initiation mode in transition-metal-free
cross-coupling reactions following a base-promoted homolytic aromatic
substitution (BHAS) mechanism, and may also help to understand the
mechanism of relevant reactions
