Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 419

was shown by Liu and co-workers, the protocol can even be further simpli-
fied to rely on an unsubstituted phenanthroline ligand. 300
This encouraging metamorphosis, however, should not conceal the
problems with this chemistry. Moreover, these problems should in fact be
welcomed because any progress in solving them would inevitably reciprocate
in Heck chemistry as a whole. One of the most intriguing problems, in our
opinion, is the low eciency of the existing protocols, the need for high
loadings of Pd, commonly in the 5-10% range, but very rarely decreasing
even to 1 mol%. But why is so much palladium used in these reactions?
Indeed, arenediazonium salts can hardly be less reactive than aryl iodides,
the reactions of which are reliably conducted with 0.01-0.1 mol% Pd under
mild conditions (record-making TON/TOF runs are not good reference
points for comparison, as they usually require harsh conditions that cannot
be reproduced in the reactions with arenediazonium salts). In the case of
arenediazonium salts, neither oxidative addition, carbopalladation, nor re-
ductive elimination can be rate-limiting steps. The only step that is sub-
stantially different is the regeneration of catalytically active Pd(0) species. In
the base-free protocols, it relies on spontaneous deprotonation and thus on
a priori unknown Brønsted acidity of PdH depending on a dozen different
factors (e.g. the nature of ancillary ligands, media effects). This process is
indeed very likely to be ineffective, which may prompt a further search for
reactivation methods in addition to what is occasionally applied now (the
addition of various reducing agents, such as CO, carbonyls, etc.). In the base-
assisted reactions, the properties of arenediazonium salts dictate the choice
of weak and often heterogeneous bases, such as CaCO 3 . Needless to say,
such bases, insoluble in the reaction medium, cannot take part in the re-
action directly, rather serving as scavengers of the liberated strong acid.
Therefore, the means of regeneration of Pd(0) is actually the same as in the
base-free reactions - the spontaneous deprotonation of PdH, and the same
restrictions apply.
To conclude, we believe that further progress in Heck reactions with
arenediazonium salts has to rely on further judicious refinement of the
methodology, probably through the search for stable ancillary ligands that
would allow for tuning of the PdH acidity and more effective regeneration
of Pd(0). There is also an encouraging parallel between Heck chemistry
involving arenediazonium salts and oxidative Heck reactions - the two
types actually differ only in the way in which the catalytic cycle is initiated
and terminated, while everything in between is very similar, including
mild conditions, low catalytic eciency, a clear preference for a polar
pathway, regioselectivity, the role of stable ancillary ligands, if any are
used, and the fate of PdH species in base-free environments, where they are
not trapped but rather left to choose their fate themselves. The parallel
development and analysis of regular Heck reactions of arenediazonium
salts and oxidative Heck reactions (particularly the demetallative reactions)
would definitely bring forward new ideas and trends in Heck chemistry
overall.