Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 378

The fourth type of catalytic systems is those which also rely on stable an-
cillaries, but not to increase the reactivity towards oxidative addition. The
role of ligands in this approach is to direct the reaction on to a definite
pathway with high regio- or stereoselectivity and to suppress all alternative
pathways of lower selectivity. Such systems can be defined as ligand-restricted
and are best served by bidentate P,P-, P,N- and N,N-chelators. Such pathways
are by default polar (pathway C in Scheme 9.30), but it is the nature of the
ligands and their effect on reactivity and selectivity that matter, not the
polarity of the pathway. The other important feature of ligand-restricted
Heck reactions is their validity not only for Mizoroki-Heck reactions but also
for oxidative Heck reactions and other extensions of Heck chemistry. The
widest known implementations of ligand-restricted Heck chemistry are the
regioselective reactions of electron-rich olefins and enantioselective Heck
reactions.
9.2.2 Ligand-Accelerated Reactions
As stated above, such reactions rely on stable ancillary ligands, usually
phosphines. However, even the presence of such ligands is not a guarantee
of a ligand-acceleration effect and many such reactions actually belong to the
first and second types - indeed, there are many ''phosphine-free'' reactions
using precatalysts bearing phosphine ligands or their peer analogues (see
below). In order to be treated as ligand-accelerated, the ancillary ligand ef-
fects should be explicitly manifested. The most important manifestations
are as follows:
1. the ability of a given catalytic system to process less reactive substrates
under mild conditions, near room temperatures (20-50 1C) for re-
actions of deactivated aryl bromides and modest temperatures (100-
110 1C or below) for reactions of deactivated aryl chlorides;
2. the ability to process triflates and nonaflates;
3. a wide substrate scope allowing both more reactive and less reactive
substrates to be processed;
4. robustness of the protocols, predictable trends in the dependence of
yields on the reactivity of substrates. This is the robustness which
makes ligand-accelerated reactions the tools of choice for product-
oriented synthetic studies, which indeed often prefer reliable ''load-
and-forget'' protocols, rather than the prospect of tedious tailoring of
some exceptionally ecient and economical procedure developed and
polished for a handful of model substrates.
As already stated, the classical ligand-accelerated protocol developed by
Heck uses Ph 3 Por(o-tol) 3 P to ensure stable reproducible procedures in-
volving iodo- and bromoarenes. Stability and reproducibility are the key
notions here - it is well known that Mizoroki-Heck reactions of iodoarenes
catalysed by phosphine complexes are many orders of magnitude slower