Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 397

Ph

Cl Ph

Pd precat (0.5 mol% )
NaOAc
Bu 4 NBr, 140°C, 12-24 h

MeO MeO 82%

Pd precat
(14)
(15)

Time
24 h
12 h

82%
65%

Scheme 9.60 The use of precatalysts 14 and 15 in the arylation of styrene by an
electron-rich chloroarene.

Cl

R'

(16) (1 mol%)
LiO H·H 2 O
DMA, 160°C, 44 h

+

R

R R'

62-8 0%

R = H, Me, OMe; R' = Me, OMe

Scheme 9.61 Arylation of styrenes by electron-rich chloroarenes using

precatalyst 16.

Exceptionally thermally stable complexes, such as 16, were shown by
Kantam and co-workers to be among the best so far known precatalysts to
afford the Mizoroki-Heck reaction of electron-rich chloroarenes with styr-
enes 223,224 (Scheme 9.61). These precatalysts work at 160 1C provided that
LiOH H 2 O is used as base in a polar solvent (DMA or NMP). These pre-
catalysts under such conditions apparently provide optimal levels of active
Pd release, so no common additives are required for extra stabilization. The
reactions were very slow, however, which reflects both the rate of release and
the rate of oxidative addition to C-Cl bonds, which are presumably matched
to each other. Reactions were carried out with a 1 mol% Pd loading, but
0.1 mol% could also be used with an insignificant deterioration of the yield
to achieve a TON of 620.
These new systems, capable of involving electron-rich chloroarenes, are
evidently too different to allow for identification of general trends to account
for a high reactivity and performance. Each individual parameter (nature of
precatalyst, loading, media, additives, base, temperature, concentrations,
etc.) can be varied, with the proper combination and conditions to be arrived
at only by optimization of a chosen system, and remain valid only for a
relatively narrow set of substrates.
For more reactive bromo- and iodoarenes, the offer of new systems is
naturally broader. Such systems may not seem very practical, but each shows
something important about the operation of ''phosphine-free'' catalytic
cycles based on both regular and slow-release precatalysts. Moreover, it
could be argued that the difference between the chloroarene-enabled sys-
tems and those developed for more reactive substrates is not dramatic. In
fact, further optimization of any less active system can result in a substantial