Modern Heck Reactions - New Trends in Cross-Coupling: Theory and Applications - page 410

N 2 BF 4

Pd(OAc) 2 (1 0 mol%)
NaOAc, MeOH, 50°C, 0.5 h

N
CO 2 Me

N
CO 2 Me

85%

Scheme 9.82 The first intramolecular arylation using a diazonium substituent
formed in situ.

until recently. The intramolecular Heck reaction with arenediazonium salts
was discovered by Correia and co-workers. 272 Diazotization is compatible
with various alkenyl pendants, thus opening up the possibility of performing
ring closures. In this way, a number of indoles, benzofurans, chromenes and
similar heterocycles were prepared. In this case, the double bond migrates
into the new ring (Scheme 9.82).
The catalytic systems used for different diazonium salts had to be opti-
mized separately in each case, with either Pd(OAc) 2 or Pd 2 (dba) 3 , NaOAc as
base or base free, and the presence or absence of additives securing the
regeneration of Pd(0) being required to achieve good yields. Very high sen-
sitivity towards remote substituents in the benzene ring was also noted, with
yields varying dramatically along series of similar substrates. Such a thor-
ough study is very important for understanding not only the clear and
spectacular benefits of arenediazonium salts, but also the need for further
investigation and understanding of the factors that control the performance
of catalytic systems involving such reactive substrates and the nature of side
reactions decreasing the output of the desired catalytic process.

9.2.6.1 Base-Free Arylation by Arenediazonium Salts
A special feature of arylation by arenediazonium salts is the possibility of
running the reactions in the absence of base. This possibility was observed
not simply as a strange irregularity, but as a valuable feature opening up new
possibilities only recently, and such base-free Heck reactions have been
swiftly developing since 2008, showing many benefits and special features.
The first examples of base-free reactions were attributed to the use of special
donor ligands, which were considered to increase the acidity of LPdH
intermediates to the extent of permitting spontaneous dissociation and re-
lease of Pd(0) species entering a new turn of the catalytic cycle (for a dis-
cussion, see Ref. 124). Now it is evident that the interpretation was most
likely wrong, and a number of base-free procedures not involving any special
ancillary ligands have been discovered since then. It is therefore more
probable that all PdH intermediates can behave as Brønsted protic acids to
be in equilibrium with Pd(0) and the conjugate acid of whatever is capable of
protonation among the system components. The high reactivity of diazo-
nium salts enables them to capture low concentrations of Pd(0), even when
the increasing acidity of the reaction medium in base-free processes shifts
the PdH deprotonation equilibrium to the left and therefore the build-up of