Obora et al. have synthesised and characterised highly catalytically active
DMF-stabilised PdNPs and Cu/PdNPs; these catalysts can be prepared in a facile
manner by simply refluxing PdCl 2 in DMF [41–43]. As palladaphilic solvents such
as DMF along with high-temperature conditions are commonly employed in C–H
activation processes, a role for DMF-stabilised PdNPs (either as a catalyst reservoir)
for catalytically active leached catalyst species or as a directly acting heterogeneous
should not be dismissed. Generally speaking, solvents do play an important role in
cross-coupling chemistry – a recent review discusses these roles in detail [44].
Given the evidence that metal particles can mediate cross-coupling processes via
surface catalysis, highly active Pd particles (/clusters) forming en route to the
inactive Pd black are likely strong contenders for being the active catalytic species
in these cases.
3 The Case for Quasi-Heterogeneous Catalysis in C–H
Activation: Importance of Reaction Conditions
in the Evolution of Heterogeneous Species from
Homogeneous Sources
Common, soluble metal salts, e.g. Pd(OAc) 2 (which is most often derived from its
trimer; Pd 3 (OAc) 6 ) [45], have long been the “go-to” catalysts for homogeneous
catalytic processes, including C–H activation, due to their relative cheapness and
activity as simple Pd
II salts. It is important to note that soluble (homogeneous)
species like Pd(OAc) 2 may be acting as a reservoir for the formation of higherorder species such as Pd
0 clusters or nanoparticles (PdNPs), which may be the true
active species in a given process.
The prevalence of such PdNPs (and whether they are indeed catalytically active)
can vary as a function of the reaction conditions. For example, Fairlamb et al.
investigated a site-selective Pd/Cu-mediated direct C–H arylation reaction of the
nucleotide 2
0 -deoxyadenosine (Scheme 3) [46–48].
It was initially found that the trace impurity in DMF, dimethylamine, was critical
for synthetically significant yields. Another secondary amine, piperidine, which was
observed to bring about a similar activity, was investigated closely. Direct reaction
of Pd 3 (OAc) 6 with an excess of piperidine resulted in the formation of trans-Pd
(OAc) 2 (N-piperidyl) 2 which was found to degrade via a hypothesised DMF-ligated
intermediate to well-defined DMF-stabilised PdNPs (around 1.7 nm, analysed by
TEM) under the C–H arylation reaction conditions (80
C). Thus, the presence of
amines was found to be able to promote the reduction of Pd
II to catalytically active
Pd
0 NPs. Alami et al. showed that the heterogeneous source Pd(OH) 2 /C could be
employed in the C–H arylation of unprotected 8-adenenines using aryl halides in
polar aprotic solvents DMF and NMP [49–50].
The Role of Polar Solvents in Pd Speciation and Propagation
Polar solvents such as DMF, DMAc, NMP (polar aprotic) and H 2 O are commonly
employed as solvents in catalytic C–H bond functionalising processes. There is
180
I. J. S. Fairlamb and N. W. J. Scott
DMF-stabilised PdNPs and Cu/PdNPs; these catalysts can be prepared in a facile
manner by simply refluxing PdCl 2 in DMF [41–43]. As palladaphilic solvents such
as DMF along with high-temperature conditions are commonly employed in C–H
activation processes, a role for DMF-stabilised PdNPs (either as a catalyst reservoir)
for catalytically active leached catalyst species or as a directly acting heterogeneous
should not be dismissed. Generally speaking, solvents do play an important role in
cross-coupling chemistry – a recent review discusses these roles in detail [44].
Given the evidence that metal particles can mediate cross-coupling processes via
surface catalysis, highly active Pd particles (/clusters) forming en route to the
inactive Pd black are likely strong contenders for being the active catalytic species
in these cases.
3 The Case for Quasi-Heterogeneous Catalysis in C–H
Activation: Importance of Reaction Conditions
in the Evolution of Heterogeneous Species from
Homogeneous Sources
Common, soluble metal salts, e.g. Pd(OAc) 2 (which is most often derived from its
trimer; Pd 3 (OAc) 6 ) [45], have long been the “go-to” catalysts for homogeneous
catalytic processes, including C–H activation, due to their relative cheapness and
activity as simple Pd
II salts. It is important to note that soluble (homogeneous)
species like Pd(OAc) 2 may be acting as a reservoir for the formation of higherorder species such as Pd
0 clusters or nanoparticles (PdNPs), which may be the true
active species in a given process.
The prevalence of such PdNPs (and whether they are indeed catalytically active)
can vary as a function of the reaction conditions. For example, Fairlamb et al.
investigated a site-selective Pd/Cu-mediated direct C–H arylation reaction of the
nucleotide 2
0 -deoxyadenosine (Scheme 3) [46–48].
It was initially found that the trace impurity in DMF, dimethylamine, was critical
for synthetically significant yields. Another secondary amine, piperidine, which was
observed to bring about a similar activity, was investigated closely. Direct reaction
of Pd 3 (OAc) 6 with an excess of piperidine resulted in the formation of trans-Pd
(OAc) 2 (N-piperidyl) 2 which was found to degrade via a hypothesised DMF-ligated
intermediate to well-defined DMF-stabilised PdNPs (around 1.7 nm, analysed by
TEM) under the C–H arylation reaction conditions (80
C). Thus, the presence of
amines was found to be able to promote the reduction of Pd
II to catalytically active
Pd
0 NPs. Alami et al. showed that the heterogeneous source Pd(OH) 2 /C could be
employed in the C–H arylation of unprotected 8-adenenines using aryl halides in
polar aprotic solvents DMF and NMP [49–50].
The Role of Polar Solvents in Pd Speciation and Propagation
Polar solvents such as DMF, DMAc, NMP (polar aprotic) and H 2 O are commonly
employed as solvents in catalytic C–H bond functionalising processes. There is
180
I. J. S. Fairlamb and N. W. J. Scott