Selective Palladium-Catalysed Aerobic Oxidation of Alcohols - Transition Metal Catalysis in Aerobic Alcohol Oxidation - page 113

numbers (TONs) were modest. Despite this report, developments in this area
really only picked up pace in the late 1990s. 144,145 In 1998, two different
systems were reported that seemed to mark the start of an intense period of
research in this area. Peterson and Larock reported a Pd(OAc) 2 -dimethyl
sulfoxide (DMSO) system, 146 and Uemura and co-workers reported the use of
pyridines. 147,148 In the DMSO case, the solvent is most likely acting as both a
solvent and a ligand, while the pyridine system allows the use of weakly
coordinating solvents (in that case toluene). The pyridine system was con-
ceivably the first to explore the use of oxidatively stable ligands in this way,
and since that time this is an approach that has been built on by others.
Uemura and co-workers screened a number of pyridine-based ligands, but
simple pyridine was the most effective and their general system consisted of
Pd(OAc) 2 (5 mol%), pyridine (20 mol%) and MS3A (3 Å molecular sieves) in
toluene at 80 1C under 1 atm of O 2 . It was shown to be effective for oxidizing
a wide range of benzylic and aliphatic alcohols, including diols. However, it
is desirable to reduce the loading of Pd, as a loading of 5 mol% (the loading
used in both the DMSO and pyridine systems) is too high to be practical for
many applications. Therefore, although there have been a number of studies
exploiting pyridine-based ligands, we highlight here other ligand systems
that enable lower catalyst loadings to be employed.
The use of bidentate ligands will lead to a more stable catalyst complex
and this means that catalysts do not require an excess of ligand in the same
way that the pyridine system does. Some of the most active systems reported
are based on the use of phenanthroline-type ligands, with initial reports in
this area being published in 2000. 149,150 Sheldon, Arends and co-workers
studied phenanthroline-based systems in detail, examining the influence of
factors such as ligands, pH, solvents, gas pressure/composition and sub-
strates. 151-154 Ligands with methyl groups in the 2- and 9- positions gave the
best performance and the potential of 2,9-dimethyl-1,10-phenanthroline
(neocuproine) was examined in detail. The optimized system is notable be-
cause it can oxidize even unactivated aliphatic substrates with comparatively
low catalyst loadings (down to 0.1 mol%), as shown in Table 4.2.
In the case of aliphatic primary alcohols, the aldehyde is not stable under
the reaction conditions and is common with such substrates it produces the
over-oxidized product, the carboxylic acid. It was demonstrated that the
aldehyde could be produced selectively if the stable free radical TEMPO
(2,2,6,6-tetramethylpiperidine-1-oxyl) was added, as this prevents the
autoxidation of the aldehyde to the acid. It was shown that (neocuproine)-
Pd(OAc) 2 could oxidize smoothly a range of substrates (including
unactivated aliphatic substrates). The catalyst could tolerate the presence of
functional groups such as alkenes, alkynes, halides, ethers, thioethers,
sulfoxides, sulfones, sulfonates, amines, cyanides, amides, carbonates and
esters, although in many of these cases their presence resulted in slower
reaction rates.
More recently, Waymouth and co-workers studied neocuproine-based
catalysts, and prepared [(neocuproine)Pd(m-OAc)] 2 [OTf] 2 (Figure 4.14), which

d n 4 r 4 n g | 2

.