Palladium-nanoparticle-catalysed ullmann reactions in ionic liquids with aldehydes as the reductants: Scope and mechanism

Article abstract of DOI:10.1002/chem.200801621

An efficient Ullmann-type reductive homocoupling of aryl, vinyl and heteroaryl halides can be promoted by an aldehyde in tetraalkylammonium ionic liquids under very mild reaction conditions. This simple procedure generates symmetrical biaryls under relatively mild conditions. The ionic liquid is crucial for this process because it behaves simultaneously as a base, ligand and reaction medium. The role of the aldehyde is also discussed and a general mechanism for this unusual reaction is proposed. These results open the way to a new efficient method of Pd-catalysed dehydrogenation of carbonyl compounds.

Full text of DOI:10.1002/chem.200801621

DOI: 10.1002/chem.200801621
Palladium-Nanoparticle-Catalysed Ullmann Reactions in Ionic Liquids with
Aldehydes as the Reductants: Scope and Mechanism
Vincenzo Calꢀ,[a] Angelo Nacci,*[a, b] Antonio Monopoli,[a] and Pietro Cotugno[a]
Abstract: An efficient Ullmann-type
reductive homocoupling of aryl, vinyl
and heteroaryl halides can be promot-
ed by an aldehyde in tetraalkylammo-
nium ionic liquids under very mild re-
action conditions. This simple proce-
dure generates symmetrical biaryls
under relatively mild conditions. The
ionic liquid is crucial for this process
because it behaves simultaneously as a
base, ligand and reaction medium. The
role of the aldehyde is also discussed
and a general mechanism for this un-
usual reaction is proposed. These re-
sults open the way to a new efficient
method of Pd-catalysed dehydrogena-
tion of carbonyl compounds.
Keywords: biaryls · ionic liquids ·
nanoparticles · palladium · Ullmann
reactions
Introduction
known Ullmann[8] reaction is a useful process, but it requires
an excess of copper[9] and harsh reaction conditions (T>
2008C). A valuable and milder catalytic alternative is the
palladium-catalysed reductive coupling of haloarenes, which
affords symmetrical biaryls and usually requires the pres-
ence of reducing agents such as amines,[10] zinc dust,[11] mo-
lecular hydrogen,[12] hydroquinone,[13] alcohols,[14] carbon
monoxide,[15] ascorbic acid[16] or formic acid salts.[17]
Besides being performed in traditional solvents, these re-
actions have also been carried out in environmentally com-
patible solvents, such as water,[18] poly(ethylene glycol)[19]
and supercritical CO2.[20] In this context, little attention has
been paid to ionic liquids (ILs)[21] as the reaction media,
with a few exceptions.[22]
ILs are more and more frequently suggested as ideal sub-
stitutes for traditional solvents in catalysis, due to their abili-
ty in the immobilisation of transition-metal catalysts. They
are also suitable media for the dissolution of ionic com-
plexes because ILs are capable of retaining these complexes
in a polar state and thus providing remarkable advantages
in terms of activity and selectivity. In addition, ILs open the
route to multiphase processes and easier catalyst recov-
ery.[23]
Biaryls are useful compounds: their skeleton is commonly
found in a variety of bioactive natural substances[1] and they
are key building blocks for the synthesis of pharmaceuti-
cals,[2] conducting materials,[3] agrochemicals, supramole-
cules[4] and ligands for asymmetric catalysis.[5]
Several modern methods for the preparation of biaryls
are available, such as the Suzuki, Stille, Negishi, Kumada
and Hiyama cross-coupling reactions, which involve the pal-
ladium- or nickel-catalysed coupling of aryl halides with an
aryl organometallic reagent.[6] Alternatively, the direct cata-
lytic arylation of simple arenes[7] is another useful route for
the construction of aryl–aryl bonds. However, most of these
methodologies suffer the two major drawbacks of requiring
the preparation of the aryl metal nucleophiles and the use
of these nucleophiles in stoichiometric amounts.
As a consequence, the direct dimerisation of aryl halides
is considered to be a more convenient and straightforward
method for the synthesis of biaryls. In this context, the well-
[a] Prof. V. Calꢀ, Prof. A. Nacci, Dr. A. Monopoli, P. Cotugno
Department of Chemistry
During the last five years, we have shown that a number
of well-known Pd-catalysed reactions, such as Heck, Suzuki
and Stille cross-couplings or hydro-dechlorinations of chlor-
oarenes, can be performed with excellent yields and under
mild conditions by using tetrabutylammonium salt ILs as
the reaction media with Pd colloids as the catalysts.[24]
Indeed, these solvents provide a special colloid stabilisation
by surrounding the Pd nanoparticles with a protecting shell
University of Bari
Via Orabona, 4, 70126 Bari (Italy)
E-mail: nacci@chimica.uniba.it
[b] Prof. A. Nacci
Department of Chemistry, CNR—ICCOM
University of Bari
Via Orabona 4, 70126-Bari (Italy)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801621.
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FULL PAPER
Table 1. Pd-colloid-catalysed arylation of heptanal (1a) in ionic liquids.[a]
that impedes them from aggre-
gating. This type of “ligand-
free” catalysis is gaining consid-
erable importance because it
avoids the use of toxic or ex-
pensive phosphane ligands and
allows catalyst recycling.
In addition, we have recently
found that both the catalyst ac-
tivity and the selectivity are
strictly dependent on the nature
of the anion of the tetraalkyl-
Entry
IL
Base
Conversion [%][b]
Product ratio [%][c]
1a
PhBr
1b
1c
25
1d
2
other by-products
1
2
3
4
5
6
7
8
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
BmimBr[d]
BupyBr[e]
TBAB
TBAB
TBAB
TBAA
K2CO3
Na2CO3
Cs2CO3
NaHCO3
Bu3N
KOAc
K2CO3
K2CO3
TBAA
TBAA
TBAA
–
>99
>99
>99
14
21
46
95
95
95
7
4
3
–
5
>99
>99
>99
>99
47
43
38
32
29
–
–
–
75
34
22
7
21
18
23
–
7
3
4
15
–
–
–
–
–
–
36
35
53
71
95
100
85
10
13
15
–
–
–
2
3
70
–
–
–
5
–-
5
ACHTUNGTRENNUNGammonium salt in these IL
>99
>99
75
70
60
9[f]
10[g]
11[h]
12
8
7
–
media. A clear example was
provided by us in the Heck ary-
lations of allyl alcohols,[24b] in
which the regioselectivity total-
ly changed according to wheth-
er tetrabutylammonium bro-
mide (TBAB) or tetrabutylam-
monium acetate (TBAA) was
used as the reaction medium.
When extending our protocol
to the a arylation of aldehydes,
3
5
5
36
43
78
14
15
10
[a] General conditions: IL (1 g), aryl halide (1 mmol), heptanal (1a; 1 mmol), PdACTHNUTRGNEUNG(OAc)2 (1.5 mol%) and base
(2 mmol) stirred under an inert atmosphere at 1308C. [b] Conversions of both 1a and bromobenzene were
evaluated by GLC with decane as an internal standard. [c] Ratios evaluated on the basis of the GLC peak
areas of all of the products detected. [d] BmimBr: 1-butyl-3-methylimidazolium bromide. [e] BupyBr: N-butyl-
pyridinium bromide. [f] TBAB:TBAA ratio of 5:1 (w/w). [g] TBAB:TBAA ratio of 1:1 (w/w).
[h] TBAB:TBAA ratio of 1:3 (w/w).
we noted that the catalyst behaviour in the latter two ionic
media was so different as to switch the reaction mechanism
from the Heck arylation to a reductive homocoupling. We
report here that, in a reaction unprecedented in the litera-
ture, under typical Heck conditions with TBAA as the
medium, aldehydes promoted a very convenient homocou-
pling of aryl halides under relatively mild reaction condi-
tions.
With weaker bases, such as sodium bicarbonate, tributyl-
AHCTUNGTRENNUNG
Interestingly, when tetrabutylammonium acetate was used
as the base, the selectivity proved to be strictly dependent
on the TBAB:TBAA ratio. Indeed, with an increase in that
ratio up to 5:1 (w/w), the selectivity in favour of the Heck
product 1b was improved to 75% (Table 1, entry 9), al-
though all attempts aimed at totally suppressing the by-
products failed.
Conversely, when the TBAB:TBAA ratio was inverted in
favour of the latter or was 1:1, a remarkable increase in the
biphenyl yields was observed (Table 1, entries 10–12). In
these cases, the bromobenzene was completely converted,
while the initial aldehyde was partially recovered (20–40%).
In addition, besides the expected products 1b–d, small
amounts of a great number of by-products were also detect-
ed (10–15% of the overall peaks). When TBAA was used as
both base and reaction medium, the homocoupling product
became predominant (Table 1, entry 12).
Due to the synthetic importance of biaryls, we decided to
investigate this process in more depth with the aim of devel-
oping a new method for the synthesis of biaryls by using al-
dehydes as sacrificial reagents. As it is known that during
the reductive homocoupling of aryl halides, Pd2+ is generat-
ed and reduced back to Pd0 by using an external reducing
agent and that, in principle, this process requires only two
electrons to close the catalytic cycle,[26] we thought, based on
Results and Discussion
As part of our program aimed at developing powerful cata-
lytic methods in ILs, we were initially interested in the Heck
a arylation of aldehydes, a process that provides very useful
synthons for organic chemistry, such as the a-aryl carbonyl
compounds, but that has remained relatively unexplored.[25]
Following a protocol we have previously reported,[24b] we
were studying Pd-catalysed substitution with bromobenzene
at the a position via the enolate of heptanal (1a). The reac-
tions were carried out by treating aldehyde (1 mmol) with
bromobenzene (1 mmol) in TBAB (1 g) under nitrogen at
1308C for 2 h in the presence of Pd colloids (1.5 mol%) and
a base (2 mmol).
As already reported by Miura and co-workers,[25b] the re-
actions reached complete conversion in the presence of inor-
ganic bases such as potassium, sodium and cesium carbonate
and afforded mixtures of the a-phenylated aldehyde (2-phe-
nylheptanal, 1b), the aldol condensation compound ((E)-2-
pentyl-2-nonenal, 1c) and its g-phenylated derivative ((E)-2-
pentyl-4-phenyl-2-nonenal, 1d) as the main products
(Table 1, entries 1–3). Besides these products, small amounts
of biphenyl (2) were also detected.
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A. Nacci et al.
the data in Table 1, that the aldehyde could behave as the
reductant.
fact that by using aldehydes with short alkyl chains, such as
propanal (6a), the process proved to be highly selective,
with only trace amounts of cinnamic aldehyde as the sole
by-product (Table 2, entry 6). In addition, reactions on iodo-
benzene occurred under very mild conditions (even at
408C), whereas chlorobenzene proved to be unreactive
(Table 2, entries 7–9).
Further mechanistic insights were obtained by using an a-
substituted aldehyde such as 2-phenylpropanal (7a; Table 2,
entry 10). As expected, because the aldol condensation reac-
tion is inhibited in this case, two main by-products, 7b and
Searching for evidence to support this hypothesis, we car-
ried out a series of reactions for the homocoupling of halo-
benzenes, with TBAA as the solvent and with variations in
the structure of the aldehyde (Table 2). After optimisation
of the reaction conditions, we established that by-product
formation was limited by performing the reaction at 908C[27]
with 3 mol% of catalyst and with the minimum amount of
aldehyde required by stoichiometry (0.5 equiv relative to
the aryl halide).
Under these conditions, the
homocoupling of bromoben-
Table 2. Pd-catalysed homocoupling of aryl halides with aldehydes as reductants in TBAA.[a]
zene was totally inhibited in the
absence of aldehyde (Table 2,
entry 1), whereas it proceeded
smoothly in the presence of the
linear aldehydes 1a and 3a–5a
(Table 2, entries 2–5). However,
in these cases variable amounts
of by-products were detected.
Careful GC–MS analyses of the
reaction mixtures allowed the
identification of the by-prod-
ucts as coming from three main
reactions that occur randomly
on the initial aldehydes: Heck
arylation, aldol condensation
Entry
X
Aldehyde
T [8C]
t [h]
Yields [%] of:
biphenyl[b]
by-products
of aldehyde[c]
1
2
3
4
5
6
7
8
9
Br
Br
Br
Br
Br
Br
I
–
90
90
90
90
90
90
70
40
90
90
90
90
90
90
90
14
2
2
5
3
2
4
6
14
1
14
14
14
14
14
–
88
91
86
75
95
90
85
–
80
–
–
–
–
–
22[d]
14[d]
41[d]
37
heptanal (1a)
nonanal (3a)
tetradecanal (4a)
3-phenylpropanal (5a)
propanal (6a)
propanal (6a)
propanal (6a)
propanal (6a)
2-phenylpropanal (7a)
benzaldehyde (8a)
pivalaldehyde (9a)
acetaldehyde (10a)
diphenylacetaldehyde (11a)
diphenylacetaldehyde (11a)
traces[e]
traces[e]
5[e]
I
Cl
Br
Br
Br
Br
Br
Br
–
17
–
–
10
11
and palladium(II)-catalysed de- 12
hydrogenation. Plausible reac-
tion pathways for the formation
13
15[f]
–
14
15[g]
78
60
of most of detected by-products
are given in Scheme 1 for 3-
phenylpropanal (5a). Studies
are in progress to ascertain the
exact mechanisms.
[a] General conditions: TBAA (1 g), aryl halide (1 mmol), aldehyde (0.5 mmol), and PdACHTNUTGRNEUNG(OAc)2 (3 mol%)
stirred under an inert atmosphere at the stated reaction temperature. [b] Reactions were monitored for a max-
imum of 14 h. Yields of biphenyl were evaluated by GLC with decane as an internal standard. [c] By-products
yields were evaluated on the basis of their GLC peak areas with respect to that of the standard. [d] In these
cases, up to 0.2 of an equivalent of the starting aldehyde was recovered depending on the reaction time.
[e] Small amounts of cinnamic aldehyde were detected. [f] Only the aldol condensation compound was detect-
ed. [g] In a reaction carried out under air, benzophenone was the sole by-product.
Of fundamental importance
in understanding the mecha-
nism was the fact that, among
the three processes mentioned,
only the palladium(II)-catalysed
dehydrogenation is suitable to
reduce Pd2+ to Pd0 and close
the cycle of homocoupling. It is
also noteworthy that the effi-
ciency of this catalyst system
proved to be so high that multi-
ple dehydrogenations occurred
and afforded, at first, polyunsa-
turated aldehydes (products 5d
and 5e) and then, after cyclis-
ing condensation (product 5g),
very intriguing polysubstituted
aromatic compounds (product
5h).[28]
Very interesting from the
synthetic point of view was the
Scheme 1. Possible reaction pathways in the presence of 3-phenylpropanal (5a): i) PhPdX (Heck reaction);
ii) aldol condensation with 5a; iii) PdII-catalysed dehydrogenation.
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Pd-Catalysed Reactions in Ionic Liquids
FULL PAPER
5 f, were detected to arise from the Pd-catalysed dehydro-
genation of the initial aldehyde, followed by the Heck aryla-
tion (Scheme 2).
the particular reactivity of that aldehyde. It is known[33] that
the base-catalysed autoxidation of diphenylacetaldehyde can
release formate anions; therefore, it can be assumed that
these latter ions can take the place of enolate 13 as the re-
ducing agent for palladium,[17] as depicted in Scheme 4. It is
noteworthy that the air oxidation of the enolate ion of di-
phenylacetaldehyde most probably proceeds via the dioxe-
tane intermediate 22.[34]
Scheme 2. Major by-products of 2-phenylpropanal (7a).
A
number of proofs supporting the mechanisms in
Scheme 3 and Scheme 4 are given below:
Conclusive confirmation of our hypothesis was found by
using aldehydes 8a–10a, which are totally devoid of protons
at either the a or b position. Indeed, these types of com-
pounds were unable to promote the coupling (Table 2, en-
tries 11–13).
Based on these data, we proposed the general mechanism
depicted in Scheme 3, whereby the generic aldehyde 12,
which must possess at least one proton on both the a and
the b positions, undergoes a fast enolisation equilibrium
under the basic conditions furnished by TBAA[29] to afford
high amounts of enolate 13.
1) Experimental evidence established that homocoupling
was complete with reagents in the following stoichiomet-
ric ratios: ArX:Aldehyde:TBAA=1:0.5:1. This confirms
the mass balance shown in the mechanisms of Scheme 3
and Scheme 4 and reported in Equations (1) and (2) in
Pd
2 ArꢀXþCH CH CHOþ2 AcOꢁ ðTBAAÞ
ƒ!
3
2
ð1Þ
ð2Þ
ArꢀArþCH2¼CHCHOþ2 AcOHþ2 Xꢁ
Pd
2 ArꢀXþPh2CHCHOþ2 AcOꢁ ðTBAAÞþO2
ArꢀArþPh2COþ2 AcOHþ2 XꢁþCO2
ƒ!
The latter compound enters the catalytic cycle by being
ꢀ
ꢀ
coordinated by palladium centre of the Ar Pd X intermedi-
ate 14 to provide the p complex
15.[30] Next, the palladium atom
gives rise to the addition on the
double bond (s complex 16)
followed by the b-hydride elim-
ination, which releases both the
a,b-unsaturated carbonyl com-
pound 17 and the Pd hydride
species 18.[31] The involvement
of the TBAA as a base provides
the anionic s-aryl palladium(0)
complex 19,[32] which in turn
furnishes
the
bisaryl
A
ACHTUNGTRENNUNG
means of oxidative addition to
ꢀ
Ar X. Finally, reductive elimi-
nation to form the biaryl com-
ꢀ
pound (Ar Ar) closes the
cycle.
Scheme 3. The general mechanism, illustrated with propanal.
A special trend was observed
in the case of diphenylacetalde-
hyde (11a; Table 2, entries 14
and 15). As expected, this com-
pound proved to be unable to
promote the coupling, due to
the absence of protons at the b
position. However, when the re-
action was carried out under
air, biphenyl was slowly formed
and the initial aldehyde was
stoichiometrically
converted
into benzophenone.
The singular behaviour ob-
served in this case is related to Scheme 4. The reductive homocoupling with formate anions promoted by diphenylacetaldehyde.
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A. Nacci et al.
Table 3. Pd-colloid-catalysed reductive homocoupling promoted by pro-
pionaldehyde in TBAA.[a]
the case of propanal and diphenylacetaldehyde, respec-
tively.
2) In the cases with aldehydes bearing long alkyl chains,
less than 0.5 of an equivalent of the carbonyl reagents is
needed because of the possibility of multiple dehydro-
genations (Scheme 1, Table 2).
3) Related to the mechanism depicted in Scheme 4, the re-
action carried out by replacing aldehyde with sodium for-
mate occurred in TBAA in a similar way, although with
ꢀ
ꢀ
Entry R X
t
Product R R
Yield
[%][b]
[h]
1
2
2
4
90
88
some minor selectivity due to the formation of noticea-
[35]
ꢀ
ble amounts of hydro-dehalogenation product (Ar H).
4) The air oxidation of diphenylacetaldehyde in TBAA at
908C furnishes, after neutralisation of the reaction mix-
ture with HCl (6N), 1 equivalent of formic acid, as quan-
titatively determined by GC–MS.[36]
3
4
85
5) The formation of carbon dioxide was confirmed by a
positive test with barium hydroxide that was carried out
on the gaseous mixture released during the reaction.
4
5
6
7
7
2
4
1
81
86
90
85
It is evident a key role is exerted by the ionic liquid in
this process. As already found by us for experiments with
allyl alcohols,[24b] the coordinating ability of the anion is cru-
cial in controlling the reaction selectivity. In this regard, the
decisive step can be the addition of the palladium centre to
the enolate ion. Indeed, it can be assumed that the p-com-
plex intermediate 15 (Scheme 3) can follow one of two reac-
tion pathways according to the nature of the anion of the IL
(Scheme 5). If TBAB is the reaction medium, the palladium
atom will be anionic in nature and its addition will occur at
the more electrophilic side of the double bond (Scheme 5;
path a), which will give rise to the migratory insertion and
consequently the Heck product (the a-aryl aldehyde). By
contrast, with TBAA as the solvent, the weakly coordinating
ability of the acetate ion renders the palladium atom cation-
ic in nature, which leads to addition of the metal to the
more nucleophilic position of the double bond of the eno-
late ion, that is, the a position (Scheme 5, path b). This
could be the reason why the homocoupling process occurs
in place of the classical Heck arylation in TBAA.
8
1
4
90
9[c]
92[d]
10
11
4
1
89
86
[a] General conditions: TBAA (1 g), aryl, vinyl or heteroaryl halide
(1 mmol), proprionaldehyde (0.5 mmol) and Pd(OAc)2 (3 mol%) stirred
under an inert atmosphere at 908C. [b] Yields of isolated products.
[c] The initial halide was used as a mixture of E/Z isomers in 85:15 ratio.
[d] A mixture of E,E and E,Z dienes was obtained in a 4.3:1 ratio (see
the Supporting Information).
AHCTUNGTRENNUNG
Finally, the scope and limitation of this methodology have
been investigated by using several aryl, vinyl and heteroaryl
halides as substrates with propionaldehyde as the reducing
agent (Table 3). By using this
latter reagent, in fact, the reac-
tion proved to be very clean, as
very small amounts of by-prod-
ucts were detected (see Table 2,
entry 6). This was probably due
to two main reasons: 1) the low
boiling point of the by-product
acrolein and 2) the tendency of
this latter compound to give
anionic polymerisation promot-
ed by TBAA, as also confirmed
by a separate reaction carried
out by dissolving pure acrolein
in molten TBAA. The data in
Scheme 5. Dependence of the reaction pathway on the nature of the IL anion.
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Pd-Catalysed Reactions in Ionic Liquids
FULL PAPER
the Table 3 show that reactions proceed smoothly on bro-
mides. Iodides and chlorides were excluded from this moni-
toring because the former were synthetically useless and the
latter were unreactive.
to traditional solvents, is the possibility to tune their
chemical properties by simply varying the nature of the
cation and anion (so-called designer solvents). Our re-
sults fall in line with this principle and are in perfect
accord with our previous findings on allyl alcohols[24b] in
that they demonstrate, once again, the extraordinary
effect exerted by the nature of ionic liquids on reaction
outcomes.
Conclusion
In summary, the results presented here proved to be of par-
ticular interest for the following reasons:
1) A new method for synthesising symmetrical biaryls has
been developed, by making use of Pd colloids as the cat-
alyst, an aldehyde as the reducing agent and an ionic
liquid as the reaction medium. Aryl bromides and io-
dides are activated without the use of special additives
or ligands, under relatively mild conditions (reaction
temperatures ranging from 40 to 908C). The procedure is
very simple: the reagents and catalyst source (Pd ace-
tate) are mixed together in the molten IL, with the latter
assuring the almost immediate formation of the catalyti-
cally active species. With propanal as the reducing agent,
the work-up proved to be particularly easy, due to the
volatility of the reaction by-product (acrolein). In addi-
tion, the nature of the surfactant of the tetraalkylammo-
nium IL allows the stabilisation of the Pd nanoparticles,
which behave as a reservoir of catalyst.
2) The role of TBAA is crucial for this process, as this ionic
liquid behaves simultaneously as a base, ligand and reac-
tion medium.[37] Indeed, it first generates the enolate ion,
which is the key intermediate for the Pd reduction
(Scheme 3) and then, due to its weakly coordinating abil-
ity, renders the catalytically active palladium species cat-
ionic in nature, which definitely changes the selectivity
from the expected Heck arylation to the reductive homo-
coupling (Scheme 5). These findings are mechanistically
innovative and unprecedented in the literature, because
TBAA, to our knowledge, is the one and only reaction
medium in which an aldehyde gives rise, in the presence
of an aryl halide, to Pd-catalysed dehydrogenation in-
stead of an a arylation.
Experimental Section
General procedure for the Heck phenylation of heptanal (1a): The tet-
raalkylammonium salt (TBAB or TBAA, 1 g), PdACTHNURGTNEUNG(OAc)2 (6.7 mg,
0.03 mmol), heptanal (1 mmol), base (2 mmol, except for the cases with
TBAA), bromobenzene (1 mmol) and an internal standard (decane,
0.5 mmol) were placed in a 25 mL three-necked flask equipped with a
magnetic bar. The flask was connected with a nitrogen line to create an
inert atmosphere and heated at 1308C. The reaction mixture rapidly
darkened under heating to give a dark brown suspension of very active
Pd nanoparticles. Reactions were monitored by GLC and GC–MS for 2 h
(Table 1).
General procedure for the homocoupling of aryl halides promoted by al-
dehydes in molten tetrabutylammonium acetate: Tetrabutylammonium
acetate (TBAA, 1 g), PdACHTUNTRGNEUNG(OAc)2 (6.7 mg, 0.03 mmol), aldehyde
(0.5 mmol), an internal standard (decane, 0.5 mmol) and aryl halide
(1 mmol) were placed in a 25 mL three-necked flask equipped with a
magnetic bar. The flask was connected with a nitrogen line to create an
inert atmosphere and heated at the reaction temperature for the appro-
priate time (Table 2). All reactions were monitored by GLC and GC-MS
until the disappearance of the starting aldehyde.
In the case with iodobenzene described in entry 8 in Table 2, TBAA, Pd-
AHCTUNGRTEG(NUNN OAc)2 and the aryl halide were added together and the mixture was
melted at approximately 708C. Then, with vigorous stirring, the mixture
was cooled to 408C and the aldehyde was added.
In the case of coupling promoted by diphenylacetaldehyde described in
entry 15 in Table 2, the reaction was conducted in the same manner but
under air.
General procedure for the propanal-promoted synthesis of biaryl in
molten tetrabutylammonium acetate: Tetrabutylammonium acetate
(TBAA, 1 g), PdACTHUNRGTNEUNG(OAc)2 (6.7 mg, 0.03 mmol), propanal (0.5 mmol), and
aryl halide (1 mmol) were placed in a 25 mL 3-necked flask equipped
with a magnetic bar. The flask was connected with a nitrogen line to
create an inert atmosphere and heated at the reaction temperature for
the appropriate time (Table 3). After completion of reaction, the mixture
was washed with dilute HCl, to remove most of the tetraalkyammonium
salt and trialkylammine derived from the IL decomposition, and extract-
ed with 3ꢂ15 mL portions of ethyl acetate. After solvent removal in
vacuo, the organic residue was poured over a short pad of silica gel. The
yields are reported in Table 3.
3) Of similar novelty are our findings on the special behav-
iour of diphenylacetaldehyde, which acts, in this medium,
as a latent source of formate anions and, ultimately, as a
reducing agent for palladium.
4) These results are innovative also from the synthetic
point of view, as they open the way to a new and very ef-
ficient method of Pd-catalysed dehydrogenation of car-
bonyl compounds. A representative example of the dehy-
drogenating ability of this catalyst system has been de-
picted in Scheme 1. By starting from a simple commer-
cially available aldehyde, such as 3-phenylpropanal, it is
possible to obtain, in a one-pot process, a multisubstitut-
ed aromatic compound. Studies aimed at the optimisa-
tion of this protocol are in progress.
Acknowledgement
This work was, in part, financially supported by the Ministero dellꢃUni-
versitꢄ e della Ricerca Scientifica e Tecnologica, Rome, and the Universi-
ty of Bari.
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ꢀ
0
ever, the redox reaction (PdII+2CH3CO2 !Pd +2CO2+CH3 ) re-
leased a methyl radical, which promoted radical chain processes in-
volving the reaction product biphenyl. As a consequence, remark-
able amounts of ortho-, meta- and para-terphenyl and -tetraphenyl
isomers were formed; this lowers the yield and selectivity of the
coupling.
C
[28] To obtain experimental proof, we decided to use an excess of bro-
mobenzene and prolong the reaction time for 5 h. Product 5h was
then isolated as the major by-product and was completely character-
ised (see the Experimental Section).
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butyl chains; as a consequence, the more naked acetate anions pro-
vide conditions that are more basic than those in water.
[30] The free coordination sites of palladium are presumably occupied
by AcOꢀ anions from TBAA. Their exact number is not specified; if
the reaction occurs on the nanoparticle surface, it could be smaller
than four due to linkage of the Pd atom to the metal bulk.
[31] Good evidence for the formation of intermediate 18 is the detection,
in some cases, of small amounts (<2%) of the reductive dehaloge-
ꢀ
nation product Ar H.
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formate is used as the reagent, instead of being generated in situ as
in this case, the side reaction of hydro-dehalogenation occurs to a
greater extent.
1278
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Chem. Eur. J. 2009, 15, 1272 – 1279

Pd-Catalysed Reactions in Ionic Liquids
FULL PAPER
[36] It can be supposed that this reaction can be promoted by metallic
impurities (particularly copper and iron) that are present in ppm
amounts in the ionic liquid. See: M. Tokunaga, Y. Shirogane, H.
Aoyama, Y. Obora, Y. Tsuji, J. Organomet. Chem. 2005, 690, 5378–
5382.
use of KOAc (entry 6) in place of TBAA (entries 9–11) gives rise to
quite different reaction outcomes. Two plausible explanations can
be given: 1) the low solubility of KOAc in TBAB and 2) the pres-
ence of the inorganic cation (K+), which can change the interactions
between ions in the IL.
[37] The role played by TBAA is really unique. Indeed, the same effect
on the chemoselectivity of the catalysis cannot be obtained by re-
placing this ionic liquid with a generic source of acetate anions.
Good evidence is shown in Table 1, in which it can be seen that the
Received: August 6, 2008
Revised: October 15, 2008
Published online: December 15, 2008
Chem. Eur. J. 2009, 15, 1272 – 1279
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1279