Anilide activation of adjacent C-H bonds in the palladium-catalysed Fujiwara-Moritani reaction

Article abstract of DOI:10.1039/c0dt00378f

The Pd(ii)-catalysed oxidative counterpart of the Heck reaction, originally described by Fujiwara and Moritani, has been studied in detail by a combination of NMR, single-crystal X-ray diffraction and substrate variation. The process involves a palladacycle that is a true intermediate in catalysis. Pd(OAc) ₂ is first converted into a more electrophilic palladium species for effective catalysis, defining the main role of added acid. In the course of these studies, three palladacyclic intermediates have been characterised by X-ray diffraction, firstly the directly produced acetate complex 1, the camphorsulfonate complex 2, and additionally tosylate 3, isolated from a reacting system, demonstrating the accessibility of a cationic or comparably electrophilic palladium entity under turnover conditions. The isolated palladacycle 3 is also an effective catalyst. The reaction rate shows a first-order dependency on [anilide] and [Pd], but not on benzoquinone, alkene or p-TsOH. Acid, in the form of p-TsOH, is an essential component, whereas acetate is dispensable. A crossover experiment involving distinct substitution in reactant and palladacycle demonstrates that the palladacycle is directly involved in the catalysis.

Full text of DOI:10.1039/c0dt00378f

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www.rsc.org/dalton | Dalton Transactions
Anilide activation of adjacent C–H bonds in the palladium-catalysed
Fujiwara–Moritani reaction†‡
Waqar Rauf, Amber L. Thompson and John M. Brown*
Received 27th April 2010, Accepted 17th June 2010
DOI: 10.1039/c0dt00378f
The Pd(II)-catalysed oxidative counterpart of the Heck reaction, originally described by Fujiwara and
Moritani, has been studied in detail by a combination of NMR, single-crystal X-ray diffraction and
substrate variation. The process involves a palladacycle that is a true intermediate in catalysis. Pd(OAc)2
is first converted into a more electrophilic palladium species for effective catalysis, defining the main role
of added acid. In the course of these studies, three palladacyclic intermediates have been characterised
by X-ray diffraction, firstly the directly produced acetate complex 1, the camphorsulfonate complex 2,
and additionally tosylate 3, isolated from a reacting system, demonstrating the accessibility of a
cationic or comparably electrophilic palladium entity under turnover conditions. The isolated
palladacycle 3 is also an effective catalyst. The reaction rate shows a first-order dependency on [anilide]
and [Pd], but not on benzoquinone, alkene or p-TsOH. Acid, in the form of p-TsOH, is an essential
component, whereas acetate is dispensable. A crossover experiment involving distinct substitution in
reactant and palladacycle demonstrates that the palladacycle is directly involved in the catalysis.
A stoichiometric version of the Heck reaction, claimed to
Introduction
involve the palladacycle intermediates that were characterised in
solution by 1H NMR, is shown in Scheme 1.7 Somewhat unusually,
Horino used acetanilides as palladacycle precursor. Over the next
twenty years there were only sporadic developments to encourage
the prospect of a general C–H activation based Heck reaction, one
similar to the Fujiwari–Moritani protocol but with the advantage
of regioselectivity arising from an adjacent activating and directing
group.8 The remarkably simple expedient of modifying Horino’s
reaction by adding stoichiometric amounts of p-benzoquinone
and acid was successful.9 In this way de Vries and colleagues
provided a benchmark example of a Pd(II)-catalysed regiospecific
Heck process (Scheme 1). More recent work has broadened
the scope, particularly by variation of the directing group, and
activation of the sp3-carbon.10
The chemistry of palladacycles, in which an aryl–palladium bond
is stabilised by an ortho-substituent capable of forming a donor
bond to the metal, is long-standing.1 Early studies focused on the
conditions of synthesis and their stoichiometric reactions. With the
upsurge of interest in palladium catalysis, stable palladacycles were
found to be useful pre-catalysts providing a useful entry into the
reaction cycle, without necessarily being involved directly.2 Over-
all, the twin process of palladacycle formation, and substitution at
the same site, constitute C–H activation promoted by palladium.
Since the first step is formally an electrophilic substitution, and
the second is formally a reductive elimination, the reaction is
stoichiometric in palladium unless re-oxidation can be effected.
The initial oxidation state is Pd(II), retained in the palladacycle,
but Pd(0) is formed in the second step.
There are two good analogies in the early palladium literature.
Fujiwari and Moritani showed that the alkenylation of benzene,
which must involve an arylpalladium species, can be a catalytic
process.3 Later work has established good conditions for a catalytic
procedure, using oxygen as the re-oxidant.4 The original papers of
Heck showed examples of catalysis of the catalytic alkenylation
of arylmercurials when Cu(II) was present as a re-oxidant.5 Here,
the aryl group is delivered to palladium as a nucleophile; only the
later note of Mizoroki involves an electrophilic aryl group in the
alkenylation process, and dispenses with the need for an oxidant.6
This of course prevailed as the standard variant, for what has
become one of the most widely used catalytic synthetic processes
in organic chemistry.
Scheme 1 The basis of stoichiometric (ref. 7) and catalytic (ref. 9)
alkenylations of anilides.
Chemistry Research Laboratory, Department of Chemistry, Oxford Univer-
sity, Oxford, UK, OX1 3TA. E-mail: john.brown@chem.ox.ac.uk; Fax: 44
1865 285002
† Based on the presentation given at Dalton Discussion No. 12, 13–15th
September 2010, Durham University, UK.
Results and discussion
Background
In an early entry into directed C–H activation, we showed that
substitution of indole by an N-(2-pyridylmethyl) group enabled
‡ CCDC reference numbers 775340–775342. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/c0dt00378f
10414 | Dalton Trans., 2010, 39, 10414–10421
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The Royal Society of Chemistry 2010
©

regiospecific catalytic C–H activation and alkenylation at the
indole 2-position (Scheme 2).11 In contrast, we were unable to
observe catalysis with either of the other N-substituted indoles
shown in Scheme 2. These latter reactants readily formed well-
characterised palladacycles, however, whilst the N-pyridylmethyl
derivative did not.12 This led us to consider alternative possibilities
for the role of the directing group, including promotion of proton
transfer without direct formation of a Pd–C bond.
of the intermediacy of palladacycles, and the role of added acid.
The final component is benzoquinone as Pd(0) re-oxidant, and a
recent detailed study of the re-oxidation step has been reported,
albeit in a different context.17
Structure and reactivity of palladacyclic species
Palladacycles derived from acetanilides had been reported
previously,7 but not structurally characterised until very recently;19
this was the first objective. We were successful in solving the
structures of three related palladacyclic complexes as indicated
in Scheme 4.
Scheme 2 Previous work involving activation of the 2-position of indole.
In a similar vein, questions have been raised concerning the
mechanism of palladacycle formation, and whether this is a
simple electrophilic substitution or a concerted process in which
the formation of the Pd–C bond is coupled to a separate
proton transfer to palladium-bound acetate or to another base.13
Davies, MacGregor and colleagues have provided support for the
second pathway from DFT calculations on the metallation of
N,N-dimethylbenzylamine by Pd(OAc)2. Similarly, Maseras and
Echavarren find a low-energy proton transfer pathway to coordi-
nated acetate in computed arylation reactions. The barrier is lower
when an electron-poor arene is involved.14 Fagnou has proposed a
similar route and described this as the “concerted protonation-
demetallation” pathway, based on experimental data for Pd-
catalysed non-directed C–H activation/arylation reactions.15 The
relative reactivity shows some correlation with C–H pKa in many
cases. Hence, a classical Wheland-type intermediate is not well
supported by computation or experiment, based on these examples
(Scheme 3).
Scheme 4 Synthetic routes to palladacycles 1–3; (a) as ref. 7, then CH3CN,
re-crystallise CH3CN–pentane; (b) anilide,1-(S)-camphorsulfonic acid,
re-crystallise ppt from CH3CN; (c) anilide, p-TsOH, Pd(OAc)2,(1 : 1 : 2)
acetone; re-crystallise CH3CN.
First of all, the palladacycle 1 was formed by refluxing 4-
methylacetanilide and Pd(OAc)2 in toluene and was then charac-
terised by 1H and 13C NMR in CD3CN. Attempts to re-crystallize
the dimer were not successful due to its poor solubility. Although
soluble in MeOH and AcOH when freshly prepared, it precipitates
gradually, possibly because of polymerization. Addition of MeCN
formed a derivative which was recrystallized from acetonitrile–
pentane. The resulting crystals were analyzed by X-ray and the
ensuing structure is shown in Fig. 1.
The coordination geometry of the Pd atom is almost perfectly
planar (rms deviation of the metal and directly-bonded atoms from
˚
their best plane = 0.05 A). The phenyl ring is inclined slightly away
from this plane by a rotation about the Pd–C bond (interplanar
angle between the PdCN2O and C6 best planes 19.4◦). The acetate
group is coordinated through a single oxygen and the C–O
distances suggest that the double bond is partially localised. The
interplanar angle between the C2O2 plane and that of the PdCN2O
fragment is 89.9◦. The amide NH forms a hydrogen bond to the
non-coordinated oxygen atom of a second molecule (N(1) ◊ ◊ ◊ O(3)’
Scheme 3 Possible pathways for the C–H activation of anilides by Pd(II);
A via a Wheland intermediate, B via ambiphilic metal–ligand activation.
The conditions for Fujiwara–Moritani reaction in the ac-
etanilide series are among the mildest recorded for C–H activa-
tions, and furthermore, electron rich aromatics are favoured.16
This raises the possibility that a more conventional electrophilic
substitution mechanism will be worth consideration in this case.
The reaction additionally affords an opportunity for a formal test
˚
2.837(5) A). The two molecules form a centrosymmetric dimer
in which the two ArNHCOMe fragments make a face-to-face
contact but there is no evidence of any direct interaction between
˚
the two metal centres. The Pd ◊ ◊ ◊ Pd distance is 5.9618(6) A. Our
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©

Fig. 3 The crystal structure of the tosylate complex 3; displacement
ellipsoids are drawn at 50% probability.
crystal structure is shown in Fig. 3 and reveals a covalently coor-
dinated tosylate, located trans- to the C–Pd bond. The remaining
coordination site is occupied by an adventitious water molecule.
The only close relative of this structure was reported recently by
Yu and co-workers, as noted above. A CDS search reveals several
Fig. 1 The crystal structure of palladacycle 1; displacement ellipsoids are
drawn at 50% probability.
1
further structures of h -bound Pd tosylates, although none of the
preliminary publication on the regiochemistry of cyclopalladation
and catalysis included two related ring-substituted structures.19
Very recently, Yu and co-workers reported a further example, that
also included a covalent Pd tosylate.18
others involve palladacycles.20,21
NMR observation of catalytic turnover
In the course of surveying reaction conditions, the methane-
sulfonate (MeSO3)2Pd was prepared, and shown to catalyse
alkenylation, albeit slowly in the absence of acid; the dimeric
mesylate palladacycle 4 derived from 4-methylacetanilide was
prepared as well. Additionally, it was discovered that (+/-)-
camphorsulfonic acid was ineffective as an acid additive when used
in place of p-TsOH. Essentially all the palladium was precipitated
under these conditions (Scheme 4). The precipitated product was
shown to be acetate-free by NMR; there are precedents for bridged
dipalladium disulfonates.19 By dissolution of this precipitate in
MeCN it proved possible to grow X-ray quality crystals of an
ionic product 2. The structure is shown in Fig. 2.
Preliminary experiments were carried out, in order to establish
suitable conditions for monitoring the reaction by H NMR. A
1
survey of oxidants did not reveal any reagent that was superior
to p-benzoquinone The solvent of choice proved to be acetone-d6,
and conversions of ≥90% were obtained under standard ambient
conditions. A specific advantage of acetone as solvent was the lack
of any tendency to precipitate quinhydrone during turnover. It
was confirmed that catalytic turnover was higher for electron-rich
acetanilides (e.g. p-Me > p-F). The alkenylated p-fluoro derivative
could however be prepared effectively under these conditions. This
accords with the stoichiometric studies of Ryabov and co-workers
in which good Hammett correlations were found for the reaction
of ring-substituted anilide-derived palladacycles with styrenes.22
This same study demonstrated the positive influence of added
acid, and later catalytic work employed p-TsOH.
Taken together, the combined results indicate that formation
of the palladacycle and its reaction with alkenes takes place after
the displacement of acetate by tosylate. This encouraged a closer
analysis of the role of tosylate in the catalytic reaction. The present
observations indicate that it displaces acetate from palladium,
and early work by Backva¨ll and co-workers indicates that acid
may be required to complete the re-oxidation of palladium and
regeneration of the catalyst.23 Two sets of experiments were carried
out, with progress being monitored by NMR. In the first set, [p-
TsOH] was varied whilst other concentrations were kept constant,
with Pd(OAc)2 as the palladium source and 4-methylacetanilide
as reactant. The results are shown in Fig. 4. The effect of excess
acid appears to reach saturation around 0.2 M, and further
doubling does not affect the rate. This is expected, since the
acid is regenerated in each cycle and does not appear in the rate
equation. The palladacyclic complex at 5 mol% is as efficient
a catalyst as Pd(OAc)2 at 10 mol%. Additional acid is however
needed to establish effective turnover. In separate experiments it
was demonstrated that preformed palladacyclic tosylate 3 was an
effective catalyst, of at least comparable activity to Pd(OAc)2. In
Fig. 2 The crystal structure of ion-pair 2, showing H-bonding of the
amide to the camphorsulfonate anion; displacement ellipsoids are drawn
at 50% probability and the water of crystallisation is omitted for clarity.
Since a palladium sulfonate derivative will be a far stronger
electrophile that the corresponding acetate, we wondered whether
a palladium tosylate could be a potential intermediate in catalysis
under the defined reaction conditions. The palladacycle synthesis
was carried out without intervention of MeCN, this time crystalli-
sation of complex 3 was carried out from pentane/acetone. The
10416 | Dalton Trans., 2010, 39, 10414–10421
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©

Table 1 Initial rates of product formation vs. [p-TsOH] variation
Table 2 Initial rate dependence on the concentration of reactants
(Fig. 5a)
Run
Catalyst/M
p-TsOH
Initial rate/M-1s-1
Run
Amide
Alkene
p-BQ
p-TsOH
Rate/M-1min-1
A
B
C
0.02
0.02
0.02
0.12
0.24
0.48
0.000194
0.000239
0.000249
A
B
C
D
0.2
0.2
0.2
0.4
0.4
0.2
0.2
0.4
0.2
0.4
0.2
0.4
0.2
0.2
0.2
0.4
0.000109
0.000129
0.000115
0.000432
Acetanilide, butyl acrylate used; catalyst concentration for A-C, 0.01 M,
for D 0.02M; solvent: acetone-d6, 298 K, all R ≥ 0.998.
1
Fig. 4 Decay of H NMR signal intensity of the reactant vs. [p-TsOH];
see Table 1 for conditions.
the absence of excess p-TsOH the rate tailed off rapidly however,
and ca. 0.5 equivalents based on substrate was required for
effective turnover.
The order in the other reactants was established by conventional
1
means, again following the reaction course by H NMR. In this
way the data shown in Fig. 5a was acquired. They show (a) that
the reaction rate is independent of [p-benzoquinone]; (b) that the
effect of changing the concentration of [alkene] is modest and even
counter-productive at the higher concentration, and (c) that the
reaction is first order in anilide, and first order in Pd(OAc)2. In
Fig. 5b, the data for run D is simulated according to the optimised
kinetic model shown:
This further suggests that the turnover-limiting step is early in
the catalytic cycle, indicating but not proving that the observed
palladacycle is a true intermediate in catalysis. In order to
affirm this, a crossover experiment was carried out for which
the palladacycle was employed as the palladium source, and
the reactant was structurally distinct from the organic moiety
of the catalyst (p-n-Bu vs. p-Me substitution in the anilide).24
If palladium is pooled before catalysis the two products will be
formed at comparable rates. If reaction is channelled through
the palladacycle, then there should be an initial lag between the
Fig. 5 (a) Dependence of the catalytic reaction rate on component
concentrations; see Table 2 for conditions; (b) the simulation of product
formation for D with optimised parameters shown; circles experimental
points; line is rate constant simulation for k1 = 0.11 M-1min-1, k2 = 0.31
M-1min-1.
formation of the products derived from the free and Pd bound
anilides, the former giving 5, which was independently synthesised
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Dalton Trans., 2010, 39, 10414–10421 | 10417
©

and characterised. A simple model was set up to simulate the data,
and the relevant rate constants modified for best fit.25 It will be
seen from this that the palladacycle model survives the test, and
provides a robust description of the reaction pathway (Scheme 5
and Fig. 6; see Scheme 6 for a model of the catalytic cycle).
Scheme 6 Mechanistic proposal for the Pd-catalysed alkenylation of
anilides abased on the work described here.
Scheme 5 The model used in Fig. 6.
Conclusions
As well as securing the direct involvement of a palladacyclic
intermediate formed in the rate-limiting stage, these results
demonstrate the involvement of an electrophilic palladium entity
as the true catalyst. Unlike the examples studied computationally
by MacGregor and experimentally by Fagnou, there is no obvious
residual role for palladium acetate; indeed reaction occurs as
rapidly under conditions where acetates are omitted from the reac-
tion system. The earlier examples involved a tertiary benzylamine
(5-ring palladacycle) or directing-group free, largely heterocyclic
systems. In these cases the fastest palladations were associated with
enhanced C–H acidity, where concerted removal of the proton and
formation of the C–Pd bond has most to gain. In the present case,
the experiments are in accord with the mechanistic scheme shown
in Figure 8. The cyclopalladation step is best considered here as an
electrophilic substitution, with the irreversible step being proton
removal.
The present paper addresses the mechanism of directed C–H
activation/alkenylation of anilides. We note the discovery by Bris-
tol and Oxford groups (in our case adventitious) of the enhanced
reactivity of arylureas over anilides in palladations, and future
work will endeavour to rationalise this effect by experimental
and computational methods.26,27,28 Notably, Pd(OTs)2 was the Pd
source in ref. 26.
Fig. 6 Crossover experiment. Open circles—product arising from pal-
ladacycle; filled circles—product arising from anilide. Full lines are
simulations according to Scheme 5.
Experimental
General
All reactions were conducted in oven- or flame-dried glassware.
Reactions involving air- and water-sensitive reagents were per-
formed under a dry argon atmosphere using standard vacuum
line and Schlenk techniques
Melting points were recorded using a Reichert-Koffler block
apparatus and are uncorrected. Nuclear Magnetic Resonance
(NMR) spectra were recorded using a Bruker AV400 spectrometer,
Bruker DPX400, Bruker AVB500 or Bruker DRX500 (FTIR)
spectra were recorded on a Perkin-Elmer Paragon 1000 FTIR
10418 | Dalton Trans., 2010, 39, 10414–10421
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©

spectrometer. Mass Spectra (MS) were recorded by the author
and Mr. R. Proctor using a Micromass GCT (CI) or a V.G.
Autospec spectrometer (EI; CI). Exact masses were measured on
a Waters 2790-Micromass LCT spectrometer or a V.G. Autospec
spectrometer using CI.
882, 810, 755, 706, 680; 1H NMR (500 MHz, DMSO-d6)) d/ppm:
11.96 (1 H, s, NH), 7.51 (2 H, d, J = 7.9 Hz, 2 x C(10)H), 7.41
(1 H, s, C(3)H), 7.13 (2 H, d, J = 7.9 Hz, 2 x C(11)H), 7.00 (1 H,
d, J = 7.8 Hz, C(6)H), 6.94 (1 H, d, J = 7.8 Hz, C(5)H), 2.38 (3
H, s, C(9)H3), 2.29 (3 H, s, C(7)H3), 2.23 (3 H, s, C(15)H3), 13C
NMR (126 MHz, DMSO-d6)) d/ppm: 168.4 (C(8)), 146.0 (C(9)),
138.2 (C(12)), 135.2 (C(3)), 134.4 (C(4)), 129.9 (2 x C(11)), 128.6
(C(6)), 127.6 (C(1)), 126.0 (2 x C(10)), 121.0 (C(2)), 117.5 (C(5)),
21.5 (C(7)), 21.3 (C(15)), 21.2 (C(9)). The aquo derivative 3 was
obtained on crystallisation from acetone–pentane.
Acetato(acetonitrile-N)(2-acetamino-5-methylphenyl-
C,O)dipalladium(II) (1)
Di-m-acetatobis(2-acetamino-5-methylphenyl-C,O) dipalladium-
(II) was prepared as described,7 on a 1.0 mmol scale, to give a
greenish yellow precipitate (287 mg, 77%) nmax/cm-1 3285, 1623
and 1572. The complex was insoluble in CDCl3 or CD3COOD
hence 1H and 13C NMR spectra were taken in CD3CN. This
precipitate (156 mg, 0.5 mmol) was dissolved in acetonitrile, stirred
for 30 min and then filtered. Concentration of the filtrate in vacuo
Di-l-methanesulfonatobis(2-acetamino-5-methylphenyl-
C,O)dipalladium(II) (4)
A mixture of N-p-tolylacetamide (30 mg, 0.2 mmol) and Pd(OAc)2
(45 mg, 0.2 mmol) was dissolved in toluene (3 mL). A solution of
CH3SO3H (38 mg, 0.4 mmol) in acetone (0.3 mL) was added to
this mixture and stirred at room temperature for 1 h. The greenish
yellow precipitates in the reaction mixture were filtered off, washed
with toluene and dried under vacuum to give the product (65 mg,
93%); m.p. 187 ◦C (dec.); nmax (CHCl3) 3347, 1604, 1477, 1195,
1043, 754, 668; 1H NMR (400 MHz, DMSO-d6) d/ppm: 12.01 (1
H, s, NH), 7.38 (1 H, s, C(3)H), 6.99 (1 H, d, J = 7.9 Hz, C(6)H),
6.93 (1 H, d, J = 7.9 Hz, C(5)H), 2.41 (3 H, s, C(10)H3), 2.37 (3 H,
s, C(9)H3), 2.21 (3 H, s, C(7)H3); 13C NMR (101 MHz, DMSO-d6)
d/ppm: 168.88 (C(8)), 135.53 (C(3)), 134.79 (C(4)), 130.29 (C(5)),
128.01 (C(1)), 121.39 (C(2)), 117.92 (C(6)), 40.63 (C(10)), 21.87
(C(7)), 21.57 (C(9)).
◦
gave a yellow solid (170 mg, 96%); m.p. 220 C (dec.); nmax/cm-1
3268, 1603, 1587, 1580, 1385; NMR 1H (400 MHz, CDCl3) d/ppm:
10.5 (1 H, s, NH), 6.84 (1 H, s, C(3)H), 6.78 (1 H, d, J = 7.8 Hz,
C(5)H), 6.65 (1 H, d, J = 7.8 Hz, C(6)H), 2.35 (3 H, s, C(7)H3),
2.20 (3 H, s, C(9)H3), 1.92 (3 H, s, C(11)H3), 1.33 (3 H, s, C(13)H3);
13C (101 MHz, CDCl3) d/ppm: 181.2 (C(8)), 167.5 (C(10)), 135.5
(C(2)), 134.8 (C(3)), 132.8 (C(1)), 130.9 (C(4)), 120.2 (C(6)), 119.1
(C(12)), 116.1 (C(5)), 30.9 (C(7)), 24.7 (C(9)), 21.2 (C(11)), 20.4
(C(13)); m/z: 297.02 (ESI+) [M - OAc]+. A sample was crystallised
from CH3CN–pentane and the crystal structure recorded.
Di-l-camphorsulfonatobis(2-acetamino-5-methylphenyl-
C,O)dipalladium(II) (precursor of 2)
A mixture of N-p-tolylacetamide (30 mg, 0.2 mmol) and Pd(OAc)2
(45 mg, 0.2 mmol) was dissolved in toluene (4 mL). A solution
of camphorsulfonic acid (93 mg, 0.4 mmol) in acetone (0.3 mL)
was added to this mixture and stirred at room temperature for
2 h. The yellow precipitates in the reaction mixture were filtered
off, washed with toluene and dried under vacuum to give pure
(dimeric) product (89 mg, 92%); m.p. 202 ◦C (dec.); nmax (CHCl3)
3265, 3099, 2950, 2917, 2860, 1702, 1609, 1475, 1282, 1136, 1008;
1H NMR (400 MHz, CD3OD) d/ppm: 6.94 (1 H, d, J = 7.9 Hz),
6.78 (1 H, s), 6.77 (1 H, d, J = 7.9 Hz), 3.35 (1 H, d, J = 14.9 Hz),
2.79 (1 H, d, J = 14.9 Hz), 2.74–2.59 (1 H, m), 2.30 (1 H, s),
2.26 (1 H, s), 2.38–2.30 (1 H, m), 2.07–1.98 (1 H, m), 1.89 (1 H,
d, J = 18.3 Hz), 1.67–1.57 (1 H, m), 1.45–1.34 (1 H, m), 1.13 (3
H, s), 0.85 (3 H, s); 13C NMR (101 MHz, CD3OD) d/ppm: 217.4,
166.5, 133.1, 132.6, 128.9, 127.0, 116.0, 113.4, 58.6, 47.2, 43.1, 42.6,
26.8, 24.8, 23.2, 20.2, 19.7, 19.5, 19.2. The cationic bisacetonitrile
derivative 2 was prepared by crystallisation from CH3CN and the
X-ray crystal structure determined.
(E)-Butyl 3-(2-acetamido-5-butylphenyl)acrylate (5)
N-(4-Butylphenyl)acetamide (95.5 mg, 0.5 mmol), p-
toluenesulfonic acid monohydrate (64 mg, 0.5 mmol), p-
benzoquinone (55 mg, 0.5 mmol) and Pd(OAc)2 (5.6 mg,
0.025 mmol) were dissolved in acetone (2 mL). n-Butyl acrylate
(64 mg, 0.05 mmol) in acetone (0.5 mL) was added in the above
mixture and stirred at room temperature for 24 h. The reaction
mixture was concentrated in vacuo and dissolved in ether (5 mL).
The solution was washed with 0.1 N NaOH (3 ¥ 5 mL), water
(3 ¥ 5 mL) and saturated NaCl (1 ¥ 5 mL) and dried over
MgSO4. After filtration and concentration in vacuo the residue
was subjected to column chromatography (ethyl acetate–pentane,
3 : 1) to yield the product as white solid (107 mg, 68%); m.p.
123–125 ◦C; nmax (CHCl3) 3288, 3018, 2961, 2874, 2401, 2252,
1711, 1633, 1585, 1521, 1372, 1216, 1178, 1064, 1025, 982, 909,
865; 1H NMR (400 MHz, CDCl3) d/ppm: 8.02 (1 H, s, NH), 7.76
(1 H, d, J = 15.9 Hz, C(13)H), 7.42 (1 H, d, J = 8.2 Hz, C(5)H),
7.31 (1 H, s, C(3)H), 7.11 (1 H, d, J = 8.2 Hz, C(6)H), 6.32 (1 H,
d, J = 15.9 Hz, C(14)H), 4.12 (2 H, t, J = 6.7 Hz, C(16)H2), 2.53
(2 H, t, J = 7.7 Hz, C(9)H2), 2.13 (3 H, s, C(8)H3), 1.67–1.49 (4
H, m, C(10)H3, C(17)H3), 1.43–1.27 (4 H, m, C(11)H2, C(18)H2),
0.95–0.87 (6 H, m, C(12)H3, C(19)H3); 13C NMR (101 MHz,
CDCl3) d/ppm: 169.5 (C(7)), 167.1 (C(15)), 140.7 (C(4)), 140.0
(C(13)), 133.8 (C(1)), 130.9 (C(6)), 128.1 (C(2)), 126.5 (C(3)),
125.9 (C(5)), 119.5 (C(14)), 64.5 (C(16)), 35.1 (C(9)), 33.5 (C(10)),
30.7 (C(17)), 23.8 (C(8)), 22.3 (C(11)), 19.2 (C(18)), 13.9 (C(12)),
13.7 (C(19)); HRMS (ESI) m/z: calcd for C19H27NO3 [M + Na]:
340.1883, Found 340.1878.
Di-l-p-toluenesulfonatobis(2-acetamino-5-methylphenyl-
C,O)dipalladium(II) (precursor of 3)
A mixture of N-p-tolylacetamide (30 mg, 0.2 mmol) and Pd(OAc)2
(45 mg, 0.2 mmol) was dissolved in toluene (3 mL). A solution of
p-TsOH (76 mg, 0.4 mmol) in acetone (0.3 mL) was added to
this mixture and stirred at room temperature for 2 h. The yellow
precipitates in the reaction mixture were filtered off, washed with
toluene and dried under vacuum to give the p-toluenesulfonate
palladacycle, pure by NMR (82 mg, 96%); m.p. 192 ◦C (dec.);
n
max (CHCl3) 3300, 1625, 1498, 1475, 1337, 1215, 1039, 1013, 919,
This journal is The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10414–10421 | 10419
©

Conditions for NMR kinetic experiments
Acknowledgements
Reactions were carried out in 5 mm NMR tubes held in the
500 MHz probe at 298 K and sampled at fixed intervals. The
full spectral range was accumulated; the signal chosen for analysis
was based on the clearest separation over the reaction course.
(a) p-Toluenesulfonic acid variation, Fig. 4; internal standard
total OCH2 ca. 4.15 ppm, assay C(O)CH3 signal of reactant (b)
Fig. 5; internal standard total OCH2 ca. 4.15 ppm, assay C(O)CH3
signal of product 2.25 ppm; (c) crossover experiment, Fig. 6;
internal standard OTs signal 7.75 ppm; assay palladacycle-derived
product 7.81 ppm, substrate derived product 7.83 ppm.
W. R. is grateful to the Pakistan Government for a Scholarship,
and J. M. B. thanks the Leverhulme Trust for a Fellowship. We are
most grateful to Dr David Watkin and Dr Andrew Cowley for help
in the data collection and refinement of compounds 1 and 3. We
wish to acknowledge use of the CDS crystallographic database in
Daresbury. We thank Johnson-Matthey for the loan of palladium
salts.
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˚
˚
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3
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©