8-Methylquinoline palladacycles: Stable and efficient catalysts for carbon-carbon bond formation

Article abstract of DOI:10.1016/j.tet.2005.06.118

Cyclopalladated, phosphine free, 8-methyl quinoline based complexes (2a-j) are excellent catalysts for the Heck vinylation of aryl iodides and bromides with turnover numbers of greater than 25 million observed in some cases. The catalysts are air and moisture stable.

Full text of DOI:10.1016/j.tet.2005.06.118

Tetrahedron 61 (2005) 9696–9704
8-Methylquinoline palladacycles: stable and efficient catalysts
for carbon–carbon bond formation
a
a
Paul Evans,a Paul Hogg,a Ronald Grigg,a, Mohamed Nurnabi, Joanne Hinsley,
*
Visuvanathar Sridharan,a Selvaratnam Suganthan,a Stewart Korn,c Simon Collardb
and Jane E. Muirb
aMolecular Innovation, Diversity and Automated Synthesis (MIDAS) Centre, School of Chemistry, The University of Leeds,
Leeds LS2 9JT, UK
bJohnson Matthey, Orchard Road, Royston, Herts SG8 5HE, UK
cAvecia, PO Box 521, Leeds Road, Huddersfield HD2 1EA, UK
Received 4 April 2005; revised 24 June 2005; accepted 26 June 2005
Available online 19 August 2005
Abstract—Cyclopalladated, phosphine free, 8-methyl quinoline based complexes (2a–j) are excellent catalysts for the Heck vinylation of
aryl iodides and bromides with turnover numbers of greater than 25 million observed in some cases. The catalysts are air and moisture stable.
q 2005 Elsevier Ltd. All rights reserved.
Palladium mediated reactions are firmly positioned as one of
the ‘power tools’ of modern organic synthesis. A variety of
diverse catalytic manipulations may be accomplished using
its salts and complexes. For example, the Heck reaction,1 is
a versatile and widely used method for C–C bond formation
where much recent attention has focused on finding novel
catalysts with high turnover numbers (TON). New
developments in the area of high turnover palladium
catalysts principally consist of palladacycles2,3 and coordi-
natively unsaturated palladium catalysts featuring bulky
phosphanes of high s-donor abilities.3 A variety of
palladacycles incorporating cyclometallated phosphines,4
phosphites,5 carbenes,6 imines,7 heterocycles,8 thioethers9
and oximes10 have been reported with high turnover
numbers for this process. These precatalysts invariably
contain sp2 carbon–palladium bonds but the utility of
palladacycles in other non-catalytic roles is also
expanding.11
reaction in that they posses an sp3 carbon–palladium bond
rather than an sp2 carbon–palladium bond. A series of 5-
substituted 8-methylquinolines (1a–d) were synthesised
from 8-methylquinoline. A standard nitration was carried
out to give 5-nitro-8-methylquinoline (1a), which was
converted to 5-fluoro-8-methylquinoline (1b) via the
corresponding diazonium salt (Scheme 1).12
Scheme 1.
Bromination of 8-methylquinoline at C-(5) to afford (1c)
was achieved by bromine in the presence of silver sulfate13
whilst 5-trifluoromethyl 8-methylquinoline (1d) was pre-
pared from (1c) using sodium trifluoroacetate in the
presence of copper (I) iodide (Scheme 2).13 5-Methoxy-8-
methylquninoline (1e) was also derived from (1c) using
1. Introduction
We now report that palladacycles (2a–j) are good catalysts
for both the Heck reaction and three component cascade
reactions. Notably these systems differ from other phos-
phine free, nitrogen based palladacycles used in the Heck
Keywords: Precatalyst; Allene; Cascade.
*
Corresponding author. Tel.: C44 113 343 6501; fax: C44 113 343 6530;
e-mail: r.grigg@leeds.ac.uk
Scheme 2.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.118

P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
9697
sodium methoxide together with copper (I) bromide
(Scheme 2).14
in the proton NMR spectra of (2a–j) from the set of broad
AB signals, due to the diastereotopic C(8)–CH2 protons (see
Section 2) and the corresponding additional complexity of
the aromatic proton signals.
The substituted 8-methylquinolines (1f–j) were synthesised
by a two step procedure adapted from the literature15 from
the appropriate aniline and 1,3-diketone in 82–96% yield
(Scheme 3).
We explored the Heck reaction between iodobenzene and
n-butyl acrylate or benzyl acrylate in the presence of (2a–j)
in DMF/DMA at 140 8C (Table 1) (Scheme 4). Introducing
a C(5)-electron donating group, increases the rate of
reaction and TON (Table 1, entry 6).
Scheme 3.
Scheme 4.
Introducing a C(2)-electron withdrawing group further
increases the rate and TON (Table 1, entry 9). A C(7)-
electron donating group combined with a C(2)-electron
withdrawing group also produces a highly active catalyst
(Table 1, entry 11). Introducing fluorine (-I and p-donor)
substituents at C(5) and C(7) did not produce a higher TON
(Table 1, entries 3 and 8). However, a C(5)–CF3 group gave
a good TON (Table 1, entry 5). We also carried out an
experiment on (2i) to determine the recyclability of the
catalyst. Thus, a fresh charge of iodobenzene, n-butyl
acrylate and base were added to the reaction mixture after
100% conversion of the previous run. In this way it was
found that catalyst was still active after 30 days and a TON
of 25 million (Table 1, entry 10). In this latter case PVP
polyvinyl pyrrolidone (Pd/PVPZ13:1) was added at the
start of the reaction (Table 1, entry 10). This additive is
known to prolong catalyst life by the polymer chains
‘wrapping up’ the individual palladium nanoparticles thus
preventing them colliding with each other and aggregating,
that is, stablises the nanoparticles.17 The palladacycles
(2a–j) could operate via Pd(II)/Pd(IV)18 or Pd(0)/Pd(II)
catalytic cycles.19 It appears probable, on our current
Following a procedure adapted from literature the 8-methyl
quinoline derivatives and palladium acetate (1 equiv) were
heated in glacial acetic acid at 100 8C16 to afford the desired
palladacyclic dimers (2a–j) in 55–65% yield. The mixture
of isomeric species (cis and trans dimers) is clearly evident
Table 1. Catalytic Heck reaction of iodobenzene with n-butyl acrylate (2 equiv) or benzyl acrylate (2 equiv) with palladacycles (2a–j) precatalysts
Entry
Catalyst (mol%)
Temperature (8C) Solvent
Time (h)
Base (2 equiv)
Conversion (%)a
TONb
1c
2c
3
4
5
6
7
8
9
2a (0.01)
2b (0.00017)
2c (0.001)
2c (0.0001)
2d (0.00001)
2e (0.00001)
2f (0.0001)
2g (0.001)
100
100
140
140
140
140
140
140
140
140
140
DMF
DMF
DMF
DMA
DMA
DMF
DMF
DMF
DMF
DMF
DMF
60
16
96
96
96
96
44
16
47
720
94
K2CO3
K2CO3
K2CO3
CsOAc
CsOAc
CsOAc
KOAc
KOAc
CsOAc
KOAc
CsOAc
85
99
89
34
87
98
8,500
581,600
89,000
340,000
8,700,000
9,800,000
700,000
100,000
10,000,000
25,500,000
7,800,000
70d
100
100
2i (0.00001)
2i (0.0001)
2j (0.00001)
e
10
11
—
78
a Conversion by NMR.
b TON based on consumption of iodobenzene.
c Benzyl acrylate and Et4NCl (1 equiv) were used.
d GC conversion.
e PVP (Mw 3000) (pd/PVPZ13:1) were used.

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P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
evidence, that the active species are Pd(0) nanoparticles.20
We have also shown that treatment of palladacycles or
palladium salts with carbon monoxide (1 atm) in DMF
or toluene at room temperature results in a solution of
palladium nanoparticles whose morphology depends on the
palladacycle or palladium salt precursors.21 Blackmond et
al. have developed a detailed kinetic model of a Heck
reaction catalysed by dimeric palladacycles.22 This model
explains the experimental observations and is consistent
with an active species being slowly metered into the
reaction. Comparison between phosphine and non-phos-
phine based palladacycles suggests that they follow the
same reaction mechanism. They have also highlighted the
role of water in accelerating the formation of the active
catalyst species. Thus, the rate-determining ‘metering’ step
is outside the true catalytic cycle, in the case of aryl iodides
and activated aryl bromides and this has important
consequences for the use of these catalysts. This, of course,
does not apply to cases of ‘unreactive’ aryl chlorides and
bromides where oxidative addition is rate determining.
Seminal contributions to these multifactorial processes have
also been made by van Leeuwen’s and Hartwig’s groups19a,23
and by Amatore and Jutand.24 TONs with these pallada-
cycles would appear even more impressive if based on the
actual amount of Pd present in the catalytic cycle itself. The
function of the substitutents in (2a–j) can be interpreted as
perturbing the sp3 C–Pd covalent bond and the N–Pd dative
bond and in so doing controlling the rate of release of Pd
nanoparticles into solution. In the most active catalyst (2i)
the substitutent effects conspire to weaken both bonds by a
combination of mesomeric [C(5)–OMe] and inductive
effects [C(2)–CF3] (Scheme 4, 2i, arrows). The reductive
elimination implied by (2i, arrows) could also proceed via
bridge splitting and intramolecular acetate transfer or an
SN2 process (Scheme 5). This is considered infinitely more
probable than an alternative olefin insertion in the C–Pd
bond as the initiation step followed by b-hydride elimi-
nation, resulting in palladium nanoparticles, which has also
been proposed.25
Table 2. Effect of base on the Heck reaction of iodobenzene with n-butyl
acrylate (2 equiv) using catalysts 2d and 2f
Entry
Catalysta
Time
(h)
Base
(2 equiv)
Conversion
(%)b
1
2
3
4
5
6
7
2d
2d
2d
2d
2f
48
48
48
48
24
61
20
NaOAc
K2CO3
KOAc
CsOAc
K2CO3
NaOAc
KOAc
24
35
99
97
10c
8c
2f
2f
100c
a 0.001 mol% catalyst.
b Conversion by NMR.
c GC conversion.
entries 1 and 6), closely followed by potassium carbonate.
Potassium acetate and cesium acetate were the best of those
studied (Table 2, entries 3, 4 and 7). The nature of the
inorganic base has a clear effect on TON/conversion (Tables
1 and 2). This is ascribed to involvement of the base in
formation of the catalytically active Pd(0) species as well
documented by the work of Amatore and Jutand24 and as
noted in Scheme 5. Caution is necessary in applying these
conclusions more widely since it is likely the base order is
palladacycle dependent. The effect of inorganic bases in
Heck reaction is an area that is still imperfectly understood.
It is clear both anion and cation play a role and this suggests
that anionic palladium complexes,24 incorporating the base
anion, associated with the base cation, play a significant role
in the catalysis. Recently Beletskaya et al. briefly reported
the catalytic activity of 2a26 in the Heck reaction. We briefly
explored the Heck reaction of bromo and chlorobenzene
with (2a) and (2e) and n-butyl acrylate in DMA at 140 8C
(Table 3).
Thus, 4-bromoacetophenone with catalyst 2e afforded
TON’s of up to a million (Table 3, entry 5).In the absence
of any additives, rates of the reaction, when bromobenzene
was the substrate were poor (Table 3, entry 10). However,
the addition of 2 mol equiv of tetrabutylammonium bromide
increased the TON’s to reasonable values (Table 3, entry
13). The role of halide ions in stablising Pd(0) species has
been extensively studied and documented by Amatore and
Jutand,25 Reetz et al.27 and others.19 In the case of dimeric
palladacycles the role of the soluble Bu4NBr in bridge
splitting to furnish monomeric species and in participating
in processes analogus to those in Scheme 5 also needs to be
considered. Again the effect is on catalyst metering and or
structure with the results (Table 3) indicating the Pd(0)
species is now able to process bromobenzene (oxidative—
addition not rate determining) whilst oxidative addition of
ArCl (Table 3, entry 14) remains rate determining.
Finally we explored a three component cascade involving
aryl halides, allenes and secondary amines in the presence of
K2CO3 as a base in DMF (Scheme 6) using precatalysts
(2d), (2e) and (2i). All three precatalysts functioned
efficiently at 80 8C at the 1 mol% level (Table 4, entries
1–7) affording the 2-arylallylamines (4a–c) in 76–90% yield
over 24 h. When the precatalyst loading was reduced to
0.25 mol% of (2i) the process was less efficient at 80 8C
(Table 4, entry 9) but on raising the temperature to 120 8C
Scheme 5.
Next, we briefly studied the effects of base in the Heck
reactions employing palladacycle (2d) and (2f) precatalysts.
These results are summarised in Table 2. Sodium acetate
was the least effective of the bases evaluated (Table 2,

P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
Table 3. Palladacycles in Heck reactions with aryl bromidesa
9699
Entry
Catalyst (mol%)
Aryl halide
Additive
Conversion (%)b
TON
1
2
3
4
5
6
7
2a (0.01)
2a (0.001)
2e (0.01)
2e (0.001)
2e (0.0001)
2e (0.00001)
2a (0.1)
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
Bromobenzene
—
—
—
—
—
—
—
100
88
100
100
100
44
1,000
88,000
10,000
10,0000
1,000,000
4,400,000
100
10
8
9
2a (0.1)
Bromobenzene
Bromobenzene
Bromobenzene
Bromobenzene
Bromobenzene
Bromobenzene
4-Chloroacetophenone
Bu4NBr
Bu4NBr
—
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
100
40
47
100
100
96
1,000
4,000
470
1,000
10,000
960,000
0
2a (0.01)
2e (0.1)
2e (0.1)
2e (0.01)
2e (0.0001)
2e (1)
10
11
12
13
14
0
a Reactions carried out in DMA for 48 h at 140 8C employing aryl halide (1 mmol), n-butyl acrylate (2 mmol), Bu4NBr (2 mmol) and CsOAc (2 mmol).
b Conversion measured by GLC.
the precatalyst performed as well as the 1 mol% loading at
80 8C (Table 4, entries 8, 10 and 11). This trend accords
with the temperature controlled breakdown of (2i) metering
the release of the catalytically active Pd nanoparticles.
2. Experimental
2.1. General
Melting points were determined using a Reichert apparatus
and are uncorrected. Mass spectral data was obtained from a
VG Autospec mass spectrometer operating at 70 cV at the
National MS Service, Swansea. Nuclear magnetic reso-
nance spectra were recorded on Bruker 250, 300, 400 and
500 MHz machines. Unless otherwise specified deutereo-
chloroform was used as solvent with tetramethylsilane as
internal standard. Microanalyses were obtained using a
Carlo Erba MOD 11016 instrument. Thin-layer chromato-
graphy was carried out on Whatmann PGSILG/UV polyster
plate coated with a 0.2 mm layer of silica gel 60 (Merck
9385). Petroleum ether refers to the fraction with bp 40–
60 8C. anhydrous DMF and DMA were commercially
available (Aldrich). PVP (Mw 30,000) was purchased from
Aldrich and used as received. Conversions measured by
GLC. (GC-FID was performed on a GC equipped with
12QC31 BP5 column 0.5 mm diameter, using the following
program. Flow rates, HeZ20 mL/min, starting temperature
70 8C rising by 20 8C/min to 170 8C then 1 8C/min.
Retention timeZ13 min).
In summary we have developed a range of non-phosphine
8-methyl quinoline based dimeric palladacycles, possessing
an sp3 C–Pd bond, which are efficient precatalysts for both
Heck reactions and a 3-component cascade process. The
palladacycles function via a temperature controlled break-
down of the precatalysts (2a–j) to Pd nanoparticles, which
are metered into the reaction mixture. The precatalyst /
active catalyst breakdown/metering mechanism is sensitive
to substitution on the quinoline ring. Substituents that
facilitate sp3 C–Pd s-bond and N–Pd dative bond cleavage
deliver Pd nanoparticles more rapidly and this process is
strongly influenced by metal acetate and Bu4NBr additives.
The hitherto neglected area of sp3 C–Pd palladacycles28
will, we believe, find many more applications in the future.
2.1.1. 8-Methyl-5-nitroquinoline (1a).12 Concentrated
sulfuric acid (4.7 mL) was added dropwise over 10 min to
8-methylquinoline (3 mL, 21.60 mmol) at 0 8C. A mixture
Scheme 6.
Table 4. Three component cascade involving aryl iodide or bromide, allene and a secondary amine in the presence of (2d, 2e, 2i)a
Entry
Catalyst (mol%)
Temperature (8C)
Aryl halide
Product
Yield (%)b
1
2
3
4
5
6
7
8
2d (1.0)
2d (1.0)
2d (1.0)
2e (1.0)
2e (1.0)
2e (1.0)
2i (1.0)
2i (0.25)
2i (0.25)
2i (0.25)
2i (0.25)
80
80
80
80
80
80
80
120
80
120
120
Iodobenzene
Iodobenzene
4-Bromoacetophenone
Iodobenzene
Iodobenzene
4-Bromoacetophenone
Iodobenzene
Iodobenzene
Iodobenzene
Iodobenzene
4-Bromoacetophenone
3a
3b
3c
3a
3b
3c
3a
3a
3b
3b
3c
89
94
85
79
82
76
90
90
55
80
73
9
10
11
a Reactions carried out in DMF for 24 h at 80 or 120 8C employing aryl halide (1 mmol), amine (1.2 mol equiv), allene (1 atm) and K2CO3 (2 mol equiv).
b Isolated yield.

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P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
of concentrated nitric acid (2.7 mL) and concentrated
sulfuric acid (2.3 mL) was then added dropwise over
20 min. The reaction mixture was stirred for 2 days at
0 8C then poured onto ice and neutralised using sodium
hydroxide solution. The product was extracted into ether
(!3), the combined organic extracts washed with brine,
dried (MgSO4), filtered and the filtrate concentrated to give
the product (3.62 g, 89%) as pale yellow prisms, mp 94–
95 8C (lit. 93–93.5 8C). dH (300 MHz): 2.91 (3H, s, Me),
7.65 (2H, m, ArH), 8.33 (1H, d, JZ7.9 Hz, ArH), 9.06 (2H,
m, ArH), m/z (%) (EI): 188 (MC, 100), 158 (39), 142 (62),
115 (18).
m/z (%) (EI): 222 (MC, 97), 142 (100), 115 (25), 70 (30),
63 (20).
2.1.5. 8-Methyl-5-(trifluoromethyl)quinoline (1d).13 5-
Bromo-8-methylquinoline (2.50 g, 11.26 mmol), sodium
trifluoroacetate (6.74 g, 49.53 mmol) and cuprous iodide
(4.76 g, 24.99 mmol) were combined in N-methylpyrroli-
done (80 mL) and heated to 160 8C for 5 days. After cooling
the reaction mixture was poured into water and extracted
with ether (!3). The combined organic extracts were
washed with brine, dried (MgSO4), filtered and the filtrate
concentrated. The residual brown oil was purified by flash
column chromatography, eluting with 10% ether in
petroleum ether to give the product (1.40 g, 59% yield) as
a pale yellow oil. Found: C, 62.55; H, 4.10; N, 6.70;
C11H8F3N requires C, 62.55; H, 3.85; N, 6.65%, dH
(300 MHz): 2.86 (3H, s, Me), 7.55 (1H, m, ArH), 7.60
(1H, d, JZ7.5 Hz, ArH), 7.81 (1H, d, JZ7.5 Hz, ArH), 8.49
(1H, d, JZ8.7 Hz, ArH), 9.02 (1H, m, ArH), m/z (%) (EI):
211 (MC, 100), 142 (26), nmax/cmK1 (film): 1118.8 (s,
C–F), 1321.4 (s, C–F), 1506.6 (m, aromatic ring).
2.1.2. 5-Amino-8-methylquinoline.12 Concentrated hydro-
chloric acid (35 mL) was added dropwise over 20 min to
8-methyl-5-nitroquinoline (3.0 g, 15.94 mmol) at 0 8C. Tin
(II) chloride (6.04 g, 31.88 mmol) was then added and the
reaction mixture was allowed to reach room temperature
and stirred for 48 h then neutralised by careful addition of
sodium hydroxide solution. The product was extracted into
ether (!3) and the combined organic extracts were washed
with brine, dried (MgSO4), filtered and the filtrate
concentrated to give the product (1.99 g, 79%) as yellow
prisms, mp 144–145 8C (lit. 143–143.5 8C). dH (300 MHz):
2.91 (3H, s, Me), 7.66 (2H, m, ArH), 8.32 (1H, d, JZ7.9 Hz,
ArH), 9.06 (2H, m, ArH), m/z (%) (EI): 158 (MC, 65), 142
(100), 115 (33), 89 (15), 63 (22).
2.1.6. 5-Methoxy-8-methylquinoline (1e).14 A mixture of
5-bromo-8-methylquinoline (1.00 g, 4.50 mmol), sodium
methoxide (2.43 g, 45.03 mmol), DMF (6 mL) and metha-
nol (15 mL) was stirred and heated at 90 8C under nitrogen.
Cuprous bromide (0.32 g, 2.25 mmol) was added and the
reaction mixture was maintained at 90 8C for 16 h, poured
into water and extracted with ether (!3). The combined
organic layers were washed with water and brine, dried
(MgSO4), filtered and the filtrate concentrated. The residual
brown oil was purified by flash column chromatography,
eluting with 10% ether in petroleum ether to give the
product (762 mg, 98% yield) as a pale yellow oil. Found: C,
75.40; H, 6.50; N, 8.05; C11H11NO requires C, 76.30; H,
6.40; N, 8.10%, dH (300 MHz): 2.71 (3H, s, Me), 3.91 (3H,
s, OMe), 6.68 (1H, d, JZ7.8 Hz, ArH), 7.33 (1H, m, ArH),
7.39 (1H, d, JZ7.8 Hz, ArH), 8.53 (1H, d, JZ8.4 Hz, ArH),
8.92 (1H, m, ArH), m/z (%) (EI): 173 (MC, 51), 158 (100),
130 (19), 77 (17), nmax/cmK1 (film): 1091.8 (s, C–O),
1402.4 and 1475.7 (m, C–H deformations), 1593.4 (s,
aromatic ring), 2848 (m, OMe).
2.1.3. 5-Fluoro-8-methylquinoline (1b).12 5-Amino-8-
methylquinoline (2.60 g, 16.43 mmol) was dissolved in
fluoroboric acid (50 mL) and cooled to 0 8C. Sodium nitrite
(1.19 g, 17.26 mmol) in water (10 mL) was added and the
mixture stirred at 0 8C for 30 min. The resulting colourless
precipitate was filtered off and thoroughly dried in a
desiccator for 16 h. The dried tetrafluoroborate salt was
suspended in toluene (20 mL), heated to reflux for 32 h, and
quenched with 10% hydrochloric acid solution. The layers
were separated, the aqueous layer basified to pH 9–10 with
2 M sodium hydroxide solution and the mixture extracted
with ether (!3). The combined organic layers were washed
with brine, dried (MgSO4), filtered and the filtrate
concentrated. The residual brown oil was purified by flash
column chromatography, eluting with 2:3v/v ether–petro-
leum ether to give the product (1.27 g, 48% yield) as a
colourless oil. dH (300 MHz): 2.76 (3H, s, Me), 7.12 (1H, t,
JZ8.0 Hz, ArH), 7.47 (2H, m, ArH), 8.42 (1H, d, JZ
8.4 Hz, ArH), 8.99 (1H, m, ArH), m/z (%) (EI): 161 (MC,
100), 143 (16), 133 (13), 71 (17).
2.2. General procedure for anilide synthesis15
Anilides were synthesised by the literature procedure.
A mixture of the appropriately substituted aniline
(1.0 equiv) and the dicarbonyl compound (1.1 equiv) was
heated in an oil bath under reflux for 4 h. After cooling to
room temperature, water (100 mL) was added and the
mixture extracted with DCM (3!100 mL). The DCM layer
was dried (MgSO4), filtered and the filtrate evaporated
under reduced pressure. The residual solid was crystallised
from petroleum ether.
2.1.4. 5-Bromo-8-methylquinoline (1c).13 Bromine
(0.76 mL, 14.69 mmol) was added dropwise over 15 min
to a solution of 8-methylquinoline (2.0 mL, 14.69 mmol)
and silver sulphate (2.29 g, 7.35 mmol) in concentrated
sulphuric acid (15 mL). The reaction mixture was stirred for
30 min at room temperature then poured into water and
basified using sodium hydroxide solution. The mixture was
extracted with ether (!3) and the combined organic
extracts were washed with brine, dried (MgSO4), filtered
and concentrated to give the product (2.80 g, 86% yield) as
pale fawn prisms, mp 38–39 8C (lit. 37–38 8C). dH
(300 MHz): 2.76 (3H, s, Me), 7.41 (1H, d, JZ7.6 Hz,
ArH), 7.50 (1H, m, ArH), 7.70 (1H, d, JZ7.6 Hz, ArH),
8.52 (1H, d, JZ8.5 Hz, ArH), 8.95 (1H, d, JZ4.2 Hz, ArH),
2.3. General procedure for quinoline synthesis from
anilides15
Anilide (10.0 mmol) was added to 98% sulfuric acid
(20 mL) and the mixture stirred for 4 h at room temperature.
The reaction mixture was then carefully poured into
ice-water (200 mL) with swirling. NaOH pellets were
then added carefully until the mixture was strongly basic

P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
9701
(pH 10–12). The mixture was extracted with DCM (3!
100 mL), the combined organic layer dried (MgSO4),
filtered and the filtrate evaporated under reduced pressure.
The solid residue was purified by crystallisation from an
appropriate solvent.
3006, 2980, 2844, 2501, 2084, 1888, 1720 (CO), 1593,
1495, 1459, 1391, 1366, 1275, 1260, 1112, 1044, 1011, 975,
857, 812, 766, 748, 727, 704, 653, 584, 567, 553, 512 and
466.
The anilide (0.50 g, 1.83 mmol) was reacted according to
the general procedure to give the product (1i) (0.38 g, 82%),
which crystallised from petroleum ether as colourless
needles, mp 76–78 8C. Found: C, 61.00; H, 4.80; N, 5.20;
C13H12F3NO requires C, 61.20; H, 4.70; N, 5.50%. dH
(250 MHz, CDCl3) 2.7, 2.8 (2!3H, 2!s, 2!Me), 3.95
(3H, s, OMe), 6.9 (1H, d, JZ8.0 Hz, ArH), 7.5 (1H, d, JZ
8.0 Hz, ArH), 7.65 (1H, s, ArH), m/z (FAB): 255 (100%,
MC). nmax/cmK1 (solid) 2978, 2923, 2851, 1607, 1581,
1513, 1471, 1388, 1343, 1257, 1155, 1140, 1099, 959, 879,
823 and 803.
2.3.1. 2,4,5,8-Tetramethyquinoline (1f). Synthesised by
the general procedure from 2,5-dimethyl aniline (12.1 g,
100 mmol, 1.0 equiv) and 2,4-pentanedione (11.3 mL,
110 mmol, 1.1 equiv) over 5 h at 130 8C. The crude anilide
was reacted according to the general procedure to give the
product (11.0 g, 59.5%), which crystallised from petroleum
ether as colourless plates, mp 36–38 8C. Found: C, 84.50; H,
8.20; N, 7.50; C13H15N requires C, 84.30; H, 8.10; N,
7.60%. dH (250 MHz, CDCl3) 2.65, 2.70, 2.80. 2.81 (4!3H,
4!s, 4!Me), 7.0 (1H, s, ArH), 7.1 (1H, d, JZ7.2 Hz,
ArH), 7.3 (1H, d, JZ7.2 Hz, ArH), m/z (FAB): 186 (100%,
MCCH), 172 (53), 158 (20), 141 (10), 128 (25) and 115
(16). nmax/cmK1 (solid) 2962, 2918, 2840, 1864, 1721,
1602, 1572, 1460, 1438, 1383, 1366, 1328, 1144, 1041, 862,
818, 696 and 618.
2.4. General procedure for the synthesis of 8-methyl-
quinoline palladacycles16
The quinoline (1a–j) (2.50 mmol) was added to a solution of
palladium acetate (0.51 g, 2.27 mmol) in acetic acid
(12 mL) and the reaction mixture was heated to 100 8C for
2 h. Once cooled to room temperature DCM (10 mL) and
then water (10 mL) were added. The layers were separated
and two more portions of DCM were used to extract the
product. The combined organic extracts were washed with
water and brine, dried (MgSO4), filtered and the filtrate
concentrated. The residue was crystallised from DCM/
petroleum ether to give the product.
2.3.2. 7-Fluoro-2,4,8-trimethyquinoline (1g). The anilide
was synthesised by the general procedure from 3-fluoro-2-
methyl aniline (3.13 g, 25.0 mmol, 1.0 equiv) and 2,4-
pentanedione (2.83 mL, 27.4 mmol, 1.1 equiv) over 5 h at
130 8C. The crude anilide was reacted according to the
general procedure to give the product (2.0 g, 98%), which
crystallised from petroleum ether as colourless needles, mp
26–28 8C. Found: C, 76.10; H, 6.45; N, 7.30; C12H12FN
requires C, 76.20; H, 6.35; N, 7.40%. dH (250 MHz, CDCl3)
2.6, 2.65, 2.70 (3!3H, 3!s, 3!Me), 7.1 (1H, s, ArH), 7.2
(1H, t, JZ9.0 Hz, ArH) (J H–HzJ H–19F), 7.8 (1H, dd, JZ
9.0, 6.1 Hz, ArH), m/z (FAB): 190 (100%, MCCH), 174
(14), 146 (10), 97 (8) and 83 (16). nmax/cmK1 (solid) 2956,
2923, 1605, 1510, 1439, 1378, 1338, 1317, 1229, 1210,
1155, 1080, 1036, 963, 936, 874, 816 and 781.
2.4.1. Di(m-aceto)bis[8-methylquinoline]dipalladium
(2a). 8-Methylquinoline (0.34 mL) was reacted by the
general procedure. The product (1.11 g, 72% yield) was
obtained as orange prisms as a 4:1 mixture of trans and cis-
isomers. mp O200 8C. Found: C, 47.20; H, 3.80, N, 4.30;
C24H22N2O4Pd2 requires C, 46.90; H, 3.60; N, 4.60%, dH
(250 MHz): 2.11 (6H, s, Me), 2.52 (2H, d, JZ13.8 Hz,
CH2), 3.43 (2H, d, JZ13.8 Hz, CH2), 6.69 (2H, dd, JZ1.1,
7.1 Hz, ArH), 6.88 (2H, t, JZ7.2 Hz, ArH), 6.97–7.03 (2H,
m, ArH), 7.21–7.22 (2H, m, ArH), 7.85 (2H, dd, JZ1.4,
8.3 Hz, ArH), 8.51 (2H, dd, JZ1.4, 5.0 Hz, ArH), m/z (%)
(FAB): 616 (MC, 23), 557 (37), 458 (19), 414 (69), 389
(41), 354 (49), 248 (100), 142 (73), nmax/cmK1 (GG):
1412.1 (m, C]N), 1504.7 (s, aromatic ring), 1568.3 (s,
aromatic ring).
2.3.3. 2,4,7,8-Tetramethyquinoline (1h). The anilide was
synthesised by the general procedure from 2,3-dimethyl
aniline (30 mL, 247.0 mmol, 1.0 equiv) and 2,4-pentane-
dione (28 mL, 274.0 mmol, 1.1 equiv) over 4 h at 155 8C.
Crystallisation from petroleum ether afforded the product
(20.0 g, 79%) as colourless plates, mp 90–92 8C (lit.15 83–
84 8C).
Anilide (2.0 g, 9.85 mmol) was converted to the quinoline
1h by the general procedure to give the product (1.8 g, 98%)
as colourless needles, mp 26–28 8C (lit.15 30–31 8C).
2.4.2. Di(m-aceto)bis[5-nitro-8-methylquinoline]dipalla-
dium (2b). 5-Nitro-8-methylquinoline (0.47 g) was reacted
by the general procedure. The product (1.20 g, 68% yield)
was obtained as black prisms as a 2.3:1 mixture of trans and
cis-isomers. mp O200 8C. Found: C, 41.70; H, 2.85; N,
8.20; C24H20N4O8Pd2 requires: C, 41.85; H, 2.85; N, 7.95%,
dH (300 MHz): 2.15 (6H, s, Me), 2.36 (2H, d, JZ15.0 Hz,
CH2), 3.56 (2H, d, JZ15.0 Hz, CH2), 6.75 (2H, d, JZ
8.0 Hz, ArH), 7.60 (2H, dd, JZ5.0, 8.8 Hz, ArH), 7.85 (2H,
d, JZ8.0 Hz, ArH), 8.71 (2H, dd, JZ1.3, 5.0 Hz, ArH),
8.97 (2H, dd, JZ1.3, 8.8 Hz, ArH), m/z (%) (FAB): 706
2.3.4. 5-Methoxy-4,8-dimethyl-2-(trifluoromethyl)quino-
line (1i). The anilide was synthesised by the general
procedure from 5-methoxy-2-methyl aniline (0.62 g,
5.0 mmol, 1.0 equiv) and 1,1,1-trifluoro-2,4-pentanedione
(0.73 mL, 6.0 mmol, 1.1 equiv) over 5 h at 130 8C. Crystal-
lisation from petroleum ether gave the product (0.92 g,
70%) as colourless plates, mp 53–55 8C. Found: C, 57.10;
H, 5.20; N, 5.00; C13H14F3NO2 requires C, 57.10; H, 5.10;
N, 5.10%. dH (250 MHz, CDCl3) 2.0, 2.2 (2!3H, 2!s, 2!
Me), 3.8 (3H, s, OMe), 5.55 (1H, s, ]CH), 6.65 (1H, d, JZ
2.6 Hz, ArH), 6.8 (1H, dd, JZ8.4, 2.6 Hz, ArH), 7.2 (1H, d,
JZ8.4 Hz, ArH), m/z (FAB): 274 (100%, MCCH), 204
(16), 174 (7) and 162 (12). nmax/cmK1 (solid) 3192, 3126,
(MCCH, 18), 647 (23), 295 (27), 189 (52), 149 (100), nmax
/
cmK1 (GG): 1336.8 (s, CNO2), 1414.0 (s, C]N), 1502.7 (s,
CN]O), 1505.8 (m, aromatic ring), 1568.3 (s, CNO2),
1570.4 (s, aromatic ring).

9702
P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
2.4.3. Di(m-aceto)bis[5-fluoro-8-methylquinoline]dipal-
ladium (2c). 5-Fluoro-8-methylquinoline (0.40 g) was
reacted by the general procedure. The product (1.16 g,
71% yield) was obtained as orange prisms as a 4:1 mixture
of trans and cis-isomers. mp O200 8C. Found: C, 44.05; H,
3.40; N, 4.15; C24H20F2N2O4Pd2 requires: C, 44.25; H,
3.10; N, 4.30%, dH (300 MHz): 2.13 (6H, s, Me), 2.44 (2H,
d, JZ14.8 Hz, CH2), 3.48 (2H, d, JZ14.8 Hz, CH2), 6.61–
6.80 (4H, m, ArH), 7.34 (2H, dd, JZ5.1, 8.6 Hz, ArH), 8.13
(2H, dd, JZ1.2, 5.1 Hz, ArH), 9.06 (2H, d, JZ8.6 Hz,
ArH), m/z (%) (FAB): 651 (MC, 8), 591 (10), 391 (100),
326 (37), 279 (27), 266 (50), nmax/cmK1 (GG): 1140.1 (m,
C–F), 1408.2 (m, C]N), 1475.7 (w, aromatic ring), 1570.2
(m, aromatic ring).
(65) and 105 (73). nmax/cmK1 (solid) 3055, 2978, 2933,
2888, 1694, 1575, 1417, 1276, 1261, 1032, 851, 824, 763,
750 and 726.
2.4.7. Di(m-acetato)-bis[(7-fluoro-2,4,8-trimethylquino-
line)]dipalladium (2g). 7-Fluoro-2,4,8-trimethylquinoline
(0.75 g, 4.0 mmol) was reacted by the general procedure.
The product (0.40 g, 60%) was obtained as a yellow
amorphous solid, mp 165 8C (dec.), which comprised a ca.
7: 1 mixture of trans and cis-isomers. Found: C, 47.90; H,
4.05; N, 3.70; C28H28N2O4F2Pd2 requires C, 47.60; H, 4.00;
N, 4.00%. dH (300 MHz, CDCl3) 2.0, 2.4 (2!6H, 2!s, 2!
2Me), 2.65 (2H, d, JZ13.8 Hz, CH2), 2.7 (6H, s, 2Me), 2.9*
(2H, d, JZ13.3 Hz, CH2), 3.2 (2H, d, JZ13.8 Hz, CH2)
3.5* (2H, d, JZ13.3 Hz, CH2), 6.6 (2H, t, JZ8.7 Hz, ArHc)
(J Hc–HbzJ Hc–19F), 6.7* (2H, t, JZ8.7 Hz, ArHc) (J Hc–
HbzJ Hc–19F), 6.9 (2H, s, ArHa), 6.95* (2H, s, ArHa), 7.1
(2H, dd, JZ8.7, 5.1 Hz, ArHb, Hb couples with Hc and F),
7.15* (2H, dd, JZ8.70, 5.1 Hz, ArHb, Hb couples with Hc
and F). *Indicates minor isomer. m/z (FAB): 712–702 (MC,
Pd isotope cluster, 707, 10%), 648 (15), 413 (28), 391 (40),
294 (41), 188 (35), 167 (25), 149 (100), 132 (52) and 113
(25). nmax/cmK1 (solid) 2988, 2918, 2883, 1718, 1583,
1514, 1407, 1275, 1261, 1099, 1043, 863, 812, 764 and 750.
2.4.4. Di(m-aceto)bis[5-trifluoromethyl-8-methylquino-
line]dipalladium (2d). 5-Trifluoromethyl-8-methylquino-
line (0.53 g) was reacted by the general procedure. The
product (1.41 g, 75% yield) was obtained as red prisms as a
2.3:1 mixture of trans and cis-isomers. mp O200 8C. Found:
C, 41.45; H, 2.75; N, 3.55, C26H20F6N2O4Pd2 requires: C,
41.55; H, 2.70; N, 3.75%, dH (300 MHz): 2.15 (6H, s, Me),
2.36 (2H, d, JZ14.6 Hz, CH2), 3.48 (2H, d, JZ14.6 Hz,
CH2), 6.67 (2H, d, JZ7.6 Hz, ArH), 7.26–7.27 (2H, m,
ArH), 7.48 (2H, dd, JZ5.0, 8.7 Hz, ArH), 8.28 (2H, d, JZ
8.7 Hz, ArH), 8.67 (2H, dd, JZ1.3, 5.0 Hz), m/z (%) (FAB):
752 (MCCH, 13), 693 (19), 524 (24), 421 (27), 391 (23),
315 (100), 210 (29), 149 (29), nmax/cmK1 (GG): 781.3 (m,
C–F), 884.9 (m, aromatic ring), 1317.5 (s, C–F), 1414.0 (m,
C]N), 1510.4 (m, aromatic ring), 1570.2 (s, aromatic ring).
2.4.8. Di(m-acetato)-bis[(2,4,7,8-tetramethylquinoline)]
dipalladium (2h). 2,4,7,8-Tetramethylquinoline (0.93 g,
5.0 mmol) was reacted by the general procedure. The
product (1.1 g, 68%) was obtained as a yellow amorphous
solid, mp 147 8C (dec.), which comprised a ca. 6.5:1
mixture of trans and cis-isomers. Found: C, 51.70; H, 4.85;
N, 4.00; C30H34N2O4Pd2 requires C, 51.60; H, 4.90; N,
4.00%. dH (300 MHz, CDCl3) 1.95* (6H, s, 2Me), 2.0, 2.05
(2!6H, 2!s, 2!2Me), 2.1*, 2.15* (2!6H, 2!s, 2!
2Me), 2.35 (6H, s, 2Me), 2.4* (6H, s, 2Me), 2.7 (6H, s,
2Me), 2.8 (2H, d, JZ13.3 Hz, CH2), 3.25* (2H, d, JZ
12.8 Hz, CH2), 3.35 (2H, d, JZ13.3 Hz, CH2), 3.6* (2H, d,
JZ12.8 Hz, CH2), 6.5* (2H, s, ArH), 6.7 (2H, d, JZ8.7 Hz,
ArH), 6.75 (2H, s, ArH), 6.95 (2H, d, JZ8.7 Hz, ArH), 7.0*
(2H, d, JZ8.2 Hz, ArH), *indicates minor isomer. m/z
(FAB): 704–694 (MC, Pd isotope cluster, 700, 10%), 641
(25), 557 (22), 395 (16), 292 (67), 184 (100) and 115 (12).
nmax/cmK1 (solid) 3051, 2973, 2925, 2855, 1704, 1583,
1519, 1411, 1344, 1175, 1066, 1027, 856, 779 and 720.
2.4.5. Di(m-aceto)bis[5-methoxy-8-methylquinoline]
dipalladium (2e). 5-Methoxy-8-methylquinoline (0.43 g)
was reacted by the general procedure. The product (1.25 g,
74% yield) was obtained as orange prisms as a 9:1 mixture
of trans and cis-isomers. mp O200 8C. Found: C, 46.05; H,
4.10; N, 3.90; C26H26N2O6Pd2 requires C, 46.20; H, 3.90;
N, 4.10%, dH (300 MHz): 2.13 (6H, s, Me), 2.47 (2H, d, JZ
12.4 Hz, CH2), 3.35 (2H, d, JZ12.4 Hz, CH2), 3.85 (6H, s,
OMe), 6.28 (2H, d, JZ7.9 Hz, ArH), 6.57 (2H, d, JZ
7.9 Hz, ArH), 7.17 (2H, dd, JZ5.0, 8.4 Hz, ArH), 8.17 (2H,
dd, JZ1.4, 8.4 Hz, ArH), 8.53 (2H, dd, JZ1.4, 5.0 Hz,
ArH), m/z (%) (FAB): 675 (MC, 9), 616 (15), 448 (24), 278
(37), 172 (100), 149 (47), nmax/cmK1 (GG): 771.6 (m,
aromatic ring), 806.3 (aromatic ring), 1479.6 (m, C]N),
1574.1 (s, aromatic ring), 1614.6 (m, aromatic ring), 2841.6
(w, O–Me).
2.4.9. Di(m-acetato)-bis[(5-methoxy-2-trifluoromethyl-4,
8-dimethyl quinoline)]dipalladium (2i). 5-Methoxy-4,8-
dimethyl-2-(trifluoromethyl)quinoline (0.25 g, 1.0 mmol)
was reacted by the general procedure. The product
(0.42 g, 50%) was obtained as a orange amorphous solid,
mp 157 8C (dec.), which comprised a ca. 12:1 mixture of
trans and cis-isomers. Found: C, 42.60; H, 3.45; N, 3.10;
C30H28N2O6F6Pd2 requires C, 42.90; H, 3.35; N, 3.30%. dH
(300 MHz, CDCl3) 2.0 (6H, s, 2Me), 2.1* (6H, s, 2Me), 2.73
(2H, d, JZ12.5 Hz, CH2), 2.85 (6H, s, 2OAc), 2.9* (6H, s,
2OAc), 3.33* (2H, d, JZ12.5 Hz, CH2), 3.47 (2H, d, JZ
12.5 Hz, CH2) 3.73* (2H, d, JZ12.5 Hz, CH2), 3.79* (6H,
s, 2OMe), 3.82 (6H, s, 2OMe), 6.38 (2H, d, JZ8.1 Hz,
ArH), 6.63 (2H, d, JZ8.1 Hz, ArH), 6.98* (2H, d, JZ
8.5 Hz, ArH), 7.15* (2H, d, JZ8.5 Hz, ArH), 7.42 (2H, s,
ArH), 7.62* (2H, s, ArH), *indicates minor isomer. m/z
(FAB): 844–832 (MC, Pd isotope cluster, 839, 7%), 780
(13), 610 (8), 525 (14), 465 (17), 359 (35) and 254 (100).
2.4.6. Di(m-acetato)-bis[(2,4,5,8-tetramethylquinoline)]
dipalladium (2f). 2,4,5,8-Tetramethylquinoline (0.93 g,
5.0 mmol) was reacted by the general procedure. The
product (1.1 g, 68%) was obtained as a yellow amorphous
solid, mp 160 8C (dec.), which comprised a ca. 6:1 mixture
of trans and cis-isomers. Found: C, 51.70; H, 5.05; N, 3.70;
C30H34N2O4Pd2 requires C, 51.60; H, 4.90; N, 4.00%. dH
(300 MHz, CDCl3) 1.92* (6H, s, 2Me), 2.01 (6H, s, 2Me),
2.08*, 2.1*, 2.3* (3!6H, 3!s, 3!2Me), 2.6, 2.65, 2.67
(3!6H, 3!s, 3!2Me), 2.8 (2H, d, JZ13.5 Hz, CH2),
3.26* (2H, d, JZ12.1 Hz, CH2), 3.53 (2H, d, JZ13.5 Hz,
CH2), 3.7* (2H, d, JZ12.1 Hz, CH2), 6.5–6.6 (4H, br, ArH),
6.75* (2H, s, ArH), 6.8 (2H, s, ArH, *indicates minor
isomer. m/z (FAB): 704–694 (MC, Pd isotope cluster, 700,
10%), 643 (7), 473 (15), 395 (20), 292 (65), 184 (100), 123

P. Evans et al. / Tetrahedron 61 (2005) 9696–9704
9703
nmax/cmK1 (solid) 2951, 2887, 2849, 1708, 1675, 1612,
1575, 1515, 1472, 1403, 1342, 1327, 1166, 1141, 1087, 975,
948, 828, 751 and 685.
Synthesised by the general procedure from iodobenzene
(0.21 g, 1.0 mmol), morpholine (0.11 mL, 1.2 equiv) and
allene (1 bar). Purification by column chromatography
eluting with 4:1 v/v petroleum ether–Et2O gave the product
(0.15 g, 75%) (Rf 0.10) as a colourless oil. dH (300 MHz,
CDCl3) 2.45–2.5 (4H, m, morpholinyl H), 3.0 (2H, d, JZ
0.8 Hz, CH2), 3.65–3.7 (4H, m, morpholinyl H) 5.25 (1H, d,
JZ1.4 Hz, C]CH2), 5.5 (1H, d, JZ1.4 Hz, C]CH2),
7.25–7.35 (3H, m, ArH), 7.55 (2H, dd, JZ7.5, 1.0 Hz,
ArH), m/z (EI) 203 (17%, MC), 144 (13), 118 (48), 100
(100), 91 (24), 77 (7), 56 (30), and 42 (21).
2.4.10. General procedure for the Heck reaction.
Palladacycle (2a–j) was added to a stirred solution of
iodobenzene or 4-bromoacetophenone (1.0 mmol), n-butyl-
acrylate (2.0 mol equiv) or benzyl acrylate (2.0 mol equiv)
and metal acetate (2.0 mol equiv) or potassium carbonate
(2.0 mol equiv) in DMF (GPR grade 10 mL). The reaction
mixture was heated at 140 8C (oil bath) for 16–96 h (see
Table 1). After cooling to room temperature water (10 mL)
was added and the mixture extracted with ether (2!20 mL).
The combined organic layer was washed with water (2!
20 mL), dried (MgSO4), filtered and the filtrate evaporated
under reduced pressure to give the crude product as a light
The 1H NMR and mass spectroscopic data of the compound
3b are in full agreement with those reported in the
literature.29
1
yellow oil. The conversion was determined by H NMR
2.5.3. 1-{4-[1-(Morpholin-4-ylmethyl)vinyl]phenyl}etha-
none (3c). Synthesised by the general procedure from
4-bromoacetophenone (0.20 g, 1.0 mmol), morpholine
(0.11 mL, 1.2 equiv) and allene (1 bar). Purification by
column chromatography eluting with 4:1 v/v petroleum
ether–Et2O gave the product (0.18 g, 73%) (Rf 0.08) as a
colourless oil. dH (300 MHz, CDCl3) 2.45–2.50 (4H, m,
morpholinyl H), 2.6 (3H, s, Me), 3.35 (2H, d, JZ0.6 Hz,
CH2), 3.65–3.7 (4H, m, morpholinyl H) 5.35 (1H, d, JZ
1.1 Hz, C]CH2), 5.6 (1H, d, JZ1.1 Hz, C]CH2), 7.6 (2H,
d, JZ8.5 Hz, ArH), 7.9 (2H, d, JZ8.5 Hz, ArH), m/z (EI)
245 (26%, MC), 186 (15), 160 (20), 145 (37), 115 (47), 100
(100), and 56 (50).
spectroscopy comparing the ratio of the integrals of
iodobenzene (7.1 ppm, 2H, t, JZ7.5 Hz, ArH) or 4-bromo-
acetophenone (2.6 ppm, 3H, s, MeC]O) and that of butyl
(2E)-3-phenylacrylate (4.21 ppm, t, 2H, JZ6.6 Hz, OCH2;
6.44 ppm, 1H, d, JZ16.0 Hz, PhCH]CH; 7.7, 1H, d, JZ
16.0 Hz, PhCH]CH) or that of butyl (2E)-3-(4-acetyl-
phenyl)acrylate (2.62 ppm, s, 3H, MeC]O; 4.22 ppm, t,
JZ6.6 Hz, 2H, OCH2; 6.53 ppm, 1H, d, JZ16.0 Hz,
PhCH]CH; 8.0 ppm, 1H, d, JZ16.0 Hz, PhCH]CH).
2.5. General procedure for termolecular cascade
involving arylhalide, allene and N-nucleophiles
The 1H NMR and mass spectroscopic data of the compound
3c are in full agreement with those reported in the
literature.29
A mixture of palladacycle (2d, e or 2i) (0.25–1.0 mol%),
iodobenzene or 4-bromoacetophenone (0.20 g, 1.0 mmol),
morpholine or piperidine (1.2 mol equiv) and potassium
carbonate (0.27 g, 2.0 mol equiv) in DMF (GPR grade,
10 mL) was stirred for 15 min in a Schlenk tube. The
mixture was then degassed, frozen, evacuated and filled
with allene gas (1 bar). After warming to room temperature,
it was heated at 80–120 8C (Table 4) in an oil bath for 24 h.
The reaction mixture was cooled to room temperature,
excess allene vented, water (10 mL) added and the mixture
extracted with ether (2!20 mL). The combined organic
layer was washed with water (2!20 mL), dried (MgSO4),
filtered and the filtrate evaporated under reduced pressure.
The residue was purified by column chromatography on
silica gel.
Acknowledgements
We thank Leeds University, the EPRSC, Johnson Mathey
and Avecia for support
References and notes
1. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009–3066. Crisp, G. T. Chem. Soc. Rev. 1998, 27, 427–436.
Whitcombe, N. J.; Hii, S. E.; Gibson, S. E. Tetrahedron 2001,
57, 7449–7476.
2.5.1. 1-(2-Phenylprop-2-enyl)piperidine (3a). Synthe-
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1.0 mmol), piperidine (0.12 mL, 1.2 equiv) and allene
(1 bar). Purification by column chromatography eluting
with 9:1 v/v petroleum ether–EtOAc gave the product
(0.17 g, 92%) (Rf 0.11) as a colourless oil. dH (300 MHz,
CDCl3) 1.4–1.45 (2H, m, piperidinyl H), 1.5–1.6 (4H, m,
piperidinyl H), 2.35–2.4 (4H, m, piperidinyl H), 3.3 (2H, d,
JZ0.8 Hz, CH2), 5.25 (1H, d, JZ1.5 Hz, C]CH2), 5.45
(1H, d, JZ1.5 Hz, C]CH2), 7.2–7.45 (3H, m, ArH), 7.5
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