Palladium-catalysed heck reactions of alk-1-en-3-ones with aryl bromides: A very simple access to (E)-1-arylalk-1-en-3-ones

Article abstract of DOI:10.1055/s-0028-1087976

When appropriate reaction conditions are used, very high yields of (E)-1-arylalk-1-en-3-one derivatives can be obtained by palladium-catalysed reactions of alk-1-en-3-ones with aryl bromides. The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane in combination with [Pd(C₃H₅)Cl]₂ was found to be a very efficient catalyst for this reaction. In general, higher reaction rates were observed with electron-poor aryl bromides, but the electron-rich aryl bromides 1-bromo-4-(dimethylamino)benzene and 4-bromoanisole also led to the arylated enones in high yields. Even with sterically very congested aryl bromides such as 9-bromoanthracene, 1-bromo-2,4,6-trimethylbenzene or 1-bromo-2,4,6-triisopropylbenzene, the expected (E)-1-arylalk-1-en-3-ones were obtained in moderate to good yields. These enones appear to be unstable under the reaction conditions, and the addition of a small amount of hydroquinone to the reaction mixture was found to be crucial, especially for the vinylation of electron-deficient aryl bromides. A variety of alk-1-en-3-ones has been employed, and better results in terms of substrate/ catalyst ratios were obtained when oct-1-en-3-one or hex-1-en-3-one was used than when but-1-en-3-one or pent-1-en-3-one was used. It should be noted that several reactions can be performed with as little as 0.1-0.001 mol% catalyst. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087976

PAPER
1021
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides:
A Very Simple Access to (E)-1-Arylalk-1-en-3-ones
Pall adium- Catal ysed
H
h
ec
k
React io
a
ns of
A
lk-
1
m
-en-3-one
s
w
i th Ar
e
yl Bromi de
d
s
Lemhadri,a Yacoub Fall,a Henri Doucet,*b Maurice Santelli*a
a
Laboratoire de Synthèse Organique, Faculté des Sciences de Saint Jérôme, Université d’Aix-Marseille III, Avenue Escadrille Normandie-
Niemen, 13397 Marseille Cedex 20, France
Fax +33(4)91289112; E-mail: m.santelli@univ-cezanne.fr
Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1 ‘Catalyse et Organometalliques’, Campus de Beau-
lieu, 35042 Rennes, France
b
Fax +33(2)23236939; E-mail: henri.doucet@univ-rennes1.fr
Received 6 November 2008; revised 18 November 2008
presence of 2 mol% [PdCl2(PPh3)2] as catalyst gave the
expected arylated enone in 45–92% yield.32,33 The reac-
tion of 2-bromo-1,4-dimethoxynaphthalene and but-1-en-
3-one with 20 mol% tetrakis(triphenylphosphine)palladi-
Abstract: When appropriate reaction conditions are used, very high
yields of (E)-1-arylalk-1-en-3-one derivatives can be obtained by
palladium-catalysed reactions of alk-1-en-3-ones with aryl bro-
mides. The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphe-
nylphosphinomethyl)cyclopentane
in
combination
with um led to the desired coupling product in 73% yield.34 The
[Pd(C3H5)Cl]2 was found to be a very efficient catalyst for this re-
action. In general, higher reaction rates were observed with elec-
tron-poor aryl bromides, but the electron-rich aryl bromides 1-
bromo-4-(dimethylamino)benzene and 4-bromoanisole also led to
the arylated enones in high yields. Even with sterically very con-
gested aryl bromides such as 9-bromoanthracene, 1-bromo-2,4,6-
trimethylbenzene or 1-bromo-2,4,6-triisopropylbenzene, the ex-
pected (E)-1-arylalk-1-en-3-ones were obtained in moderate to
good yields. These enones appear to be unstable under the reaction
conditions, and the addition of a small amount of hydroquinone to
the reaction mixture was found to be crucial, especially for the vi-
nylation of electron-deficient aryl bromides. A variety of alk-1-en-
reactions of bromobenzene, bromo(methoxy)benzenes,
bromonaphthalenes, a bromophenylcarbohydrate, or a
bromoindole with alk-1-en-3-ones in the presence of 10–
20 mol% of a palladium(II) acetate/triphenylphosphine
catalyst also gave the 1-aryl alk-1-en-3-ones in good
yields.35–38
On the other hand, in several other cases, moderate yields
were obtained. The reaction of 2-bromotoluene or 1-bro-
mo-2,4,5-trimethylbenzene with but-1-en-3-one in the
presence of palladium(II) acetate/triphenylphosphine as
3-ones has been employed, and better results in terms of substrate/ catalyst and triethylamine as base gave the target products
in 49 and 39% yields, respectively.39 Under the same re-
catalyst ratios were obtained when oct-1-en-3-one or hex-1-en-3-
one was used than when but-1-en-3-one or pent-1-en-3-one was
action conditions, a 5-bromopyrimidine afforded the ex-
used. It should be noted that several reactions can be performed with
as little as 0.1–0.001 mol% catalyst.
pected products in only 7–31% yields.40
A 2-
bromoanisole derivative was reacted with but-1-en-3-one
in the presence of 25 mol% of [PdCl2(P-2-Tol3)2] to give
the desired product in 49% isolated yield.41 The very low
yield of 30% was obtained for the reaction of a 2-bro-
mothiophene derivative with but-1-en-3-one in the pres-
ence of 10 mol% tetrakis(triphenylphosphine)palladium
as catalyst.42 For the Heck vinylation with acrylates, better
results are generally obtained when electron-poor aryl
bromides are used rather than electron-rich ones, due to a
faster oxidative addition to palladium. Surprisingly, very
few examples of reactions of alk-1-en-3-ones with elec-
tron-deficient aryl bromides have been described. Molnar
and co-workers reported the reaction of but-1-en-3-one
with 4-bromoacetophenone in the presence of a palladium
catalyst deposited onto an organic–inorganic hybrid sup-
port. However, the desired product was obtained in a very
low 6% yield.43
Key words: Heck reaction, palladium, catalysis, enones, arylations
The palladium-catalysed Heck vinylation is one of the
most efficient methods for the formation of C–C bonds.1–4
The reaction between aryl halides and alk-1-en-3-ones
should give an economically and environmentally attrac-
tive access to 1-arylalk-1-en-3-one derivatives. In the lit-
erature, such reactions are generally performed with very
reactive, but generally expensive, aryl iodides.5–31 The use
of aryl bromides would be more interesting both for envi-
ronmental and economical reasons. In most cases, aryl
bromides are cheaper than iodides, and with these sub-
strates a lower mass of waste would be formed. However,
so far, the Heck vinylation with alk-1-en-3-ones and aryl
bromides, especially under low catalyst loading, has at-
tracted less attention.32,33 Moreover, surprisingly, most of
the results were obtained using electron-neutral or elec-
tron-rich aryl bromides. For example, the reaction of 2-
bromo-6-methoxynaphthalene with but-1-en-3-one in the
In summary, Heck reactions of alk-1-en-3-one derivatives
with aryl bromides at low catalyst loadings have not been
reported. Moreover, higher yields for the reactions of such
compounds, especially with electron-poor aryl bromides,
have to be obtained by use of a more efficient catalyst and
more effective reaction conditions to achieve economical-
ly viable procedures.
SYNTHESIS 2009, No. 6, pp 1021–1035
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Advanced online publication: 24.02.2009
DOI: 10.1055/s-0028-1087976; Art ID: Z25008SS
© Georg Thieme Verlag Stuttgart · New York

1022
M. Lemhadri et al.
PAPER
We have already reported that the tetraphosphine ligand
cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cy-
clopentane or Tedicyp (Figure 1) gives a highly stable
palladium catalyst.44 The presence of four phosphines
close to the metal centre seems to increase the stability of
the catalyst and prevent the decomposition pathways
through under-ligation and subsequent colloid formation.
We have described several results obtained in allylic sub-
stitution,45 for Suzuki,46 Sonogashira,47 or Negishi48 reac-
tions, and also for direct C–H activation/arylation49,50
where Tedicyp was used as the ligand. We have also re-
ported several results for the Heck reaction using
acrylates51–54 and enol ethers.55,56 Preliminary results of
the reactions of alk-1-en-3-ones and aryl57 or vinyl
bromides58 have also been reported. Here, we wish to re-
port on the influence of the reaction conditions and on the
scope and limitations of the reactions of a set of alk-1-en-
3-one derivatives with electron-deficient, electron-exces-
Table 1 Tedicyp–Palladium Catalysed Synthesis of 1-Phenylbut-1-
en-3-one (1) from But-1-en-3-one and Iodobenzene: Influence of
Base and Solvent on the Reactiona,b
Entry
Base
Temp (°C)
110
Yieldc (%)
1
K2CO3
K2CO3
K2CO3
Et3N
0
2
70
0
3
50
0
4
110
0
5
KF
110
0
6
NaOAc
Na2CO3
NaHCO3
110
100 (91)
100
7
110
8
110
100
a See Scheme 1.
sive, and congested aryl bromides, as well as hetaryl bro- b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2) (0.01 equiv),
PhI (1 equiv), but-1-en-3-one (4 equiv), base (2 equiv), DMF, 20 h.
mides. To obtain economically attractive procedures, the
catalyst loading has been optimised for all the substrates.
c Yields as determined by GC and NMR; yield in parentheses is the
isolated yield.
Ph2P
PPh2
bicarbonate, sodium carbonate, or sodium acetate was
used. With these bases, (E)-1-phenylbut-1-en-3-one (1)
Ph2P
PPh2
was regio- and stereoselectively obtained with complete
conversion of iodobenzene in the presence of 1 mol% cat-
Figure 1 Tedicyp
alyst (Table 1, entries 6–8). Moreover, a high isolated
First, we studied the influence of several reaction condi- yield of 91% of 1 was obtained in the presence of sodium
tions on the coupling of aryl halides with but-1-en-3-one acetate.
(Scheme 1, Tables 1 and 2). For this reaction, on the basis
Next, we examined the scope and limitations of this pro-
of our previous results,44 the first experiments were per-
cedure with regard to electron-poor and electron-rich aryl
formed with N,N-dimethylformamide as the solvent and
potassium carbonate as the base. The reactions were per-
bromides (Table 2). This procedure appeared to be limited
to electron-rich aryl bromides.
formed at 110 °C, under argon, and [Pd(C3H5)Cl]2/
When sodium acetate or sodium bicarbonate was used as
Tedicyp was used at a ratio of 1:2 as catalyst.
the base in N,N-dimethylformamide at 110 °C in the pres-
ence of 1 mol% [Pd(C3H5)Cl]2/Tedicyp, the electron-poor
O
X
aryl bromides 4-bromoacetophenone, 4-bromobenzoni-
trile, and 4-bromobenzophenone were recovered un-
changed (Table 2, entries 1–6). On the other hand, under
these conditions, 1-bromo-4-tert-butylbenzene and 1-bro-
mo-4-fluorobenzene gave the expected products 5 and 6
in good yields and with complete conversion of the aryl
bromides (Table 2, entries 7–9). 4-Bromoanisole, which
is known to be less reactive than electron-neutral or elec-
tron-poor aryl bromides for most Heck reactions, due to a
relatively slow oxidative addition to palladium, gave 7 in
good yield, but 28% of this substrate was recovered un-
changed (Table 2, entry 10). Next, we studied the influ-
ence of a few solvents on the reaction of 1-bromo-4-tert-
butylbenzene with but-1-en-3-one, but N-methylpyrroli-
din-2-one, N,N-dimethylacetamide, and xylene led to
lower conversions than the reaction performed in N,N-
dimethylformamide (Table 1, entries 11–16).
[Pd(C3H5)Cl]2/
Tedicyp (1:2)
R1
R2
+
O
hydroquinone
DMF, NaOAc
R1
1–62
R2
R1 = H, Me, Et, i-Pr, t-Bu, OMe, NMe2, F, CF3, Ac, CHO, Bz,
CO2Me, CN, NO2
R2 = Me (1–10), Et (11–32), n-Pr (33–50), (CH2)4Me (51–62)
Scheme 1
Surprisingly, under these conditions, no coupling product
was obtained, even with the very reactive substrate iodo-
benzene (Table 1, entry 1). We then investigated the influ-
ence of temperature, base, and solvent on the yield of this
reaction with our catalyst. The first modifications of the
reaction conditions were quite unsuccessful. Lower reac-
tion temperatures gave no target product 1, and iodoben-
zene was recovered unchanged (Table 1, entries 2 and 3).
Using triethylamine or potassium fluoride as bases with
iodobenzene also gave no coupling product (Table 1, en-
tries 4 and 5). Better results were obtained when sodium
We then examined the influence of the addition of a cata-
lytic amount of hydroquinone to the reaction mixture.
Commercially available alk-1-en-3-ones are often stabi-
lised with 0.5% of hydroquinone. We observed that the
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1023
Table 2 Tedicyp–Palladium Catalysed Synthesis of 1-Arylbut-1-en-3-ones from But-1-en-3-one and Aryl Bromides: Influence of Base,
Solvent, and Additives on the Reactiona,b
Entry
Ar of aryl bromide
Ratio substrate/ Base
catalyst
Solvent
Hydroquinone
(equiv)
Product
Yieldc (%)
1
2
4-AcC6H4
4-BzC6H4
4-NCC6H4
4-AcC6H4
4-BzC6H4
4-NCC6H4
4-FC6H4
100
100
100
100
100
100
100
100
250
100
100
100
100
100
100
100
250
250
1000
1000
250
1000
100
250
250
100
250
NaOAc
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NMP
xylene
DMF
NMP
xylene
Me2NAc
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
–
2
3
4
2
3
4
5
6
6
7
6
6
6
6
6
6
2
3
2
3
6
6
6
6
2
3
3
0
NaOAc
NaOAc
NaHCO3
NaHCO3
NaHCO3
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
–
0
3
–
0
4
–
0
5
–
0
6
–
0
7
–
100
100
25
8
4-t-BuC6H4
4-t-BuC6H4
4-MeOC6H4
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
4-AcC6H4
4-BzC6H4
4-AcC6H4
4-BzC6H4
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
4-t-BuC6H4
4-AcC6H4
4-BzC6H4
4-BzC6H4
–
9
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
–
72
–
68
–
0
–
100
78
–
–
40
–
28
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
100
100 (94)
95 (91)
91
100 (90)
20
100
16
100
100
14
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), ArBr (1 equiv), but-1-en-3-one (4 equiv), base (2 equiv), 110 °C, 20 h.
c Yields as determined by GC and NMR; yields in parentheses are isolated yields.
addition of 8% hydroquinone to the reaction mixture led very unstable compound at elevated temperature, espe-
to complete conversion of 4-bromoacetophenone and 4- cially in the presence of palladium and electron-poor aryl
bromobenzophenone into the corresponding (E)-1-aryl- bromides. The addition of hydroquinone probably reduces
but-1-en-3-ones 2 and 3 in the presence of as little as 0.4 the rate of the polymerisation or decomposition of this
mol% catalyst (Table 2, entries 17 and 18). Even in the enone. Addition of hydroquinone was also found to be
presence of only 0.1 mol% catalyst, products 2 and 3 were very useful for the reaction of electron-rich aryl bromides.
obtained in good yields under these conditions (Table 2, Vinylation of 1-bromo-4-tert-butylbenzene with but-1-
entries 19 and 20). In fact, but-1-en-3-one appears to be a en-3-one in the presence of 0.4 mol% catalyst in absence
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

1024
M. Lemhadri et al.
PAPER
of hydroquinone gave a conversion of only 25%, whereas
in the presence of hydroquinone a complete conversion of
the aryl bromide and a high isolated yield of 6 was ob-
tained (Table 2, entries 9, 21, and 22). In the presence of
this additive, the best base for the reaction was sodium
acetate, although sodium bicarbonate also gave satisfacto-
ry results (Table 2, entries 23–27).
Table 4 Tedicyp–Palladium Catalysed Heck Reaction of Pent-1-
en-3-one with para-Substituted Aryl Halidesa,b
Entry Aryl halide
Ratio substrate/ Product Yieldc (%)
catalyst
1
2
PhI
250
11
11
12
12
12
12
13
13
14
14
15
15
16
17
17
18
18
19
19
11
11
20
20
21
100 (93)
32
PhI
1000
1000
1000
250
Next we applied this procedure to the vinylation of 1-bro-
3
4-AcC6H4Br
4-AcC6H4Br
4-AcC6H4Br
4-AcC6H4Br
4-OHCC6H4Br
4-OHCC6H4Br
4-BzC6H4Br
4-BzC6H4Br
90d
mo-4-(trifluoromethyl)benzene,
4-bromobenzonitrile,
4
91e
and 1-bromo-4-fluorobenzene with but-1-en-3-one
(Table 3). In all cases, the (E)-1-arylated but-1-en-3-ones
4, 5, and 8 were obtained in high yields in the presence of
0.1–1 mol% catalyst (Table 3, entries 1–5). As expected,
electron-rich 4-bromoanisole was found to be less reac-
tive, but product 7 was isolated in 87% yield in the pres-
ence of 1 mol% catalyst (Table 3, entry 6). Sterically
congested 1-bromonaphthalene led to 9 in good yield in
the presence of the same amount of catalyst (Table 3, en-
tries 8 and 9). A very high yield of 10 was obtained from
the reaction of the hetaryl bromide 3-bromoquinoline in
the presence of only 0.1 mol% catalyst (Table 3, entry
10).
5
100 (96)
94
6
1000
250
7
100 (95)
85
8
1000
250
9
100 (92)
85
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1000
4-MeO2CC6H4Br 250
4-MeO2CC6H4Br 1000
100 (91)
33
Table 3 Tedicyp–Palladium Catalysed Heck Reaction of But-1-en-
4-O2NC6H4Br
4-FC6H4Br
4-FC6H4Br
4-t-BuC6H4Br
4-t-BuC6H4Br
4-MeC6H4Br
4-MeC6H4Br
PhBr
100
100
250
100
250
100
250
100
250
100
250
32 (28)
100 (94)
52
3-one with a Variety of Aryl Bromidesa,b
Entry Ar of aryl bromide Ratio substrate/ Product Yieldc (%)
catalyst
100 (93)
53
1
2
4-F3CC6H4
4-F3CC6H4
4-NCC6H4
4-FC6H4
100
250
1000
100
250
100
250
100
250
1000
8
100 (91)
90
8
3
4
100 (85)
100 (91)
78
82 (75)
65
4
5
100 (91)
54
5
4-FC6H4
5
6
4-MeOC6H4
4-MeOC6H4
1-naphthyl
1-naphthyl
3-quinolyl
7
93 (87)
0
PhBr
7
7
4-MeOC6H4Br
4-MeOC6H4Br
100 (92)
67
8
9
100 (94)
54
2-bromo-6-meth- 250
oxynaphthalene
100 (88)
9
9
10
10
96 (90)
25
2-bromo-6-meth- 1000
oxynaphthalene
21
65
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), ArBr (1
equiv), but-1-en-3-one (4 equiv), NaOAc (2 equiv), hydroquinone
(0.08 equiv), DMF, 110 °C, 20 h.
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), aryl halide
(1 equiv), pent-1-en-3-one (4 equiv), NaOAc (2 equiv), hydroquinone
(0.08 equiv), DMF, 110 °C, 20 h.
c Yields as determined by GC and NMR; yields in parentheses are iso-
lated yields.
c Yields as determined by GC and NMR; yields in parentheses are iso-
lated yields.
d [Pd(C3H5)Cl]2/PPh3 (1:4) was used as catalyst.
e [Pd(C3H5)Cl]2/dppe (1:2) was used as catalyst.
After that, we studied the scope and limitations for the
coupling reactions of aryl bromides with pent-1-en-3-one,
hex-1-en-3-one, and oct-1-en-3-one with N,N-dimethyl-
formamide as the solvent, sodium acetate as the base, and
hydroquinone as stabilising agent (Tables 4– 9).
zoate with pent-1-en-3-one as vinylation partner, products
12–15 were obtained with turnover numbers (TONs) of
330–940 (Table 4, entries 5–12). These reactions were
performed in the presence of only 0.4–0.1 mol% catalyst.
On the other hand, a low isolated yield of 28% of 16 was
obtained in the presence of 1-bromo-4-nitrobenzene
From the reactions of the para-substituted electron-poor
aryl bromides 4-bromoacetophenone, 4-bromobenzalde-
hyde, 4-bromobenzophenone, and methyl 4-bromoben-
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1025
(Table 4, entry 13). The nitro function of this substrate try 13). In the presence of 1 mol% catalyst the desired
might partially poison the catalyst. Slightly activated aryl product 28 was obtained in 52% isolated yield.
bromide 1-bromo-4-fluorobenzene gave 17 in 94% isolat-
Palladium chemistry involving heterocycles has unique
ed yield in the presence of 1 mol% catalyst and a TON of
characteristics stemming from the inherently different
130 (Table 4, entries 14 and 15). Similar TONs were ob-
structural and electronic properties of heterocycles in
tained in the presence of the electron-rich aryl bromides 1-
comparison to the corresponding carbocyclic arenes. Py-
bromo-4-tert-butylbenzene (132), 4-bromotoluene (162),
ridines are p-electron deficient and, therefore, their oxida-
bromobenzene (135), and 4-bromoanisole (167) (Table 4,
tive addition to palladium is generally relatively easy.
entries 16–23). 2-Bromo-6-methoxynaphthalene gave 21
From the heteroaromatic substrates 3- and 4-bromopyri-
dine, 3-bromoquinoline, and 4-bromoisoquinoline, 29–32
were obtained in high TONs of 220–950 in the presence
of only 0.1–0.4 mol% catalyst (Table 6). These reactions
in a higher TON of 650 and also in good isolated yield
(88%) in the presence of 0.4–0.1 mol% catalyst (Table 4,
entries 24 and 25).
are extremely clean, and very high isolated yields were
obtained in all cases.
Table 5 Tedicyp–Palladium Catalysed Heck Reaction of Pent-1-
en-3-one with ortho-Substituted Aryl Bromidesa,b
Entry Ar of aryl bromide Ratio substrate/ Product Yieldc (%)
catalyst
Table 6 Tedicyp–Palladium Catalysed Heck Reaction of Pent-1-
en-3-one with Hetaryl Bromidesa,b
Entry Ar of hetaryl
bromide
Ratio substrate/ Product Yieldc (%)
catalyst
1
2
2-AcC6H4
2-AcC6H4
1-naphthyl
1-naphthyl
2-tolyl
100
250
250
1000
100
250
250
100
250
100
250
22
22
23
23
24
24
25
25
25
26
26
27
28
100 (87)
32
1
2
3
4
5
6
7
8
3-pyridyl
250
29
29
30
30
31
31
32
32
100 (94)
52
3
100 (92)
82
3-pyridyl
1000
250
4
4-pyridyld
4-pyridyld
3-quinolyl
3-quinolyl
4-isoquinolyl
4-isoquinolyl
100 (94)
22
5
75 (65)
18
1000
250
6
2-tolyl
100 (92)
92
7
anthracen-9-yl
anthracen-9-yl
anthracen-9-yl
mesityl
0d
1000
250
8
100 (89)
62
100 (93)
95
9
1000
10
11
12
13
75 (67)
20
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), ArBr (1
equiv), pent-1-en-3-one (4 equiv), NaOAc (2 equiv), hydroquinone
(0.08 equiv), DMF, 110 °C, 20 h.
mesityl
2,6-Et2-4-MeC6H2 100
2,4,6-i-Pr3C6H2 100
70 (62)
60 (52)
c Yields as determined by GC and NMR; yields in parentheses are iso-
lated yields.
d 4-Bromopyridine hydrochloride was used directly with NaOAc (3
equiv).
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), ArBr (1
equiv), pent-1-en-3-one (4 equiv), NaOAc (2 equiv), hydroquinone
(0.08 equiv), DMF, 110 °C, 20 h.
Subsequently we examined the influence of a longer alkyl
chain on the alk-1-en-3-one. Hex-1-en-3-one was found to
be more reactive than pent-1-en-3-one and but-1-en-3-one
(Tables 7 and 8). With this alkenone, 4-bromoacetophe-
none, 4-bromobenzaldehyde, 4-bromobenzophenone, and
4-bromobenzonitrile can be reacted in the presence of as
little as 0.001 mol% catalyst (substrate/catalyst ratio of
100000), and extremely high TONs of 64000–85000 were
obtained (Table 7, entries 2–14). It should be noted that,
again, in the absence of hydroquinone, much lower TONs
were obtained from 4-bromobenzophenone (TON of 420
instead of 75 000) and 4-bromobenzonitrile (TON of 138
instead of 82 000) (Table 7, compare entries 9 and 12 with
entries 11 and 14, respectively). As expected, slightly ac-
tivated 1-bromo-4-fluorobenzene and the electron-rich
aryl bromides 1-bromo-4-tert-butylbenzene and 4-bromo-
toluene gave the expected products in lower TONs of
670–950 (Table 7, entries 17–24). Strongly deactivated
c Yields as determined by GC and NMR; yields in parentheses are iso-
lated yields.
d [Pd(C3H5)Cl]2/PPh3 (1:4) was used as catalyst.
We also studied this reaction employing sterically con-
gested aryl bromides (Table 5). 2-Bromoacetophenone, 1-
bromonaphthalene, and 2-bromotoluene reacted with
pent-1-en-3-one to give the corresponding (E)-1-arylpent-
1-en-3-ones 22–24 in good yields in the presence of 0.1–
1 mol% catalyst (Table 5, entries 1–6). Di-ortho-
substituted aryl bromides are also suitable reactants for
this reaction. 9-Bromoanthracene, 1-bromo-2,4,6-trimeth-
ylbenzene, and 1-bromo-2,6-diethyl-4-methylbenzene
gave 25–27 in 62–89% yields in the presence of 1–0.4
mol% catalyst (Table 5, entries 7–12). Even the sterically
extremely hindered substrate 2,4,6-triisopropylbromo-
benzene can be reacted with pent-1-en-3-one (Table 5, en-
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

1026
M. Lemhadri et al.
PAPER
aryl bromides 4-bromoanisole or 1-bromo-4-(dimethyl-
amino)benzene gave the vinylation products in TONs of
150 and 190, respectively (Table 7, entries 26 and 30).
Under these reaction conditions, the oxidative addition of
the aryl bromide to palladium appears to be the rate-limit-
ing step of the catalytic cycle.
Table 7 Tedicyp–Palladium Catalysed Heck Reaction of Hex-1-en-
3-one with para-Substituted Aryl Halidesa,b
Entry Aryl halide
Ratio substrate/ Product Yieldc (%)
catalyst
1
2
PhI
100000
10000
100000
10000
100000
10000
10000
100000
1000
10000
100000
250
33
34
34
35
35
35
35
35
36
36
36
37
37
37
38
38
39
39
39
40
40
40
41
41
42
42
43
43
43
43
44
89 (80)
100 (94)
64
The reactions of other challenging aryl bromides and hex-
1-en-3-one generally gave good yields in the presence of
0.4–0.1 mol% catalyst (Table 8). For example, 2-bromo-
toluene gave 46 in 88% yield in the presence of only 0.4
mol% catalyst (Table 8, entry 3). Sterically very hindered
1-bromo-2,4,6-trimethylbenzene was found to be less re-
active, but 47 was obtained in 67% yield in the presence
of 1 mol% catalyst (Table 8, entry 5). The p-electron-ex-
cessive heterocycle 3-bromothiophene was also success-
fully reacted with hex-1-en-3-one to give the arylated
alkenone 48 in good isolated yield (87%) (Table 8, entries
9 and 10). As expected, the p-electron-deficient heterocy-
cles 3-bromopyridine and 3-bromoquinoline are more re-
active than 3-bromothiophene, and the products 49 and 50
were obtained in TONs of 940 (Table 8, entries 11–14).
4-AcC6H4Br
4-AcC6H4Br
4-OHCC6H4Br
4-OHCC6H4Br
4-OHCC6H4Br
4-OHCC6H4Br
4-OHCC6H4Br
4-BzC6H4Br
4-BzC6H4Br
4-BzC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-O2NC6H4Br
4-O2NC6H4Br
4-FC6H4Br
3
4
100d
5
37d
6
100e
7
100 (90)
85
8
9
42f
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
100 (92)
75
55f
Table 8 Tedicyp–Palladium Catalysed Heck Reaction of Hex-1-en-
3-one with meta- or ortho-Substituted Aryl Bromides or Hetaryl Bro-
midesa,b
10000
100000
250
100 (90)
82
Entry Ar of aryl bromide Ratio substrate/ Product Yieldc (%)
catalyst
100 (88)
92
1000
100
1
2
3-AcC6H4
3-AcC6H4
2-tolyl
250
45
45
46
46
47
47
48
48
48
48
49
49
50
50
100 (91)
74
72f
1000
250
4-FC6H4Br
250
100 (89)
67
3
100 (88)
33
4-FC6H4Br
1000
100
4-t-BuC6H4Br
4-t-BuC6H4Br
4-t-BuC6H4Br
4-MeC6H4Br
4-MeC6H4Br
4-MeOC6H4Br
4-MeOC6H4Br
4-Me2NC6H4Br
4-Me2NC6H4Br
4-Me2NC6H4Br
4-Me2NC6H4Br
45f
4
2-tolyl
1000
100
250
100 (87)
78
5
mesityl
75 (67)
20
1000
250
6
mesityl
250
5d
100 (88)
95
7
3-thienyl
3-thienyl
3-thienyl
3-thienyl
3-pyridyl
3-pyridyl
3-quinolyl
3-quinolyl
1000
1000
250
1000
100
8
7e
100 (90)
60
9
100 (87)
42
250
10
11
12
13
14
1000
250
250
10d
100 (88)
94
250
11e
1000
250
100
60f
100 (91)
94
250
76 (68)
92 (79)
1000
2-bromo-6-methox- 10000
ynaphthalene
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), ArBr (1
equiv), hex-1-en-3-one (2 equiv), NaOAc (2 equiv), hydroquinone
(0.08 equiv), DMF, 110 °C, 20 h.
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (1:2), aryl halide
(1 equiv), hex-1-en-3-one (2 equiv), NaOAc (2 equiv), hydroquinone
(0.08 equiv), DMF, 110 °C, 20 h.
c Yields as determined by GC and NMR; yields in parentheses are iso-
lated yields.
c Yields as determined by GC and NMR; yields in parentheses are iso-
lated yields.
d [Pd(C3H5)Cl]2/PPh3 (1:4) was used as catalyst.
e [Pd(C3H5)Cl]2/dppe (1:2) was used as catalyst.
d [Pd(C3H5)Cl]2/PPh3 (1:4) was used as catalyst
e [Pd(C3H5)Cl]2/dppe (1:2) was used as catalyst.
f Reaction performed without hydroquinone.
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1027
To confirm the higher reactivity of enones bearing longer
alkyl chains, we performed a few reactions using oct-1-
en-3-one (Table 9). Again, clean and selective reactions
were observed in all cases. Several activated aryl bro-
mides were reacted in the presence of only 0.01–0.001
mol% catalyst, and TONs of 44000–92000 were obtained
with such substrates (Table 9, entries 2–13). Also for this
enone the addition of hydroquinone to the reaction mix-
ture was found to be crucial if high yields and TONs were
to be obtained. For example, the reaction of 4-bromoben-
zonitrile gave 56 with a TON of 33 in the absence of hyd-
roquinone, whereas a TON of 90000 was obtained when
8 mol% of hydroquinone was added (Table 9, entries 11
and 13). Deactivated aryl bromides or heteroaromatics
gave lower TONs (Table 9, entries 14–25).
Table 9 Tedicyp–Palladium Catalysed Heck Reaction of Oct-1-en-
3-onea,b
Entry Aryl halide
Ratio substrate/ Product Yieldc
catalyst
100000
10000
100000
10000
100000
10000
100000
100
(%)
1
2
PhI
51
52
52
53
53
54
54
55
55
55
56
56
56
57
57
58
58
51
59
59
60
60
61
62
62
90 (86)
100 (90)
44
4-AcC6H4Br
4-AcC6H4Br
4-OHCC6H4Br
4-OHCC6H4Br
4-BzC6H4Br
4-BzC6H4Br
4-F3CC6H4Br
4-F3CC6H4Br
4-F3CC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-NCC6H4Br
4-t-BuC6H4Br
4-t-BuC6H4Br
4-MeC6H4Br
4-MeC6H4Br
PhBr
3
4
100 (81)
65
5
6
100
7
77 (68)
92d
Finally, to provide a procedure employing commercially
available ligands, we studied this reaction in the presence
of catalytic systems made up of triphenylphosphine (4
equiv) or 1,2-bis(diphenylphosphino)ethane (dppe) (2
equiv) and [Pd(C3H5)Cl]2 (1 equiv) for the arylation of
pent-1-en-3-one or hex-1-en-3-one and with hydroquinone
employed as additive. Under these reaction conditions,
satisfactory results in terms of substrate/catalyst ratios and
also of yields of arylated enones were obtained with 4-
bromoacetophenone and 4-bromobenzaldehyde (Table 4,
entries 3 and 4; Table 7, entries 4–6). On the other hand,
with the more challenging substrates 9-bromoanthracene
(Table 5, entry 7), 1-bromo-4-(dimethylamino)benzene
(Table 7, entries 27 and 28), and 3-bromothiophene
(Table 8, entries 7 and 8), products were obtained in low
yields and side products formed in some cases.
8
9
10000
100000
100
100
10
11
12
13
14
15
16
17
18
19
20
92 (86)
33d
1000
100
100000
1000
90 (84)
100 (92)
72
10000
1000
100 (88)
65
10000
1000
100 (87)
100
In summary, the Heck reaction of aryl bromides with alk-
1-en-3-ones in the presence of the Tedicyp/palladium
complex affords a simple access to the corresponding 1-
arylalk-1-en-3-ones. In all cases, the E-isomers were re-
gio- and stereoselectively obtained, but the yields of these 21
vinylations strongly depend on the reaction conditions.
4-MeOC6H4Br
4-MeOC6H4Br
100
250
92 (85)
100
2,6-Et2-4-MeC6H2Br 100
2,6-Et2-4-MeC6H2Br 250
22
86 (77)
100 (75)
100e
The major problem of this coupling appears to be the low
stability of alk-1-en-3-ones in the reaction mixture, espe-
cially for the reactions performed with electron-poor aryl
bromides. With these substrates, a fast decomposition/po-
lymerisation of the alkenones is observed. However, the
addition of a small amount of hydroquinone to the reac-
tion mixture allows the efficient coupling of electron-poor
aryl bromides with a variety of alk-1-en-3-ones. The na-
ture of the solvent and base also appears to be of impor-
tance for this reaction. We obtained the highest yields
using sodium acetate as base and N,N-dimethylformamide
as solvent. A very wide variety of functional groups such
as acetyl, formyl, alkoxycarbonyl, cyano, nitro, trifluo-
romethyl, fluoro, methoxy, and amino on the aryl bro-
mides is tolerated. The highest reaction rates were
observed in the presence of activated aryl bromides, espe-
cially when hex-1-en-3-one or oct-1-en-3-one was used.
However, this method is also applicable to electron-rich
aryl bromides, to the sterically very congested aryl bro-
mides 1-bromo-2,6-diethyl-4-methylbenzene or 1-bromo-
2,4,6-triisopropylbenzene, and also to hetaryl bromides. It
23
24
25
3-bromopyridine
4-bromopyridine
4-bromopyridine
250
100
250
67 (59)e
a See Scheme 1.
b Reagents and conditions: [Pd(C3H5)Cl]2/Tedicyp (2:1), aryl halide
(1 equiv), oct-1-en-3-one (2 equiv), NaOAc (2 equiv), DMF, hydro-
quinone (0.08 equiv), 130 °C, 20 h.
c Yields are conversions as determined by GC and NMR; yields in pa-
rentheses are isolated yields.
d Reaction performed without hydroquinone.
e 4-Bromopyridine hydrochloride was used directly with NaOAc (3
equiv).
should be noted that most of these reactions could be per-
formed in the presence of 0.4–0.01 mol% catalyst and
some of them with as little as 0.001 mol% catalyst. This
low-catalyst-loading procedure is economically and envi-
ronmentally attractive, with the formation of acetic acid,
sodium bromide, and hydroquinone as major wastes.
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

1028
M. Lemhadri et al.
PAPER
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.001 mmol) under argon
afforded 4.
Moreover, these alk-1-en-3-ones are commercially avail-
able. This is a practical advantage of this reaction.
Yield: 145 mg (85%).
All reactions were run under argon in Schlenk tubes attached to vac-
uum lines. Analytical grade DMF, Me2NAc, NMP, and xylene were
not distilled before use. K2CO3 (99+%), Na2CO3 (99%), NaHCO3
(99%), NaOAc (99%), KF, Et3N, the alk-1-en-3-ones, and commer-
cially available aryl halides were used without purification. 1H and
13C NMR spectra of samples as CDCl3 solns were recorded on a
Bruker 300-MHz spectrometer. Chemical shift are reported relative
to CDCl3 (1H, d = 7.25; 13C, d = 77.0). Flash chromatography was
performed on silica gel (230–400 mesh).
4-(4-Fluorophenyl)but-3-en-2-one (5) (Table 3, entry 4)
The reaction of 4-FC6H4Br (175 mg, 1 mmol), but-1-en-3-one (280
mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg,
0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
5.
Yield: 149 mg (91%).
Pd–Tedicyp Catalyst45
(E)-4-(4-tert-Butylphenyl)but-3-en-2-one (6) (Table 2, entry 21)
The reaction of 4-t-BuC6H4Br (213 mg, 1 mmol), but-1-en-3-one
(280 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 6.
An oven-dried 40-mL Schlenk tube equipped with a magnetic stir-
ring bar, under argon atmosphere, was charged with [Pd(C3H5)Cl]2
(4.2 mg, 11.6 mmol) and Tedicyp (20 mg, 23.2 mmol). Anhyd DMF
(2.5 mL) was added, then the soln was stirred at r.t. for 10 min.
Coupling of Alk-1-en-3-ones with Aryl Halides; General Proce-
dure
Yield: 182 mg (90%).
The reaction of a mixture of the aryl halide (1 mmol), the alk-1-en-
3-one (2 or 4 mmol, see tables), and hydroquinone (9 mg, 0.08
mmol), and NaOAc (164 mg, 2 mmol) with the [Pd(C3H5)Cl]2/
Tedicyp (1:2) complex under argon was carried out in anhyd DMF
(3 mL) at 110 or 130 °C (see tables) for 20 h. After addition of H2O
(20 mL), extraction with CH2Cl2 (20 mL), separation, drying
(MgSO4), evaporation, and purification by chromatography (silica
gel), the corresponding (E)-1-arylalk-1-en-3-one was obtained.
(E)-4-(4-Methoxyphenyl)but-3-en-2-one (7) (Table 3, entry 6)
The reaction of PMPBr (187 mg, 1 mmol), but-1-en-3-one (280 mg,
4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
7.
Yield: 153 mg (87%).
(E)-4-[4-(Trifluoromethyl)phenyl]but-3-en-2-one (8) (Table 3,
entry 1)
The reaction of 1-bromo-4-(trifluoromethyl)benzene (225 mg, 1
mmol), but-1-en-3-one (280 mg, 4 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.01 mmol) under argon afforded 8.
(E)-4-Phenylbut-3-en-2-one (1) (Table 1, entry 6)
The reaction of PhI (204 mg, 1 mmol), but-1-en-3-one (280 mg, 4
mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
1.
Yield: 133 mg (91%).
Yield: 195 mg (91%).
(E)-4-(4-Acetylphenyl)but-3-en-2-one (2) (Table 2, entry 19)
The reaction of 4-AcC6H4Br (199 mg, 1 mmol), but-1-en-3-one
(280 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.001 mmol) under argon
afforded 2.
(E)-4-(1-Naphthyl)but-3-en-2-one (9) (Table 3, entry 8)
The reaction of 1-bromonaphthalene (207 mg, 1 mmol), but-1-en-3-
one (280 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under
argon afforded 9.
Yield: 171 mg (91%).
Yield: 184 mg (94%).
(E)-4-(4-Benzoylphenyl)but-3-en-2-one (3) (Table 2, entry 18)
The reaction of 4-BzC6H4Br (261 mg, 1 mmol), but-1-en-3-one
(280 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 3.
(E)-4-(3-Quinolyl)but-3-en-2-one (10) (Table 3, entry 10)
The reaction of 3-bromoquinoline (208 mg, 1 mmol), but-1-en-3-
one (280 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.001 mmol) un-
der argon afforded 10.
Yield: 235 mg (94%).
Yield: 177 mg (90%).
1H NMR (300 MHz, CDCl3): d = 7.81 (d, J = 8.0 Hz, 2 H), 7.79 (d,
J = 8.0 Hz, 2 H), 7.68–7.55 (m, 5 H), 7.48 (t, J = 7.6 Hz, 1 H), 6.79
(d, J = 16.3 Hz, 1 H), 2.40 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 197.5, 195.8, 141.7, 138.8, 138.1,
137.2, 132.6, 130.6, 129.9, 128.9, 128.4, 128.0, 27.7.
1H NMR (300 MHz, CDCl3): d = 9.09 (s, 1 H), 8.26 (s, 1 H), 8.11
(d, J = 8.5 Hz, 1 H), 7.85 (d, J = 8.5 Hz, 1 H), 7.75 (t, J = 7.8 Hz, 1
H), 7.66 (d, J = 16.1 Hz, 1 H), 7.58 (t, J = 7.8 Hz, 1 H), 6.94 (d,
J = 16.1 Hz, 1 H), 2.44 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 197.7, 149.3, 139.7, 135.7, 130.8,
129.5, 128.4, 128.3, 127.6, 127.5, 127.4, 127.0, 27.9.
Anal. Calcd for C17H14O2: C, 81.58; H, 5.64. Found: C, 81.47; H,
5.73.
Anal. Calcd for C13H11NO: C, 79.16; H, 5.62. Found: C, 79.42; H,
5.69.
(E)-4-(3-Oxobut-1-enyl)benzonitrile (4) (Table 3, entry 3)
The reaction of 4-NCC6H4Br (182 mg, 1 mmol), but-1-en-3-one
(280 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1029
(E)-1-Phenylpent-1-en-3-one (11) (Table 4, entry 1)
The reaction of PhI (204 mg, 1 mmol), pent-1-en-3-one (336 mg, 4
mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon afford-
ed 11.
(E)-1-(4-Nitrophenyl)pent-1-en-3-one (16) (Table 4, entry 13)
The reaction of 4-O2NC6H4Br (202 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon af-
forded 16.
Yield: 149 mg (93%).
Yield: 58 mg (28%).
(E)-1-(4-Acetylphenyl)pent-1-en-3-one (12) (Table 4, entry 5)
The reaction of 4-AcC6H4Br (199 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 12.
(E)-1-(4-Fluorophenyl)pent-1-en-3-one (17) (Table 4, entry 14)
The reaction of 4-FC6H4Br (175 mg, 1 mmol), pent-1-en-3-one (336
mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg,
0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
17.
Yield: 194 mg (96%).
Yield: 168 mg (94%).
1H NMR (300 MHz, CDCl3): d = 7.95 (d, J = 8.3 Hz, 2 H), 7.61 (d,
J = 8.3 Hz, 2 H), 7.55 (d, J = 16.3 Hz, 1 H), 6.80 (d, J = 16.3 Hz, 1
H), 2.70 (q, J = 7.4 Hz, 2 H), 2.55 (s, 3 H), 1.16 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.5, 197.3, 140.4, 139.0, 138.0,
128.8, 128.2, 128.0, 34.4, 26.6, 8.0.
(E)-1-(4-tert-Butylphenyl)pent-1-en-3-one (18) (Table 4, entry
16)
The reaction of 4-t-BuC6H4Br (213 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon af-
forded 18.
Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.35; H,
6.87.
Yield: 201 mg (93%).
(E)-4-(3-Oxopent-1-enyl)benzaldehyde (13) (Table 4, entry 7)
The reaction of 4-OHCC6H4Br (185 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 13.
1H NMR (300 MHz, CDCl3): d = 7.46 (d, J = 16.3 Hz, 1 H), 7.40 (d,
J = 8.5 Hz, 2 H), 7.35 (d, J = 8.5 Hz, 2 H), 6.63 (d, J = 16.3 Hz, 1
H), 2.61 (q, J = 7.4 Hz, 2 H), 1.32 (s, 9 H), 1.07 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 201.0, 153.9, 142.1, 131.8, 128.1,
125.9, 125.3, 34.9, 33.9, 31.1, 8.3.
Yield: 179 mg (95%).
Anal. Calcd for C15H20O: C, 83.28; H, 9.32. Found: C, 83.01; H,
9.12.
1H NMR (300 MHz, CDCl3): d = 9.98 (s, 1 H), 7.84 (d, J = 8.1 Hz,
2 H), 7.65 (d, J = 8.1 Hz, 2 H), 7.54 (d, J = 16.3 Hz, 1 H), 6.80 (d,
J = 16.3 Hz, 1 H), 2.68 (q, J = 7.4 Hz, 2 H), 1.13 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.3, 191.4, 140.3, 140.2, 137.2,
130.1, 128.6, 128.5, 34.5, 8.0.
(E)-1-(4-Tolyl)pent-1-en-3-one (19) (Table 4, entry 18)
The reaction of TolBr (171 mg, 1 mmol), pent-1-en-3-one (336 mg,
4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
19.
Anal. Calcd for C12H12O2: C, 76.57; H, 6.43. Found: C, 76.69; H,
6.30.
Yield: 131 mg (75%).
(E)-1-(4-Benzoylphenyl)pent-1-en-3-one (14) (Table 4, entry 9)
The reaction of 4-BzC6H4Br (261 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 14.
(E)-1-(4-Methoxyphenyl)pent-1-en-3-one (20) (Table 4, entry
22)
The reaction of PMPBr (187 mg, 1 mmol), pent-1-en-3-one (336
mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg,
0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
20.
Yield: 243 mg (92%).
1H NMR (300 MHz, CDCl3): d = 7.81 (d, J = 8.0 Hz, 2 H), 7.79 (d,
J = 8.0 Hz, 2 H), 7.68–7.55 (m, 4 H), 7.49 (t, J = 7.6 Hz, 2 H), 6.83
(d, J = 16.3 Hz, 1 H), 2.72 (q, J = 7.4 Hz, 2 H), 1.18 (t, J = 7.4 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 200.6, 195.9, 140.6, 138.7, 138.4,
137.3, 132.6, 130.6, 130.0, 128.4, 128.0, 127.9, 34.2, 8.1.
Yield: 175 mg (92%).
(E)-1-(6-Methoxy-2-naphthyl)pent-1-en-3-one (21) (Table 4, en-
try 24)
The reaction of 2-bromo-6-methoxynaphthalene (237 mg, 1 mmol),
pent-1-en-3-one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and
hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL)
in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004
mmol) under argon afforded 21.
Anal. Calcd for C18H16O2: C, 81.79; H, 6.10. Found: C, 81.61; H,
6.12.
Methyl (E)-4-(3-Oxopent-1-enyl)benzoate (15) (Table 4, entry
11)
The reaction of 4-MeO2CC6H4Br (215 mg, 1 mmol), pent-1-en-3-
one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 15.
Yield: 211 mg (88%).
1H NMR (300 MHz, CDCl3): d = 7.85 (s, 1 H), 7.78–7.60 (m, 4 H),
7.17 (d, J = 7.7 Hz, 1 H), 7.11 (s, 1 H), 6.79 (d, J = 15.8 Hz, 1 H),
3.91 (s, 3 H), 2.71 (q, J = 7.4 Hz, 2 H), 1.18 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.9, 158.8, 142.5, 135.7, 130.1,
130.0, 129.9, 128.6, 127.4, 125.1, 124.1, 119.4, 105.9, 55.3, 34.0,
8.3.
Yield: 199 mg (91%).
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

1030
M. Lemhadri et al.
PAPER
Anal. Calcd for C16H16O2: C, 79.97; H, 6.71. Found: C, 80.10; H,
6.61.
13C NMR (75 MHz, CDCl3): d = 201.0, 140.7, 138.3, 136.8, 131.2,
129.2, 128.2, 34.0, 21.1, 20.2, 8.2.
Anal. Calcd for C14H18O: C, 83.12; H, 8.97. Found: C, 83.00; H,
8.87.
(E)-1-(2-Acetylphenyl)pent-1-en-3-one (22) (Table 5, entry 1)
The reaction of 2-AcC6H4Br (199 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon af-
forded 22.
(E)-1-(2,6-Diethyl-4-methylphenyl)pent-1-en-3-one (27) (Table
5, entry 12)
The reaction of 1-bromo-2,6-diethyl-4-methylbenzene (227 mg, 1
mmol), pent-1-en-3-one (336 mg, 4 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.01 mmol) under argon afforded 27.
Yield: 176 mg (87%).
1H NMR (300 MHz, CDCl3): d = 8.07 (d, J = 16.5 Hz, 1 H), 7.78
(dd, J = 7.6, 1.5 Hz, 1 H), 7.59 (dd, J = 7.6, 1.3 Hz, 1 H), 7.52 (td,
J = 7.6, 1.3 Hz, 1 H), 7.46 (td, J = 7.6, 1.5 Hz, 1 H), 6.51 (d, J = 16.5
Hz, 1 H), 2.75 (q, J = 7.4 Hz, 2 H), 2.63 (s, 3 H), 1.17 (t, J = 7.4 Hz,
3 H).
13C NMR (75 MHz, CDCl3): d = 201.4, 200.8, 142.2, 137.8, 135.4,
132.2, 129.6, 129.4, 129.3, 128.4, 32.9, 29.1, 8.2.
Yield: 143 mg (62%).
1H NMR (300 MHz, CDCl3): d = 7.75 (d, J = 16.4 Hz, 1 H), 6.91 (s,
2 H), 6.31 (d, J = 16.4 Hz, 1 H), 2.69 (q, J = 7.4 Hz, 2 H), 2.62 (q,
J = 7.6 Hz, 4 H), 2.32 (s, 3 H), 1.19 (t, J = 7.4 Hz, 3 H), 1.16 (t,
J = 7.6 Hz, 6 H).
Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.30; H,
6.81.
13C NMR (75 MHz, CDCl3): d = 200.8, 142.4, 141.1, 138.3, 131.8,
130.5, 127.2, 34.0, 26.8, 21.2, 15.4, 8.2.
Anal. Calcd for C16H22O: C, 83.43; H, 9.63. Found: C, 83.52; H,
9.77.
(E)-1-(1-Naphthyl)pent-1-en-3-one (23) (Table 5, entry 3)
The reaction of 1-bromonaphthalene (207 mg, 1 mmol), pent-1-en-
3-one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydro-
quinone (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 23.
(E)-1-(2,4,6-Triisopropylphenyl)pent-1-en-3-one (28) (Table 5,
entry 13)
The reaction of 1-bromo-2,4,6-triisopropylbenzene (283 mg, 1
mmol), pent-1-en-3-one (336 mg, 4 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.01 mmol) under argon afforded 28.
Yield: 193 mg (92%).
(E)-1-(2-Tolyl)pent-1-en-3-one (24) (Table 5, entry 5)
The reaction of 2-bromotoluene (171 mg, 1 mmol), pent-1-en-3-one
(336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon af-
forded 24.
Yield: 149 mg (52%).
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 16.4 Hz, 1 H), 7.02 (s,
2 H), 6.23 (d, J = 16.4 Hz, 1 H), 3.08 (sept, J = 6.8 Hz, 2 H), 2.88
(sept, J = 6.8 Hz, 1 H), 2.70 (q, J = 7.4 Hz, 2 H), 1.28–1.12 (m, 21
H).
13C NMR (75 MHz, CDCl3): d = 200.6, 148.9, 146.3, 142.0, 132.6,
130.4, 120.8, 34.3, 34.1, 30.2, 24.0, 23.9, 8.1.
Yield: 113 mg (65%).
(E)-1-Anthracen-9-ylpent-1-en-3-one (25) (Table 5, entry 8)
The reaction of 9-bromoanthracene (257 mg, 1 mmol), pent-1-en-3-
one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under
argon afforded 25.
Anal. Calcd for C20H30O: C, 83.86; H, 10.56. Found: C, 84.02; H,
10.78.
(E)-1-(3-Pyridyl)pent-1-en-3-one (29) (Table 6, entry 1)
The reaction of 3-bromopyridine (158 mg, 1 mmol), pent-1-en-3-
one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 29.
Yield: 232 mg (89%).
1H NMR (300 MHz, CDCl3): d = 8.50 (d, J = 16.0 Hz, 1 H), 8.42 (s,
1 H), 8.20 (m, 2 H), 7.98 (m, 2 H), 7.50 (m, 4 H), 6.72 (d, J = 16.0
Hz, 1 H), 2.84 (q, J = 7.4 Hz, 2 H), 1.28 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.3, 139.2, 134.7, 131.2, 129.5,
129.3, 128.8, 128.2, 126.2, 125.3, 125.1, 34.5, 8.1.
Yield: 151 mg (94%).
1H NMR (300 MHz, CDCl3): d = 8.75 (s, 1 H), 8.59 (d, J = 4.7 Hz,
1 H), 7.85 (d, J = 5.8 Hz, 1 H), 7.53 (d, J = 16.2 Hz, 1 H), 7.32 (dd,
J = 5.8, 4.7 Hz, 1 H), 6.80 (d, J = 16.2 Hz, 1 H), 2.71 (q, J = 7.4 Hz,
2 H), 1.17 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C19H16O: C, 87.66; H, 6.19. Found: C, 87.54; H,
6.32.
13C NMR (75 MHz, CDCl3): d = 200.2, 151.0, 149.9, 138.3, 134.3,
(E)-1-Mesitylpent-1-en-3-one (26) (Table 5, entry 10)
The reaction of MesBr (199 mg, 1 mmol), pent-1-en-3-one (336 mg,
4 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
26.
130.4, 127.7, 123.7, 34.3, 8.0.
Anal. Calcd for C10H11NO: C, 74.51; H, 6.88. Found: C, 74.24; H,
6.64.
(E)-1-(4-Pyridyl)pent-1-en-3-one (30) (Table 6, entry 3)
The reaction of 4-bromopyridine hydrochloride (195 mg, 1 mmol),
pent-1-en-3-one (336 mg, 4 mmol), NaOAc (246 mg, 3 mmol), and
hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL)
in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004
mmol) under argon afforded 30.
Yield: 136 mg (67%).
1H NMR (300 MHz, CDCl3): d = 7.63 (d, J = 16.4 Hz, 1 H), 6.81 (s,
2 H), 6.27 (d, J = 16.4 Hz, 1 H), 2.61 (q, J = 7.4 Hz, 2 H), 2.24 (s, 6
H), 2.20 (s, 3 H), 1.10 (t, J = 7.4 Hz, 3 H).
Yield: 151 mg (94%).
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1031
1H NMR (300 MHz, CDCl3): d = 8.61 (d, J = 6.0 Hz, 2 H), 7.44 (d,
J = 16.2 Hz, 1 H), 7.37 (d, J = 6.0 Hz, 2 H), 6.84 (d, J = 16.2 Hz, 1
H), 2.69 (q, J = 7.4 Hz, 2 H), 1.13 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C14H16O2: C, 77.75; H, 7.46. Found: C, 77.60; H,
7.52.
(E)-4-(3-Oxohex-1-enyl)benzaldehyde (35) (Table 7, entry 7)
The reaction of 4-OHCC6H4Br (185 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.0001 mmol) under argon
afforded 35.
13C NMR (75 MHz, CDCl3): d = 200.2, 150.5, 141.9, 138.9, 129.6,
121.9, 34.5, 7.9.
Anal. Calcd for C10H11NO: C, 74.51; H, 6.88. Found: C, 74.62; H,
6.99.
(E)-1-(3-Quinolyl)pent-1-en-3-one (31) (Table 6, entry 5)
The reaction of 3-bromoquinoline (208 mg, 1 mmol), pent-1-en-3-
one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 31.
Yield: 182 mg (90%).
1H NMR (300 MHz, CDCl3): d = 9.99 (s, 1 H), 7.86 (d, J = 8.1 Hz,
2 H), 7.66 (d, J = 8.1 Hz, 2 H), 7.53 (d, J = 16.3 Hz, 1 H), 6.80 (d,
J = 16.3 Hz, 1 H), 2.63 (t, J = 7.4 Hz, 2 H), 1.70 (sext, J = 7.4 Hz,
2 H), 0.95 (t, J = 7.4 Hz, 3 H).
Yield: 194 mg (92%).
13C NMR (75 MHz, CDCl3): d = 199.9, 191.3, 140.3, 140.2, 137.1,
130.0, 128.6, 128.5, 43.1, 17.5, 13.7.
1H NMR (300 MHz, CDCl3): d = 9.07 (s, 1 H), 8.23 (s, 1 H), 8.09
(d, J = 8.5 Hz, 1 H), 7.81 (d, J = 8.5 Hz, 1 H), 7.73 (t, J = 7.8 Hz, 1
H), 7.68 (d, J = 16.1 Hz, 1 H), 7.56 (t, J = 7.8 Hz, 1 H), 6.94 (d,
J = 16.1 Hz, 1 H), 2.73 (q, J = 7.4 Hz, 2 H), 1.18 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.34; H,
6.97.
(E)-1-(4-Benzoylphenyl)hex-1-en-3-one (36) (Table 7, entry 10)
The reaction of 4-BzC6H4Br (261 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.0001 mmol) under argon
afforded 36.
13C NMR (75 MHz, CDCl3): d = 200.2, 149.2, 148.5, 138.5, 135.6,
130.6, 129.3, 128.3, 127.6, 127.5, 127.4, 127.3, 34.5, 8.0.
Anal. Calcd for C14H13NO: C, 79.59; H, 6.20. Found: C, 79.47; H,
6.31.
(E)-1-(4-Isoquinolyl)pent-1-en-3-one (32) (Table 6, entry 7)
The reaction of 4-bromoisoquinoline (208 mg, 1 mmol), pent-1-en-
3-one (336 mg, 4 mmol), NaOAc (164 mg, 2 mmol), and hydro-
quinone (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 32.
Yield: 256 mg (92%).
1H NMR (300 MHz, CDCl3): d = 7.81 (d, J = 8.0 Hz, 2 H), 7.78 (d,
J = 8.0 Hz, 2 H), 7.68–7.43 (m, 6 H), 6.82 (d, J = 16.3 Hz, 1 H),
2.66 (t, J = 7.4 Hz, 2 H), 1.70 (sext, J = 7.4 Hz, 2 H), 0.97 (t, J = 7.4
Hz, 3 H).
Yield: 196 mg (93%).
13C NMR (75 MHz, CDCl3): d = 200.1, 195.8, 140.6, 138.7, 138.3,
137.2, 132.6, 130.5, 129.9, 128.3, 128.1, 127.9, 43.0, 17.6, 13.8.
1H NMR (300 MHz, CDCl3): d = 9.21 (s, 1 H), 8.73 (s, 1 H), 8.22
(d, J = 15.9 Hz, 1 H), 8.10 (d, J = 8.5 Hz, 1 H), 7.99 (d, J = 8.5 Hz,
1 H), 7.77 (t, J = 7.9 Hz, 1 H), 7.64 (t, J = 7.8 Hz, 1 H), 6.97 (d,
J = 15.9 Hz, 1 H), 2.73 (q, J = 7.4 Hz, 2 H), 1.19 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C19H18O2: C, 81.99; H, 6.52. Found: C, 81.99; H,
6.35.
(E)-4-(3-Oxohex-1-enyl)benzonitrile (37) (Table 7, entry 13)
The reaction of 4-NCC6H4Br (182 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.0001 mmol) under argon
afforded 37.
13C NMR (75 MHz, CDCl3): d = 200.1, 153.9, 141.5, 135.9, 133.8,
131.2, 129.3, 128.2, 128.1, 127.6, 125.9, 122.5, 34.9, 8.0.
Anal. Calcd for C14H13NO: C, 79.59; H, 6.20. Found: C, 79.50; H,
6.12.
(E)-1-Phenylhex-1-en-3-one (33) (Table 7, entry 1)
The reaction of PhI (204 mg, 1 mmol), hex-1-en-3-one (196 mg, 2
mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.000 01 mmol) under argon af-
forded 33.
Yield: 179 mg (90%).
1H NMR (300 MHz, CDCl3): d = 7.66 (d, J = 8.4 Hz, 2 H), 7.61 (d,
J = 8.4 Hz, 2 H), 7.49 (d, J = 16.5 Hz, 1 H), 6.77 (d, J = 16.5 Hz, 1
H), 2.63 (t, J = 7.4 Hz, 2 H), 1.70 (sext, J = 7.4 Hz, 2 H), 0.95 (t,
J = 7.4 Hz, 3 H).
Yield: 139 mg (80%).
13C NMR (75 MHz, CDCl3): d = 199.7, 139.5, 138.9, 132.6, 128.9,
128.5, 118.3, 113.3, 43.2, 17.5, 13.7.
(E)-1-(4-Acetylphenyl)hex-1-en-3-one (34) (Table 7, entry 2)
The reaction of 4-AcC6H4Br (199 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.000 1 mmol) under argon
afforded 34.
Anal. Calcd for C13H13NO: C, 78.36; H, 6.58. Found: C, 78.45; H,
6.60.
(E)-1-(4-Nitrophenyl)hex-1-en-3-one (38) (Table 7, entry 15)
The reaction of 4-O2NC6H4Br (202 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 38.
Yield: 203 mg (94%).
1H NMR (300 MHz, CDCl3): d = 7.95 (d, J = 8.3 Hz, 2 H), 7.61 (d,
J = 8.3 Hz, 2 H), 7.54 (d, J = 16.3 Hz, 1 H), 6.80 (d, J = 16.3 Hz, 1
H), 2.65 (t, J = 7.4 Hz, 2 H), 2.60 (s, 3 H), 1.70 (sext, J = 7.4 Hz, 2
H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.1, 197.2, 140.5, 139.0, 138.0,
128.8, 128.2, 128.1, 43.0, 16.6, 17.6, 13.8.
Yield: 193 mg (88%).
1H NMR (300 MHz, CDCl3): d = 8.19 (d, J = 8.3 Hz, 2 H), 7.67 (d,
J = 8.3 Hz, 2 H), 7.53 (d, J = 16.5 Hz, 1 H), 6.80 (d, J = 16.5 Hz, 1
H), 2.64 (t, J = 7.4 Hz, 2 H), 1.69 (sext, J = 7.4 Hz, 2 H), 0.94 (t,
J = 7.4 Hz, 3 H).
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13C NMR (75 MHz, CDCl3): d = 199.7, 148.5, 140.8, 139.0, 129.5,
Yield: 148 mg (68%).
128.7, 124.1, 43.3, 17.5, 13.7.
1H NMR (300 MHz, CDCl3): d = 7.49 (d, J = 16.0 Hz, 1 H), 7.43 (d,
J = 8.4 Hz, 2 H), 6.67 (d, J = 8.4 Hz, 2 H), 6.55 (d, J = 16.0 Hz, 1
H), 3.01 (s, 6 H), 2.60 (t, J = 7.4 Hz, 2 H), 1.69 (sext, J = 7.4 Hz, 2
H), 0.96 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98. Found: C, 65.61; H,
6.12.
(E)-1-(4-Fluorophenyl)hex-1-en-3-one (39) (Table 7, entry 18)
The reaction of 4-FC6H4Br (175 mg, 1 mmol), hex-1-en-3-one (196
mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg,
0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon afford-
ed 39.
13C NMR (75 MHz, CDCl3): d = 200.7, 151.8, 143.2, 130.0, 122.2,
121.6, 111.8, 42.4, 40.1, 18.2, 13.9.
Anal. Calcd for C14H19NO (217): C, 77.38; H, 8.81. Found: C,
77.19; H, 8.80.
(E)-1-(6-Methoxy-2-naphthyl)hex-1-en-3-one (44) (Table 7, en-
try 31)
The reaction of 2-bromo-6-methoxynaphthalene (237 mg, 1
mmol), hex-1-en-3-one (196 mg, 2 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.0001 mmol) under argon afforded 44.
Yield: 171 mg (89%).
1H NMR (300 MHz, CDCl3): d = 7.51 (m, 3 H), 7.06 (t, J = 7.5 Hz,
2 H), 6.65 (d, J = 16.5 Hz, 1 H), 2.62 (t, J = 7.4 Hz, 2 H), 1.69 (sext,
J = 7.4 Hz, 2 H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.3, 163.1 (d, J = 251.4 Hz),
140.9, 130.8 (d, J = 3.5 Hz), 130.0 (d, J = 8.6 Hz), 125.9 (d, J = 2.3
Hz), 116.1 (d, J = 21.8 Hz), 43.1, 17.6, 13.7.
Yield: 201 mg (79%).
Anal. Calcd for C12H13FO: C, 74.98; H, 6.82. Found: C, 74.87; H,
6.69.
1H NMR (300 MHz, CDCl3): d = 7.85 (s, 1 H), 7.78–7.60 (m, 4 H),
7.16 (d, J = 7.7 Hz, 1 H), 7.12 (s, 1 H), 6.79 (d, J = 15.8 Hz, 1 H),
3.91 (s, 3 H), 2.66 (t, J = 7.4 Hz, 2 H), 1.70 (sext, J = 7.4 Hz, 2 H),
0.99 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.5, 158.8, 142.6, 135.7, 130.1,
130.0, 129.9, 128.7, 127.5, 125.4, 124.2, 119.4, 105.9, 55.3, 42.8,
17.9, 13.9.
(E)-1-(4-tert-Butylphenyl)hex-1-en-3-one (40) (Table 7, entry
21)
The reaction of 4-t-BuC6H4Br (213 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 40.
Anal. Calcd for C17H18O2: C, 80.28; H, 7.13. Found: C, 80.38; H,
7.22.
Yield: 200 mg (87%).
(E)-1-(3-Acetylphenyl)hex-1-en-3-one (45) (Table 8, entry 1)
The reaction of 3-AcC6H4Br (199 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 45.
1H NMR (300 MHz, CDCl3): d = 7.51 (d, J = 16.3 Hz, 1 H), 7.47 (d,
J = 8.5 Hz, 2 H), 7.40 (d, J = 8.5 Hz, 2 H), 6.69 (d, J = 16.3 Hz, 1
H), 2.63 (t, J = 7.4 Hz, 2 H), 1.69 (sext, J = 7.4 Hz, 2 H), 1.32 (s, 9
H), 0.96 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.6, 153.9, 142.2, 131.8, 128.0,
125.9, 125.6, 42.6, 34.8, 31.1, 17.8, 13.8.
Yield: 196 mg (91%).
Anal. Calcd for C16H22O: C, 83.43; H, 9.63. Found: C, 83.57; H,
9.54.
1H NMR (300 MHz, CDCl3): d = 8.09 (s, 1 H), 7.92 (d, J = 7.5 Hz,
1 H), 7.69 (d, J = 7.5 Hz, 1 H), 7.54 (d, J = 16.0 Hz, 1 H), 7.46 (t,
J = 7.5 Hz, 1 H), 6.77 (d, J = 16.0 Hz, 1 H), 2.59 (t, J = 7.4 Hz, 2
H), 2.56 (s, 3 H), 1.66 (sext, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3
H).
13C NMR (75 MHz, CDCl3): d = 200.1, 197.4, 140.9, 137.6, 135.1,
132.3, 129.8, 129.2, 127.7, 127.3, 42.9, 26.6, 17.6, 13.7.
(E)-1-(4-Tolyl)hex-1-en-3-one (41) (Table 7, entry 23)
The reaction of TolBr (171 mg, 1 mmol), hex-1-en-3-one (196 mg,
2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon afford-
ed 41.
Anal. Calcd for C14H16O2: C, 77.75; H, 7.46. Found: C, 77.71; H,
7.51.
Yield: 166 mg (88%).
(E)-1-(2-Tolyl)hex-1-en-3-one (46) (Table 8, entry 3)
The reaction of 2-bromotoluene (171 mg, 1 mmol), hex-1-en-3-one
(196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 46.
(E)-1-(4-Methoxyphenyl)hex-1-en-3-one (42) (Table 7, entry 25)
The reaction of PMPBr (187 mg, 1 mmol), hex-1-en-3-one (196 mg,
2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
42.
Yield: 166 mg (88%).
Yield: 184 mg (90%).
1H NMR (300 MHz, CDCl3): d = 7.85 (d, J = 16.0 Hz, 1 H), 7.57 (d,
J = 7.0 Hz, 1 H), 7.35–7.10 (m, 3 H), 6.67 (d, J = 16.0 Hz, 1 H),
2.64 (t, J = 7.4 Hz, 2 H), 2.44 (s, 3 H), 1.70 (sext, J = 7.4 Hz, 2 H),
0.98 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.4, 139.7, 137.9, 133.5, 130.8,
130.0, 127.2, 126.3, 126.2, 43.1, 19.7, 17.8, 13.8.
(E)-1-[4-(Dimethylamino)phenyl]hex-1-en-3-one (43) (Table 7,
entry 30)
The reaction of 1-bromo-4-(dimethylamino)benzene (200 mg, 1
mmol), hex-1-en-3-one (196 mg, 2 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 110 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.004 mmol) under argon afforded 43.
Anal. Calcd for C13H16O: C, 82.94; H, 8.57. Found: C, 82.82; H,
8.59.
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Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1033
(E)-1-Mesitylhex-1-en-3-one (47) (Table 8, entry 5)
The reaction of MesBr (199 mg, 1 mmol), hex-1-en-3-one (196 mg,
2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 110 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.01 mmol) under argon afforded
47.
13C NMR (75 MHz, CDCl3): d = 199.9, 149.3, 148.5, 138.7, 135.7,
130.6, 129.4, 128.3, 127.7, 127.6, 127.4, 116.2, 43.2, 17.6, 13.8.
Anal. Calcd for C15H15NO: C, 79.97; H, 6.71. Found: C, 80.11; H,
6.62.
(E)-1-Phenyloct-1-en-3-one (51) (Table 9, entry 1)
The reaction of PhI (204 mg, 1 mmol), oct-1-en-3-one (252 mg, 2
mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 130 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.00001 mmol) under argon af-
forded 51.
Yield: 145 mg (67%).
1H NMR (300 MHz, CDCl3): d = 7.69 (d, J = 16.4 Hz, 1 H), 6.89 (s,
2 H), 6.34 (d, J = 16.4 Hz, 1 H), 2.63 (t, J = 7.4 Hz, 2 H), 2.31 (s, 6
H), 2.27 (s, 3 H), 1.70 (sext, J = 7.4 Hz, 2 H), 0.99 (t, J = 7.4 Hz, 3
H).
Yield: 174 mg (86%).
13C NMR (75 MHz, CDCl3): d = 200.6, 140.8, 138.3, 136.8, 131.5,
131.1, 129.1, 42.8, 21.1, 21.0, 17.9, 13.8.
(E)-1-(4-Acetylphenyl)oct-1-en-3-one (52) (Table 9, entry 2)
The reaction of 4-AcC6H4Br (199 mg, 1 mmol), oct-1-en-3-one
(252 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.0001 mmol) under argon
afforded 52.
Anal. Calcd for C15H20O: C, 83.28; H, 9.32. Found: C, 83.56; H,
9.54.
(E)-1-(3-Thienyl)hex-1-en-3-one (48) (Table 8, entry 9)
The reaction of 3-bromothiophene (163 mg, 1 mmol), hex-1-en-3-
one (196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 48.
Yield: 220 mg (90%).
1H NMR (300 MHz, CDCl3): d = 7.93 (d, J = 8.3 Hz, 2 H), 7.58 (d,
J = 8.3 Hz, 2 H), 7.51 (d, J = 16.3 Hz, 1 H), 6.77 (d, J = 16.3 Hz, 1
H), 2.63 (t, J = 7.4 Hz, 2 H), 2.57 (s, 3 H), 1.66 (m, 2 H), 1.40–1.25
(m, 4 H), 0.88 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.3, 197.3, 140.5, 139.0, 138.0,
128.8, 128.3, 128.2, 41.2, 31.4, 26.7, 23.9, 22.5, 13.9.
Yield: 157 mg (87%).
1H NMR (300 MHz, CDCl3): d = 7.53 (d, J = 16.4 Hz, 1 H), 7.50
(m, 1 H), 7.33 (dd, J = 5.1, 3.0 Hz, 1 H), 7.29 (dd, J = 5.1, 1.3 Hz,
1 H), 2.60 (t, J = 7.4 Hz, 2 H), 1.67 (sext, J = 7.4 Hz, 2 H), 0.96 (t,
J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.8, 137.7, 135.8, 128.4, 127.0,
126.1, 125.1, 42.7, 17.8, 13.8.
Anal. Calcd for C16H20O2: C, 78.65; H, 8.25. Found: C, 78.73; H,
8.31.
(E)-4-(3-Oxooct-1-enyl)benzaldehyde (53) (Table 9, entry 4)
The reaction of 4-OHCC6H4Br (185 mg, 1 mmol), oct-1-en-3-one
(252 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.0001 mmol) under argon
afforded 53.
Anal. Calcd for C10H12OS: C, 66.63; H, 6.71. Found: C, 66.79; H,
6.71.
(E)-1-(3-Pyridyl)hex-1-en-3-one (49) (Table 8, entry 11)
The reaction of 3-bromopyridine (158 mg, 1 mmol), hex-1-en-3-
one (196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 49.
Yield: 187 mg (81%).
1H NMR (300 MHz, CDCl3): d = 9.96 (s, 1 H), 7.84 (d, J = 8.1 Hz,
2 H), 7.63 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 16.3 Hz, 1 H), 6.78 (d,
J = 16.3 Hz, 1 H), 2.62 (t, J = 7.4 Hz, 2 H), 1.65 (m, 2 H), 1.35–1.25
(m, 4 H), 0.84 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.6, 191.3, 140.3, 140.2, 137.1,
130.1, 128.7, 128.6, 41.3, 31.4, 23.8, 22.4, 13.8.
Yield: 154 mg (88%).
1H NMR (300 MHz, CDCl3): d = 8.74 (s, 1 H), 8.58 (d, J = 4.7 Hz,
1 H), 7.84 (d, J = 5.8 Hz, 1 H), 7.52 (d, J = 16.1 Hz, 1 H), 7.31 (dd,
J = 5.8, 4.7 Hz, 1 H), 6.77 (d, J = 16.1 Hz, 1 H), 2.64 (t, J = 7.4 Hz,
2 H), 1.70 (sext, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 199.8, 151.0, 149.9, 138.4, 134.3,
130.4, 127.9, 123.7, 43.0, 17.6, 13.8.
Anal. Calcd for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.41; H,
7.90.
(E)-1-(4-Benzoylphenyl)oct-1-en-3-one (54) (Table 9, entry 7)
The reaction of 4-BzC6H4Br (261 mg, 1 mmol), oct-1-en-3-one
(252 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.000 01 mmol) under ar-
gon afforded 54.
Anal. Calcd for C11H13NO: C, 75.40; H, 7.48. Found: C, 75.51; H,
7.38.
(E)-1-(3-Quinolyl)hex-1-en-3-one (50) (Table 8, entry 13)
The reaction of 3-bromoquinoline (208 mg, 1 mmol), hex-1-en-3-
one (196 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroqui-
none (9 mg, 0.08 mmol) at 110 °C for 20 h in DMF (3 mL) in the
presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) un-
der argon afforded 50.
Yield: 208 mg (68%).
1H NMR (300 MHz, CDCl3): d = 7.81 (d, J = 8.0 Hz, 2 H), 7.79 (d,
J = 8.0 Hz, 2 H), 7.68–7.43 (m, 6 H), 6.82 (d, J = 16.3 Hz, 1 H),
2.67 (t, J = 7.4 Hz, 2 H), 1.69 (m, 2 H), 1.40–1.25 (m, 4 H), 0.90 (t,
J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.3, 195.8, 140.7, 138.7, 138.4,
137.2, 132.6, 130.6, 130.0, 128.4, 128.1, 128.0, 41.2, 31.4, 23.9,
22.5, 13.9.
Yield: 205 mg (91%).
1H NMR (300 MHz, CDCl3): d = 9.08 (s, 1 H), 8.25 (s, 1 H), 8.09
(d, J = 8.5 Hz, 1 H), 7.82 (d, J = 8.5 Hz, 1 H), 7.73 (t, J = 7.8 Hz, 1
H), 7.68 (d, J = 16.1 Hz, 1 H), 7.57 (t, J = 7.8 Hz, 1 H), 6.94 (d,
J = 16.1 Hz, 1 H), 2.68 (t, J = 7.4 Hz, 2 H), 1.74 (sext, J = 7.4 Hz,
2 H), 0.99 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C21H22O2: C, 82.32; H, 7.24. Found: C, 82.39; H,
7.12.
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(E)-1-[4-(Trifluoromethyl)phenyl]oct-1-en-3-one (55) (Table 9,
entry 10)
The reaction of 1-bromo-4-(trifluoromethyl)benzene (225 mg, 1
mmol), oct-1-en-3-one (252 mg, 2 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 130 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.00001 mmol) under argon afforded 55.
mmol) at 130 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon afford-
ed 59.
Yield: 197 mg (85%).
(E)-1-(2,6-Diethyl-4-methylphenyl)oct-1-en-3-one (60) (Table 9,
entry 22)
Yield: 232 mg (86%).
The reaction of 1-bromo-2,6-diethyl-4-methylbenzene (227 mg, 1
mmol), oct-1-en-3-one (252 mg, 2 mmol), NaOAc (164 mg, 2
mmol), and hydroquinone (9 mg, 0.08 mmol) at 130 °C for 20 h in
DMF (3 mL) in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex
(0.004 mmol) under argon afforded 60.
1H NMR (300 MHz, CDCl3): d = 7.63 (m, 4 H), 7.54 (d, J = 16.0
Hz, 1 H), 6.77 (d, J = 16.0 Hz, 1 H), 2.66 (t, J = 7.4 Hz, 2 H), 1.67
(m, 2 H), 1.40–1.25 (m, 4 H), 0.90 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.8, 140.2, 138.0, 131.8 (q,
2JC-F = 32.7 Hz), 128.3, 128.2, 125.8 (q, 3JC-F = 4.0 Hz), 123.9 (q,
JC-F = 271.7 Hz), 41.2, 31.4, 23.8, 22.4, 13.9.
Yield: 210 mg (77%).
1H NMR (300 MHz, CDCl3): d = 7.74 (d, J = 16.4 Hz, 1 H), 6.91 (s,
2 H), 6.31 (d, J = 16.4 Hz, 1 H), 2.63 (t, J = 7.4 Hz, 2 H), 2.62 (q,
J = 7.6 Hz, 4 H), 2.31 (s, 3 H), 1.67 (m, 2 H), 1.40–1.25 (m, 4 H),
1.17 (t, J = 7.4 Hz, 3 H), 0.90 (t, J = 7.6 Hz, 6 H).
Anal. Calcd for C15H17F3O: C, 66.65; H, 6.34. Found: C, 66.79; H,
6.21.
(E)-4-(3-Oxooct-1-enyl)benzonitrile (56) (Table 9, entry 13)
The reaction of 4-NCC6H4Br (182 mg, 1 mmol), oct-1-en-3-one
(252 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.00001 mmol) under ar-
gon afforded 56.
13C NMR (75 MHz, CDCl3): d = 200.6, 142.4, 141.2, 138.3, 132.0,
130.6, 127.2, 40.9, 31.5, 26.8, 24.2, 22.5, 21.2, 15.4, 13.9.
Anal. Calcd for C19H28O: C, 83.77; H, 10.36. Found: C, 83.88; H,
10.24.
(E)-1-(3-Pyridyl)oct-1-en-3-one (61) (Table 9, entry 23)
The reaction of 3-bromopyridine (158 mg, 1 mmol), oct-1-en-3-one
(252 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004 mmol) under argon
afforded 61.
Yield: 191 mg (84%).
1H NMR (300 MHz, CDCl3): d = 7.67 (d, J = 8.4 Hz, 2 H), 7.61 (d,
J = 8.4 Hz, 2 H), 7.50 (d, J = 16.5 Hz, 1 H), 6.78 (d, J = 16.5 Hz, 1
H), 2.65 (t, J = 7.4 Hz, 2 H), 1.67 (m, 2 H), 1.40–1.25 (m, 4 H), 0.89
(t, J = 7.4 Hz, 3 H).
Yield: 152 mg (75%).
13C NMR (75 MHz, CDCl3): d = 199.9, 139.6, 139.0, 132.6, 128.9,
128.5, 118.3, 113.4, 41.4, 31.4, 23.8, 22.4, 13.9.
1H NMR (300 MHz, CDCl3): d = 8.74 (s, 1 H), 8.57 (d, J = 4.7 Hz,
1 H), 7.85 (d, J = 5.8 Hz, 1 H), 7.50 (d, J = 16.2 Hz, 1 H), 7.32 (dd,
J = 5.8, 4.7 Hz, 1 H), 6.77 (d, J = 16.2 Hz, 1 H), 2.64 (t, J = 7.4 Hz,
2 H), 1.66 (m, 2 H), 1.40–1.25 (m, 4 H), 0.88 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C15H17NO: C, 79.26; H, 7.54. Found: C, 79.29; H,
7.61.
(E)-1-(4-tert-Butylphenyl)oct-1-en-3-one (57) (Table 9, entry 14)
The reaction of 4-t-BuC6H4Br (213 mg, 1 mmol), oct-1-en-3-one
(252 mg, 2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9
mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL) in the presence
of the [Pd(C3H5)Cl]2/Tedicyp complex (0.001 mmol) under argon
afforded 57.
13C NMR (75 MHz, CDCl3): d = 199.9, 150.5, 149.4, 138.1, 134.6,
130.5, 128.0, 123.8, 41.1, 31.3, 23.7, 22.4, 13.8.
Anal. Calcd for C13H17NO: C, 76.81; H, 8.43. Found: C, 76.64; H,
8.51.
(E)-1-(4-Pyridyl)oct-1-en-3-one (62) (Table 9, entry 25)
The reaction of 4-bromopyridine hydrochloride (195 mg, 1 mmol),
oct-1-en-3-one (252 mg, 2 mmol), NaOAc (246 mg, 3 mmol), and
hydroquinone (9 mg, 0.08 mmol) at 130 °C for 20 h in DMF (3 mL)
in the presence of the [Pd(C3H5)Cl]2/Tedicyp complex (0.004
mmol) under argon afforded 62.
Yield: 238 mg (92%).
1H NMR (300 MHz, CDCl3): d = 7.53 (d, J = 16.3 Hz, 1 H), 7.48 (d,
J = 8.5 Hz, 2 H), 7.39 (d, J = 8.5 Hz, 2 H), 6.70 (d, J = 16.3 Hz, 1
H), 2.64 (t, J = 7.4 Hz, 2 H), 1.68 (m, 2 H), 1.40–1.25 (m, 4 H), 1.32
(s, 9 H), 0.90 (t, J = 7.4 Hz, 3 H).
Yield: 120 mg (59%).
13C NMR (75 MHz, CDCl3): d = 200.8, 153.9, 142.2, 131.8, 128.1,
125.9, 125.5, 40.7, 34.8, 31.5, 31.1, 24.1, 22.5, 13.9.
1H NMR (300 MHz, CDCl3): d = 8.64 (d, J = 6.0 Hz, 2 H), 7.43 (d,
J = 16.2 Hz, 1 H), 7.37 (d, J = 6.0 Hz, 2 H), 6.85 (d, J = 16.2 Hz, 1
H), 2.66 (t, J = 7.4 Hz, 2 H), 1.68 (m, 2 H), 1.40–1.25 (m, 4 H), 0.90
(t, J = 7.4 Hz, 3 H).
Anal. Calcd for C18H26O: C, 83.67; H, 10.14. Found: C, 83.79; H,
10.31.
(E)-1-(4-Tolyl)oct-1-en-3-one (58) (Table 9, entry 16)
The reaction of TolBr (171 mg, 1 mmol), oct-1-en-3-one (252 mg,
2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
mmol) at 130 °C for 20 h in DMF (3 mL) in the presence of the
[Pd(C3H5)Cl]2/Tedicyp complex (0.001 mmol) under argon afford-
ed 58.
13C NMR (75 MHz, CDCl3): d = 199.9, 150.6, 141.9, 139.1, 129.9,
121.9, 41.3, 31.4, 30.3, 23.7, 22.4, 13.9.
Anal. Calcd for C13H17NO: C, 76.81; H, 8.43. Found: C, 76.72; H,
8.38.
CAS numbers: 1, 1896-62-4; 2, 115665-94-6; 4, 30626-00-7; 5,
65300-29-0; 6, 55047-62-6; 7, 3815-30-3; 8, 115665-92-4; 9,
51557-09-6; 11, 3152-68-9; 15, 76322-81-1; 16, 54951-55-2; 17,
921206-14-6; 19, 69849-80-5; 20, 104-27-8; 23, 51650-63-6; 24,
863970-09-6; 33, 82297-62-9; 41, 100765-39-7; 42, 82297-65-2;
51, 29478-39-5; 58, 100765-41-1; 59, 82297-67-4.
Yield: 191 mg (88%).
(E)-1-(4-Methoxyphenyl)oct-1-en-3-one (59) (Table 9, entry 20)
The reaction of PMPBr (187 mg, 1 mmol), oct-1-en-3-one (252 mg,
2 mmol), NaOAc (164 mg, 2 mmol), and hydroquinone (9 mg, 0.08
Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Heck Reactions of Alk-1-en-3-ones with Aryl Bromides
1035
(30) Arcadi, A.; Attanasi, O. A.; Berretta, S.; Bianchi, G.;
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Synthesis 2009, No. 6, 1021–1035 © Thieme Stuttgart · New York