The Heck reaction of allylic alcohols catalysed by an air-stable phosphinito complex of palladium(II)

Article abstract of DOI:10.1055/s-0031-1289639

The Heck coupling of aryl bromides with primary and secondary allylic alcohols, performed in the presence of an air-stable- phosphinito complex of palladium(II), produced the corresponding carbonyl compounds. Reactions with tertiary allylic alcohols under the same conditions generated the aromatic conjugated alcohols. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289639

272
PAPER
The Heck Reaction of Allylic Alcohols Catalysed by an Air-Stable Phosphinito
Complex of Palladium(II)
Heck
Reactionof
A
ryl Br
e
omides
w
it
j
hAllyl
a
ic Alcoholsndro Sauza, José Antonio Morales-Serna, Mónica García-Molina, Rubén Gaviño,* Jorge Cárdenas*
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, 04510 México, D.F., México
Fax +52(55)56162217; E-mail: rjcp@unam.mx
Received 8 September 2011; revised 24 October 2011
cross-coupling of bromobenzene with butyl acrylate.
Abstract: The Heck coupling of aryl bromides with primary and
Based on this interesting background, we aimed to synthe-
sise aldehydes and ketones by means of the Heck reaction
of allylic alcohols using the phosphinito complex 1 of pal-
secondary allylic alcohols, performed in the presence of an air-
stable phosphinito complex of palladium(II), produced the corre-
sponding carbonyl compounds. Reactions with tertiary allylic alco-
hols under the same conditions generated the aromatic conjugated ladium(II).
alcohols.
The palladium-catalysed reaction of allylic alcohols with
Key words: allylic alcohols, Heck reaction, palladium, aldehydes,
aryl halides is one of the most powerful methods for the
formation of C–C bonds in the synthesis of saturated16 and
a,b-unsaturated17 aldehydes and ketones, and in the syn-
thesis of allylic alcohols,18 which represent an attractive
building block in organic synthesis.19 One of the draw-
backs of using the Heck reaction of allylic alcohols to ob-
tain aldehydes and ketones is the formation of a reaction
mixture17 with both saturated and unsaturated carbonyl
compounds as principal products, which must be con-
trolled to exclusively obtain the saturated16 or unsaturated
product.20 In this context, we now disclose that the phos-
phinito complex 1 of palladium(II) can be used in the b-
arylation of allylic alcohols with highly regioselective re-
sults, without recourse to strict anhydrous reaction condi-
tions.
ketones
Transition-metal-mediated reactions allow transforma-
tions of organic substrates that are difficult to achieve via
transition-metal-free procedures.1 The importance of
these reactions has stimulated the creativity of chemists to
design new catalytic systems and ligands. Recently, as
part of our research on the Heck reaction,2 we have dem-
onstrated the utility of the phosphinito complex 1 of pal-
ladium(II)3 (Scheme 1) in the formation of C–C bonds.4
This type of palladium compound has not been thoroughly
explored in homogeneous catalysis despite its high air and
water stability. These properties, however, have recently
attracted interest in the phosphinito complexes because of
their potential as catalysts in homogeneous reactions.
Similar transition-metal compounds containing hydro-
gen-bonded P–O–H–O–P ligands have been synthesised,
including complexes of palladium,5 platinum,6 molybde-
num,7 iridium8 and ruthenium.9 The stability of these
ligand pairs is an interesting result of the additional hydro-
gen bonding. This proton can be substituted by other
Lewis acids to furnish a complex with ‘hard’ and ‘soft’
centres. Additionally, the same proton is easily removed
by titration with a base.10 The term ‘diphenylphosphinito’
was introduced by Roundhill11 to differentiate this type of
Ph
O
H
O
P
Ph
PPh2Cl
Cl Pd Cl
4 H2O
6 HCl
Cl Pd
P
Ph
Ph
2
Ph
P
Pd Cl Ph
Ph
Ph
PPh2Cl
O
P
H
O
1
Scheme 1 Phosphinito complex of palladium(II)
A simple hydrolysis reaction of a chlorodiphenylphos-
phine complex of palladium made it possible to obtain a
binuclear chloride-bridged organopalladium(II) complex
(Scheme 1). It is noteworthy that, in our hands, the com-
plex has been stable for two years, stored at room temper-
ature and without any special conditions. 31P NMR
spectroscopy showed that the complex was stable in the
presence of water or methanol for 5 and 10 hours, respec-
tively. Considering these previous observations, we ini-
tially decided to explore the reaction of 4-
bromobenzophenone (2) with 1-phenyl-2-propen-1-ol (3)
in N,N-dimethylformamide at different temperatures, as a
simple model to find the best conditions for the reaction.
When the reaction was performed at room temperature,
the ketone 4 was not observed (Table 1, entry 1); howev-
–
compound from diphenylphosphinate (Ph2PO2 ). The
application of these phosphinito ligands in catalysis has
been limited to the platinum phosphinito complex
[PtCl(PR2OH){(PR2O)2H}] (R = Me, Ph), which hydrol-
yses nitriles to amides12 and catalyses the hydration of
cyanohydrins to obtain a-hydroxy amides.13 Tanaka and
co-workers have demonstrated that similar complexes of
platinum and palladium are useful in the hydrophosphinyl-
ation of alkynes.14 Recently, Trzeciak and co-workers15
reported the use of a palladium phosphinito complex in
the methoxycarbonylation of iodobenzene and the Heck
SYNTHESIS 2012, 44, 272–282
Advanced online publication: 08.12.2011
DOI: 10.1055/s-0031-1289639; Art ID: M87711SS
x
x
.x
x
.2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

PAPER
Heck Reaction of Aryl Bromides with Allylic Alcohols
273
er, 4 was obtained in a 74% yield when the reaction was
performed at 50 °C (Table 1, entry 2). The yield increased
to 91% when the reaction mixture was heated to 90 °C for
18 hours (Table 1, entry 3). The yield remained similar af-
ter only 6 hours (92%; Table 1, entry 4); however, a short-
er reaction time affected the yield of the reaction: only
53% of 4 was observed after 2 hours (Table 1, entry 5).
Next, we explored the reaction with other solvents com-
monly used for the Heck reaction. When the reaction was
performed in toluene at 90 °C, ketone 4 was obtained in a
31% yield (Table 1, entry 6). The yield decreased to 27%
when dimethyl sulfoxide was used (Table 1, entry 7), and
the worst result was obtained when the reaction was per-
formed in tetrahydrofuran under reflux (Table 1, entry 8).
Santelli and co-workers have demonstrated the impor-
tance of N,N-dimethylformamide in similar reactions.16c
Table 1 Heck Coupling of Aryl Bromide 2 with Allylic Alcohol 3
in the Presence of Complex 1a
O
O
Br
2
1 (1 mol%)
+
O
4
OH
3
Entry
Solvent
DMF
Temp (°C) Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
r.t.
50
18
18
18
6
0
74
91
92
53
31
27
0
DMF
To examine the scope of the reaction, we performed ex-
periments with the aryl bromides 2 and 7 and the primary
allylic alcohol 9 under the optimised reaction conditions,
which produced good yields of the corresponding alde-
hydes 13 and 23 (Table 2, entries 1 and 10). Next, the re-
action was performed with the aryl bromides 5 to 8 and the
secondary allylic alcohols 3, 11 and 12 to obtain the cor-
responding ketones 16 to 19, 22, and 24 to 26 (Table 2, en-
tries 3–6, 9, and 11–13). In the case of fluorene 7 as
starting material, the products were the corresponding flu-
orenones. Those reactions were carried out in the presence
and absence of oxygen, and in both cases the fluorenones
were obtained (Table 2, entries 9–11).
DMF
90
DMF
90
DMF
90
2
toluene
DMSO
THF
90
18
18
18
140
reflux
a Reaction conditions: 2 (1 mmol), 3 (1 mmol), NaOAc (1.2 mmol),
catalyst 1 (1 mol%).
b Yield of isolated product after chromatographic purification.
Table 2 Scope of the Palladium-Catalysed Allylic Alcohol Heck Reactiona
Entry
Aryl bromide
Alcohol
Product
Yieldb (%)
O
O
1
85
OH
H
9
Br
O
2
2
13
14
O
OH
OH
89
2
94c
O
10
15
16
O
Br
3
91
OH
NO2
NO2
11
5
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A. Sauza et al.
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Table 2 Scope of the Palladium-Catalysed Allylic Alcohol Heck Reactiona (continued)
Entry
4
Aryl bromide
Alcohol
Product
Yieldb (%)
91
O
O
5
OH
NO2
12
17
5
6
7
8
5
3
3
79
57
68
80
NO2
18
19
20
21
O
Br
CN
CN
CN
CN
6
O
H
6
6
9
OH
10
9
3
80
Br
O
7
7
O
22
23
24
25
26
H
O
O
10
11
12
13
9
11
11
12
70
85
72
61
O
O
7
Br
O
O
8
8
a Reaction conditions: aryl bromide (1 mmol), allylic alcohol (1.1 mmol), NaOAc (1.2 mmol), catalyst 1 (1 mol%), DMF, 90 °C, 6 h.
b Yield of isolated product after chromatographic purification.
c The reaction was performed under microwave conditions: aryl bromide (1 mmol), allylic alcohol (1.1 mmol), NaOAc (1.2 mmol), catalyst 1
(1 mol%), DMF, 200 °C, 20 min.
Synthesis 2012, 44, 272–282
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Heck Reaction of Aryl Bromides with Allylic Alcohols
275
Based on these results, we tried to extend the methodolo- To our delight, however, the carbonyl compound 32 was
gy to the tertiary allylic alcohol 10. Thus, we conducted obtained in good yield (78%) under microwave conditions
the b-arylation reaction of alcohol 10 with aryl bromide 2, (Table 3, entry 1). The reaction performed with the tertia-
focusing on the possible formation of elimination prod- ry allylic alcohol 10 provided compound 33 as the only
ucts. As shown in Table 2 (entry 2), the allylic alcohol 14 product, in a similar yield and with high regioselectivity
was exclusively obtained in excellent yield. Despite the (Table 3, entry 2). Next, the reaction was performed with
basicity of the reaction medium, no elimination products 3,5-dibromopyridine (28) and 2-methyl-3-buten-2-ol (10;
(dienes) were observed; however, when the reaction of al- 2.2 equiv), which produced compound 34 in 84% yield
cohol 10 was carried out under microwave conditions, the (Table 3, entry 3). Similar results were obtained when 3-
diene 15 was formed as the only product. This observation bromoquinoline (29) and 4-bromoisoquinoline (30) were
allowed our group to glimpse the possibility of obtaining subjected to the alkylation conditions (Table 3, entries 4–
1-aryl-1,3-dienes, which is currently under investigation. 9). To test the extension of the palladium-catalysed reac-
Finally, we attempted the reaction with electron-rich aryl tion to other heterocyclic aromatics, we also investigated
bromides; unfortunately, formation of the desired prod- the reaction of allylic alcohols 3 and 9 to 12 with 5-bromo-
ucts was not observed.
2-furaldehyde (31) which gave compounds 41 to 45 in
good yields (Table 3, entries 10–14). Oxidation products
of aldehydes were not observed in 1H NMR analysis of the
crude reaction mixtures of these examples, and it was gen-
erally possible to obtain an extremely clean reaction.
Finally, we attempted the alkylation of 2-iodothiophene,
which represents an interesting template for building
more complex molecules. Unfortunately, when the reac-
tion was performed under standard conditions with 1-phe-
nyl-2-propen-1-ol (3) in N,N-dimethylformamide, the
desired product was not formed.
Following these results, we tried to extend this methodol-
ogy to other aromatic systems. First, this study focused on
the reaction of 3-bromopyridine with allylic alcohols. The
alkylation approach for the synthesis of 3-alkylpyridines
can be classified into three categories: alkylation of 3-py-
ridyllithium,21 alkylation via nicotinic acid22 and palladi-
um-catalysed alkylation.23 In this context, and with the
purpose of preparing useful building blocks for employ-
ment in the synthesis of alkaloids, 3-bromopyridine (27)
was alkylated with the allylic alcohol 3 under the same re-
action conditions used for aryl bromide 2. Surprisingly,
when the reaction was performed in N,N-dimethylform-
amide at 90 °C, only the starting material was recovered.
Table 3 Heck Reaction of Heteroaryl Bromides with Allylic Alcoholsa
Entry
Aryl bromide
Alcohol
Product
Yieldb (%)
78c
O
Br
1
3
N
N
27
32
OH
2
3
4
27
10
10
12
88
N
33
HO
OH
Br
Br
84d
77
N
N
28
34
O
O
Br
N
N
N
29
29
35
36
H
5
9
88
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Table 3 Heck Reaction of Heteroaryl Bromides with Allylic Alcoholsa (continued)
Entry
6
Aryl bromide
Alcohol
Product
Yieldb (%)
92
OH
29
10
N
37
38
39
Br
O
O
7
8
9
11
12
9
87
84
91
N
N
N
30
30
H
O
30
N
40
H
Br
10
3
H
91
O
O
O
O
O
O
O
O
O
O
31
41
H
H
11
12
13
14
31
9
10
11
12
89
88
83
80
O
42
H
31
31
31
OH
O
O
43
H
O
44
H
O
O
45
a Reaction conditions: aryl bromide (1 mmol), allylic alcohol (1.1 mmol), NaOAc (1.2 mmol), catalyst 1 (1 mol%), DMF, 90 °C, 6 h.
b Yield of isolated product after chromatographic purification.
c The reaction was performed under microwave conditions: aryl bromide (1 mmol), allylic alcohol (1.1 mmol), NaOAc (1.2 mmol), catalyst 1
(1 mol%), DMF, 200 °C, 20 min.
d The reaction was carried out with 2.2 mmol of 10.
A plausible reaction mechanism for how the phosphinito workers have demonstrated, by deuterium labelling, that
complex 1 of palladium(II), as catalytic precursor, cataly- the carbinol hydrogen can undergo elimination.24 The re-
ses the alkylation of aryl halides is shown in Scheme 2. action conditions were modified in an attempt to obtain
The first step involves the oxidative addition of aryl ha- the thermodynamically favoured a,b-unsaturated carbonyl
lides, followed by regioselective alkene insertion and Pd– compounds. Thus, the reaction of aryl bromide 2 and al-
H b-elimination involving the carbinol hydrogen, which lylic alcohol 3 was performed in the presence of oxygen
furnishes the desired carbonyl compound. Norrby and co- with the goal of promoting a second insertion of palladi-
Synthesis 2012, 44, 272–282
© Thieme Stuttgart · New York

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Heck Reaction of Aryl Bromides with Allylic Alcohols
277
um;20 however, the formation of the a,b-unsaturated ke-
tone was not observed. Additionally, cinnamyl alcohol
was treated with the phosphinito complex 1 of palladi-
um(II) in N,N-dimethylformamide at 80 °C for 24 hours
to confirm that the carbonyl compounds obtained in the
present protocol were not products of a Pd–H elimina-
tion–readdition process. Thus, the reaction was performed
in an NMR tube and monitored for 6 hours. The 1H NMR
spectrum of the reaction mixture showed only the pres-
ence of the (E)-cinnamyl alcohol (67%), cinnamaldehyde
(24%), 3-phenyl-1-propanol (6%) and (Z)-cinnamyl alco-
hol (2%); however, 3-phenylpropanal was not observed.
Based on these observations, it is reasonable to explain
plates. Developed TLC plates were visualized under a short-wave
UV lamp and by heating plates that were dipped in Ce(SO4)2. Flash
column chromatography (FCC) was performed using flash silica gel
(230–400 mesh) and employed a solvent polarity correlated with
TLC mobility. Microwave reactions were performed in an Anton
Paar Monowave 300 in sealed reaction vessels. NMR experiments
were conducted on Bruker Avance 400 MHz, Bruker Avance 300
MHz and Varian Genimi 200 MHz instruments using CDCl3
(99.9% D) as the solvent, with chemical shifts (d) referenced to in-
1
ternal standards CDCl3 (7.26 ppm for H, 77.0 ppm for 13C) or
Me4Si as an internal reference (0.00 ppm). Chemical shifts are in
parts per million (ppm). Mass spectra were recorded on a Jeol JS102
high-resolution mass spectrometer.
Palladium(II) Complex 1
our results by the reaction mechanism depicted in A soln of Ph2PCl (0.75 mL, 4.05 mmol) in THF (5 mL) was added
dropwise whilst stirring to a soln of [PdCl2(C6H5CN)2] (0.76 g, 2.0
Scheme 2. It is noteworthy that Santelli has proposed that
mmol) in THF (10 mL) placed in a Schlenk flask at r.t. When the
the interaction of the alcohol function with the palladium
complete formation of the dichlorophosphane complex was con-
centre plays an important role in olefin migration.16c In
firmed by 31P NMR spectroscopy (d = 87 ppm), H2O (0.5 mL) was
our case, there is no evidence of a similar interaction.
added to the reaction mixture, which was stirred at r.t. After 48 h,
the 31P NMR analysis of an aliquot exclusively showed the signal of
Pd2+
complex 1 at 78.6 ppm. After this time, the solvent was removed un-
der reduced pressure. A yellow crystalline powder was obtained;
yield: 92%; mp 113–116 °C.
IR: 3441 (m, O–H–O), 1479 (w), 1435 (Ph), 1023 cm–1 (m, P–O).
1H NMR (300 MHz, CDCl3): d = 7.7–7.2 (Ph).
31P NMR (121.4 MHz, CDCl3): d = 78.6.
R1
Br
AcOH
reductive
Pd0
elimination
R1
AcO–
oxidative
addition
R2
General Procedure for the Catalytic Reactions
O
R1
In all Heck reactions, a soln of aryl bromide (1 mmol), allylic alco-
hol (1.1 mmol), NaOAc (1.2 mmol) and catalyst 1 (1 mol%) in
DMF (3 mL) was heated for 6 h, in a 90 °C silicon oil bath, using a
condenser system. Then, the mixture was cooled to r.t., diluted with
EtOAc (15 mL), washed with brine (3 × 10 mL), dried (Na2SO4)
and concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography (25 × 2.5 cm,
EtOAc–hexane gradient).
PdII
R1
Br
PdII
Br
H
R2
OH
coordination
Br
PdII
R1
β-elimination
R1
PdII
H
R2
OH
3-(4-Benzoylphenyl)-1-phenyl-1-propanone (4)
[CAS Reg. No. 1093625-76]
Br
R2
insertion
OH
Following the general procedure, the reaction was carried out start-
ing from 4-bromobenzophenone (2; 261 mg, 1 mmol), 1-phenyl-2-
propen-1-ol (3; 147 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the
reaction crude was purified by flash column chromatography on sil-
ica gel (EtOAc–hexane gradient) to give 4; yield: 287 mg (92%).
IR: 1670 (C=O), 1647 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 8.10–7.30 (m, 14 H), 3.36 (t,
J = 7.0 Hz, 2 H), 3.16 (t, J = 7.0 Hz, 2 H).
Scheme 2 Proposed reaction mechanism
In conclusion, we have demonstrated that it is possible to
use an air-stable phosphinito complex of palladium(II) to
perform the alkylation of aromatic systems. Because com-
plex 1 does not need to be used under anhydrous condi-
tions, this compound can be readily utilised for the
synthesis of attractive building blocks. The procedure pro-
vides efficient access to functionalised aldehydes, ketones
and aromatic allylic alcohols with full regioselectivity,
which can provide avenues for the preparation of mole-
cule libraries. Additionally, the proposed method has ap-
plications in the preparation of biologically valuable
substances.
13C NMR (50 MHz, DEPT, CDCl3): d = 198.6, 196.3, 146.3, 137.6,
136.5, 135.4, 133.1, 132.2, 130.4, 129.8, 128.5, 128.3, 128.1, 127.9,
39.7, 29.9.
MS (EI): m/z (%) = 105 (88), 77 (37), 58 (34), 43 (100), 28 (85).
HRMS–FAB: m/z calcd for C22H18O2: 314.1307; found: 314.1301.
3-(4-Benzoylphenyl)butanal (13)
Following the general procedure, the reaction was carried out start-
ing from 4-bromobenzophenone (2; 261 mg, 1 mmol), crotyl alco-
hol (9; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst
1 (10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 13; yield: 214 mg (85%).
All the chemicals were purchased from Aldrich Chemical Co. and
were used without further purification unless stated otherwise.
Yields refer to the chromatographically and spectroscopically (1H
and 13C NMR) homogeneous materials, unless otherwise stated. All
glassware utilized was flame-dried before use. Reactions were mon-
itored by TLC carried out on 0.25-mm Macherey Nagel silica gel
IR: 1708 (C=O), 1672 cm–1 (C=O).
© Thieme Stuttgart · New York
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278
A. Sauza et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 9.74 (t, J = 1.7 Hz, 1 H), 7.80 (m,
4 H), 7.58 (t, J = 8.0 Hz, 1 H), 7.42 (t, J = 8.0 Hz, 2 H), 7.31 (d,
J = 8.0 Hz, 2 H), 3.43 (sextet, J = 7.0 Hz, 1 H), 2.82 (ddd, J = 1.6,
6.8, 17 Hz, 1 H), 2.73 (ddd, J = 1.9, 7.5, 17 Hz, 1 H), 1.35 (d, J = 7
Hz, 3 H).
13C NMR (75 MHz, DEPT, CDCl3): d = 201.0, 196.3, 150.4, 137.6,
135.9, 132.3, 130.5, 129.9, 128.2, 126.7, 51.3, 34.1, 21.9.
ol (12; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst
1 (10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 17; yield: 176 mg (91%).
1H NMR (200 MHz, CDCl3): d = 7.88 (d, J = 8.0 Hz, 1 H), 7.60–
7.30 (m, 3 H), 3.11 (t, J = 7.0 Hz, 2 H), 2.83 (t, J = 7.0 Hz, 2 H),
2.13 (s, 3 H).
MS (EI): m/z (%) = 252 (48), 209 (82), 191 (49), 105 (100), 77 (51).
HRMS–FAB: m/z calcd for C17H16O2: 252.1150; found: 252.1144.
13C NMR (50 MHz, DEPT, CDCl3): d = 206.8, 148.9, 136.0, 133.0,
132.1, 127.2, 124.6, 43.9, 29.7, 27.0.
HRMS–FAB: m/z calcd for C10H11NO3: 193.0739; found:
{4-[(E)-3-Hydroxy-3-methyl-1-butenyl]phenyl}(phenyl)meth-
anone (14)
[CAS Reg. No. 943897-30-1]
193.0734.
3-(2-Nitrophenyl)-1-phenyl-1-propanone (18)
[CAS Reg. No. 58751-63-6]
Following the general procedure, the reaction was carried out start-
ing from 4-bromobenzophenone (2; 261 mg, 1 mmol), 2-methyl-3-
buten-2-ol (10; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and
catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the re-
action crude was purified by flash column chromatography on silica
gel (EtOAc–hexane gradient) to give 14; yield: 237 mg (89%).
1H NMR (400 MHz, CDCl3): d = 7.80 (m, 4 H), 7.60 (t, J = 8.0 Hz,
1 H), 7.50 (m, 4 H), 6.67 (d, J = 16.0 Hz, 1 H), 6.49 (d, J = 16.0 Hz,
1 H), 1.61 (s, 1 H, OH), 1.45 (s, 6 H).
Following the general procedure, the reaction was carried out start-
ing from 1-bromo-2-nitrobenzene (5; 202 mg, 1 mmol), 1-phenyl-
2-propen-1-ol (3; 147 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the
reaction crude was purified by flash column chromatography on sil-
ica gel (EtOAc–hexane gradient) to give 18; yield: 201 mg (79%).
1H NMR (200 MHz, CDCl3): d = 7.95 (m, 3H), 7.60–7.30 (m, 6 H),
3.47–3.26 (m, 4 H).
13C NMR (100 MHz, DEPT, CDCl3): d = 196.2, 141.2, 140.3,
137.8, 136.3, 132.3, 130.6, 129.9, 128.3, 126.2, 125.6, 71.1, 29.9.
13C NMR (50 MHz, DEPT, CDCl3): d = 198.4, 149.2, 136.5, 136.4,
133.2, 133.1, 132.5, 128.5, 128.0, 127.4, 124.8, 39.3, 27.6.
HRMS–FAB: m/z calcd for C18H18O2: 266.1307; found: 266.1298.
HRMS–FAB: m/z calcd for C15H13NO3: 255.0895; found:
255.0889.
{4-[(E)-3-Methyl-1,3-butadienyl]phenyl}(phenyl)methanone
(15)
2-(3-Oxo-3-phenylpropyl)benzonitrile (19)
[CAS Reg. No. 898793-86-7]
A mixture of 4-bromobenzophenone (2; 261 mg, 1 mmol), 2-meth-
ylbut-3-en-2-ol (10; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%) in DMF (3 mL) was reacted in an
Anton Paar Monowave 300 in a sealed reaction vessel at 200 °C and
27 bar for 20 min. Then, the mixture was cooled to r.t., diluted with
EtOAc (15 mL), washed with brine (3 × 10 mL), dried (Na2SO4)
and concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography (25 × 2.5 cm,
EtOAc–hexane gradient) to give 15; yield: 232 mg (94%).
Following the general procedure, the reaction was carried out start-
ing from 2-bromobenzonitrile (6; 182 mg, 1 mmol), 1-phenyl-2-
propen-1-ol (3; 147 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the
reaction crude was purified by flash column chromatography on sil-
ica gel (EtOAc–hexane gradient) to give 19; yield: 134 mg (57%).
1H NMR (200 MHz, CDCl3): d = 7.94 (m, 2 H), 7.70–7.20 (m, 7 H),
3.45–3.20 (m, 4 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 197.8, 145.1, 136.3, 133.1,
132.8, 132.7, 129.9, 128.5, 127.9, 126.7, 117.9, 112.2, 38.9, 28.6.
1H NMR (200 MHz, CDCl3): d = 7.90–7.40 (m, 9 H), 7.01 (d,
J = 15.9 Hz, 1 H), 6.59 (d, J = 15.9 Hz, 1 H), 5.21 (s, 1 H), 5.18 (s,
1 H), 2.01 (s, 3 H).
HRMS–FAB: m/z calcd for C16H13NO: 235.0997; found: 235.0991.
HRMS–FAB: m/z calcd for C18H16O: 248.1201; found: 248.1297.
2-(1-Methyl-3-oxopropyl)benzonitrile (20)
1-(2-Nitrophenyl)-3-pentanone (16)
Following the general procedure, the reaction was carried out start-
ing from 2-bromobenzonitrile (6; 182 mg, 1 mmol), crotyl alcohol
(9; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1
(10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 20; yield: 118 mg (68%).
[CAS Reg. No. 1094463-35-0]
Following the general procedure, the reaction was carried out start-
ing from 1-bromo-2-nitrobenzene (5; 202 mg, 1 mmol), 1-penten-3-
ol (11; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst
1 (10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 16; yield: 188 mg (91%).
IR: 2225 (CN), 1711 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): d = 9.84 (t, J = 1.4 Hz, 1 H), 7.75–
7.50 (m, 2 H), 7.30–7.10 (m, 2 H), 3.69 (sextet, J = 7.2 Hz, 1 H),
2.75 (dd, J = 7.2, 16 Hz, 1 H), 2.66 (dd, J = 7.2, 16 Hz, 1 H), 1.34
(d, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, DEPT, CDCl3): d = 200.2, 148.9, 133.3,
133.1, 127.0, 126.4, 117.8, 112.0, 50.5, 32.4, 21.4.
1H NMR (200 MHz, CDCl3): d = 7.87 (d, J = 8.0 Hz, 1 H), 7.60–
7.20 (m, 3 H), 3.10 (t, J = 7.4 Hz, 2 H), 2.78 (t, J = 7.4 Hz, 2 H),
2.39 (q, J = 7.4 Hz, 2 H), 1.00 (t, J = 7.4 Hz, 3 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 209.7, 149.0, 136.3, 133.1,
132.3, 127.3, 124.7, 42.6, 35.7, 27.1, 7.6.
HRMS–FAB: m/z calcd for C11H13NO3: 207.0895; found:
207.0887.
MS (EI): m/z (%) = 143 (100), 130 (60), 103 (19), 77 (13), 28 (20).
HRMS–FAB: m/z calcd for C11H11NO: 173.0841; found: 173.0837.
4-(2-Nitrophenyl)-2-butanone (17)
[CAS Reg. No. 58751-62-5]
2-[(E)-3-Hydroxy-3-methyl-1-butenyl]benzonitrile (21)
Following the general procedure, the reaction was carried out start-
ing from 2-bromobenzonitrile (6; 182 mg, 1 mmol), 2-methyl-3-
Following the general procedure, the reaction was carried out start-
ing from 1-bromo-2-nitrobenzene (5; 202 mg, 1 mmol), 3-buten-2-
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Heck Reaction of Aryl Bromides with Allylic Alcohols
279
buten-2-ol (10; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and
catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the re-
action crude was purified by flash column chromatography on silica
gel (EtOAc–hexane gradient) to give 21; yield: 150 mg (80%).
13C NMR (50 MHz, DEPT, CDCl3): d = 210.4, 194.4, 144.6, 142.8,
138.1, 136.9, 135.3, 134.5, 133.8, 124.8, 124.4, 124.1, 123.9, 122.6,
43.8, 29.8, 20.6, 7.5.
MS (EI): m/z (%) = 264 (74), 235 (31), 207 (51), 193 (100).
IR: 3434 (OH), 2225 cm–1 (CN).
HRMS–FAB: m/z calcd for C18H16O2: 264.1150; found: 264.1144.
1H NMR (200 MHz, CDCl3): d = 7.60–7.30 (m, 3 H), 7.16 (dt,
J = 2.0, 8.0 Hz, 1 H), 6.79 (d, J = 16.0 Hz, 1 H), 6.43 (d, J = 16.0
Hz, 1 H), 2.50 (s, 1 H, OH), 1.34 (s, 6 H).
1-(1-Naphthalenyl)-3-pentanone (25)
[CAS Reg. No. 1099621-55-2]
13C NMR (50 MHz, DEPT, CDCl3): d = 142.9, 140.3, 132.7, 132.6,
Following the general procedure, the reaction was carried out start-
ing from 1-bromonaphthalene (8; 207 mg, 1 mmol), 1-penten-3-ol
(11; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1
(10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 25; yield: 152 mg (72%).
127.2, 125.7, 122.2, 117.8, 110.6, 71.0, 29.4.
MS (EI): m/z (%) = 172 (30), 144 (40), 130 (100), 43 (46), 28 (24).
HRMS–FAB: m/z calcd for C12H13NO: 187.0997; found: 187.0989.
2-(3-Oxo-3-phenylpropyl)-9H-fluoren-9-one (22)
IR: 1712 cm–1 (C=O).
Following the general procedure, the reaction was carried out start-
ing from 2-bromofluorene (7; 245 mg, 1 mmol), 1-phenyl-2-prop-
en-1-ol (3; 147 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and
catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the re-
action crude was purified by flash column chromatography on silica
gel (EtOAc–hexane gradient) to give 22; yield: 250 mg (80%).
1H NMR (200 MHz, CDCl3): d = 8.40–7.20 (m, 7 H), 3.48 (t,
J = 7.4 Hz, 2 H), 2.84 (t, J = 7.4 Hz, 2 H), 2.47 (q, J = 7.2 Hz, 2 H),
1.17 (t, J = 7.2 Hz, 3 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 210.4, 137.0, 133.6, 131.7,
128.7, 127.7, 127.1, 125.8, 125.4, 125.3, 123.3, 42.8, 35.8, 26.6,
7.6.
IR: 1713 (C=O alkyl), 1684 cm–1 (C=O fluorenyl).
1H NMR (400 MHz, CDCl3): d = 8.40–7.20 (m, 7 H), 3.48 (t,
J = 7.4 Hz, 2 H), 2.84 (t, J = 7.4 Hz, 2 H), 2.47 (q, J = 7.2 Hz, 2 H),
1.17 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, DEPT, CDCl3): d = 198.7, 194.0, 144.5,
142.7, 142.5, 136.7, 134.9, 134.7, 134.6, 134.3, 133.2, 128.7, 128.6,
128.0, 124.3, 124.2, 120.4, 120.1, 39.8, 29.8.
MS (EI): m/z (%) = 212 (81), 210 (41), 181 (100), 155 (61), 141
(94).
HRMS–FAB: m/z calcd for C15H16O: 212.1201; found: 212.1198.
4-(1-Naphthalenyl)-2-butanone (26)
[CAS Reg. No. 3506-84-1]
MS (EI): m/z (%) = 312 (39), 207 (44), 193 (23), 105 (100), 77 (35).
HRMS–FAB: m/z calcd for C22H16O2: 312.1150; found: 312.1145.
Following the general procedure, the reaction was carried out start-
ing from 1-bromonaphthalene (8; 207 mg, 1 mmol), 3-buten-2-ol
(12; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1
(10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 26; yield: 121 mg (61%).
IR: 1715 cm–1 (C=O).
1H NMR (300 MHz, CDCl3): d = 7.90–7.30 (m, 7 H), 3.30 (t,
J = 7.5 Hz, 2 H), 2.79 (t, J = 7.5 Hz, 2 H), 2.07 (s, 3 H).
3-(9-Oxo-9H-fluoren-2-yl)butanal (23)
Following the general procedure, the reaction was carried out start-
ing from 2-bromofluorene (7; 245 mg, 1 mmol), crotyl alcohol (9;
79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1 (10
mg, 1 mol%). When the reaction was finished, the reaction crude
was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 23; yield: 176 mg (70%).
13C NMR (75 MHz, DEPT, CDCl3): d = 207.7, 136.9, 133.6, 131.5,
128.8, 127.8, 126.8, 125.9, 125.8, 125.4, 125.3, 44.2, 29.9, 26.6.
IR: 1708 (C=O), 1605 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 9.75 (t, J = 1.6 Hz, 1 H), 8.00–
7.20 (m, 7 H), 3.57 (sextet, J = 7.2 Hz, 1 H), 2.89 (ddd, J = 1.4, 6.8,
17.2 Hz, 1 H), 2.77 (ddd, J = 1.4, 7.4, 17.2 Hz, 1 H), 1.40 (d, J = 7.0
Hz, 3 H).
MS (EI): m/z (%) = 198 (100), 183 (38), 155 (90), 141 (66), 127
(70), 101 (50), 43 (33).
HRMS–FAB: m/z calcd for C14H14O: 198.1045; found: 198.1041.
13C NMR (50 MHz, DEPT, CDCl3): d = 200.8, 194.4, 144.6, 142.8,
138.1, 136.9, 135.3, 134.5, 133.8, 124.8, 124.4, 124.1, 123.9, 122.6,
50.9, 26.9, 21.3.
1-Phenyl-3-(3-pyridinyl)-1-propanone (32)
[CAS Reg. No. 39976-56-2]
A mixture of 3-bromopyridine (27; 158 mg, 1 mmol), 1-phenyl-
prop-2-en-1-ol (3; 147 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%) in DMF (3 mL) was reacted in an
Anton Paar Monowave 300 in a sealed reaction vessel at 200 °C and
27 bar for 20 min. Then, the mixture was cooled to r.t., diluted with
EtOAc (15 mL), washed with brine (3 × 10 mL), dried (Na2SO4)
and concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography (25 × 2.5 cm,
EtOAc–hexane gradient) to give 32; yield: 164 mg (78%).
1H NMR (200 MHz, CDCl3): d = 8.44 (s, 1 H), 8.35 (d, J = 3.6 Hz,
1 H), 7.86 (d, J = 7.0 Hz, 2 H), 7.60–7.10 (m, 5 H), 3.19 (t, J = 7.2
Hz, 2 H), 2.98 (t, J = 7.2 Hz, 2 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 198.1, 149.3, 146.9, 136.5,
136.2, 136.1, 133.0, 128.4, 127.7, 123.2, 39.3, 26.7.
MS (EI): m/z (%) = 250 (70), 235 (20), 221 (30), 207 (100), 178
(20).
HRMS–FAB: m/z calcd for C17H14O2: 250.0994; found: 250.0991.
2-(3-Oxopentyl)-9H-fluoren-9-one (24)
Following the general procedure, the reaction was carried out start-
ing from 2-bromofluorene (7; 245 mg, 1 mmol), 1-penten-3-ol (11;
95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1 (10
mg, 1 mol%). When the reaction was finished, the reaction crude
was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 24; yield: 224 mg (85%).
IR: 1708 (C=O), 1605 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 7.62 (d, J = 8.0 Hz, 1 H), 7.50–
7.20 (m, 6 H), 2.90 (t, J = 7.2 Hz, 2 H), 2.76 (t, J = 7.2 Hz, 2 H),
2.43 (q, J = 7.4 Hz, 2 H), 1.05 (t, J = 7.4 Hz, 3 H).
HRMS–FAB: m/z calcd for C14H13NO: 211.0997; found: 211.0991.
© Thieme Stuttgart · New York
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280
A. Sauza et al.
PAPER
(E)-2-Methyl-4-(3-pyridinyl)-3-buten-2-ol (33)
IR: 2725 (C–H), 1722 cm–1 (C=O).
[CAS Reg. No. 943897-36-7]
1H NMR (200 MHz, CDCl3): d = 9.73 (t, J = 1.4 Hz, 1 H), 8.81 (d,
J = 2.3 Hz, 1 H), 8.08 (d, J = 7.0 Hz, 1 H), 7.97 (d, J = 2.3 Hz, 1
H), 7.78 (d, J = 7.0 Hz, 1 H), 7.64 (t, J = 7.0 Hz, 1 H), 7.56 (t,
J = 7.0 Hz, 1 H), 3.57 (sextet, J = 7.2 Hz, 1 H), 2.89 (ddd, J = 1.4,
6.8, 17.2 Hz, 1 H), 2.77 (ddd, J = 1.4, 7.4, 17.2 Hz, 1 H), 1.40 (d,
J = 7.0 Hz, 3 H).
Following the general procedure, the reaction was carried out start-
ing from 3-bromopyridine (27; 158 mg, 1 mmol), 2-methyl-3-
buten-2-ol (10; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and
catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the re-
action crude was purified by flash column chromatography on silica
gel (EtOAc–hexane gradient) to give 33; yield: 143 mg (88%).
13C NMR (50 MHz, DEPT, CDCl3): d = 200.5, 150.5, 146.9, 137.9,
132.8, 128.9 (2C), 127.9, 127.4, 126.7, 51.2, 31.6, 21.8.
IR: 3356 cm–1 (OH).
1H NMR (400 MHz, CDCl3): d = 8.80 (s, 1 H), 8.64 (d, J = 5.6 Hz,
1 H), 7.72 (t, J = 5.6 Hz, 1 H), 7.26 (t, J = 5.6 Hz, 1 H), 6.59 (d,
J = 16.0 Hz, 1 H), 6.42 (d, J = 16.0 Hz, 1 H), 2.47 (s, 1 H, OH), 1.43
(s, 6 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 151.2, 147.7, 142.3, 134.7,
133.3, 124.5, 122.6, 70.9, 29.8.
MS (EI): m/z (%) = 199 (40), 184 (18), 156 (100), 128 (21).
HRMS–FAB: m/z calcd for C13H13NO: 199.0997; found: 199.0994.
(E)-2-Methyl-4-(3-quinolinyl)-3-buten-2-ol (37)
Following the general procedure, the reaction was carried out start-
ing from 3-bromoquinoline (29; 208 mg, 1 mmol), 2-methyl-3-
buten-2-ol (10; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and
catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the re-
action crude was purified by flash column chromatography on silica
gel (EtOAc–hexane gradient) to give 37; yield: 196 mg (92%).
MS (EI): m/z (%) = 163 (27), 148 (100), 121 (25), 105 (27).
HRMS–FAB: m/z calcd for C10H13NO: 163.0997; found: 163.0989.
3,5-Bis[(E)-3-hydroxy-3-methyl-1-butenyl]pyridine (34)
IR: 3380 cm–1 (OH).
Following the general procedure, the reaction was carried out start-
ing from 3,5-dibromopyridine (28; 237 mg, 1 mmol), 2-methyl-3-
buten-2-ol (10; 190 mg, 2.2 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the
reaction crude was purified by flash column chromatography on sil-
ica gel (EtOAc–hexane gradient) to give 34; yield: 207 mg (84%).
1H NMR (200 MHz, CDCl3): d = 8.64 (d, J = 3.2 Hz, 1 H), 8.04 (d,
J = 3.2 Hz, 1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.44 (m, 1 H), 7.42 (m,
1 H), 7.36 (t, J = 7.2 Hz, 1 H), 6.60 (d, J = 16.0 Hz, 1 H), 6.44 (d,
J = 16.0 Hz, 1 H), 3.75 (s, 1 H, OH), 1.33 (s, 6 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 150.9, 145.8, 140.3, 136.8,
129.4, 129.1, 128.6, 126.6 (2C), 122.6, 116.8, 70.3, 29.7.
IR: 3361 cm–1 (OH).
1H NMR (400 MHz, CDCl3): d = 8.56 (d, J = 2.1 Hz, 2 H), 7.98 (t,
J = 2.1 Hz, 1 H), 6.51 (d, J = 16.0 Hz, 2 H), 6.38 (d, J = 16.0 Hz, 2
H), 2.37 (s, 2 H, OH), 1.39 (s, 12 H).
MS (EI): m/z (%) = 213 (100), 128 (86), 101 (44), 75 (23), 28 (23).
HRMS–FAB: m/z calcd for C14H15NO: 213.1154; found: 213.1149.
13C NMR (100 MHz, DEPT, CDCl3): d = 149.0, 141.7, 135.3,
1-(4-Isoquinolinyl)-3-pentanone (38)
121.4, 120.8, 70.9, 29.8.
Following the general procedure, the reaction was carried out start-
ing from 4-bromoisoquinoline (30; 208 mg, 1 mmol), 1-penten-3-ol
(11; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1
(10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 38; yield: 185 mg (87%).
MS (EI): m/z (%) = 247 (25), 226 (100), 201 (47), 199 (37), 184
(30).
HRMS–FAB: m/z calcd for C15H21NO2: 247.1572; found:
247.1568.
IR: 1712 cm–1 (C=O).
4-(3-Quinolinyl)-2-butanone (35)
Following the general procedure, the reaction was carried out start-
ing from 3-bromoquinoline (29; 208 mg, 1 mmol), 3-buten-2-ol (12;
79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1 (10
mg, 1 mol%). When the reaction was finished, the reaction crude
was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 35; yield: 153 mg (77%).
1H NMR (200 MHz, CDCl3): d = 9.13 (s, 1 H), 8.38 (s, 1 H), 7.88
(d, J = 8.2 Hz, 2 H), 7.65 (ddd, J = 1.4, 8.2, 8.2 Hz, 1 H), 7.51 (ddd,
J = 1.0, 8.2, 8.2 Hz, 1 H), 3.32 (t, J = 8.0 Hz, 2 H), 2.86 (t, J = 8.0
Hz, 2 H), 2.37 (q, J = 7.2 Hz, 2 H), 1.07 (t, J = 7.2 Hz, 3 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 209.5, 151.0, 141.9, 133.9,
130.0, 129.9, 127.9, 127.8, 126.5, 122.1, 42.1, 35.6, 23.3, 7.3.
IR: 1715 cm–1 (C=O).
MS (EI): m/z (%) = 213 (100), 184 (22), 156 (97), 142 (84).
1H NMR (200 MHz, CDCl3): d = 8.70 (s, 1 H), 8.06 (s, 1 H), 7.88
(d, J = 8.0 Hz, 1 H), 7.57 (d, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.0 Hz,
1 H), 7.38 (t, J = 8.0 Hz, 1 H), 2.85 (t, J = 7.4 Hz, 2 H), 2.63 (t,
J = 7.4 Hz, 2 H), 1.95 (s, 3 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 206.6, 150.9, 146.3, 136.8,
129.4, 129.1, 127.3, 127.1, 126.9, 44.0, 29.7, 26.5.
HRMS–FAB: m/z calcd for C14H15NO: 213.1154; found: 213.1151.
4-(4-Isoquinolinyl)-2-butanone (39)
Following the general procedure, the reaction was carried out start-
ing from 4-bromoisoquinoline (30; 208 mg, 1 mmol), 3-buten-2-ol
(12; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1
(10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 39; yield: 167 mg (84%).
MS (EI): m/z (%) = 199 (38), 198 (92), 184 (13), 155 (76), 141
(100), 128 (33).
HRMS–FAB: m/z calcd for C13H13NO: 199.0997; found: 199.0985.
IR: 1713 cm–1 (C=O).
3-(3-Quinolinyl)butanal (36)
1H NMR (200 MHz, CDCl3): d = 9.10 (s, 1 H), 8.60 (s, 1 H), 8.04
(d, J = 8.0 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 7.70 (t, J = 8.0 Hz,
1 H), 7.60 (t, J = 8.0 Hz, 1 H), 3.27 (t, J = 7.2 Hz, 2 H), 2.85 (t,
J = 7.2 Hz, 2 H), 2.16 (s, 3 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 206.8, 151.3, 144.2, 134.1,
129.2, 127.8, 127.3, 125.3, 119.2, 43.4, 29.6, 23.2.
Following the general procedure, the reaction was carried out start-
ing from 3-bromoquinoline (29; 208 mg, 1 mmol), crotyl alcohol (9;
79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1 (10
mg, 1 mol%). When the reaction was finished, the reaction crude
was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 36; yield: 175 mg (88%).
Synthesis 2012, 44, 272–282
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Heck Reaction of Aryl Bromides with Allylic Alcohols
281
MS (EI): m/z (%) = 199 (100), 156 (92), 142 (65), 129 (22), 28 (42).
HRMS–FAB: m/z calcd for C13H13NO: 199.0997; found: 199.0993.
reaction crude was purified by flash column chromatography on sil-
ica gel (EtOAc–hexane gradient) to give 43; yield: 158 mg (88%).
1H NMR (200 MHz, CDCl3): d = 9.45 (d, J = 0.6 Hz, 1 H), 7.17 (dd,
J = 0.6, 3.6 Hz, 1 H), 6.64 (d, J = 16.0 Hz, 1 H), 6.45 (d, J = 16.0
Hz, 1 H), 6.34 (d, J = 3.6 Hz, 1 H), 2.84 (s, 1 H, OH), 1.34 (s, 6 H).
13C NMR (50 MHz, DEPT, CDCl3): d = 176.9, 158.3, 151.2, 143.1,
124.1, 113.8, 109.9, 70.7, 29.5.
3-(4-Isoquinolinyl)butanal (40)
Following the general procedure, the reaction was carried out start-
ing from 4-bromoisoquinoline (30; 208 mg, 1 mmol), crotyl alcohol
(9; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst 1
(10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 40; yield: 181 mg (91%).
HRMS–FAB: m/z calcd for C10H12O3: 180.0786; found: 180.0782.
5-(3-Oxopentyl)-2-furaldehyde (44)
[CAS Reg. No. 1262222-47-8]
IR: 1721 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 9.84 (t, J = 1.4 Hz, 1 H), 9.15 (s,
1 H), 8.44 (s, 1 H), 8.08 (d, J = 8.6 Hz, 1 H), 8.00 (dd, J = 8.4, 1.0
Hz, 1 H), 7.77 (ddd, J = 1.4, 6.8, 8.6 Hz, 1 H), 7.63 (ddd, J = 1.0,
7.0, 8.4 Hz, 1 H), 4.16 (sextet, J = 6.8 Hz, 1 H), 3.00 (ddd, J = 1.2,
5.6, 17.6 Hz, 1 H), 2.88 (ddd, J = 1.8, 8.2, 17.6 Hz, 1 H), 1.48 (d,
J = 6.8 Hz, 3 H).
Following the general procedure, the reaction was carried out start-
ing from 5-bromo-2-furaldehyde (31; 175 mg, 1 mmol), 1-penten-
3-ol (11; 95 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and cata-
lyst 1 (10 mg, 1 mol%). When the reaction was finished, the reac-
tion crude was purified by flash column chromatography on silica
gel (EtOAc–hexane gradient) to give 44; yield: 149 mg (83%).
13C NMR (50 MHz, DEPT, CDCl3): d = 200.8, 151.6, 140.0, 134.4,
133.7, 130.6, 128.6, 128.4, 126.9, 121.9, 50.9, 26.9, 21.3.
IR: 1713 (C=O), 1675 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 9.65 (s, 1 H), 7.33 (d, J = 3.6 Hz,
1 H), 6.43 (d, J = 3.6 Hz, 1 H), 3.16 (t, J = 6.8 Hz, 2 H), 3.02 (t,
J = 6.8 Hz, 2 H), 2.62 (q, J = 7.4 Hz, 2 H), 1.21 (t, J = 7.4 Hz, 3 H).
MS (EI): m/z (%) = 199 (26), 156 (100), 128 (21), 43 (18), 28 (21).
HRMS–FAB: m/z calcd for C13H13NO: 199.0997; found: 199.0992.
13C NMR (50 MHz, DEPT, CDCl3): d = 208.9, 176.7, 161.9, 151.7,
5-(3-Oxo-3-phenylpropyl)-2-furaldehyde (41)
123.6, 109.0, 39.2, 35.7, 22.2, 7.5.
Following the general procedure, the reaction was carried out start-
ing from 5-bromo-2-furaldehyde (31; 175 mg, 1 mmol), 1-phenyl-
2-propen-1-ol (3; 147 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol)
and catalyst 1 (10 mg, 1 mol%). When the reaction was finished, the
reaction crude was purified by flash column chromatography on sil-
ica gel (EtOAc–hexane gradient) to give 41; yield: 207 mg (91%).
1H NMR (400 MHz, CDCl3): d = 9.41 (s, 1 H), 7.87 (d, J = 7.5 Hz,
2 H), 7.60–7.20 (m, 3 H), 7.11 (d, J = 3.6 Hz, 1 H), 6.25 (d, J = 3.6
Hz, 1 H), 3.32 (t, J = 7.2 Hz, 2 H), 3.08 (t, J = 7.2 Hz, 2 H).
MS (EI): m/z (%) = 180 (14), 123 (100), 109 (30), 57 (23), 28 (24).
HRMS–FAB: m/z calcd for C10H12O3: 180.0786; found: 180.0779.
5-(3-Oxobutyl)-2-furaldehyde (45)
Following the general procedure, the reaction was carried out start-
ing from 5-bromo-2-furaldehyde (31; 175 mg, 1 mmol), 3-buten-2-
ol (12; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst
1 (10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 45; yield: 132 mg (80%).
1H NMR (300 MHz, CDCl3): d = 9.43 (s, 1 H), 7.12 (d, J = 3.6 Hz,
1 H), 6.21 (d, J = 3.6 Hz, 1 H), 2.93 (m, 2 H), 2.82 (m, 2 H), 2.11
(s, 3 H).
13C NMR (75 MHz, DEPT, CDCl3): d = 197.4, 176.7, 162.0, 151.6,
136.0, 132.9, 128.4, 127.7, 123.7, 109.1, 35.7, 22.4.
HRMS–FAB: m/z calcd for C14H12O3: 228.0786; found: 228.0781.
5-(1-Methyl-3-oxopropyl)-2-furaldehyde (42)
[CAS Reg. No. 1001388-45-9]
13C NMR (50 MHz, DEPT, CDCl3): d = 206.0, 176.7, 161.8, 151.6,
123.5, 109.0, 40.5, 29.6, 22.1.
Following the general procedure, the reaction was carried out start-
ing from 5-bromo-2-furaldehyde (31; 175 mg, 1 mmol), crotyl alco-
hol (9; 79 mg, 1.1 mmol), NaOAc (100 mg, 1.2 mmol) and catalyst
1 (10 mg, 1 mol%). When the reaction was finished, the reaction
crude was purified by flash column chromatography on silica gel
(EtOAc–hexane gradient) to give 42; yield: 148 mg (89%).
HRMS–FAB: m/z calcd for C9H10O3: 166.0630; found: 166.0628.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. It in-
cludes the 1H and 13C NMR spectra of all compounds prepared.
1H NMR (400 MHz, CDCl3): d = 9.78 (t, J = 1.6 Hz, 1 H), 9.54 (s,
1 H), 7.18 (d, J = 3.6 Hz, 1 H), 6.29 (d, J = 3.6 Hz, 1 H), 3.55 (sex-
tet, J = 6.8 Hz, 1 H), 2.96 (ddd, J = 1.6, 6.4, 17.6 Hz, 1 H), 2.72 Acknowledgment
(ddd, J = 1.6, 7.6, 17.6 Hz, 1 H), 1.37 (d, J = 7.2 Hz, 3 H).
Support for this research has been provided by the Programa de
13C NMR (100 MHz, DEPT, CDCl3): d = 199.8, 177.1, 167.3,
Apoyo a Proyectos de Investigación e Inovación Tecnológica (PA-
PIIT-UNAM, Project No. IN207602-3). We wish to thank Eréndira
García Ríos and Itzel Chacón for their technical assistance.
151.9, 123.2, 107.9, 48.5, 27.9, 18.6.
HRMS–FAB: m/z calcd for C9H10O3: 166.0630; found: 166.0629.
5-[(E)-3-Hydroxy-3-methyl-1-butenyl]-2-furaldehyde (43)
[CAS Reg. No. 117252-40-1]
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© Thieme Stuttgart · New York
Synthesis 2012, 44, 272–282

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A. Sauza et al.
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