Heck reaction of aryl bromides with pent-4-en-2-ol, 2-phenylpent-4-en-2-ol, or hept-6-en-3-ol catalysed by a palladium-tetraphosphine complex

Article abstract of DOI:10.1055/s-2005-918427

The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane in combination with [Pd(η³-C₃H ₅)Cl]₂ affords a very efficient catalyst for the Heck reaction of aryl bromides with pent-4-en

Full text of DOI:10.1055/s-2005-918427

PAPER
3589
Heck Reaction of Aryl Bromides with Pent-4-en-2-ol, 2-Phenylpent-4-en-2-ol,
or Hept-6-en-3-ol Catalysed by a Palladium–Tetraphosphine Complex
Heck
R
eaction
l
of
A
ry
o
l
Bromides
r
atalyse
d
by
a
Pa
lladium–T
n
etraphosphine Com
B
ple
x
erthiol, Henri Doucet,* Maurice Santelli*
UMR 6180 CNRS and Université d'Aix-Marseille III: ‘Chirotechnologies: catalyse et biocatalyse’, Laboratoire de Synthèse Organique, Fa-
culté des Sciences de Saint Jérôme, Université d'Aix-Marseille III, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20,
France
Fax +33(4)91983865; E-mail: henri.doucet@univ.u-3mrs.fr; E-mail: m.santelli@univ.u-3mrs.fr
Received 2 June 2005
quired and 2–45% catalyst had to be used. Moreover, sev-
Abstract: The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphe-
eral results were described with very reactive, but
nylphosphinomethyl)cyclopentane in combination with [Pd(h3-
expensive aryl iodides.8–10 We found only one example of
C3H5)Cl]2 affords a very efficient catalyst for the Heck reaction of
the formation of such products using triphenylphosphine
aryl bromides with pent-4-en-2-ol, 2-phenylpent-4-en-2-ol, or hept-
6-en-3-ol. With pent-4-en-2-ol or hept-6-en-3-ol, the selectivity in (Ph3P) ligands.17 In this paper, the reaction of pent-4-en-
favour of the formation of the 5-arylpentan-2-one or 7-arylheptan-
2-ol with 2-bromothiophene in the presence of 1%
3-one derivatives, respectively, depends on the substituents on the
Pd(OAc)2 and 3% Ph3P as catalyst gave the corresponding
aryl bromide and on the base. Sterically congested and electron-rich
ketone in 55% yield.17 However, to our knowledge, low-
aryl bromides gave selectively the linear ketones by migration of
catalyst loading Heck reactions using b- or g-alk-1-enol
the double bond. With electron-poor aryl bromides, the formation of
derivatives have not been reported.
large amounts of (E)-1-arylalk-1-enol derivatives or side products
was observed in some cases. Similar reactions rates were observed
with electron-poor and electron-rich aryl bromides. Several reac-
tions can be performed with as little as 0.01% catalyst. A wide va-
riety of substituents, such as methoxy, dimethylamino, fluoro,
trifluoromethyl, acetyl, benzoyl, formyl, carboxy, or cyano groups,
on the aryl bromides are tolerated. The coupling of very sterically
In order to obtain a highly stable palladium catalyst, we
have prepared the tetraphosphine ligand cis,cis,cis-
1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane
or Tedicyp18 (Figure 1). We have already reported the re-
sults obtained for allylic substitution,18 Suzuki cross cou-
congested aryl bromides, such as 9-bromoanthracene or 2-bromo- pling,19 and the Sonogashira reaction20 using Tedicyp as
1,3,5-triisopropylbenzene, also proceeds in good yields. Heck reac-
the ligand. We have also reported several results obtained
for the Heck reaction.21–31 In order to further establish the
tion with 2-phenylpent-4-en-2-ol gave the expected (E)-5-aryl-2-
phenylpent-4-en-2-ol derivatives in high turnover numbers (TONs)
requirements for a successful Heck reaction using our cat-
and high selectivities in most cases. However, with some electron-
alyst, we herein report the synthesis of g- or d-aryl-substi-
poor aryl bromides the selective formation of 1-arylprop-1-ene de-
rivatives resulting from a C–C bond cleavage was observed.
tuted ketones by the reaction of aryl bromides with pent-
4-en-2-ol or hept-6-en-3-ol, and also the synthesis of 5-
aryl-2-phenylpent-4-en-2-ol derivatives by using 2-phe-
nylpent-4-en-2-ol as reactant.
Key words: Heck reaction, aryl bromides, palladium catalysis, alk-
enols
Ph2P
PPh2
Ph2P
The palladium-catalysed so-called Heck reaction is one of
the most powerful methods for the formation of C–C
bonds.1–6 In recent years, several thermally stable palladi-
um catalysts have been successfully used in Heck reac-
tions, but most of these catalysts have not been tested for
use in the synthesis of enols or ketones by coupling aryl
halides with b- or g-alk-1-enol derivatives. The reaction
of aryl halides with b- or g-alk-1-enol derivatives can af-
ford the corresponding arylalkenols, or b- or g-aryl-sub-
stituted ketones by migration of the double bond, and is a
very powerful method for the preparation of such com-
pounds.7 Most of the results described for this reaction
were obtained using palladium(II) acetate [Pd(OAc)2] in
association with ammonium halides and in the absence of
ligand in most cases.8–16 As a catalyst, Pd(OAc)2 was not
very efficient in terms of the substrate/catalyst ratio re-
PPh2
Tedicyp
Figure 1
For this study, based on our previous results,21–31 N,N-
dimethylformamide (DMF) was chosen as the solvent and
potassium carbonate (K2CO3) as the base. The reactions
were performed at 130 °C, under argon, in the presence of
a 1:2 ratio of [Pd(h3-C3H5)Cl]2/Tedicyp as catalyst.
First, we studied the coupling of pent-4-en-2-ol with sev-
eral aryl bromide derivatives (Scheme 1, Table 1). The
para substituents on the aryl bromide have a minor influ-
ence on the selectivity for this reaction. We observed that
in most cases the formation of the linear ketones 1a–7a in
60–81% selectivity together with the linear and branched
nonisomerised alcohols 1b–7b and 1c–7c (Scheme 1,
Table 1, entries 1, 3, 6, 9, 11, 13 and 15). Similar reactions
rates were observed with electron-poor and electron-rich
aryl bromides. These results seem to indicate that the ox-
SYNTHESIS 2005, No. 20, pp 3589–3602
x
x.
x
x
.
2
0
0
5
Advanced online publication: 25.10.2005
DOI: 10.1055/s-2005-918427; Art ID: Z10705SS
© Georg Thieme Verlag Stuttgart · New York

3590
F. Berthiol et al.
PAPER
idative addition of aryl bromides to palladium is not the ketone 12a was selectively obtained, but the use of 0.1–
rate-determining step of this reaction. Turnover numbers 0.4% catalyst was necessary (Table 1, entries 26 and 27).
(TONs) of up to 19000 can be achieved with this catalyst
(Table 1, entry 16). In order to improve the selectivity of
these reactions we also studied the influence of bases. In
We have also investigated this reaction using four het-
eroaryl bromides. The expected linear ketones 13a–16a
were obtained in moderate yields in the presence of 0.1–
the presence of sodium hydrogen carbonate (NaHCO3),
1% catalyst with 2- or 3-bromothiophenes and 0.01–0.4%
higher selectivities in favour of the formation of isomers
catalyst with 3-bromopyridine and 3-bromoquinoline
(Table 1, entries 28–38). In all cases, significant amounts
of the linear alcohols 13b–16b were also obtained in the
reaction when K2CO3 was used as base. These results
1a–7a were generally observed (Table 1, entries 2, 4, 5, 7,
10, 12, 14 and 17). For example, 4-bromoacetophenone in
the presence of K2CO3 gave the isomer 1a in 77% selec-
tivity and with NaHCO3 a selectivity of 89% was obtained
seem to indicate that with these heteroaryl bromides, a
(Table 1, entries 1 and 2, respectively). However, with
possible interaction between the nitrogen or sulfur atom
electron-rich aryl bromides slower reactions were ob-
and the palladium complex affects the selectivity of the
reaction. With these substrates, better selectivity, but low-
served in the presence of this base.
er TONs were obtained using NaHCO3 as base.
O
We then studied the coupling reactions of a variety of aryl
bromides with 2-phenylpent-4-en-2-ol (Schemes 2 and 3,
Table 2). With this tertiary alcohol, the formation of an
1a–16a
HO
R
aryl ketone by migration of the double bond is not possi-
+
ble; therefore, the selectivity of the reaction should be in
favour of the formation of the (E)-5-aryl-2-phenylpent-4-
1b–16b
[Pd(C3H5)Cl]2
0.5 Tedicyp,
/
Br
R
R
en-2-ol derivatives 19a–26a. However, we observed that
in the presence of electron-poor aryl bromides, such as 4-
bromoacetophenone, 4-bromobenzophenone, or 3-bro-
moquinoline, the formation of such compounds was not
observed. In the reaction with these substrates, an aryl–al-
lyl elimination occurs and the arylpropene derivatives
17c, 17d, 18c, 27c, and 27d were obtained, together with
acetophenone (Scheme 2, Table 2, entries 1–4, 21, and
22). Even at a lower temperature (100 °C), or in the pres-
ence of NaHCO3 as base, the formation of these arylpro-
penes was observed, but the reactions were slower.
Similar allyl eliminations via the selective cleavage of C–
C bonds in homoallylic alcohols at elevated temperature32
or catalysed by ruthenium or rhodium complexes have al-
ready been described.33
+
+
R
+
DMF, K2CO3 or
NaHCO3, 130 °C
OH
OH
1c–16c
HO
R = Me, i-Pr, t-Bu, OMe, F, CF3,
MeCO, PhCO, CHO, CN
10d
Scheme 1
Then, we studied the influence of the presence of ortho
substituents on the aryl bromides on the selectivity and on
the reaction rate with K2CO3 and NaHCO3 as bases. We
observed that the coupling of 1-bromo-2-(trifluorometh-
yl)benzene or 2-bromotoluene with pent-4-en-2-ol pro-
ceeds in the presence of 0.01 and 0.1% catalyst with
K2CO3 (Table 1, entries 18, 20 and 21); the ketones 8a and
9a were obtained in 76–78% selectivity. The reactions
performed using NaHCO3 with these two substrates were
much slower (Table 1, entries 19 and 22).
O
Br
OH
R
[Pd(C3H5)Cl]2
0.5 Tedicyp,
/
R
17c, 18c, 27c
+
+
Ph
DMF, K2CO3, 130 °C
R = MeCO, PhCO
and 3-bromoquinoline
R
17d, 27d
Next, we tried to evaluate the difference in selectivity for
this reaction using mono- and di-ortho-substituted aryl
bromides with K2CO3, and we observed that even highly
hindered aryl bromides could be coupled efficiently with
pent-4-en-2-ol. For example, in the reaction with 2-bro-
mo-1,3,5-trimethylbenzene and 9-bromoanthracene in the
presence of 0.01 and 0.1% catalyst, the corresponding ke-
tones 10a and 11a were obtained in 4900 and 1000 TONs,
respectively (Table 1, entries 24 and 25). Because of ster-
ic reasons, in the reactions with these two di-ortho-substi-
tuted aryl bromides very high selectivities in favour of the
formation of the ketones were observed. This coupling re-
action also proceeds using highly sterically hindered 2-
bromo-1,3,5-triisopropylbenzene. With this substrate, the
Scheme 2
With electron-rich aryl bromides, and even with 1-bromo-
4-fluorobenzene, this C–C bond cleavage was not ob-
served, and the (E)-5-aryl-2-phenylpent-4-en-2-ol deriva-
tives 19a–26a were obtained in high selectivities
(Scheme 3, Table 2, entries 5–20). Bromobenzene and 1-
bromo-4-fluorobenzene gave mainly derivatives 19a and
20a, respectively, but 6–9% of the branched alcohols 19b
and 20b and approximately 10% of unidentified isomers
were also observed (Table 2, entries 5–8). 1-Bromo-4-
tert-butylbenzene, 4-bromoanisole, 2-bromo-6-methoxy-
naphthalene, and 1-bromo-4-(dimethylamino)benzene
also led to linear/branched alcohol mixtures in 91:9 to
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

PAPER
Heck Reaction of Aryl Bromides Catalysed by a Palladium–Tetraphosphine Complex
3591
Table 1 Palladium-Catalysed Coupling of Aryl Bromides with Pent-4-en-2-ola
Entry
Aryl bromide
Ratio (substrate/catalyst)
Product
Ratio (a/b/c)
Yieldb (%)
1
2
4-bromoacetophenone
4-bromoacetophenone
1000
1000
1a–c
1a and b
77:21:2
89:11:0
100
100 (77)c
3
4
5
4-bromobenzophenone
4-bromobenzophenone
4-bromobenzophenone
1000
1000
5000
2a–c
2a and b
2a–c
64:32:4
87:13:0
84:15:1
100
100 (80)c
49c
6
7
8
4-bromobenzaldehyde
4-bromobenzaldehyde
4-bromobenzaldehyde
1000
1000
10000
3a–c
3a–c
3a–c
62:35:3
74:25:1
57:41:2
100
100 (70)c
8c
9
10
4-bromobenzonitrile
4-bromobenzonitrile
1000
1000
4a–c
4a–c
60:35:5
84:15:1
100 (55)
72c
11
12
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
10000
5000
5a–c
5a–c
69:26:5
86:13:1
100
100 (81)c
13
14
1-bromo-4-tert-butylbenzene
1-bromo-4-tert-butylbenzene
25000
1000
6a–c
6a–c
81:18:1
85:14:1
100 (75)
80c
15
16
17
4-bromoanisole
4-bromoanisole
4-bromoanisole
10000
100000
1000
7a–c
7a–c
7a and b
69:26:5
65:32:3
88:12:0
100 (63)
19
69c
18
19
1-bromo-2-(trifluoromethyl)benzene
1-bromo-2-(trifluoromethyl)benzene
10000
1000
8a and b
8a–c
78:22:0
90:7:3
100 (73)
84c
20
21
22
2-bromotoluene
2-bromotoluene
2-bromotoluene
1000
10000
1000
9a–c
9a–c
9a and b
76:22:2
77:22:1
78:22:0
100
98 (72)
25c
23
24
2-bromo-1,3,5-trimethylbenzene
2-bromo-1,3,5-trimethylbenzene
1000
10000
10a, c, and d
10a, c, and d
81:0:2d
88:0:1e
100 (60)
49
25
9-bromoanthracene
1000
11a and c
99:0:1f
100 (81)
26
27
2-bromo-1,3,5-triisopropylbenzene
2-bromo-1,3,5-triisopropylbenzene
250
1000
12a
12a
100:0:0f
100:0:0f
100 (46)
50
28
29
30
3-bromopyridine
3-bromopyridine
3-bromopyridine
1000
250
1000
13a–c
13a and b
13a and b
61:32:7
89:11:0
83:17:0
100
100 (80)c
53c
31
32
33
3-bromoquinoline
3-bromoquinoline
3-bromoquinoline
1000
10000
1000
14a–c
14a–c
14a–c
56:37:7
57:36:7
87:12:1
100
69
100 (79)c
34
35
2-bromothiophene
2-bromothiophene
250
250
15a–c
15a–c
48:43:9
66:31:3
76
74 (42)c
36
37
38
3-bromothiophene
3-bromothiophene
3-bromothiophene
250
1000
100
16a–c
16a–c
16a–c
40:53:7
41:51:8
79:19:2
100 (36)
87
48c
a See Scheme 1; conditions: ratio of [Pd(h3-C3H5) Cl]2/Tedicyp 1:2, aryl bromide (1 mmol), pent-4-en-2-ol (2 mmol), K2CO3 (2 mmol), DMF,
argon, 130 °C, 20 h; GC and NMR spectroscopic yields of the product mixtures are given.
b Yields in parentheses are isolated yields of the ketone a.
c NaHCO3 (2 mmol) was used as base.
d The formation of alcohol 10d (17%) was also observed.
e The formation of alcohol 10d (11%) was also observed.
f Debromination product was also observed.
96:4 ratios (Table 2, entries 9–16). With these substrates, monaphthalene was also studied. In both cases, high se-
only traces of unidentified isomers were detected by GC lectivities in favour of the formation of linear alcohols 25a
and NMR spectroscopy. The reactivity of the two ortho- and 26a were observed (Table 2, entries 17–20).
substituted aryl bromides, 2-bromotoluene and 1-bro-
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

3592
F. Berthiol et al.
PAPER
OH
Ph
of the strong base sodium tert-butoxide in tetrahydrofu-
ran.34,35 They have also reported that in polar solvents,
such as DMF, little or no tetrahydrofuran compound was
obtained.
Br
OH
[Pd(C3H5)Cl]2
0.5 Tedicyp,
/
19a–26a
R
+
R
R
Ph DMF, K2CO3, 130 °C
+
With our catalyst and using standard conditions (DMF,
K2CO3, 130 °C), we observed the formation of mixtures
of isomers in most cases. Potassium carbonate appeared to
be strong enough to promote the formation of the tetrahy-
drofuran products d when electron-poor aryl bromides
were used, even in DMF (Table 3, entries 1, 3, 6, 8, 11,
and 16). On the other hand, in the presence of electron-
rich aryl bromides, such as 1-bromo-4-tert-butylbenzene,
4-bromoanisole, 2-bromotoluene, 1-bromonaphthalene,
2-bromo-1,3,5-trimethylbenzene, or 2-bromo-1,3,5-tri-
isopropylbenzene, the formation of the corresponding tet-
rahydrofuran derivatives was not observed, and the aryl-
substituted ketones 33a, 34a, 36a–39a were obtained in
high selectivities (80–100%) and good yields (Table 3,
entries 13–15 and 18–23). With 1-bromo-4-tert-butylben-
zene and 4-bromoanisole, the formation of the aryl alco-
hols 33b and c and 34b and c, respectively, in low yields
was also observed. Because of steric reasons, such aryl al-
cohols were observed in very low yields or were not de-
OH
R = H, Me, t-Bu, OMe, F, NMe2
and 1-bromonaphthalene
19b–26b
Ph
Scheme 3
Finally, we studied the reactivity of hept-6-en-3-ol to-
wards several aryl bromides (Scheme 4, Table 3). Few re-
sults have been described with such g-alk-1-enols.16,34,35
The corresponding linear aryl-substituted ketone was ob-
tained in 85% selectivity by Larock et al. using iodoben-
zene in the presence of a mixture of lithium acetate,
lithium chloride, and tetrabutylammonium chloride with
3% Pd(OAc)2 as catalyst. The formation of 15% of a
branched alcohol, such as c (Scheme 4), was also ob-
served. Wolfe et al. recently described the selective direct
synthesis of tetrahydrofuran derivatives, such as d
(Scheme 4), by intramolecular cyclisation in the presence
Table 2 Palladium-Catalysed Coupling of Aryl Bromides with 2-Phenylpent-4-en-2-ola
Entry
Aryl bromide
Ratio (substrate/catalyst)
Product
Ratio (a/b/c/d) Yieldb (%)
1
2
4-bromoacetophenone
4-bromoacetophenone
250
1000
17c
17c and d
0:0:100:0
0:0:85:15
100 (81)
44
3
4
4-bromobenzophenone
4-bromobenzophenone
250
1000
18c
18c
0:0:100:0
0:0:100:0
100 (78)
70
5
6
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
10000
25000
19a and b
19a and b
93:7:0:0c
93:7:0:0c
100 (71)
96
7
8
bromobenzene
bromobenzene
1000
10000
20a and b
20a and b
94:6:0:0c
91:9:0:0c
100 (70)
82
9
10
1-bromo-4-tert-butylbenzene
1-bromo-4-tert-butylbenzene
10000
25000
21a and b
21a and b
93:7:0:0d
94:6:0:0d
100 (84)
67
11
12
4-bromoanisole
4-bromoanisole
10000
25000
22a and b
22a and b
92:8:0:0d
92:8:0:0d
100 (84)
96
13
14
2-bromo-6-methoxynaphthalene
2-bromo-6-methoxynaphthalene
1000
5000
23a and b
23a and b
95:5:0:0d
96:4:0:0d
100 (82)
44
15
16
1-bromo-4-(dimethylamino)benzene
1-bromo-4-(dimethylamino)benzene
100
250
24a and b
24a and b
91:9:0:0d
91:9:0:0d
100 (86)
70
17
18
2-bromotoluene
2-bromotoluene
1000
10000
25a and b
25a and b
95:5:0:0
96:4:0:0
100 (73)
66
19
20
1-bromonaphthalene
1-bromonaphthalene
1000
10000
26a and b
26a and b
96:4:0:0c
96:4:0:0c
100 (70)
27
21
22
3-bromoquinoline
3-bromoquinoline
250
1000
27c and d
27c and d
0:0:65:35
0:0:52:48
100 (56)
50
a See Schemes 2 and 3; conditions: ratio of [Pd(h3-C3H5)Cl]2/Tedicyp 1:2, aryl bromide (1 mmol), 2-phenylpent-4-en-2-ol (2 mmol), K2CO3
(2 mmol), DMF, argon, 130 °C, 20 h; GC and NMR spectroscopic yields of the product mixtures are given.
b Yields in parentheses are isolated yields of products a or c.
c The formation of other isomers was also observed by GC and NMR spectroscopy.
d Traces of other isomers were also detected by GC and NMR spectroscopy.
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

PAPER
Heck Reaction of Aryl Bromides Catalysed by a Palladium–Tetraphosphine Complex
3593
tected at all in the reactions performed with ortho- and K2CO3 or NaHCO3 as bases, selectivities of 30 and
substituted aryl bromides.
90% towards the formation of ketone 30a were obtained,
respectively (Table 3, entries 6 and 7).
In order to reduce the amount of tetrahydrofuran deriva-
tive obtained in the reactions of the electron-poor aryl bro- Finally, we studied the reaction with heteroaryl bromides.
mides, we performed a few reactions using other bases. 3-Bromopyridine and 3-bromoquinoline gave the ketones
We observed that in the presence of NaHCO3, much high- 40a and 41a, respectively, in high selectivities using
er selectivities (up to 100%) in favour of the formation of NaHCO3 as base (Table 3, entries 25 and 27); however, 2-
ketones a were observed (Table 3, entries 2, 4, 5, 7, 9, 10, and 3-bromothiophene gave mixtures of isomers (Table 3,
12, and 17). For example, with methyl 4-bromobenzoate entries 28–32).
Table 3 Palladium-Catalysed Coupling of Aryl Bromides with Hept-6-en-3-ola
Entry
Aryl bromide
Ratio (substrate/catalyst)
Product
Ratio (a/b/c/d) Yieldb (%)
1
2
4-bromoacetophenone
4-bromoacetophenone
1000
1000
28a–d
28a and b
67:14:3:16
93:7:0:0
100
100 (83)c
3
4
5
4-bromobenzophenone
4-bromobenzophenone
4-bromobenzophenone
1000
1000
10000
29a–d
29a–c
29a–d
52:12:4:32
89:10:1:0
78:18:1:3
100
100 (81)c
34c
6
7
methyl 4-bromobenzoate
methyl 4-bromobenzoate
25000
1000
30a–d
30a–c
30:25:7:38
90:9:1:0
100
100 (80)c
8
9
10
1-bromo-4-(trifluoromethyl)benzene
1-bromo-4-(trifluoromethyl)benzene
1-bromo-4-(trifluoromethyl)benzene
1000
1000
10000
31a–d
31a and b
31a and b
69:14:3:14
94:6:0:0
94:6:0:0
100
100 (82)c
21c
11
12
1-bromo-4-fluorobenzene
1-bromo-4-fluorobenzene
10000
1000
32a–d
32a–c
77:12:7:4
91:8:1:0
100
80 (71)c
13
1-bromo-4-tert-butylbenzene
10000
33a–c
83:14:3:0
100 (75)
14
15
4-bromoanisole
4-bromoanisole
100
25000
34a–c
34a–c
80:15:5:0
80:15:5:0
100
100 (74)
16
17
1-bromo-2-(trifluoromethyl)benzene
1-bromo-2-(trifluoromethyl)benzene
5000
1000
35a, b, and d
35a
72:7:0:21
100:0:0:0
100
81 (74)c
18
2-bromotoluene
10000
36a and b
91:9:0:0
100 (80)
19
20
1-bromonaphthalene
1-bromonaphthalene
1000
10000
37a and b
37a and b
97:3:0:0
97:3:0:0
100 (83)
97
21
22
2-bromo-1,3,5-trimethylbenzene
2-bromo-1,3,5-trimethylbenzene
1000
10000
38a and e
38a and e
86:0:0:0d
86:0:0:0d
100 (77)
68
23
2-bromo-1,3,5-triisopropylbenzene
100
39a
100:0:0:0e
100 (69)
24
25
3-bromopyridine
3-bromopyridine
1000
1000
40a–d
40a–c
56:18:4:22
91:8:1:0
100
100 (83)c
26
27
3-bromoquinoline
3-bromoquinoline
1000
1000
41a–d
41a–d
50:21:6:23
89:8:2:1
100
100 (80)c
28
29
30
2-bromothiophene
2-bromothiophene
2-bromothiophene
250
1000
250
42a–d
42a–d
42a–c
46:29:8:17
49:17:2:32
44:52:4:0
100 (41)
92
100c
31
32
3-bromothiophene
3-bromothiophene
500
1000
43a–c
43a–c
65:28:7:0
55:33:12:0
100 (56)
75
a See Scheme 4; conditions: ratio of [Pd(h3-C3H5)Cl]2/Tedicyp 1:2, aryl halide (1 mmol), hept-6-en-3-ol (2 mmol), K2CO3 (2 mmol), DMF,
argon, 130 °C, 20 h; GC and NMR spectroscopic yields of the product mixtures are given; tetrahydrofuran derivatives d are mixtures of dia-
stereomers.
b Yields in parentheses are isolated yields.
c NaHCO3 (2 mmol) was used as base.
d The formation of alcohol 38e (14%) was also observed.
e Debromination product was also observed.
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

3594
F. Berthiol et al.
PAPER
tion conditions. As expected, both the steric hindrance and
the electronic properties of the aryl bromides have an ef-
fect on the reaction rate. The presence of ortho substitu-
ents generally led to lower TONs than those reactions
performed with para-substituted aryl bromides. Di-ortho-
substituted aryl bromides also gave the coupling products,
but lower TONs were observed with the very sterically
congested 1-bromo-1,3,5-triisopropylbenzene. We be-
lieve that this catalytic system compares favourably with
the other catalysts that have been reported for this process.
Due to the high price of palladium, the practical advantage
of such low catalyst loading reactions could become in-
creasingly important for industrial processes.
O
28a–43a
R
+
+
+
OH
28b–43b
R
R
Br
[Pd(C3H5)Cl]2
0.5 Tedicyp,
/
28c–43c
28d–43d
R
+
DMF, K2CO3 or
NaHCO3, 130 °C
HO
O
OH
R = Me, t-Bu, i-Pr, OMe, F, CF3,
MeCO, PhCO, CO2Me
Analytical grade DMF (99.8%) was not distilled before use. 99%
Potassium carbonate and 99% NaHCO3 were used. All reactions
were run under argon using vacuum lines in Schlenk tubes and in
oven-dried glassware. The reactions were followed by GC and
NMR spectroscopy for high boiling point substrates and by GC for
low boiling point substrates. 1H (300 MHz) and 13C (75 MHz) NMR
spectra were recorded in CDCl3 solution with a Bruker spectrome-
ter. Chemical shifts (d) are reported in ppm relative to CDCl3. GC/
MS were recorded with a Varian Saturn 2100T spectrometer. Flash
chromatography was performed on silica gel (230–400 mesh).
R
+
OH
38e
Scheme 4
The use of the tetradentate ligand Tedicyp associated to a
palladium complex provides a convenient catalyst for the
reaction of pent-4-en-2-ol, 2-phenylpent-4-en-2-ol, or
hept-6-en-3-ol with substituted aryl bromides. In general,
the formation of mixtures of isomers was observed. The
reactions of pent-4-en-2-ol and hept-6-en-3-ol with aryl
bromides allowed for the synthesis of a variety of 5-aryl-
pentan-2-one and 7-arylhept-3-one derivatives by migra-
tion of the double bond, but the (E)-4-aryl- and 5-
arylpent-4-en-2-ol and (E)-6-aryl- and 7-arylhept-6-en-3-
ol derivatives, respectively, were also observed. The se-
lectivities of the reactions depend on the substituents of
the aryl bromide and on the base. Higher selectivities in
favour of the formation of the ketones were observed in
several cases in the presence of NaHCO3 as base instead
of K2CO3; however, with this base, slower reactions were
observed in some cases. With sterically congested or elec-
tron-rich aryl bromides, high selectivities in favour of the
formation of the ketones were obtained. With hept-6-en-
3-ol, the formation of furan derivatives as side products by
intramolecular cyclisation was also observed in the pres-
Preparation of the Palladium–Tedicyp Catalyst18
An oven-dried, 40-mL Schlenk tube equipped with a magnetic stir-
ring bar and under an argon atmosphere was charged with [Pd(h3-
C3H5)Cl]2 (4.2 mg, 11.6 mmol) and Tedicyp (20 mg, 23.2 mmol).
Then, anhyd DMF (2.5 mL) was added, and the solution was stirred
at r.t. for 10 min. The catalyst solution was used without purifica-
tion.
Heck Reaction of Aryl Bromides with Alkenols Using the Palla-
dium–Tedicyp Catalyst; General Procedure
A mixture of the aryl halide (1 mmol), alkenol (2 mmol), and K2CO3
(0.276 g, 2 mmol) or NaHCO3 (0.168 g, 2 mmol) in dry DMF (3
mL) and in the presence of [Pd(h3-C3H5)Cl]2/Tedicyp (1:2) was re-
acted for a period of 20 h under argon at 130 °C (see Tables 1– 3 for
the base and amounts of catalyst used). The corresponding products
were obtained after addition of H2O (20 mL), extraction with
CH2Cl2 (20 mL), separation, drying (MgSO4), evaporation, and pu-
rification by chromatography (silica gel, pentane–Et2O).
5-(4-Acetylphenyl)pentan-2-one (1a) (Table 1, Entry 2)
The reaction of 4-bromoacetophenone (0.199 g, 1 mmol), pent-4-
en-2-ol (0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded
1a.
ence of K2CO3 with electron-poor aryl bromides, but the Yield: 0.157 g (77%).
1H NMR (300 MHz, CDCl3): d = 7.82 (d, J = 8.1 Hz, 2 H), 7.20 (d,
J = 8.1 Hz, 2 H), 2.61 (t, J = 7.6 Hz, 2 H), 2.51 (s, 3 H), 2.38 (t, J =
7.2 Hz, 2 H), 2.05 (s, 3 H), 1.85 (quin, J = 7.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 208.3, 197.7, 147.4, 135.1, 128.6,
128.5, 42.5, 34.9, 29.9, 26.1, 24.7.
use of NaHCO3 as base suppressed this side reaction.
Electron-poor and electron-rich aryl bromides can be re-
acted using similar substrate/catalyst ratios indicating that
the oxidative addition of the aryl bromide is not the rate-
determining step for the reaction with this catalyst. 2-Phe-
nylpent-4-en-2-ol gave 5-aryl-2-phenylpent-4-en-2-ol de-
rivatives in high selectivities. However, with electron-
poor aryl bromides, C–C bond cleavage led to (E)-1-aryl-
and 3-arylprop-1-ene derivatives. The complex seems to
possess a fine balance of steric and electronic properties
that generally allow fast catalytic processes. For many
substrates, the reactions can be performed with as little as
0.01% catalyst without further optimisation of the reac-
MS (EI, 70 eV): m/z (%) = 204 (64) [M+].
Anal. Calcd for C13H16O2: C, 76.44; H, 7.90. Found: C, 76.18; H,
8.00.
Before purification 1b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.49 (d, J = 15.8 Hz, 1 H), 6.36
(dt, J = 15.8, 6.8 Hz, 1 H).
Alcohol 1c was also observed in the reaction described in Table 1,
entry 1.
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

PAPER
Heck Reaction of Aryl Bromides Catalysed by a Palladium–Tetraphosphine Complex
3595
1H NMR (300 MHz, CDCl3): d = 5.47 (s, 1 H), 5.25 (s, 1 H).
5-(4-Fluorophenyl)pentan-2-one (5a)36 (Table 1, Entry 12)
The reaction of 1-bromo-4-fluorobenzene (0.175 g, 1 mmol), pent-
4-en-2-ol (0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) af-
forded 5a.
5-(4-Benzoylphenyl)pentan-2-one (2a) (Table 1, Entry 4)
The reaction of 4-bromobenzophenone (0.261 g, 1 mmol), pent-4-
en-2-ol (0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded
2a.
Yield: 0.146 g (81%).
1H NMR (300 MHz, CDCl3): d = 7.10 (dd, J = 8.7, 5.5 Hz, 2 H),
6.94 (t, J = 8.7 Hz, 2 H), 2.57 (t, J = 7.5 Hz, 2 H), 2.41 (t, J = 7.4
Hz, 2 H), 2.10 (s, 3 H), 1.88 (quin, J = 7.2 Hz, 2 H).
Yield: 0.213 g (80%).
1H NMR (300 MHz, CDCl3): d = 7.76 (d, J = 6.8 Hz, 2 H), 7.72 (d,
J = 8.2 Hz, 2 H), 7.55 (t, J = 7.4 Hz, 1 H), 7.44 (dt, J = 6.8, 7.4 Hz,
2 H), 7.26 (d, J = 8.2 Hz, 2 H), 2.68 (t, J = 7.5 Hz, 2 H), 2.44 (t, J =
7.3 Hz, 2 H), 2.10 (s, 3 H), 1.92 (quin, J = 7.4 Hz, 2 H).
MS (EI, 70 eV): m/z (%) = 180 (16) [M+].
Before purification 5b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.43 (d, J = 15.8 Hz, 1 H), 6.13
(dt, J = 15.8, 7.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 208.3, 196.4, 146.9, 137.9, 135.5,
132.3, 130.4, 130.0, 128.4, 128.3, 42.7, 35.1, 30.0, 24.9.
MS (EI, 70 eV): m/z (%) = 266 (99) [M+].
Alcohol 5c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.34 (s, 1 H), 5.14 (s, 1 H).
Anal. Calcd for C18H18O2: C, 81.17; H, 6.81. Found: C, 81.41; H,
6.71.
5-(4-tert-Butylphenyl)pentan-2-one (6a) (Table 1, Entry 13)
The reaction of 1-bromo-4-tert-butylbenzene (0.213 g, 1 mmol),
pent-4-en-2-ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) af-
forded 6a.
Before purification 2b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.53 (d, J = 16.1 Hz, 1 H), 6.38
(dt, J = 16.1, 6.7 Hz, 1 H).
Alcohol 2c was also observed in the reactions described in Table 1,
Yield: 0.164 g (75%).
entries 3 and 5.
1H NMR (300 MHz, CDCl3): d = 7.32 (d, J = 8.3 Hz, 2 H), 7.11 (d,
J = 8.3 Hz, 2 H), 2.60 (t, J = 7.6 Hz, 2 H), 2.45 (t, J = 7.4 Hz, 2 H),
2.12 (s, 3 H), 1.91 (quin, J = 7.4 Hz, 2 H), 1.32 (s, 9 H).
1H NMR (300 MHz, CDCl3): d = 5.48 (d, J = 1.1 Hz, 1 H), 5.27 (d,
J = 1.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 208.7, 148.7, 138.4, 128.1, 125.2,
4-(4-Oxopentyl)benzaldehyde (3a) (Table 1, Entry 7)
The reaction of 4-bromobenzaldehyde (0.185 g, 1 mmol), pent-4-
en-2-ol (0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded
3a.
42.9, 34.5, 34.3, 31.4, 29.8, 25.2.
MS (EI, 70 eV): m/z (%) = 218 (6) [M+].
Anal. Calcd for C15H22O: C, 82.52; H, 10.16. Found: C, 82.34; H,
9.99.
Yield: 0.133 g (70%).
1H NMR (300 MHz, CDCl3): d = 9.96 (s, 1 H), 7.79 (d, J = 8.3 Hz,
2 H), 7.32 (d, J = 8.1 Hz, 2 H), 2.69 (t, J = 7.3 Hz, 2 H), 2.44 (t, J =
7.3 Hz, 2 H), 2.11 (s, 3 H), 1.91 (quin, J = 7.3 Hz, 2 H).
Before purification 6b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.47 (d, J = 15.9 Hz, 1 H), 6.16
(dt, J = 15.9 and 7.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 208.2, 191.9, 149.1, 134.6, 130.0,
Alcohol 6c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.41 (d, J = 1.2 Hz, 1 H), 5.13 (d,
J = 1.2 Hz, 1 H).
129.1, 42.6, 35.2, 30.0, 24.7.
MS (EI, 70 eV): m/z (%) = 190 (73) [M+].
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.54; H,
7.57.
5-(4-Methoxyphenyl)pentan-2-one (7a)37 (Table 1, Entry 15)
The reaction of 4-bromoanisole (0.187 g, 1 mmol), pent-4-en-2-ol
(0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 7a.
Before purification 3b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.54 (d, J = 15.9 Hz, 1 H), 6.41
(dt, J = 16.0, 6.4 Hz, 1 H).
Yield: 0.121 g (63%).
1H NMR (300 MHz, CDCl3): d = 7.06 (d, J = 8.7 Hz, 2 H), 6.81 (d,
J = 8.7 Hz, 2 H), 3.76 (s, 3 H), 2.54 (t, J = 7.5 Hz, 2 H), 2.40 (t, J =
7.5 Hz, 2 H), 2.08 (s, 3 H), 1.85 (quin, J = 7.2 Hz, 2 H).
Alcohol 3c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.51 (s, 1 H), 5.31 (s, 1 H).
MS (EI, 70 eV): m/z (%) = 192 (8) [M+].
4-(4-Oxopentyl)benzonitrile (4a)15 (Table 1, Entry 9)
The reaction of 4-bromobenzonitrile (0.182 g, 1 mmol), pent-4-en-
2-ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 4a.
Before purification 7b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.43 (d, J = 16.0 Hz, 1 H).
Yield: 0.103 g (55%).
Alcohol 7c was also observed.
1H NMR (300 MHz, CDCl3): d = 7.54 (d, J = 8.4 Hz, 2 H), 7.25 (d,
J = 8.4 Hz, 2 H), 2.65 (t, J = 7.7 Hz, 2 H), 2.43 (t, J = 7.2 Hz, 2 H),
2.10 (s, 3 H), 1.90 (quin, J = 7.5 Hz, 2 H).
1H NMR (300 MHz, CDCl3): d = 5.33 (s, 1 H), 5.07 (s, 1 H).
5-[2-(Trifluoromethyl)phenyl]pentan-2-one (8a) (Table 1,
Entry 18)
The reaction of 1-bromo-2-(trifluoromethyl)benzene (0.225 g, 1
mmol), pent-4-en-2-ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2
mmol) afforded 8a.
MS (EI, 70 eV): m/z (%) = 187 (21) [M+].
Before purification 4b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.49 (d, J = 15.9 Hz, 1 H), 6.37
(dt, J = 15.9, 6.4 Hz, 1 H).
Yield: 0.168 g (73%).
Alcohol 4c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.47 (s, 1 H), 5.30 (s, 1 H).
1H NMR (300 MHz, CDCl3): d = 7.60 (d, J = 8.1 Hz, 1 H), 7.47 (t,
J = 7.2 Hz, 1 H), 7.38–7.25 (m, 2 H), 2.77 (t, J = 7.5 Hz, 2 H), 2.49
(t, J = 7.5 Hz, 2 H), 2.13 (s, 3 H), 1.88 (quin, J = 7.5 Hz, 2 H).
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

3596
F. Berthiol et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 208.3, 140.5, 131.7, 130.9, 128.4
1H NMR (300 MHz, CDCl3): d = 8.34 (s, 1 H), 8.32 (d, J = 9.3 Hz,
2 H), 8.00 (d, J = 8.3 Hz, 2 H), 7.57–7.42 (m, 4 H), 3.62 (t, J = 6.8
Hz, 2 H), 2.59 (t, J = 6.8 Hz, 2 H), 2.13 (s, 3 H), 2.13 (quin, J = 6.8
Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 208.6, 134.1, 131.5, 129.7, 129.1,
125.8, 125.5, 124.8, 124.3, 43.1, 30.0, 26.9, 24.8.
2
3
(q, JC–F = 29.8 Hz), 126.0, 125.8 (q, JC–F = 5.7 Hz), 124.6 (q,
JC–F = 273.8 Hz), 43.0, 31.6, 29.8, 25.3.
MS (EI, 70 eV): m/z (%) = 230 (1) [M+].
Anal. Calcd for C12H13F3O: C, 62.60; H, 5.69. Found: C, 62.47; H,
5.84.
MS (EI, 70 eV): m/z (%) = 262 (100) [M+].
Before purification 8b was also observed.
Anal. Calcd for C19H18O: C, 86.99; H, 6.92. Found: C, 87.12; H,
6.78.
1H NMR (300 MHz, CDCl3): d = 6.84 (d, J = 16.1 Hz, 1 H), 6.22
(dt, J = 16.1, 7.6 Hz, 1 H).
Before purification 11c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.88 (s, 1 H), 5.33 (s, 1 H).
5-(2-Tolyl)pentan-2-one (9a)38 (Table 1, Entry 21)
The reaction of 2-bromotoluene (0.171 g, 1 mmol), pent-4-en-2-ol
(0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 9a.
5-(2,4,6-Triisopropylphenyl)pentan-2-one (12a) (Table 1, Entry
26)
Yield: 0.127 g (72%).
The reaction of 2-bromo-1,3,5-triisopropylbenzene (0.283 g, 1
mmol), pent-4-en-2-ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2
mmol) afforded 12a.
1H NMR (300 MHz, CDCl3): d = 7.20–7.05 (m, 4 H), 2.61 (t, J =
7.6 Hz, 2 H), 2.48 (t, J = 7.2 Hz, 2 H), 2.31 (s, 3 H), 2.13 (s, 3 H),
1.90 (quin, J = 7.5 Hz, 2 H).
Yield: 0.133 g (46%).
13C NMR (75 MHz, CDCl3): d = 208.6, 139.8, 135.9, 130.2, 128.9,
126.1, 125.9, 43.1, 32.4, 29.9, 24.0, 19.2.
1H NMR (300 MHz, CDCl3): d = 6.99 (s, 2 H), 3.20 (sept, J = 7.0
Hz, 2 H), 2.87 (sept, J = 7.0 Hz, 1 H), 2.70–2.52 (m, 4 H), 2.15 (s,
3 H), 1.86–1.65 (m, 2 H), 1.25 (d, J = 7.0 Hz, 18 H).
13C NMR (75 MHz, CDCl3): d = 208.5, 146.5, 146.3, 132.8, 120.9,
43.8, 34.1, 29.8, 29.1, 27.2, 25.9, 24.5, 24.0.
MS (EI, 70 eV): m/z (%) = 176 (1) [M+].
Before purification 9b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.68 (d, J = 15.6 Hz, 1 H), 6.09
(dt, J = 15.6, 7.6 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 288 (30) [M+].
Alcohol 9c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.29 (d, J = 2.1 Hz, 1 H), 5.00 (d,
J = 2.1 Hz, 1 H).
Anal. Calcd for C20H32O: C, 83.27; H, 11.18. Found: C, 83.41; H,
11.29.
5-Pyridin-3-ylpentan-2-one (13a)40 (Table 1, Entry 29)
The reaction of 3-bromopyridine (0.158 g, 1 mmol), pent-4-en-2-ol
(0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded 13a.
5-Mesitylpentan-2-one (10a)39 (Table 1, Entry 23)
The reaction of 2-bromo-1,3,5-trimethylbenzene (0.199 g, 1 mmol),
pent-4-en-2-ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) af-
forded 10a.
Yield: 0.131 g (80%).
1H NMR (300 MHz, CDCl3): d = 8.35–8.45 (m, 2 H), 7.45 (d, J =
7.8 Hz, 1 H), 7.16 (dd, J = 7.8, 4.9 Hz, 1 H), 2.56 (t, J = 7.7 Hz, 2
H), 2.40 (t, J = 7.3 Hz, 2 H), 2.07 (s, 3 H), 1.84 (quin, J = 7.5 Hz, 2
H).
13C NMR (75 MHz, CDCl3): d = 208.1, 149.8, 147.4, 136.7, 135.7,
123.3, 42.4, 32.0, 29.9, 24.7.
Yield: 0.123 g (60%).
1H NMR (300 MHz, CDCl3): d = 6.83 (s, 2 H), 2.57 (t, J = 8.3 Hz,
2 H), 2.53 (t, J = 7.3 Hz, 2 H), 2.29 (s, 6 H), 2.24 (s, 3 H), 2.15 (s, 3
H), 1.73 (quin, J = 7.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 208.8, 136.1, 135.6, 135.2, 129.0,
43.8, 30.1, 28.9, 23.4, 20.9, 19.8.
MS (EI, 70 eV): m/z (%) = 163 (8) [M+].
MS (EI, 70 eV): m/z (%) = 204 (6) [M+].
(E)-5-Pyridin-3-ylpent-4-en-2-ol (13b) has also been isolated in
pure form. Yield: 0.011 g (7%).
Before purification 10c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.37 (d, J = 1.8 Hz, 1 H), 4.96 (d,
J = 1.8 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 8.53 (d, J = 1.9 Hz, 1 H), 8.40 (dd,
J = 4.8, 1.2 Hz, 1 H), 7.67 (dt, J = 7.9, 1.9 Hz, 1 H), 7.23 (dd, J =
7.9, 4.8 Hz, 1 H), 6.43 (d, J = 16.0 Hz, 1 H), 6.31 (dt, J = 16.0, 6.8
Hz, 1 H), 3.94 (sept, J = 6.2 Hz, 1 H), 2.50–2.30 (m, 2 H), 1.24 (d,
J = 6.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 147.4, 147.3, 133.2, 133.1, 129.5,
128.9, 123.6, 67.2, 42.8, 23.0.
(E)-5-Mesitylpent-3-en-2-ol (10d) has also been isolated in pure
form.
Yield: 0.026 g (13%).
1H NMR (300 MHz, CDCl3): d = 6.84 (s, 2 H), 5.68 (dtd, J = 15.4,
5.8, 0.9 Hz, 1 H), 5.40 (ddt, J = 15.4, 6.3, 1.5 Hz, 1 H), 4.24 (quin,
J = 6.5 Hz, 1 H), 3.33 (d, J = 5.7 Hz, 2 H), 2.35 (s, 9 H), 1.21 (d,
J = 6.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 136.4, 135.5, 134.6, 133.2, 128.9,
127.6, 68.8, 31.8, 23.3, 20.8, 19.8.
MS (EI, 70 eV): m/z (%) = 163 (7) [M+].
Anal. Calcd for C10H13NO: C, 73.59; H, 8.03. Found: C, 73.41; H,
7.87.
Compound 13c was also observed in the reaction described in Table
1, entry 28.
MS (EI, 70 eV): m/z (%) = 204 (30) [M+].
1H NMR (300 MHz, CDCl3): d = 5.41 (s, 1 H), 5.24 (s, 1 H).
Anal. Calcd for C14H20O: C, 82.30; H, 9.87. Found: C, 82.14; H,
9.97.
5-Quinolin-3-ylpentan-2-one (14a) (Table 1, Entry 33)
The reaction of 3-bromoquinoline (0.208 g, 1 mmol), pent-4-en-2-
ol (0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded 14a.
5-Anthracen-9-ylpentan-2-one (11a) (Table 1, Entry 25)
The reaction of 9-bromoanthracene (0.257 g, 1 mmol), pent-4-en-2-
ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 11a.
Yield: 0.169 g (79%).
Yield: 0.212 g (81%).
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1H NMR (300 MHz, CDCl3): d = 8.73 (s, 1 H), 8.04 (d, J = 8.5 Hz,
1 H), 7.88 (s, 1 H), 7.73 (d, J = 8.2 Hz, 1 H), 7.64 (td, J = 7.7, 1.4
Hz, 1 H), 7.48 (t, J = 7.5 Hz, 1 H), 2.76 (t, J = 7.8 Hz, 2 H), 2.45 (t,
J = 7.2 Hz, 2 H), 2.09 (s, 3 H), 1.96 (quin, J = 7.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 208.0, 151.8, 146.8, 134.2, 134.1,
129.0, 128.6, 128.0, 127.2, 126.5, 42.4, 32.1, 29.9, 24.7.
13C NMR (75 MHz, CDCl3): d = 139.9, 127.4, 126.1, 125.9, 124.9,
121.2, 67.3, 42.8, 22.9.
MS (EI, 70 eV): m/z (%) = 168 (63) [M+].
Anal. Calcd for C9H12OS: C, 64.24; H, 7.19. Found: C, 64.41; H,
7.41.
Before purification 16c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.47 (s, 1 H), 5.10 (s, 1 H).
MS (EI, 70 eV): m/z (%) = 213 (35) [M+].
Anal. Calcd for C14H15NO: C, 78.84; H, 7.09. Found: C, 78.69; H,
7.21.
(E)-1-(4-Propenylphenyl)ethanone (17c)41 (Table 2, Entry 1)
The reaction of 4-bromoacetophenone (0.199 g, 1 mmol), 2-phenyl-
pent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) af-
forded 17c.
(E)-5-(Quinolin-3-yl)pent-4-en-2-ol (14b) has also been isolated in
pure form. Yield: 0.019 g (9%).
1H NMR (300 MHz, CDCl3): d = 8.86 (s, 1 H), 8.01 (d, J = 8.5 Hz,
1 H), 7.84 (s, 1 H), 7.67 (d, J = 8.1 Hz, 1 H), 7.60 (td, J = 7.7, 1.5
Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 6.50 (d, J = 16.1 Hz, 1 H), 6.47
(ddt, J = 16.1, 6.2, 1.8 Hz, 1 H), 3.99 (sept, J = 6.2 Hz, 1 H), 2.50–
2.30 (m, 2 H), 1.26 (d, J = 6.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 148.8, 146.8, 131.8, 130.2, 129.7,
129.0, 128.9, 128.7, 127.9, 127.6, 126.8, 67.1, 43.0, 23.1.
Yield: 0.130 g (81%).
1H NMR (300 MHz, CDCl3): d = 7.88 (d, J = 8.3 Hz, 2 H), 7.39 (d,
J = 8.3 Hz, 2 H), 6.44 (d, J = 15.8 Hz, 1 H), 6.42–6.30 (m, 1 H), 2.57
(s, 3 H), 1.91 (d, J = 5.1 Hz, 3 H).
Compound 17d42 was also observed in the reaction described in Ta-
ble 2, entry 2.
MS (EI, 70 eV): m/z (%) = 213 (30) [M+].
1H NMR (300 MHz, CDCl3): d = 6.00–5.85 (m, 1 H), 5.15–5.05 (m,
2 H).
Anal. Calcd for C14H15NO: C, 78.84; H, 7.09. Found: C, 78.62; H,
7.14.
(E)-Phenyl(4-propenylphenyl)methanone (18c)43 (Table 2,
Entry 3)
The reaction of 4-bromobenzophenone (0.261 g, 1 mmol), 2-phe-
nylpent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol)
afforded 18c.
Before purification 14c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.52 (s, 1 H), 5.31 (s, 1 H).
5-Thiophen-2-ylpentan-2-one (15a)11 (Table 1, Entry 35)
The reaction of 2-bromothiophene (0.163 g, 1 mmol), pent-4-en-2-
ol (0.172 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded 15a.
Yield: 0.173 g (78%).
1H NMR (300 MHz, CDCl3): d = 7.85–7.70 (m, 4 H), 7.63–7.50 (m,
1 H), 7.50–7.35 (m, 4 H), 6.47 (d, J = 16.4 Hz, 1 H), 6.44–6.30 (m,
1 H), 1.92 (d, J = 5.3 Hz, 3 H).
Yield: 0.071 g (42%).
1H NMR (300 MHz, CDCl3): d = 7.12 (dd, J = 5.1, 0.9 Hz, 1 H),
6.91 (dd, J = 5.1, 3.4 Hz, 1 H), 6.78 (dd, J = 3.4, 0.9 Hz, 1 H), 2.84
(t, J = 7.4 Hz, 2 H), 2.47 (t, J = 7.3 Hz, 2 H), 2.12 (s, 3 H), 1.95
(quin, J = 7.3 Hz, 2 H).
(E)-5-Thiophen-2-ylpent-4-en-2-ol (15b)11 has also been isolated in
pure form. Yield: 0.042 g (25%).
1H NMR (300 MHz, CDCl3): d = 7.11 (d, J = 4.7 Hz, 1 H), 6.94 (dd,
J = 4.7, 1.9 Hz, 1 H), 6.90 (d, J = 1.9 Hz, 1 H), 6.60 (d, J = 15.7 Hz,
1 H), 6.04 (dt, J = 15.7, 7.6 Hz, 1 H), 3.90 (sept, J = 6.3 Hz, 1 H),
2.43–2.17 (m, 2 H), 1.26 (d, J = 6.3 Hz, 3 H).
5-(4-Fluorophenyl)-2-phenylpent-4-en-2-ol (19a) (Table 2,
Entry 5)
The reaction of 1-bromo-4-fluorobenzene (0.175 g, 1 mmol), 2-phe-
nylpent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol)
afforded 19a.
Yield: 0.182 g (71%).
1H NMR (300 MHz, CDCl3): d = 7.47 (d, J = 7.2 Hz, 2 H), 7.36 (t,
J = 7.2 Hz, 2 H), 7.26 (t, J = 7.2 Hz, 1 H), 7.24 (dd, J = 8.8, 5.6 Hz,
2 H), 6.95 (d, J = 8.8 Hz, 2 H), 6.42 (d, J = 15.8 Hz, 1 H), 5.93 (ddd,
J = 15.8, 8.4, 6.6 Hz, 1 H), 2.81 (ddd, J = 13.8, 6.6, 1.3 Hz, 1 H),
2.64 (ddd, J = 13.8, 8.4, 0.9 Hz, 1 H), 2.05 (br s, 1 H), 1.59 (s, 3 H).
Before purification 15c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.50 (s, 1 H), 5.09 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 162.1 (d, JC–F = 246.5 Hz), 147.6,
5-Thiophen-3-ylpentan-2-one (16a) (Table 1, Entry 36)
The reaction of 3-bromothiophene (0.163 g, 1 mmol), pent-4-en-2-
ol (0.172 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 16a.
4
3
133.3 (d, JC–F = 3.3 Hz), 133.1, 128.3, 127.6 (d, JC–F = 8.3 Hz),
2
126.7, 124.8 (d, 5JC–F = 2.2 Hz), 124.7, 115.3 (d, JC–F = 21.4 Hz),
74.2, 47.7, 29.9.
MS (EI, 70 eV): m/z (%) = 256 (1) [M+].
Yield: 0.061 g (36%).
1H NMR (300 MHz, CDCl3): d = 7.22–7.12 (m, 1 H), 6.92–6.82 (m,
2 H), 2.58 (t, J = 7.5 Hz, 2 H), 2.37 (t, J = 7.3 Hz, 2 H), 2.05 (s, 3
H), 1.84 (quin, J = 7.4 Hz, 2 H).
Anal. Calcd for C17H17FO: C, 79.66; H, 6.69. Found: C, 79.34; H,
6.59.
13C NMR (75 MHz, CDCl3): d = 208.7, 141.9, 128.1, 125.4, 120.4,
Before purification 19b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.24 (d, J = 1.5 Hz, 1 H), 4.99 (d,
J = 1.5 Hz, 1 H).
42.8, 29.9, 29.4, 24.4.
MS (EI, 70 eV): m/z (%) = 168 (64) [M+].
Anal. Calcd for C9H12OS: C, 64.24; H, 7.19. Found: C, 64.12; H,
7.01.
2,5-Diphenylpent-4-en-2-ol (20a)44 (Table 2, Entry 7)
The reaction of bromobenzene (0.157 g, 1 mmol), 2-phenylpent-4-
en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded
20a.
(E)-5-Thiophen-3-ylpent-4-en-2-ol (16b) has also been isolated in
pure form. Yield: 0.079 g (47%).
1H NMR (300 MHz, CDCl3): d = 7.30–7.15 (m, 2 H), 7.09 (s, 1 H),
6.49 (d, J = 15.9 Hz, 1 H), 6.06 (dt, J = 15.9, 7.6 Hz, 1 H), 3.90 (sept,
J = 5.8 Hz, 1 H), 2.25–2.20 (m, 2 H), 1.24 (d, J = 5.8 Hz, 3 H).
Yield: 0.167 g (70%).
1H NMR (300 MHz, CDCl3): d = 7.48 (d, J = 7.6 Hz, 2 H), 7.37 (t,
J = 7.6 Hz, 2 H), 7.31–7.16 (m, 6 H), 6.48 (d, J = 15.9 Hz, 1 H), 6.03
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F. Berthiol et al.
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(ddd, J = 15.9, 8.4, 6.7 Hz, 1 H), 2.83 (ddd, J = 13.7, 6.7, 1.0 Hz, 1
H), 2.66 (dd, J = 13.7, 8.4 Hz, 1 H), 2.10 (br s, 1 H), 1.60 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 157.6, 147.7, 134.5, 134.0, 132.5,
129.4, 128.9, 128.2, 126.9, 126.6, 125.7, 124.8, 124.3, 124.1, 118.9,
105.8, 74.1, 55.2, 47.8, 29.8.
Before purification 20b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.30 (d, J = 1.5 Hz, 1 H), 5.02 (d,
J = 1.5 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 198 (100) [M+ – 120].
Anal. Calcd for C22H22O2: C, 82.99; H, 6.96. Found: C, 82.79; H,
7.10.
5-(4-tert-Butylphenyl)-2-phenylpent-4-en-2-ol (21a) (Table 2,
Entry 9)
The reaction of 1-bromo-4-tert-butylbenzene (0.213 g, 1 mmol), 2-
phenylpent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2
mmol) afforded 21a.
Before purification 23b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.42 (d, J = 1.3 Hz, 1 H), 5.07 (d,
J = 1.3 Hz, 1 H).
5-[4-(Dimethylamino)phenyl]-2-phenylpent-4-en-2-ol (24a)
(Table 2, Entry 15)
Yield: 0.247 g (84%).
1H NMR (300 MHz, CDCl3): d = 7.48 (d, J = 7.2 Hz, 2 H), 7.38 (t,
J = 7.2 Hz, 2 H), 7.32 (d, J = 8.5 Hz, 2 H), 7.26 (t, J = 7.2 Hz, 1 H),
7.24 (d, J = 8.5 Hz, 2 H), 6.48 (d, J = 15.9 Hz, 1 H), 5.98 (ddd, J =
15.9, 8.4, 6.6 Hz, 1 H), 2.83 (ddd, J = 13.7, 6.6, 1.4 Hz, 1 H), 2.65
(ddd, J = 13.7, 8.4, 1.1 Hz, 1 H), 2.16 (br s, 1 H), 1.60 (s, 3 H), 1.31
(s, 9 H).
13C NMR (75 MHz, CDCl3): d = 150.5, 147.7, 134.2, 128.2, 128.1,
126.6, 125.9, 125.4, 124.8, 124.2, 74.1, 47.7, 34.5, 31.2, 29.8.
MS (EI, 70 eV): m/z (%) = 276 (7) [M+ – 18].
The reaction of 1-bromo-4-(dimethylamino)benzene (0.200 g, 1
mmol), 2-phenylpent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3
(0.276 g, 2 mmol) afforded 24a.
Yield: 0.242 g (86%).
1H NMR (300 MHz, CDCl3): d = 7.49 (d, J = 7.2 Hz, 2 H), 7.37 (t,
J = 7.2 Hz, 2 H), 7.26 (t, J = 7.2 Hz, 1 H), 7.20 (d, J = 8.8 Hz, 2 H),
6.66 (d, J = 8.8 Hz, 2 H), 6.43 (d, J = 15.9 Hz, 1 H), 5.80 (ddd, J =
15.9, 8.4, 6.6 Hz, 1 H), 3.94 (s, 6 H), 2.82 (ddd, J = 13.6, 6.6, 1.3
Hz, 1 H), 2.62 (ddd, J = 13.6, 8.4, 0.7 Hz, 1 H), 2.24 (br s, 1 H), 1.59
(s, 3 H).
13C NMR (75 MHz, CDCl3): d = 150.0, 147.9, 134.5, 128.1, 127.1,
126.5, 125.7, 124.8, 120.3, 112.4, 74.0, 47.8, 40.5, 29.8.
MS (EI, 70 eV): m/z (%) = 281 (14) [M+].
Anal. Calcd for C21H26O: C, 85.67; H, 8.90. Found: C, 85.38; H,
9.11.
Before purification 21b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.31 (d, J = 1.3 Hz, 1 H), 4.99 (d,
J = 1.3 Hz, 1 H).
Anal. Calcd for C19H23NO: C, 81.10; H, 8.24. Found: C, 80.92; H,
8.43.
5-(4-Methoxyphenyl)-2-phenylpent-4-en-2-ol (22a) (Table 2,
Entry 11)
The reaction of 4-bromoanisole (0.187 g, 1 mmol), 2-phenylpent-4-
en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded
22a.
Before purification 24b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.24 (d, J = 1.6 Hz, 1 H), 4.86 (d,
J = 1.6 Hz, 1 H).
2-Phenyl-5-(2-tolyl)pent-4-en-2-ol (25a) (Table 2, Entry 17)
The reaction of 2-bromotoluene (0.171 g, 1 mmol), 2-phenylpent-4-
en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded
25a.
Yield: 0.225 g (84%).
1H NMR (300 MHz, CDCl3): d = 7.48 (d, J = 7.2 Hz, 2 H), 7.36 (t,
J = 7.2 Hz, 2 H), 7.26 (t, J = 7.2 Hz, 1 H), 7.23 (d, J = 8.8 Hz, 2 H),
6.83 (d, J = 8.8 Hz, 2 H), 6.43 (d, J = 15.9 Hz, 1 H), 5.88 (ddd, J =
15.9, 8.5, 6.6 Hz, 1 H), 3.78 (s, 3 H), 2.82 (ddd, J = 13.7, 6.6, 1.4
Hz, 1 H), 2.64 (ddd, J = 13.7, 8.5, 1.0 Hz, 1 H), 2.17 (br s, 1 H), 1.59
(s, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.0, 147.7, 133.8, 129.9, 128.2,
127.3, 126.6, 124.8, 122.6, 113.8, 74.1, 55.2, 47.7, 29.8.
MS (EI, 70 eV): m/z (%) = 268 (1) [M+].
Yield: 0.184 g (73%).
1H NMR (300 MHz, CDCl3): d = 7.49 (d, J = 7.2 Hz, 2 H), 7.37 (t,
J = 7.2 Hz, 2 H), 7.33–7.24 (m, 2 H), 7.18–7.08 (m, 3 H), 6.66 (d,
J = 15.7 Hz, 1 H), 5.91 (ddd, J = 15.7, 8.3, 6.7 Hz, 1 H), 2.85 (ddd,
J = 13.7, 6.7, 1.4 Hz, 1 H), 2.69 (ddd, J = 13.7, 8.3, 0.9 Hz, 1 H),
2.29 (s, 3 H), 2.11 (br s, 1 H), 1.62 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 147.6, 136.3, 135.1, 132.4, 130.2,
128.2, 127.3, 126.7, 126.4, 126.0, 125.6, 124.8, 74.1, 48.0, 29.9,
19.8.
Anal. Calcd for C18H20O2: C, 80.56; H, 7.51. Found: C, 80.30; H,
7.49.
Before purification 22b was also observed.
MS (EI, 70 eV): m/z (%) = 234 (76) [M+ – 18].
1H NMR (300 MHz, CDCl3): d = 5.26 (d, J = 1.3 Hz, 1 H), 4.93 (d,
J = 1.3 Hz, 1 H).
Anal. Calcd for C18H20O: C, 85.67; H, 7.99. Found: C, 85.47; H,
7.87.
Before purification 25b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.17 (d, J = 2.0 Hz, 1 H), 4.99 (d,
J = 2.0 Hz, 1 H).
5-(6-Methoxynaphthalen-2-yl)-2-phenylpent-4-en-2-ol (23a)
(Table 2, Entry 13)
The reaction of 2-bromo-6-methoxynaphthalene (0.237 g, 1 mmol),
2-phenylpent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2
mmol) afforded 23a.
5-Naphthalen-1-yl-2-phenylpent-4-en-2-ol (26a) (Table 2, Entry
19)
Yield: 0.261 g (82%).
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol), 2-phenyl-
pent-4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) af-
forded 26a.
1H NMR (300 MHz, CDCl3): d = 7.75–7.23 (m, 9 H), 7.19–7.06 (m,
2 H), 6.62 (d, J = 15.9 Hz, 1 H), 6.12 (ddd, J = 15.9, 8.3, 6.6 Hz, 1
H), 3.90 (s, 3 H), 2.89 (ddd, J = 13.8, 6.6, 1.2 Hz, 1 H), 2.70 (ddd,
J = 13.8, 8.3, 0.9 Hz, 1 H), 2.23 (br s, 1 H), 1.64 (s, 3 H).
Yield: 0.202 g (70%).
1H NMR (300 MHz, CDCl3): d = 8.04–7.97 (m, 1 H), 7.87–7.81 (m,
1 H), 7.75 (d, J = 8.1 Hz, 1 H), 7.55–7.35 (m, 8 H), 7.28 (t, J = 7.2
Hz, 1 H), 7.22 (d, J = 15.6 Hz, 1 H), 6.07 (ddd, J = 15.6, 8.2, 6.8 Hz,
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1 H), 2.95 (ddd, J = 13.7, 6.8, 1.4 Hz, 1 H), 2.81 (ddd, J = 13.7, 8.2,
1.1 Hz, 1 H), 2.19 (br s, 1 H), 1.68 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 147.6, 135.0, 133.5, 131.7, 131.0,
128.4, 128.2, 128.1, 127.7, 126.7, 125.9, 125.7, 125.5, 124.8, 123.8,
123.7, 74.3, 48.1, 29.9.
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 7.6 Hz, 2 H), 7.73 (d,
J = 8.3 Hz, 2 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.44 (td, J = 7.6, 6.0 Hz,
2 H), 7.26 (d, J = 8.3 Hz, 2 H), 2.75–2.60 (m, 2 H), 2.50–2.30 (m, 4
H), 1.75–1.55 (m, 4 H), 1.03 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.3, 206.2, 147.4, 137.9, 135.3,
132.1, 130.3, 129.9, 128.3, 128.2, 42.0, 35.9, 35.8, 30.6, 23.4, 7.8.
MS (EI, 70 eV): m/z (%) = 288 (1) [M+].
MS (EI, 70 eV): m/z (%) = 294 (100) [M+].
Anal. Calcd for C21H20O: C, 87.46; H, 6.99. Found: C, 87.21; H,
7.12.
Anal. Calcd for C20H22O2: C, 81.60; H, 7.53. Found: C, 81.49; H,
7.37.
Before purification 26b was also observed.
Before purification 29b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.49 (d, J = 16.1 Hz, 1 H), 6.38
(dt, J = 16.1, 6.4 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 5.39 (d, J = 1.2 Hz, 1 H), 5.22 (d,
J = 1.2 Hz, 1 H).
(E)-3-Propenylquinoline (27c)45 (Table 2, Entry 21)
The reaction of 3-bromoquinoline (0.208 g, 1 mmol), 2-phenylpent-
4-en-2-ol (0.324 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded
27c.
Alcohol 29c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.39 (s, 1 H), 5.20 (s, 1 H).
Tetrahydrofuran 29d was also observed in the reactions described
in Table 3, entries 3 and 5.
Yield: 0.095 g (56%).
1H NMR (300 MHz, CDCl3): d = 4.10 (quin, J = 6.5 Hz, 1 H), 3.79
(quin, J = 6.5 Hz, 1 H) and 4.22 (quin, J = 6.1 Hz, 1 H), 3.90 (quin,
J = 6.1 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 8.95 (d, J = 1.9 Hz, 1 H), 8.05 (d,
J = 8.4 Hz, 1 H), 7.95 (d, J = 1.9 Hz, 1 H), 7.76 (d, J = 8.4 Hz, 1 H),
7.63 (td, J = 8.4, 1.4 Hz, 1 H), 7.50 (td, J = 8.3, 1.1 Hz, 1 H), 6.55
(d, J = 16.0 Hz, 1 H), 6.51–6.40 (m, 1 H), 1.96 (d, J = 5.1 Hz, 3 H).
Methyl 4-(5-Oxoheptyl)benzoate (30a) (Table 3, Entry 7)
The reaction of methyl 4-bromobenzoate (0.215 g, 1 mmol), hept-
6-en-3-ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) af-
forded 30a.
3-Prop-2-enylquinoline (27d)46 has also been isolated in pure form.
Yield: 0.051 g (30%).
1H NMR (300 MHz, CDCl3): d = 8.76 (d, J = 1.4 Hz, 1 H), 8.09 (d,
J = 8.4 Hz, 1 H), 7.92 (d, J = 1.4 Hz, 1 H), 7.76 (d, J = 8.4 Hz, 1 H),
7.66 (td, J = 8.4, 1.5 Hz, 1 H), 7.53 (td, J = 8.4, 1.5 Hz, 1 H), 6.10–
5.90 (m, 1 H), 5.19–5.06 (m, 2 H), 3.57 (d, J = 6.5 Hz, 2 H).
Yield: 0.199 g (80%).
1H NMR (300 MHz, CDCl3): d = 7.93 (d, J = 8.2 Hz, 2 H), 7.23 (d,
J = 8.2 Hz, 2 H), 3.89 (s, 3 H), 2.74–2.57 (m, 2 H), 2.50–2.30 (m, 4
H), 1.75–1.50 (m, 4 H), 1.03 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.4, 167.1, 147.8, 129.7, 128.4
(2 C), 52.0, 42.0, 35.9, 35.8, 30.6, 23.4, 7.8.
7-(4-Acetylphenyl)heptan-3-one (28a) (Table 3, Entry 2)
The reaction of 4-bromoacetophenone (0.199 g, 1 mmol), hept-6-
en-3-ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded
28a.
MS (EI, 70 eV): m/z (%) = 248 (5) [M+].
Yield: 0.193 g (83%).
Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C, 72.56; H,
8.30.
1H NMR (300 MHz, CDCl3): d = 7.86 (d, J = 8.4 Hz, 2 H), 7.24 (d,
J = 8.4 Hz, 2 H), 2.70–2.60 (m, 2 H), 2.56 (s, 3 H), 2.45–2.30 (m, 4
H), 1.65–1.55 (m, 4 H), 1.02 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.3, 197.8, 148.0, 135.0, 128.6,
128.5, 42.0, 35.9, 35.7, 30.6, 26.5, 23.4, 7.8.
Before purification 30b was also observed in the reaction described
in Table 3, entry 6.
1H NMR (300 MHz, CDCl3): d = 6.46 (d, J = 15.9 Hz, 1 H), 6.35
(dt, J = 15.9, 5.9 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 232 (90) [M+].
Alcohol 30c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.36 (s, 1 H), 5.18 (s, 1 H).
Anal. Calcd for C15H20O2: C, 77.55; H, 8.68. Found: C, 77.71; H,
8.80.
Tetrahydrofuran 30d was also observed.
1H NMR (300 MHz, CDCl3): d = 4.02 (quin, J = 6.4 Hz, 1 H) and
4.15 (quin, J = 6.5 Hz, 1 H).
Before purification 28b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.46 (d, J = 16.0 Hz, 1 H), 6.38
(dt, J = 16.0, 6.0 Hz, 1 H).
Alcohol 28c was also observed in the reaction described in Table 3,
entry 1.
7-[4-(Trifluoromethyl)phenyl]heptan-3-one (31a) (Table 3,
Entry 9)
1H NMR (300 MHz, CDCl3): d = 5.38 (d, J = 1.3 Hz, 1 H), 5.20 (d,
J = 1.3 Hz, 1 H).
The reaction of 1-bromo-4-(trifluoromethyl)benzene (0.225 g, 1
mmol), hept-6-en-3-ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2
mmol) afforded 31a.
Tetrahydrofuran 28d was also observed in the reaction described in
Table 3, entry 1.
Yield: 0.212 g (82%).
1H NMR (300 MHz, CDCl3): d = 7.52 (d, J = 8.2 Hz, 2 H), 7.27 (d,
J = 8.2 Hz, 2 H), 2.71–2.61 (m, 2 H), 2.47–2.33 (m, 4 H), 1.65–1.56
(m, 4 H), 1.03 (t, J = 7.4 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 4.07 (quin, J = 6.4 Hz, 1 H), 3.76
(quin, J = 6.6 Hz, 1 H) and 4.20 (quin, J = 6.2 Hz, 1 H), 3.88 (quin,
J = 6.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 211.4, 146.3, 128.6, 128.1 (q,
2JC–F = 32.1 Hz), 125.2 (q, 3JC–F = 4.0 Hz), 124.3 (q, JC–F = 271.7
Hz), 42.0, 35.9, 35.6, 30.7, 23.3, 7.8.
7-(4-Benzoylphenyl)heptan-3-one (29a) (Table 3, Entry 4)
The reaction of 4-bromobenzophenone (0.261 g, 1 mmol), hept-6-
en-3-ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded
29a.
MS (EI, 70 eV): m/z (%) = 258 (8) [M+].
Anal. Calcd for C14H17F3O: C, 65.10; H, 6.63. Found: C, 64.95; H,
6.69.
Yield: 0.238 g (81%).
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7-(4-Methoxyphenyl)heptan-3-one (34a) (Table 3, Entry 15)
Before purification 31b was also observed.
The reaction of 4-bromoanisole (0.187 g, 1 mmol), hept-6-en-3-ol
(0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 34a.
1H NMR (300 MHz, CDCl3): d = 6.45 (d, J = 16.0 Hz, 1 H), 6.34
(dt, J = 16.0, 6.4 Hz, 1 H).
Yield: 0.163 g (74%).
Alcohol 31c was also observed in the reaction described in Table 3,
entry 8.
1H NMR (300 MHz, CDCl3): d = 7.07 (d, J = 8.7 Hz, 2 H), 6.81 (d,
J = 8.7 Hz, 2 H), 3.77 (s, 3 H), 2.60–2.50 (m, 2 H), 2.45–2.29 (m, 4
H), 1.65–1.50 (m, 4 H), 1.03 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.6, 157.7, 134.3, 129.2, 113.8,
55.2, 42.2, 35.8, 34.8, 31.2, 23.5, 7.8.
1H NMR (300 MHz, CDCl3): d = 5.34 (d, J = 1.2 Hz, 1 H), 5.19 (d,
J = 1.2 Hz, 1 H).
Tetrahydrofuran 31d was also observed in the reaction described in
Table 3, entry 8.
1H NMR (300 MHz, CDCl3): d = 4.06 (quin, J = 6.4 Hz, 1 H), 3.77
(quin, J = 6.4 Hz, 1 H) and 4.19 (quin, J = 6.2 Hz, 1 H), 3.88 (quin,
J = 6.2 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 220 (57) [M+].
Anal. Calcd for C14H20O2: C, 76.33; H, 9.15. Found: C, 76.17; H,
9.00.
Before purification 34b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.36 (d, J = 15.7 Hz, 1 H), 6.08
(dt, J = 15.7, 7.0 Hz, 1 H).
7-(4-Fluorophenyl)heptan-3-one (32a) (Table 3, Entry 12)
The reaction of 1-bromo-4-fluorobenzene (0.175 g, 1 mmol), hept-
6-en-3-ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) af-
forded 32a.
Alcohol 34c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.21 (d, J = 1.0 Hz, 1 H), 5.00 (d,
J = 1.0 Hz, 1 H).
Yield: 0.148 g (71%).
1H NMR (300 MHz, CDCl3): d = 7.10 (dd, J = 8.7, 5.5 Hz, 2 H),
6.93 (t, J = 8.7 Hz, 2 H), 2.62–2.53 (m, 2 H), 2.45–2.29 (m, 4 H),
1.65–1.50 (m, 4 H), 1.03 (t, J = 7.4 Hz, 3 H).
7-[2-(Trifluoromethyl)phenyl]heptan-3-one (35a) (Table 3,
Entry 17)
The reaction of 1-bromo-2-(trifluoromethyl)benzene (0.225 g, 1
mmol), hept-6-en-3-ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2
mmol) afforded 35a.
13C NMR (75 MHz, CDCl3): d = 211.5, 161.2 (d, JC–F = 243.2 Hz),
137.8 (d, 4JC–F = 2.8 Hz), 129.6 (d, 3JC–F = 7.5 Hz), 115.0 (d, 2JC–F
=
21.3 Hz), 42.1, 35.9, 34.9, 31.1, 23.4, 7.8.
MS (EI, 70 eV): m/z (%) = 208 (46) [M+].
Yield: 0.191 g (74%).
Anal. Calcd for C13H17FO: C, 74.97; H, 8.23. Found: C, 74.81; H,
8.07.
1H NMR (300 MHz, CDCl3): d = 7.59 (d, J = 7.8 Hz, 1 H), 7.44 (t,
J = 7.5 Hz, 1 H), 7.35–7.20 (m, 2 H), 2.76 (t, J = 7.4 Hz, 2 H), 2.50–
2.34 (m, 4 H), 1.77–1.62 (m, 4 H), 1.04 (t, J = 7.4 Hz, 3 H).
Before purification 32b was also observed in the reaction described
in Table 3, entry 11.
1H NMR (300 MHz, CDCl3): d = 6.37 (d, J = 15.9 Hz, 1 H), 6.14
(dt, J = 15.9, 6.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 211.4, 141.1, 131.7, 130.9, 128.3
(q, JC–F = 30.0 Hz), 125.9 (q, JC–F = 5.7 Hz), 125.8, 124.6 (q,
JC–F = 273.8 Hz), 42.0, 35.9, 32.4, 31.2, 23.8, 7.8.
2
3
Alcohol 32c was also observed.
MS (EI, 70 eV): m/z (%) = 258 (1) [M+].
1H NMR (300 MHz, CDCl3): d = 5.21 (d, J = 1.1 Hz, 1 H), 5.07 (d,
J = 1.1 Hz, 1 H).
Anal. Calcd for C14H17F3O: C, 65.10; H, 6.63. Found: C, 65.31; H,
6.50.
Tetrahydrofuran 32d was also observed.
Compound 35b was also observed in the reaction described in Table
3, entry 16.
1H NMR (300 MHz, CDCl3): d = 6.77 (d, J = 16.0 Hz, 1 H), 6.32
(dt, J = 16.0, 6.4 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 4.01 (quin, J = 6.5 Hz, 1 H), 3.75
(quin, J = 6.5 Hz, 1 H) and 4.13 (quin, J = 6.2 Hz, 1 H), 3.87 (quin,
J = 6.2 Hz, 1 H).
Tetrahydrofuran 35d was also observed in the reaction described in
Table 3, entry 16.
1H NMR (300 MHz, CDCl3): d = 4.10 (quin, J = 6.4 Hz, 1 H), 3.79
(quin, J = 6.5 Hz, 1 H) and 4.25 (quin, J = 6.2 Hz, 1 H), 3.93 (quin,
J = 6.2 Hz, 1 H).
7-(4-tert-Butylphenyl)heptan-3-one (33a) (Table 3, Entry 13)
The reaction of 1-bromo-4-tert-butylbenzene (0.213 g, 1 mmol),
hept-6-en-3-ol (0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) af-
forded 33a.
Yield: 0.185 g (75%).
1H NMR (300 MHz, CDCl3): d = 7.29 (d, J = 8.3 Hz, 2 H), 7.10 (d,
J = 8.3 Hz, 2 H), 2.62–2.53 (m, 2 H), 2.46–2.33 (m, 4 H), 1.70–1.52
(m, 4 H), 1.30 (s, 9 H), 1.03 (t, J = 7.4 Hz, 3 H).
7-(2-Tolyl)heptan-3-one (36a) (Table 3, Entry 18)
The reaction of 2-bromotoluene (0.171 g, 1 mmol), hept-6-en-3-ol
(0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 36a.
13C NMR (75 MHz, CDCl3): d = 211.7, 148.5, 139.1, 128.0, 125.2,
Yield: 0.164 g (80%).
42.2, 35.9, 35.2, 34.3, 31.4, 31.0, 23.6, 7.8.
1H NMR (300 MHz, CDCl3): d = 7.20–7.05 (m, 4 H), 2.61 (t, J =
6.6 Hz, 2 H), 2.49–2.36 (m, 4 H), 2.31 (s, 3 H), 1.74–1.51 (m, 4 H),
1.06 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.5, 140.3, 135.7, 130.1, 128.7,
125.8 (2 C), 42.1, 35.8, 33.0, 29.8, 23.8, 19.2, 7.8.
MS (EI, 70 eV): m/z (%) = 246 (24) [M+].
Anal. Calcd for C17H26O: C, 82.87; H, 10.64. Found: C, 82.97; H,
10.78.
Before purification 33b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.38 (d, J = 15.9 Hz, 1 H), 6.16
(dt, J = 15.9, 6.9 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 204 (20) [M+].
Anal. Calcd for C14H20O: C, 82.30; H, 9.87. Found: C, 82.49; H,
10.10.
Alcohol 33c was also observed.
Before purification 36b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.26 (d, J = 1.1 Hz, 1 H), 5.03 (d,
J = 1.1 Hz, 1 H).
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Heck Reaction of Aryl Bromides Catalysed by a Palladium–Tetraphosphine Complex
3601
1H NMR (300 MHz, CDCl3): d = 6.61 (d, J = 15.6 Hz, 1 H), 6.10
(dt, J = 15.6, 7.0 Hz, 1 H).
1H NMR (300 MHz, CDCl3): d = 8.42 (s, 2 H), 7.48 (dt, J = 7.7, 2.0
Hz, 1 H), 7.20 (dd, J = 7.9, 4.7 Hz, 1 H), 2.64–2.56 (m, 2 H), 2.45–
2.31 (m, 4 H), 1.65–1.56 (m, 4 H), 1.03 (t, J = 7.3 Hz, 3 H).
7-Naphthalen-1-ylheptan-3-one (37a) (Table 3, Entry 19)
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol), hept-6-en-
3-ol (0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 37a.
13C NMR (75 MHz, CDCl3): d = 211.3, 149.7, 147.2, 137.4, 135.9,
123.3, 41.9, 35.9, 32.8, 30.6, 23.3, 7.8.
MS (EI, 70 eV): m/z (%) = 191 (8) [M+].
Yield: 0.200 g (83%).
Anal. Calcd for C12H17NO: C, 75.35; H, 8.96. Found: C, 75.21; H,
9.14.
1H NMR (300 MHz, CDCl3): d = 8.03 (dd, J = 7.0, 2.1 Hz, 1 H),
7.86 (dd, J = 6.0, 3.1 Hz, 1 H), 7.72 (d, J = 7.8 Hz, 1 H), 7.56–7.27
(m, 4 H), 3.20–3.02 (m, 2 H), 2.53–2.30 (m, 4 H), 1.85–1.64 (m, 4
H), 1.05 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.5, 138.2, 133.8, 131.8, 128.7,
126.5, 125.9, 125.7, 125.5, 125.3, 123.7, 42.1, 35.8, 32.9, 30.3,
23.9, 7.8.
Before purification 40b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.38 (d, J = 15.9 Hz, 1 H), 6.26
(dt, J = 15.9, 6.2 Hz, 1 H).
Alcohol 40c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.32 (d, J = 1.3 Hz, 1 H), 5.15 (d,
J = 1.3 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 240 (100) [M+].
Anal. Calcd for C17H20O: C, 84.96; H, 8.39. Found: C, 85.17; H,
8.21.
Tetrahydrofuran 40d was also observed in the reaction described in
Table 3, entry 24.
1H NMR (300 MHz, CDCl3): d = 4.05 (quin, J = 6.4 Hz, 1 H), 3.76
(quin, J = 6.4 Hz, 1 H) and 4.17 (quin, J = 6.2 Hz, 1 H), 3.86 (quin,
J = 6.4 Hz, 1 H).
Before purification 37b was also observed.
1H NMR (300 MHz, CDCl3): d = 7.17 (d, J = 15.7 Hz, 1 H), 6.26
(dt, J = 15.7, 7.0 Hz, 1 H).
7-Quinolin-3-ylheptan-3-one (41a) (Table 3, Entry 27)
The reaction of 3-bromoquinoline (0.208 g, 1 mmol), hept-6-en-3-
ol (0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded 41a.
7-Mesitylheptan-3-one (38a) (Table 3, Entry 21)
The reaction of 2-bromo-1,3,5-trimethylbenzene (0.199 g, 1 mmol),
hept-6-en-3-ol (0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) af-
forded 38a.
Yield: 0.193 g (80%).
1H NMR (300 MHz, CDCl3): d = 8.76 (d, J = 2.0 Hz, 1 H), 8.09 (d,
J = 8.6 Hz, 1 H), 7.93 (d, J = 2.0 Hz, 1 H), 7.76 (d, J = 8.0 Hz, 1 H),
7.66 (td, J = 6.9, 5.3 Hz, 1 H), 7.52 (td, J = 8.0, 6.9 Hz, 1 H), 2.88–
2.72 (m, 2 H), 2.50–2.32 (m, 4 H), 1.80–1.54 (m, 4 H), 1.03 (t, J =
7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.3, 151.7, 146.5, 134.8, 134.5,
128.9, 128.8, 128.2, 127.3, 126.7, 42.0, 36.0, 33.1, 30.6, 23.4, 7.8.
Yield: 0.179 g (77%).
1H NMR (300 MHz, CDCl3): d = 6.82 (s, 2 H), 2.62–2.53 (m, 2 H),
2.49–2.36 (m, 4 H), 2.26 (s, 6 H), 2.23 (s, 3 H), 1.77–1.62 (m, 2 H),
1.50–1.36 (m, 2 H), 1.05 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.6, 136.0, 135.8, 134.9, 128.8,
42.2, 35.9, 29.2, 29.0, 24.4, 20.7, 19.7, 7.8.
MS (EI, 70 eV): m/z (%) = 232 (45) [M+].
MS (EI, 70 eV): m/z (%) = 241 (50) [M+].
Anal. Calcd for C16H24O: C, 82.70; H, 10.41. Found: C, 82.89; H,
10.18.
Anal. Calcd for C16H19NO: C, 79.63; H, 7.94. Found: C, 79.78; H,
7.77.
Before purification 38e was also observed.
1H NMR (300 MHz, CDCl3): d = 5.68–5.52 (m, 1 H), 5.39–5.25 (m,
1 H).
Before purification 41b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.43 (d, J = 15.9 Hz, 1 H), 6.30
(dt, J = 15.9, 6.4 Hz, 1 H).
7-(2,4,6-Triisopropylphenyl)heptan-3-one (39a) (Table 3, Entry
23)
The reaction of 2-bromo-1,3,5-triisopropylbenzene (0.283 g, 1
mmol), hept-6-en-3-ol (0.228 g, 2 mmol), and K2CO3 (0.276 g, 2
mmol) afforded 39a.
Alcohol 41c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.34 (d, J = 1.3 Hz, 1 H), 5.19 (d,
J = 1.3 Hz, 1 H).
Tetrahydrofuran 41d was also observed.
1H NMR (300 MHz, CDCl3): d = 4.06 (quin, J = 6.4 Hz, 1 H), 3.77
(quin, J = 6.4 Hz, 1 H) and 4.19 (quin, J = 6.2 Hz, 1 H), 3.88 (quin,
J = 6.2 Hz, 1 H).
Yield: 0.219 g (69%).
1H NMR (300 MHz, CDCl3): d = 6.95 (s, 2 H), 3.11 (sept, J = 6.8
Hz, 2 H), 2.84 (sept, J = 6.8 Hz, 1 H), 2.66–2.56 (m, 2 H), 2.49–2.36
(m, 4 H), 1.72 (quin, J = 7.6 Hz, 2 H), 1.50–1.36 (m, 2 H), 1.22 (d,
J = 6.9 Hz, 18 H), 1.05 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.6, 146.3, 146.1, 133.4, 120.9,
42.3, 35.9, 34.1, 31.7, 29.2, 27.7, 24.6, 24.5, 24.0, 7.9.
7-Thiophen-2-ylheptan-3-one (42a) (Table 3, Entry 28)
The reaction of 2-bromothiophene (0.163 g, 1 mmol), hept-6-en-3-
ol (0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 42a.
Yield: 0.081 g (41%).
MS (EI, 70 eV): m/z (%) = 316 (25) [M+].
1H NMR (300 MHz, CDCl3): d = 7.09 (dd, J = 5.1, 1.1 Hz, 1 H),
6.90 (dd, J = 5.1, 3.3 Hz, 1 H), 6.77 (dd, J = 3.3, 1.1 Hz, 1 H), 2.89–
2.75 (m, 2 H), 2.48–2.32 (m, 4 H), 1.71–1.59 (m, 4 H), 1.04 (t, J =
7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.5, 145.1, 126.7, 124.1, 122.9,
42.0, 35.9, 31.3, 29.7, 23.3, 7.8.
Anal. Calcd for C22H36O: C, 83.48; H, 11.46. Found: C, 83.74; H,
11.60.
7-Pyridin-3-ylheptan-3-one (40a) (Table 3, Entry 25)
The reaction of 3-bromopyridine (0.158 g, 1 mmol), hept-6-en-3-ol
(0.228 g, 2 mmol), and NaHCO3 (0.168 g, 2 mmol) afforded 40a.
MS (EI, 70 eV): m/z (%) = 196 (38) [M+].
Yield: 0.159 g (83%).
Anal. Calcd for C11H16OS: C, 67.30; H, 8.22. Found: C, 67.48; H,
8.22.
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York

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F. Berthiol et al.
PAPER
Before purification 42b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.54 (d, J = 15.5 Hz, 1 H), 6.06
(dt, J = 15.5, 7.0 Hz, 1 H).
(16) Larock, R. C.; Leung, W.-Y.; Stolz-Dunn, S. Tetrahedron
Lett. 1989, 30, 6629.
(17) Tamaru, Y.; Yamada, Y.; Yoshida, Z. Tetrahedron 1979, 35,
329.
(18) Laurenti, D.; Feuerstein, M.; Pèpe, G.; Doucet, H.; Santelli,
M. J. Org. Chem. 2001, 66, 1633.
(19) Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. (Cambridge) 2001, 325.
(20) Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Org.
Biomol. Chem. 2003, 1, 2235.
Alcohol 42c was also observed.
1H NMR (300 MHz, CDCl3): d = 5.39 (s, 1 H), 4.98 (s, 1 H).
Tetrahydrofuran 42d was also observed.
1H NMR (300 MHz, CDCl3): d = 4.08 (quin, J = 6.6 Hz, 1 H), 3.79
(quin, J = 6.6 Hz, 1 H) and 4.20 (quin, J = 6.6 Hz, 1 H), 3.91 (quin,
J = 6.6 Hz, 1 H).
(21) Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem. 2001,
66, 5923.
7-Thiophen-3-ylheptan-3-one (43a) (Table 3, Entry 31)
The reaction of 3-bromothiophene (0.163 g, 1 mmol), hept-6-en-3-
ol (0.228 g, 2 mmol), and K2CO3 (0.276 g, 2 mmol) afforded 43a.
(22) Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001, 1980.
(23) Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2002, 43, 2191.
(24) Berthiol, F.; Feuerstein, M.; Doucet, H.; Santelli, M.
Yield: 0.110 g (56%).
Tetrahedron Lett. 2002, 43, 5625.
(25) Berthiol, F.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2003, 44, 1221.
(26) Berthiol, F.; Doucet, H.; Santelli, M. Synlett 2003, 841.
(27) Kondolff, I.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2003, 44, 8487.
1H NMR (300 MHz, CDCl3): d = 7.23 (t, J = 4.2 Hz, 1 H), 6.92 (m,
2 H), 2.70–2.59 (m, 2 H), 2.48–2.32 (m, 4 H), 1.70–1.55 (m, 4 H),
1.04 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.6, 142.5, 128.2, 125.2, 120.0,
42.1, 35.9, 30.1, 30.0, 23.5, 7.8.
(28) Kondolff, I.; Doucet, H.; Santelli, M. Synlett 2004, 1561.
(29) Berthiol, F.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2004, 45, 5633.
(30) Lemhadri, M.; Doucet, H.; Santelli, M. Tetrahedron 2004,
50, 11533.
(31) Berthiol, F.; Doucet, H.; Santelli, M. Eur. J. Org. Chem.
2005, 1367.
(32) Ranganathan, S.; Kumar, R.; Maniktala, V. Tetrahedron
MS (EI, 70 eV): m/z (%) = 196 (47) [M+].
Anal. Calcd for C11H16OS: C, 67.30; H, 8.22. Found: C, 67.49; H,
8.10.
Before purification 43b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.43 (d, J = 15.7 Hz, 1 H), 6.08
(dt, J = 15.7, 7.0 Hz, 1 H).
1984, 40, 1167.
Alcohol 43c was also observed.
(33) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.; Morisaki,
Y.; Watanabe, Y.; Mitsudo, T.-A. J. Am. Chem. Soc. 1998,
120, 5587.
1H NMR (300 MHz, CDCl3): d = 5.35 (d, J = 1.2 Hz, 1 H), 5.04 (d,
J = 1.2 Hz, 1 H).
(34) Wolfe, J. P.; Rossi, M. A. J. Am. Chem. Soc. 2004, 126,
1620.
(35) Hay, M. B.; Hardin, A. R.; Wolfe, J. P. J. Org. Chem. 2005,
70, 3099.
(36) Bradshaw, J.; Collins, I. DE 19770217, 1977.
(37) Wennerberg, J.; Olofsson, C.; Frejd, T. J. Org. Chem. 1998,
63, 3595.
(38) Kise, N.; Suzumoto, T.; Shono, T. J. Org. Chem. 1994, 59,
1407.
(39) Bohlmann, F.; Krueger, M. Liebigs Ann. Chem. 1985, 560.
(40) Guthrie, R. W.; Kaplan, G. L.; Mennona, F. A.; Tilley, J. W.;
Kierstead, R. W.; Mullin, J. G.; LeMahieu, R. A.; Zawoiski,
S.; O' Donnell, M.; Crowley, H.; Yaremko, B.; Welton, A. F.
J. Med. Chem. 1989, 32, 1820.
References
(1) de Meijere, A.; Meyer, F. Angew. Chem., Int. Ed. Engl.
1994, 33, 2379.
(2) Reetz, M. T. In Transition Metal Catalysed Reactions;
Davies, S. G.; Murahashi, S.-I., Eds.; Blackwell Science:
Oxford, 1999.
(3) Beletskaya, I.; Cheprakov, A. Chem. Rev. 2000, 100, 3009.
(4) Withcombe, N.; Hii (Mimi), K. K.; Gibson, S. Tetrahedron
2001, 57, 7449.
(5) Littke, A.; Fu, G. Angew. Chem. Int. Ed. 2002, 41, 4176.
(6) Farina, V. Adv. Synth. Catal. 2004, 346, 1553.
(7) Muzart, J. Tetrahedron 2005, 61, 4176.
(8) Dyker, G.; Markwitz, H. Synthesis 1998, 1750.
(9) Qadir, M.; Priestley, R. E.; Rising, T. W. D. F.; Gelbrich, T.;
Coles, S. J.; Hursthouse, M. B.; Sheldrake, P. W.; Whittall,
N.; Hii (Mimi), K. K. Tetrahedron Lett. 2003, 44, 3675.
(10) Dyker, G.; Kadzimirsz, D. Eur. J. Org. Chem. 2003, 3167.
(11) Dyker, G.; Grundt, P.; Markwitz, H.; Henkel, G. J. Org.
Chem. 1998, 63, 6043.
(41) Peyroux, E.; Berthiol, F.; Doucet, H.; Santelli, M. Eur. J.
Org. Chem. 2004, 1075.
(42) Kayaki, Y.; Koda, T.; Ikariya, T. Eur. J. Org. Chem. 2004,
4989.
(43) Fuerstner, A.; Seidel, G. Synlett 1998, 161.
(44) Araki, S.; Hatano, M.; Ito, H.; Butsugan, Y. J. Organomet.
Chem. 1987, 333, 329.
(12) Taylor, E. C.; Wang, Y. Heterocycles 1998, 48, 1537.
(13) Dyker, G.; Grundt, P. Helv. Chim. Acta 1999, 82, 588.
(14) Ohno, H.; Okumura, M.; Maeda, S.-I.; Iwasaki, H.;
Wakayama, R.; Tanaka, T. J. Org. Chem. 2003, 68, 7722.
(15) Gangjee, A.; Yu, J.; Kisliuk, R. L.; Haile, W. H.; Sobrero,
G.; McGuire, J. J. J. Med. Chem. 2003, 46, 591.
(45) Fakhfakh, M. A.; Fournet, A.; Prina, E.; Mouscadet, J.-F.;
Franck, X.; Hocquemiller, R.; Figadere, B. Bioorg. Med.
Chem. 2003, 11, 5013.
(46) Ota, T.; Terashima, M. J. Heterocycl. Chem. 1987, 24, 377.
Synthesis 2005, No. 20, 3589–3602 © Thieme Stuttgart · New York