Heck reaction of protected allyl alcohols with aryl bromides catalyzed by a tetraphosphanepalladium complex

Article abstract of DOI:10.1002/ejoc.200400797

A range of aryl bromides undergo a Heck vinylation reaction with a protected allyl alcohol in the presence of [PdCl(C₃H ₅)]₂/cis, cis, cis-1 r2,3,4- tetrakis(diphenylphosphanylmethyl)cyclopentane as a catalyst. The reactivity of these allyl alcohol derivatives using a variety of protecting groups has been studied. The best results in terms of substrate/catalyst ratio were obtained with a THP protecting group. In most cases, the major isomer obtained was the (E)-cinnamyl alcohol derivative. The reaction tolerates several functionalities, such as trifluoromethyl, methoxy, dimethylamino, acetyl, formyl or nitrite. Furthermore, this catalyst can be used at low loadings, even for reactions with sterically hindered substrates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400797

FULL PAPER
Heck Reaction of Protected Allyl Alcohols with Aryl Bromides Catalyzed by a
Tetraphosphanepalladium Complex
Florian Berthiol,[a] Henri Doucet,*[a] and Maurice Santelli*[a]
Keywords: Allylic compounds / Alcohols / Heck reaction / Palladium / Phosphanes
A range of aryl bromides undergo a Heck vinylation reaction
with protected allyl alcohol in the presence of
alcohol derivative. The reaction tolerates several functionali-
ties, such as trifluoromethyl, methoxy, dimethylamino, acetyl,
formyl or nitrile. Furthermore, this catalyst can be used at
low loadings, even for reactions with sterically hindered sub-
strates.
a
[PdCl(C3H5)]2/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphan-
ylmethyl)cyclopentane as a catalyst. The reactivity of these
allyl alcohol derivatives using a variety of protecting groups
has been studied. The best results in terms of substrate/cata-
lyst ratio were obtained with a THP protecting group. In most
cases, the major isomer obtained was the (E)-cinnamyl
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Suzuki cross-coupling,[31,32] in Sonogashira[33] and
Heck[34–42] reactions using Tedicyp as ligand. For example,
a TON of 69 000 for the coupling of 4-bromobenzophenone
with hex-1-en-3-ol has been reported.[41] For this reaction
the corresponding ketone was selectively obtained. Here, in
order to further establish the requirements for a successful
Heck reaction, we wish to report on the reaction of a pro-
tected allyl alcohol with a variety of aryl bromides using
Tedicyp as the ligand (Figure 1).
Introduction
The Heck reaction is one of the most widely used palla-
dium-catalyzed methodologies in organic synthesis. The
efficiency of several catalysts for the reaction of aryl halides
with acrylates or styrene derivatives has been studied in de-
tail.[1–6] The Heck reaction between an allyl alcohol or pro-
tected allyl alcohol and an aryl halide has attracted less
attention; however, this is a powerful method for the syn-
thesis of 3-arylpropionaldehyde derivatives. Most of the re-
sults described with allyl alcohols were obtained in the pres-
ence of expensive aryl iodides.[7–26] Few results have been
described in the presence of aryl bromides.[27] 3-Arylpro-
pionaldehyde derivatives are generally thermally unstable in
organic solvents and the elevated temperatures required for
the coupling of aryl bromides with an allyl alcohol gen-
erally lead to the decomposition of the product. The use of
protected allyl alcohol derivatives should therefore lead to
more satisfactory results with these aryl bromides; however
few results have been described with such substrates.[28,29]
In order to find stable and efficient palladium catalysts,
we have prepared the tetrapodal phosphane ligand
cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphanylmethyl)cyclo-
pentane or Tedicyp (Figure 1)[30] in which the four di-
phenylphosphanylalkyl groups are stereospecifically bound
to the same face of the cyclopentane ring. We have already
reported the results obtained in allylic substitution,[30] in
Figure 1. The structure of Tedicyp.
Results and Discussion
For this study, based on previous results,[34] DMF was
chosen as the solvent and potassium carbonate as the base.
The reactions were generally performed at 130 °C under ar-
gon in the presence of a 1:2 [Pd(C3H5)Cl]2/Tedicyp ratio as
catalyst. Seven isomers can be obtained from this reaction
(Scheme 1): the three branched isomers coming from the
attack at the central carbon of the allyl alcohol derivative
[gem-branched a and (Z/E)-branched b] and the four linear
isomers coming from the attack at the terminal carbon of
the allyl alcohol derivative [(E)-allyl c, (Z)-allyl d, (E)-enol
e, (Z)-enol f]. The formation of this mixture is probably due
to the involvement of both the available β-hydrogen atoms
of the [PdCH(CH2Ar)(CH2OR2)] intermediate in the elimi-
nation step of the catalytic cycle.
[a] UMR 6180 CNRS and Université dЈAix-Marseille III: “Chiro-
technologies: catalyse et biocatalyse”, Laboratoire de Synthèse
Organique, Faculté des Sciences de Saint Jérôme,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex
20, France
Fax: +33-049-198-3865
First we studied the reactivity of allyloxytrimethylsilane
and allyloxy-tert-butyldimethylsilane. In the presence of al-
E-mail: henri.doucet@univ.u-3mrs.fr
m.santelli@univ.u-3mrs.fr
Eur. J. Org. Chem. 2005, 1367–1377
DOI: 10.1002/ejoc.200400797
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1367

F. Berthiol, H. Doucet, M. Santelli
FULL PAPER
Scheme 1.
Table 1. Heck reaction with allyloxy-tert-butyldimethylsilane (Scheme 1).
Substrate/catalyst gem-Branched a/(Z,E)-branched b/(E)-allyl c/
Yield
[%]
Entry[a]
ArBr
ratio
(Z)-allyl d/(E)-enol e/(Z)-enol f
Product
1
2
3
4
5
6
7
8
4-MeCOC6H4Br
4-HCOC6H4Br
4-CF3C6H4Br
1000
100
250
100
100
100
100
100
0:0:100:0:0:0
0:0:100:0:0:0
0:0:100:0:0:0
0:0:100:0:0:0
0:0:100:0:0:0
18:0:82:0:0:0
22:0:78:0:0:0
0:0:100:0:0:0
1c
2c
74
54[b]
31[b]
40[b]
32[b]
44[b]
72
3c
4-tBuC6H4Br
4c
5c
6a, 6c
7a, 7c
8c
4-MeOC6H4Br
2,4,6-Me3C6H2Br
3-bromopyridine
3-bromoquinoline
76
[a] Conditions: catalyst see ref.[30]; substrate/catalyst ratio calculated relative to Pd atom; aryl bromide (1 equiv.), allyloxy-tert-butyldime-
thylsilane (1.2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h, complete conversion of the aryl bromide, isolated yield of the mixture of
isomers. [b] The formation of side-products was also observed.
lyloxytrimethylsilane, 4-tert-butylbromobenzene and 1mol- mers. In general the major isomer was the (E)-allyl c. Up
% catalyst complete conversion of the aryl bromide was ob- to 79% of this isomer was obtained for the reaction with 4-
served, although the formation of [3-(4-tert-butylphenyl)al- tert-butylbromobenzene, but the presence of the two iso-
lyloxy]trimethylsilane was not detected. The trimethylsilane mers (E)-enol e and (Z)-enol f was also observed. These
protecting group is not stable under the reaction conditions two isomers were obtained in larger quantities with 1-
(90 °C, K2CO3) and the 3-(4-tert-butylphenyl)propionalde- bromo-2,4,6-trimethylbenzene. This sterically congested
hyde decomposes. Next, we studied the reaction with al- substrate led to the formation of (E)-allyl c, (E)-enol e and
lyloxy-tert-butyldimethylsilane (Table 1). With this alkene (Z)-enol f in a 38:38:24 ratio, thus indicating that the β-
the vinylation products were obtained using 1–0.1% cata- hydrogen elimination of the [PdCH(CH2Ar)(CH2OR2)] in-
lyst. In most cases the (E)-allyl isomer c (Scheme 1) was termediate is easier with the CH2OR2 substituent, probably
obtained selectively together with decomposition products. for steric reasons.
The reaction proceeds with electron-poor aryl bromides
Subsequently we studied the reaction of 2-allyloxytetra-
such as 4-bromoacetophenone or 4-bromobenzaldehyde hydropyran with aryl bromides. The THP protecting group
and also with electron-rich aryl bromides such as 4-bromo- gave better results than those obtained with MEM. For ex-
anisole (entries 1–5, Table 1). With two substrates (3-bro- ample, the reaction of 4-bromoacetophenone gave a mix-
mopyridine and 1-bromo-2,4,6-trimethylbenzene) the for- ture of adducts in 91% yield in the presence of 0.01% cata-
mation of the gem-branched a isomer was also observed lyst (entry 1, Table 3). With 4-tert-butylbromobenzene, a
(entries 6 and 7, Table 1). With this protecting group the TON of 34 000 was obtained with THP (entries 10 and 11,
(E)- and (Z)-enol isomers e, f were not observed. These iso- Table 3). Under similar reactions conditions with MEM as
mers are probably unstable under the reactions conditions. protecting group a TON of 40 was obtained. Having dem-
Next we studied the reactivity and the selectivity of the onstrated that 2-allyloxytetrahydropyran can be efficiently
reaction using MEM as protecting group on the allyl reacted with aryl bromides, we investigated the scope of the
alcohol (Table 2). The reaction was possible with a high coupling reaction using substituted aryl bromides and het-
substrate/catalyst ratio in the presence of 4-bromoacetophe- eroaryl bromides. The results presented in Table 3 show a
none (entries 1 and 2, Table 2). On the other hand, with minor substituent effect of the aryl bromide on the reaction
electron-rich aryl bromides lower reaction rates were ob- rate. Electron-withdrawing groups in the aryl bromides sup-
served and 0.4% catalyst was used (entries 3 and 6, Table 2). port the reaction, while electron-donating groups are
In all cases we obtained mixtures of regio- and stereoiso- slightly unfavourable. For example, turnover numbers of
1368
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1367–1377

Heck Reaction of Protected Allyl Alcohols with Aryl Bromides
FULL PAPER
Table 2. Heck reaction with 3-(2-methoxyethoxymethoxy)propene (Scheme 1).
Entry[a]
ArBr
Substrate/catalyst
ratio
gem-Branched a/(Z,E)-branched b/(E)-allyl c/
(Z)-allyl d/(E)-enol e/(Z)-enol f
Product
Yield
[%]
1
2
3
4
5
6
4-MeCOC6H4Br
4-MeCOC6H4Br
4-tBuC6H4Br
4-tBuC6H4Br
4-MeOC6H4Br
2,4,6-Me3C6H2Br
1000
10 000
250
1000
250
0:0:60:0:18:22
0:0:71:0:10:19
0:0:79:0:9:12
0:0:79:0:9:12
1:7:54:0:18:20
0:0:38:0:38:24
9c–f
9c–f
10c–f
10c–f
11a–f
12c–f
88
10[b]
91
32[b]
92
250
86
[a] Conditions: catalyst see ref.[30]; substrate/catalyst ratio calculated with respect to Pd atom; aryl bromide (1 equiv.), 3-(2-methoxyethoxy-
methoxy)propene (1.2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h, isolated yield of the mixture of isomers. [b] GC and NMR conver-
sions.
3300–10 000 can be achieved with this catalyst for activated mers c, d, e and f were obtained with 86–96% selectivity.
substrates such as 4-bromobenzophenone, 4-bromobenzal- Among them the (E)-allyl c isomer was obtained in 52–71%
dehyde, 4-(trifluoromethyl)bromobenzene and 4-bromo- selectivity.
benzonitrile (entries 2–8, Table 3). On the other hand, with
Next, we studied the influence of one ortho substituent
deactivated 4-bromoanisole or 4-(dimethylamino)bromo- on the aryl bromide. 2-Bromoacetophenone led to a lower
benzene, we obtained TONs of 940 and 670, respectively TON (225) than para-substituted bromoacetophenone (en-
(entries 12–14, Table 3). With these substrates the linear iso- try 17, Table 3). 2-Fluorobromobenzene, 2-bromotoluene
Table 3. Heck reaction with 2-allyloxytetrahydropyran (Scheme 1).
Entry[a]
ArBr
Substrate/catalyst
ratio
gem-Branched a/(Z,E)-branched b/(E)-allyl c/
(Z)-allyl d/(E)-enol e/(Z)-enol f
Product
Yield
[%]
1
2
3
4
5
6
7
8
4-MeCOC6H4Br
4-PhCOC6H4Br
4-PhCOC6H4Br
4-HCOC6H4Br
4-CF3C6H4Br
4-CF3C6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-FC6H4Br
4-tBuC6H4Br
10 000
1000
10 000
10 000
1000
10 000
1000
10 000
10 000
10 000
100 000
1000
250
1000
1000
10 000
250
1000
10 000
1000
10 000
100 000
1000
10 000
1000
1000
10 000
1000
10 000
100
1000
5:2:58:5:12:18
1:3:64:0:16:16
1:3:64:0:16:16
4:1:64:2:9:20
5:0:71:2:10:12
5:0:68:2:11:14
4:3:58:2:11:22
4:3:58:2:11:22
8:1:61:2:14:14
7:6:58:2:13:14
7:6:58:2:13:14
10:4:54:2:15:15
8:6:67:6:7:6
13a–f
14a–f
14a–f
15a–f
16a–f
16a–f
17a–f
17a–f
18a–f
19a–f
19a–f
20a–f
21a–f
21a–f
22a–f
22a–f
23a–f
24a–f
24a–f
25c–f
26a–f
26a–f
27c–f
27c–f
28c–f
29c–f
29c–f
30c–f
30c–f
31e–f
31e–f
32a–f
32a–f
33a–f
34a–f
34a–f
35a–f
17a–f
91
88
33[b]
90
93
72[b]
93
82[b]
90
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
94
4-tBuC6H4Br
4-MeOC6H4Br
34[b]
92
4-NMe2C6H4Br
4-NMe2C6H4Br
2-bromo-6-methoxynaphthalene
2-bromo-6-methoxynaphthalene
2-MeCOC6H4Br
2-FC6H4Br
83
9:7:67:3:7:7
6:6:69:3:8:8
8:8:69:3:8:4
67[b]
91
73[b]
90
7:0:61:7:11:14
6:0:36:2:27:29
5:0:41:4:24:26
0:0:59:0:19:22
6:4:36:0:25:29
5:4:44:0:23:24
0:0:17:0:47:36
0:0:16:0:44:40
0:0:34:0:42:34
0:0:45:0:25:30
0:0:56:0:18:26
0:0:6:0:46:48
0:0:6:0:48:46
0:0:0:0:50:50
0:0:0:0:50:50
8:0:62:3:12:15
7:0:57:1:15:20
7:0:67:5:8:13
9:0:60:7:14:10
10:0:59:8:11:12
21:9:64:0:3:3
6:1:55:0:14:24
94
2-FC6H4Br
2-MeC6H4Br
1-bromonaphthalene
1-bromonaphthalene
2,6-F2C6H3Br
88[b]
92
92
57[b]
94
2,6-F2C6H3Br
86[b]
88
2,4,6-Me3C6H2Br
2,6-Et2-4-MeC6H2Br
2,6-Et2-4-MeC6H2Br
9-bromoanthracene
9-bromoanthracene
2,4,6-iPr3C6H2Br
2,4,6-iPr3C6H2Br
3-bromopyridine
3-bromopyridine
3-bromoquinoline
2-bromothiophene
2-bromothiophene
3-bromothiophene
4-CN-C6H4Cl
87
33[b]
88
78[b]
79
55[b]
90
10 000
100 000
10 000
250
1000
10 000
250
29[b]
92
85
75[b]
86
64
[a] Conditions: catalyst see ref.[30]; substrate/catalyst ratio calculated with respect to Pd atom; aryl bromide (1 equiv.), 2-allyloxytetra-
hydropyran (2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h, isolated yield of the mixture of isomers. [b] GC and NMR conversions.
Eur. J. Org. Chem. 2005, 1367–1377
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1369

F. Berthiol, H. Doucet, M. Santelli
FULL PAPER
or 1-bromonaphthalene led to higher TONs of 920–57 000, to 84% of these two enol isomers was obtained (entries 6
thus indicating that the low TON obtained with 2-bromo- and 7, Table 4). In most cases, only traces of the branched
acetophenone does not comes from steric reasons, but is isomer were detected. The reaction also proceeds in good
more likely due to poisoning of the catalyst. We then yield with heteroaromatic substrates (entries 10–15,
studied the reactivity of di-ortho-substituted aryl bromides. Table 4).
Even in the presence of highly congested substrates such as
Finally, we performed several reactions with 3-butoxy-
9-bromoanthracene, 2,4,6-trimethylbromobenzene or 2,6- propene and 2-allyloxyethanol (Table 5 and Table 6). With
diethyl-4-methylbromobenzene satisfactory TONs were ob- these two substituents on the allyl alcohol the deprotection
tained (1000–7800; entries 25–29, Table 3). A very high re- of the allyl isomers c and d to give cinnamyl derivatives
gioselectivity (94%) in favour of formation of the isomers e should be not simple. However, the deprotection of the en-
and f was observed in the presence of 9-bromoanthracene. ols e and f should be easy and would lead selectively to the
This selectivity in favour of the formation of the isomers e aldehydes. In the presence of 4-bromoacetophenone, 4-tert-
and f was complete (100%) with 1-bromo-2,4,6-triisoprop- butylbromobenzene or 4-bromoanisole, 3-butoxypropene
ylbenzene but a lower TON was obtained (550; entries 25– gave the expected mixture of products in good yields with
29, Table 3). We also studied the reactivity of heteroaryl high substrate/catalyst ratios (Table 5). The two enol iso-
bromides. Pyridines are π-electron-deficient heterocycles, mers e and f were obtained with 42–65% selectivity. 2-Allyl-
whereas thiophenes and furans are rich in π-electrons. Oxi- oxyethanol is a commercially available and very cheap sub-
dative addition to palladium should be faster with π-elec- stituted allyl alcohol. We observed that this alkene also re-
tron-deficient heterocycles; however, we observed similar re- acts with aryl bromides (Table 6). The best selectivity in fav-
action rates with 3-bromopyridine, 3-bromoquinoline and our of the formation of the enol isomers e and f (73%) was
3-bromothiophene (entries 32–34 and 37, Table 3). These obtained with the electron-poor aryl bromide 4-bromoace-
observations suggest that the oxidative addition of the aryl tophenone.
or heteroaryl bromide is not the rate-limiting step of the
reaction with this catalyst. On the other hand the TON ob-
tained for the reaction with 2-bromothiophene (750) indi-
cates that with this α-substituted heteroaryl bromide, a pos-
Conclusions
sible interaction between the hetero element and the palla-
dium complex seems to be deleterious for the reaction (en- dium system is an efficient catalyst for the reaction of pro-
tries 35 and 36, Table 3). tected allyl alcohols with aryl bromides. In the presence of
In summary, we have established that the Tedicyp–palla-
Benzyl groups are also very useful protecting groups in allyloxytrimethylsilane, decomposition of the products was
organic synthesis, so we performed a few reactions with al- observed. Better results were obtained with allyloxy-tert-bu-
lyl benzyl ether (Table 4). The reactions rates using this allyl tyldimethylsilane as alkene. The cinnamyl derivatives were
ether are similar to those observed with 2-allyloxytetra- obtained selectively, although in low yields in some cases,
hydropyran. 4-Bromoacetophenone and 4-tert-butylbro- due to partial decomposition of the products. The use of
mobenzene led to the expected mixtures of adducts in good MEM, THP and Bn as protecting groups led to the ex-
yields in the presence of 0.01–0.001% catalyst (entries 1–4, pected adducts, but higher substrate/catalyst ratios were
Table 4). The selectivities are slightly different than with needed with THP or Bn as protecting groups. Both the ste-
THP as protecting group − larger amounts of (E)-enol e ric hindrance and the electronic properties of the aryl bro-
and (Z)-enol f were observed. With 2-bromobenzonitrile up mide have an effect on the reaction rates and the selectivi-
Table 4. Heck reaction with allyloxymethylbenzene (Scheme 1).
Entry[a]
ArBr
Substrate/catalyst
ratio
gem-Branched a/(Z,E)-branched b/(E)-allyl c/
(Z)-allyl d/(E)-enol e/(Z)-enol f
Product
Yield
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
4-MeCOC6H4Br
4-MeCOC6H4Br
4-tBuC6H4Br
4-tBuC6H4Br
4-MeOC6H4Br
2-CNC6H4Br
10 000
100 000
10 000
100 000
10 000
250
1000
250
1000
10 000
100 000
250
1000
250
0:0:35:10:22:33
1:0:32:14:20:33
0:0:47:0:23:30
0:0:52:0:23:25
7:2:50:3:20:18
2:0:14:0:37:47
1:3:15:4:35:42
0:0:40:0:31:29
0:0:34:0:36:30
7:0:36:2:22:33
4:0:32:0:27:37
0:0:46:8:22:24
0:0:48:9:20:23
0:0:44:0:25:31
0:0:44:0:21:35
36c–f
36a–f
37c–f
37c–f
38a–f
39a–f
39a–f
40c–f
40c–f
41a–f
41a–f
42c–f
42c–f
43c–f
43c–f
92
36[b]
90
87[b]
91
89
2-CNC6H4Br
50[b]
87
2,4,6-Me3C6H2Br
2,4,6-Me3C6H2Br
3-bromopyridine
3-bromopyridine
2-bromothiophene
2-bromothiophene
3-bromothiophene
3-bromothiophene
34[b]
92
27[b]
89
75[b]
89
1000
68[b]
[a] Conditions: catalyst see ref.[30]; substrate/catalyst ratio calculated with respect to Pd atom; aryl bromide (1 equiv.), allyloxymethylben-
zene (2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h, isolated yield of the mixture of isomers. [b] GC and NMR conversions.
1370
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1367–1377

Heck Reaction of Protected Allyl Alcohols with Aryl Bromides
Table 5. Heck reaction with 3-butoxypropene (Scheme 1).
FULL PAPER
Entry[a]
ArBr
Substrate/catalyst
ratio
gem-Branched a/(Z,E)-branched b/(E)-allyl c/
(Z)-allyl d/(E)-enol e/(Z)-enol f
Product
Yield
[%]
1
2
3
4
5
6
7
8
4-MeCOC6H4Br
4-MeCOC6H4Br
4-tBuC6H4Br
1000
10 000
1000
10 000
10 000
100 000
100
5:3:37:0:24:31
5:3:37:0:24:31
8:4:37:0:26:25
8:4:41:2:24:21
10:3:47:1:22:17
12:3:41:2:23:19
4:0:38:0:28:30
3:0:32:0:34:31
44a–f
44a–f
45a–f
45a–f
46a–f
46a–f
47a–f
47a–f
93
77[b]
90
4-tBuC6H4Br
82[b]
92
4-MeOC6H4Br
4-MeOC6H4Br
2,4,6-Me3C6H2Br
2,4,6-Me3C6H2Br
27[b]
89
250
48[b]
[a] Conditions: catalyst see ref.[30]; substrate/catalyst ratio calculated with respect to Pd atom; aryl bromide (1 equiv.), 3-butoxypropene
(2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h, isolated yield of the mixture of isomers. [b] GC and NMR conversions.
Table 6. Heck reaction with 2-allyloxyethanol (Scheme 1).
Entry[a]
ArBr
Substrate/catalyst
ratio
gem-Branched a/(Z,E)-branched b/(E)-allyl c/
(Z)-allyl d/(E)-enol e/(Z)-enol f
Product
Yield
[%]
1
2
3
4
5
6
7
4-MeCOC6H4Br
4-MeCOC6H4Br
4-tBuC6H4Br
1000
10 000
1000
10 000
1000
10 000
50
2:0:25:0:33:40
2:0:25:0:33:40
1:13:32:0:26:28
1:13:32:0:26:28
2:18:32:0:22:26
2:18:32:0:22:26
70:0:0:0:22:8
48a–f
48a–f
49a–f
49a–f
50a–f
50a–f
51a–f
83
13[b]
84
4-tBuC6H4Br
73[b]
100[b]
80
4-MeOC6H4Br
4-MeOC6H4Br
2,4,6-Me3C6H2Br
38[c]
[a] Conditions: catalyst see ref.[30]; substrate/catalyst ratio calculated with respect to Pd atom; aryl bromide (1 equiv.), 2-allyloxyethanol
(2 equiv.), K2CO3 (2 equiv.), DMF, 130 °C, 20 h, isolated yield of the mixture of isomers. [b] GC and NMR conversions. [c] The formation
of mesitylene was also observed.
= 77 ppm for 13C). Flash chromatography was performed on silica
ties, but even the o,o-disubstituted aryl bromide substrates
gel (230–400 mesh). GC and NMR conversions in the tables are
provide the desired products. In most cases the linear iso-
conversions of the aryl halides into the mixture of products calcu-
mers were obtained with high selectivity (70–100%). The
lated by GC and from the 1H NMR spectrum of the crude mix-
ratio between the cinnamyl and enol isomers depends on
tures. Ratios of regio- and stereoisomers were determined by GC
the protecting group and the substituents on the aryl bro-
and NMR spectroscopy.
mide. In the course of these reactions, only minor variations
General Procedure for the Coupling of Protected Alk-1-en-3-ols with
Aryl Bromides: Treatment of a mixture of the aryl bromide
(10 mmol) and K2CO3 (2.76 g, 20 mmol) with the protected allyl
alcohol (12–20 mmol) at the appropriate temperature for 20 h in
DMF (10 mL) in the presence of the Tedicyp-palladium complex
(see Tables 1–6 for the substrate/catalyst ratio and other experimen-
tal conditions) under argon afforded the corresponding mixture of
products after addition of water, extraction with dichloromethane
or diethyl ether, separation, drying (MgSO4), evaporation and fil-
tration through silica gel. The major isomer was purified by
chromatography on silica gel.
of the proportions of isomers formed were observed. With
sterically congested aryl bromides larger amounts of the
enol isomers were observed. Several reactions were per-
formed with as little as 0.01% catalyst. Due to the high
price of palladium, the practical advantage of such low cat-
alyst loadings can become increasingly important for indus-
trial processes. The functional group tolerance is remark-
able: substituents such as fluoro, trifluoromethyl, methyl,
methoxy, acetyl, formyl, benzoyl, dimethylamino and nitrile
on the aryl bromide have been used successfully. Even
though mixtures of isomers are generally obtained, this pro-
cedure should be a powerful method to access 3-arylpro-
pionaldehyde and 3-arylpropan-1-ol derivatives by hydro-
genation of the mixture of isomers.
(E)-1-(4-Acetylphenyl)-3-(tert-butyldimethylsilanyloxy)propene (1c):
1H NMR: δ = 0.10 (s, 6 H, MeSi), 0.93 (s, 9 H, tBuSi), 2.58 (s, 3
H, MeCO), 4.37 (dd, J = 4.6, 1.7 Hz, 2 H, CH2), 6.41 (dt, J = 15.9,
4.6 Hz, 1 H, CH=), 6.65 (d, J = 15.9 Hz, 1 H, CH=), 7.44 (d, J =
8.4 Hz, 2 H, Ar), 7.90 (d, J = 8.4 Hz, 2 H, Ar) ppm. 13C NMR: δ
= –5.23, 18.4, 25.9, 26.54, 63.5, 126.4, 128.1, 128.7, 132.3, 135.8,
141.9, 197.6 ppm. C17H26O2Si (290.5): calcd. C 70.29, H 9.02;
found C 70.47, H 8.87. MS (EI, 70 eV): m/z (%) = 290 (2) [M+].
Experimental Section
General Remarks: All reactions were run under argon using stan-
dard Schlenk techniques. Analytical grade DMF was used as re-
ceived. Potassium carbonate (99+) was used without drying. The
reactions were followed by GC and NMR spectroscopy for high-
boiling-point substrates and by GC for low-boiling-point sub-
strates. GC/mass spectra were recorded with a Varian Saturn 2100T
spectrometer. 1H and 13C NMR spectra were recorded with a
Bruker 300 MHz spectrometer in CDCl3 solutions. Chemical shift
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(4-formylphenyl)propene (2c):
1H NMR: δ = 0.10 (s, 6 H, MeSi), 0.94 (s, 9 H, tBuSi), 4.38 (dd, J
= 4.5, 1.8 Hz, 2 H, CH2), 6.45 (dt, J = 15.9, 4.5 Hz, 1 H, CH=),
6.67 (dt, J = 15.9, 1.8 Hz, 1 H, CH=), 7.51 (d, J = 8.2 Hz, 2 H,
Ar), 7.82 (d, J = 8.2 Hz, 2 H, Ar), 9.96 (s, 1 H, CHO) ppm. 13C
NMR: δ = –5.24, 18.4, 25.9, 63.5, 126.8, 128.0, 130.1, 133.1, 135.2,
143.3, 191.7 ppm. C16H24O2Si (276.4): calcd. C 69.51, H 8.75;
found C 69.24, H 8.61. MS (EI, 70 eV): m/z (%) = 276 (1) [M+].
1
are reported in ppm relative to CDCl3 (δ = 7.25 ppm for H and δ
Eur. J. Org. Chem. 2005, 1367–1377
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1371

F. Berthiol, H. Doucet, M. Santelli
FULL PAPER
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(4-trifluoromethylphenyl)pro-
pene (3c): H NMR: δ = 0.11 (s, 6 H, MeSi), 0.94 (s, 9 H, tBuSi),
Characteristic bands of isomer 9e: δ = 5.21 (dt, J = 12.3, 7.4 Hz, 1
H, CH=), 6.35 (dt, J = 12.3, 1.2 Hz, 1 H, CH=) ppm; 9f: δ = 4.67
(dt, J = 7.5, 6.2 Hz, 1 H, CH=), 6.29 (dt, J = 6.2, 1.4 Hz, 1 H,
CH=) ppm.
1
4.37 (dd, J = 4.6, 1.6 Hz, 2 H, CH2), 6.37 (dt, J = 15.9, 4.6 Hz, 1
H, CH=), 6.64 (d, J = 15.9 Hz, 1 H, CH=), 7.46 (d, J = 8.2 Hz, 2
H, Ar), 7.57 (d, J = 8.2 Hz, 2 H, Ar) ppm. 13C NMR: δ = –5.2,
(E)-1-(4-tert-Butylphenyl)-3-(2-methoxyethoxymethoxy)propene
3
18.5, 26.0, 63.5, 124.7 (q, JC,F = 271.3 Hz), 125.5 (q, JC,F
=
1
(10c): H NMR: δ = 1.30 (s, 9 H, Me), 3.40 (s, 3 H, CH3), 3.58 (t,
4.0 Hz), 126.5, 127.9, 129.1 (q, 2JC,F = 32.7 Hz), 132.0, 140.7 ppm.
C16H23F3OSi (316.4): calcd. C 60.73, H 7.33; found C 60.99, H
7.48. MS (EI, 70 eV): m/z (%) = 316 (1) [M+].
J = 4.7 Hz, 2 H, CH2), 3.73 (t, J = 4.7 Hz, 2 H, CH2), 4.24 (dd, J
= 6.3, 1.4 Hz, 2 H, CH2), 4.78 (s, 2 H, CH2), 6.24 (dt, J = 15.9,
6.3 Hz, 1 H, CH=), 6.60 (d, J = 15.9 Hz, 1 H, CH=), 7.35 (m, 4
H, Ar) ppm. 13C NMR: δ = 31.3, 34.6, 59.0, 66.9, 68.0, 71.8, 94.6,
124.7, 125.5, 126.2, 132.5, 133.9, 150.8 ppm. C17H26O3 (278.4):
calcd. C 73.34, H 9.41; found C 73.12, H 9.24. MS (EI, 70 eV):
m/z (%) = 189 (90) [M+ – 89]. Characteristic bands of isomer 10e:
δ = 5.22 (dt, J = 12.3, 6.5 Hz, 1 H, CH=), 6.31 (d, J = 12.3 Hz, 1
H, CH=) ppm; 10f: δ = 4.71 (q, J = 6.4 Hz, 1 H, CH=), 6.25 (d,
J = 6.4 Hz, 1 H, CH=) ppm.
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(4-tert-butylphenyl)propene
1
(4c): H NMR: δ = 0.11 (s, 6 H, MeSi), 0.95 (s, 9 H, tBuSi), 1.32
(s, 9 H, Me), 4.35 (dd, J = 5.1, 1.6 Hz, 2 H, CH2), 6.25 (dt, J =
15.8, 5.1 Hz, 1 H, CH=), 6.57 (dt, J = 15.8, 1.6 Hz, 1 H, CH=),
7.33 (m, 4 H, Ar) ppm. 13C NMR: δ = –5.1, 18.5, 26.0, 31.3, 34.5,
64.0, 125.4, 126.1, 128.4, 129.3, 134.3, 150.4 ppm. C19H32OSi
(304.5): calcd. C 74.93, H 10.59; found C 74.87, H 10.41. MS (EI,
70 eV): m/z (%) = 304 (2) [M+].
(E)-3-(2-Methoxyethoxymethoxy)-1-(4-methoxyphenyl)propene
1
(11c): H NMR: δ = 3.39 (s, 3 H, CH3), 3.58 (t, J = 4.8 Hz, 2 H,
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(4-methoxyphenyl)propene
1
CH2), 3.73 (t, J = 4.8 Hz, 2 H, CH2), 3.77 (s, 3 H, MeO), 4.22 (dd,
J = 6.2, 1.3 Hz, 2 H, CH2), 4.78 (s, 2 H, CH2), 6.14 (dt, J = 15.9,
6.2 Hz, 1 H, CH=), 6.56 (d, J = 15.9 Hz, 1 H, CH=), 6.84 (d, J =
8.8 Hz, 2 H, Ar), 7.31 (d, J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR: δ
= 55.2, 59.0, 66.9, 68.1, 71.8, 94.6, 114.0, 123.3, 127.7 (2 C), 132.4,
159.3 ppm. MS (EI, 70 eV): m/z (%) = 252 (2) [M+]. Compound
11c was characterised by deprotection.[43] Characteristic bands of
isomer 11a: δ = 5.26 (d, J = 1.1 Hz, 1 H, CH=), 5.43 (d, J = 1.1 Hz,
1 H, CH=) ppm; 11b: δ = 6.58 (q, J = 1.4 Hz, 1 H, CH=) ppm;
11e: δ = 5.21 (dt, J = 12.4, 7.5 Hz, 1 H, CH=), 6.29 (dt, J = 12.4,
1.3 Hz, 1 H, CH=) ppm; 11f: δ = 4.69 (dt, J = 7.5, 6.3 Hz, 1 H,
CH=), 6.24 (dt, J = 6.3, 1.5 Hz, 1 H, CH=) ppm.
(5c): H NMR: δ = 0.10 (s, 6 H, MeSi), 0.93 (s, 9 H, tBuSi), 3.80
(s, 3 H, MeO), 4.32 (dd, J = 5.3, 1.6 Hz, 2 H, CH2), 6.14 (dt, J =
15.8, 5.3 Hz, 1 H, CH=), 6.52 (d, J = 15.8 Hz, 1 H, CH=), 6.84 (d,
J = 9.0 Hz, 2 H, Ar), 7.31 (d, J = 9.0 Hz, 2 H, Ar) ppm. Compound
5c was characterised by deprotection.[46]
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(2,4,6-trimethylphenyl)pro-
1
pene (6c): H NMR: δ = 0.12 (s, 6 H, MeSi), 0.95 (s, 9 H, tBuSi),
2.27 (s, 9 H, Me), 4.38 (dd, J = 4.9, 1.8 Hz, 2 H, CH2), 5.79 (dt, J
= 16.1, 4.9 Hz, 1 H, CH=), 6.55 (d, J = 16.1 Hz, 1 H, CH=), 6.86
(s, 2 H, Ar) ppm. 13C NMR: δ = –5.13, 18.4, 20.2, 20.9, 25.9, 64.0,
126.8, 127.9, 128.5, 133.8, 133.9, 135.9 ppm. MS (EI, 70 eV): m/z
(%) = 290 (2) [M+]. Compound 6c was characterised by deprotec-
tion.[43] Characteristic bands of isomer 6a: δ = 4.92 (d, J = 2.1 Hz,
1 H, CH=), 5.60 (d, J = 2.1 Hz, 1 H, CH=) ppm.
(E)-3-(2-Methoxyethoxymethoxy)-1-(2,4,6-trimethylphenyl)propene
1
(12c): H NMR: δ = 2.26 (s, 9 H, Me), 3.40 (s, 3 H, CH3), 3.58 (t,
J = 4.6 Hz, 2 H, CH2), 3.75 (t, J = 4.6 Hz, 2 H, CH2), 4.27 (dd, J
= 6.0, 1.3 Hz, 2 H, CH2), 4.81 (s, 2 H, CH2), 5.77 (dt, J = 16.3,
6.0 Hz, 1 H, CH=), 6.57 (d, J = 15.9 Hz, 1 H, CH=), 6.85 (s, 2 H,
Ar) ppm. 13C NMR: δ = 20.9 (3C), 59.0, 66.9, 68.2, 71.8, 94.5,
128.5, 130.4, 130.5, 133.5, 135.8, 136.2 ppm. MS (EI, 70 eV): m/z
(%) = 175 (100) [M+ – 89]. Compound 12c was characterised by
deprotection.[44] Characteristic bands of isomer 12e: δ = 5.10 (dt, J
= 12.5, 6.3 Hz, 1 H, CH=), 6.10 (dt, J = 12.5, 1.3 Hz, 1 H, CH=)
ppm; 12f: δ = 4.40 (q, J = 7.0 Hz, 1 H, CH=), 6.18 (dt, J = 6.2,
1.7 Hz, 1 H, CH=) ppm.
1
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(3-pyridyl)propene (7c): H
NMR: δ = 0.11 (s, 6 H, MeSi), 0.94 (s, 9 H, tBuSi), 4.36 (dd, J =
4.6, 1.8 Hz, 2 H, CH2), 6.36 (dt, J = 15.9, 4.6 Hz, 1 H, CH=), 6.59
(dt, J = 15.9, 1.8 Hz, 1 H, CH=), 7.22 (dd, J = 8.0, 4.0 Hz, 1 H,
Ar), 7.67 (d, J = 8.0 Hz, 1 H, Ar), 8.44 (d, J = 4.0 Hz, 1 H, Ar),
8.58 (s, 1 H, Ar) ppm. 13C NMR: δ = –5.23, 18.4, 25.9, 63.5, 123.4,
125.6, 131.6, 132.7, 132.8, 148.3, 148.4 ppm. C14H23NOSi (249.4):
calcd. C 67.42, H 9.29; found C 67.70, H 9.42. MS (EI, 70 eV):
m/z (%) = 249 (1) [M+]. Characteristic bands of isomer 7a: δ = 4.50
(d, J = 1.4 Hz, 1 H, CH=), 5.45 (d, J = 1.4 Hz, 1 H, CH=) ppm.
(E)-1-(4-Acetylphenyl)-3-(tetrahydropyran-2-yloxy)propene (13c):
1H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 2.56 (s, 3 H, MeCO), 3.40–
3.60 (m, 1 H, CH2O), 3.80–4.00 (m, 1 H, CH2O), 4.18 (ddd, J =
13.5, 6.0, 1.0 Hz, 1 H, CH2CH=), 4.38 (ddd, J = 13.5, 5.1, 1.4 Hz,
1 H, CH2CH=), 4.69 (t, J = 3.3 Hz, 1 H, CH), 6.42 (dt, J = 15.9,
5.3 Hz, 1 H, CH=), 6.65 (d, J = 15.9 Hz, 1 H, CH=), 7.44 (d, J =
8.3 Hz, 2 H, Ar), 7.88 (d, J = 8.3 Hz, 2 H, Ar) ppm. 13C NMR: δ
= 19.4, 25.3, 26.5, 30.5, 62.2, 67.3, 98.1, 126.4, 128.6, 129.2, 130.6,
136.0, 141.4, 197.4 ppm. C16H20O3 (260.3): calcd. C 73.82, H 7.74;
found C 73.74, H 7.65. MS (EI, 70 eV): m/z (%) = 260 (5) [M+].
Characteristic bands of isomer 13a: δ = 5.40 (d, J = 1.3 Hz, 1 H,
CH=), 5.54 (d, J = 1.3 Hz, 1 H, CH=) ppm; 13b: δ = 6.82 (q, J =
1.2 Hz, 1 H, CH=) ppm; 13d: δ = 5.90 (dt, J = 12.1, 6.5 Hz, 1 H,
CH=), 6.92 (d, J = 12.1 Hz, 1 H, CH=) ppm; 13e: δ = 5.14 (dt, J
= 12.4, 7.6 Hz, 1 H, CH=), 6.37 (d, J = 12.4 Hz, 1 H, CH=) ppm;
13f: δ = 4.67 (q, J = 6.3 Hz, 1 H, CH=), 6.33 (dt, J = 6.3, 1.3 Hz,
1 H, CH=) ppm.
1
(E)-3-(tert-Butyldimethylsilanyloxy)-1-(3-quinolyl)propene (8c): H
NMR: δ = 0.13 (s, 6 H, MeSi), 0.96 (s, 9 H, tBuSi), 4.41 (dd, J =
4.5, 1.6 Hz, 2 H, CH2), 6.51 (dt, J = 15.9, 4.5 Hz, 1 H, CH=), 6.76
(dt, J = 15.9, 1.6 Hz, 1 H, CH=), 7.53 (dd, J = 8.0, 1.2 Hz, 1 H,
Ar), 7.64 (d, J = 8.0 Hz, 1 H, Ar), 7.8 (dd, J = 8.0, 1.2 Hz, 1 H,
Ar), 7.98–8.15 (m, 2 H, Ar), 8.99 (d, J = 2.1 Hz, 1 H, Ar) ppm.
13C NMR: δ = –5.22, 18.4, 25.9, 63.6, 125.9, 126.8, 127.7, 128.0,
129.0, 129.2, 130.0, 131.7, 132.3, 147.4, 149.4 ppm. C18H25NOSi
(299.5): calcd. C 72.19, H 8.41; found C 72.04, H 8.57. MS (EI,
70 eV): m/z (%) = 299 (1) [M+].
(E)-1-(4-Acetylphenyl)-3-(2-methoxyethoxymethoxy)propene (9c):
1H NMR: δ = 2.56 (s, 3 H, MeCO), 3.38 (s, 3 H, CH3), 3.57 (t, J
= 4.4 Hz, 2 H, CH2), 3.72 (t, J = 4.4 Hz, 2 H, CH2), 4.27 (dd, J =
5.6, 1.3 Hz, 2 H, CH2), 4.78 (s, 2 H, CH2), 6.40 (dt, J = 15.9,
5.6 Hz, 1 H, CH=), 6.66 (d, J = 15.9 Hz, 1 H, CH=), 7.43 (d, J =
8.4 Hz, 2 H, Ar), 7.89 (d, J = 8.4 Hz, 2 H, Ar) ppm. 13C NMR: δ
= 26.5, 59.0, 66.9, 67.7, 71.8, 94.9, 126.5, 128.7 (2 C), 131.0, 136.1,
141.3, 197.4 ppm. C15H20O4 (264.3): calcd. C 68.16, H 7.63; found
(E)-1-(4-Benzoylphenyl)-3-(tetrahydropyran-2-yloxy)propene (14c):
1H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
C 68.40, H 7.51. MS (EI, 70 eV): m/z (%) = 264 (20) [M+ – 89]. 3.80–4.00 (m, 1 H, CH2O), 4.16 (ddd, J = 13.4, 6.1, 1.1 Hz, 1 H,
1372
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1367–1377

Heck Reaction of Protected Allyl Alcohols with Aryl Bromides
FULL PAPER
CH2CH=), 4.44 (ddd, J = 13.4, 5.1, 1.4 Hz, 1 H, CH2CH=), 4.70
(t, J = 3.3 Hz, 1 H, CH), 6.44 (dt, J = 15.9, 5.6 Hz, 1 H, CH=),
3.80–4.00 (m, 1 H, CH2O), 4.13 (ddd, J = 12.9, 6.6, 1.2 Hz, 1 H,
CH2CH=), 4.37 (ddd, J = 12.9, 5.6, 1.2 Hz, 1 H, CH2CH=), 4.69
6.65 (d, J = 15.9 Hz, 1 H, CH=), 7.39–7.61 (m, 5 H, Ar), 7.71–7.81 (t, J = 3.3 Hz, 1 H, CH), 6.22 (dt, J = 15.9, 6.1 Hz, 1 H, CH=),
(m, 4 H, Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.5, 62.2, 67.3, 98.0,
6.58 (d, J = 15.9 Hz, 1 H, CH=), 7.01 (m, 2 H, Ar), 7.35 (m, 2 H,
126.2, 128.2, 129.1, 129.8, 130.5, 130.7, 132.2, 136.3, 137.7, 140.9,
Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.6, 62.2, 67.5, 97.9, 115.4 (d,
196.0 ppm. C21H22O3 (322.4): calcd. C 78.23, H 6.88; found C 2JC,F = 31.6 Hz), 125.7 (d, JC,F = 2.2 Hz), 127.9 (d, JC,F
=
5
3
78.03, H 6.96. MS (EI, 70 eV): m/z (%) = 322 (5) [M+]. Characteris-
tic bands of isomer 14a: δ = 5.42 (s, 1 H, CH=), 5.57 (s, 1 H, CH=)
8.0 Hz), 131.0, 132.9 (d, 4JC,F = 3.3 Hz), 162.3 (d, JC,F = 246.7 Hz)
ppm. MS (EI, 70 eV): m/z (%) = 236 (1) [M+]. Compound 18c was
ppm; 14b: δ = 6.85 (q, J = 1.2 Hz, 1 H, CH=) ppm; 14e: δ = 5.17 characterised by deprotection.[45] Characteristic bands of isomer
(dt, J = 12.2, 7.6 Hz, 1 H, CH=), 6.40 (d, J = 12.2 Hz, 1 H, CH=) 18a: δ = 5.36 (d, J = 1.3 Hz, 1 H, CH=), 5.46 (d, J = 1.3 Hz, 1 H,
ppm; 14f: δ = 4.63 (q, J = 6.3 Hz, 1 H, CH=), 6.27 (d, J = 6.3 Hz,
1 H, CH=) ppm.
CH=) ppm; 18b: δ = 6.65 (q, J = 1.3 Hz, 1 H, CH=) ppm; 18d: δ
= 5.85 (dt, J = 11.7, 6.3 Hz, 1 H, CH=), 6.54 (d, J = 11.7 Hz, 1 H,
CH=) ppm; 18e: δ = 5.23 (dt, J = 12.2, 7.6 Hz, 1 H, CH=), 6.35
(dt, J = 12.2, 1.3 Hz, 1 H, CH=) ppm; 18f: δ = 4.67 (q, J = 6.4 Hz,
1 H, CH=), 6.29 (dt, J = 6.4, 1.3 Hz, 1 H, CH=) ppm.
(E)-1-(4-Formylphenyl)-3-(tetrahydropyran-2-yloxy)propene (15c):
1H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–4.00 (m, 1 H, CH2O), 4.17 (ddd, J = 13.7, 6.0, 1.1 Hz, 1 H,
CH2CH=), 4.44 (ddd, J = 13.7, 5.1, 1.6 Hz, 1 H, CH2CH=), 4.70
(t, J = 3.2 Hz, 1 H, CH), 6.46 (dt, J = 15.9, 5.8, 5.1 Hz, 1 H, CH=),
6.69 (d, J = 15.9 Hz, 1 H, CH=), 7.52 (d, J = 8.3 Hz, 2 H, Ar),
7.81 (d, J = 8.3 Hz, 2 H, Ar), 9.96 (s, 1 H, CHO) ppm. 13C NMR:
δ = 20.2, 26.2, 31.3, 63.1, 68.0, 98.9, 127.7, 130.9, 130.8, 131.3,
136.2, 143.7, 192.5 ppm. C15H18O3 (246.3): calcd. C 73.15, H 7.37;
found C 72.97, H 7.29. MS (EI, 70 eV): m/z (%) = 246 (5) [M+].
Characteristic bands of isomer 15a: δ = 5.53 (s, 1 H, CH=), 5.65
(s, 1 H, CH=) ppm; 15b: δ = 6.94 (q, J = 1.3 Hz, 1 H, CH=) ppm;
15e: δ = 5.22 (dt, J = 12.4, 7.6 Hz, 1 H, CH=), 6.38 (d, J = 12.4 Hz,
1 H, CH=) ppm; 15f: δ = 4.68 (q, J = 6.3 Hz, 1 H, CH=), 6.36 (d,
J = 6.3 Hz, 1 H, CH=) ppm.
(E)-1-(4-tert-Butylphenyl)-3-(tetrahydropyran-2-yloxy)propene
1
(19c): H NMR: δ = 1.31 (s, 9 H, Ar), 1.40–2.00 (m, 6 H, CH2),
3.45–3.60 (m, 1 H, CH2O), 3.80–4.00 (m, 1 H, CH2O), 4.13 (ddd,
J = 12.6, 6.6, 1.2 Hz, 1 H, CH2CH=), 4.37 (ddd, J = 12.6, 5.5,
1.5 Hz, 1 H, CH2CH=), 4.70 (t, J = 3.4 Hz, 1 H, CH), 6.18 (dt, J
= 15.9, 5.8 Hz, 1 H, CH=), 6.56 (d, J = 15.9 Hz, 1 H, CH=), 7.33
(m, 4 H, Ar) ppm. 13C NMR: δ = 19.5, 25.5, 30.6, 31.3, 34.5, 62.2,
67.7, 97.7, 125.2, 125.4, 126.2, 132.2, 134.0, 150.7 ppm. C18H26O2
(274.4): calcd. C 78.79, H 9.55; found C 78.58, H 9.61. MS (EI,
70 eV): m/z (%) = 274 (1) [M+]. Characteristic bands of isomer 19a:
δ = 5.28 (d, J = 1.5 Hz, 1 H, CH=), 5.44 (d, J = 1.5 Hz, 1 H, CH=)
ppm; 19b: δ = 6.67 (q, J = 1.5 Hz, 1 H, CH=) ppm; 19d: δ = 5.76
(dt, J = 12.1, 6.3 Hz, 1 H, CH=), 6.85 (d, J = 12.1 Hz, 1 H, CH=)
ppm; 19e: δ = 5.22 (dt, J = 12.4, 7.6 Hz, 1 H, CH=), 6.32 (dt, J =
12.4, 0.8 Hz, 1 H, CH=) ppm; 19f: δ = 4.67 (q, J = 6.3 Hz, 1 H,
CH=), 6.25 (dt, J = 6.3, 1.5 Hz, 1 H, CH=) ppm.
(E)-3-(Tetrahydropyran-2-yloxy)-1-(4-trifluoromethylphenyl)propene
1
(16c): H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H,
CH2O), 3.80–4.00 (m, 1 H, CH2O), 4.17 (ddd, J = 13.4, 6.1, 1.2 Hz,
1 H, CH2CH=), 4.40 (ddd, J = 13.4, 5.1, 1.2 Hz, 1 H, CH2CH=),
4.70 (t, J = 3.3 Hz, 1 H, CH), 6.40 (dt, J = 15.9, 5.7 Hz, 1 H,
CH=), 6.40 (d, J = 15.9 Hz, 1 H, CH=), 7.46 (d, J = 8.3 Hz, 2 H,
(E)-1-(4-Methoxyphenyl)-3-(tetrahydropyran-2-yloxy)propene (20c):
1H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.45–3.60 (m, 1 H, CH2O),
3.78 (s, 3 H, MeO), 3.80–4.00 (m, 1 H, CH2O), 4.13 (ddd, J = 12.6,
6.8, 1.5 Hz, 1 H, CH2CH=), 4.37 (ddd, J = 12.6, 5.8, 1.3 Hz, 1 H,
CH2CH=), 4.70 (t, J = 3.5 Hz, 1 H, CH), 6.18 (dt, J = 15.9, 5.8 Hz,
1 H, CH=), 6.56 (d, J = 15.9 Hz, 1 H, CH=), 6.83 (d, J = 8.7 Hz,
2 H, Ar), 7.32 (d, J = 8.7 Hz, 2 H, Ar) ppm. 13C NMR: δ = 19.4,
25.4, 30.6, 55.1, 62.1, 67.7, 97.7, 113.8, 123.6, 127.6, 129.5, 132.0,
159.1 ppm. MS (EI, 70 eV): m/z (%) = 248 (5) [M+]. Compound
20c was characterised by deprotection.[43] Characteristic bands of
isomer 20a: δ = 5.29 (d, J = 1.3 Hz, 1 H, CH=), 5.44 (d, J = 1.3 Hz,
1 H, CH=) ppm; 20b: δ = 6.62 (q, J = 1.3 Hz, 1 H, CH=) ppm;
20d: δ = 5.77 (dt, J = 11.9, 6.3 Hz, 1 H, CH=), 6.77 (d, J = 11.9 Hz,
1 H, CH=) ppm; 20e: δ = 5.24 (dt, J = 12.2, 7.6 Hz, 1 H, CH=),
6.33 (dt, J = 12.2, 0.8 Hz, 1 H, CH=) ppm; 20f: δ = 4.67 (q, J =
6.3 Hz, 1 H, CH=), 6.28 (dt, J = 6.3, 1.5 Hz, 1 H, CH=) ppm.
Ar), 7.55 (d, J = 8.3 Hz, 2 H, Ar) ppm. 13C NMR: δ = 19.4, 25.4,
3
30.6, 62.3, 67.3, 98.1, 124.2 (q, JC,F = 271.9 Hz), 125.5 (q, JC,F
=
4.0 Hz), 126.6, 128.9, 129.3 (q, 2JC,F = 32.1 Hz), 130.4, 140.3 ppm.
C15H17F3O2 (286.3): calcd. C 62.93, H 5.99; found C 62.99, H 6.05.
MS (EI, 70 eV): m/z (%) = 286 (2) [M+]. Characteristic bands of
isomer 16a: δ = 5.49 (d, J = 1.2 Hz, 1 H, CH=), 5.59 (d, J = 1.2 Hz,
1 H, CH=) ppm; 16d: δ = 5.99 (dt, J = 12.1, 6.3 Hz, 1 H, CH=),
6.60 (d, J = 12.1 Hz, 1 H, CH=) ppm; 16e: δ = 5.23 (dt, J = 12.2,
7.6 Hz, 1 H, CH=), 6.38 (dt, J = 12.2, 0.8 Hz, 1 H, CH=) ppm;
16f: δ = 4.67 (q, J = 6.3 Hz, 1 H, CH=), 6.25 (dt, J = 6.3, 1.5 Hz,
1 H, CH=) ppm.
(E)-1-(4-Cyanophenyl)-3-(tetrahydropyran-2-yloxy)propene (17c):
1H NMR: δ = 1.43–1.98 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–3.95 (m, 1 H, CH2O), 4.16 (dd, J = 13.8, 6.0 Hz, 1 H,
CH2CH=), 4.42 (dd, J = 13.8, 5.1 Hz, 1 H, CH2CH=), 4.68 (t, J =
3.3 Hz, 1 H, CH), 6.42 (dt, J = 16.1, 5.6 Hz, 1 H, CH=), 6.63 (d,
J = 16.1 Hz, 1 H, CH=), 7.44 (d, J = 8.2 Hz, 2 H, Ar), 7.63 (d, J
= 8.2 Hz, 2 H, Ar) ppm. 13C NMR: δ = 19.4, 25.3, 30.5, 62.3, 67.1,
98.2, 110.7, 118.9, 126.8, 129.8, 130.3, 132.3, 141.3 ppm.
C15H17NO2 (243.3): calcd. C 74.05, H 7.04; found C 73.84, H 7.00.
MS (EI, 70 eV): m/z (%) = 243 (2) [M+]. Characteristic bands of
isomer 17a: δ = 5.50 (s, 1 H, CH=), 5.61 (s, 1 H, CH=) ppm; 17b:
δ = 6.88 (q, J = 1.1 Hz, 1 H, CH=) ppm; 17d: δ = 6.02 (dt, J =
12.0, 6.4 Hz, 1 H, CH=), 6.56 (d, J = 12.0 Hz, 1 H, CH=) ppm;
17e: δ = 5.18 (dt, J = 12.4, 7.6 Hz, 1 H, CH=), 6.38 (d, J = 12.4 Hz,
1 H, CH=) ppm; 17f: δ = 4.64 (q, J = 6.3 Hz, 1 H, CH=), 6.35 (dt,
J = 6.3, 1.4 Hz, 1 H, CH=) ppm.
(E)-1-(4-Dimethylaminophenyl)-3-(tetrahydropyran-2-yloxy)propene
1
(21c): H NMR: δ = 1.50–2.00 (m, 6 H, CH2), 2.95 (s, 6 H, Me),
3.44–3.58 (m, 1 H, CH2O), 3.85–3.95 (m, 1 H, CH2O), 4.12 (ddd,
J = 12.3, 7.0, 1.0 Hz, 1 H, CH2CH=), 4.36 (ddd, J = 12.3, 5.9,
1.3 Hz, 1 H, CH2CH=), 4.70 (t, J = 3.6 Hz, 1 H, CH), 6.11 (dt, J
= 15.7, 6.5 Hz, 1 H, CH=), 6.53 (d, J = 15.7 Hz, 1 H, CH=), 7.07
(d, J = 8.2 Hz, 2 H, Ar), 7.28 (d, J = 8.2 Hz, 2 H, Ar) ppm. 13C
NMR: δ = 19.5, 25.5, 30.7, 40.4, 62.2, 68.1, 97.6, 112.3, 121.3,
125.2, 127.5, 132.9, 150.1 ppm. C16H23NO2 (261.3): calcd. C 73.53,
H 8.87; found C 73.67, H 8.99. MS (EI, 70 eV): m/z (%) = 261 (60)
[M+]. Characteristic bands of isomer 21a: δ = 5.21 (s, 1 H, CH=),
5.41 (s, 1 H, CH=) ppm; 21b: δ = 6.60 (s, 1 H, CH=) ppm; 21d: δ
= 5.68 (dt, J = 11.9, 6.3 Hz, 1 H, CH=) ppm; 21e: δ = 5.23 (dt, J
= 12.3, 5.5 Hz, 1 H, CH=), 6.33 (d, J = 12.3 Hz, 1 H, CH=) ppm;
(E)-1-(4-Fluorophenyl)-3-(tetrahydropyran-2-yloxy)propene (18c): 21f: δ = 4.73 (q, J = 6.2 Hz, 1 H, CH=), 6.26 (d, J = 6.2 Hz, 1 H,
1H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O), CH=) ppm.
Eur. J. Org. Chem. 2005, 1367–1377
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1373

F. Berthiol, H. Doucet, M. Santelli
(E)-1-(6-Methoxynaphthalen-2-yl)-3-(tetrahydropyran-2-yloxy)pro- 1 H, CH=), 6.31 (m, 1 H, CH=) ppm; 25f: δ = 4.63 (q, J = 6.3 Hz,
FULL PAPER
1
pene (22c): H NMR: δ = 1.50–2.00 (m, 6 H, CH2), 3.50–3.60 (m,
1 H, CH2O), 3.90 (s, 3 H, MeO), 3.80–4.00 (m, 1 H, CH2O), 4.20
(ddd, J = 12.8, 6.6, 1.1 Hz, 1 H, CH2CH=), 4.57 (ddd, J = 12.8,
5.6, 1.5 Hz, 1 H, CH2CH=), 4.45 (t, J = 3.5 Hz, 1 H, CH), 6.39
(dt, J = 15.9, 6.2 Hz, 1 H, CH=), 6.76 (d, J = 15.9 Hz, 1 H, CH=),
7.07–7.16 (m, 2 H, Ar), 7.58 (dd, J = 8.7, 1.5 Hz, 1 H, Ar), 7.64–
7.72 (m, 3 H, Ar) ppm. 13C NMR: δ = 19.5, 25.4, 30.6, 55.2, 62.2,
67.8, 97.9, 105.8, 118.9, 124.2, 125.2, 126.2, 127.0, 128.9, 129.4,
132.2, 132.5, 134.1, 157.7 ppm. C19H22O3 (298.4): calcd. C 76.48,
H 7.43; found C 76.27, H 7.33. MS (EI, 70 eV): m/z (%) = 298 (40)
[M+]. Characteristic bands of isomer 22a: δ = 5.48 (s, 1 H, CH=),
5.67 (s, 1 H, CH=) ppm; 22b: δ = 6.85 (q, J = 1.3 Hz, 1 H, CH=)
ppm; 22d: δ = 5.94 (dt, J = 12.0, 6.0 Hz, 1 H, CH=), 6.73 (d, J =
12.0 Hz, 1 H, CH=) ppm; 22e: δ = 5.36 (dt, J = 12.2, 6.6 Hz, 1 H,
CH=), 6.43 (dt, J = 12.2, 1.2 Hz, 1 H, CH=) ppm; 22f: δ = 4.76
(q, J = 6.2 Hz, 1 H, CH=), 6.33 (d, J = 6.2 Hz, 1 H, CH=) ppm.
1 H, CH=), 6.31 (m, 1 H, CH=) ppm.
(E)-1-(Naphthalen-1-yl)-3-(tetrahydropyran-2-yloxy)propene (26c):
1H NMR: δ = 1.50–2.20 (m, 6 H, CH2), 3.55–3.75 (m, 1 H, CH2O),
3.90–4.15 (m, 1 H, CH2O), 4.32 (ddd, J = 13.1, 6.5, 1.4 Hz, 1 H,
CH2CH=), 4.57 (ddd, J = 13.1, 5.5, 1.8 Hz, 1 H, CH2CH=), 4.82
(t, J = 3.4 Hz, 1 H, CH), 6.39 (dt, J = 15.7, 6.3 Hz, 1 H, CH=),
7.37–7.60 (m, 4 H, Ar and CH=), 7.66 (d, J = 6.8 Hz, 1 H, Ar),
7.81 (d, J = 8.3 Hz, 1 H, Ar), 7.84–7.92 (m, 1 H, Ar), 8.13–8.23
(m, 1 H, Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.6, 62.2, 67.7, 97.9,
123.7, 123.8, 125.5, 125.6, 125.9, 127.8, 128.4, 129.1, 129.2, 131.1,
133.5, 134.5 ppm. C18H20O2 (268.3): calcd. C 80.56, H 7.51; found
C 80.40, H 7.32. MS (EI, 70 eV): m/z (%) = 268 (15) [M+]. Charac-
teristic bands of isomer 26a: δ = 5.32 (q, J = 1.8 Hz, 1 H, CH=),
5.80 (q, J = 1.8 Hz, 1 H, CH=) ppm; 26b: δ = 6.63 (q, J = 1.5 Hz,
1 H, CH=) ppm; 26e: δ = 5.47 (dt, J = 12.4, 7.3 Hz, 1 H, CH=),
6.45 (dt, J = 12.4, 1.5 Hz, 1 H, CH=) ppm; 26f: δ = 4.78 (q, J =
6.5 Hz, 1 H, CH=), 6.35 (d, J = 6.0 Hz, 1 H, CH=) ppm.
(E)-1-(2-Acetylphenyl)-3-(tetrahydropyran-2-yloxy)propene (23c):
1H NMR: δ = 1.45–2.00 (m, 6 H, CH2), 2.56 (s, 3 H, MeCO), 3.45–
3.65 (m, 1 H, CH2O), 3.80–4.00 (m, 1 H, CH2O), 4.18 (ddd, J =
13.2, 6.5, 1.4 Hz, 1 H, CH2CH=), 4.41 (ddd, J = 13.2, 5.3, 1.7 Hz,
1 H, CH2CH=), 4.72 (t, J = 3.4 Hz, 1 H, CH), 6.19 (dt, J = 16.0,
6.0 Hz, 1 H, CH=), 7.12 (d, J = 16.0 Hz, 1 H, CH=), 7.31 (td, J =
6.3, 1.3 Hz, 1 H, Ar), 7.43 (td, J = 6.4, 1.3 Hz, 1 H, Ar), 7.53–7.66
(m, 2 H, Ar) ppm. 13C NMR: δ = 19.5, 25.5, 29.9, 30.6, 62.3,
67.7, 98.0, 127.2, 127.8, 128.6, 129.2, 130.7, 131.4, 136.7, 137.6,
202.1 ppm. C16H20O3 (260.3): calcd. C 73.82, H 7.74; found C
73.99, H 7.61. MS (EI, 70 eV): m/z (%) = 260 (1) [M+]. Characteris-
tic bands of isomer 23a: δ = 5.07 (s, 1 H, CH=), 5.45 (s, 1 H, CH=)
ppm; 23b: δ = 6.62 (s, 1 H, CH=) ppm; 23d: δ = 5.92 (dt, J = 12.0,
6.0 Hz, 1 H, CH=), 6.95 (d, J = 12.0 Hz, 1 H, CH=) ppm; 23e: δ
= 5.21 (dt, J = 12.4, 7.6 Hz, 1 H, CH=), 6.31 (d, J = 12.4 Hz, 1 H,
CH=) ppm; 23f: δ = 4.71 (q, J = 6.4 Hz, 1 H, CH=), 6.27 (d, J =
6.0 Hz, 1 H, CH=) ppm.
(E)-1-(2,6-Difluorophenyl)-3-(tetrahydropyran-2-yloxy)propene
(27c): H NMR: δ = 1.45–2.00 (m, 6 H, CH2), 3.45–3.60 (m, 1 H,
1
CH2O), 3.85–4.00 (m, 1 H, CH2O), 4.17 (dd, J = 13.6, 4.1 Hz, 1
H, CH2CH=), 4.43 (dd, J = 13.6, 3.4 Hz, 1 H, CH2CH=), 4.71 (t,
J = 3.5 Hz, 1 H, CH), 6.60–6.65 (m, 1 H, CH=), 6.68 (d, J =
16.4 Hz, 1 H, CH=), 6.85 (t, J = 8.2 Hz, 2 H, Ar), 7.46 (tt, J = 8.4,
6.3 Hz, 1 H, Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.6, 62.1, 68.1,
2
2
98.0, 111.4 (dd, JC,F = 18.1, 6.3 Hz), 114.1 (t, JC,F = 15.5 Hz),
3
3
118.1, 128.0 (t, JC,F = 11.0 Hz), 133.3 (t, JC,F = 7.7 Hz), 160.9
(dd, JC,F = 251.3, 8.1 Hz). C14H16F2O (254.3): calcd. C 66.13, H
6.34; found C 65.97, H 6.47. MS (EI, 70 eV): m/z (%) = 254 (1)
[M+]. Characteristic bands of isomer 27e: δ = 5.20 (dt, J = 12.5,
7.4 Hz, 1 H, CH=), 6.40 (d, J = 12.5 Hz, 1 H, CH=) ppm; 27f: δ
= 4.61 (q, J = 6.2 Hz, 1 H, CH=), 6.23 (dt, J = 6.2, 1.5 Hz, 1 H,
CH=). Compounds 27e and 27f were characterised by deprotec-
tion. 3-(2,6-Difluorophenyl)propionaldehyde: 1H NMR: δ = 2.72
(t, J = 7.8 Hz, 2 H, CH2), 2.99 (t, J = 7.8 Hz, 2 H, CH2), 6.84 (t,
J = 8.0 Hz, 2 H, Ar), 7.15 (tt, J = 8.0, 6.6 Hz, 1 H, Ar), 9.79 (s, 1
(E)-1-(2-Fluorophenyl)-3-(tetrahydropyran-2-yloxy)propene (24c):
1H NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–4.00 (m, 1 H, CH2O), 4.17 (ddd, J = 13.2, 6.3, 1.3 Hz, 1 H,
CH2CH=), 4.43 (ddd, J = 13.2, 5.3, 1.5 Hz, 1 H, CH2CH=), 4.71
(t, J = 3.2 Hz, 1 H, CH), 6.39 (dt, J = 16.0, 6.3 Hz, 1 H, CH=),
6.79 (d, J = 16.0 Hz, 1 H, CH=), 6.95–7.25 (m, 3 H, Ar), 7.46 (dt,
J = 7.6, 2.0 Hz, 1 H, Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.6,
2
H, CHO) ppm. 13C NMR: δ = 15.1, 43.0, 111.1 (dd, JC,F = 17.8,
8.0 Hz), 115.8 (t, 2JC,F = 20.1 Hz), 127.9 (t, 3JC,F = 10.4 Hz), 161.4
(dd, JC,F = 246.7, 8.6 Hz), 200.8 ppm. MS (EI, 70 eV): m/z (%) =
170 (100) [M+].
(E)-3-(Tetrahydropyran-2-yloxy)-1-(2,4,6-trimethylphenyl)propene
2
3
1
62.2, 67.7, 98.0, 115.6 (d, JC,F = 22.4 Hz), 124.0 (d, JC,F
=
(28c): H NMR: δ = 1.45–2.00 (m, 6 H, CH2), 2.27 (s, 9 H, Me),
3
3
3.5 Hz), 124.5 (d, JC,F = 3.4 Hz), 124.7, 127.5 (d, JC,F = 4.0 Hz),
128.7, 128.8 (d, JC,F = 12.6 Hz), 160.7 (d, JC,F = 248.9 Hz).
3.45–3.65 (m, 1 H, CH2O), 3.75–4.05 (m, 1 H, CH2O), 4.21 (ddd,
J = 12.9, 6.6, 1.3 Hz, 1 H, CH2CH=), 4.42 (ddd, J = 12.9, 5.6,
1.5 Hz, 1 H, CH2CH=), 4.74 (t, J = 3.4 Hz, 1 H, CH), 5.79 (dt, J
= 16.2, 6.6 Hz, 1 H, CH=), 6.57 (d, J = 16.2 Hz, 1 H, CH=), 6.85
(s, 2 H, Ar) ppm. 13C NMR: δ = 19.6, 20.9, 21.3, 25.5, 30.7, 62.4,
67.9, 97.6, 128.5, 129.6, 130.0, 130.8, 135.9, 136.1 ppm. MS (EI,
70 eV): m/z (%) = 260 (10) [M+]. Compound 28c was characterised
by deprotection.[44] Characteristic bands of isomer 28e: δ = 5.13
(dt, J = 12.6, 6.3 Hz, 1 H, CH=), 6.23 (dt, J = 12.6, 1.3 Hz, 1 H,
CH=) ppm; 28f: δ = 4.43 (q, J = 6.5 Hz, 1 H, CH=), 6.18 (dt, J =
6.5, 1.3 Hz, 1 H, CH=) ppm.
2
C14H17FO2 (236.3): calcd. C 71.16, H 7.25; found C 70.94, H 7.04.
MS (EI, 70 eV): m/z (%) = 236 (2) [M+]. Characteristic bands of
isomer 24a: δ = 5.41 (s, 1 H, CH=), 5.56 (s, 1 H, CH=) ppm; 24d:
δ = 5.98 (dt, J = 12.1, 6.0 Hz, 1 H, CH=), 6.63 (d, J = 12.1 Hz, 1
H, CH=) ppm; 24e: δ = 5.23 (dt, J = 12.3, 7.6 Hz, 1 H, CH=), 6.38
(d, J = 12.3 Hz, 1 H, CH=) ppm; 24f: δ = 4.68 (q, J = 6.4 Hz, 1
H, CH=), 6.32 (dt, J = 6.4, 1.4 Hz, 1 H, CH=) ppm.
(E)-1-(2-Methylphenyl)-3-(tetrahydropyran-2-yloxy)propene (25c):
1H NMR: δ = 1.50–2.00 (m, 6 H, CH2), 2.35 (s, 3 H, Me), 3.45–
3.60 (m, 1 H, CH2O), 3.80–4.00 (m, 1 H, CH2O), 4.19 (ddd, J =
12.6, 6.6, 1.5 Hz, 1 H, CH2CH=), 4.42 (ddd, J = 12.6, 5.6, 1.3 Hz,
(E)-1-(2,6-Diethyl-4-methylphenyl)-3-(tetrahydropyran-2-yloxy)pro-
pene (29c): 1H NMR: δ = 1.15 (t, 6 H, Me), 1.50–2.00 (m, 6 H,
1 H, CH2CH=), 4.70 (t, J = 3.3 Hz, 1 H, CH), 6.18 (dt, J = 15.6, CH2), 2.30 (s, 3 H, Me), 2.62 (q, 4 H, CH2), 3.45–3.60 (m, 1 H,
6.6 Hz, 1 H, CH=), 6.84 (d, J = 15.6 Hz, 1 H, CH=), 7.10–7.25 CH2O), 3.85–4.00 (m, 1 H, CH2O), 4.21 (ddd, J = 12.9, 6.6, 1.2 Hz,
(m, 3 H, Ar), 7.40–7.50 (m, 1 H, Ar) ppm. 13C NMR: δ = 19.5,
19.7, 25.5, 30.6, 62.3, 67.8, 97.8, 125.7, 126.0, 127.3, 127.5, 130.1,
130.2, 135.4, 135.9 ppm. C15H20O2 (232.3): calcd. C 77.55, H 8.68;
found C 77.71, H 8.80. MS (EI, 70 eV): m/z (%) = 232 (1) [M+].
Characteristic bands of isomer 25e: δ = 5.18 (dt, J = 12.3, 7.2 Hz,
1 H, CH2CH=), 4.38 (ddd, J = 12.9, 5.3, 1.5 Hz, 1 H, CH2CH=),
4.74 (t, J = 3.5 Hz, 1 H, CH), 5.74 (dt, J = 16.2, 6.6 Hz, 1 H,
CH=), 6.63 (d, J = 16.2 Hz, 1 H, CH=), 6.88 (s, 2 H, Ar) ppm.
13C NMR: δ = 15.3, 19.6, 21.1, 25.5, 26.7, 30.7, 62.4, 67.6, 97.5,
126.7, 129.6, 130.9, 132.9, 136.5, 142.1 ppm. C19H28O2 (288.4):
1374
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1367–1377

Heck Reaction of Protected Allyl Alcohols with Aryl Bromides
FULL PAPER
calcd. C 79.12, H 9.78; found C 79.25, H 9.89. MS (EI, 70 eV):
m/z (%) = 288 (8) [M+]. Characteristic bands of isomer 29e: δ =
5.19 (dt, J = 12.6, 6.3 Hz, 1 H, CH=), 6.23 (dt, J = 12.6, 1.0 Hz,
1 H, CH=) ppm; 29f: δ = 4.46 (q, J = 6.4 Hz, 1 H, CH=), 6.24 (dt,
J = 6.4, 1.3 Hz, 1 H, CH=) ppm.
CH2CH=), 4.35 (ddd, J = 13.1, 5.6, 1.5 Hz, 1 H, CH2CH=), 4.69
(t, J = 3.4 Hz, 1 H, CH), 6.14 (dt, J = 15.7, 5.6 Hz, 1 H, CH=),
6.75 (d, J = 15.7 Hz, 1 H, CH=), 6.90–6.96 (m, 2 H, Ar), 7.14 (dd,
J = 3.8, 2.5 Hz, 1 H, Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.6,
62.1, 67.2, 97.8, 124.2, 125.3, 125.7 (2 C), 127.3, 141.9 ppm. MS
(EI, 70 eV): m/z (%) = 224 (2) [M+]. Compound 34c was character-
ised by deprotection.[45] Characteristic bands of isomer 34a: δ =
5.27 (s, 1 H, CH=), 5.54 (s, 1 H, CH=) ppm; 34d: δ = 5.78 (dt, J
= 12.1, 6.1 Hz, 1 H, CH=), 6.52 (dt, J = 12.1, 1.5 Hz, 1 H, CH=)
ppm; 34e: δ = 5.29 (dt, J = 12.2, 7.6 Hz, 1 H, CH=), 6.42 (d, J =
12.1 Hz, 1 H, CH=) ppm; 34f: δ = 4.75 (q, J = 6.3 Hz, 1 H, CH=),
6.30 (dt, J = 6.3, 1.5 Hz, 1 H, CH=) ppm.
(E)-3-(Anthracen-9-yl)-1-(tetrahydropyran-2-yloxy)propene (30e and
30f): Characteristic bands observed before hydrolysis: 30e: 1H
NMR: δ = 5.47 (dt, J = 12.5, 6.4 Hz, 1 H, CH=), 6.37 (dt, J =
12.5, 1.5 Hz, 1 H, CH=) ppm; 30f: δ = 4.78 (q, J = 6.6 Hz, 1 H,
CH=), 6.31 (dt, J = 6.6, 1.6 Hz, 1 H, CH=) ppm; 30e and 30f were
characterised by deprotection. 3-(Anthracen-9-yl)propionaldehyde:
1H NMR: δ = 2.95 (td, J = 8.0, 1.2 Hz, 2 H, CH2), 3.94 (t, J =
8.0 Hz, 2 H, CH2), 7.42–7.57 (m, 4 H, Ar), 8.02 (d, J = 7.8 Hz, 2
H, Ar), 8.19 (d, J = 7.8 Hz, 2 H, Ar), 8.37 (s, 1 H, Ar), 9.95 (s, 1
H, CHO) ppm.
(E)-3-(Tetrahydropyran-2-yloxy)-1-(3-thienyl)propene (35c): 1H
NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–4.00 (m, 1 H, CH2O), 4.13 (ddd, J = 12.8, 6.7, 1.3 Hz, 1 H,
CH2CH=), 4.39 (ddd, J = 12.8, 5.7, 1.5 Hz, 1 H, CH2CH=), 4.71
(t, J = 3.4 Hz, 1 H, CH), 6.18 (dt, J = 15.9, 6.7 Hz, 1 H, CH=),
6.67 (d, J = 15.9 Hz, 1 H, CH=), 7.13–7.17 (dd, J = 2.9, 1.2 Hz, 1
H, Ar), 7.19–7.23 (dd, J = 5.0, 1.2 Hz, 1 H, Ar), 7.23–7.28 (m, 1
H, Ar) ppm. 13C NMR: δ = 19.4, 25.4, 30.6, 62.2, 67.5, 97.8, 122.1,
125.0, 125.8, 125.9, 126.6, 139.4 ppm. C12H16O2S (224.3): calcd. C
64.25, H 7.19; found C 63.97, H 7.00. MS (EI, 70 eV): m/z (%) =
224 (4) [M+]. Characteristic bands of isomer 35a: δ = 5.33 (s, 1 H,
CH=), 5.53 (s, 1 H, CH=) ppm; 35b: δ = 6.83 (q, J = 1.3 Hz, 1 H,
CH=) ppm; 35e: δ = 5.27 (dt, J = 12.4, 7.6 Hz, 1 H, CH=), 6.36
(dt, J = 12.4, 1.3 Hz, 1 H, CH=) ppm; 35f: δ = 4.71 (q, J = 6.3 Hz,
1 H, CH=), 6.29 (dt, J = 6.3, 1.5 Hz, 1 H, CH=) ppm.
(E)-1-(Tetrahydropyran-2-yloxy)-3-(2,4,6-triisopropyl)propene (31e
1
and 31f): Characteristic bands observed before hydrolysis: 31e: H
NMR: δ = 5.22 (dt, J = 12.4, 6.1 Hz, 1 H, CH=), 6.11 (dt, J =
12.4, 1.5 Hz, 1 H, CH=) ppm; 31f: δ = 4.47 (q, J = 6.3 Hz, 1 H,
CH=), 6.21 (dt, J = 6.3, 1.8 Hz, 1 H, CH=) ppm; 31e and 31f were
characterised by deprotection. 3-(2,4,6-Triisopropylphenyl)propi-
1
onaldehyde: H NMR: δ = 1.70 (d, J = 6.8 Hz, 18 H, CH3), 2.55
(td, J = 8.0, 0.8 Hz, 2 H, CH2), 2.88 (sept, J = 6.8 Hz, 1 H, CH),
3.01 (td, J = 8.0, 1.2 Hz, 2 H, CH2), 3.09 (sept, J = 6.8 Hz, 2 H,
CH), 7.01 (s, 2 H, Ar), 9.88 (t, J = 1.2 Hz, 1 H, CHO) ppm. 13C
NMR: δ = 19.8, 24.0, 24.4, 29.2, 34.1, 45.8, 121.1, 131.1, 146.4,
146.8, 201.5 ppm. MS (EI, 70 eV): m/z (%) = 260 (10) [M+].
1
(E)-1-(3-Pyridyl)-3-(tetrahydropyran-2-yloxy)propene (32c): 1H
NMR: δ = 1.45–2.10 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–4.00 (m, 1 H, CH2O), 4.15 (ddd, J = 13.4, 5.8, 1.0 Hz, 1 H,
CH2CH=), 4.41 (ddd, J = 13.4, 5.3, 1.3 Hz, 1 H, CH2CH=), 4.69
(t, J = 3.3 Hz, 1 H, CH), 6.37 (dt, J = 16.2, 5.8 Hz, 1 H, CH=),
6.61 (d, J = 16.2 Hz, 1 H, CH=), 7.18–7.26 (m, 1 H, Ar), 7.69 (dd,
J = 8.0, 1.7 Hz, 1 H, Ar), 8.45 (br. s, 1 H, Ar), 8.59 (br. s, 1 H, Ar)
ppm. 13C NMR: δ = 19.4, 25.4, 30.5, 62.3, 67.3, 98.1, 123.4, 128.2,
128.5, 132.8, 135.7, 148.4, 148.6 ppm. C13H17NO2 (219.3): calcd. C
71.21, H 7.81; found C 71.04, H 7.94. MS (EI, 70 eV): m/z (%) =
219 (2) [M+]. Characteristic bands of isomer 32a: δ = 5.47 (s, 1 H,
CH=), 5.57 (s, 1 H, CH=) ppm; 32d: δ = 5.95 (dt, J = 12.0, 6.0 Hz,
1 H, CH=) ppm; 32e: δ = 5.20 (dt, J = 12.4, 7.6 Hz, 1 H, CH=)
ppm; 32f: δ = 4.66 (q, J = 6.3 Hz, 1 H, CH=), 6.34 (dt, J = 6.1,
1.5 Hz, 1 H, CH=) ppm.
(E)-1-(4-Acetylphenyl)-3-benzyloxypropene (36c): H NMR: δ =
2.58 (s, 3 H, MeCO), 4.22 (dd, J = 5.7, 1.6 Hz, 2 H, CH2), 4.59 (s,
2 H, CH2), 6.45 (dt, J = 16.1, 5.7 Hz, 1 H, CH=), 6.68 (d, J =
16.1 Hz, 1 H, CH=), 7.26–7.40 (m, 5 H, Ar), 7.46 (d, J = 7.8 Hz,
2 H, Ar), 7.91 (d, J = 7.8 Hz, 2 H, Ar) ppm. 13C NMR: δ = 27.0,
70.8, 72.9, 126.9, 128.1, 128.2, 128.9, 129.1, 129.6, 131.3, 136.5,
138.4, 141.8, 198.0 ppm. C18H18O2 (266.3): calcd. C 81.17, H 6.81;
found C 81.01, H 6.98. MS (EI, 70 eV): m/z (%) = 266 (6) [M+].
Characteristic bands of isomer 36a: δ = 5.48 (s, 1 H, CH=), 5.66
(s, 1 H, CH=) ppm; 36d: δ = 6.03 (dt, J = 12.1, 6.1 Hz, 1 H, CH=),
36e: 5.02 (dt, J = 12.5, 7.4 Hz, 1 H, CH=), 6.47 (d, J = 12.5 Hz, 1
H, CH=) ppm; 36f: δ = 4.61 (dt, J = 7.5, 6.3 Hz, 1 H, CH=), 6.20
(dt, J = 6.3, 1.3 Hz, 1 H, CH=) ppm.
1
(E)-3-Benzyloxy-1-(4-tert-butylphenyl)propene (37c): H NMR: δ =
1.20 (s, 9 H, Ar), 4.07 (d, J = 6.1 Hz, 2 H, CH2), 4.44 (s, 2 H,
CH2), 6.18 (dt, J = 16.0, 6.1 Hz, 1 H, CH=), 6.50 (d, J = 16.0 Hz,
1 H, CH=), 7.11–7.33 (m, 9 H, Ar) ppm. 13C NMR: δ = 31.2, 34.5,
70.8, 71.9, 125.2, 125.4, 126.2, 127.5, 127.7, 128.3, 132.4, 133.9,
138.3, 150.7 ppm. C20H24O (280.4): calcd. C 85.67, H 8.63; found
C 85.40, H 8.51. MS (EI, 70 eV): m/z (%) = 189 (40) [M+ – 91].
Characteristic bands of isomer 37e: δ = 4.98 (dt, J = 12.8, 7.5 Hz,
1 H, CH=), 6.36 (d, J = 12.8 Hz, 1 H, CH=) ppm; 37f: δ = 4.53
(q, J = 6.3 Hz, 1 H, CH=), 6.04 (d, J = 6.3 Hz, 1 H, CH=) ppm.
1
(E)-1-(3-Quinolyl)-3-(tetrahydropyran-2-yloxy)propene (33c): H
NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–4.00 (m, 1 H, CH2O), 4.19 (ddd, J = 13.4, 6.1, 1.3 Hz, 1 H,
CH2CH=), 4.46 (ddd, J = 13.4, 5.3, 1.3 Hz, 1 H, CH2CH=), 4.71
(t, J = 3.3 Hz, 1 H, CH), 6.50 (dt, J = 16.0, 5.6 Hz, 1 H, CH=),
6.76 (d, J = 16.0 Hz, 1 H, CH=), 7.49 (dd, J = 8.1, 1.2 Hz, 1 H,
Ar), 7.62 (d, J = 8.3 Hz, 1 H, Ar), 7.75 (dd, J = 8.1, 1.3 Hz, 1 H,
Ar), 8.06 (d, J = 8.9 Hz, 2 H, Ar), 9.00 (d, J = 2.3 Hz, 1 H, Ar)
ppm. 13C NMR: δ = 19.4, 25.3, 30.5, 62.2, 67.4, 98.1, 126.8, 127.7,
127.9, 128.5, 128.6, 129.1, 129.2, 129.7, 132.4, 147.4, 149.3 ppm.
C17H19NO2 (269.3): calcd. C 75.80, H 7.11; found C 75.69, H 7.21.
MS (EI, 70 eV): m/z (%) = 269 (7) [M+]. Characteristic bands of
isomer 33a: δ = 5.50 (s, 1 H, CH=), 5.61 (s, 1 H, CH=) ppm; 33d:
δ = 6.09 (dt, J = 11.9, 6.1 Hz, 1 H, CH=), 6.61 (d, J = 11.9 Hz, 1
H, CH=) ppm; 33e: δ = 5.27 (dt, J = 12.1, 7.6 Hz, 1 H, CH=), 6.42
(dt, J = 12.1, 1.2 Hz, 1 H, CH=) ppm; 33f: δ = 4.75 (q, J = 6.3 Hz,
1 H, CH=), 6.39 (dt, J = 6.1, 1.5 Hz, 1 H, CH=) ppm.
(E)-3-Benzyloxy-1-(4-methoxyphenyl)propene (38c): 1H NMR: δ =
3.81 (s, 3 H, MeO), 4.19 (dd, J = 6.3, 1.2 Hz, 2 H, CH2), 4.58 (s,
2 H, CH2), 6.22 (dt, J = 15.9, 6.3 Hz, 1 H, CH=), 6.59 (d, J =
15.9 Hz, 1 H, CH=), 6.87 (d, J = 8.7 Hz, 2 H, Ar), 7.35 (d, J =
8.7 Hz, 2 H, Ar), 7.26–7.40 (m, 5 H, Ar) ppm. 13C NMR: δ = 55.2,
70.9, 72.0, 113.9, 123.7, 127.6, 127.7, 127.8, 128.4, 129.4, 132.2,
138.3, 159.3 ppm. MS (EI, 70 eV): m/z (%) = 254 (10) [M+]. Com-
pound 38c was characterised by deprotection.[43] Characteristic
bands of isomer 38a: δ = 5.27 (d, J = 1.1 Hz, 1 H, CH=), 5.47 (d,
(E)-3-(Tetrahydropyran-2-yloxy)-1-(2-thienyl)propene (34c): 1H J = 1.1 Hz, 1 H, CH=) ppm; 38b: δ = 6.52 (q, J = 1.3 Hz, 1 H,
NMR: δ = 1.40–2.00 (m, 6 H, CH2), 3.40–3.60 (m, 1 H, CH2O),
3.80–4.00 (m, 1 H, CH2O), 4.10 (ddd, J = 13.1, 6.6, 1.3 Hz, 1 H,
CH=) ppm; 38d: δ = 5.90 (dt, J = 12.1, 6.1 Hz, 1 H, CH=), 38e:
5.08 (dt, J = 12.5, 7.4 Hz, 1 H, CH=), 6.48 (d, J = 12.5 Hz, 1 H,
Eur. J. Org. Chem. 2005, 1367–1377
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1375

F. Berthiol, H. Doucet, M. Santelli
CH=) ppm; 38f: δ = 4.66 (d, J = 6.2 Hz, 1 H, CH=), 6.17 (dt, J = (E)-1-(4-Acetylphenyl)-3-butoxypropene (44c): 1H NMR: δ = 0.93
FULL PAPER
6.2, 1.4 Hz, 1 H, CH=) ppm.
(t, J = 7.2 Hz, 3 H, Me), 1.38 (sext., J = 7.2 Hz, 2 H, CH2), 1.50–
1.70 (m, 2 H, CH2), 2.57 (s, 3 H, MeCO), 3.49 (t, J = 6.5 Hz, 2 H,
CH2), 4.14 (dd, J = 5.5, 1.3 Hz, 2 H, CH2), 6.41 (dt, J = 16.0,
5.5 Hz, 1 H, CH=), 6.64 (d, J = 15.9 Hz, 1 H, CH=), 7.44 (d, J =
8.5 Hz, 2 H, Ar), 7.90 (d, J = 8.5 Hz, 2 H, Ar) ppm. 13C NMR: δ
= 13.9, 19.3, 26.5, 31.8, 70.5, 71.0, 126.5, 128.7, 129.6, 130.5, 136.0,
141.5, 197.5 ppm. C15H20O2 (232.3): calcd. C 77.55, H 8.68; found
C 77.31, H 8.58. MS (EI, 70 eV): m/z (%) = 232 (46) [M+]. Charac-
teristic bands of isomer 44a: δ = 5.44 (s, 1 H, CH=), 5.62 (s, 1 H,
CH=) ppm; 44b: δ = 6.81 (s, 1 H, CH=) ppm; 44e: δ = 4.89 (dt, J
= 12.6, 7.4 Hz, 1 H, CH=), 6.35 (d, J = 12.6 Hz, 1 H, CH=) ppm;
44f: δ = 4.52 (dt, J = 7.5, 6.2 Hz, 1 H, CH=), 6.08 (dt, J = 6.2,
1.4 Hz, 1 H, CH=) ppm.
(E)-3-Benzyloxy-1-(2-cyanophenyl)propene (39c): 1H NMR: δ =
4.25 (dd, J = 5.8, 1.5 Hz, 2 H, CH2), 4.59 (s, 2 H, CH2), 6.51 (dt,
J = 15.9, 5.8 Hz, 1 H, CH=), 6.99 (d, J = 15.9 Hz, 1 H, CH=),
7.26–7.40 (m, 6 H, Ar), 7.53 (t, J = 7.4 Hz, 1 H, Ar), 7.59–7.66 (m,
2 H, Ar) ppm. 13C NMR: δ = 70.3, 72.6, 111.1, 117.8, 125.8, 127.7,
127.8, 127.9 (2 C), 128.5, 131.7, 132.7, 133.0, 137.9, 140.0 ppm.
C17H15NO (249.3): calcd. C 81.90, H 6.06; found C 82.11, H 6.19.
MS (EI, 70 eV): m/z (%) = 249 (1) [M+]. Characteristic bands of
isomer 39a: δ = 5.53 (s, 1 H, CH=), 5.70 (s, 1 H, CH=) ppm; 39b:
δ = 6.93 (q, J = 1.3 Hz, 1 H, CH=) ppm; 39d: δ = 6.19 (dt, J =
12.0, 6.0 Hz, 1 H, CH=), 6.87 (d, J = 12.0 Hz, 1 H, CH=) ppm;
39e: δ = 5.01 (dt, J = 12.6, 7.5 Hz, 1 H, CH=), 6.51 (d, J = 12.6 Hz,
1 H, CH=) ppm; 39f: δ = 4.62 (q, J = 6.3 Hz, 1 H, CH=), 6.20 (dt,
J = 6.3, 1.3 Hz, 1 H, CH=) ppm.
(E)-3-Benzyloxy-1-(2,4,6-trimethylphenyl)propene (40c): 1H NMR:
δ = 2.29 (s, 3 H, Me), 2.31 (s, 6 H, Me), 3.89 (dd, J = 6.1, 1.5 Hz,
2 H, CH2), 4.63 (s, 2 H, CH2), 5.85 (dt, J = 16.3, 6.1 Hz, 1 H,
CH=), 6.61 (d, J = 16.3 Hz, 1 H, CH=), 6.89 (s, 2 H, Ar), 7.26–
7.40 (m, 5 H, Ar) ppm. 13C NMR: δ = 20.9 (3C), 71.1, 71.8, 127.6,
127.8, 128.4, 128.5, 130.4, 130.9, 133.5, 135.8, 136.2, 138.4 ppm.
C19H22O (266.4): calcd. C 85.67, H 8.32; found C 85.41, H 8.22.
MS (EI, 70 eV): m/z (%) = 266 (1) [M+]. Characteristic bands of
isomer 40e: δ = 5.02 (dt, J = 12.6, 6.4 Hz, 1 H, CH=), 6.32 (d, J
= 12.6 Hz, 1 H, CH=) ppm; 40f: δ = 4.39 (q, J = 6.5 Hz, 1 H,
CH=), 6.12 (dt, J = 6.5, 1.3 Hz, 1 H, CH=) ppm.
1
(E)-3-Butoxy-1-(4-tert-butylphenyl)propene (45c): H NMR: δ =
0.92 (t, J = 7.3 Hz, 3 H, Me), 1.31 (s, 9 H, Me), 1.25–1.45 (m, 2
H, CH2), 1.50–1.65 (m, 2 H, CH2), 3.46 (t, J = 6.5 Hz, 2 H, CH2),
4.15 (dd, J = 6.0, 1.2 Hz, 2 H, CH2), 6.24 (dt, J = 15.9, 6.0 Hz, 1
H, CH=), 6.57 (d, J = 15.9 Hz, 1 H, CH=), 7.32 (m, 4 H, Ar) ppm.
13C NMR: δ = 13.9, 19.4, 31.3, 31.9, 34.6, 70.1, 71.5, 125.4, 125.7,
126.2, 132.0, 134.0, 150.7 ppm. C17H26O (246.4): calcd. C 82.87, H
10.64; found C 82.61, H 10.81. MS (EI, 70 eV): m/z (%) = 246 (43)
[M+]. Characteristic bands of isomer 45a: δ = 5.27 (d, J = 1.3 Hz,
1 H, CH=), 5.47 (d, J = 1.3 Hz, 1 H, CH=) ppm; 45b: δ = 6.47 (q,
J = 1.2 Hz, 1 H, CH=) ppm; 45d: δ = 5.74 (dt, J = 12.0, 6.0 Hz, 1
H, CH=), 45e: 4.95 (dt, J = 12.6, 7.4 Hz, 1 H, CH=), 6.37 (d, J =
12.6 Hz, 1 H, CH=) ppm; 45f: δ = 4.58 (dt, J = 7.5, 6.2 Hz, 1 H,
CH=), 6.07 (dt, J = 6.2, 1.4 Hz, 1 H, CH=) ppm.
(E)-3-Benzyloxy-1-(3-pyridyl)propene (41c): 1H NMR: δ = 4.20 (dd,
J = 5.6, 1.3 Hz, 2 H, CH2), 4.58 (s, 2 H, CH2), 6.38 (dt, J = 16.1,
5.6 Hz, 1 H, CH=), 6.63 (d, J = 16.1 Hz, 1 H, CH=), 7.26–7.40
(m, 6 H, Ar), 7.70 (dt, J = 8.0, 1.9 Hz, 1 H, Ar), 8.40–8.65 (m, 2
H, Ar) ppm. 13C NMR: δ = 70.3, 72.5, 102.7, 123.4, 127.5, 127.7,
127.8, 128.4, 128.5, 132.8, 138.0, 148.3, 148.6 ppm. C15H15NO
(225.3): calcd. C 79.97, H 6.71; found C 80.20, H 6.74. MS (EI,
70 eV): m/z (%) = 225 (1) [M+]. Characteristic bands of isomer 41a:
δ = 5.42 (s, 1 H, CH=), 5.57 (s, 1 H, CH=) ppm; 41d: δ = 5.96 (dt,
J = 12.0, 6.0 Hz, 1 H, CH=), 6.89 (d, J = 12.0 Hz, 1 H, CH=)
ppm; 41e: δ = 4.97 (dt, J = 12.7, 7.4 Hz, 1 H, CH=), 6.43 (d, J =
12.7 Hz, 1 H, CH=) ppm; 41f: δ = 4.58 (dt, J = 7.4, 6.1 Hz, 1 H,
CH=), 6.18 (dt, J = 6.1, 1.4 Hz, 1 H, CH=) ppm.
(E)-3-Benzyloxy-1-(2-thienyl)propene (42c): 1H NMR: δ = 4.18 (dd,
J = 6.0, 1.2 Hz, 2 H, CH2), 4.59 (s, 2 H, CH2), 6.19 (dt, J = 15.8,
6.0 Hz, 1 H, CH=), 6.69 (d, J = 15.8 Hz, 1 H, CH=), 6.91–7.09
(m, 2 H, Ar), 7.11–7.21 (m, 1 H, Ar), 7.26–7.49 (m, 5 H, Ar) ppm.
13C NMR: δ = 70.3, 72.2, 124.3, 125.5, 125.7 (2 C), 127.3, 127.6,
127.7, 128.4, 138.2, 141.8 ppm. C14H14OS (230.3): calcd. C 73.01,
H 6.13; found C 72.87, H 6.01. MS (EI, 70 eV): m/z (%) = 230 (1)
[M+]. Characteristic bands of isomer 42d: δ = 5.84 (dt, J = 12.0,
6.0 Hz, 1 H, CH=), 6.69 (d, J = 12.0 Hz, 1 H, CH=) ppm; 42e: δ
= 5.12 (dt, J = 12.5, 7.3 Hz, 1 H, CH=), 6.51 (d, J = 12.5 Hz, 1 H,
CH=) ppm; 42f: δ = 4.70 (dt, J = 7.4, 6.1 Hz, 1 H, CH=), 6.18 (dt,
J = 6.1, 1.4 Hz, 1 H, CH=) ppm.
(E)-3-Butoxy-1-(4-methoxyphenyl)propene (46c): 1H NMR: δ = 0.93
(t, J = 7.2 Hz, 3 H, Me), 1.25–1.55 (m, 2 H, CH2), 1.55–1.85 (m,
2 H, CH2), 3.47 (t, J = 6.5 Hz, 2 H, CH2), 3.80 (s, 3 H, MeO), 4.17
(dd, J = 6.1, 1.3 Hz, 2 H, CH2), 6.16 (dt, J = 15.9, 6.1 Hz, 1 H,
CH=), 6.55 (d, J = 15.9 Hz, 1 H, CH=), 6.85 (d, J = 8.7 Hz, 2 H,
Ar), 7.33 (d, J = 8.7 Hz, 2 H, Ar) ppm. 13C NMR: δ = 13.8, 19.2,
31.7, 55.1, 70.0, 71.4, 113.8, 124.1, 127.5, 129.5, 131.6, 159.1 ppm.
C14H20O2 (220.3): calcd. C 76.33, H 9.15; found C 76.17, H 9.30.
MS (EI, 70 eV): m/z (%) = 220 (70) [M+]. Characteristic bands of
isomer 46a: δ = 5.24 (d, J = 1.2 Hz, 1 H, CH=), 5.43 (d, J = 1.2 Hz,
1 H, CH=) ppm; 46b: δ = 6.41 (q, J = 1.4 Hz, 1 H, CH=) ppm;
46d: δ = 5.77 (dt, J = 12.0, 6.0 Hz, 1 H, CH=), 46e: 4.94 (dt, J =
12.5, 7.4 Hz, 1 H, CH=), 6.36 (d, J = 12.5 Hz, 1 H, CH=) ppm;
46f: δ = 4.56 (dt, J = 7.4, 6.2 Hz, 1 H, CH=), 6.07 (dt, J = 6.2,
1.4 Hz, 1 H, CH=) ppm.
1
(E)-3-Butoxy-1-(2,4,6-trimethylphenyl)propene (47c): H NMR: δ =
0.96 (t, J = 7.2 Hz, 3 H, Me), 1.30–1.55 (m, 2 H, CH2), 1.55–1.75
(m, 2 H, CH2), 2.23–2.41 (m, 9 H, Me), 3.53 (t, J = 6.5 Hz, 2 H,
CH2), 4.18 (dd, J = 5.9, 1.4 Hz, 2 H, CH2), 5.80 (dt, J = 16.3,
6.0 Hz, 1 H, CH=), 6.57 (d, J = 16.3 Hz, 1 H, CH=), 6.88 (s, 2 H,
Ar) ppm. 13C NMR: δ = 13.9, 19.4, 19.6, 20.8, 31.9, 69.9, 71.7,
128.5, 129.8, 131.4, 133.6, 135.8, 136.1 ppm. C16H24O (232.3):
calcd. C 82.70, H 10.41; found C 82.46, H 10.24. MS (EI, 70 eV):
m/z (%) = 232 (14) [M+]. Characteristic bands of isomer 47a: δ =
5.04 (d, J = 2.0 Hz, 1 H, CH=), 5.65 (d, J = 2.0 Hz, 1 H, CH=)
ppm; 47e: δ = 5.22 (dt, J = 12.7, 6.4 Hz, 1 H, CH=), 6.35 (dt, J =
12.7, 1.4 Hz, 1 H, CH=) ppm; 47f: δ = 4.69 (q, J = 6.7 Hz, 1 H,
CH=), 6.39 (dt, J = 6.2, 1.7 Hz, 1 H, CH=) ppm.
(E)-3-Benzyloxy-1-(3-thienyl)propene (43c): 1H NMR: δ = 4.17 (dd,
J = 6.0, 1.3 Hz, 2 H, CH2), 4.57 (s, 2 H, CH2), 6.18 (dt, J = 15.9,
6.0 Hz, 1 H, CH=), 6.65 (d, J = 15.9 Hz, 1 H, CH=), 7.11–7.51
(m, 8 H, Ar) ppm. 13C NMR: δ = 70.7, 72.1, 122.2, 125.1, 125.9,
126.0, 126.8, 127.6, 127.7, 128.4, 138.3, 139.4 ppm. C14H14OS
(230.3): calcd. C 73.01, H 6.13; found C 72.78, H 6.22. MS (EI,
70 eV): m/z (%) = 230 (3) [M+]. Characteristic bands of isomer 43e:
δ = 5.10 (dt, J = 12.7, 7.3 Hz, 1 H, CH=), 6.46 (d, J = 12.7 Hz, 1
(E)-1-(4-Acetylphenyl)-3-(2-hydroxyethoxy)propene (48c): 1H
NMR: δ = 1.79 (br. s, 1 H, OH), 2.57 (s, 3 H, MeCO), 3.61 (t, J =
4.6 Hz, 2 H, CH2), 3.76 (t, J = 4.6 Hz, 2 H, CH2), 4.21 (dd, J =
5.7, 1.3 Hz, 2 H, CH2), 6.40 (dt, J = 16.1, 5.7 Hz, 1 H, CH=), 6.65
H, CH=) ppm; 43f: δ = 4.67 (dt, J = 7.4, 6.1 Hz, 1 H, CH=), 6.16 (d, J = 16.0 Hz, 1 H, CH=), 7.44 (d, J = 8.3 Hz, 2 H, Ar), 7.89 (d,
(dt, J = 6.1, 1.4 Hz, 1 H, CH=) ppm.
J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR: δ = 26.5, 61.8, 71.4, 71.6,
1376
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1367–1377

Heck Reaction of Protected Allyl Alcohols with Aryl Bromides
FULL PAPER
[5] N. Withcombe, K. K. Hii (Mimi), S. Gibson, Tetrahedron 2001,
57, 7449.
[6] A. Littke, G. Fu, Angew. Chem. Int. Ed. 2002, 41, 4176.
[7] T. Jeffery, J. Chem. Soc., Chem. Commun. 1984, 1287.
[8] T. Jeffery, Tetrahedron Lett. 1991, 32, 2121.
[9] J.-L. Reymond, G. K. Jahangiri, C. Stoudt, R. A. Lerner, J.
Am. Chem. Soc. 1993, 115, 3909.
[10] C. J. Barnett, T. M. Wilson, Heterocycles 1993, 35, 925.
[11] J.-L. Reymond, Y. Chen, J. Org. Chem. 1995, 60, 6970.
[12] S.-K. Kang, H.-W. Lee, S.-B. Jang, T.-H. Kim, S.-J. Pyun, J.
Org. Chem. 1996, 61, 2604.
126.5, 128.7, 128.8, 131.1, 136.1, 141.2, 197.5 ppm. C13H16O3
(220.2): calcd. C 70.89, H 7.32; found C 70.97, H 7.41. MS (EI,
70 eV): m/z (%) = 220 (100) [M+]. Characteristic bands of isomer
48a: δ = 5.44 (d, J = 1.1 Hz, 1 H, CH=), 5.63 (d, J = 1.1 Hz, 1 H,
CH=) ppm; 48e: δ = 4.92 (dt, J = 12.5, 7.4 Hz, 1 H, CH=), 6.38
(dt, J = 12.5, 1.2 Hz, 1 H, CH=) ppm; 48f: δ = 4.58 (dt, J = 7.5,
6.2 Hz, 1 H, CH=), 6.12 (dt, J = 6.2, 1.4 Hz, 1 H, CH=) ppm.
1
(E)-1-(4-tert-Butylphenyl)-3-(2-hydroxyethoxy)propene (49c): H
NMR: δ = 1.58 (s, 9 H, Me), 2.61 (br. s, 1 H, OH), 3.86 (t, J =
4.7 Hz, 2 H, CH2), 4.03 (t, J = 4.4 Hz, 2 H, CH2), 4.46 (d, J =
6.1 Hz, 2 H, CH2), 6.53 (dt, J = 15.9, 6.1 Hz, 1 H, CH=), 6.86 (d,
J = 15.9 Hz, 1 H, CH=), 7.60 (m, 4 H, Ar) ppm. 13C NMR: δ =
31.2, 34.5, 61.8, 71.2, 71.8, 124.8, 125.4, 126.2, 132.6, 133.7,
150.9 ppm. C15H22O (234.3): calcd. C 76.88, H 9.46; found C 76.69,
H 9.35. MS (EI, 70 eV): m/z (%) = 234 (2) [M+]. Characteristic
bands of isomer 49a: δ = 5.32 (d, J = 0.9 Hz, 1 H, CH=), 5.55 (d,
J = 0.9 Hz, 1 H, CH=) ppm; 49b: δ = 6.52 (q, J = 1.3 Hz, 1 H,
CH=) ppm; 49e: δ = 5.02 (dt, J = 12.6, 7.4 Hz, 1 H, CH=), 6.42
(d, J = 12.6 Hz, 1 H, CH=) ppm; 49f: δ = 4.68 (dt, J = 7.6, 6.2 Hz,
1 H, CH=), 6.13 (dt, J = 6.2, 1.5 Hz, 1 H, CH=) ppm.
[13] G. Pattenden, P. Wiedenau, Tetrahedron Lett. 1997, 38, 3647.
[14] D. Bruyère, G. Gaignard, D. Bouyssi, G. Balme, J.-M. Lance-
lin, Tetrahedron Lett. 1997, 38, 827.
[15] J. Li, A. W.-H. Mau, C. R. Strauss, Chem. Commun. 1997,
1275.
[16] S. Sengupta, S. K. Sadhukhan, Tetrahedron Lett. 1998, 39,
1237.
[17] E. C. Taylor, B. Liu, Tetrahedron Lett. 1999, 40, 4023.
[18] J.-R. Labrosse, C. Poncet, P. Lhoste, D. Sinou, Tetrahedron:
Asymmetry 1999, 10, 1069.
[19] S. E. Gibson, J. O. Jones, R. McCague, M. J. Tozer, N. J. Whit-
combe, Synlett 1999, 954.
[20] D. Villemin, B. Nechab, J. Chem. Res. Synopsis 2000, 429.
[21] S. Bouquillon, B. Ganchegui, B. Estrine, F. Hénin, J. Muzart,
J. Organomet. Chem. 2001, 634, 153.
[22] H. Zhao, M.-Z. Cai, R.-H. Hu, C.-S. Song, Synth. Commun.
2001, 31, 3665.
[23] C. Kapplinger, R. Beckert, Synthesis 2002, 1843.
[24] L. F. Tietze, K. Kahle, T. Raschke, Chem. Eur. J. 2002, 8, 401.
[25] A. Padwa, A. Zanka, M. P. Cassidy, J. M. Harris, Tetrahedron
2003, 59, 4939.
[26] S. B. Solabannavar, V. B. Helavi, U. V. Desai, R. B. Mane,
Synth. Commun. 2003, 33, 361.
[27] S. E. Watson, Synth. Commun. 1998, 28, 1897.
[28] K. Ono, K. Fugami, S. Tanaka, Y. Tamaru, Tetrahedron Lett.
1994, 35, 4133.
[29] T. Fukuyama, X. Chen, G. Peng, J. Am. Chem. Soc. 1994, 116,
3127.
(E)-3-(2-Hydroxyethoxy)-1-(4-methoxyphenyl)propene (50c): 1H
NMR: δ = 2.22 (br. s, 1 H, OH), 3.60 (t, J = 4.6 Hz, 2 H, CH2),
3.71 (t, J = 4.6 Hz, 2 H, CH2), 3.86 (s, 3 H, MeO), 4.46 (dd, J =
6.2, 1.2 Hz, 2 H, CH2), 6.15 (dt, J = 16.0, 6.2 Hz, 1 H, CH=), 6.55
(d, J = 16.0 Hz, 1 H, CH=), 6.85 (d, J = 8.8 Hz, 2 H, Ar), 7.31 (d,
J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR: δ = 55.2, 62.9, 71.2, 71.9,
114.0, 123.4, 127.7, 129.3, 132.5, 159.4 ppm. C12H16O3 (208.2):
calcd. C 69.21, H 7.74; found C 68.94, H 7.64. MS (EI, 70 eV):
m/z (%) = 208 (75) [M+]. Characteristic bands of isomer 50a: δ =
5.20 (d, J = 0.8 Hz, 1 H, CH=), 5.42 (d, J = 0.8 Hz, 1 H, CH=)
ppm; 50b: δ = 6.41 (q, J = 1.4 Hz, 1 H, CH=) ppm; 50e: δ = 4.97
(dt, J = 12.6, 7.3 Hz, 1 H, CH=), 6.35 (d, J = 12.6 Hz, 1 H, CH=)
ppm; 50f: δ = 4.62 (dt, J = 7.5, 6.2 Hz, 1 H, CH=), 6.08 (dt, J =
6.2, 1.4 Hz, 1 H, CH=) ppm.
[30] D. Laurenti, M. Feuerstein, G. Pèpe, H. Doucet, M. Santelli,
J. Org. Chem. 2001, 66, 1633.
[31] M. Feuerstein, D. Laurenti, C. Bougeant, H. Doucet, M. San-
telli, Chem. Commun. 2001, 325.
[32] E. Peyroux, F. Berthiol, H. Doucet, M. Santelli, Eur. J. Org.
Chem. 2004, 1075.
[33] M. Feuerstein, F. Berthiol, H. Doucet, M. Santelli, Org. Bi-
omol. Chem. 2003, 1, 2235.
[34] M. Feuerstein, H. Doucet, M. Santelli, J. Org. Chem. 2001, 66,
5923.
[35] M. Feuerstein, H. Doucet, M. Santelli, Synlett 2001, 1980.
[36] M. Feuerstein, H. Doucet, M. Santelli, Tetrahedron Lett. 2002,
43, 2191.
(E)-3-(2-Hydroxyethoxy)-2-(2,4,6-trimethylphenyl)propene (51a): 1H
NMR: δ = 1.64 (br. s, 1 H, OH), 2.15–2.35 (m, 9 H, Me), 3.65 (t,
J = 4.8 Hz, 2 H, CH2), 3.71 (t, J = 4.8 Hz, 2 H, CH2), 4.05 (t, J =
1.7 Hz, 2 H, CH2), 4.98 (q, J = 1.7 Hz, 1 H, CH=), 5.56 (q, J =
1.7 Hz, 1 H, CH=), 6.86 (s, 2 H, Ar) ppm. 13C NMR: δ = 19.7,
20.8, 61.9, 72.1, 73.2, 113.7, 128.1, 128.7, 135.7, 136.6, 144.9 ppm.
C14H20O2 (220.3): calcd. C 76.33, H 9.15; found C 76.01, H 9.18.
MS (EI, 70 eV): m/z (%) = 220 (27) [M+]. Characteristic bands of
isomer 50e: δ = 4.84 (dt, J = 12.6, 6.3 Hz, 1 H, CH=), 6.15 (dt, J
= 12.6, 1.4 Hz, 1 H, CH=) ppm; 50f: δ = 4.33 (q, J = 6.6 Hz, 1 H,
CH=), 5.95 (dt, J = 6.2, 1.7 Hz, 1 H, CH=) ppm.
[37] F. Berthiol, M. Feuerstein, H. Doucet, M. Santelli, Tetrahedron
Lett. 2002, 43, 5625.
[38] F. Berthiol, H. Doucet, M. Santelli, Tetrahedron Lett. 2003, 44,
1221.
Acknowledgments
[39] F. Berthiol, H. Doucet, M. Santelli, Synlett 2003, 841.
[40] I. Kondolff, H. Doucet, M. Santelli, Tetrahedron Lett. 2003,
44, 8487.
We thank the CNRS and the Conseil Général des Bouches-du-
Rhône, France, for providing financial support.
[41] I. Kondolff, H. Doucet, M. Santelli, Synlett 2004, 1561.
[42] F. Berthiol, H. Doucet, M. Santelli, Tetrahedron Lett. 2004, 45,
5633.
[43] G. Pandey, A. Krishna, J. Org. Chem. 1988, 53, 2364.
[44] E. Medina, A. Moyano, M. A. Pericas, A. Riera, Helv. Chim.
Acta 2000, 83, 972.
[1] R. F. Heck, Vinyl Substitution with Organopalladium Intermedi-
ates, in Comprehensive Organic Synthesis, vol. 4 (Eds.: B. M.
Trost, I. Fleming), Pergamon: Oxford, 1991.
[2] A. de Meijere, F. Meyer, Angew. Chem. Int. Ed. Engl. 1994, 33,
2379.
[3] M. T. Reetz, Transition Metal Catalysed Reactions (Eds.: S. G.
Davies, S.-I. Murahashi), Blackwell Science, Oxford, 1999.
[4] I. Beletskaya, A. Cheprakov, Chem. Rev. 2000, 100, 3009.
[45] R. Takeuchi, N. Ue, K. Tanabe, K. Yamashita, N. Shiga, J.
Am. Chem. Soc. 2001, 123, 9525.
Received: November 05, 2004
Eur. J. Org. Chem. 2005, 1367–1377
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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