Mild copper-catalyzed vinylation reactions of azoles and phenols with vinyl bromides

Article abstract of DOI:10.1002/chem.200501411

An efficient and straightforward copper-catalyzed method allowing vinylation of N- or O-nucleophiles with di- or trisubstituted vinyl bromides is reported. The procedure is applicable to a broad range of substrates since N-vinylation of mono-, di-, and tr

Full text of DOI:10.1002/chem.200501411

FULL PAPER
DOI: 10.1002/chem.200501411
Mild Copper-Catalyzed Vinylation Reactionsof Azolesand Phenolswith
Vinyl Bromides
[b]
Marc Taillefer,*[a] Armelle Ouali,[a] Brice Renard,[a] and Jean-FrancisSpindler
Abstract: An efficient and straightfor-
ward copper-catalyzed method allow-
ing vinylation of N- or O-nucleophiles
with di- or trisubstituted vinyl bro-
mides is reported. The procedure is ap-
plicable to a broad range of substrates
since N-vinylation of mono-, di-, and
triazoles as well as O-vinylation of
phenol derivatives can be performed
with catalytic amounts of copper iodide
and inexpensive nitrogen ligands 3 or
8. In the case of more hindered vinyl
bromides, the use of the original biden-
tate chelator 8 was shown to be more
efficient to promote the coupling reac-
tions than our key tetradentate ligand
3. The corresponding N-(1-alkenyl)-
under very mild temperature condi-
tions (35–1108C for N-vinylation reac-
tions and 50–808C for O-vinylation re-
actions). Moreover, to our knowledge,
this method is the first example of a
copper-catalyzed vinylation of various
azoles. Finally, this protocol, practical
on a laboratory scale and easily adapta-
ble to an industrial scale, is very com-
petitive compared to the existing meth-
ods that allow the synthesis of such
compounds.
A
tained in high yields and selectivities
Keywords: copper · homogeneous
catalysis · nitrogen heterocycles ·
phenols · vinylation
Introduction
intermediates in a wide range of reactions (for example, cy-
cloaddition,[1] cyclopropanation,[2] or metathesis reactions[3])
and they find applications in the synthesis of natural product
analogues,[4] biologically active molecules,[5] and polymers.[6]
N-vinylazoles have also been widely used in the preparation
of structural templates. In particular, 1-(1-alkenyl)benzotri-
azoles are of considerable interest because of their thermal
and photochemical transformations.[7] Moreover, N-vinyl-
N-(1-Alkenyl)azoles 1 and 1-alkenyl aryl ethers 2 (Scheme 1)
are important classes of building blocks in organic synthesis
as well as synthetic targets throughout the polymer and life
science industries. Indeed, vinyl aryl ethers constitute useful
A
meric materials with various properties. For instance,
poly(1-vinylimidazole)s and poly(1-vinyl-1,2,4-triazole)s are
involved in the preparation of polymeric dyes, catalysts, and
ion-exchange resins,[8] while poly(1-vinylindole)s display
good photorefractive properties.[9] Otherwise, the vinyl
group can act as an efficient protecting group of azole and
phenol derivatives.[10] Interestingly, the N-vinylazole and the
vinyl aryl ether moieties are found in numerous biologically
active molecules. For example, vinylimidazole and 1-vinyl-
1,2,4-triazole derivatives have been found to display antifun-
gal activity[11,12] and 1-phenoxy-3-triazolyl-1-hexene deriva-
tives constitute plant growth regulators.[13]
Scheme 1. Target molecules. Alk=alkyl, Ar=aryl.
[a] Dr. M. Taillefer, Dr. A. Ouali, B. Renard
CNRS UMR 5076, HØtØrochimie molØculaire et macromolØculaire
Ecole Nationale SupØrieure de Chimie de Montpellier
8 rue de lꢀEcole Normale, 34296 Montpellier Cedex 5 (France)
Fax : (+33)4671-44-319
The main routes to form N-(1-alkenyl)azoles 1 and alken-
yl aryl ethers 2 (summarized in Scheme 2) are similar. They
include alkylation of the azole or phenol with 1,2-dibromo-
E-mail: Marc.taillefer@enscm.fr
[b] Dr. J.-F. Spindler
ethane[14a,b,h] or related compounds[2,14c–g] followed by dehy-
Rhodia Organique Fine
Centre de Recherches de Lyon (CRL)
85 avenue des Fr›res Perret, BP 62, 69192 Saint-Fons Cedex (France)
drohalogenation of the corresponding 2-haloethylazole or
aryl 2-haloethyl ether in the presence of a base (Scheme
Chem. Eur. J. 2006, 12, 5301 – 5313
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5301

Scheme 2. Main routes to form N-vinylazoles and vinyl aryl ethers. Nu=nucleophile, Tf=trifluoromethansulfonyl, Ts=toluene-4-sulfonyl.
2a). Preparation of the desired 1-alkenyl derivatives can
also be achieved by alkylation with allyl bromide and subse-
quent base-[15] or transition-metal-catalyzed isomerization[16]
to yield the desired alkenyl derivatives (Scheme 2b). The
major drawbacks of both procedures are the lack of general-
ity and substrate scope. The synthesis of compounds 1 or 2
involving addition of the corresponding azole or phenol to
an acetylenic compound in the presence of a strong base re-
quires harsh conditions (high temperature (>1258C) and
pressure) and generally leads to the target products in poor
yields (Scheme 2c).[17] Another way to prepare N-(1-alkenyl)-
catalysts can also promote the cross-coupling of a wide
range of phenols with vinyl triflates: alkenyl aryl ethers are
thus obtained in good yields at 1008C.[24] Nevertheless, the
use of expensive palladium limits the attractiveness of these
methods for industrial applications. As far as copper-mediat-
ed methods are concerned, those involving vinyl boronic
acids (N- and O-vinylation)[25] or tetravinyltin (O-vinyla-
tion)[26] as vinylating agents display the major advantage of
proceeding at room temperature but suffer from the re-
quirements for stoichiometric amounts of the cupric acetate.
A procedure involving vinylation of phenols by easily avail-
able vinyl bromides in the presence of the system CuI
(25 mol%)/2,2,6,6-tetramethylheptane-3,5-dione (25 mol%)
constitutes an attractive alternative to the above-mentioned
methods.[27] It requires, however, high copper salt and ligand
loadings and proceeds at a relatively high temperature
(1108C). More recently, a similar copper-mediated method
involving N,N-dimethylglycine hydrochloride as the ligand
(30 mol%) enabled the coupling of vinyl iodides and bro-
mides with phenols under milder temperature conditions
(60–908C).[28] It is worth noting that, although strategies in-
volving the use of copper-based catalysts to promote N-ami-
dation of vinyl halides have been reported,[29] no analogous
method for achieving N-vinylation of azoles has been descri-
bed, to the best of our knowledge.
A
bond by Wittig,[18e] Wittig–Horner,[19] Horner–Wadsworth–
Emmons,[20] or Peterson[18] olefination reactions. These
methods give access to a wide range of di-, tri-, or tetrasub-
stituted olefins but require time-consuming multistep syn-
theses and may thus suffer from low yields (Scheme 2d).
Syntheses of alkenyl aryl ethers through olefination of car-
bonyl compounds have been achieved more efficiently.[21]
More often than not, all of the above-mentioned procedures
(Scheme 2a–d) lead to a mixture of Z and E stereoisomers.
This last feature can be considered as a strong drawback
and underlies the necessity to develop stereospecific meth-
ods.
The most appropriate methods for the synthesis of N-(1-
alkenyl)azoles 1 and alkenyl aryl ethers 2 are thus based
upon transition-metal-mediated coupling of azoles and phe-
nols with different vinyl sources (Scheme 2e). N-vinylation
of azoles with vinyl acetate in the presence of mercuric ace-
tate has extensively been used to synthesize the correspond-
ing N-vinylazoles.[22] The toxicity of mercury derivatives can,
however, be considered disadvantageous for such methodol-
ogies. A general and efficient method for the synthesis of N-
(1-alkenyl)monoazoles involves palladium-catalyzed vinyla-
tion by vinyl bromides to yield a wide range of target prod-
ucts under mild conditions (50–1008C).[23] Palladium-based
The development of general, mild, cheap, stereospecific
ꢀ
ꢀ
synthetic methodologies to create alkenyl C N and C O
bonds and thus give access to N-(1-alkenyl)azoles 1 and al-
kenyl aryl ethers 2 is thus particularly challenging.
ꢀ
ꢀ
ꢀ
The quest for new catalysts to promote C N, C O, or C
C bond cross-coupling reactions has become a major topic
in our group.[30,31] In that context, we developed catalysts in-
volving copper salts and new nitrogen and/or oxygen li-
gands;[31c] these catalysts are able to promote arylation reac-
tions of N-, O-, and C-nucleophiles that are useful for the
synthesis of N-arylated heterocycles,[31c] N-arylated ami-
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Copper-Catalyzed Vinylation Reactions
FULL PAPER
Table 1. N-Vinylation of mono- and diazoles by b-bromostyrenes (E/Z=90:10).[a]
des,[31d] diaryl ethers,[31b] C-ary-
lated malonic derivatives,[31b]
or aryl nitriles.[31a] These
copper-based
methodologies
are characterized by very mild
reaction conditions with re-
spect to the classical Ullmann
condensations since most of
these coupling reactions can
be performed at temperatures
of 25–808C. We now report
further important synthetic uti-
lizations of our catalytic sys-
tems, namely, the copper-cata-
lyzed N-vinylation of azoles
and the O-vinylation of phenol
derivatives.
Entry Azole
1
T [8C] t [h]
(E)-Styrylazole
(E)-4 Conversion [%] Yield of 1 [%][b]
50
30
1a
1b
100
100 (94)
35
50
55
30
100
100
100
2
3
4
100 (98)
Results and Discussion
1c
1d
70 (combined: 89)
30
50
30
100
N-Vinylation of mono- and di-
azolesby
b-bromostyrenes:
Our initial exploration of reac-
tion conditions focused on the
coupling of pyrazole with b-
50
60
30
24
1e
93
93 (90)
100
bromostyrene,
a commercial
100
vinyl source available as a mix-
ture of both E and Z isomers
in a E-to-Z ratio of 90:10. The
reaction was performed in the
presence of CuI (10 mol%)
1 f
1g
80
13
5
60
80
24
24
93
and tetradentate ligand
(5 mol%) by using cesium car-
bonate as base (Table 1,
3
a
1 f
1g
100
85 (80)
15 (9)
entry 1). We were pleased to
find that, under these condi-
tions, the coupling was success-
ful, with (E)-b-bromostyrene
being quantitatively and ster-
eoselectively converted into
(E)-b-styrylpyrazole (1a) after
30 h at 508C.[32] If reaction
time is not an issue, it is even
possible to perform the con-
densation at a lower tempera-
ture, with 1a being obtained in
100% yield after 55 h at 358C
(Table 1, entry 1). Moreover,
whatever the temperature,
(Z)-b-bromostyrene was total-
6
7
60
80
24
24
1h
76
75
100
99 (89)
60
24
1i
74
74
80
24
100
100 (83)
[a] Reaction conditions for yields of isolated products: b-bromostyrene (E/Z=90:10, 2 mmol), azole (3 mmol),
Cs2CO3 (4 mmol), CuI (0.20 mmol), ligand 3 (0.10 mmol), CH3CN (1.2 mL); reaction conditions for yields
measured by GC analysis: b-bromostyrene (E/Z=90:10, 0.5 mmol), azole (0.75 mmol), Cs2CO3 (1 mmol), CuI
(0.05 mmol), ligand 3 (0.025 mmol), CH3CN (300 mL). [b] Yields refer to GC yields (with 1,3-dimethoxyben-
zene as an internal standard) and yields in brackets refer to yields of isolated products; yields are based on
(E)-b-bromostyrene.
ly transformed into phenylacetylene by a competitive dehy-
drobromination reaction. Under basic conditions, Z-alkenyl
bromides are indeed known to undergo an E2-type elimina-
tion more easily than the corresponding E isomers.[33] We
thus decided to express the yields of (E)-b-styrylpyrazole
(1a) with respect to (E)-b-bromostyrene.
We afterwards investigated the coupling reactions of b-
bromostyrene with various azoles under analogous condi-
tions.[34] N-vinylations of substituted pyrazoles were first at-
tempted and it was found that the presence of a substituent
in position 3 did not affect the reactivity of the nitrogen het-
erocycle since 3-trifluoromethylpyrazole and 3-methylpyra-
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M. Taillefer et al.
zole were also quantitatively converted into the correspond-
ing 1-(E)-b-styrylazoles within 30 h at 508C (Table 1, en-
tries 2 and 3). In the case of these unsymmetrical pyrazoles,
N-vinylation can theoretically lead to two regioisomers that
result from the substitution of two tautomers at the NH po-
sition.[35] Structures can easily be assigned according to their
1H/13C NMR spectroscopic data, particularly if the coupling
constant of hydrogen atoms on the N-substituted pyrazole
ring (by a styryl group in our case) is considered: 1-b-styryl-
Furthermore, the same catalytic system was shown to effi-
ciently promote N-vinylations of monoazoles such as pyrrole
and indole (Table 1, entries 6 and 7). The couplings occurred
at 608C, with 1-(E)-b-styrylpyrrole (1h) and 1-(E)-b-styryl-
indole (1i) being obtained in 75 and 74% yields, respective-
ly, after 24 h at this temperature. An increase of the temper-
ature of the reaction mixture allowed completion of the re-
action within the same time and isolation of the target prod-
ucts in good yields. It is worth noting that the palladium-
mediated preparation of 1h and 1i has already been report-
ed: the N-vinylation of pyrrole by (E)-b-bromostyrene at
508C was not selective and gave rise to 1-(E)-b-styryl-pyr-
role in poor yield, while quantitative N-vinylation of indole
occurred at 858C.[23]
3
3-substituted pyrazoles are expected to exhibit a JH,H value
of 2.4–2.9 Hz, while the corresponding constant in 1-b-
styryl-5-substituted pyrazoles is about 1.5–1.9 Hz.[36] Vinyla-
tion of 3-trifluoromethylpyrazole is however totally regiose-
lective and exclusively gave rise to 1-(E)-b-styryl-3-trifluoro-
methylpyrazole (1b), which could be isolated in 98% yield.
Such behavior was probably due to the inductive effect (ꢀI)
of the trifluoromethyl group, which deactivates the a-nitro-
gen atom and in this way favors substitution on the b atom.
By contrast, 3-methylpyrazole led to the formation of two
regioisomers, 1-(E)-b-styryl-3-methylpyrazole (1c) and 1-
(E)-b-styryl-5-methylpyrazole (1d), in a 70:30 ratio with the
major product being the former compound. The inductive
effect of the methyl group (+I) is expected to favor vinyla-
tion on the a-nitrogen atom but this effect is probably coun-
terbalanced by the induced steric hindrance, which is appa-
rently predominant. The regioselectivity observed for con-
densation of 3-methylpyrazole and 3-trifluoromethylpyra-
zole with (E)-b-bromostyrene is similar to that already re-
ported for N-arylation reactions of these nitrogen
heterocycles.[31c]
The scope of the process was also investigated in the case
of other nitrogen heterocycles. Imidazole proved to be as re-
active as pyrazole since 1-(E)-b-styrylimidazole (1e) could
also be isolated in 90% yield (Table 1, entry 4) after 30 h at
508C. Our procedure is complementary to that involving ad-
dition of this nitrogen heterocycle across phenylacetylene in
the presence of sodium, as described by Bourgeois and Lu-
crece (Scheme 2, c), a process that exclusively yields the Z
stereoisomer.[17f] It is moreover both simpler and more effi-
cient than the synthesis of alkylation/dehydrohalogenation
(Scheme 2a) that was proposed by Cooper and Irwin, which
leads to 1e in 49% yield after alkylation of imidazole by
styrene oxide, chlorination of the corresponding 1-(2-hy-
droxy-2-phenylethyl)imidazole by thionyl chloride, and sub-
sequent dehydrochloration in the presence of KOH.[14f] N-vi-
nylation of indazole by (E)-b-bromostyrene, almost quanti-
tative after 24 h at 608C and quantitative at 808C (Table 1,
entry 5), gave rise to a mixture of two regioisomers that
were easily separated by column chromatography, 1-(E)-b-
styrylindazole (1 f) and, to a minor extent, 2-(E)-b-styrylin-
dazole (1g). Indazoles 1 f and 1g, which result from substi-
tution on the N1 and N2 positions, respectively, are obtained
in an approximately 6:1 ratio and can be distinguished by
their NMR spectra. Both display a greater JH6,H7 coupling
constant than the JH5,H6 one, but this difference is weaker in
the case of the 1-substituted indazole (JH6,H7/JH5,H6 =1.1 for
1 f and 1.3 for 1g; see the Experimental Section).[37]
N-Vinylation of tri- and tetrazolesby b-bromostyrenes: We
then focused our attention on extending this methodology
to the N-vinylation of tri- and tetrazoles (Table 2). We first
investigated the N-vinylation of benzotriazole, 1,2,4-triazole,
and 1,2,3-triazole by b-bromostyrene in the presence of the
same catalytic system, CuI/3 in a 2:1 ratio and cesium carbo-
nate in acetonitrile at 808C. Unfortunately, the correspond-
ing styryltriazoles were not formed under these conditions
(Table 2, entries 1, 4, and 7). Yields were however signifi-
cantly increased by replacing acetonitrile with N,N-dime-
thylformamide (DMF), in which the cesium salts of the tri-
azoles were probably more soluble (Table 2, entries 2 and
5), and we were pleased to find that total conversion of (E)-
b-bromostyrene occurred at 1108C in this solvent (Table 2,
entries 3 and 6). N-Substitution of 1,2,4-triazole (entry 6) re-
giospecifically took place at the N1(2) atom whose en-
hanced nucleophilicity in comparison with the N4 nitrogen
atom could be due to an a effect. By contrast, N-vinylation
of benzotriazole gave rise to two regioisomeric compounds,
1-(E)-b-styrylbenzotriazole (1j) and 2-(E)-b-styrylbenzotri-
A
matography. The substitution preferentially occurred at the
N1 position (ratio of 1j/1kꢁ10:1), which is in agreement
with the highest electronic density being found on this atom
in the benzotriazolate anion.[38] Once more, the structures of
both regioisomers could be assigned according to their
1H/13C NMR spectra since the benzotriazole unit in the N2-
substituted compound 1k has a symmetry and thus displays
equivalent signals for the protons and respective carbon
atoms at positions 4 and 7 on the one hand and for the pro-
tons and respective carbon atoms at positions 5 and 6 on the
other hand. The coupling reaction of 1,2,3-triazole and
(E)-b-bromostyrene also led to a mixture of 1-(E)-b-styryl-
1,2,3-triazole (1m) and 2-(E)-b-styryl-1,2,3-triazole (1n);
both regioisomers were formed in comparable amounts
(ratio of 1n/1mꢁ1.3:1). This result is in agreement with the
fact that the electron densities on the N1 and N2 atoms of
the triazole ring are similar.[38]
We then tried to extend our methodology to N-vinylation
of tetrazole derivatives. Unfortunately, attempts to achieve
the coupling reaction of 5-phenyltetrazole and b-bromostyr-
ene at 1108C was unsuccessful, with the vinylating agent
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Copper-Catalyzed Vinylation Reactions
FULL PAPER
Table 2. N-Vinylation of tri- and tetrazoles by b-bromostyrenes (E/Z=90:10).[a]
nylation of 1,2,4- and 1,2,3-tri-
azoles was performed at 1108C,
small amounts (4–5%)[39] of 1-
(Z)-styryl-1,2,4-triazole (1’l), 1-
(Z)-styryl-1,2,3-triazole (1’m),
and 2-(Z)-styryl-1,2,3-triazole
(1’n) were formed (Table 2, en-
tries 6 and 8, footnote [d]). At
this temperature, the side de-
hydrobromination of (Z)-b-
bromostyrene ((Z)-4), which
occurred exclusively in the
case of mono- and diazoles
(50–808C; Table 1), was in
competition with the N-vinyla-
tion of triazoles. It is notewor-
thy that, under these condi-
tions, N-vinylation of the more
hindered benzotriazole by (Z)-
4 was not observed (Table 2,
entry 3).
Moreover, whatever the
nature of the solvent (CH3CN
or DMF) and the temperature
(80 or 1108C), (Z)-4 also led
to phenylacetylene (5; ꢂ5%)
and to 1,4-diphenylbutadiyne
(6; ꢂ2%; Table 2, footnote
[a]). 1-(E)-4-diphenyl-but-1-en-
3-yne (7), the major side prod-
uct obtained from the N-vinyl-
Entry Azole
Solvent T [8C]
(E)-Styrylazole 1
(E)-4 Conversion [%] Yield of 1 [%][b]
1j
1k
<1
0
1
CH3CN 80
ꢁ2[c]
2
3
DMF
DMF
80
1j
1k
1j
44[c]
40
2
110
100[c]
89 (87)
9 (7)
1k
4
CH3CN 80
1l
ꢁ2[c]
<1
5
DMF
DMF
80
110
54
54
6[d]
100
100 (94)
1m
1n
0
<1
7
CH3CN 80
ꢁ2[c]
ation
of
5-phenyltetrazole
(Table 2, entry 9), was also oc-
casionally observed in small
amounts (ꢂ2%; Table 2, foot-
note [c]). To better understand
the origin of these by-products,
the mixture of both stereo-
isomers was heated for 24 h at
808C in the presence of differ-
ent additives (Table 3). The
presence of only cesium carbo-
nate led to quantitative dehy-
8[d]
DMF
DMF
110
110
1m
1n
100
43 (38)
57 (50)
9
–
–
100[e]
0
[a] Reaction conditions for yields of isolated product: b-bromostyrene (E/Z=90:10, 2 mmol), azole (3 mmol),
Cs2CO3 (4 mmol), CuI (0.20 mmol), ligand 3 (0.10 mmol), CH3CN (1.2 mL); reaction conditions for yields
measured by GC analysis: b-bromostyrene (E/Z=90:10) (0.5 mmol), azole (0.75 mmol), Cs2CO3 (1 mmol),
CuI (0.05 mmol), ligand 3 (0.025 mmol), CH3CN (300 mL). Byproducts detected whatever the solvent and the
temperature: phenylacetylene 5 (ꢂ5%) and diyne 6 (ꢂ2%; structure given in Table 3). [b] Yields refer to GC
yields (with 1,3-dimethoxybenzene as an internal standard) and yields in brackets refer to yields of isolated
products; yields are based on (E)-b-bromostyrene. [c] Formation of 7 with ꢂ2% yield (structure given in
Table 3). [d] (Z)-Styrylazoles 1’l, 1’m, and 1’n formed from (Z)-4 in 4–5% yield. [e] Total conversion of (E)-
and (Z)-b-bromostyrene into styrene (30%) and enyne 7 (35%). [f] By-products detected whatever the solvent
and the temperature: phenylacetylene 5 (5%) and diyne 6 (2%).
drobromination of the
Z
isomer, with the corresponding
(E)-b-bromostyrene, in con-
trast, being totally recovered
being quantitatively consumed to yield styrene and enyne 7
in 30 and 35% yields, respectively (Table 2, entry 9). The
low reactivity of this nitrogen heterocycle may be attributed
to its poor nucleophilicity. To our knowledge, the only
method enabling metal-catalyzed N-vinylation of tetrazole
derivatives involves mercuric acetate, whose disadvantages
were mentioned in the Introduction.
after 24 h at 808C (Table 3, entry 2). Finally, it was highlight-
ed that the combined action of both the catalytic system and
cesium carbonate enabled two further copper-catalyzed side
reactions (Table 3, entry 3): 1) the self-coupling of 5 to yield
diyne 6 and 2) the cross-coupling of 5 with (E)-4 to form
enyne 7. The ability of copper iodide to catalyze coupling
reactions of acetylenic compounds and vinyl iodides to yield
1,3-enynes has also been recently reported.[40]
By-productsderived from ( Z)-b-bromostyrene ((Z)-4) and
proposed pathways to explain their formation: When N-vi-
To sum up (Scheme 3), the more sterically encumbered
(Z)-b-bromostyrene was less reactive than the correspond-
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5305

M. Taillefer et al.
Table 3. Evolution of b-bromostyrenes (E/Z=90:10) in the presence of different additives.[a]
nitrogen heterocycle, among
which are 1) the nucleophilici-
ty, which is generally weaker
when the azole displays more
nitrogen atoms, 2) the ease
of ionization, which can be
estimated from the pKHA
values (Scheme 4), and 3) the
ability to efficiently coordi-
nate copper salts, which de-
pends on both electronic and
steric properties of the sub-
strate.
Entry
Additives
Yield [%]
(E)-4
(Z)-4
5
6
7
1
2
3
no additive
Cs2CO3 (2 equiv)
CuI (10 mol%) + 3 (5 mol%) + Cs2CO3 (2 equiv)
90
90
85
10
0
0
0
10
<1
0
0
2
0
0
5
[a] The compositions of the final mixtures were determined by GC analysis with 1,3-dimethoxybenzene as an
internal standard.
ing E isomer towards coupling with mono-, di-, and triazoles
and was thus mainly or even quantitatively consumed by the
above-mentioned side reactions, namely, dehydrobromina-
tion leading to 5 and, for reaction temperatures higher than
808C, further copper-catalyzed formation of diyne 6 and
enyne 7.
O-Vinylation of phenol derivativesby b-bromostyrenes: The
scope of the above-described methodology was then extend-
ed to vinylation of phenol derivatives by (E)-b-bromosty-
rene. The same catalytic system involving copper iodide
(10 mol%) and ligand 3 (5 mol%) was found to efficiently
promote the coupling reaction of electron-neutral and elec-
tron-rich phenols (Table 4, entries 1–3). O-vinylation of less
reactive substrates substituted with more electron-withdraw-
ing chloro and fluoro groups also proved to be successful
(Table 4, entries 4 and 5). In all cases, b-styryl aryl ethers
were formed in high yields and selectivities and the coupling
reactions proceeded under very mild temperature conditions
in comparison with the existing methods (Scheme 1). More-
over, lower ligand loadings than in other copper-mediated
O-vinylation reactions can be employed.[27,28] Our methodol-
ogy encountered, however, some limitation in the case of
phenols bearing the strongly electron-withdrawing nitro
group (Table 4, entry 6); O-vinylation of 4-nitrophenol did
not occur, even under more forcing conditions (DMF,
1108C; Table 4, footnote [c]). The poor reactivity of such
acidic phenols in Ullmann-type couplings is well-known.[41]
Finally, whatever the nature of the phenol derivative, no
traces of (Z)-styryl aryl ethers resulting from O-vinylation
by (Z)-b-bromostyrene ((Z)-4) were detected. As for azoles,
(Z)-4 proved to be less reactive than its corresponding E
Comparative reactivitiesof nitrogen heterocycles : The order
of reactivity in the azole series emerging from our studies is
given in Scheme 4. Diazoles (pyrazoles, imidazole, indazole)
were found to be the most reactive, since they underwent
almost quantitative N-vinylation after 24–30 h at tempera-
tures of 50–608C. We observed that less acidic monoazoles
(pyrrole and indole) were a bit less reactive since a tempera-
ture of 808C was required to obtain (E)-b-styryl-monoazoles
1h and 1i in quantitative yields within the same time. Both
pyrrole and indole exhibited similar reactivity, which could
mean that the steric hindrance of the latter was counterbal-
anced by its greater ability to be deprotonated (pKHA values
are given in Scheme 4). Finally, despite their higher acidity
and their consequently greater ease of ionization, triazoles
required more forcing conditions than mono- and diazoles
to undergo N-vinylation by (E)-b-bromostyrene (DMF,
1108C). This result can be rationalized by invoking their
poorer nucleophilicity.
The order we observed can reasonably be considered as a
result of several parameters controlling the reactivity of the
Scheme 3. Formation of by-products derived from (Z)-b-bromostyrene ((Z)-4).
Scheme 4. Order of reactivity in the azole series for N-vinylation by (E)-b-bromostyrene. DMSO=dimethyl sulfoxide.
5306
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Chem. Eur. J. 2006, 12, 5301 – 5313

Copper-Catalyzed Vinylation Reactions
FULL PAPER
Table 4. O-Vinylation of substituted phenols by b-bromostyrenes (E/Z=90:10).[a]
were here formed in poor
yields after 24 h at 808C (21%
and 5%, respectively; Table 5,
entries 1 and 4). It was noticed
that an increase of the ligand
loading (from 5% up to 20%)
significantly improved the effi-
ciency of both coupling reac-
tions (Table 5, entries 2 and 5).
Finally, we were pleased to
find that quantitative O-vinyla-
tion of 3,5-dimethylphenol
could be achieved by replacing
tetradentate ligand 3 with the
original bidentate ligand 8 and
that ether 2g could thus be iso-
lated in 89% yield (Table 5,
entry 3). The action of ligand 8
also improved the yield for N-
vinylation of pyrazole since N-
vinylpyrazole 1o was obtained
in 55% after 24 h at 808C
(Table 5, entry 6) and the out-
come of this reaction could be
improved by increasing the re-
action time. The weaker steric
hindrance of ligand 8, in com-
parison with that of ligand 3,
may allow the promotion of
the coupling of more encum-
bered substrates, such as 1-
bromo-2-methylpropene. These
last results highlight the neces-
sity of having a diverse range
of ligand frameworks to tune
the behavior of our catalytic
systems with a view to extend-
ing their scope. We have al-
ready underlined this fact in
Entry Phenol
(E)-b-Styryl aryl ether 2[a]
(E)-4 Conversion [%] Yield of 2 [%][b]
1
2a
92
92 (75)
2
2b
2c
2d
2e
2 f
100
95
100
89
0
100 (90)
95 (82)
100 (82)
89 (74)
–
3
4
5
6[c]
[a] Reaction conditions for yields of isolated products: b-bromostyrene (E/Z=90:10, 5 mmol), phenol
(7.5 mmol), Cs2CO3 (10 mmol), CuI (0.5 mmol), ligand 3 (0.25 mmol), CH3CN (3 mL); reaction conditions for
yields measured by GC analysis: b-bromostyrene (E/Z=90:10, 0.5 mmol), phenol (0.75 mmol), Cs2CO3
(1 mmol), CuI (0.05 mmol), ligand 3 (0.025 mmol), CH3CN (300 mL). [b] Yields refer to GC yields (with 1,3-di-
methoxybenzene as an internal standard) and yields in brackets refer to yields of isolated products after purifi-
cation by column chromatography on alumina; yields are based on (E)-b-bromostyrene. [c] DMF, 1108C.
isomer and was quantitatively converted into phenylacety-
lene (5).
the case of arylation reactions of N-, C-, and O-nucleo-
philes.[30,31]
N-/O-Vinylation by 1-bromo-2-methylpropene: The scope
of the process with respect to the vinyl bromide structure
was next investigated. 1-bromo-2-methylpropene was chosen
as the vinylating agent: this trisubstituted substrate is more
sterically encumbered than (E)-b-bromostyrene and cannot
undergo dehydrobromination as (Z)-b-bromostyrene did.
The coupling of 3,5-dimethylphenol and pyrazole with 1-
bromo-2-methylpropene was first carried out in the presence
of the catalytic system involving copper iodide (10 mol%)
and ligand 3 (5 mol%), with cesium carbonate as a base, in
acetonitrile. Whereas these conditions enabled quantitative
vinylation of both nucleophiles by (E)-b-bromostyrene
under very mild conditions (Table 1, entry 1 and Table 4,
entry 1), the expected 3,5-dimethylphenyl 2-methyl-1-pro-
penyl ether (2g) and 1-(2-methyl-1-propenyl)pyrazole (1o)
Proposed mechanism for N- and O-vinylation of azoles and
phenolsby vinyl bromides : The proposed mechanism for
the N- and O-vinylation reactions with vinyl bromides is
similar to that we described for arylation reactions with our
copper-based systems (Scheme 5).[31a,d] To our knowledge, no
mechanism has been proposed in the literature for copper-
catalyzed vinylations of nucleophiles. The first step should
involve oxidative addition of the vinyl bromide to the cata-
lytically active copper species A, which is thought to be a
copper(i) complex involving ligands. The resulting copper-
A
tion of the copper-bound bromide by a nucleophile to give
C. The third step should consist of the reductive elimination
of N-(1-alkenyl)azoles 1 or alkenyl aryl ethers 2 and the
subsequent regeneration of the active copper(i) species. It is
Chem. Eur. J. 2006, 12, 5301 – 5313
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5307

M. Taillefer et al.
Table 5. Vinylation of pyrazole and 3,5-dimethyphenol by 1-bromo-2-methylpropene.[a]
slower) than that of the corre-
sponding E isomer, probably
because of its greater steric
hindrance.[42] The improved ef-
ficiency of bidentate ligand 8
over that of tetradentate ligand
3 for achieving N- and O-vi-
nylations with the trisubstitut-
ed 1-bromo-2-methylpropene
could be rationalized by invok-
ing the smaller steric bulk it
generates on the active cop-
per(i) species A. The latter
species would consequently
more easily accept sterically
hindered substrates during the
oxidative addition.
Entry
1
Nucleophile
Ligand (mol%)
Product
Yield [%][b]
3 (5)
2g
1o
21
2
3
3 (20)
8 (20)
50
100 (89)
4
3 (5)
5
Conclusion
5
6
3 (20)
8 (20)
35
55 (47)
We have developed a straight-
forward and efficient method
allowing quantitative N-vinyla-
tion of nitrogen heterocycles
by (E)-b-bromostyrene under
the catalysis of an inexpensive
copper-based system involving
CuI (10 mol%) and tetraden-
tate ligand 3 (5 mol%). This
method is general since it is
applicable to a wide range of
mono-, di-, and triazoles and,
to the best of our knowledge,
this is the first copper catalytic
system allowing N-vinylation
of these substrates. (E)-styryl
aryl ethers could also be ob-
tained in high yields and selec-
tivities by O-vinylation of vari-
ous substituted phenols with
[a] Reaction conditions for yields of isolated products: nucleophile (2 mmol), 1-bromo-2-methylpropene
(3 mmol), Cs2CO3 (4 mmol), CuI (0.2 mmol), ligand 8 (0.4 mmol), CH3CN (1.2 mL); reaction conditions for
yields measured by GC analysis: nucleophile (0.5 mmol), 2-methyl-1-bromopropene (0.75 mmol), Cs2CO3
(1 mmol), CuI (0.05 mmol), ligand 3 or 8 (see Table), CH3CN (300 mL). [b] Yields refer to GC yields (with 1,3-
dimethoxybenzene as an internal standard) and yields in brackets refer to yields of isolated products after pu-
rification by column chromatography on silica gel or alumina; yields are based on nucleophile.
(E)-b-bromostyrene
under
similar conditions. Finally, it
was noticed that (Z)-b-bro-
mostyrene was less reactive
Scheme 5. Possible mechanism for copper-catalyzed N- and O-vinylation of azoles and phenols by vinyl bro-
mides. OA=oxidative addition, NS=nucleophilic substitution, RE=reductive elimination.
than the corresponding
E
isomer and mainly gave rise to
byproducts. This copper-based
worth noting that the nucleophilic substitution step could
also precede the oxidative addition step.
methodology could successfully be extended to N- and O-vi-
nylation with more encumbered vinylating agents such as
the trisubstituted 1-bromo-2-methylpropene. In this case,
the less hindered bidentate ligand 8 was shown to be more
efficient for promoting the coupling.
Whatever the nature of the nucleophile (either azole or
phenol) and the vinylating agent, coupling reactions proceed
under mild temperature conditions (35–1108C for N-vinyla-
tion reactions; 50–808C for O-vinylation reactions) and by
The poorer reactivity of the more hindered (Z)-b-bromo-
styrene and 1-bromo-2-methylpropene towards N- and O-
nucleophiles in comparison with that of (E)-b-bromostyrene
may be explained by their lower ease for performing oxida-
tive addition on the copper(i) complex. Indeed, Jutand has
shown that oxidative addition of (Z)-b-bromostyrene on pal-
ladium-based catalysts was significantly slower (35 times
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Chem. Eur. J. 2006, 12, 5301 – 5313

Copper-Catalyzed Vinylation Reactions
FULL PAPER
under a stream of nitrogen at room temperature, followed by anhydrous
and degassed solvent (acetonitrile or DMF, 1.2 mL). The tube was sealed
under a positive pressure of nitrogen and the mixture was stirred and
heated to the required temperature for the required time period. After
cooling to room temperature, the mixture was diluted with dichlorome-
thane (ꢁ25 mL) and filtered through a plug of celite, with the filter cake
being further washed with dichloromethane (ꢁ5 mL). The filtrate was
washed twice with water (ꢁ10 mL”2). The collected aqueous phases
were extracted twice with dichloromethane (ꢁ10 mL”2). The organic
layers were collected, dried over MgSO4, filtered, and concentrated in
vacuo to yield a brown oil. The crude product obtained was purified by
silica gel or alumina chromatography with an appropriate eluent (men-
tioned below for each target product).
using particularly low copper and ligand loadings. Thus, this
practical protocol, which is very competitive compared to all
of the existing methods for the synthesis of N-(1-alkenyl)-
A
industrial applications.
Work to extend the scope of our vinylation method to
other vinyl bromides and chlorides as well as to other nucle-
ophiles is in progress in our laboratory. Other applications
of our copper catalytic systems and a general mechanistic
study concerning copper-catalyzed arylations and vinylations
of nucleophiles will also be reported soon.
General procedure for the N-vinylation of pyrazole and O-vinylation of
3,5-dimethylphenol by 1-bromo-2-methylpropene (2-mmol scale): After
standard cycles of evacuation and back-filling with dry and pure nitrogen,
an oven-dried Radley tube equipped with a magnetic stirring bar was
charged with CuI (38.0 mg, 0.2 mmol), ligand 8 (72.8 mg, 0.4 mmol), the
nucleophile (136.2 mg of pyrazole or 244.4 mg of 3,5-dimethylphenol,
2 mmol), and Cs2CO3 (1.303 g, 4 mmol). The tube was evacuated and
back-filled with nitrogen. 1-bromo-2-methylpropene (307 mL, 3 mmol)
was added by syringe under a stream of nitrogen at room temperature,
followed by anhydrous and degassed acetonitrile (1.2 mL). The tube was
sealed under a positive pressure of nitrogen and the mixture was stirred
and heated to 808C for 24 h. The workup was the same as that for vinyla-
tion by b-bromostyrenes.
Experimental Section
General: Column chromatography was performed with SDS 60 A C.C
silica gel (35–70 mm). Thin-layer chromatography was carried out by
using Merck silica gel 60 F254 plates. Products were characterized by their
NMR, GC/MS, and IR spectra. NMR spectra were recorded at 208C on
DRX-250 and DRX-400 spectrometers working at 250.13 and
400.13 MHz, respectively, for 1H spectra, at 62.90 and 100.61 MHz, re-
spectively, for 13C spectra, and at 236.36 and 376.50 for 19F spectra. Cou-
pling constants are reported in Hz and chemical shifts (d) in ppm relative
to tetramethylsilane for 1H and {1H}13C spectra (d=77.00 ppm for the
CDCl3 signal in the 13C spectra) and in ppm relative to CFCl3 for {1H}19F
spectra. The first-order peak patterns are indicated as s (singlet), d (dou-
blet), t (triplet), and q (quadruplet). Complex non-first-order signals are
indicated as m (multiplet) and broad signals as br. 13C NMR signals were
assigned by using HMQC and HMBC sequences. Gas chromatography–
mass spectrometry (GC/MS) spectra were recorded on an Agilent Tech-
nologies 6890 N instrument with an Agilent 5973 N mass detector (EI)
and an HP5-MS 30 m”0.25 mm capillary apolar column (stationary
phase: 5% diphenyldimethylpolysiloxane film, 0.25 mm). GC/MS
method: initial temperature=458C, initial time=2 min, gradient=
108Cminꢀ1, final temperature=2508C, final time=10 min. IR spectra
were recorded on a Nicolet 210 FT-IR instrument (a neat thin film for
liquid products and a KBr pellet or carbon tetrachloride solution for
solid products). FAB+ and high-resolution mass spectra were recorded
on a JEOL JMS-DX300 spectrometer (3 keV, xenon) in a meta-nitroben-
zylalcohol matrix. Melting points were determined by using a Büchi B-
540 apparatus and are uncorrected.
General procedure for reactivity comparisons or screening of reaction
conditions(0.5-mmol csale) : The above procedures were applied on a
0.5-mmol scale. After heating for the required time period at the re-
quired temperature, the reaction mixture was allowed to cool to room
temperature and was diluted with dichloromethane (5 mL). 1,3-Dimeth-
oxybenzene (65 mL, as an internal standard) was added. A small sample
of the reaction mixture was taken and filtered through a plug of celite,
with the filter cake being further washed with dichloromethane. The fil-
trate was washed three times with water and analyzed by gas chromatog-
raphy. The GC yields were determined by obtaining correction factors by
using authentic samples of the expected products.
Materials: All reactions were carried out in 35-mL Schlenk tubes or in
Carousel “reaction stations RR98030” Radley tubes, under a pure and
dry nitrogen atmosphere. Acetonitrile was distilled from P4O10 and DMF
was distilled under vacuum from MgSO4; both were stored protected
from light over 4-Š activated molecular sieves under a nitrogen atmos-
phere. Cesium carbonate (Aldrich) was ground to a fine powder and
stored under vacuum in the presence of P4O10. All other solid materials
were stored in the presence of P4O10 in a bench-top desiccator under
vacuum at room temperature and weighed in air. Copper(i) iodide was
purified according to literature procedures[43] and stored protected from
light. The synthesis of ligand 1 was reported in our previous papers[30]
and the procedure to obtain ligand 7 is reported below. Vinyl halides,
azoles, and phenols were purchased from commercial sources (Aldrich,
Acros, Avocado, Fluka, or Lancaster). Solids were recrystallized in an ap-
propriate solvent.[44] Liquids were distilled under vacuum and stored
under an atmosphere of nitrogen.
2-Pyridylidenaminobenzene (8): Anhydrous magnesium sulphate (18.0 g,
0.15 mol) and rac-trans-1,2-diaminocyclohexane (9.31 g, 0.10 mol) were
successively added to a solution of 2-pyridylaldehyde (10.7 g, 0.10 mol) in
absolute ethanol (60 mL). The mixture was stirred for 16 h at room tem-
perature and filtered through a frit. The solid was discarded and the fil-
trate was concentrated in vacuo. Trituration in pentane led to the precipi-
tation of the desired product (16 g, 88%): 1H NMR (CDCl3): d=8.75
(ddd, 1H, 3JH5,H6 =4.9, 4JH4,H6 =1.8, 5JH3,H6 =1.0 Hz, H6), 8.64 (brs, 1H,
H7), 8.24 (ddd, 1H, 3JH3,H4 =7.9, 4JH3,H5 =1.3, 5JH3,H6 =1.0 Hz, H3), 7.86
3
3
4
5
General procedure for the N-vinylation of azolesand O-vinylation of
phenolsby b-bromostyrenes (2-mmol scale): After standard cycles of
evacuation and back-filling with dry and pure nitrogen, an oven-dried
Radley tube equipped with a magnetic stirring bar was charged with CuI
(38.0 mg, 0.2 mmol), ligand 3 (29.2 mg, 0.1 mmol), the nucleophile if a
solid (the azole or the phenol, 3 mmol), and Cs2CO3 (1.303 g, 4 mmol).
The tube was evacuated and back-filled with nitrogen. b-Bromostyrene
(256 mL, 3 mmol) and the nucleophile if a liquid were added by syringe
(dddd, 1H, JH3,H4 =7.9, JH4,H5 =7.5, JH4,H6 =1.8, JH4,H7 =0.6 Hz, H4), 7.41
(ddd, 2H, 3JH4,H5 =7.5, 3JH5,H6 =4.9, 4JH3,H5 =1.3 Hz, H5), 7.45 (m, 2H,
H11), 7.31 ppm (m, 3H, H10, H12); 13C NMR: d=160.43 (C7), 154.34
(C2), 150.77 (C9), 149.51 (C6), 136.45 (C4), 129.04 (C11), 126.54 (C12),
124.94 (C5), 121.68 (C3), 120.92 ppm (C10); GC/MS (EI): rt=19.39 min,
m/z: 182; IR (CCl4): n˜ =3050, 2893, 1622 (m, C=N), 1588, 1563, 1483,
1463, 1449, 1431, 1345, 1199, 1165, 1144, 1090, 989, 978, 912, 873, 778,
762, 739, 689, 666, 618, 550, 534, 405 cmꢀ1
.
Chem. Eur. J. 2006, 12, 5301 – 5313
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5309

M. Taillefer et al.
3JH3,H4 =0.9, 4JH4,H6 =0.9, 5JH1’,H4 =0.9 Hz, H4), 2.31 ppm (brs, CH3);
13C{1H} NMR (CD2Cl2): d=140.75 (C3), 139.16 (C5), 136.08 (C3’), 129.16
(C5’), 127.72 (C6’), 126.53 (C4’), 123.40 (C1’), 117.65 (C2’), 107.04 (C4),
11.24 ppm (C6); GC/MS (EI): rt=19.87 min, m/z: 184; Rf =0.38 (di-
chloromethane); IR (KBr): same as for 1c.
1-(E)-Styrylimidazole (1e): N-Vinylation of imidazole (204 mg, 3 mmol)
was achieved by following the general procedure (acetonitrile, 508C,
30 h). The crude oily residue was purified by flash chromatography on
silica gel (eluent: hexanes/CH2Cl2 100:0!50:50) to provide the desired
product (280 mg, 90% yield) as a white solid: M.p. 86–878C (dichlorome-
thane/hexane; Lit.:[45] 87–888C (diethyl ether)); 1H NMR (CD2Cl2): d=
3
7.78 (t, 4JH2,H4 =4JH2,H5 =1.2 Hz, H2), 7.47 (m, H4’), 7.43 (d, JH1’,H2’
=
14.6 Hz, H1’), 7.41 (m, H5’), 7.35 (dd, 3JH4,H5 =3.9, 4JH2,H4 =1.2 Hz, H4),
7.33 (m, H6’), 7.14 (m, H5), 6.81 ppm (d, 3JH1’,H2’ =14.6 Hz, H2’); 13C{1H}
NMR (CD2Cl2): d=136.87 (C2), 135.05 (C3’), 130.61 (C5), 129.28 (C5’),
128.30 (C6’), 126.50 (C4’), 123.24 (C1’), 118.75 (C2’), 116.64 ppm (C4);
GC/MS (EI): rt=20.03 min, m/z: 169; Rf =0.25 (dichloromethane); IR
(KBr): n˜ =3148, 3109, 3095, 3069, 3032, 3000, 1656, 1511, 1496, 1485,
1454, 1291, 1252, 1217, 1199, 1162, 1105, 1078, 1019, 937, 903, 838, 826,
N-Alkenylazolesand alkenyl aryl ethers : Chemical shifts have been as-
signed by using the following numbering systems. The numbering systems
of the different azole moieties are given in Table 1 and Table 2.
N-Alkenylazoles:
761, 728, 695, 655, 618, 582, 509 cmꢀ1
.
1-(E)-Styrylpyrazole (1a): N-Vinylation of pyrazole (204 mg, 3 mmol)
was achieved by following the general procedure (acetonitrile, 508C,
30 h). The crude oily residue was purified by flash chromatography on
silica gel (eluent: hexanes/CH2Cl2 100:0!50:50) to provide the desired
product (290 mg, 94% yield) as a white solid: M.p. 53–548C (hexanes/
1-(E)-Styrylindazole (1 f) and 2-(E)-styrylindazole (1g): N-Vinylation of
indazole (354 mg, 3 mmol) was achieved by following the general proce-
dure (acetonitrile, 808C, 24 h). The crude oily residue was purified by
flash chromatography on silica gel (eluent: hexanes/CH2Cl2 100:0!
50:50) to provide 1 f (317 mg, 80% yield) and 1g (35 mg, 9% yield) as
white solids: 1 f: M.p. 124–1268C; 1H NMR (CD2Cl2): d=8.20 (dd,
4JH3,H4 =1.0, 5JH1’,H3 =0.9 Hz, H3), 7.88 (dd, 3JH1’,H2’ =14.2, 5JH1’,H3 =0.9 Hz,
1
CH2Cl2; Lit.:[31d] 538C (hexanes/CH2Cl2)); H NMR (CD2Cl2): d=7.75 (d,
3
3JH4,H5 =2.3 Hz, H5), 7.68 (d, 3JH3,H4 =1.3 Hz, H3), 7.59 (d, JH1’,H2’
=
14.5 Hz, H1’), 7.50 (m, H4’), 7.40 (m, H5’), 7.34 (m, H6’), 7.10 (d,
3JH1’,H2’ =14.5 Hz, H2’), 6.45 ppm (m, H4); 13C{1H} NMR (CD2Cl2): d=
141.13 (C3), 135.09 (C3’), 128.89 (C5’), 128.14 (C1’), 127.60 (C6’), 126.48
(C5), 126.26 (C4’), 116.88 (C2’), 107.34 ppm (C4); GC/MS (EI): rt=
18.81 min, m/z: 169; Rf =0.30 (dichloromethane); IR (KBr): n˜ =3138,
3121, 3078, 3024, 2964, 1656, 1596, 1517, 1441, 1394, 1378, 1337, 1261,
1227, 1091, 1046, 967, 939, 911, 860, 851, 778, 760, 748, 690, 608, 585, 502,
3
4
5
H1’), 7.83 (ddd, JH6,H7 =8.0, JH5,H7 =1.0, JH4,H7 =1.0 Hz, H7), 7.73 (dddd,
3JH4,H5 =8.0, 4JH3,H4 =1.0, 4JH4,H6 =1.0, 5JH4,H7 =1.0 Hz, H4), 7.57 (m, H4’),
7.54 (ddd, 3JH4,H5 =8.0, 3JH5,H6 =7.0, 4JH5,H7 =1.0 Hz, H5), 7.42 (m, H5’),
3
3
7.30 (d, JH1’,H2’ =14.2 Hz, H2’), 7.29 (m, H6’), 7.29 ppm (ddd, JH6,H7 =8.0,
3JH5,H6 =7.0, 4JH4,H6 =1.0 Hz, H6); 13C{1H} NMR (CD2Cl2): d=139.12
(C8), 136.36 (C3), 136.32 (C3’), 129.18 (C5’), 127.69 (C5), 127.48 (C6’),
126.33 (C4’), 125.34 (C9), 123.75 (C1’), 122.29 (C6), 121.75 (C7), 115.53
(C2’), 109.75 ppm (C4); GC/MS (EI): rt=24.19 min, m/z: 220; HRMS:
calcd for C15H13N2 [M++H]: 221.1079; found: 221.1079; Rf =0.65 (di-
chloromethane); IR (KBr): n˜ =3109, 3052, 3024, 1653, 1613, 1597, 1576,
1490, 1468, 1449, 1423, 1361, 1326, 1290, 1268, 1216, 1177, 1156, 1147,
1116, 1024, 1003, 985, 964, 940, 908, 860, 844, 763, 755, 743, 690, 630, 578,
480 cmꢀ1
.
1-(E)-Styryl-3-trifluoromethylpyrazole (1b): N-Vinylation of 3-trifluoro-
methylpyrazole (408 mg, 3 mmol) was achieved by following the general
procedure (acetonitrile, 508C, 30 h). The crude oily residue was purified
by flash chromatography on silica gel (eluent: hexanes/CH2Cl2 100:0!
50:50) to provide the desired product (430 mg, 98% yield) as a colorless
507, 434 cmꢀ1
;
1g: M.p. 122–1248C; 1H NMR (CD2Cl2): d=8.21 (d,
1
3
5
oil: H NMR (CD2Cl2): d=7.80 (dq, JH4,H5 =2.5, JH5,F =0.9 Hz, H5), 7.57
(d, 3JH1’,H2’ =14.5 Hz, H1’), 7.52 (m, H4’), 7.43 (m, H5’), 7.35 (m, H6’),
7.23 (d, 3JH1’,H2’ =14.5 Hz, H2’), 6.45 ppm (dd, 3JH4,H5 =2.5, 4JH4,F =0.5 Hz,
H4); 13C{1H} NMR (CD2Cl2): d=144.26 (q, 2JC3,F =38.0 Hz, C3), 134.52
3
4JH3,H4 =0.9 Hz, H3), 7.81 (d, 3JH1’,H2’ =14.4 Hz, H1’), 7.71 (ddd, JH6,H7
=
4
5
3
4
8.5, JH5,H7 =0.9, JH4,H7 =0.9 Hz, H7), 7.70 (dddd, JH4,H5 =7.7, JH3,H4 =0.9,
4JH4,H6 =0.9, 5JH4,H7 =0.9 Hz, H4), 7.59 (m, H4’), 7.54 (d, 3JH1’,H2’ =14.4 Hz,
H2’), 7.44 (m, H5’), 7.37 (m, H6’), 7.34 (ddd, 3JH4,H5 =7.7, 3JH5,H6 =6.5,
(C3’), 129.99 (C5), 129.31 (C5’), 128.68 (C6’), 126.86 (C4’), 126.00 (C1’),
4JH5,H7 =0.9 Hz, H5), 7.12 ppm (ddd, 3JH6,H7 =8.5, 3JH5,H6 =6.5, JH4,H6
=
4
3
121.67 (q, 1JC6,F =269.0 Hz, C6), 120.14 (C2’), 105.90 ppm (q, JC4,F
=
0.9 Hz, H6); 13C{1H} NMR (CD2Cl2): d=148.84 (C8), 133.79 (C3’), 128.15
(C5’), 127.46 (C6’), 126.24 (C1’), 126.00 (C5), 125.84 (C4’), 121.57 (C3),
121.55 (C6), 121.19 (C9), 120.19 (C2’), 119.54 (C7), 116.66 ppm (C4);
GC/MS (EI): rt=25.23 min, m/z: 220; HRMS: calcd for C15H13N2 [M+
+H]: 221.1079; found: 221.1081; Rf =0.25 (dichloromethane); IR (KBr):
n˜ =3123, 3061, 2964, 1655, 1626, 1516, 1396, 1378, 1332, 1262, 1160, 1140,
1,5 Hz, C4); 19F NMR (CD2Cl2): d=ꢀ62.43 ppm (s); GC/MS (EI): rt=
18.46 min, m/z: 238; HRMS: calcd for C12H9N2F3 [M+]: 238.0718; found:
238.0718; Rf =0.65 (dichloromethane); IR (KBr): n˜ =3151, 3083, 3064,
3032, 1660, 1483, 1389, 1265, 1226, 1170, 1132, 1056, 1004, 965, 939, 785,
764 748, 691, 668, 508 cmꢀ1
.
1-(E)-Styryl-3-methylpyrazole (1c) and 1-(E)-styryl-5-methylpyrazole
(1d): N-Vinylation of 3-methylpyrazole (242 mL, 3 mmol) was achieved
by following the general procedure (acetonitrile, 508C, 30 h). The crude
oily residue was purified by flash chromatography on silica gel (eluent:
hexanes/CH2Cl2 100:0!50:50) to provide a mixture of the regioisomers
1097, 1022, 942, 800, 754, 695, 641, 614, 511, 442 cmꢀ1
.
1-(E)-Styrylpyrrole (1h): N-Vinylation of pyrrole (208 mL, 3 mmol) was
achieved by following the general procedure (acetonitrile, 808C, 24 h).
The crude oily residue was purified by flash chromatography on silica gel
(eluent: hexanes/CH2Cl2 100:0!50:50) to provide the desired product
(260 mg, 89% yield) as a white solid: M.p. 98–1018C (dichloromethane;
Lit.:[46] 98–1008C (diethyl ether/water)); 1H NMR (CD2Cl2): d=7.44 (m,
H4’), 7.39 (d, 3JH1’,H2’ =14.6 Hz, H1’), 7.38 (m, H5’), 7.27 (m, H6’), 7.05
1c and 1d (300 mg, 89% yield, 1c/1d=70:30) as a colorless oil: 1c:
3
1H NMR (CD2Cl2): d=7.60 (d, 3JH4,H5 =2.4 Hz, H5), 7.49 (d, JH1’,H2’
=
14.4 Hz, H1’), 7.47 (m, H4’), 7.40 (m, H5’), 7.29 (m, H6’), 7.03 (d,
3JH1’,H2’ =14.4 Hz, H2’), 6.23 (d, 3JH4,H5 =2.4 Hz, H4), 2.21 ppm (s, CH3);
13C{1H} NMR (CD2Cl2): d=151.51 (C3), 135.88 (C3’), 129.42 (C5), 129.16
(C5’), 127.58 (C6’), 126.78 (C1’), 126.34 (C4’), 115.56 (C2’), 107.49 (C4),
13.89 ppm (C6); GC/MS (EI): rt=19.50 min, m/z: 184; Rf =0.38 (di-
chloromethane); IR (KBr): n˜ =3134, 3107, 3081, 3060, 3028, 2984, 2927,
1657, 1601, 1577, 1553, 1534, 1450, 1415, 1397, 1365, 1334, 1299, 1226,
1203, 1191, 1094, 1073, 1056, 989, 938, 924, 862, 827, 783, 747, 692, 673,
3
(AA’ system, H2), 6.66 (d, JH1’,H2’ =14.6 Hz, H2’), 6.30 ppm (XX’ system,
H3); 13C{1H} NMR (CD2Cl2): d=136.18 (C3’), 129.15 (C5’), 127.34 (C6’),
127.28 (C1’), 126.03 (C4’), 119.42 (C2), 114.33 (C2’), 110.70 ppm (C3);
GC/MS (EI): rt=18.28 min, m/z: 169; Rf=0.35 (hexanes); IR (KBr): n˜ =
3126, 3098, 3063, 3027, 2965, 1659, 1596, 1520, 1481, 1449, 1374, 1339,
1321, 1306, 1288, 1230, 1200, 1153, 1097, 1072, 1049, 1026, 969, 940, 828,
802, 750, 728, 690, 614, 582, 506, 477 cmꢀ1
.
1
3
651, 591, 581, 510, 491 cmꢀ1; 1d: H NMR (CD2Cl2): d=7.55 (br, JH3,H4
=
0.9 Hz, H3), 7.49 (m, H4’), 7.47 (dd, 3JH1’,H2’ =14.4, 5JH1’,H4 =0.9 Hz, H1’),
1-(E)-Styrylindole (1i): N-Vinylation of indole (351 mg, 3 mmol) was ach-
ieved by following the general procedure (acetonitrile, 808C, 24 h). The
7.40 (m, H5’), 7.29 (m, H6’), 7.27 (d, 3JH1’,H2’ =14.4 Hz, H2’), 6.17 (sextet,
5310
www.chemeurj.org
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 5301 – 5313

Copper-Catalyzed Vinylation Reactions
FULL PAPER
crude oily residue was purified by flash chromatography on silica gel
(eluent: hexanes/ethyl acetate 100:0!80:20) to provide the desired prod-
uct (220 mg, 83% yield) as a white solid: M.p. 115–1178C;[23] 1H NMR
(CD2Cl2): d=8.78 (d, 3JH1’,H2’ =14.5 Hz, H1’), 7.67 (ddd, 3JH4,H5 =7.9,
4JH4,H6 =1.3, 5JH4,H7 =0.9 Hz, H4), 7.63 (dddd, 3JH6,H7 =8.3, 4JH5,H7 =1.0,
5JH3,H7 =0.7, 5JH4,H7 =0.9 Hz, H7), 7.61 (d, 3JH2,H3 =3.4 Hz, H2), 7.53 (m,
H4’), 7.41 (m, H5’), 7.33 (ddd, 3JH6,H7 =8.3, 3JH5,H6 =7.1, 4JH4,H6 =1.3 Hz,
121.60 ppm (C5); GC/MS (EI): rt=20.29 min, m/z: 171; HRMS: calcd
for C10H9N3 [M+]: 171.0802; found: 171.0796; Rf =0.50 (ethyl acetate/di-
chloromethane 1:1); IR (KBr): n˜ =3140, 3123, 3108, 3030, 2963, 1658,
1578, 1489, 1477, 1454, 1435, 1311, 1285, 1262, 1227, 1207, 1178, 1156,
1107, 1076, 1025, 1015, 940, 802, 752, 697, 670, 636, 584, 507, 469 cmꢀ1
;
1n: M.p. 45–488C (ethyl acetate/dichloromethane); 1H NMR (CD2Cl2):
d=7.86 (d, 3JH1’,H2’ =14.4 Hz, H1’), 7.80 (s, H4, H5), 7.55 (m, H4’), 7.47
(d, 3JH1’,H2’ =14.4 Hz, H2’), 7.43 (m, H5’), 7.35 ppm (m, H6’); 13C{1H}
NMR (CD2Cl2): d=134.67 (C4, C5), 133.50 (C3’), 128.11 (C5’), 127.45
(C6’), 125.85 (C4’), 125.66 (C1’), 119.30 ppm (C2’); GC/MS (EI): rt=
17.48 min, m/z: 171; HRMS: calcd for C10H10N3 [M++H]: 172.0875;
found: 172.0867; Rf =0.70 (ethyl acetate/dichloromethane 1:1); IR (KBr):
n˜ =3117, 3084, 3058, 3030, 2964, 1654, 1601, 1541, 1576, 1494, 1448, 1410,
1374, 1332, 1258, 1151, 1071, 1029, 962, 945, 865, 823, 790, 748, 694, 672,
H6), 7.28 (m, H6’), 7.21 (ddd, 3JH4,H5 =7.9, 3JH5,H6 =7.1, 4JH5,H7 =1.0 Hz,
5
H5), 6.77 (d, 3JH1’,H2’ =14.5 Hz, H2’), 6.73 ppm (ddd, 3JH2,H3 =3.4, JH3,H7
=
0.7, JH3,H1’ =0.7 Hz, H3); 13C{1H} NMR (CD2Cl2): d=136.55 (C3’), 136.13
(C8), 129.63 (C9), 129.18 (C5’), 127.26 (C6’), 126.03 (C4’), 124.16 (C7),
123.94 (C1’), 123.12 (C6), 121.51 (C5), 121.28 (C4), 114.31 (C2’), 110.00
(C2), 105.62 ppm (C3); GC/MS (EI): rt=24.34 min, m/z: 219; Rf =0.80
(ethyl acetate/hexanes 1:4); IR (KBr): n˜ =3114, 3043, 3024, 1650, 1596,
1518, 1461, 1365, 1326, 1269, 1230, 1200, 1120, 1089, 1012, 935, 745, 717,
5
588, 512, 479 cmꢀ1
.
695 cmꢀ1
.
1-(2-Methyl-1-propenyl)pyrazole (1o): N-Vinylation of pyrazole by 2-
methyl-1-bromopropene was achieved by following the general proce-
dure. The crude oily residue was purified by flash chromatography on
silica gel (eluent: dichloromethane) to provide 1o (115 mg, 47% yield)
as a colorless oil:[48] 1H NMR (CD2Cl2): d=7.60 (d, 3JH4,H5 =1.8 Hz, H5),
1-(E)-Styrylbenzotriazole (1j) and 2-(E)-styrylbenzotriazole (1k): N-Vi-
nylation of benzotriazole (357 mg, 3 mmol) was achieved by following
the general procedure (DMF, 1108C, 24 h). The crude oily residue was
purified by flash chromatography on silica gel (eluent: hexanes/dichloro-
methane) to provide 1j (354 mg, 87% yield) and 1k (36 mg, 7% yield)
as white solids: 1j: M.p. 116–1198C (dichloromethane/hexanes; Lit.:[47]
115–1168C (benzene/chloroform)); 1H NMR (CD2Cl2): d=8.14 (ddd,
4
4
7.46 (d, 3JH3,H4 =2.4 Hz, H3), 6,70 (dq, JH1’,H3’ or 4JH1’,H4’ =1.6, JH1’,H4’ or
4JH1’,H3’ =1.4 Hz, H1’), 6.32 (dd, 3JH3,H4 =2.4, 3JH4,H5 =1.8 Hz, H4), 1.88 (d,
4JH1’,H3’ or 4JH1’,H4’ =1.6 Hz, H3’ or H4’), 1.85 ppm (d, JH1’,H4’ or JH1’,H3’
=
4
4
1.4 Hz, H4’ or H3’); 13C{1H} NMR (CD2Cl2): d=143.25 (C3), 132.57 (C5),
123.05 (C1’), 121.94 (C2’), 105.05 (C4), 20.12 (C3’ or C4’), 19.25 ppm (C4’
or C3’); GC/MS (EI): rt=9.81 min, m/z: 122; Rf =0.35 (dichlorome-
thane).
3JH4,H5 =8.4, 4JH4,H6 =1.0, 4JH4,H7 =0.9 Hz, H4), 8.03 (d, 3JH1’,H2’ =14.6, H1’),
4
7.86 (ddd, 3JH6,H7 =8.4, 4JH5,H7 =0.9, 4JH4,H7 =0.9, H7), 7.65 (ddd, JH4,H6
=
3
3
3
1.0, JH5,H6 =7.0, JH6,H7 =8.4 Hz, H6), 7.63 (m, H4’), 7.54 (d, JH1’,H2’ =14.6,
H2’), 7.50 (m, H5), 7.48 (m, H5’), 7.39 ppm (m, H6’); 13C{1H} NMR
(CD2Cl2): d=146.32 (C9), 131.57 (C3’), 134.50 (C8), 128.96 (C5’), 128.26
(C6 or C6’), 128.39 (C6 or C6’), 126.56 (C4’), 124.57 (C5), 121.89 (C1’),
120.72 (C2’), 120.17 (C4), 110.17 ppm (C7); GC/MS (EI): rt=25.00 min,
m/z: 221; Rf =0.38 (dichloromethane/hexane 3:1); IR (KBr): n˜ =3069,
3060, 3035, 1655, 1609, 1598, 1486, 1455, 1400, 1326, 1307, 1286, 1267,
1242, 1208, 1164, 1142, 1117, 1076, 1058, 999, 944, 917, 779, 766, 747,
Alkenyl aryl ethers:
3,5-Dimethylphenyl (E)-styryl ether (2a): O-Vinylation of 3,5-dimethyl-
phenol (363 mg, 3 mmol) was achieved by following the general proce-
dure (acetonitrile, 508C, 30 h). The crude oily residue was purified by
flash chromatography on alumina (eluent: hexanes) to provide 2a
(336 mg, 75% yield) as a colorless oil: 1H NMR (CD2Cl2): d=7.25 (m,
695 cmꢀ1
;
1k: M.p. 104–1078C (dichloromethane/hexanes); 1H NMR
3
5H, H4’, H5’, H6’), 7.21 (d, 1H, JH1’,H2’ =12.4 Hz, H1’), 6.79 (m, 1H, H5),
3
(CD2Cl2): d=8.10 (d, 3JH1’,H2’ =14.6 Hz, H1’), 7.92 (AA’ system, JH4,H5
=
6.72 (m, 2H, H3), 6.37 (d, 1H, 3JH1’,H2’ =12.4 Hz, H2’), 2.35 ppm (s, 6H,
CH3); 13C{1H} NMR (CD2Cl2): d=157.17 (C2), 143.67 (C1’), 139.59 (C4),
135.28 (C3’), 128.66 (C5’), 126.53 (C5), 125.60 (C4’), 124.96 (C6’), 114.61
(C3), 113.18 (C2’), 21.33 ppm (C6); GC/MS (EI): rt=22.00 min, m/z:
224; Rf =0.76 (hexanes).
3JH6,H7 =8.8, 4JH4,H6 =3JH5,H7 =1.0, 5JH4,H7 =1.0 Hz, H4, H7), 7.88 (d,
3JH1’,H2’ =14.6 Hz, H2’), 7.65 (m, H4’), 7.48 (m, H5’), 7.47 (XX’ system,
3JH4,H5 =3JH6,H7 =8.8, 3JH5,H6 =6.7, 4JH4,H6 =3JH5,H7 =1.0 Hz, H5, H6),
7.41 ppm (m, H6’); 13C{1H} NMR (CD2Cl2): d=143.58 (C8, C9), 132.53
(C3’), 127.71 (C5’), 127.67 (C6’), 125.94 (C5, C6), 125.90 (C1’), 125.82
(C4’), 123.06 (C2’), 116.68 ppm (C4, C7); GC/MS (EI): rt=23.94 min,
m/z: 221; Rf=0.20 (dichloromethane/hexanes 3:1); IR (KBr): n˜ =3083,
3032, 2964, 1562, 1498, 1447, 1341, 1330, 1291, 1261, 1205, 1187, 1144,
4-tert-Butylphenyl (E)-styryl ether (2b): O-Vinylation of 4-tert-butylphe-
nol (450 mg, 3 mmol) was achieved by following the general procedure
(acetonitrile, 508C, 30 h). The crude oily residue was purified by flash
chromatography on alumina (eluent: hexanes) to provide 2b (482 mg,
90% yield) as a colorless oil: 1H NMR (CD2Cl2): d=7.42 (m, 2H, H4),
7.27 (m, 5H, H4’, H5’, H6’), 7.24 (d, 1H, 3JH1’,H2’ =12.4 Hz, H1’), 7.06 (m,
2H, H3), 6.39 (d, 1H, 3JH1’,H2’ =12.4 Hz, H2’), 1.36 ppm (s, 9H, CH3);
13C{1H} NMR (CD2Cl2): d=154.89 (C2), 146.15 (C1’), 143.91 (C5), 137.27
(C3’), 128.66 (C5’), 126.51 (C4), 126.35 (C6’), 125.58 (C4’), 116.49 (C3),
113.01 (C2’), 34.28 (C6), 31.46 ppm (C7); GC/MS (EI): rt=23.52 min,
m/z: 252; Rf =0.76 (hexanes).
1098, 1021, 958, 917, 887, 844, 801, 756, 741, 693, 624 cmꢀ1
.
1-(E)-Styryl-1,2,4-triazole (1l): N-Vinylation of 1,2,4-triazole (207 mg,
3 mmol) was achieved by following the general procedure (DMF, 1108C,
24 h). The crude oily residue was purified by flash chromatography on
silica gel (eluent: hexanes/ethyl acetate) to provide 1l (322 mg, 94%
1
yield) as an oil: H NMR (CD2Cl2): d=8.37 (s, H5), 8.06 (s, H3), 7.60 (d,
3JH1’,H2’ =14.3 Hz, H1’), 7.51 (m, H4’), 7.42 (m, H5’), 7.35 (m, H6’),
7.30 ppm (d, 3JH1’,H2’ =14.3 Hz, H2’); 13C{1H} NMR (CD2Cl2): d=152.66
(C3), 142.93 (C5), 134.51 (C3’), 129.32 (C5’), 128.37 (C6’), 126.94 (C4’),
122.62 (C1’), 121.10 ppm (C2’); GC/MS (EI): rt=19.13 min, m/z: 171;
HRMS: calcd for C10H10N3 [M++H]: 172.0875; found: 172.0880; Rf =0.65
(ethyl acetate/hexanes 2:1); IR (KBr): n˜ =3119, 3086, 3029, 2865, 1705,
1661, 1601, 1505, 1451, 1420, 1362, 1346, 1300, 1275, 1241, 1196, 1136,
4-Methoxyphenyl (E)-styryl ether (2c): O-Vinylation of 4-methoxyphenol
(372 mg, 3 mmol) was achieved by following the general procedure (ace-
tonitrile, 508C, 30 h). The crude oily residue was purified by flash chro-
matography on alumina (eluent: hexanes/dichloromethane) to provide 1c
(370 mg, 82% yield) as a colorless oil; 1H NMR (CD2Cl2): d=7.26 (m,
3
5H, H4’, H5’, H6’), 7.18 (d, 1H, JH1’,H2’ =12.5 Hz, H1’), 7.06 (m, 2H, H4),
1015, 1001, 943, 863, 780, 749, 693, 672, 647, 586, 509 cmꢀ1
.
6.93 (m, 2H, H3), 6.31 (d, 1H, 3JH1’,H2’ =12.5 Hz, H2’), 3.83 ppm (s, 3H,
CH3); 13C{1H} NMR (CD2Cl2): d=155.65 (C5), 150.90 (C2), 144.72 (C1’),
135.26 (C3’), 128.60 (C5’), 126.38 (C6’), 125.47 (C4’), 118.32 (C3), 114.67
(C4), 112.29 (C2’), 55.56 ppm (C6); GC/MS (EI): rt=23.45 min, m/z:
226; Rf=0.42 (hexanes).
1-(E)-Styryl-1,2,3-triazole (1m) and 2-(E)-styryl-1,2,3-triazole (1n): N-Vi-
nylation of 1,2,3-triazole (138 mL, 3 mmol) was achieved by following the
general procedure (DMF, 1108C, 24 h). The crude oily residue was puri-
fied by flash chromatography on silica gel (eluent: ethyl acetate/dichloro-
methane) to provide 1m (130 mg, 38% yield) as a white solid and 1n
(180 mg, 50% yield) as a greenish solid: 1m: M.p. 95–978C (ethyl ace-
4-Fluorophenyl (E)-styryl ether (2d): O-Vinylation of 4-fluorophenol
(336 mg, 3 mmol) was achieved by following the general procedure (ace-
tonitrile, 508C, 30 h). The crude oily residue was purified by flash chro-
matography on alumina (eluent: hexanes) to provide 1d (351 mg, 82%
yield) as a white solid: 1H NMR (CD2Cl2): d=7.29 (m, 5H, H4’, H5’,
tate/dichloromethane); 1H NMR (CD2Cl2): d=7.96 (d, 3JH4,H5 =1.1 Hz,
5
H5), 7.86 (d, 3JH1’,H2’ =14.9 Hz, H1’), 7.79 (dd, 3JH4,H5 =1.1 Hz, JH1’,H4
=
0.5 Hz, H4), 7.55 (m, H4’), 7.49 (m, H5’), 7.38 (m, H6’), 7.27 ppm (d,
3JH1’,H2’ =14.9 Hz, H2’); 13C{1H} NMR (CD2Cl2): d=134.29 (C4), 134.15
(C3’), 129.37 (C5’), 129.09 (C6’), 127.08 (C4’), 123.45 (C1’), 121.94 (C2’),
3
H6’), 7.16 (d, 1H, JH1’,H2’ =12.4 Hz, H1’), 7.07 (m, 4H, H3, H4), 6.36 ppm
(d, 1H, 3JH1’,H2’ =12.4 Hz, H2’); 13C{1H} NMR (CD2Cl2): d=158.76 (d,
Chem. Eur. J. 2006, 12, 5301 – 5313
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5311

M. Taillefer et al.
1JC5’,F =242.0 Hz, C5), 153.13 (C2), 143.83 (C1’), 134.93 (C3’), 128.69
1982, 97, 216191]; c) B. Zeeh, E. Bucshmann, E. H. Pommer, BASF,
EP 28363, 1981 [Chem. Abstr. 1981, 95, 150670].
[13] U. Kratz, K. Luerssen, Bayer, EP 297393 A2, 1989 [Chem. Abstr.
1989, 110, 231640].
3
(C5’), 126.72 (C6’), 125.63 (C4’), 118.40 (d, JC3’,F =8.0 Hz, C3), 116.21 (d,
2JC4’,F =23.0 Hz, C4), 113.50 ppm (C2’); GC/MS (EI): rt=19.80 min, m/z:
214; Rf=0.71 (hexanes).
[14] For the synthesis of N-alkenylazoles, see: a) E. Abele, O. Dzenitis,
K. Rubina, E. Lukevics, Chem. Heterocycl. Compd. 2002, 38, 682–
685; b) B. Iddon, D. J. Hartley, Tetrahedron Lett. 1997, 38, 4647–
4650; c) T. Kakimoto, JP 04021672 A2, 1992 [Chem. Abstr. 1992,
116, 235635]; d) M. Märky, H. Schmidt, H.-J. Hansen, Helv. Chim.
Acta 1979, 62, 2129–2153; e) G. Cooper, W. J. Irwin, J. Chem. Soc.
Perkin Trans. 1 1976, 798–803; f) G. Cooper, W. J. Irwin, J. Chem.
Soc. Perkin Trans. 1 1976, 545–549; g) G. Cooper, W. J. Irwin, J.
Chem. Soc. Perkin Trans. 1 1976, 75–80. For the synthesis of alkenyl
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4-Chlorophenyl (E)-styryl ether (2e): O-Vinylation of 4-chlorophenol
(386 mg, 3 mmol) was achieved by following the general procedure (ace-
tonitrile, 508C, 30 h). The crude oily residue was purified by flash chro-
matography on alumina (eluent: hexanes) to provide 1e (340 mg, 74%
1
yield) as a white solid: H NMR (CD2Cl2): d=7.22–7.36 (m, 5H, H4’,H5’,
3
H6’), 7.16 (d, 1H, JH1’,H2’ =12.4 Hz, H1’), 7.07 (m, 4H, H3, H4), 6.36 ppm
(d, 1H, 3JH1’,H2’ =12.4 Hz, H2’); 13C{1H} NMR (CD2Cl2): d=155.64 (C2),
142.88 (C1’), 134.72 (C3’), 129.63 (C5’), 128.69 (C4), 128.21 (C5), 126.83
(C6’), 125.68 (C4’), 118.15 (C3), 114.31 ppm (C2’); GC/MS (EI): rt=
21.95 min, m/z: 230; Rf =0.74 (hexanes).
3,5-Dimethylphenyl 2-methylpropenyl ether (2g): O-Vinylation of 3,5-di-
methylphenol by 2-methyl-1-bromopropene was achieved by following
the general procedure. The crude oily residue was purified by flash chro-
matography on alumina (eluent: hexanes) to provide 2g (313 mg, 89%
yield) as a colorless oil: 1H NMR (CDCl3): d=6.72 (m, H3), 6.67 (m,
4
4
4
4
H5), 6.24 (dq, JH1’,H3’ or JH1’,H4’ =1.6, JH1’,H4’ or JH1’,H3’ =1.4 Hz, H1’), 2.36
(m, H6), 1.78 (d, JH1’,H3’ or 4JH1’,H4’ =1.6 Hz, H3’ or H4’), 1.76 ppm (d,
4
4JH1’,H4’ or JH1’,H3’ =1.4 Hz, H4’ or H3’); 13C{1H} NMR (CDCl3): d=158.31
4
(C2), 139.73 (C1’), 135.80 (C4), 124.08 (C5), 117.59 (C2’), 113.96 (C3),
21.79 (C6), 19.95 (C3’ or C4’), 15.59 ppm (C4’ or C3’); GC/MS (EI): rt=
14.98 min, m/z: 176; Rf =0.72 (hexanes).
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Acknowledgements
We thank RHODIA Organique Fine and CNRS for a PhD grant and fi-
nancial support. Prof. A. Fruchier and Karen Lamour are gratefully ac-
knowledged.
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Chem. Eur. J. 2006, 12, 5301 – 5313

Copper-Catalyzed Vinylation Reactions
FULL PAPER
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Received: November 12, 2005
Revised: January 27, 2006
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