A new method for the preparation of aryl vinyl ethers

Full text of DOI:10.1021/jo016037z

J . Org. Chem. 2001, 66, 9043-9045
9043
A New Meth od for th e P r ep a r a tion of Ar yl
Vin yl Eth er s
Marc Blouin* and Richard Frenette
Department of Medicinal Chemistry, Merck Frosst Centre
for Therapeutic Research, P.O. Box 1005,
these processes,11a the discovery of a mild method to
Pointe-Claire - Dorval, Qu e´ bec, Canada, H9R 4P8
prepare aryl vinyl ethers of type 1 is highly desirable.
Recently, Evans published a procedure for the synthe-
sis of diaryl ethers involving a mild copper(II)-promoted
coupling of arylboronic acids and phenols.1 A logical
extension to aryl vinyl ethers of type 1 would be to couple
phenols with vinylboronic acid, but unfortunately this
acid is not very stable.13 In their report, Evans et al.
mention that aryltrialkylstannanes also participate in
this transformation, albeit in lower yields compared to
arylboronic acids. Herein, we report a mild and efficient
copper(II)-promoted conversion of phenols to aryl vinyl
ethers, in a single step, using tetravinyltin as the
vinylating agent.
marc_blouin@merck.com
Received August 16, 2001
2
In tr od u ction
Vinyl ethers are valuable chemical entities that can
be used in a wide array of chemical transformations.1
More specifically, aryl vinyl ethers of the general struc-
ture 1, where the vinyl moiety is unsubstituted, have
2
,3
4,5
been involved in reactions such as [2 + 2], [4 + 2],
6
7
and 1,3-dipolar cycloadditions, cyclopropanations, and
8
hydroformylations. Under acidic conditions, they react
Resu lts a n d Discu ssion
9
with alcohols to give acetals that can act as protecting
groups.9a
We submitted 4-phenylphenol (3a ) to Evans’s reaction
conditions [Cu(OAc)
dered 4 Å molecular sieves, CH
2
(1.0 equiv), Et
3
N (5.0 equiv), pow-
2
(0.1 M in phenol),
Aryl vinyl ethers of the structure 1 are generally
2
Cl
prepared according to either of the following methods:
1
0
room temperature, air exposure] using commercially
available tributyl(vinyl)tin (1.5 equiv) as the vinylating
agent. After 4 days, a filtration workup and chromatog-
raphy afforded the desired vinyl ether 1a in a 22% yield,
slightly contaminated with tin-containing residues. In
attempts to optimize this reaction, only the use of
acetonitrile as the solvent instead of dichloromethane had
a beneficial effect, bringing up the yield to 41%.
the addition of phenols to acetylene and the dehydro-
halogenation of aryl 2-haloethyl ethers (2).11 Both pro-
cedures require strong bases and elevated tempera-
tures. Low to moderate yields of aryl vinyl ethers are
usually obtained and such reactions conditions are
unsuitable for sensitive substrates. Even considering the
improvements brought by Mizuno et al. to the second of
*
To whom correspondence should be addressed. Phone: (514) 428-
240. Fax: (514) 428-4900.
1) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
3
(
Pergamon: Oxford, 1991; Vol. 9, Cumulative Indexes. See enol ethers;
ethers, phenyl vinyl; ethers, vinyl; vinyl ethers.
(
2) For selected examples of [2 + 2] cycloadditions, see: (a) El-Nabi,
H. A. A. Tetrahedron 1997, 53, 1813. (b) Griesbeck, A. G.; Stadtm u¨ ller,
S.; Busse, H.; Bringmann, G.; Buddrus, J . Chem. Ber. 1992, 125, 933.
(
c) Br u¨ ckner, R.; Huisgen, R. Tetrahedron Lett. 1990, 31, 2557.
3) For selected examples of hetero [2 + 2] cycloadditions, see: (a)
Futamura, S.; Ohta, H.; Kamiya, Y. Bull. Chem. Soc. J pn. 1982, 55,
190. (b) Firl, J .; Sommer, S. Tetrahedron Lett. 1970, 11, 1929.
(
Our investigations took a sharp turn when we decided
to substitute tetravinyltin for tributyl(vinyl)tin. This
reagent, in the same conditions, using CH CN as the
3
2
(
4) For selected examples of Diels-Alder reactions, see: (a) Eibler,
E.; H o¨ cht, P.; Prantl, B.; Roâmaier, H.; Schuhbauer, H. M.; Wiest, H.;
Sauer, J . Liebigs Ann./ Recueil 1997, 2741. (b) Mark o´ , I. E.; Evans, G.
R.; Declercq, J .-P. Tetrahedron 1994, 50, 4557.
(
5) For selected examples of hetero Diels-Alder reactions, see: (a)
(10) (a) Skvortsova, G. G.; Stepanova, Z. V.; Andriyankova, L. V.;
Voronov, V. K. Chem. Heterocycl. Compd. (Engl. Transl.) 1983, 19, 379;
Khim. Geterosikl. Soedin 1983, 469. (b) Andriyankov, M. A.; Skvort-
sova, G. G.; Malkova, T. I.; Platonova, A. T. Pharm. Chem. J . (Engl.
Transl.) 1981, 15, 190. (c) Levcenko, A. I.; Moroz, R. A.; Zatolokin, J .
I.; Sminych, V. V. DE Patent 1 802 602, 1970. (d) Turner, J . O.;
Glickman, S. A. DE Patent 1 812 602, 1969. (e) Kalabina, A. V.;
Tyukavkina, N. A.; Bardamova, M. I.; Lavrova, A. S. J . Org. Chem.
USSR (Engl. Transl.) 1961, 31, 3006; Zh. Org. Khim. 1961, 31, 3222.
(f) Reppe, W. Liebigs Ann. Chem. 1956, 601, 81. (g) Reppe, W. U.S.
Patent 2 716 666, 1955. (h) Wilkinson, J . M.; Miller, E. S. U.S. Patent
2 695 920, 1954. (i) Insinger, T. H. U.S. Patent 2 615 050, 1952.
(11) (a) Mizuno, K.; Kimura, Y.; Otsuji, Y. Synthesis 1979, 688. (b)
McClelland, R. A. Can. J . Chem. 1977, 55, 548. (c) Dombroski, J . R.;
Hallensleben, M. L. Synthesis 1972, 693. (d) Oae, S.; Yano, Y.
Tetrahedron 1968, 24, 5721. (e) Fueno, T.; Matsumura, I.; Okuyama,
T.; Furukawa, J . Bull. Chem. Soc. J pn. 1968, 41, 818. (f) J ulia, M.;
Tchernoff, G. Bull. Soc. Chim. Fr. 1956, 181.
Wada, E.; Yasuoka, H.; Kanemasa, S. Chem. Lett. 1994, 145. (b) Hojo,
M.; Masuda, R.; Okada, E. Synthesis 1990, 347.
(6) For selected examples of 1,3-dipolar cycloadditions, see: (a)
Savinov, S. N.; Austin, D. J . J . Chem. Soc., Chem. Commun. 1999,
813. (b) Shimizu, T.; Hayashi, Y.; Teramura, K. J . Org. Chem. 1983,
8, 3053. (c) Samuilov, Ya. D.; Solov’eva, S. E.; Konovalov, A. I. J . Org.
1
4
Chem. USSR (Engl. Transl.) 1980, 16, 1061; Zh. Org. Khim. 1980, 16,
1
228.
(7) (a) Furukawa, J .; Kawabata, N.; Nishimura, J . Tetrahedron
1
968, 24, 53. (b) Loosli, T.; Borer, M.; Kulakowska, I.; Minger, A.;
Neuenschwander, M. Helv. Chim. Acta 1995, 78, 1144. (c) de Meijere,
A.; Schulz, T.-J .; Kostikov, R. R.; Graupner, F.; Murr, T.; Bielfeldt, T.
Synthesis 1991, 547. (d) Wenkert, E.; Alonso, M. E.; Buckwalter, B.
L.; Sanchez, E. L. J . Am. Chem. Soc. 1983, 105, 2021.
(8) (a) Nait Ajjou A.; Alper, H. J . Am. Chem. Soc. 1998, 120, 1466.
(
b) Abu-Gnim, C.; Amer, I. J . Organomet. Chem. 1996, 516, 235. (c)
Basoli, C.; Botteghi, C.; Cabras, M. A.; Chelucci, G.; Marchetti, M. J .
Organomet. Chem. 1995, 488, C20.
(12) Evans, D. A.; Katz, J . L.; West, T. R. Tetrahedron Lett. 1998,
39, 2937.
(13) (a) Braun, J .; Normant, H. Bull. Soc. Chim. Fr. 1966, 2557. (b)
Matteson, D. S. J . Am. Chem. Soc. 1960, 82, 4228.
(
9) (a) Matysiak, S.; Fitznar, H.-P.; Schnell, R.; Pfleiderer, W. Helv.
Chem. Acta 1998, 81, 1545. (b) Hallensleben, M. L. Chem. Ber. 1971,
04, 3778.
1
1
0.1021/jo016037z CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/21/2001

9
044 J . Org. Chem., Vol. 66, No. 26, 2001
Ta ble 1. P r ep a r a tion of Ar yl Vin yl Eth er s 1a -j fr om P h en ols 3a -j
Notes
a
Isolated yield after purification. b [R]22D +51 (c ) 1, CHCl3). c [R]22D +55 (c ) 1, CHCl3).
solvent, afforded the desired aryl vinyl ether 1a in 74%
yield. Control experiments revealed that while oxygen
is necessary for high conversion, molecular sieves and
triethylamine are not. Thus, under optimized conditions,
when phenol 3a was treated with tetravinyltin (1.2
phenol (3c) (entries 2 and 3) were converted to their
respective vinyl ethers 1b and 1c in yields essentially
identical to their para analogue 3a (entry 1). Similar
results were observed with a substrate bearing an
electron-donating group (EDG), as p-hexyloxyphenyl
vinyl ether (1d ) was obtained in 89% isolated yield (entry
4). Such a substituent increases the reaction rate. On the
other hand, electron-withdrawing groups (EWG) decrease
the rate, as illustrated by entries 5-8. While the weak
4-bromo EWG did not affect the transformation (entry
5), 4-cyanophenol (3f) and 4-nitrophenol (3g) required a
temperature increase (60 °C) to be vinylated. The yield
of their respective products 1f and 1g is also lower
(entries 6 and 7). A mild EWG, such as carbomethoxy,
had a moderate effect. Heat was not necessary for the
reaction to proceed, but more time (96 h) was needed to
reach maximum conversion (entry 8). An acetamido
group in the para position had no effect on the reaction
(entry 9). The mildness of this vinylating process is
clearly demonstrated with entry 10, as the vinyl deriva-
tive of BOC-protected L-tyrosine methyl ester (1j) was
prepared in 92% isolated yield without racemization.
equiv), in the presence of Cu(OAc)
2
(1.2 equiv), in
1
4
CH CN (0.3 M) and under an atmosphere of pure O ,
3
2
the vinyl ether 1a was isolated in 93% yield after an
aqueous workup and chromatography.
Even though tetravinyltin could potentially deliver
more than one vinyl unit per mole, at least 1 equiv is
needed to achieve a >90% conversion to 1a .15 In addition,
we demonstrated that this process could not be run under
catalytic copper(II) conditions.16 Cu(OAc)
was found to
be the best copper promoter for this transformation.
Copper powder, CuCl , Cu(TFA) , and CuOAc allowed
2
2
2
conversions of 5, 10, 50, and 90%, respectively. Other
divalent transition metals, such as Ni(II), Pd(II), and
Hg(II) did not promote the reaction.
To evaluate the scope of this transformation, a variety
of phenols, with different substitution patterns, were
subjected to the reaction conditions. The results are out-
lined in Table 1. The reaction seems insensitive to prox-
imal substitution. Isomeric 3-phenyl (3b) and 2-phenyl-
Hydroxylated heterocycles such as hydroxypyridines
and hydroxyquinolines can be vinylated under the condi-
tions reported herein. While 4-hydroxypyridine (7a ) and
1
7
(
14) A similar yield can be obtained upon exposure to ambient
atmosphere, but the transformation is slower.
15) When 3a was treated with tetravinyltin (0.5 equiv) and
2-hydroxyquinoline (7b) were selectively N-vinylated,
18
6
-hydroxyquinoline (7c) was O-vinylated (Table 2).
(
1
Cu(OAc)
2
(1.0 equiv), 80% conversion to 1a was measured at 48 h ( H
A possible mechanism for the reaction, analogous to
NMR spectrum of crude product).
12
one proposed for the diaryl ether formation, is outlined
in Scheme 1. The attack of the phenol on the vinylcopper
species 4 could lead to vinylcopper(II) phenoxide 5. The
1
(
16) 40% conversion ( H NMR spectrum of crude product) of 3a to
a was observed when 1.5 equiv and 0.3 equiv of tetravinyltin and
Cu(OAc) respectively, were used.
1
2

Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9045
Sch em e 1
Ta ble 2. Vin yla tion of Hyd r oxyla ted Heter ocycles 7a -c
recorded at 125.8 MHz in CDCl
standard. Anhydrous Cu(OAc) , tetravinyltin, and anhydrous
CH CN were purchased from Aldrich. Flash chromatography
3 3
, using CDCl as internal
2
3
was performed using 230-400 mesh silica gel and compound
detection from analytical TLC plates was performed using UV
light. FAB high-resolution mass spectra were run in glycerol at
The Biomedical Mass Spectrometry Unit, McGill University,
Montr e´ al, Qu e´ bec, Canada. Elemental analyses were performed
at Le Laboratoire d’Analyse EÄ l e´ mentaire, Universit e´ de Mont-
r e´ al, Montr e´ al, Qu e´ bec, Canada.
P r ep a r a tion of Ar yl Vin yl Eth er s 1a -j a n d Vin yla ted
Heter ocycles 8a -c. The procedure described below for the
preparation of aryl vinyl ether 1a is typical. Footnotes b and c
of Table 2 indicate minor modifications in the workup for
compounds 8a and 8c. Details regarding the purification of each
compound appear in the Supporting Information. Only aryl vinyl
ethers 1d and 1j are new compounds. They were fully character-
ized and their data appear in the Supporting Information. All
1
9
the other vinyl ethers have been previously reported. Although
characterization data for compounds 1a -c, 1e-i, and 8a -c are
in agreement with those reported, they were also fully charac-
terized, except for 1e for which a satisfactory HRMS was not
obtained (see the Supporting Information). Litterature data for
these compounds were often found to be incomplete. Starting
materials (3a -j and 7a -c) are commercially available.
4
-(Vin yloxy)-1,1′-bip h en yl (1a ). Anhydrous Cu(OAc)
mg, 1.20 mmol) was added to a solution of 4-phenylphenol (3a )
170 mg, 1.00 mmol) in CH CN (3 mL). The mixture was purged
under vacuum, and dry O was introduced in the septum-capped
flask, via a balloon fitted with a needle. Tetravinyltin (218 µL,
.20 mmol) was then added to the turquoise mixture that
2
(218
a
Isolated yield after purification. b No workup (8a is water
(
3
soluble); reaction stopped with 3 drops of concentrated NH4OH
2
(
10 min), mixture directly applied on column for chromatography.
Reaction stopped with 1 mL of concentrated NH4OH (10 min),
c
1
then 25% NH4OAc added and usual workup.
subsequently faded (∼3 min) to a grayish color. After 22 h at
room temperature, the resulting dark green mixture was poured
latter could subsequently be oxidized, through the action
of oxygen, to the copper(III) intermediate 6 prior to
reductive elimination to the vinyl ether product. Most
into aqueous 25% NH OAc (25 mL). After 10 min of stirring,
4
the blue aqueous layer was extracted with EtOAc (3×). The
combined organic layers were washed with brine, dried
(
Na
2
SO
4
), and concentrated. The gummy residue was subjected
/hexane 10:90), affording the
3
likely, the solvent (CH CN) acts as ligand (L).
to column chromatography (CHCl
vinyl ether 1a as a white solid (182 mg, 93%): H NMR (500
3
1
Con clu sion
MHz, acetone-d ) δ 4.47 (dd, J ) 6.0, 1.5 Hz, 1H), 4.75 (dd, J )
6
1
7
3.6, 1.5 Hz, 1H), 6.85 (dd, J ) 13.6, 6.0 Hz, 1H), 7.13 (m, 2H),
In summary, we have developed a mild, single-step
procedure for the preparation of aryl vinyl ethers,
through the copper(II)-promoted vinylation of phenols,
with tetravinyltin, in acetonitrile and under an oxygen
atmosphere. The reaction is applicable to a variety of
phenolic substrates. In particular, sensitive molecules
such as L-tyrosine derivative 3j, impossible to vinylate
by current methods, can be obtained in high yield via this
new procedure.
13
.33 (m, 1H), 7.44 (m, 2H), 7.61-7.66 (m, 4H); C NMR δ 95.4,
117.4, 126.9, 127.1, 128.4, 128.9, 136.2, 140.5, 148.1, 156.4; IR
(KBr) 3050, 3020, 1635, 1595, 1510, 1475, 1240, 1135, 825, 755,
6
found 197.0966. Anal. Calcd for C14
Found: C, 85.58; H, 6.24.
-
1
+
85 cm ; HRMS (FAB) calcd for C14
H
H
13O (M + H) 197.0966,
12O: C, 85.68; H, 6.16.
Su p p or t in g In for m a t ion Ava ila b le: Details on the
purification and characterization data for compounds 1b-j and
1
13
8a -c; copies of H NMR and C NMR spectra for 1b-i and
8
a -c. This material is available free of charge via the Internet
at http://pubs.acs.org.
Exp er im en ta l Section
J O016037Z
1
Gen er a l. H NMR spectra were recorded at 400 or 500 MHz
6 3
in acetone-d or CDCl , using their respective signal for stan-
dardization. Broad band proton-decoupled C NMR spectra were
1
3
(19) (a) For data on compounds 1a and 1c, see ref 10e. (b) For 1b,
see: Wagner, P. J .; Kl a´ n, P. J . Am. Chem. Soc. 1999, 121, 9626. (c)
For 1e and 1g, see: Afonin, A. V.; Vashchenko, A. V.; Tagaki, T.;
Kimura, A.; Fujiwara, H. Can. J . Chem. 1999, 77, 416. (d) For 1f and
1h , see: Bzhezovskii, V. M.; Finkel’shtein, B. L.; Kushnarev, D. F.;
Kalabin, G. A.; Trofimov, B. A. J . Org. Chem. USSR (Engl. Transl.)
1990, 26, 15; Zh. Org. Khim. 1990, 26, 19. (e) For 1i, see: Skvortsova,
G. G.; Kurov, G. N.; Samoilova, M. Ya. J . Org. Chem. USSR (Engl.
Transl.) 1966, 2, 1046; Zh. Org. Khim. 1966, 2, 1054. (f) For 8a ,b, see
ref 17; (g) For 8c, see ref 18.
1
(
17) H and 13C NMR data obtained for 8a and 8b are in complete
agreement with those reported. See: Afonin, A. V.; Andriyankov, M.
A.; Pertsikov, B. Z.; Voronov, V. K. Zh. Org. Khim. 1986, 22, 2451.
1
13
(
18) H and C NMR data obtained for 8c are in complete agreement
with those reported. See: Afonin, A. V.; Vashchenko, A. V.; Contreras,
R. H. Russ. J . Org. Chem. 1997, 33, 1427; Zh. Org. Khim. 1997, 33,
1
507.