Synthesis of benzofurans with remote bromide functionality by domino "ring-cleavage-deprotection-cyclization" reactions of 2-alkylidenetetrahydrofurans with boron tribromide

Article abstract of DOI:10.1021/jo051079z

Bromination and subsequent Suzuki reactions of 2- alkylidenetetrahydrofurans, readily available by [3+2] cyclizations, afforded 1′-(2″-methoxyphenyl)-2-alkylidenetetrahydrofurans. Treatment of the latter with boron tribromide and subsequent addition of wa

Full text of DOI:10.1021/jo051079z

Synthesis of Benzofurans with Remote Bromide Functionality by
Domino “Ring-Cleavage-Deprotection-Cyclization” Reactions of
2-Alkylidenetetrahydrofurans with Boron Tribromide
Esen Bellur†,‡ and Peter Langer*,†,§
Institut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Strasse 3a, 18059 Rostock, Germany,
Institut fu¨r Chemie und Biochemie, Universita¨t Greifswald, Soldmannstrasse 16,
17487 Greifswald, Germany, and Leibniz-Institut fu¨r Organische Katalyse an der
Universita¨t Rostock e. V. (IfOK), Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
peter.langer@uni-rostock.de
Received May 30, 2005
Bromination and subsequent Suzuki reactions of 2-alkylidenetetrahydrofurans, readily available
by [3+2] cyclizations, afforded 1′-(2′′-methoxyphenyl)-2-alkylidenetetrahydrofurans. Treatment of
the latter with boron tribromide and subsequent addition of water resulted in the chemoselective
formation of functionalized benzofurans containing a remote bromide functionality. The products
are formed by a new domino “ring-cleavage-deprotection-cyclization” reaction. The addition of an
aqueous solution of potassium tert-butoxide, rather than water, afforded saturated analogues of
calycine by a “ring-cleavage-deprotection-ring-closure-lactonization” reaction.
Introduction
Functionalized benzofurans1,2 represent important syn-
thetic building blocks and occur in a variety of pharma-
cologically relevant natural products, such as diazon-
amide A, anigopreissin A (Figure 1), euparin (Figure 2),
coumestrol (Figure 3), dehydrotremetone, or cicerfuran
(Figure 4).1 Synthetic amiodarone represents a potent
antiarrythmic and antianginal drug that is used in the
clinic.3
FIGURE 1. Anigopreissin A.
FIGURE 2. Euparin.
2-Alkylidenetetrahydrofurans represent useful syn-
thetic building blocks.4-6 We and others have reported a
* Corresponding author. Fax: +381 4986412.
† Universita¨t Rostock.
‡ Universita¨t Greifswald.
§ Leibniz-Institut fu¨r Organische Katalyse an der Universita¨t
Rostock e. V. (IfOK).
(1) For benzofuran natural products: (a) Fuerst, D. E.; Stoltz, B.
M.; Wood, J. L. Org. Lett. 2000, 22, 3521. (b) Schneider, B. Phytochem-
istry 2003, 64, 459. (c) Katritzky, A. R.; Kirichenkok, K.; Ji, Y.; Steel,
P. J.; Karelson, M. ARKIVOC 2003, vi, 49. (d) Czekei, M.; Nova´k, Z.;
Tima´ri, G.; Kotschy, A. ARKIVOC 2004, vii, 285 and references therein.
(2) For benzofuran syntheses: (a) Miyata, O.; Takeda, N.; Morikami,
Y.; Naito, T. Org. Biomol. Chem. 2003, 1, 254. (b) Xie, X.; Chen, B.;
Lu, J.; Han, J.; She, X.; Pan, X. Tetrahedron Lett. 2004, 45, 6235. (c)
Zhang, H.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem., Int. Ed. 2004,
43, 6144. (d) Kurfurst, P.; Marek, J.; Vanco, J.; Cso¨llei, J. Acta
Crystallogr. 2004, E60, 1989. For a review, see: (e) Butin, A. V.;
Gutnow, A. V.; Abaev, V. T.; Krapivin, G. D. Molecules 1999, 4, 52.
FIGURE 3. Coumesterol.
number of one-pot syntheses of 2-alkylidenetetrahydro-
furans by [3+2] cyclizations of 1,3-dicarbonyl dianions
and 1,3-bis-silyl enol ethers with 1,2-dielectrophiles,7 and
10.1021/jo051079z CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/17/2005
7686
J. Org. Chem. 2005, 70, 7686-7693

Synthesis of Benzofurans with Bromide Functionality
SCHEME 1. Bromination of
2-Alkylidenetetrahydrofurans 2a-ca
FIGURE 4. Cicerfuran.
also by other methods.8c-e 2-Alkylidenetetrahydrofurans
have been functionalized by lithiation and subsequent
alkylations;8a,b in addition, the bromination of the exo-
cyclic double bond and subsequent cross-coupling reac-
tions have been reported.8f Recently, we have reported
the synthesis of 6-bromo-3-oxoalkanoates by reaction of
2-alkylidenetetrahydrofurans with boron tribromide
(BBr3).9 Herein, we wish to report the synthesis of
benzofurans by BBr3-mediated domino “ring-cleavage-
deprotection-cyclization” reactions of 2-alkylidenetet-
rahydrofurans. In addition, the synthesis of calycine
analogues,10 based on Suzuki-cross-coupling and BBr3
reactions, is reported. From a preparative viewpoint, our
methodology allows a convenient access to functionalized
benzofurans, containing a remote bromide functionality,
which are not readily available by other methods. The
chemistry reported herein complements our recently
reported synthetic approach to benzofurans based on a
“[3+2] cyclization/oxidation” 11 strategy. The reactions
a (i) (1) 2.3 equiv of LDA, THF, 0 °C, 1 h, (2) Br(CH2)2Cl,
-78 f 20 °C, 14 h, then reflux, 12 h; (ii) NBS (1.1-1.3 equiv),
CCl4, reflux, 3 h.
SCHEME 2. Bromination of
2-Alkylidenetetrahydrofuran 2da
(3) (a) Wendt, B.; Ha, H. R.; Hesse, M. Helv. Chim. Acta 2002, 85,
2990. (b) Carlsson, B.; Singh, B. N.; Temciuc, M.; Nilsson, S.; Li, Y.
L.; Mellin, C.; Malm, J. J. Med. Chem. 2002, 45, 623 and references
therein. (c) Kwiecien, H.; Baumann, E. J. Heterocycl. Chem. 1997, 34,
1587. (d) Larock, R. C.; Harrison, L. W. J. Am. Chem. Soc. 1984, 106,
4218. (e) Ma´tyus, P.; Varga, I.; Rettegi, T.; Simay, A.; Kallay, N.;
Ka´rolyha´zy, L.; Kocsis, A.; Varro, A.; Penzes, I.; Papp, J. G. Curr. Med.
Chem. 2004, 1, 61.
(4) For cycloadditions, see: (a) Weichert, A.; Hoffmann, H. M. R. J.
Org. Chem. 1991, 56, 4098. (b) Tchelitcheff, P. Bull. Soc. Chim. Fr.
1954, 672. (c) Ireland, R. E.; Haebich, D. Chem. Ber. 1981, 114, 1418.
(d) Audrain, H.; Thorhauge, J.; Hazell, R. G.; Jørgensen, K. A. J. Org.
Chem. 2000, 65, 4487. For reactions with amines, see: (e) Detty, M.
R. J. Org. Chem. 1979, 44, 2073. (f) Batra, S.; Srivastava, S.; Singh,
K.; Chander, R.; Khanna, A. K.; Bhaduri, A. P. Bioorg. Med. Chem.
2000, 8, 2195. For cyclopropanations: (g) Kirmse, W.; Rode, K. Chem.
Ber. 1987, 120, 847. For hydrogenations: (h) Ohta, T.; Miyake, T.;
Seido, N.; Kumobayashi, H.; Takaya, H. J. Org. Chem. 1995, 60, 357.
See also ref 2.
a (i) 2 equiv of TiCl4, CH2Cl2, -78 f 20 °C; (ii) NBS (1.1 equiv),
CCl4, reflux, 3 h.
(5) Reviews: (a) Oivin, T. L. B. Tetrahedron 1987, 43, 3309. (b)
Barrett, A. G. M.; Sheth, H. G. J. Org. Chem. 1983, 48, 5017. (c) Rao,
Y. S. Chem. Rev. 1976, 76, 625. (d) Pattenden, G. Prog. Chem. Nat.
Prod. 1978, 35, 133. (e) Knight, D. W. Contemp. Org. Synth. 1994, 1,
287. (f) Gerlach, H.; Wetter, H. Helv. Chim. Acta 1974, 57, 2306. (g)
Schmidt, U.; Gombos, J.; Haslinger, E.; Zak, H. Chem. Ber. 1976, 109,
2628. (h) Bartlett, P. A.; Meadows, J. D.; Ottow, E. J. Am. Chem. Soc.
1984, 106, 5304. (i) Lygo, B. Tetrahedron 1988, 44, 6889.
(6) (a) Ley, S. V.; Lygo, B.; Organ, H. M.; Wonnacott, A. Tetrahedron
1985, 41, 3825. (b) Booth, P. M.; Fox, C. M. J.; Ley, S. V. J. Chem.
Soc., Perkin Trans. 1 1987, 121. (c) Mori, K.; Sasaki, M.; Tamada, S.;
Suguro, T.; Masuda, S. Tetrahedron 1979, 35, 1601.
(7) For reviews of cyclization reactions of free and masked dianions,
see: (a) Langer, P. Chem.-Eur. J. 2001, 7, 3858. (b) Langer, P.
Synthesis 2002, 441. (c) Langer, P.; Freiberg, W. Chem. Rev. 2004,
104, 4125.
(8) (a) Langer, P.; Bellur, E. J. Org. Chem. 2003, 68, 9742. See
also: (b) Edwards, G. L.; Sinclair, D. J. Tetrahedron Lett. 1999, 40,
3933. (c) Krueger, S. A.; Bryson, T. A. J. Org. Chem. 1974, 39, 3167.
(d) Gabriele, B.; Salerno, G.; Pascali, F. D.; Costa, M.; Chiusoli, G. P.
J. Organomet. Chem. 2000, 593, 1, 409. (e) Pflieger, D.; Muckensturn,
B. Tetrahedron 1989, 45, 7, 2031. (f) Bellur, E.; Langer, P. Synlett 2004,
2169.
reported herein are of interest also from a methodology
viewpoint: whereas the BBr3-mediated cleavage of meth-
ylaryl ethers is well known and broadly used,12 reactions
of other ethers are more rare. Known examples include
the formation of ω-bromoalkanols by ring-opening of
cyclic ethers with BBr3/MeOH,13a or the transformation
of lactones into ω-halocarboxylic acids.13b
Results and Discussion
Our first aim was the synthesis of the required starting
materials (Schemes 1 and 2). The reaction of 2-alkyli-
denetetrahydrofurans 2a-c, prepared by cyclization of
1-bromo-2-chloroethane with the dianions of 1,3-dicar-
bonyl compounds 1a-c,8a,14 with NBS (1.1-1.3 equiv)
(11) (a) Bellur, E.; Freifeld, I.; Langer, P. Tetrahedron Lett. 2005,
46, 2185. (b) Bellur, E.; Go¨rls, H.; Langer, P. Eur. J. Org. Chem. 2005,
2074.
(12) Review: (a) Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249.
See also: (b) McOmie, J. F. W.; Watts, M. L.; West, D. E. Tetrahedron
1968, 24, 2289.
(13) For the cleavage of cyclic ethers, see: (a) Kulkarni, S. U.; Patil,
V. D. Heterocycles 1982, 18, 163. For the cleavage of lactones, see: (b)
Olah, G. A.; Karpeles, R.; Narang, S. C. Synthesis 1982, 963.
(9) For an isolated example of the domino “ring-cleavage-deprotec-
tion-cyclization” reaction, see: (a) Bellur, E.; Langer, P. Synlett 2004,
2172. For open-chained products: (b) Bellur, E.; Langer, P. J. Org.
Chem. 2005, 70, 3819.
(10) (a) Akermark, B. Acta Chem. Scand. 1961, 15, 1695. (b) The
2,3′-bifuranylidene subunit is present in the natural products charlic
acid, charolic acid, and terrestric acid: Arai, H.; Miyajima, H.;
Mushiroda, T.; Yamamoto, Y. Chem. Pharm. Bull. 1989, 12, 3229.
J. Org. Chem, Vol. 70, No. 19, 2005 7687

Bellur and Langer
TABLE 1. Synthesis of Benzofuran Derivatives
SCHEME 3. Synthesis of Benzofuran 8aa
a (i) [2-(MeO)C6H4]B(OH)2 (3.0 equiv), Pd(PPh3)4 (3 mol-%),
K3PO4 (6.0 equiv), 1,4-dioxane, reflux, 6 h; (ii) (1) 4 equiv of BBr3,
CH2Cl2, 0 f 20 °C, 12 h, 20 °C, 6 h; (2) H2O.
afforded the 1′-bromo-2-alkylidenetetrahydrofurans 3a-c
and the 1′,3-dibromo-2-alkylidenetetrahydrofurans 4a-c
(Scheme 1).
The NBS-mediated (1.1 equiv) bromination of 5-chlo-
romethyl-2-alkylidenetetrahydrofuran 2d, prepared by
TiCl4-mediated cyclization of 1,3-bis-silyl enol ether 5
with epichlorohydrin,15 afforded the 1′-bromo-2-alkyli-
denetetrahydrofuran 3d and the 1′,3-dibromo-2-alkyli-
denetetrahydrofuran 6 (Scheme 2). The desired product
3d could be isolated in pure form when 1.1 equiv of NBS
was employed; however, the formation of 6 could not be
entirely avoided. The use of 1.3 equiv of NBS resulted in
a decrease of the yield of 3d and gave an inseparable
mixture of 3d and 6.
The synthesis of functionalized benzofurans by sequen-
tial Suzuki and BBr3 reactions was studied next (Scheme
3, Table 1). The Pd(PPh3)4 (3 mol-%) catalyzed Suzuki
reaction of 3a with (2-methoxyphenyl)boronic acid gave
the desired 2-alkylidenetetrahydrofuran 7a with excel-
lent E-diastereoselectivity. Treatment of 7a with BBr3
afforded the benzofuran 8a.9a We propose a mechanism
that involves the formation of 8a (Scheme 3). The latter
is formed by BBr3-mediated ring-opening of 7a and
cleavage of the arylmethyl ether to give intermediate A.
Addition of water results in hydrolysis of the boronic ester
moieties, to give boronic and hydrobromic acid (interme-
diate B), and subsequent acid-mediated cyclization and
aromatization by extrusion of water. During the optimi-
zation, the use of an excess of BBr3 (4 equiv) proved to
be important.
a Yields of isolated products. b E/Z > 98:2.
(14) Langer, P.; Holtz, E.; Karime´, I.; Saleh, N. N. R. J. Org. Chem.
2001, 66, 6057.
(15) (a) Langer, P.; Armbrust, H.; Eckardt, T.; Magull, J. Chem.-
Eur. J. 2002, 8, 1443. (b) For an alternative synthesis of 2d, see:
Pound, M. K.; Davies, D. L.; Pilkington, M.; de Pina Vaz Sousa, M.
M.; Wallis, J. D. Tetrahedron Lett. 2002, 43, 1915.
The preparative scope of our methodology was studied
(Table 1). The Suzuki reaction of 3a with 2,5-dimethoxy-
phenylboronic acid gave 2-alkylidenetetrahydrofuran 7b.
7688 J. Org. Chem., Vol. 70, No. 19, 2005

Synthesis of Benzofurans with Bromide Functionality
SCHEME 4. Lactonization of 7a,ga
furans, were prepared by bromination and subsequent
Suzuki reactions of 2-alkylidenetetrahydrofurans avail-
able by [3+2] cyclizations. In addition, we have reported
the synthesis of saturated analogues of calycine, prepared
by reaction of 1′-(2′′-methoxyphenyl)-2-alkylidenetetrahy-
drofurans with BBr3 and subsequent addition of an
aqueous solution of KOtBu.
Experimental Section
General Procedure for the Reaction of 2-Alkylidene-
tetrahydrofurans with N-Bromosuccinimide (NBS). To
a CCl4-solution (5 mL/mmol) of the 2-alkylidenetetrahydrofu-
ran 2 (1 equiv) was added N-bromosuccinimide (1.1 equiv) at
20 °C. The reaction mixture was heated and stirred at reflux
for 3 h. The reaction mixture was then allowed to cool to
ambient temperature, and the solvent was removed in vacuo.
The residue was purified by chromatography (silica gel,
n-hexane/EtOAc) to give the bromo-2-alkylidenetetrahydro-
furans 3,4,6.
Synthesis of 3,4a. Starting with 2a (4.000 g, 28.0 mmol)
and NBS (6.511 g, 36.6 mmol) in CCl4 (40 mL), Z-3a (5.212 g,
84%) and E-4a (0.937 g, 11%) were isolated after chromatog-
raphy (silica gel, n-hexane/EtOAc ) 100:1 f 1:1) as yellowish
and colorless solids, respectively.
a
(i) (1) 4 equiv of BBr3, CH2Cl2, 0 f 20 °C, 12 h, 20 °C, 6 h; (2)
KOtBu, H2O (1 M), 1 h, 20 °C.
Treatment of the latter with BBr3 afforded the benzofu-
ran 8b. The reaction of 3b with 2-methoxyphenyl-, 2,4-
dimethoxyphenyl-, and 2,6-dimethoxyphenylboronic acid
afforded the functionalized 2-alkylidenetetrahydrofurans
7c-e, which were transformed into 8c-e. Likewise, the
reaction of 3c with 2-methoxyphenylboronic acid afforded
7f, which was transformed into the 3-benzoylbenzofuran
8f by treatment with BBr3. 2-Alkylidenetetrahydrofuran
7g was prepared by reaction of 3d with 2-methoxyphen-
ylboronic acid; treatment of 7g with BBr3 gave the
benzofuran 8g. The Suzuki reaction of dibromide 4a with
2-methoxyphenylboronic acid afforded 2-alkylidene-1′,3-
diaryltetrahydrofuran 7h, which was formed by a double-
Suzuki reaction of the 1,3-dibromoprop-1-ene moiety; the
reaction of 7h with BBr3 afforded the benzofuran 8h. All
reactions proceeded in good to very good yields and with
very good chemoselectivity. In addition, all Suzuki reac-
tions proceeded with excellent E-diastereoselectivity.
The application of our methodology to the synthesis of
3-(dihydrofuran-2(3H)-ylidene)-3H-benzofuran-2-one 9a
and of 3-[(5-chloromethyl)dihydrofuran-2(3H)-ylidene]-
3H-benzofuran-2-one 9b, saturated analogues of caly-
cine,10 was studied next (Scheme 4).8c Treatment of 7a
and 7g with BBr3 (CH2Cl2) and subsequent addition of
an aqueous solution of KOtBu (1 M) afforded 9a and 9b
as separable mixtures of E/Z-isomers, respectively. We
propose a mechanism that involves the formation of 9a
and 9b by BBr3-mediated ring-cleavage of 7a,g and
cleavage of the arylmethyl ether (intermediate C). Ad-
dition of the aqueous solution of KOtBu (KOtBu + H2O
f KOH + tBuOH) results in hydrolysis of the boronic
ester moieties (intermediate D) and subsequent base-
mediated recyclization of the tetrahydrofuran moiety and
lactonization. The formation of 9a,b as a mixture of E/Z-
isomers can be explained by keto-enol tautomerism of
intermediate C.
Methyl Bromo(dihydrofuran-2(3H)-ylidene)acetate (Z-
1
3a). H NMR (CDCl3, 300 MHz): δ 2.23 (quint, J ) 7.2 Hz,
2H, CH2), 3.19 (t, J ) 7.8 Hz, 2H, CH2), 3.78 (s, 3H, OCH3),
4.41 (t, J ) 7.2 Hz, 2H, OCH2). 13C NMR (CDCl3, 75 MHz): δ
24.8, 32.3, 52.2, 73.0, 82.7, 164.7, 172.2. IR (KBr, cm-1): ν )
2951 (w), 1699 (s), 1609 (s), 1435 (m), 1281 (s), 1213 (s), 1188
(m), 1073 (s), 973 (w), 925 (w), 879 (w), 770 (w), 759 (w). MS
(EI, 70 eV): m/z (%) ) 221 (M+ [81Br], 72), 219 (M+ [79Br], 71),
190 (87), 162 (3). Anal. Calcd for C7H9O3Br (221.050): C, 38.04;
H, 4.10. Found: C, 38.19; H, 3.64.
Methyl Bromo(3-bromodihydro-furan-2(3H)-ylidene)-
acetate (E-4a). 1H NMR (CDCl3, 300 MHz): δ 2.43-2.49 (m,
1H, CH2), 2.53-2.61 (m, 1H, CH2), 3.80 (s, 3H, OCH3), 4.74-
4.76 (m, 1H, OCH2), 4.78-4.79 (m, 1H, OCH2), 5.20 (d, J )
5.4 Hz, 1H, CH-Br). 13C NMR (CDCl3, 75 MHz): δ 34.7, 48.4,
52.1, 73.8, 87.1, 162.0, 167.0. IR (KBr, cm-1): ν ) 2950 (w),
1706 (s), 1605 (s), 1433 (m), 1271 (s), 1204 (s), 1174 (s), 1057
(w), 1039 (s), 1027 (s), 1004 (w), 765 (w). MS (EI, 70 eV): m/z
(%) ) 302 (M+ [2 × 81Br], 17), 300 (M+ [81Br79Br], 34), 298
(M+ [2 × 79Br], 17), 269 (19), 241 (2), 221 (100), 189 (22), 161
(18). Anal. Calcd for C7H8O3Br2 (299.946): C, 28.03; H, 2.69.
Found: C, 28.88; H, 2.85.
Synthesis of 3,4b. Starting with 2b (1.432 g, 9.2 mmol)
and NBS (2.122 g, 11.92 mmol) in CCl4 (25 mL), Z-4b (0.740
g, 26%), Z-3b (0.886 g, 41%), and E-4b (0.430 g, 15%) were
isolated after chromatography (silica gel, n-hexane/EtOAc )
100:1 f 1:1) as slightly yellowish solid, yellowish solid, and
yellowish oil, respectively.
Ethyl Bromo(3-bromodihydrofuran-2(3H)-ylidene)ac-
1
etate (Z-4b). H NMR (CDCl3, 300 MHz): δ 1.36 (t, J ) 7.2
Hz, 3H, CH3), 2.55-2.63 (m, 2H, CH2), 4.29 (dq, J ) 2.1, 7.2
Hz, 2H, OCH2CH3), 4.56-4.66 (m, 2H, OCH2), 5.81 (dd,
J ) 4.5, 1.5 Hz, 1H, CH-Br). 13C NMR (CDCl3, 75 MHz): δ
13.9, 36.8, 44.1, 61.7, 70.6, 87.1, 162.5, 168.5. IR (KBr, cm-1):
ν ) 2933 (w), 1701 (s), 1616 (s), 1371 (w), 1274 (s), 1216 (s),
1189 (m), 1160 (w), 1069 (s), 1026 (w), 953 (w), 928 (w), 872
(w), 757 (w). MS (EI, 70 eV): m/z (%) ) 315 (M+ [2 × 81Br],
11), 313 (M+ [81Br79Br], 33), 311 (M+ [2 × 79Br], 12), 269 (11),
235 (65), 305 (100), 189 (29), 161 (23). Anal. Calcd for C8H10O3-
Br2 (313.973): C, 30.60; H, 3.21. Found: C, 30.32; H, 3.51.
Ethyl Bromo(dihydrofuran-2(3H)-ylidene)acetate (Z-
In summary, we have reported a convenient and
chemoselective formation of functionalized benzofurans
containing a remote bromide functionality. The products
are formed by a new BBr3-mediated domino “ring-
cleavage-deprotection-cyclization” reaction. The starting
materials, 1′-(2′′-methoxyphenyl)-2-alkylidenetetrahydro-
1
3b). H NMR (CDCl3, 300 MHz): δ 1.32 (t, J ) 7.2 Hz, 3H,
CH3), 2.23 (quint, J ) 7.5 Hz, CH2), 3.18 (t, J ) 7.8 Hz, 2H,
CH2), 4.23 (q, J ) 7.2 Hz, 2H, OCH2CH3), 4.40 (t, J ) 7.2 Hz,
2H, OCH2). 13C NMR (CDCl3, 150 MHz): δ 14.0, 24.6, 32.2,
60.8, 72.7, 83.0, 163.7, 171.7. IR (KBr, cm-1): ν ) 2995 (w),
J. Org. Chem, Vol. 70, No. 19, 2005 7689

Bellur and Langer
2975 (w), 2907 (w), 1691 (s), 1608 (s), 1395 (w), 1374 (m), 1294
(s), 1276 (s), 1240 (w), 1194 (s), 1065 (s), 1038 (m), 953 (w),
931 (m), 874 (w), 762 (m). MS (EI, 70 eV): m/z (%) ) 236 (M+
[81Br], 75), 234 (M+ [79Br], 76), 206 (44), 189 (100), 161 (5),
110 (40), 81 (12). Anal. Calcd for C8H11O3Br (235.077): C,
40.88; H, 4.72. Found: C, 41.04; H, 4.61.
MHz): δ 2.11-2.22 (m, 1H, CH2), 2.35-2.46 (m, 1H, CH2),
3.09-3.21 (m, 1H, CH2), 3.30-3.41 (m, 1H, CH2), 3.63-3.73
(m, 2H, CH2-Cl), 3.78 (s, 3H, OCH3), 4.80-4.87 (m, 1H, OCH).
13C NMR (CDCl3, 75 MHz): δ 27.3, 31.9, 45.1, 52.1, 82.8, 82.9,
164.2, 171.1. IR (KBr, cm-1): ν ) 2953 (w), 1701 (s), 1614 (s),
1434 (m), 1346 (w), 1280 (s), 1221 (m), 1192 (m), 1122 (w),
1075 (s), 1037 (m), 883 (w), 760 (w), 748 (w), 738 (w). MS (EI,
70 eV): m/z (%) ) 272 (M+ [81Br37Cl], 8), 270 (M+ [81Br35Cl],
48), 268 (M+ [79Br35Cl], 39), 238 (100), 235 (72), 219 (5), 201
(14), 191 (5), 159 (23), 117 (11), 69 (36). Anal. Calcd for C8H10-
BrClO3 (269.522): C, 35.65; H, 3.74. Found: C, 35.38; H, 4.00.
General Procedure for the Suzuki Reaction of 2-Alky-
lidenetetrahydrofurans with Arylboronic Acids. To a 1,4-
dioxane solution (3 mL/mmol) of the bromo-2-alkylidenetet-
rahydrofuran (3,4) (1 equiv) were added potassium phosphate
(K3PO4, 6 equiv), the boronic acid (ArB(OH)2, 3 equiv), and
Pd(PPh3)4 (0.03 equiv) at 20 °C. The reaction mixture was
heated and stirred at reflux for 6 h. The reaction mixture was
then allowed to cool to ambient temperature, and diethyl ether
(10 mL/mmol) was added. The precipitate was filtered off,
washed with diethyl ether, and the filtrate was concentrated
in vacuo. The residue was purified by chromatography (silica
gel, n-hexane/EtOAc) to give the aryl-substituted 2-alkylidene-
tetrahydrofurans 7.
E-4b. 1H NMR (CDCl3, 300 MHz): δ 1.32 (t, J ) 7.2 Hz,
3H, CH3), 2.43-2.48 (m, 1H, CH2), 2.52-2.61 (m, 1H, CH2),
4.27 (q, J ) 7.2 Hz, 2H, OCH2CH3), 4.76 (dt, J ) 8.7, 0.9 Hz,
2H, OCH2), 5.20 (d, J ) 5.4 Hz, 1H, CH-Br). 13C NMR (CDCl3,
150 MHz): δ 14.1, 35.2, 48.7, 61.5, 74.0, 87.9, 162.0, 176.1. IR
(neat, cm-1): ν ) 2983 (m), 2938 (w), 2905 (m), 1737 (s), 1703
(s), 1660 (m), 1616 (s), 1471 (m), 1440 (m), 1371 (s), 1316 (m),
1283 (s), 1272 (s), 1206 (s), 1184 (s), 1157 (s), 1117 (m), 1094
(m), 1088 (s), 935 (m), 925 (m), 865 (w), 847 (w), 763 (m), 700
(w). MS (EI, 70 eV): m/z (%) ) 316 (M+ [2 × 81Br], 17), 314
(M+ [81Br79Br], 37), 312 (M+ [2 × 79Br], 18), 269 (29), 241 (3),
233 (6), 205 (100), 189 (35), 161 (23). The exact molecular mass
m/z ) 311.8997 ( 2 ppm [M+] for C8H10O3Br2 was confirmed
by HRMS (EI, 70 eV).
Synthesis of 3,4c. Starting with 2c (0.400 g, 2.13 mmol)
and NBS (0.416 g, 2.34 mmol) in CCl4 (30 mL), Z-4c (0.087 g,
12%) and Z-3c (0.302 g, 53%) were isolated after chromato-
graphy (silica gel, n-hexane/EtOAc ) 100:1 f 1:1) as yellowish
oils.
Methyl(Dihydrofuran-2(3H)-ylidene)-(2-methoxyphen-
yl)acetate (7a). Starting with 3a (0.100 g, 0.45 mmol),
2-methoxyphenylboronic acid (0.213 g, 1.36 mmol), K3PO4
(0.575 g, 2.71 mmol), and Pd(PPh3)4 (0.016 g, 0.014 mmol) in
1,4-dioxane (5 mL), 7a was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 100:1 f 1:1) as a slightly
yellowish solid (0.107 g, 96%). 1H NMR (CDCl3, 300 MHz): δ
2.12 (quint, J ) 7.2 Hz, 2H, CH2), 3.28 (t, J ) 7.8 Hz, 2H,
CH2), 3.63 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 4.19 (t, J ) 7.2
Hz, 2H, OCH2), 6.90-6.98 (m, 2H, 2 × CH), 7.19 (d, J ) 9.3
Hz, 1H, CH), 7.24-7.30 (m, 1H, CH). 13C NMR (CDCl3, 75
MHz): δ 24.0, 31.1, 51.0, 55.5, 71.9, 100.4, 110.9, 120.1, 124.6,
128.3, 131.8, 157.1, 168.9, 171.5. IR (KBr, cm-1): ν ) 2943
(w), 1704 (s), 1623 (s), 1599 (w), 1492 (m), 1464 (w), 1435 (m),
1376 (w), 1315 (m), 1271 (m), 1244 (m), 1184 (s), 1114 (w),
1075 (s), 1068 (s), 1024 (m), 979 (m). MS (EI, 70 eV): m/z (%)
) 248 (M+, 100), 216 (25), 189 (57), 174 (7), 158 (3). Anal. Calcd
for C14H16O4 (248.278): C, 67.73; H, 6.50. Found: C, 67.51;
H, 6.83.
Methyl (Dihydrofuran-2(3H)-ylidene)-(2,5-dimethoxy-
phenyl)acetate (7b). Starting with 3a (0.100 g, 0.45 mmol),
2,5-dimethoxybenzeneboronic acid (0.253 g, 1.36 mmol), K3-
PO4 (0.576 g, 2.71 mmol), and Pd(PPh3)4 (0.016 g, 0.014 mmol)
in 1,4-dioxane (5 mL), 7b was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 50:1 f 1:1) as a yellowish solid
(0.109 g, 87%). 1H NMR (CDCl3, 300 MHz): δ 2.13 (quint, J )
7.5 Hz, 2H, CH2), 3.27 (t, J ) 7.8 Hz, 2H, CH2), 3.64 (s, 3H,
OCH3), 3.73 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 4.20 (t, J )
7.2 Hz, 2H, OCH2), 6.77-6.86 (m, 3H, 3 × CH). 13C NMR
(CDCl3, 150 MHz): δ 24.2, 31.4, 51.3, 55.7, 56.5, 72.3, 100.5,
112.2, 112.8, 118.1, 125.9, 151.8, 153.3, 169.0, 171.9. IR (KBr,
cm-1): ν ) 3009 (w), 2986 (w), 2953 (m), 2900 (w), 2837 (w),
1700 (s), 1621 (s), 1609 (s), 1497 (s), 1464 (m), 1428 (m), 1377
(w), 1306 (s), 1279 (s), 1236 (s), 1217 (s), 1185 (s), 1160 (m),
1137 (s), 1072 (s), 1053 (s), 1026 (m), 983 (w), 983 (w), 964
(m), 936 (w), 899 (w), 805 (m), 779 (w), 724 (w). MS (EI, 70
eV): m/ z (%) ) 278 (M+, 100), 247 (8), 231 (3), 219 (15), 217
(1), 204 (1), 155 (28), 91 (7), 77 (5), 70 (13). Anal. Calcd for
C15H18O5 (278.304): C, 64.74; H, 6.52. Found: C, 64.75; H,
6.75.
2-Bromo-2-(3-bromodihydrofuran-2(3H)-ylidene)-1-
phenylethanone (Z-4c). 1H NMR (CDCl3, 300 MHz): δ 2.51-
2.72 (m, 2H, CH2), 4.60-4.71 (m, 2H, OCH2), 5.60 (d, J ) 5.4
Hz, 1H, CH-Br), 7.41-7.55 (m, 3H, 3 × CH of Ph), 7.75 (d,
J ) 3.9 Hz, 2H, 2 × CH of Ph). 13C NMR (CDCl3, 75 MHz): δ
36.8, 43.6, 70.5, 92.8, 127.7, 128.7, 132.0, 137.7, 166.9, 191.0.
IR (neat, cm-1): ν ) 3059 (w), 2998 (w), 2962 (w), 2906 (m),
1659 (s), 1653 (s), 1598 (s), 1584 (s), 1581 (s), 1570 (s), 1473
(w), 1444 (m), 1370 (m), 1311 (s), 1276 (s), 1220 (s), 1174 (s),
1161 (s), 1115 (w), 1076 (w), 1055 (m), 1017 (s), 964 (s), 931
(s), 909 (m), 882 (m), 836 (m), 815 (w), 794 (m), 741 (m), 687
(s), 654 (s), 522 (m). MS (EI, 70 eV): m/z (%) ) 348 (M+, [2 ×
81Br], 7), 346 (M+ [81Br79Br], 15), 344 (M+ [2 × 79Br], 7), 267
(36), 186 (100). Anal. Calcd for C12H10O2Br2 (346.018): C,
41.65; H, 2.91. Found: C, 41.35; H, 3.60.
2-Bromo-2-(dihydrofuran-2(3H)-ylidene)-1-phenyleth-
anone (Z-3c). 1H NMR (CDCl3, 300 MHz): δ 2.21 (quint, J )
7.5 Hz, 2H, CH2), 2.94 (t, J ) 7.8 Hz, 2H, CH2), 4.45 (t, J )
7.2 Hz, 2H, OCH2), 7.38-7.53 (m, 3H, 3 × CH of Ph), 7.61-
7.71 (m, 2H, 2 × CH of Ph). 13C NMR (CDCl3, 75 MHz): δ
25.2, 32.7, 72.9, 91.3, 127.9 (2C), 128.5 (2C), 131.4, 139.2, 171.5,
191.8. IR (neat, cm-1): ν ) 2959 (w), 2927 (w), 1684 (s), 1646
(s), 1596 (s), 1448 (m), 1420 (w), 1312 (m), 1285 (m), 1253 (w),
1210 (s), 1183 (m), 1118 (w), 1075 (w), 1033 (m), 995 (w), 965
(w), 930 (w), 693 (w), 649 (w). MS (EI, 70 eV): m/z (%) ) 267
(M+, [81Br], 22), 265 (M+ [79Br], 21), 186 (35), 162 (3), 146 (11),
129 (2), 105 (100), 77 (64), 70 (18).
Synthesis of 3d,6. Starting with 2d (1.000 g, 5.25 mmol)
and NBS (1.027 g, 5.77 mmol) in CCl4 (50 mL), 6 (0.680 g,
48%) and 3d (0.492 g, 35%) were isolated after chromatography
(silica gel, n-hexane/EtOAc ) 100:1 f 2:1) as a yellowish oil
and a white solid, respectively.
Methyl (3-Bromo-5-chloromethyldihydrofuran-2(3H)-
ylidene)acetate (6). 1H NMR (CDCl3, 300 MHz): δ 2.38-
2.71 (m, 2H, CH2), 3.73 (s, 3H, OCH3), 3.79 (dd, J ) 9.4, 4.9
Hz, 2H, CH2-Cl), 5.03 (sext, J ) 4.9 Hz, 1H, OCH), 5.33 (s,
1H, CHdC), 5.81 (d, J ) 5.6 Hz, 1 H, CH-Br). 13C NMR
(CDCl3, 75 MHz): δ 38.3, 43.8, 50.5, 52.2, 79.9, 90.7, 166.0,
171.8. IR (neat, cm-1): ν ) 2953 (w), 1708 (s), 1653 (s), 1625
(m), 1436 (m), 1407 (w), 1358 (m), 1335 (w), 1284 (m), 1243
(w), 1215 (m), 1194 (m), 1164 (w), 1125 (s), 1071 (m), 1048
(m), 999 (w), 944 (w), 889 (w), 837 (w), 757 (w), 716 (w). MS
(EI, 70 eV): m/z (%) ) 272 (M+ [81Br37Cl], 21), 270 (M+
[81Br35Cl], 99), 268 (M+ [79Br35Cl], 72), 239 (99), 189 (100), 157
(56), 139 (27), 125 (11), 110 (20), 101 (35), 81 (25).
Ethyl(Dihydrofuran-2(3H)-ylidene)-(2-methoxyphen-
yl)acetate (7c). Starting with 3b (0.200 g, 0.85 mmol),
2-methoxybenzeneboronic acid (0.400 g, 2.55 mmol), K3PO4
(1.085 g, 5.11 mmol), and Pd(PPh3)4 (0.030 g, 0.026 mmol) in
1,4-dioxane (8 mL), 7c was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 50:1 f 1:1) as a slightly
1
Methyl Bromo(5-chloromethyldihydrofuran-2(3H)-
yellowish solid (0.207 g, 93%), mp ) 59 °C. H NMR (CDCl3,
ylidene)acetate (3d). mp ) 40 °C. 1H NMR (CDCl3, 300
300 MHz): δ 1.17 (t, J ) 7.2 Hz, 3H, CH3), 2.12 (quint, J )
7690 J. Org. Chem., Vol. 70, No. 19, 2005

Synthesis of Benzofurans with Bromide Functionality
7.5 Hz, 2H, CH2), 3.27 (t, J ) 7.8 Hz, 2H, CH2), 3.77 (s, 3H,
OCH3), 4.13 (q, J ) 7.2 Hz, 2H, OCH2CH3), 4.18 (t, J ) 7.2
Hz, 2H, OCH2), 6.88-6.97 (m, 2H, 2 × CH), 7.18-7.29 (m,
2H, 2 × CH). 13C NMR (CDCl3, 150 MHz): δ 14.6, 24.3, 31.4,
55.6, 59.6, 72.1, 101.1, 110.9, 120.3, 125.0, 128.4, 132.1, 157.4,
168.7, 171.4. IR (KBr, cm-1): ν ) 29.82 (m), 2958 (m), 2940
(m), 2900 (m), 2836 (w), 1697 (s), 1627 (s), 1603 (m), 1492 (s),
1462 (m), 1437 (m), 1371 (m), 1304 (s), 1267 (s), 1241 (s), 1185
(s), 1115 (m), 1069 (s), 1028 (m), 1008 (m), 955 (w), 933 (m),
876 (w), 849 (w), 782 (w), 755 (m), 647 (w). MS (EI, 70 eV):
m/z (%) ) 262 (M+, 100), 217 (13), 216 (15), 189 (53), 91 (31).
Anal. Calcd for C15H18O4 (262.305): C, 68.69; H, 6.92. Found:
C, 68.78; H, 6.81.
Ethyl (Dihydrofuran-2(3H)-ylidene)-(2,4-dimethoxy-
phenyl)acetate (7d). Starting with 3b (0.150 g, 0.64 mmol),
2,4-dimethoxybenzeneboronic acid (0.355 g, 1.91 mmol), K3-
PO4 (0.813 g, 3.83 mmol), and Pd(PPh3)4 (0.022 g, 0.019 mmol)
in 1,4-dioxane (10 mL), 7d was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 50:1 f 1:1) as a white solid
(0.180 g, 96%), mp ) 91 °C. 1H NMR (CDCl3, 300 MHz): δ
1.17 (t, J ) 7.2 Hz, 3H, CH3), 2.11 (quint, J ) 7.5 Hz, 2H,
CH2), 3.25 (t, J ) 7.8 Hz, 2H, CH2), 3.75 (s, 3H, OCH3), 3.81
(s, 3H, OCH3), 4.12 (q, J ) 7.2 Hz, 2H, OCH2CH3), 4.18 (t,
J ) 7.2 Hz, 2H, OCH2), 6.48-6.51 (m, 2H, 2 × CH), 7.08-
7.11 (m, 1H, CH). 13C NMR (CDCl3, 150 MHz): δ 14.4, 24.1,
31.1, 55.1, 55.3, 59.4, 71.8, 98.5, 100.5, 103.9, 117.4, 132.1,
158.1, 159.9, 168.6, 171.09. IR (KBr, cm-1): ν ) 3000 (w), 2977
(w), 1690 (s), 1616, (s), 1584 (w), 1511 (m), 1464 (w), 1309 (m),
1289 (m), 1265 (m), 1209 (m), 1187 (m), 1167 (m), 1108 (w),
1069 (s), 1032 (m), 1008 (w), 947 (w), 819 (w). MS (EI, 70 eV):
m/z (%) ) 292 (M+, 100), 246 (20), 231 (1), 219 (16), 190 (8).
Anal. Calcd for C16H20O5 (292.331): C, 65.74; H, 6.90. Found:
C, 65.91; H, 6.87.
Ethyl (Dihydrofuran-2(3H)-ylidene)-(2,6-dimethoxy-
phenyl)acetate (7e). Starting with 3b (0.170 g, 0.72 mmol),
2,6-dimethoxybenzeneboronic acid (0.403 g, 2.17 mmol), K3-
PO4 (0.921 g, 4.34 mmol), and Pd(PPh3)4 (0.025 g, 0.022 mmol)
in 1,4-dioxane (10 mL), 7e was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 100:1 f 1:1) as a yellowish solid
(0.182 g, 87%), mp ) 82 °C. 1H NMR (CDCl3, 300 MHz): δ
1.15 (t, J ) 7.2 Hz, 3H, CH3), 2.11 (quint, J ) 7.2 Hz, 2H,
CH2), 3.29 (t, J ) 7.5 Hz, 2H, CH2), 3.76 (s, 6H, 2 × OCH3),
4.11 (q, J ) 7.2 Hz, 2H, OCH2CH3), 4.16 (t, J ) 7.2 Hz, 2H,
OCH2), 6.59 (d, J ) 8.4 Hz, 2H, 2 × CH), 7.22 (t, J ) 8.4 Hz,
1H, CH). 13C NMR (CDCl3, 150 MHz): δ 14.7, 24.3, 31.3, 56.2,
59.5, 72.0, 96.3, 104.4, 113.8, 128.7, 158.4, 168.8, 171.8. IR
(KBr, cm-1): ν ) 2976 (m), 2926 (m), 2855 (w), 1696 (s), 1630
(s), 1589 (m), 1468 (s), 1436 (m), 1378 (w), 1286 (m), 1248 (s),
1182 (s), 1112 (s), 1067 (s), 1030 (m), 931 (w), 746 (w). MS
(EI, 70 eV): m/z (%) ) 292 (M+, 95), 263 (6), 219 (100), 204
(4), 190 (15), 188 (4), 173 (8), 157 (3), 137 (5). Anal. Calcd for
C16H20O5 (292.331): C, 65.74; H, 6.90. Found: C, 65.61; H,
6.24.
(w). MS (EI, 70 eV): m/z (%) ) 294 (M+, 88), 263 (29), 217 (39,
189 (28), 171 (4), 157 (1), 105 (100), 91 (17), 77 (62).
Methyl (5-Chloromethyl-dihydrofuran-2(3H)-ylidene)-
(2-methoxyphenyl)acetate (7g). Starting with 3d (0.150 g,
0.56 mmol), 2-methoxyphenylboronic acid (0.262 g, 1.67 mmol),
K3PO4 (0.709 g, 3.34 mmol), and [Pd(PPh3)4] (0.019 g, 0.017
mmol) in 1,4-dioxane (5 mL), 7g was isolated after chroma-
tography (silica gel, n-hexane/EtOAc ) 100:1 f 1:1) as a
slightly yellowish oil (0.159 g, 96%). 1H NMR (CDCl3, 300
MHz): δ 2.02-2.14 (m, 1H, CH2), 2.19-2.31 (m, 1H, CH2),
3.26-3.36 (m, 2H, CH2), 3.54 (d, J ) 5.1 Hz, 2H, CH2-Cl),
3.60 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 4.58 (quint, J ) 7.2
Hz, 1H, OCH), 6.87-6.96 (m, 2H, 2 × CH of Ar), 7.18-7.27
(m, 2H, 2 × CH of Ar). 13C NMR (CDCl3, 75 MHz): δ 26.6,
30.7, 45.4, 51.0, 53.3, 81.6, 100.9, 110.6, 120.0, 124.2, 128.3,
131.8, 157.0, 168.7, 170.3. IR (neat, cm-1): ν ) 2950 (w), 1704
(s), 1632 (s), 1492 (m), 1460 (m), 1435 (s), 1346 (w), 1308 (m),
1265 (m), 1244 (s), 1185 (s), 1116 (m), 1072 (s), 1026 (m), 926
(w), 755 (m). MS (EI, 70 eV): m/z (%) ) 298 (M+ [37Cl], 33),
296 (M+ [35Cl], 100), 264 (50), 237 (58), 200 (7).
Methyl (2-Methoxyphenyl)-[3-(2-methoxyphenyl)-di-
hydrofuran-2(3H)-ylidene]acetate (7h). Starting with Z-4a
(0.300 g, 1.0 mmol), 2-methoxybenzeneboronic acid (0.940 g,
6.0 mmol), K3PO4 (1.274 g, 6.0 mmol), and [Pd(PPh3)4] (0.058
g, 0.05 mmol) in 1,4-dioxane (5 mL), 7h was isolated after
chromatography (silica gel, n-hexane/EtOAc ) 100:1 f 2:1)
as a white solid (0.325 g, 92%), mp ) 112 °C. 1H NMR (CDCl3,
300 MHz): δ 1.58-2.05 (m, 1H, CH2), 2.41-2.56 (m, 1H, CH),
3.43 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 3.91 (s, 3H, OCH3),
4.04-4.18 (m, 1H, OCH2), 4.24 (dt, J ) 8.4, 1.8 Hz, 1H, OCH2),
5.34 (dd, J ) 8.7, 1.5 Hz, 1H, CH), 6.86-7.05 (m, 4H, 4 × CH),
7.19-7.32 (m, 2H, 2 × CH), 7.37-7.45 (m, 1H, CH), 7.81-
7.85 (m, 1H, CH). 13C NMR (CDCl3, 75 MHz): δ 32.7, 42.7,
50.9, 55.4, 55.6, 70.0, 101.9, 110.4, 111.0, 120.1, 120.2, 125.0,
127.0, 127.6, 128.4, 130.0, 131.8, 156.5, 157.3, 167.7, 172.7.
IR (KBr, cm-1): ν ) 2946 (w), 1705 (m), 1631 (m), 1600 (s),
1577 (m), 1489 (s), 1461 (s), 1436 (s), 1402 (m), 1368 (s), 1344
(s), 1296 (m), 1270 (m), 1234 (s), 1197 (w), 1166 (m), 1109 (m),
1076 (s), 1054 (s), 1024 (s), 982 (w), 779 (m), 758 (s), 704 (w),
656 (m), 528 (w). MS (EI, 70 eV): m/z (%) ) 354 (M+, 100),
322 (39), 295 (25), 247 (32). The exact molecular mass m/z )
354.1467 ( 2 ppm [M+] for C21H22O5 was confirmed by HRMS
(EI, 70 eV).
General Procedure for the Synthesis of Benzofurans
by Reaction of 2-Alkylidenetetrahydrofurans with Bo-
rontribromide. To a CH2Cl2-solution (10 mL/mmol) of the
2-alkylidenetetrahydrofuran 7 (1 equiv) was added BBr3 (4
equiv) at 0 °C. The reaction mixture was allowed to warm to
20 °C over 12 h and was stirred for 6 h at 20 °C. Water (15
mL/mmol substrate) was slowly added to the reaction mixture,
and the organic layer was separated. The aqueous layer was
extracted with CH2Cl2 (3 × 30 mL/mmol substrate). The
combined organic extracts were dried (Na2SO4), filtered, and
the filtrate was concentrated in vacuo. The residue was
purified by chromatography (silica gel, n-hexane/EtOAc) to
give 8.
Methyl 2-(3′-Bromopropyl)benzofuran-3-carboxylate
(8a). Starting with 7a (0.150 g, 0.60 mmol) and BBr3 (0.605
g, 2.42 mmol) in CH2Cl2 (6 mL), 8a was isolated after
chromatography (silica gel, n-hexane/EtOAc ) 100:1 f 1:1)
as a yellowish oil (0.163 g, 92%). 1H NMR (CDCl3, 300 MHz):
δ 2.34 (quint, J ) 7.2 Hz, 2H, CH2), 3.35 (t, J ) 7.5 Hz, 2H,
CH2), 3.47 (t, J ) 6.9 Hz, 2H, CH2-Br), 3.95 (s, 3H, OCH3),
7.28-7.33 (m, 2H, 2 × CH), 7.42-7.45 (m, 1H, CH), 7.95-
7.98 (m, 1H, CH). 13C NMR (CDCl3, 75 MHz): δ 26.8, 30.8,
32.4, 51.4, 109.2, 110.9, 121.9, 123.9, 124.6, 125.8, 153.6, 164.5,
165.2. IR (neat, cm-1): ν ) 2952 (m), 1714 (s), 1593 (s), 1478
(m), 1451 (s), 1437 (s), 1386 (m), 1342 (w), 1284 (m), 1235 (s),
1174 (s), 1127 (w), 1106 (m), 1073 (s), 1010 (w), 959 (w), 935
(w), 861 (w), 790 (m), 752 (s). MS (EI, 70 eV): m/z (%) ) 298
(M+ [81Br], 38), 296 (M+ [79Br], 39), 266 (7), 217 (16), 203 (10),
2-(Dihydrofuran-2(3H)-ylidene)-2-(2-methoxyphenyl)-
1-phenyl-ethanone (7f). Starting with 3c (0.100 g, 0.374
mmol), 2-methoxyphenylboronic acid (0.176 g, 1.12 mmol), K3-
PO4 (0.478 g, 2.25 mmol), and Pd(PPh3)4 (0.013 g, 0.011 mmol)
in 1,4-dioxane (10 mL), 7f was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 100:1 f 2:1) as a yellowish solid
1
(0.085 g, 77%), mp ) 123 °C. H NMR (CDCl3, 300 MHz): δ
2.16 (quint, J ) 7.5 Hz, 2H, CH2), 3.22 (t, J ) 7.8 Hz, 2H,
CH2), 3.44 (s, 3H, OCH3), 4.27 (t, J ) 7.2 Hz, 2H, OCH2), 6.63
(dd, J ) 5.1, 1.2 Hz, 1H, CH), 6.94 (dt, J ) 7.5, 1.2 Hz, 1H,
CH), 7.11-7.18 (m, 3H, 3 × CH of Ar), 7.22-7.28 (m, 1H, CH),
7.45 (dt, J ) 7.5, 1.5 Hz, 3H, 3 × CH of Ar). 13C NMR (CDCl3,
50 MHz): δ 24.2, 31.4, 54.8, 71.8, 108.5, 110.7, 120.2, 126.3,
127.0 (2C), 128.1 (2C), 128.2, 130.1, 131.8, 140.6, 156.3, 171.3,
196.1. IR (KBr, cm-1): ν ) 2992 (w), 2987 (w), 2936 (w), 1654
(s), 1595 (s), 1581 (s), 1487 (m), 1458 (m), 1443 (w), 1322 (m),
1300 (w), 1260 (s), 1249 (s), 1186 (s), 1114 (m), 1051 (w), 1022
(m), 967 (s), 932 (m), 889 (m), 760 (m), 712 (w), 712 (w), 663
J. Org. Chem, Vol. 70, No. 19, 2005 7691

Bellur and Langer
188 (100), 174 (5), 170 (29), 158 (47), 144 (4). Anal. Calcd for
C13H13BrO3 (297.148): C, 52.55; H, 4.41. Found: C, 52.84; H,
4.74.
6.6 Hz, 2H, CH2-Br), 4.41 (q, J ) 7.2 Hz, 2H, OCH2), 6.70
(dd, J ) 8.1, 0.9 Hz, 1H, CH), 6.88 (dd, J ) 8.1 Hz, 0.9 Hz,
1H, CH), 7.12 (t, J ) 8.1 Hz, 1H, CH), 10.40 (s, 1H, OH). 13C
NMR (CDCl3, 150 MHz): δ 14.5, 27.6, 31.0, 32.7, 62.5, 102.4,
109.5, 110.3, 113.7, 126.9, 151.5, 155.3, 163.8, 167.4. IR (KBr,
cm-1): ν ) 3417 (w), 3146 (w), 3126 (w), 3068 (w), 3043 (w),
2974 (w), 2933 (w), 1667 (s), 1630 (m), 1595 (m), 1481 (m),
1420 (m), 1384 (m), 1353 (w), 1328 (w), 1284 (m), 1240 (m),
1201 (m), 1155 (w), 1084 (m), 1045 (m), 1022 (w), 769 (m), 750
(m), 728 (w). MS (EI, 70 eV): m/z (%) ) 328 (M+ [81Br], 61),
326 (M+ [79Br], 62), 282 (100), 219 (14), 200 (7), 186 (4), 173
(38). The exact molecular mass m/z ) 326.0154 ( 2 ppm [M+]
for C14H15O4Br was confirmed by HRMS (EI, 70 eV). Anal.
Calcd for C14H15BrO4 (327.174): C, 51.40; H, 4.62. Found: C,
52.15; H, 4.73.
3-Benzoyl-2-(3′-bromopropyl)benzofuran (8f). Starting
with 7f (0.050 g, 0.17 mmol) and BBr3 (0.171 g, 0.68 mmol) in
CH2Cl2 (3 mL), 8f was isolated after chromatography (silica
gel, n-hexane/EtOAc ) 100:1 f 1:1) as a slightly yellowish oil
(0.036 g, 71%). 1H NMR (CDCl3, 300 MHz): δ 2.35 (quint, J )
7.1 Hz, 2H, CH2), 3.10 (t, J ) 7.4 Hz, 2H, CH2), 3.44 (t, J )
6.8 Hz, 2H, CH2-Br), 7.16-7.40 (m, 3H, 3 × CH), 7.47-7.64
(m, 4H, 4 × CH), 7.81-7.84 (m, 2H, 2 × CH). 13C NMR (CDCl3,
75 MHz): δ 27.0, 31.0, 32.4, 111.1, 117.4, 121.5, 123.7, 124.6,
126.6, 128.6 (2C), 129.2 (2C), 132.9, 139.1, 153.7, 163.5, 191.9.
IR (neat, cm-1): ν ) 2968 (m), 2925 (s), 2857 (m), 1730 (m),
1652 (s), 1573 (m), 1451 (s), 1377 (m), 1281 (m), 1242 (m), 1178
(m), 1117 (s), 1075 (w), 1017 (w), 937 (w), 899 (w), 753 (m),
700 (w). MS (EI, 70 eV): m/z (%) ) 344 (M+ [81Br], 29), 342
(M+ [79Br], 30), 263 (17), 249 (40), 135 (90), 221 (159), 205 (10),
178 (13), 160 (10), 148 (100), 131 (12), 105 (44), 77 (32). HRMS
(ESI): calcd for C18H15BrO2 [M+]: 344.02349 (81Br), 342.02554
(79Br); found: 344.02303 (81Br), 342.02576 (79Br).
Methyl 2-(3′-Bromopropyl)-5-hydroxybenzofuran-3-
carboxylate (8b). Starting with 7b (0.070 g, 0.25 mmol) and
BBr3 (0.504 g, 2.0 mmol) in CH2Cl2 (5 mL), 8b was isolated
after chromatography (silica gel, n-hexane/EtOAc ) 100:1 f
5:1) as a white solid (0.076 g, 97%), mp ) 154 °C. 1H NMR
(CDCl3, 300 MHz): δ 2.34 (quint, J ) 7.05 Hz, 2H, CH2), 3.33
(t, J ) 7.5 Hz, 2H, CH2), 3.47 (t, J ) 6.6 Hz, 2H, CH2-Br),
3.95 (s, 3H, OCH3), 5.31 (broad s, 1H, OH), 6.83 (dd, J ) 8.7,
2.4 Hz, 1H, CH), 7.30 (d, J ) 8.7 Hz, 1H, CH), 7.46 (d, J ) 2.4
Hz, 1H, CH). 13C NMR (CDCl3/DMSO-d6, 150 MHz): δ 26.4,
30.2, 32.2, 50.8, 106.3, 108.4, 110.6, 112.9, 126.1, 147.4, 153.7,
163.9, 165.0. IR (KBr, cm-1): ν ) 3326 (s), 2962 (w), 2947 (w),
1687 (s), 1624 (w), 1605 (w), 1578 (m), 1488 (m), 1468 (s), 1441
(s), 1408 (m), 1382 (m), 1306 (m), 1267 (s), 1239 (m), 1224 (m),
1197 (m), 1169 (s), 1133 (w), 1111 (w), 1077 (m), 1048 (m),
955 (w), 867 (m), 816 (m), 789 (m), 731 (w), 664 (m), 623 (w).
MS (EI, 70 eV): m/z (%) ) 314 (M+ [81Br], 89), 312 (M+ [79Br],
92), 281 (7), 233 (6), 219 (6), 205 (100), 175 (18), 147 (8). The
exact molecular mass m/z ) 311.9997 ( 2 ppm [M+] for
C13H13O4Br was confirmed by HRMS (EI, 70 eV). Anal. Calcd
for C13H13BrO4 (313.147): C, 49.86; H, 4.18. Found: C, 50.14;
H, 4.88.
Ethyl 2-(3′-Bromopropyl)benzofuran-3-carboxylate (8c).
Starting with 7c (0.080 g, 0.30 mmol) and BBr3 (0.306 g, 1.2
mmol) in CH2Cl2 (3 mL), 8c was isolated after chromatography
(silica gel, n-hexane/EtOAc ) 100:1 f 50:1) as a slightly
yellowish oil (0.078 g, 84%). 1H NMR (CDCl3, 300 MHz): δ
1.46 (t, J ) 7.2 Hz, 3H, CH3), 2.36 (quint, J ) 6.6 Hz, 2H,
CH2), 3.36 (t, J ) 7.2 Hz, 2H, CH2), 3.48 (t, J ) 6.6 Hz, 2H,
CH2-Br), 4.42 (q, J ) 7.2 Hz, 2H, OCH2), 7.29-7.32 (m, 2H,
2 × CH), 7.44-7.47 (m, 1H, CH), 7.97-8.00 (m, 1H, CH). 13C
NMR (CDCl3, 150 MHz): δ 14.7, 27.2, 31.1, 32.7, 60.7, 109.6,
111.2, 122.2, 124.1, 124.8, 126.3, 153.9, 164.4, 165.3. IR (neat,
cm-1): ν ) 2979 (w), 2931 (w), 1711 (s), 1593 (m), 1479 (w),
1451 (m), 1404 (w), 1380 (m), 1347 (w), 1283 (w), 1234 (s), 1176
(m), 1128 (w), 1104 (w), 1070 (s), 1012 (w), 789 (w), 751 (m).
MS (EI, 70 eV): m/z (%) ) 312 (M+ [81Br], 88) 310 (M+ [79Br],
95), 281 (17), 265 (14), 231 (7), 217 (3), 203 (27), 189 (4), 175
(100), 157 (36), 128 (15). HRMS (FT-ICR): calcd for C14H15-
BrO3 [M+]: 313.02623 (81Br); 311.02828 (79Br); found: 313.02576
(81Br), 311.02779 (79Br).
Ethyl 2-(3′-Bromopropyl)-6-hydroxybenzofuran-3-car-
boxylate (8d). Starting with 7d (0.080 g, 0.27 mmol) and BBr3
(0.549 g, 2.2 mmol) in CH2Cl2 (3 mL), 8d was isolated after
chromatography (silica gel, n-hexane/EtOAc ) 100:1 f 5:1)
as a white solid (0.085 g, 97%), mp ) 132 °C. 1H NMR (CDCl3,
300 MHz): δ 1.44 (t, J ) 7.2 Hz, 3H, CH3), 2.33 (quint, J )
7.05 Hz, 2H, CH2), 3.31 (t, J ) 7.5 Hz, 2H, CH2), 3.47 (t, J )
6.6 Hz, 2H, CH2-Br), 4.41 (q, J ) 7.2 Hz, 2H, OCH2), 4.97
(broad s, 1H, OH), 6.84 (dd, J ) 8.7, 2.1 Hz, 1H, CH), 6.94 (d,
J ) 2.1 Hz, 1H, CH), 7.80 (d, J ) 8.7 Hz, 1H, CH). 13C NMR
(CDCl3+d6-DMSO, 150 MHz): δ 14.3, 26.7, 30.8, 32.6, 60.1,
97.8, 109.1, 113.1, 118.0, 121.7, 154.6, 155.5, 163.3, 164.2. IR
(KBr, cm-1): ν ) 3304 (s), 2987 (w), 1676 (s), 1628 (m), 1594
(m), 1510 (w), 1495 (w), 1443 (s), 1406 (w), 1367 (m), 1301 (m),
1284 (m), 1262 (m), 1247 (m), 1196 (m), 1140 (m), 1113 (s),
1076 (s), 950 (w), 838 (w), 817 (w). MS (EI, 70 eV): m/z (%) )
328 (M+ [81Br], 97), 326 (M+ [79Br], 100), 297 (2%), 281 (9),
219 (75), 191 (88), 173 (19). The exact molecular mass m/z )
326.0154 ( 2 ppm [M+] for C14H15O4Br was confirmed by
HRMS (EI, 70 eV). Anal. Calcd for C14H15BrO4 (327.174): C,
51.40; H, 4.62. Found: C, 51.30; H, 4.97.
Methyl 2-(3′-Bromo-4′-chlorobutyl)benzofuran-3-car-
boxylate (8g). Starting with 7g (0.050 g, 0.17 mmol) and BBr3
(0.171 g, 0.67 mmol) in CH2Cl2 (3 mL), 8g was isolated after
chromatography (silica gel, n-hexane/EtOAc ) 100:1 f 10:1)
as a slightly yellowish oil (0.047 g, 80%). 1H NMR (CDCl3, 300
MHz): δ 2.21-2.34 (m, 1H, CH2), 2.57-2.69 (m, 1H, CH2),
3.31-3.42 (m, 1H, CH2), 3.44-3.54 (m, 1H, CH2), 3.80 (dd,
J ) 11.4, 8.4 Hz, 1H, CH2-Cl), 3.97 (dd, J ) 11.4, 4.8 Hz, 1H,
CH2-Cl), 3.97 (s, 3H, OCH3), 4.14-4.22 (m, 1H, CH-Br),
7.30-7.33 (m, 2H, 2 × CH of Ar), 7.44-7.48 (m, 1H, CH of
Ar), 7.96-7.99 (m, 1H, CH of Ar). 13C NMR (CDCl3, 75 MHz):
δ 26.0, 33.5, 48.0, 51.6, 51.9, 109.4, 111.0, 122.0, 124.0, 124.7,
125.9, 153.9, 164.6, 164.8. IR (neat, cm-1): ν ) 2952 (w), 2926
(w), 1714 (s), 1594 (m), 1446 (m), 1383 (w), 1285 (w), 1237 (s),
1176 (m), 1106 (w), 1070 (s), 794 (w), 751 (m). MS (EI, 70 eV):
m/z (%) ) 348 (M+ [81Br37Cl], 6), 346 (M+ [81Br35Cl], 34), 344
(M+ [79Br35Cl], 24), 314 (2), 229 (18), 203 (24), 189 (100), 169
(13), 159 (22), 131 (12), 114 (8). HRMS (ESI): calcd for
C
14H14BrClO3 [M+]: 345.97944 (81Br), 343.98148 (79Br);
found: 345.96002 (81Br), 343.98353 (79Br).
Methyl 2-[3′-Bromo-1′-(2′′-hydroxyphenyl)propyl]ben-
zofuran-3-carboxylate (8h). Starting with 7h (0.030 g, 0.085
mmol) and BBr3 (0.129 g, 0.51 mmol) in CH2Cl2 (9 mL), 8h
was isolated after chromatography (silica gel, n-hexane/
EtOAc ) 100:1 f 4:1) as a colorless oil (0.019 g, 58%). 1H NMR
(CDCl3, 300 MHz): δ 2.68-2.81 (m, 1H, CH2), 2.84-2.95 (m,
1H, CH2), 3.25-3.41 (m, 2H, CH2-Br), 4.06 (s, 3H, OCH3), 5.53
(t, J ) 7.6 Hz, 1H, CH), 6.91-6.97 (m, 2H, 2 × CH), 7.13-
7.19 (m, 1H, CH), 7.29-7.35 (m, 2H, 2 × CH), 7.45-7.50 (m,
2H, 2 × CH), 7.86-7.89 (m, 1H, CH), 7.91 (s, 1H, OH). 13C
NMR (CDCl3, 75 MHz): δ 30.6, 35.0, 35.3, 52.5, 111.3, 117.9,
120.9, 121.1, 122.1, 124.3, 124.5, 124.8, 125.2, 127.7, 128.8,
153.9, 154.5, 165.5, 167.1. IR (neat, cm-1): ν ) 3354 (br), 2974
(m), 2956 (m), 2928 (m), 2858 (w), 1738 (w), 1712 (s), 1688 (s),
1588 (m), 1482 (m), 1454 (s), 1368 (m), 1288 (m), 1239 (s), 1174
(s), 1154 (m), 1108 (s), 1069 (s), 1020 (m), 984 (w), 793 (w),
754 (s). MS (EI, 70 eV): m/z (%) ) 390 (M+ [81Br], 18), 388
(M+ [79Br], 19), 356 (17), 329 (5), 281 (44), 263 (11), 249 (100),
221 (65), 205 (5), 134 (25), 107 (13). The exact molecular mass
Ethyl 2-(3′-Bromopropyl)-4-hydroxybenzofuran-3-car-
boxylate (8e). Starting with 7e (0.070 g, 0.24 mmol) and BBr3
(0.480 g, 1.92 mmol) in CH2Cl2 (3 mL), 8e was isolated after
chromatography (silica gel, n-hexane/EtOAc ) 100:1 f 50:1)
as a white solid (0.073 g, 92%); mp ) 86 °C. 1H NMR (CDCl3,
300 MHz): δ 1.40 (t, J ) 7.2 Hz, 3H, CH3), 2.27 (quint, J )
7.05 Hz, 2H, CH2), 3.23 (t, J ) 7.5 Hz, 2H, CH2), 3.41 (t, J )
7692 J. Org. Chem., Vol. 70, No. 19, 2005

Synthesis of Benzofurans with Bromide Functionality
m/z ) 388.0310 ( 2 ppm [M+] for C19H17BrO4 was confirmed
by HRMS (EI, 70 eV).
and BBr3 (0.171 g, 0.67 mmol) in CH2Cl2 (3 mL), E-9b and
Z-9b were isolated after chromatography (silica gel, n-hexane/
EtOAc ) 100:1 f 1:1) as yellowish solids (0.028 g, 65%; 0.013
g, 30%).
General Procedure for the Synthesis of 9 by Reaction
of 2-Alkylidenetetrahydrofurans with Borontribromide.
To a CH2Cl2-solution (10 mL/mmol) of the 2-alkylidenetet-
rahydrofuran (7) (1 equiv) was added BBr3 (4 equiv) at 0 °C.
The reaction mixture was allowed to warm to 20 °C over 12 h
and was stirred for 12 h at 20 °C. The reaction mixture was
then poured into an aqueous solution of KOtBu (1 M, 10 mL/
mmol). The mixture was stirred for 1 h and later extracted
with CH2Cl2 (3 × 30 mL/mmol). The combined organic extracts
were dried (Na2SO4), filtered, and the filtrate was concentrated
in vacuo. The residue was purified by chromatography (silica
gel, n-hexane/EtOAc) to give 9.
3-(Dihydro-furan-2(3H)-ylidene)-3H-benzofuran-2-
one (9a). Starting with 7a (0.070 g, 0.282 mmol) and BBr3
(0.283 g, 1.13 mmol) in CH2Cl2 (3 mL), E-9a and Z-9a were
isolated after chromatography (silica gel, n-hexane/EtOAc )
50:1 f 1:1) as yellowish solids (0.031 g, 54%; 0.020 g, 35%).
E-9a. mp ) 170 °C. 1H NMR (CDCl3, 300 MHz): δ 2.28
(quint, J ) 7.5 Hz, 2H, CH2), 3.37 (t, J ) 7.8 Hz, 2H, CH2),
4.62 (t, J ) 7.2 Hz, 2H, OCH2), 7.06-7.21 (m, 3H, 3 × CH of
Ar), 7.60 (dd, J ) 7.2, 1.2 Hz, 1H, CH of Ar). 13C NMR (CDCl3,
75 MHz): δ 23.5, 31.4, 75.0, 95.9, 110.0, 122.0, 123.5, 124.1,
126.7, 151.0, 169.8, 175.2. IR (KBr, cm-1): ν ) 2911 (w), 1750
(s), 1652 (s), 1611 (w), 1589 (w), 1479 (w), 1459 (m), 1420 (w),
1392 (m), 1247 (s), 1220 (m), 1166 (m), 1032 (m), 977 (s), 939
(m), 866 (m), 780 (m), 751 (m). MS (EI, 70 eV): m/z (%) ) 202
(M+, 100), 159 (10). The exact molecular mass m/z ) 202.0630
( 2 ppm [M+] for C12H10O3 was confirmed by HRMS (EI, 70
eV).
E-9b. mp ) 61 °C. 1H NMR (CDCl3, 300 MHz): δ 2.12-
2.23 (m, 1H, CH2), 2.39-2.52 (m, 1H, CH2), 3.25-3.38 (m, 1H,
CH2), 3.52-3.60 (m, 1H, CH2), 3.80 (d, J ) 5.1 Hz, 1H, CH2-
Cl), 3.84 (d, J ) 5.1 Hz, 1H, CH2-Cl), 5.02-5.08 (m, 1H, OCH),
7.07-7.21 (m, 3H, 3 × CH of Ar), 7.61 (dd, J ) 7.5, 1.2 Hz,
1H, CH of Ar). 13C NMR (CDCl3, 75 MHz): δ 26.1, 31.0, 45.3,
85.2, 96.3, 109.8, 122.0, 123.4, 126.8, 126.8, 150.8, 169.4, 173.3.
IR (KBr, cm-1): ν ) 2976 (s), 2932 (w), 2866 (m), 1758 (s),
1746 (s), 1655 (s), 1612 (w), 1455 (s), 1378 (m), 1360 (m), 1296
(w), 1242 (s), 1206 (s), 1151 (s), 1118 (s), 1076 (m), 1015 (s),
964 (s), 933 (w), 874 (w), 832 (w), 752 (s). MS (EI, 70 eV): m/z
(%) ) 252 (M+ [37Cl], 20), 250 (M+ [35Cl], 73), 215 (20), 187 (8),
160 (100), 104 (25), 85 (76), 76 (26). HRMS (ESI): calcd for
C13H11ClO3 [M+]: 252.03672 (37Cl), 250.03967 (35Cl); found:
252.03800 (37Cl), 250.03903 (35Cl).
Z-9b. 1H NMR (CDCl3, 300 MHz): δ 2.34-2.39 (m, 1H,
CH2), 2.45-2.58 (m, 1H, CH2), 3.14-3.39 (m, 2H, CH2), 3.86
(d, J ) 0.9 Hz, 1H, CH2-Cl), 3.87 (d, J ) 1.8 Hz, 1H, CH2-
Cl), 5.13-5.19 (m, 1H, OCH), 7.08-7.23 (m, 4H, 4 × CH of
Ar). 13C NMR (CDCl3, 75 MHz): δ 25.5, 31.0, 45.6, 85.1, 95.9,
110.5, 119.6, 123.3, 124.2, 126.6, 151.2, 167.3, 171.6. IR (KBr,
cm-1): ν ) 2927 (w), 1756 (s), 1644 (s), 1459 (w), 1243 (m),
1140 (m), 1086 (m), 1014 (m), 938 (w), 777 (w), 747 (m). MS
(EI, 70 eV): m/z (%) ) 252 (M+ [37Cl], 2), 250 (M+ [35Cl], 12),
215 (12), 187 (7), 160 (100), 104 (35), 85 (86), 76 (24). HRMS
(ESI): calcd for C13H11ClO3 [M+]: 252.03672 (37Cl), 250.03967
(35Cl); found: 252.03800 (37Cl), 250.03903 (35Cl).
Z-9a. mp ) 106 °C. 1H NMR (CDCl3, 300 MHz): δ 2.34
(quint, J ) 7.5 Hz, 2H, CH2), 3.19 (t, J ) 7.8 Hz, 2H, CH2),
4.68 (t, J ) 7.2 Hz, 2H, OCH2), 7.06-7.25 (m, 4H, 4 × CH of
Ar). 13C NMR (CDCl3, 75 MHz): δ 23.1, 32.4, 75.3, 95.9, 110.6,
119.6, 123.4, 124.7, 126.5, 151.3, 165.9, 172.9. IR (KBr, cm-1):
ν ) 2958 (w), 2928 (w), 2855 (w), 1814 (w), 1760 (s), 1638 (s),
1457 (s), 1422 (w), 1392 (w), 1349 (w), 1308 (w), 1288 (w), 1245
(s), 1221 (m), 1192 (m), 1158 (w), 1133 (s), 1084 (s), 1028 (s),
997 (m), 976 (w), 924 (s), 868 (w), 776 (m), 750 (s). MS (EI, 70
eV): m/z (%) ) 202 (M+, 87), 159 (100). The exact molecular
mass m/z ) 202.0630 ( 2 ppm [M+] for C12H10O3 was confirmed
by HRMS (EI, 70 eV).
Acknowledgment. Financial support from the DAAD
(scholarship for E.B.), from the BASF AG, and from the
Deutsche Forschungsgemeinschaft is gratefully acknowl-
edged.
Supporting Information Available: Experimental pro-
cedures, spectroscopic data, and copies of NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
3-(5-Chloromethyl-dihydro-furan-2(3H)-ylidene)-3H-
benzofuran-2-one (9b). Starting with 7g (0.050 g, 0.17 mmol)
JO051079Z
J. Org. Chem, Vol. 70, No. 19, 2005 7693