Synthesis of functionalized furans based on a '[3+2] cyclization/ bromination/elimination' strategy

Article abstract of DOI:10.1055/s-2006-926301

The bromination of 2-alkylidenetetrahydrofurans - readily available via one-pot [3+2] cyclizations - afforded 2-alkylidene-3-bromotetrahydrofurans. Elimination of hydrogen bromide and subsequent aromatization of these compounds provided a convenient appro

Full text of DOI:10.1055/s-2006-926301

480
PAPER
Synthesis of Functionalized Furans Based on a ‘[3+2] Cyclization/
Bromination/Elimination’ Strategy
S
ynthesis of Fu
s
e
a
b
c
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Institut für Chemie und Biochemie, Universität Greifswald, E-mail: Soldmannstr. 16, 17487 Greifswald, Germany
Leibniz-Institut für Organische Katalyse an der Universität Rostock e. V. (IfOK), Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
Received 10 June 2005; revised 16 August 2005
R2
O
O
O
O
Abstract: The bromination of 2-alkylidenetetrahydrofurans –
readily available via one-pot [3+2] cyclizations – afforded 2-alky-
lidene-3-bromotetrahydrofurans. Elimination of hydrogen bromide
and subsequent aromatization of these compounds provided a con-
venient approach to functionalized furans.
Cl
Br
OR3
OR3
i
R1
R2
R1
1a–h
2a–h
ii
Keywords: bromination, elimination, furans, O-heterocycles, tet-
rahydrofurans
R2
O
Br
O
O
O
OR3
OR3
2-Alkylidenetetrahydrofurans represent important syn-
thetic building blocks,1,2 which have been used for cy-
+
+
R1
R1
Br
cloadditions,1a–d
nucleophilic
additions,1e,f
4a (R2 = H)
3a–h
cyclopropanations,1g hydrogenations,1h,2h–i and spiroketal
formation.3 In recent years, we have reported a number of
one-pot syntheses of 2-alkylidenetetrahydrofurans by
[3+2] cyclizations of 1,3-dicarbonyl dianions and 1,3-bis-
silyl enol ethers.4 In this context, we have also reported
the functionalization of 2-alkylidenetetrahydrofurans by
lithiation/alkylation,5a,b by BBr3-mediated ring-open-
ings,5c,d and by bromination of the exocyclic double bond
and subsequent Suzuki cross-coupling reactions.6 Herein,
we wish to report a new approach to functionalized furans
R2
Br
O
O
OR3
OR3
R1
O
O
Br
Br
6a,b (R1 = H)
Br
5a–c (R2 = H)
Scheme 1 Preparation and bromination of 2-alkylidenetetrahydro-
furans 2a–h: i: 1) LDA (2.3 equiv), THF, 0 °C, 1 h, 2) Br(CH2)2Cl,
–78→20 °C, 14 h, then reflux, 12 h; ii: NBS (see Table 1), CCl4,
based on elimination reactions of 2-alkylidene-3-bro- reflux, 3 h
motetrahydrofurans. The synthesis and reactivity of 2-
alkylidene-3-bromotetrahydrofurans has, to the best of
heating, regioselective attack of the oxygen atom onto the
chloride group.
our knowledge, not yet been studied.7,8 Functionalized
furans are of considerable pharmacological relevance and
occur in a variety of natural products, such as terpenes.
This includes, for instance, the calicogorgins, furan fatty
The reaction of 2a with NBS (1.1 equivalents) resulted in
the formation of a separable mixture of bromination prod-
ucts 3a, 4a, and (E)-5a (Scheme 1).6 The use of an excess
of NBS (3.0 equivalents) resulted in selective formation
of the dibrominated product 5a; the latter was isolated in
high yield as a separable mixture of E/Z isomers. The em-
ployment of other bromination agents (e.g. Br2) was un-
successful. Besides the stoichiometry, the reaction time
(three hours), temperature (reflux), and solvent (CCl4)
proved to be important parameters in the optimization of
the bromination reactions. No conversion was observed
when the reaction was carried out at 20 °C. Shorter reac-
tion times resulted in incomplete conversion; in contrast,
decomposition was observed with extended reaction
times. The bromination of 2b–e, containing an alkyl sub-
stituent at C-3, resulted in bromination of C-3 and forma-
tion of the monobromides 3b–e. The best yields of 3b and
3c were obtained when 1.5 and 1.8 equivalents of NBS
was employed. In contrast, employment of only 1.1 equiv-
acids,
cyctotoxic
furanocembranes,
gersolanes,
pseudopteranes, rosefuran, agassizin, furodysin, mikani-
furan, or a-clausenan.9 Although numerous synthetic ap-
proaches to furans have been reported,10 the development
of new and convenient strategies is of considerable inter-
est.
The required starting materials, 2-alkylidenetetrahydro-
furans 2a–h, were prepared by our recently reported cy-
clization of 1-bromo-2-chloroethane with the dianions of
1,3-dicarbonyl compounds 1a–h (Scheme 1, Table 1).5a,11
These cyclizations proceed by attack of C-4 of the dianion
onto the bromide group at low temperature and, upon
SYNTHESIS 2006, No. 3, pp 0480–0488
x
x
.
x
x
.2
0
0
6
Advanced online publication: 13.01.2006
DOI: 10.1055/s-2006-926301; Art ID: T07905SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Functionalized Furans
481
Table 1 Bromination of 2-Alkylidenetetrahydrofurans
Entry Substrate 1
Substrate 2
Products 3, 4, 5, and 6 (%)a
NBS
(equiv)
O
OiPr
Br
O
O
O
O
O
O
O
Oi-Pr
Oi-Pr
Oi-Pr
1
2
3
1.1
Br
Oi-Pr
O
O
Br
1a
Br
2a
(E)-3a (21%)
(Z)-4a (65%)
(E)-5a (6%)
Br
O
O
O
O
O
Me
OMe
OEt
OMe
1.5
1.8
OMe
O
O
O
Br
Br
1b
2b
2c
(E)-3b (47%)
(Z)-5b (44%)
O
O
Br
O
OEt
O
O
O
O
O
OEt
OEt
OEt
O
Br
O
O
Br
Br
Br
1c
(E)-3c (31%)
(Z)-5c (60%)
(E)-5c (6%)
O
O
O
OEt
OEt
OEt
OEt
O
4
5
1.3
1.3
O
Br
3d (87%)
1d
2d
O
O
O
O
OEt
OEt
O
O
Br
3e (91%)
1e
2e
2f
O
O
O
O
O
O
OEt
OEt
OEt
6
7
8
1.1
1.1
1.2
OEt
OEt
O
O
O
O
O
Br
Br
Br
1f
6a (12%)
3f (56%)
O
O
O
O
OEt
OEt
Br
1g
1h
2g
2h
3g (80%)
O
O
O
O
O
O
O
O
O
O
Br
Br
O
Br
3h (76%)
6b (22%)
a Yields of isolated products.
alents of NBS again resulted in the formation of a mixture bond, resulted in monobromination of C-3 (3f and 3g) and
of products and, thus, a decreased yield. The yields of di- in double bromination (6a). Bromination (NBS, 1.2
brominated products 5b and 5c were significantly im- equivalents) of tetrahydro-2,3¢-bifuranyliden-2¢-one
proved by employing an excess of NBS. The bromination (2h)5a,11 afforded the monobromide 3h (76%) and the di-
of 2-alkylidenetetrahydrofurans 2f and 2g, containing bromide 6b (22%).
methyl and ethyl groups located on the exocyclic double
Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York

482
E. Bellur, P. Langer
PAPER
Table 2 Synthesis of Furans from 2-Alkylidene-3-bromotetra-
hydrofurans (continued)
2-Alkylidene-3-bromotetrahydrofurans proved to be ex-
cellent starting materials for the synthesis of functional-
ized furans (Scheme 2, Table 2). Treatment of 3a–h with
DBU (two equivalents) resulted in the elimination of hy-
drogen bromide and subsequent aromatization gave the
known10 furans 7a–h. Likewise, the functionalized furans
7i–k were prepared. Notably, the dehydrobromination of
5c proceeded with very good regioselectivity to give the
bromofuran 7i. The reaction of DBU with 2-alkylidene-
3,3-dibromotetrahydrofurans 6a and 6b afforded the 3-
bromofurans 7j and 7k which represent useful synthetic
building blocks for functionalization by a cross-coupling
reaction. In fact, 3-bromofurans are more difficult to pre-
pare than 2-bromofurans (vide supra).12 All furans 7a–k
were isolated in good yields.
Entry
6
Substrate
Product 7 (%) a
O
O
OEt
OEt
O
O
O
O
Br
7f (52%)
3f
O
O
OEt
OEt
7
8
Br
7g (66%)
3g
O
O
O
O
R2
R2
O
O
O
O
i
OR3
OR3
Br
7h (63%)
3h
O
O
R1 Br
R1
Br
Br
O
O
O
3a–h, 5c, 6a,b
7a–k
OEt
OEt
9
Scheme 2 Synthesis of furans 7a–k: i: DBU (2 equiv), THF, 20 °C,
12 h
O
Br
5c
7i (61%)
Table 2 Synthesis of Furans from 2-Alkylidene-3-bromotetra-
hydrofurans
O
O
OEt
OEt
10
11
Entry
1
Substrate
Product 7 (%) a
O
O
Br
Br
Br
O
6a
7j (76%)
O
Oi-Pr
Oi-Pr
O
O
O
O
O
O
Br
7a (72%)
3a
3b
O
O
Br
Br
Br
O
O
OMe
6b
OMe
OEt
7k (83%)
2
3
a Yields of isolated products.
O
O
O
Br
7b (75%)
O
The Suzuki reaction of dibromide (Z)-5c was next studied
(Scheme 3). The reaction of phenylboronic acid (3 equiv-
alents) with (Z)-5c, containing an ethyl group located at
C-3, exclusively afforded furan 8 (60%). The formation of
8 occurs through a Suzuki reaction of the alkenyl bromide,
thermal elimination of hydrogen bromide, and subsequent
aromatization. Due to steric reasons, elimination is fa-
vored over a double Suzuki reaction.6b
O
OEt
O
Br
3c
7c (64%)
O
O
OEt
OEt
O
4
5
O
Br
In summary, we have reported the synthesis of 2-alky-
lidene-3-bromotetrahydrofurans by NBS bromination of
3d
7d (55%)
O
OEt
Br
O
Ph
O
O
O
O
Ph-B(OH)2
i
OEt
O
OEt
OEt
O
Br
Br
(Z)-5c
3e
8 (60%)
7e (53%)
Scheme 3 Elimination and Suzuki reaction of 2-alkylidene-1¢,3-
dibromotetrahydrofuran (Z)-5c: i: PhB(OH)2 (3 equiv), Pd(PPh3)4
(3 mol%), K3PO4 (6 equiv), 1,4-dioxane, reflux, 6 h
Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Furans
483
1H NMR (CDCl3, 300 MHz): d = 0.91 (t, J = 7.2 Hz, 3 H, CH3),
1.26 (t, J = 7.2 Hz, 3 H, CH3), 1.30–1.43 (m, 5 H, 3 × CH2), 1.62–
1.72 (m, 1 H, CH2), 1.97 (dd, J = 12.6, 6.0 Hz, 1 H, CH2), 2.04–2.14
(m, 1 H, CH2), 3.58–3.63 (m, 1 H, CH), 4.05–4.21 (m, 3 H,
OCH2CH3, OCH2), 4.26–4.33 (m, 1 H, OCH2), 5.23 (s, 1 H, CH=C).
2-alkylidenetetrahydrofurans, which are readily available
by one-pot [3+2] cyclizations. Elimination reactions of 2-
alkylidene-3-bromotetrahydrofurans and 2-alkylidene-
1¢,3-dibromotetrahydrofurans provided a convenient ap-
proach to functionalized furans.
MS (EI, 70 eV): m/z (%) = 212 (M+, 6), 197 (9), 184 (7), 169 (32),
167 (42), 156 (37), 141 (100), 128 (15), 114 (25), 97 (42), 84 (24).
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere. MS were obtained by EI (70
eV), CI (H2O), or ESI. For preparative scale chromatography silica
gel (60–200 mesh) was used. Mps are uncorrected.
Reaction of 2-Alkylidenetetrahydrofurans or Furans with NBS;
General Procedure
To a CCl4 solution (5 mL/mmol) of 2-alkylidenetetrahydrofuran (2
or 9) or furan (10) (1 equiv) was added NBS (1.1–1.8 equiv, see
Table 1) at 20 °C. The reaction mixture was heated and stirred under
reflux for 3 h, allowed to cool to ambient temperature, and the sol-
vent was removed in vacuo. The residue was purified by chroma-
tography (n-hexane–EtOAc) to give the brominated 2-
alkylidenetetrahydrofuran (3, 4, 5, or 6) or furan (11).
Isopropyl (Dihydrofuran-2-ylidene)acetate (2a)5a
Isopropyl acetoacetate (1a; 7.28 mL, 50 mmol), i-Pr2NH (17.5 mL,
125 mmol), n-BuLi (15% in n-hexane; 78.5 mL, 125 mmol), and 1-
bromo-2-chloroethane (4.97 mL, 60 mmol) in THF (300 mL) gave
(E)-2a and (Z)-2a after chromatography (n-hexane–
EtOAc, 100:1→1:1).
2-Alkylidenetetrahydrofurans 3a, 4a, and 5a
(E)-2a
Isopropyl [dihydrofuran-2(3H)-ylidene]acetic acid isopropyl ester
(2a; 0.936 g, 5.5 mmol) and NBS (1.077 g, 6.05 mmol) in CCl4 (20
mL) at 20 °C gave (E)-3a, (Z)-4a, and (E)-5a after chromatography
(n-hexane–EtOAc, 100:1→1:1).
Yield: 5.42 g (64%); slightly yellowish oil.
1H NMR (CDCl3, 300 MHz): d = 1.26 (d, J = 6.3 Hz, 6 H, 2 × CH3),
2.09 (quint, J = 7.5 Hz, 2 H, CH2), 3.10 (dt, J = 7.8 Hz, 1.9, 2 H,
CH2), 4.21 (t, J = 6.9 Hz, 2 H, OCH2), 5.02 (sept, J = 6.3 Hz, 1 H,
OCH), 5.27 (t, J = 1.8 Hz, 1 H, CH=C).
Isopropyl [3-Bromodihydrofuran-2(3H)-ylidene]acetate
[(E)-3a]
Yield: 0.281 g (21%); yellowish oil.
(Z)-2a
Yield: 1.09 g (13%); slightly yellowish oil.
IR (neat): 2981 (m), 2935 (w), 2912 (w), 1701 (s), 1650 (s), 1464
(w), 1438 (w), 1375 (s), 1333 (w), 1302 (m), 1276 (m), 1246 (m),
1217 (w), 1179 (m), 1153 (m), 1127 (s), 1103 (s), 1060 (m), 1036
(s), 1008 (w), 958 (w), 888 (w), 834 (w), 705 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.27 (d, J = 6.3 Hz, 6 H, 2 × CH3),
2.43–2.50 (m, 2 H, CH2), 4.38–4.50 (m, 2 H, OCH2), 5.08 (quint,
J = 6.3 Hz, 1 H, CH), 5.25 (s, 1 H, CH=C), 5.76–5.78 (m, CHBr).
13C NMR (CDCl3, 75 MHz): d = 21.9, 22.0 (CH3), 36.0 (CH2), 43.0
(CHBr), 67.1 (CH), 69.6 (C-5), 91.9 (CH=C), 166.3 (O=CO), 172.8
(OCCH=).
MS (EI, 70 eV): m/z (%) = 250 (M+ [81Br], 6), 248 (M+ [79Br], 6),
208 (20), 207 (29), 206 (21), 205 (26), 191 (54), 190 (15), 189 (64),
188 (11), 187 (4), 164 (32), 162 (32), 161 (5), 159 (2), 148 (2), 146
(1), 133 (3), 131 (2), 127 (46), 110 (15), 109 (75), 108 (46), 97 (4),
83 (28), 81 (24), 70 (100).
1H NMR (CDCl3, 300 MHz): d = 1.26 (d, J = 6.3 Hz, 6 H, 2 × CH3),
2.04 (quint, J = 7.5 Hz, 2 H, CH2), 2.69 (dt, J = 7.8 Hz, 1.2, 2 H,
CH2), 4.44 (t, J = 6.9 Hz, 2 H, OCH2), 4.89 (t, J = 1.1 Hz, 1 H,
CH=C), 5.03 (sept, J = 6.3 Hz, 1 H, OCH).
Ethyl [3-Propyldihydrofuran-2(3H)-ylidene]acetate (2d)5a
Substrate 1d (3.200 g, 18.6 mmol), i-Pr2NH (6.53 mL, 46.5 mmol),
n-BuLi (15% in n-hexane; 29.2 mL, 46.5 mmol), and 1-bromo-2-
chloroethane (1.85 mL, 22.3 mmol) in THF (100 mL), gave (E)-2d
and (Z)-2d after chromatography (n-hexane–EtOAc, 100:1→1:1).
(E)-2d
Yield: 1.554 g (42%); yellowish oil.
1H NMR (CDCl3, 300 MHz): d = 0.96 (t, J = 7.2 Hz, 3 H, CH3),
1.25 (t, J = 7.2 Hz, 3 H, CH3), 1.31–1.49 (m, 3 H, 2 × CH2), 1.62–
1.71 (m, 1 H, CH2), 1.97 (dd, J = 12.6, 6.3 Hz, 1 H, CH2), 2.04–2.15
(m, 1 H, CH2), 3.60–3.65 (m, 1 H, CH), 4.09–4.20 (m, 3 H,
OCH2CH3, OCH2), 4.26–4.32 (m, 1 H, OCH2), 5.23 (s, 1 H, CH=C).
Anal. calcd for C9H13BrO3 (249.104): C, 43.40; H, 5.26. Found: C,
43.28; H, 5.48.
Isopropyl Bromo[dihydrofuran-2(3H)-ylidene]acetate [(Z)-4a]
Yield: 0.888 g (65%); yellowish oil.
(Z)-2d
Yield: 0.64 g (17%); yellowish oil.
IR (neat): 2982 (s), 2938 (m), 2905 (m), 1732 (m), 1699 (s), 1690
(s), 1658 (m), 1612 (s), 1525 (w), 1462 (m), 1455 (m), 1427 (m),
1374 (m), 1355 (m), 1335 (m), 1276 (s), 1232 (s), 1211 (s), 1182 (s),
1147 (m), 1109 (m), 1067 (s), 1022 (m), 990 (w), 960 (m), 924 (m),
896 (w), 875 (w), 856 (w), 824 (w), 805 (w), 781 (m), 760 (m), 719
(w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.95 (t, J = 7.2 Hz, 3 H, CH3),
1.26 (t, J = 7.2 Hz, 3 H, CH3), 1.31–1.49 (m, 4 H, 2 × CH2), 1.60–
1.77 (m, 1 H, CH2), 2.14–2.25 (m, 1 H, CH2), 2.75–2.85 (m, 1 H,
CH), 4.15 (q, J = 7.2 Hz, 2 H, OCH2CH3), 4.26–4.34 (m, 1 H,
OCH2), 4.45–4.52 (m, 1 H, OCH2), 4.85 (d, J = 1.5 Hz, 1 H, CH=C).
1H NMR (CDCl3, 300 MHz): d = 1.30 (d, J = 6.3 Hz, 6 H, 2 × CH3),
2.22 (quint, J = 7.5 Hz, 2 H, CH2), 3.17 (t, J = 7.8 Hz, 2 H, CH2),
4.39 (t, J = 7.2 Hz, 2 H, OCH2), 5.06 (quint, J = 6.3 Hz, 1 H, CH).
13C NMR (CDCl3, 150 MHz): d = 22.0 (CH3), 25.0, 32.5 (CH2),
68.9 (CH), 72.9 (C-5), 84.2 (BrC=C), 163.8 (O=CO), 171.6
(OC=C).
MS (EI, 70 eV): m/z (%) = 249 (M+ [81Br], 26), 247 (M+ [79Br], 26),
207 (84), 205 (88), 189 (90), 187 (88), 171 (7), 165 (12), 163 (14),
148 (29), 146 (29), 122 (8), 120 (8), 110 (17), 87 (18), 70 (33), 43
(100).
MS (EI, 70 eV): m/z (%) = 198 (M+, 5), 183 (1), 169 (20), 156 (100),
153 (61), 141 (10), 128 (6), 114 (17), 109 (14), 97 (8), 84 (35).
Ethyl (3-Butyldihydrofuran-2-ylidene)acetate (2e)5a
Substrate 1e (2.200 g, 11.8 mmol), i-Pr2NH (4.2 mL, 29.5 mmol),
n-BuLi (15% in n-hexane; 18.5 mL, 29.5 mmol), and 1-bromo-2-
chloroethane (1.2 mL, 14.2 mmol) in THF (50 mL), gave 2e after
chromatography (n-hexane–EtOAc, 100:1→1:1).
Yield: 1.723 (69%); yellowish oil.
Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York

484
E. Bellur, P. Langer
PAPER
HRMS (EI, 70 eV): m/z calcd for C9H13BrO3 [M+]: 248.0048;
found: 248.0048 2 ppm.
1H NMR (CDCl3, 300 MHz): d = 2.02 (s, 3 H, CH3), 2.11–2.22 (m,
1 H, CH2), 2.53–2.59 (m, 1 H, CH2), 3.71 (s, 3 H, OCH3), 4.55–4.60
(m, 2 H, OCH2), 5.14 (s, 1 H, CH=C).
13C NMR (CDCl3, 75 MHz): d = 28.2 (CH3), 42.2 (CH2), 50.4
(OCH3), 61.6 (CBr), 70.5 (C-5), 87.2 (CH=CO), 165.4 (O=CO),
172.6 (OC=CH).
MS (EI, 70 eV): m/z (%) = 236 (M+ [81Br], 12), 234 (M+ [79Br], 12),
205 (11), 203 (14), 155 (100), 139 (1), 123 (83), 95 (12), 81 (4), 70
(43).
Anal. calcd for C9H13BrO3 (249.104): C, 43.40; H, 5.26. Found: C,
43.28; H, 5.48.
Isopropyl Bromo[3-bromodihydrofuran-2(3H)-ylidene]acetate
[(E)-5a]
Yield: 0.219 g (12%); yellowish oil.
IR (neat): 2982 (s), 2937 (m), 2906 (m), 2883 (w), 1733 (s), 1702
(s), 1663 (m), 1615 (s), 1464 (m), 1440 (m), 1375 (s), 1315 (m),
1279 (s), 1208 (s), 1184 (s), 1159 (s), 1105 (s), 1061 (s), 1034 (s),
986 (m), 962 (w), 936 (m), 904 (m), 854 (w), 831 (w), 809 (w), 764
(w), 699 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.30 (d, J = 6.3 Hz, 6 H, 2 × CH3),
2.11–2.48 (m, 1 H, CH2), 2.52–2.60 (m, 1 H, CH2), 4.73–4.78 (m, 2
H, OCH2), 5.07 (quint, J = 6.3 Hz, 1 H, CH), 5.20 (d, J = 5.7 Hz, 1
H, CHBr).
Anal. calcd for C8H11BrO3 (235.077): C, 40.88; H, 4.72. Found: C,
41.47; H, 5.18.
2-Alkylidenetetrahydrofurans 3c and 5c
Ethyl [3-ethyldihydrofuran-2(3H)-ylidene]acetate (2c; 2.400 g, 13
mmol) and NBS (4.165 g, 23.4 mmol) in CCl4 (60 mL) gave (Z)-5c,
(E)-3c, and (E)-5c after chromatography (n-hexane–EtOAc,
100:1→1:1).
13C NMR (CDCl3, 150 MHz): d = 21.8 (CH3), 35.3 (CH2), 48.8
(CHBr), 69.2 (CH), 74.0 (C-5), 88.3 (BrC=C), 161.7 (O=CO),
166.9 (OC=C).
MS (EI, 70 eV): m/z (%) = 330 (M+ [2 × 81Br], 12), 328 (M+ [81Br,
79Br], 26), 326 (M+ [2 × 79Br], 13), 288 (31), 286 (62), 284 (32), 271
(16), 269 (33), 267 (17), 249 (10), 247 (9), 241 (3), 207 (100), 205
(98), 191 (17), 189 (40), 187 (23), 163 (13), 161 (28), 159 (15), 148
(12), 146 (11), 133 (13), 131 (12), 108 (4), 106 (3), 87 (17), 70 (16),
43 (70).
Ethyl Bromo[3-bromo-3-ethyldihydrofuran-2(3H)-ylidene]ace-
tate [(Z)-5c]
Yield: 2.681 g (60%); yellowish oil.
IR (neat): 2977 (m), 2938 (w), 2905 (w), 1706 (s), 1603 (s), 1460
(m), 1385 (w), 1367 (m), 1262 (s), 1209 (s), 1182 (s), 1114 (s), 1089
(s), 1066 (s), 1025 (m), 938 (m), 862 (w), 789 (w), 754 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.03 (t, J = 7.2 Hz, 3 H, CH3), 1.34
(t, J = 7.2 Hz, 3 H, OCH2CH3), 2.14 (sext, J = 7.2 Hz, 1 H, CH2),
2.42–2.53 (m, 1 H, CH2), 2.62–2.69 (m, 1 H, CH2), 2.71 (sext, J =
7.2 Hz, 1 H, CH2), 4.27 (dq, J = 7.2, 1.5 Hz, 2 H, OCH2CH3), 4.43–
4.48 (m, 2 H, OCH2).
HRMS (EI, 70 eV): m/z calcd for C9H12Br2O3 [M+]: 325.9153;
found: 325.9153
2-Alkylidenetetrahydrofurans 3b and 5b
13C NMR (CDCl3, 75 MHz): d = 10.0, 13.7 (CH3), 31.5, 43.8 (CH2),
61.4 (C-5), 65.4 (CBr), 68.8 (OCH2), 87.1 (BrC=C), 162.7 (O=CO),
166.8 (OC=C).
MS (EI, 70 eV): m/z (%) = 344 (M+ [2 × 81Br], 7), 342 (M+ [81Br,
79Br], 17), 340 (M+ [2 × 79Br], 8), 299 (4), 297 (10), 295 (4), 263
(87), 261 (86), 235 (22), 233 (23), 217 (100), 215 (97), 203 (8), 201
(8), 189 (6), 187 (4), 153 (7), 148 (12), 146 (13), 137 (5), 107 (12),
70 (20).
Methyl [3-methyldihydrofuran-2(3H)-ylidene]acetate (2b; 1.650 g,
10.6 mmol) and NBS (2.830 g, 15.9 mmol) in CCl4 (50 mL) gave
(Z)-5b and (E)-3b after chromatography (n-hexane–
EtOAc, 100:1→1:1).
Methyl Bromo[3-bromo-3-methyldihydrofuran-2(3H)-
ylidene]acetate [(Z)-5b]
Yield: 1.462 g (44%); yellowish oil.
Anal. calcd for C10H14Br2O3 (342.027): C, 35.12; H, 4.13. Found: C,
35.89; H, 4.11.
IR (neat): 2996 (w), 2953 (m), 2907 (w), 1709 (s), 1656 (w), 1600
(s), 1437 (s), 1377 (m), 1330 (w), 1277 (s), 1214 (s), 1186 (s), 1109
(s), 1068 (s), 1010 (s), 974 (w), 920 (m), 838 (m), 768 (m), 755 (m),
710 (w), 495 (w), 405 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.16 (s, 3 H, CH3), 2.45–2.56 (m,
1 H, CH2), 2.76–2.82 (m, 1 H, CH2), 3.83 (s, 3 H, OCH3), 4.45–4.50
(m, 2 H, OCH2).
13C NMR (CDCl3, 75 MHz): d = 27.6 (CH3), 47.8 (CH2), 52.5
(OCH3), 58.7 (CBr), 69.0 (C-5), 86.7 (BrC=C), 163.2 (O=CO)
168.8 (OC=C).
MS (EI, 70 eV): m/z (%) = 316 (M+ [2 × 81Br], 9), 314 (M+ [81Br,
79Br], 19), 312 (M+ [2 × 79Br], 10), 283 (9), 236 (15), 235 (86), 234
(17), 233 (90), 204 (26), 203 (100), 202 (27), 201 (92), 176 (3), 175
(8), 174 (3), 148 (15), 146 (16), 70 (13).
Ethyl [3-Bromo-3-ethyldihydrofuran-2(3H)-ylidene]acetate
[(E)-3c]
Yield: 1.072 g (31%; brownish oil.
IR (neat): 2978 (s), 2940 (m), 2907 (m), 1715 (s), 1652 (s), 1461
(m), 1444 (m), 1400 (m), 1386 (m), 1369 (m), 1326 (m), 1300 (m),
1271 (m), 1209 (s), 1181 (s), 1155 (s), 1108 (m), 1096 (m), 1079
(m), 1046 (s), 976 (w), 955 (w), 860 (w), 807 (m) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.16 (t, J = 7.2 Hz, 3 H, CH3), 1.28
(t, J = 7.2 Hz, 3 H, OCH2CH3), 1.88 (sext, J = 7.2 Hz, 1 H, CH2),
2.04–2.15 (m, 1 H, CH2), 2.30 (sext, J = 7.2 Hz, 1 H, CH2), 2.43
(ddd, J = 13.8, 4.8, 1.2 Hz, 1 H, CH2), 4.17 (q, J = 7.2 Hz, 2 H,
OCH2CH3), 4.49–4.62 (m, 2 H, OCH2), 5.09 (s, 1 H, CH=C).
HRMS (EI, 70 eV): m/z calcd for C8H10Br2O3: 311.8997; found:
311.8997.
13C NMR (CDCl3, 75 MHz): d = 10.4, 14.2 (CH3), 33.7, 39.3 (CH2),
59.5 (C-5), 68.7 (CBr), 71.0 (OCH2), 88.3 (CH=CO), 165.65
(O=CO), 172.23 (OC=CH).
Methyl[3-Bromo-3-methyldihydrofuran-2(3H)-ylidene]acetate
[(E)-3b]
Yield: 1.180 g (47%); brownish oil.
MS (EI, 70 eV): m/z (%) = 264 (M+ [81Br], 2), 262 (M+ [79Br], 2),
236 (1), 234 (1), 219 (6), 217 (7), 203 (1), 183 (100), 155 (10), 137
(20), 123 (11), 110 (5), 108 (5), 70 (24).
IR (neat): 2989 (w), 2951 (m), 2925 (w), 2907 (w), 1719 (s), 1655
(s), 1476 (w), 1437 (s), 1387 (m), 1333 (m), 1302 (s), 1278 (s), 1246
(s), 1211 (s), 1186 (s), 1161 (s), 1101 (s), 1088 (s), 1035 (s), 1014
(s), 973 (w), 930 (w), 903 (w), 808 (s), 698 (w), 495 (w) cm–1.
Anal. calcd for C10H15BrO3 (263.131): C, 45.65; H, 5.75. Found: C,
45.97; H, 5.81.
Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Furans
485
Ethyl Bromo[3-bromo-3-ethyldihydrofuran-2(3H)-ylidene]ace-
tate [(E)-5c]
Yield: 0.265 g (6%); brownish oil.
13C NMR (CDCl3, 75 MHz): d = 13.8 (CH3), 22.5, 28.2, 39.9, 40.4
(CH2), 59.7 (C-5), 67.9 (CBr), 71.2 (OCH2), 88.1 (CH=CO), 16.2
(O=CO), 172.5 (OC=CH).
IR (neat): 2977 (m), 2938 (w), 2904 (w), 1707 (s), 1594 (s), 1461
(m), 1370 (m), 1321 (w), 1275 (s), 1255 (s), 1233 (m), 1201 (s),
1176 (s), 1112 (s), 1089 (m), 1047 (s), 1006 (m), 972 (w), 946 (w),
846 (w), 761 (w), 710 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.05 (t, J = 7.2 Hz, 3 H, CH3), 1.33
(t, J = 7.2 Hz, 3 H, OCH2CH3), 2.44–2.54 (m, 3 H, 2 × CH2), 2.74
(sext, J = 7.2 Hz, 1 H, CH2), 4.25 (q, J = 7.2 Hz, 2 H, OCH2CH3),
4.37–4.45 (m, 1 H, OCH2), 4.53 (dt, J = 9.0, 1.5 Hz, 1 H, OCH2).
MS (EI, 70 eV): m/z (%) = 292 (M+ [81Br], 4), 290 (M+ [79Br], 4),
278 (5), 276 (5), 247 (24), 245 (23), 236 (12), 234 (12), 222 (15),
220 (16), 211 (22), 197 (35), 183 (10), 181 (9), 179 (9), 169 (83),
167 (17), 165 (47), 155 (100), 137 (31), 127 (11), 123 (71), 121 (6),
119 (11), 112 (28), 110 (12), 108 (17), 98 (24), 81 (22), 70 (64).
2-Alkylidenetetrahydrofurans 3f and 6a
Ethyl 2-[dihydrofuran-2(3H)-ylidene]propionate (2f; 0.100 g, 0.59
mmol) and NBS (0.115 g, 0.65 mmol) in CCl4 (5 mL) gave 3f and
6a after chromatography (n-hexane–EtOAc, 100:1→5:1).
13C NMR (CDCl3, 75 MHz): d = 10.1, 14.0 (CH3), 34.1, 41.7 (CH2),
61.7 (C-5), 69.1 (CBr), 70.2 (OCH2), 88.0 (BrC=C), 163.0 (O=CO),
166.3 (OC=C).
Ethyl 2-[3-Bromodihydrofuran-2(3H)-ylidene]propionate (3f)
MS (EI, 70 eV): m/z (%) = 344 (M+ [2 × 81Br], 7), 342 (M+ [81Br,
79Br], 17), 340 (M+ [2 × 79Br], 8), 299 (9), 297 (19), 295 (9), 263
(85), 261 (87), 235 (25), 233 (26), 217 (100), 215 (99), 203 (9), 201
(9), 189 (7), 187 (5), 153 (17), 148 (14), 146 (14), 137 (5), 108 (12),
70 (18).
Yield: 0.082 g (56%); slightly yellowish oil.
IR (neat): 2984 (m), 2930 (w), 2904 (w), 1699 (s), 1644 (s), 1469
(w), 1441 (m), 1390 (w), 1369 (m), 1288 (s), 1212 (m), 1185 (m),
1170 (m), 1107 (s), 1082 (s), 1024 (m), 972 (w), 933 (w), 880 (w),
767 (w), 704 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.30 (t, J = 7.2 Hz, 3 H, CH3), 1.85
(s, 3 H, CH3), 2.43–2.49 (m, 2 H, CH2), 4.22 (dq, J = 7.2, 2.7 Hz, 2
H, OCH2CH3), 4.39–4.54 (m, 2 H, OCH2), 5.81 (m, 1 H, CHBr).
13C NMR (CDCl3, 75 MHz): d = 11.6, 14.3 (CH3), 36.7 (CH2), 45.1
(CHBr), 60.1 (OCH2), 69.1 (C-5), 100.4 (C=CO), 167.1 (O=CO),
167.6 (OC=C).
MS (EI, 70 eV): m/z (%) = 250 (M+ [81Br], 29), 248 (M+ [79Br], 34),
205 (14), 203 (16), 169 (83), 141 (100), 123 (54), 99 (3), 97 (3), 95
(32), 83 (49), 68 (33).
Anal. calcd for C10H14Br2O3 (342.027): C, 35.12; H, 4.13. Found: C,
35.22; H, 4.33.
Ethyl [3-Bromo-3-propyldihydrofuran-2(3H)-ylidene]acetate
(3d)
Ethyl [3-propyldihydrofuran-2(3H)-ylidene]acetate (2d; 0.099 g,
0.50 mmol) and NBS (0.116 g, 0.65 mmol) in CCl4 (10 mL) gave
3d after chromatography (n-hexane–EtOAc, 50:1→1:1).
Yield: 0.121 g (87%); yellowish oil.
IR (neat): 2964 (m), 2935 (w), 2875 (w), 1715 (s), 1652 (s), 1463
(w), 1442 (w), 1401 (w), 1374 (w), 1332 (w), 1301 (w), 1272 (w),
1246 (w), 1208 (s), 1182 (s), 1157 (m), 1115 (m), 1100 (w), 1077
(w), 1050 (s), 1029 (m) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.03 (t, J = 7.2 Hz, 3 H, CH3),1.28
(t, J = 6.9 Hz, 3 H, OCH2CH3), 1.35–1.50 (m, 1 H, CH2), 1.71–1.85
(m, 2 H, CH2), 2.05–2.23 (m, 2 H, CH2), 2.43 (dd, J = 13.8, 4.5 Hz,
1 H, CH2), 4.17 (q, J = 7.2 Hz, 2 H, OCH2CH3), 4.51–4.59 (m, 2 H,
OCH2), 5.10 (s, 1 H, CH=C).
HRMS (ESI): m/z calcd for C9H13BrO3 [M+]: 250.00276 (81Br),
248.00481 (79Br); found: 250.00210 (81Br), 248.00485 (79Br).
Anal. calcd for C9H13BrO3 (249.104): C, 43.40; H, 5.26. Found: C,
42.74; H, 4.87.
Ethyl 2-[3,3-Dibromodihydrofuran-2(3H)-ylidene]propionate
(6a)
Yield: 0.023 g (12%); slightly yellowish oil.
IR (neat): 2981 (w), 2931 (w), 2902 (w), 1713 (s), 1636 (m), 1443
(w), 1371 (w), 1318 (w), 1290 (m), 1279 (m), 1204 (m), 1174 (m),
1141 (s), 1103 (s), 1030 (w), 1001 (w), 738 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.31 (t, J = 7.2 Hz, 3 H, CH3), 2.21
(s, 3 H, CH3), 3.27 (t, J = 6.3 Hz, 2 H, CH2), 4.22 (q, J = 7.2 Hz, 2
H, OCH2CH3), 4.32 (t, J = 6.3 Hz, 2 H, OCH2).
13C NMR (CDCl3, 75 MHz): d = 14.2, 14.6 (CH3), 50.4 (CBr2), 51.7
(CH2), 60.5 (OCH2), 68.7 (C-5), 103.2 (C=CO), 162.1 (OC=C),
167.2 (O=CO).
13C NMR (CDCl3, 75 MHz): d = 13.9, 14.3 (CH3), 19.5, 39.9, 42.8
(CH2), 59.7 (CBr), 71.1 (OCH2), 88.4 (CH=CO), 165.8 (O=CO),
172.4 (OC=CH).
MS (EI, 70 eV): m/z (%) = 278 (M+ [81Br], 4), 276 (M+ [79Br], 3),
236 (40), 234 (42), 233 (24), 231 (24), 197 (92), 183 (5), 169 (34),
150 (78), 123 (100), 114 (18), 108 (14), 95 (26), 70 (74).
HRMS (EI, 70 eV): m/z calcd for C11H17BrO3 [M+]: 276.0361;
found: 276.0361 2 ppm.
Ethyl [3-Bromo-3-butyldihydrofuran-2(3H)-ylidene]acetate
(3e)
Ethyl [3-butyldihydrofuran-2(3H)-ylidene]acetate (2e; 0.127 g, 0.6
mmol) and NBS (0.139 g, 0.78 mmol) in CCl4 (15 mL) gave 3e after
chromatography (n-hexane–EtOAc, 50:1→1:1).
MS (EI, 70 eV): m/z (%) = 328 (M+ [81Br, 79Br], 11), 326 (M+
[2 × 79Br], 2), 285 (4), 283 (16), 281 (4), 249 (54), 247 (54), 221
(59), 219 (56), 205 (3), 204 (10), 203 (12), 202 (10), 201 (6), 177
(2), 175 (14), 173 (5), 169 (21), 167 (7), 165 (6), 141 (28), 139 (77),
129 (16), 123 (16), 108 (3), 95 (18), 83 (100), 66 (54).
Yield: 0.160 g (91%); yellowish oil.
HRMS (ESI): m/z calcd for C9H12Br2O3 [M+]: 329.91127 (2 × 81Br),
327.91327 (81Br, 79Br), 325.91532 (2 × 79Br); found: 329.90904
(2 × 81Br), 327.91240 (81Br, 79Br), 325.91549 (2 × 79Br).
IR (neat): 2958 (s), 2932 (s), 2869 (m), 1717 (s), 1652 (s), 1463 (m),
1437 (m), 1388 (m), 1329 (m), 1298 (m), 1272 (m), 1206 (s), 1181
(s), 1156 (s), 1116 (m), 1102 (m), 1951 (s), 1021 (m), 964 (w), 807
(m) cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.96 (t, J = 6.9 Hz, 3 H, CH3), 1.28
(t, J = 7.2 Hz, 3 H, OCH2CH3), 1.32–1.46 (m, 3 H, 2 × CH2), 1.60–
1.74 (m, 1 H, CH2), 1.77–1.87 (m, 1 H, CH2), 2.05–2.16 (m, 1 H,
CH2), 2.20–2.30 (m, 1 H, CH2), 2.44 (dd, J = 14.1, 4.8 Hz, 1 H,
CH2), 4.17 (q, J = 7.2 Hz, 2 H, OCH2CH3), 4.49–4.61 (m, 2 H,
OCH2), 5.10 (s, 1 H, CH=C).
Ethyl 2-[3-Bromodihydrofuran-2(3H)-ylidene]butyrate (3g)
Ethyl 2-[dihydrofuran-2(3H)-ylidene]butyrate (2g; 1.000 g, 5.43
mmol) and NBS (1.063 g, 5.97 mmol) in CCl4 (30 mL), gave 3g af-
ter chromatography (n-hexane–EtOAc, 100:1→1:1).
Yield: 1.140 g (80%); yellow oil.
Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York

486
E. Bellur, P. Langer
PAPER
IR (neat): 2975 (s), 2936 (m), 2905 (w), 2877 (w), 1696 (s), 1639
(s), 1448 (m), 1371 (m), 1307 (s), 1253 (s), 1212 (m), 1185 (s), 1105
(s), 1055 (m), 1032 (s), 990 (w), 951 (w), 877 (w), 780 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.99 (t, J = 7.4 Hz, 3 H, CH3),
1.32 (t, J = 7.2 Hz, 3 H, CH3), 2.29–2.38 (m, 2 H, CH2), 2.42–2.49
(m, 2 H, CH2), 4.18–4.27 (m, 2 H, OCH2CH3), 4.41–4.50 (m, 2 H,
OCH2), 5.81 (m, 1 H, CHBr).
sualization of the spots on TLC plates was not possible by UV; they
were visualized with a dye (MeOH–AcOH–anisaldehyde, 85:14:1).
Isopropyl (Furan-2-yl)acetate (7a)7b
Substrate 3a (0.080 g, 0.32 mmol) and DBU (0.10 mL, 0.64 mmol)
in THF (3 mL) gave 7a after chromatography (n-hexane–
EtOAc, 100:1→10:1) as a colorless oil (0.036 g, 67%).
13C NMR (CDCl3, 75 MHz): d = 12.7, 13.9 (CH3), 19.2, 36.3 (CH2),
45.1 (CHBr), 59.6 (OCH2), 68.8 (C-5), 106.3 (C=CO), 166.8
(O=CO), 166.9 (OC=C).
MS (EI, 70 eV): m/z (%) = 264 (M+ [81Br], 21), 262 (M+ [79Br], 23),
249 (3), 247 (3), 219 (14), 217 (15), 203 (5), 201 (4), 191 (5), 189
(5), 183 (100), 155 (57), 137 (50), 109 (21), 81 (15), 70 (50).
Methyl (3-Methylfuran-2-yl)acetate (7b)7b
Substrate 3b (0.100 g, 0.425 mmol) and DBU (0.13 mL, 0.85 mmol)
in THF (3 mL) gave 7b after chromatography (n-hexane–
EtOAc, 100:1→50:1) as a colorless oil (0.049 g, 75%).
Ethyl (3-Ethylfuran-2-yl)acetate (7c)7b
Substrate 3c (0.080 g, 0.304 mmol) and DBU (0.09 mL, 0.61 mmol)
in THF (3 mL) gave 7c after chromatography (n-hexane–
EtOAc, 100:1→50:1) as a colorless oil (0.035 g, 64%).
Anal. calcd for C10H15BrO3 (263.131): C, 45.65; H, 5.75. Found: C,
45.05; H, 5.55.
2-Alkylidenetetrahydrofurans 3h and 6b
Ethyl (3-Propylfuran-2-yl)acetate (7d)7b
Substrate 3d (0.100 g, 0.36 mmol) and DBU (0.11 mL, 0.72 mmol)
in THF (4 mL) gave 7d after chromatography (n-hexane–
EtOAc, 100:1→50:1) as a slightly yellowish oil (0.039 g, 55%).
Tetrahydro[2,3¢]bifuranyliden-2¢-one (2h; 0.200 g, 1.30 mmol) and
NBS (0.277 g, 1.56 mmol) in CCl4 (10 mL) gave 3h and 6b after
chromatography (n-hexane–EtOAc, 20:1→1:1).
3-Bromotetrahydro[2,3¢]bifuranyliden-2¢-one (3h)
Ethyl (3-Butylfuran-2-yl)acetate (7e)7b
Substrate 3e (0.150 g, 0.52 mmol) and DBU (0.15 mL, 1.0 mmol)
in THF (5 mL), gave 7e after chromatography (n-hexane–
EtOAc, 100:1→50:1) as a slightly yellowish oil (0.058 g, 53%).
Yield: 0.229 g (76%); slightly yellowish solid.
IR (KBr): 2910 (w), 1737 (s), 1683 (s), 1366 (m), 1254 (s), 1222
(m), 1184 (m), 1166 (m), 1080 (m), 1051 (s), 1029 (s), 993 (w), 931
(w), 670 (w) cm-1.
Ethyl (2-Furan-2-yl)propionate (7f)
1H NMR (CDCl3, 300 MHz): d = 2.46–2.52 (m, 2 H, CH2), 2.75–
3.02 (m, 2 H, CH2), 4.31–4.39 (m, 2 H, OCH2), 4.47–4.58 (m, 2 H,
OCH2), 5.82–5.84 (m, 1 H, CHBr).
13C NMR (CDCl3, 150 MHz): d = 25.0, 36.1 (CH2), 41.8 (CHBr),
65.3 (OCH2), 70.4 (C-5), 95.7 (C=CO), 166.3 (O=CO), 171.1
(OC=C).
MS (EI, 70 eV): m/z (%) = 234 (M+ [81Br], 92), 232 (M+ [79Br], 86),
153 (100), 125 (14), 123 (20), 107 (32), 97 (23), 95 (39), 85 (14), 81
(23), 79 (34), 70 (35), 68 (40).
Substrate 3f (0.100 g, 0.40 mmol) and DBU (0.12 mL, 0.80 mmol)
in THF (5 mL) gave 7f after chromatography (n-hexane–
EtOAc, 100:1→10:1).
Yield: 0.035 g (52%); colorless oil.
IR (neat): 2986 (m), 2937 (w), 1738 (s), 1648 (w), 1505 (w), 1457
(m), 1376 (w), 1322 (m), 1255 (m), 1203 (s), 1169 (s), 1096 (m),
1070 (m), 1017 (m), 927 (w), 793 (w), 738 (s) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 3 H, CH3),
1.52 (d, J = 7.3 Hz, 3 H, CH3), 3.81 (q, J = 7.3 Hz, 1 H, CH), 4.13
(q, J = 7.2 Hz, 2 H, OCH2), 6.17 (dt, J = 3.2, 0.8 Hz, 1 H, CH), 6.32
(dd, J = 3.2, 1.8 Hz, 1 H, CH), 7.34 (dd, J = 1.8, 0.8 Hz, 1 H, CH).
HRMS (EI, 70 eV): m/z calcd for C8H9BrO3: 231.9735; found:
231.9735 2 ppm.
13C NMR (CDCl3, 75 MHz): d = 14.1, 15.8 (CH3), 39.5 (CH), 61.0
(OCH2), 105.9, 110.2. 141.7 (CH), 153.4 (C), 172.6 (O=CO).
3,3-Dibromotetrahydro-[2,3¢]bifuranyliden-2¢-one (6b)
Yield: 0.089 g (22%); slightly yellowish solid.
MS (EI, 70 eV): m/z (%) = 168 (M+, 13), 121 (2), 105 (2), 95 (100),
81 (2), 68 (13).
IR (KBr): 2908 (w), 1738 (s), 1663 (s), 1224 (w), 1197 (w), 1149
(s), 1134 (m), 1070 (w), 1029 (m), 991 (w), 728 (w) cm-1.
1H NMR (CDCl3, 300 MHz): d = 3.26 (t, J = 6.5 Hz, 2 H, CH2), 3.33
(t, J = 7.5 Hz, 2 H, CH2), 4.40 (t, J = 7.5 Hz, 2 H, OCH2), 4.49 (t,
J = 6.5 Hz, 2 H, OCH2).
HRMS (ESI): m/z calcd for C9H12O3 [M + 1]+: 169.08647; found:
169.08574.
Ethyl (2-Furan-2-yl)butyrate (7g)
13C NMR (CDCl3, 150 MHz): d = 26.2, 50.3 (CH2), 51.0 (CBr2),
65.7 (OCH2), 70.5 (C-5), 98.2 (C=CO), 163.0 (O=CO), 170.3
(OC=C).
MS (EI, 70 eV): m/z (%) = 314 (M+ [2 × 81Br], 2), 312 (M+ [81Br,
79Br], 6), 310 (M+ [2 × 79Br], 3), 234 (10), 233 (29), 232 (14), 231
(33), 189 (96), 188 (56), 187 (100), 186 (29), 185 (8), 184 (8), 180
(6), 178 (7), 177 (12), 175 (20), 173 (6), 153 (14), 150 (13), 148 (9),
123 (7), 121 (5), 112 (5), 107 (12), 95 (14), 81 (10), 79 (15), 77 (10),
68 (13), 66 (16).
Substrate 3g (0.090 g, 0.34 mmol) and DBU (0.10 mL, 0.48 mmol)
in THF (5 mL) gave 7g after chromatography (n-hexane–
EtOAc, 100:1→30:1).
Yield: 0.041 g (66%); colorless oil.
IR (neat): 2972 (w), 2934 (w), 1738 (s), 1650 (w), 1503 (w), 1459
(m), 1392 (w), 1376 (w), 1337 (w), 1296 (w), 1257 (m), 1231 (w),
1197 (m), 1160 (s), 1092 (w), 1018 (m), 737 (m) cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.94 (t, J = 7.2 Hz, 3 H, CH3), 1.25
(t, J = 7.2 Hz, 3 H, CH3), 1.87–2.08 (m, 2 H, CH2), 3.60 (t, J = 7.8
Hz, 1 H, CH), 4.17 (dq, J = 7.2, 1.0 Hz, 2 H, OCH2), 6.19 (dt,
J = 3.2, 0.8 Hz, 1 H, CH), 6.32 (dd, J = 3.0, 1.8 Hz, 1 H, CH), 7.34
(dd, J = 1.8, 0.8 Hz, 1 H, CH).
HRMS (EI, 70 eV): m/z calcd for C8H8BrO3: 309.8840; found:
309.8840 2 ppm.
Synthesis of Furans; General Procedure
To a THF solution (10 mL/mmol) of starting material 3, 5, or 6 (1
equiv) was added DBU (2 equiv) and the solution was stirred for 12
h at 20 °C. The solvent was removed in vacuo and the residue was
purified by chromatography (n-hexane–EtOAc) to give furan 7. Vi-
13C NMR (CDCl3, 75 MHz): d = 11.9, 14.2 (CH3), 24.4 (CH2), 47.1
(CH), 60.9 (OCH2), 106.6, 110.3, 141.7 (CH), 152.4 (C), 172.1
(O=CO).
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PAPER
Synthesis of Functionalized Furans
487
MS (EI, 70 eV): m/z (%) = 182 (M+, 100), 168 (7), 153 (58), 139
H, OCH2), 6.44 (d, J = 2.1 Hz, 1 H, CH), 7.35 (d, J = 2.1 Hz, 1 H,
(53), 125 (12), 108 (42), 91 (8), 80 (19).
CH).
Anal. calcd for C10H14O3 (182.219): C, 65.92; H, 7.74. Found: C,
66.03; H, 7.12.
13C NMR (CDCl3, 75 MHz): d = 28.0 (CH2), 38.1 (CH), 66.9
(OCH2), 99.4 (CBr), 114.2 (CH), 142.7 (OCH), 146.5 (C), 173.8
(O=CO).
MS (EI, 70 eV): m/z (%) = 232 (M+ [81Br], 40), 230 (M+ [79Br], 40),
188 (69), 186 (67), 174 (11), 172 (12), 161 (14), 159 (22), 157 (6),
145 (3), 143 (2), 107 (47), 79 (100), 77 (86), 66 (25).
HRMS (FT-ICR): m/z calcd for C8H7BrO3 [M + 1]+: 232.96363
(81Br), 230.96568 (79Br); found: 232.96319 (81Br), 230.96515
(79Br).
4¢,5¢-Dihydro-3¢H-[2,3¢]bifuranyl-2¢-one (7h)7b
Substrate 3h (0.100 g, 0.43 mmol) and DBU (0.13 mL, 0.86 mmol)
in THF (5 mL) gave 7h after chromatography (n-hexane–
EtOAc, 50:1→5:1) as a slightly yellowish oil (0.041 g, 63%).
Ethyl Bromo(3-ethylfuran-2-yl)acetate (7i)
Substrate 5c (0.080 g, 0.234 mmol) and DBU (0.07 mL, 0.468
mmol) in THF (3 mL) gave 7i after chromatography (n-hexane–
EtOAc, 100:1→5:1).
Ethyl (3-Ethylfuran-2-yl)phenylacetate (8)
To a solution of (Z)-5c (0.300 g, 0.88 mmol) in 1,4-dioxane (5 mL),
K3PO4 (1.117 g, 5.26 mmol), phenylboronic acid (0.654 g, 5.3
mmol), and Pd(PPh3)4 (0.051 g, 0.044 mmol) were added at 20 °C
under an argon atmosphere. The reaction mixture was stirred under
reflux for 6 h. The reaction mixture was allowed to cool to 20 °C
and Et2O (10 mL) was added. The precipitate was filtered, washed
with Et2O, and the filtrate was concentrated in vacuo. The residue
was purified by chromatography (n-hexane–EtOAc, 100:1→20:1)
to give 8.
Yield: 0.037 g (61%); yellowish oil.
IR (neat): 2976 (m), 2936 (m), 2879 (w), 1743 (s), 1696 (m), 1656
(w), 1631 (w), 1506 (w), 1459 (m), 1419 (m), 1376 (m), 1261 (s),
1150 (s), 1072 (s), 1019 (s), 950 (w), 889 (w), 866 (w), 759 (w)
cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.18 (t, J = 7.5 Hz, 3 H, CH3), 1.25
(t, J = 7.2 Hz, 3 H, CH3), 2.48 (q, J = 7.5 Hz, 2 H, CH2), 4.26 (q,
J = 7.2 Hz, 2 H, OCH2), 5.18 (s, 1 H, CHBr), 6.28 (d, J = 1.8 Hz, 1
H, CH), 7.29 (d, J = 1.8 Hz, 1 H, CH).
Yield: 0.135 g (60%); colorless oil.
13C NMR (CDCl3, 75 MHz): d = 14.1, 14.9 (CH3), 17.7 (CH2), 62.4
(CHBr), 65.1 (OCH2), 111.6 (CH), 125.6 (C), 142.1 (CH), 145.2
(C), 171.9 (O=CO).
IR (neat): 2969 (m), 2932 (w), 1742 (s), 1500 (w), 1457 (m), 1369
(w), 1302 (w), 1281 (w), 1261 (m), 1230 (m), 1190 (m), 1153 (s),
1115 (w), 1093 (m), 1071 (w), 1028 (m), 730 (m), 699 (m) cm–1.
MS (EI, 70 eV): m/z (%) = 246 ([M – Me]+, 1), 198 (10), 180 (1),
167 (1), 141 (1), 139 (1), 137 (1), 125 (100), 111 (4), 110 (10), 109
(13), 108 (10), 106 (2), 97 (2), 95 (4), 81 (5), 68 (9).
HRMS (ESI): m/z calcd for C10H13BrO3 [M – Br]+: 181.08647;
found: 181.08578.
1H NMR (CDCl3, 300 MHz): d = 1.03 (t, J = 7.5 Hz, 3 H, CH3), 1.17
(t, J = 7.2 Hz, 3 H, OCH2CH3), 2.31 (q, J = 7.5 Hz, 2 H, CH2), 4.13
(q, J = 7.2 Hz, 2 H, OCH2CH3), 4.96 (s, 1 H, CHPh), 6.19 (d, J = 1.8
Hz, 1 H, CH), 7.18–7.29 (m, 6 H, Ph, CH).
13C NMR (CDCl3, 75 MHz): d = 14.1, 14.8 (CH3), 18.0 (CH2), 49.3
(CHPh), 61.4 (OCH2), 111.3 (CH), 123.3 (Ph-C), 127.3, 128.4,
128.6 (Ph-CH), 136.6 (Ph-C), 141.5 (CH), 145.1 (C), 170.6
(O=CO).
Ethyl 2-(3-Bromofuran-2-yl)propionate (7j)
Substrate 6a (0.300 g, 0.915 mmol) and DBU (0.27 mL, 1.83 mmol)
in THF (10 mL) gave 7j after chromatography (n-hexane–
EtOAc, 100:1→30:1).
MS (EI, 70 eV): m/z (%) = 258 (M+, 8), 185 (100), 170 (4), 155 (2),
95 (1).
Yield: 0.171 g (76%); slightly yellowish oil.
HRMS (EI, 70 eV): m/z calcd for C16H18O3 [M+]: 258.1256; found:
IR (neat): 2987 (m), 2939 (w), 1739 (s), 1700 (w), 1650 (w), 1506
(w), 1455 (m), 1378 (w), 1318 (m), 1191 (s), 1145 (m), 1098 (m),
1070 (m), 1022 (m), 973 (w), 739 (m) cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.23 (t, J = 7.2 Hz, 3 H, CH3),
1.51 (d, J = 7.2 Hz, 3 H, CH3), 3.94 (q, J = 7.2 Hz, 1 H, CH), 4.17(q,
J = 7.2 Hz, 2 H, OCH2), 6.39 (d, J = 1.8 Hz, 1 H, CH), 7.32 (d,
J = 1.8 Hz, 1 H, CH).
258.1256 2 ppm.
Acknowledgment
We thank Dr. Ilia Freifeld for experimental contributions. Financial
support from the DAAD (scholarship for E.B.) and from the Deut-
sche Forschungsgemeinschaft is gratefully acknowledged.
13C NMR (CDCl3, 75 MHz): d = 14.0, 14.8 (CH3), 37.6 (CH), 61.1
(OCH2), 97.1 (C), 113.7, 141.9 (CH), 149.8 (C), 171.3 (O=CO).
References
MS (EI, 70 eV): m/z (%) = 248 (M+ [81Br], 12), 246 (M+ [79Br], 12),
175 (97), 173 (100), 161 (1), 157 (8), 143 (29), 121 (6), 119 (18),
116 (9), 110 (21), 101 (5), 94 (21), 83 (14), 66 (23).
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IR (neat): 2957 (w), 2922 (m), 1771 (s), 1628 (w), 1507 (w), 1454
(w), 1376 (m), 1218 (w), 1158 (m), 1143 (m), 1102 (w), 1048 (w),
1022 (m), 983 (m), 949 (w), 878 (w), 742 (w) cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.59–2.65 (m, 2 H, CH2), 4.06 (t,
J = 9.8 Hz, 1 H, CH), 4.33–4.42 (m, 1 H, OCH2), 4.52–4.59 (m, 1
Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York

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E. Bellur, P. Langer
PAPER
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Synthesis 2006, No. 3, 480–488 © Thieme Stuttgart · New York