Synthesis of functionalized 2-alkylidene-tetrahydrofurans based on a [3+2] cyclization/bromination/palladium(0) cross-coupling strategy

Article abstract of DOI:10.1002/ejoc.200500422

The bromination of 2-alkylidene-tetrahydrofurans and 2-alkylidene- pyrrolidines - readily available through one-pot [3+2] cyclization reactions - afforded 2-alkylidene-1′-bromotetrahydrofurans, 2-alkylidene-3- bromotetrahydrofurans and 2-alkylidene-1′,3-dibromotetrahydrofurans and their pyrrolidine counterparts. 2-Alkylidene-1′-bromotetrahydrofurans were functionalized by performing Suzuki and Heck reactions. 2-Alkylidene-1′, 3-dibromotetrahydrofurans were successfully employed in novel double-Suzuki reactions. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500422

FULL PAPER
Synthesis of Functionalized 2-Alkylidene-tetrahydrofurans Based on a [3+2]
Cyclization/Bromination/Palladium(0) Cross-Coupling Strategy
Esen Bellur[a,b] and Peter Langer*[a,c]
Keywords: Bromination / Cross-coupling / Palladium / Pyrrolidines / Tetrahydrofurans
The bromination of 2-alkylidene-tetrahydrofurans and 2-alk-
ylidene-pyrrolidines − readily available through one-pot
[3+2] cyclization reactions − afforded 2-alkylidene-1Ј-bromo-
tetrahydrofurans, 2-alkylidene-3-bromotetrahydrofurans and
were functionalized by performing Suzuki and Heck reac-
tions. 2-Alkylidene-1Ј,3-dibromotetrahydrofurans were suc-
cessfully employed in novel double-Suzuki reactions.
2-alkylidene-1Ј,3-dibromotetrahydrofurans and their pyrroli- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
dine counterparts. 2-Alkylidene-1Ј-bromotetrahydrofurans
Germany, 2005)
the best of our knowledge, the first double-Suzuki reactions
of 1,3-dibromoprop-1-enes. The products prepared are of
considerable pharmacological relevance and also represent
useful synthetic building blocks that are not readily avail-
able by other methods.
Introduction
2-Alkylidene-tetrahydrofurans[1,2] and 2-alkylidene-pyr-
rolidines[3,4] are important building blocks in the synthesis
of natural products. A number of synthetic transformations
of 2-alkylidene-tetrahydrofurans have been reported, in-
cluding, for example, cycloaddition,[1a–1d] nucleophilic addi-
tion,[1e,1f] cyclopropanation[1g] and oxidative carbonylation
reactions.[1h–1j] The hydrogenation[1k,2h,2i] of 2-alkylidene-
tetrahydrofurans to give tetrahydrofurans has been applied
to the synthesis of natural products such as methyl nonact-
ate.[2] The spiroketal chalcogran has been prepared from a
bicyclic 2-alkylidene-tetrahydrofuran.[5] We have a particu-
lar interest in the development of cyclization reactions of
free and masked dianions, and have reported, along with
others, a number of one-pot syntheses of 2-alkylidene-tetra-
hydrofurans by [3+2] cyclization of 1,3-dicarbonyl dianions
and 1,3-bis-silyl enol ethers.[6] In addition, the functionali-
zation of 2-alkylidene-tetrahydrofurans by lithiation/alky-
lation[7a,7b] and by BBr3-mediated ring-opening reac-
tions[7c,7d] have been reported. Recently, we studied the
functionalization of 2-alkylidene-tetrahydrofurans by bro-
mination of the exocyclic double bond and subsequent Su-
zuki cross-coupling reactions.[8] Herein, we wish to report
full details of these studies; with regard to our preliminary
communication, we have significantly extended the prepara-
tive scope. We also report double-Suzuki reactions of 2-alk-
ylidene-1Ј,3-dibromotetrahydrofurans which represent, to
Results and Discussion
Our starting point was the development of a method for
the bromination of the exocyclic double bond of 2-alkylid-
ene-tetrahydrofurans and 2-alkylidene-pyrrolidines. The re-
quired starting materials, 2-alkylidene-tetrahydrofurans 2a–
h, were prepared in accord with our recently reported cycli-
zation of 1-bromo-2-chloroethane with the dianions of 1,3-
dicarbonyl compounds 1a–h (Scheme 1, Table 1).[9] 5-Vinyl-
2-alkylidene-tetrahydrofuran 2i is available by cyclization of
dilithiated ethyl acetoacetate (1b) with 1,4-dibromo-2-but-
ene.[9] 2-Alkylidene-pyrrolidines 2j,k, were also obtained by
a known procedure: the reaction of the dianions of 1b,c
with 1-bromo-2-chloroethane gave the corresponding 6-
chloro-1,3-dioxohexanoates. These dioxohexanoates were
transformed into 2j,k by nucleophilic displacement of the
chloride group by treatment with NaN3 and subsequent
cyclization by treatment with PPh3/THF (Staudinger-aza-
Wittig reaction).[10]
The bromination of 2-alkylidene-tetrahydrofuran 2a was
studied (Scheme 1). The reaction of 2a with NBS
(1.3 equiv.) resulted in the bromination of the double bond
and the formation of the desired product Z-3a; the dibromi-
nated side-product E-4a was also formed. Optimization of
the reaction conditions showed that the use of NBS was
mandatory; the employment of bromine was unsuccessful.
In addition, the amount of NBS, the reaction time (3 h),
temperature (reflux) and solvent (CCl4) all proved to be im-
portant parameters. The formation of Z-3a can, in prin-
[a] Institut für Chemie, Universität Rostock,
Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax: +49-381-498-6412
E-mail: peter.langer@uni-rostock.de
[b] Institut für Chemie und Biochemie, Universität Greifswald,
Soldmannstr. 16, 17487 Greifswald, Germany
[c] Leibniz-Institut für Organische Katalyse an der Universität Ro-
stock e.V. (IfOK),
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Eur. J. Org. Chem. 2005, 4815–4828
DOI: 10.1002/ejoc.200500422
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E. Bellur, P. Langer
FULL PAPER
ciple, proceed by a radical or a cationic mechanism. No- at the exocyclic double bond and the higher stability of the
tably, the reactions were carried out by using CCl4 as the product containing an exocyclic double bond (conjugation
solvent under reflux; however, the use of a radical initiator, to the carbonyl group). Bromination of 5-vinyl-2-alkylid-
such as AIBN, was not required. In fact, the reaction condi- ene-tetrahydrofuran 2i with NBS (1.6 equiv.) afforded the
tions employed and the isolation of small amounts of the dibromide 4i.
mono- and dibrominated products 4, 5 and 6 suggest that
The reaction of isomerically pure (Z)-configured 2-alk-
a radical mechanism operates: the reaction of 2a with a ylidene-pyrrolidine 2j with NBS (1.3 equiv.) afforded a sep-
bromine radical (Br•) affords the allylic radical A. This re- arable mixture of 3j (66%) and 4j (30%). Likewise, the bro-
acts with bromine to give intermediate B which undergoes mination of 2k with NBS (1.3 equiv.) gave 3k (75%) and 4k
a double-bond migration to give the product Z-3a. A small (19%). The use of a smaller amount of NBS resulted in a
amount of the latter is transformed into E-4a via the allylic decrease in yield. These bromides (3j, 3k, 4j and 4k) were
radical C.
obtained as inseparable mixtures of geometric isomers. The
(E)-configured isomers were predominantly formed as a re-
sult of the formation of a stable intramolecular N–H···O
hydrogen bond.
The configurations of the exocyclic double bond of 2-
alkylidene-tetrahydrofurans 2 were established by NOESY
experiments.[7a,11] The structures of the bromo-2-alkylidene-
tetrahydrofurans were elucidated by comparison of the
chemical shifts of the C-2 carbon atom (O–C=C–Br) with
those of related 2-alkylidene-tetrahydrofurans (Table 2). As
expected, characteristic 13C NMR shifts in the range of δ =
170.8–172.2 ppm were observed for all (Z)-configured ester-
derived 1Ј-bromo-2-alkylidene-tetrahydrofurans. The (Z)-
configured
1Ј,3-dibromo-2-alkylidene-tetrahydrofurans
showed characteristic 13C NMR resonances in the range of
δ = 168.2–168.5 ppm (for ester derivatives, except for Z-4e).
In contrast, 13C shifts were observed in the range of δ =
166.2–167.1 ppm for (E)-configured 1Ј,3-dibromo-2-alk-
ylidene-tetrahydrofurans. In addition, general trends in the
polarity of the (E)/(Z) diastereomers were deduced from
TLC experiments. The chemical shifts of 2-alkylidene-pyr-
rolidines were compared with those reported for related
compounds. In addition, NMR analysis of the intramolecu-
lar hydrogen bonds N–H···O was helpful for the assignment
of the (E)/(Z) diastereomers (Table 3).
Scheme 1. Bromination of 2-alkylidene-tetrahydrofuran 2a. Rea-
gents and conditions: i: 1) 2.3 equiv. LDA, THF, 0 °C, 1 h; 2)
Br(CH2)2Cl, –78 Ǟ 20 °C, 14 h, then reflux, 12 h; ii: NBS
(1.3 equiv.), CCl4, reflux, 3 h.
The bromination of other 2-alkylidene-tetrahydrofurans
The palladium-catalyzed cross-coupling reactions of bro-
and -pyrrolidines has also been studied (Table 1). The reac- minated 2-alkylidene-tetrahydrofurans 3a,d and of 2-alk-
tion of 2b–d with NBS (1.3 equiv.) afforded the desired pro- ylidene-pyrrolidine 3k were next studied (Scheme 2,
ducts 3b–d and the dibrominated side-products 4b,c. Al- Table 4). The Suzuki reaction of 3a with PhB(OH)2 in the
though the yield of 3c was successfully improved by the presence of Pd(PPh3)4 (3 mol-%) afforded the desired 2-alk-
employment of only 1.1 equiv. of NBS, the formation of ylidene-tetrahydrofuran 7a. The best yields were obtained
side-products (5c and 4c) could not be entirely avoided. The when Pd(PPh3)4, phenylboronic acid, K3PO4 and 1,4-diox-
reaction of 2b with an excess of NBS (3.0 equiv.) resulted ane (reflux) were used. The reaction of 3a and 3d with 4-
in the selective formation of the dibrominated product 4b, tolyl-, 4-methoxyphenyl-, 4-chlorophenyl- and 2-thienyl-
which was isolated in high yield as a separable mixture of boronic acid afforded the functionalized 2-alkylidene-tetra-
(E)/(Z) isomers (Z-4b: 70%; E-4b: 23%).
hydrofurans 7b–j. The acid 7k was prepared by treatment
The bromination (NBS, 1.3 equiv.) of benzoylacetone-de- of 7c with BBr3 in CH2Cl2 and subsequent heating with
rived 2-alkylidene-tetrahydrofuran 2e exclusively gave the KOH in THF/H2O (1:1). The reaction of 2-alkylidene-pyr-
dibrominated product 4e. The bromination of 2-alkylidene- rolidine 3l [(E)/(Z) mixture] with 4-chlorophenylboronic
tetrahydrofurans 2f,g containing methyl and ethyl groups at acid gave the isomerically pure (Z)-configured 2-alkylidene-
the exocyclic double bond resulted in selective bromination pyrrolidine 7l. All the Suzuki reactions proceeded in good
of the C-3 carbon atom (5f,g) and in double bromination to very good yields (48–92%), and with excellent (E) dia-
(6f). The bromination (NBS, 1.2 equiv.) of tetrahydro-2,3Ј- stereoselectivity for 2-alkylidene-tetrahydrofurans 7a–k and
bifuranyliden-2Ј-one 2h[7a,9] afforded the monobromide 5h (Z) diastereoselectivity for 2-alkylidene-pyrrolidine 7l.
(76%) and the dibromide 6h (22%). Bromination of 2-alk-
The Suzuki reactions of dibromides 4a,b,e were next
ylidene-tetrahydrofurans 2f–h regioselectively occurred at studied (Scheme 3, Table 5). The reaction of 4a with phen-
the C-3 position, presumably as a result of steric hindrance ylboronic acid (3 equiv.) afforded a separable mixture of 2-
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Eur. J. Org. Chem. 2005, 4815–4828

Synthesis of Functionalized Alkylidene-tetrahydrofurans
FULL PAPER
Table 1. Bromination of 2-alkylidene-tetrahydrofurans and 2-alkylidene-pyrrolidines.
Eur. J. Org. Chem. 2005, 4815–4828
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E. Bellur, P. Langer
FULL PAPER
Table 1. (continued).
[a] Yields of isolated products.
Table 2. C-2 chemical shifts of brominated 2-alkylidene-tetra-
hydrofurans.
Com-
pound
Com-
pound
Com-
pound
δ [ppm][a]
δ [ppm][a]
δ [ppm][a]
Z-3a
Z-3b
Z-3c
Z-3d
172.2
171.7
171.6
170.8
Z-4b
Z-4c
Z-4e
Z-4i
168.5
168.3
166.9
168.2[b]
E-4a
E-4b
E-4c
E-4i
167.0
167.1
166.9
166.2[b]
Scheme 2. Suzuki reactions of 2-alkylidene-tetrahydrofurans and 2-
alkylidene-pyrrolidines. Reagents and conditions: i: ArB(OH)2
(3 equiv.), Pd(PPh3)4 (3 mol-%), K3PO4 (6.0 equiv.), 1,4-dioxane,
reflux, 6 h.
[a] Chemical shift (13C NMR, CDCl3) of the C-2 carbon atom (O–
C=C–Br). [b] Major diastereomer.
alkylidene-1Ј,3-diaryltetrahydrofuran 9a (41%) and furan
8a (21%). Compound 9a is formed by a double-Suzuki re-
action of the 1,3-dibromoprop-1-ene moiety, which is, to
the best of our knowledge, an unprecedented process. The
formation of 8a can be explained by Suzuki reaction of the
alkenyl bromide, thermal elimination of hydrogen bromide
and subsequent aromatization. The double-Suzuki reaction
Table 4. Suzuki reactions of 2-alkylidene-tetrahydrofurans and 2-
alkylidene-pyrrolidines.
7
X
R
Ar
7 [%][a] (E)/(Z)
a
b
c
d
e
f
g
h
i
O
O
O
O
O
O
O
O
O
O
O
NH
OMe
OMe
OMe
OMe
OMe
OtBu
OtBu
OtBu
OtBu
OtBu
OH
Ph
79
91
91
92
62
87
88
77
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͼ98:2
Ͻ2:98
4-MeC6H4
4-(MeO)C6H4
4-ClC6H4
2-thienyl
Ph
4-MeC6H4
4-(MeO)C6H4
4-ClC6H4
2-thienyl
4-(HO)C6H4
4-ClC6H4
Table 3. C-2 and N–H chemical shifts of brominated 2-alkylidene-
pyrrolidines
Com-
pound
Com-
pound
δ [ppm][a] δ [ppm][b]
δ [ppm][a] δ [ppm][b]
87
E-3j
E-4j
E-3k
E-4k
166.5
167.1
166.5
166.5
8.16
8.07
8.12
7.75
Z-3j
Z-4j
Z-3k
Z-4k
164.3
163.7
164.2
162.0
5.49
5.45
5.48
5.41
j
k
l
48[b]
80[c]
87
OiPr
[a] Yields of isolated products. [b] NMR yield (calcd. from a 1:1
[a] Chemical shift (13C NMR, CDCl3) of the C-2 carbon atom mixture of 7j and 3d). [c] From 7c: i: 1) BBr3, CH2Cl2, 0 Ǟ 20 °C;
(HN–C=C–Br). [b] Chemical shift (1H NMR, CDCl3) of N–H.
2) MeOH; ii: KOH, H2O/THF (1:1), reflux.
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Synthesis of Functionalized Alkylidene-tetrahydrofurans
FULL PAPER
of 4b with 4-methoxyphenylboronic acid afforded the 2-alk- Table 6. Suzuki reactions of 2-alkylidene-3-bromotetrahydrofurans
5f–h.
ylidene-tetrahydrofuran 9b (Table 5). Likewise, 9c was pre-
R1
R2
Ar
10 [%][a]
pared by reaction of 4e with phenylboronic acid.
10
a
b
c
OEt
OEt
Me
Et
4-ClC6H4
4-ClC6H4
Ph
52
76
55
OCH2CH2
[a] Yields of isolated products, (E)/(Z) Ͼ 98:2.
The Heck reactions of 2-alkylidene-tetrahydrofurans
were next studied. The Heck reaction of 3a with tert-butyl
acrylate, acrylonitrile, styrene and 4-methoxystyrene af-
forded
the
alkenyl-substituted
2-alkylidene-tetra-
hydrofurans 11a–d (Scheme 5, Table 7). 2-Alkylidene-tetra-
hydrofuran 11e was prepared by the reaction of 3b with
tert-butyl acrylate. The reaction of 3c with 4-methoxysty-
rene afforded 11f. Notably, the regioselectivity observed in
the reactions of styrene was different to that observed for
acrylonitrile and tert-butyl acrylate for electronic reasons.
Scheme 3. Double-Suzuki reaction of 2-alkylidene-1Ј,3-dibromo-
tetrahydrofuran E-4a. Reagents and conditions: i: PhB(OH)2
(3 equiv.), Pd(PPh3)4 (3 mol-%), K3PO4 (6 equiv.), 1,4-dioxane, re-
flux, 6 h.
Table 5. Double-Suzuki reactions of dibromides 4b,e.
Scheme 5. Heck reactions of 2-alkylidene-tetrahydrofurans. Rea-
gents and conditions: i: Pd(PPh3)4 (3 mol-%), NEt3, DMF, 100 °C,
25 h.
Table 7. Heck reactions of 2-alkylidene-tetrahydrofurans.
11
R1
R2
11 [%][a]
a
b
c
d
e
f
OMe
OMe
OMe
OMe
OEt
CO2tBu
CN
Ph
4-(MeO)C6H4
CO2tBu
4-(MeO)C6H4
85
47
56
45
51
58
[a] Yields of isolated products, (E)/(Z) Ͼ 98:2.
The Suzuki reaction of monobromides 5f–h afforded the
(E)-configured 2-alkylidene-tetrahydrofurans 10a–c in good
yields (Scheme 4, Table 6); substitution occurred exclusively
at the C-3 carbon atom.
OiPr
[a] Yields of isolated products.
In summary, we have reported the synthesis of 2-alkylid-
ene-1Ј-bromotetrahydrofurans, 2-alkylidene-3-bromotetra-
hydrofurans
and
2-alkylidene-1Ј,3-dibromotetra-
hydrofurans and their pyrrolidine counterparts by bromina-
tion of 2-alkylidene-tetrahydrofurans and 2-alkylidene-
pyrrolidines, which are readily available by one-pot [3+2]
cyclization reactions. The 2-alkylidene-1Ј-bromotetra-
hydrofurans were functionalized by Suzuki and Heck reac-
tions. 2-Alkylidene-1Ј,3-dibromotetrahydrofurans were suc-
cessfully employed in double-Suzuki reactions.
Scheme 4. Suzuki-reactions of 2-alkylidene-tetrahydrofurans 5f–h.
Reagents and conditions: i: Pd(PPh3)4 (3 mol-%), K3PO4 (6 equiv.),
1,4-dioxane, reflux, 6 h.
Eur. J. Org. Chem. 2005, 4815–4828
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E. Bellur, P. Langer
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70 eV): m/z (%) = 221 ([81Br], 72) [M]+, 219 ([79Br], 71) [M]+, 190
(63), 189 (100), 188 (71), 187 (93), 179 (10), 177 (10), 162 (3), 148
(60), 146 (59). C7H9BrO3 (221.050): calcd. C 38.04, H 4.10; found
C 38.19, H 3.64.
Experimental Section
General Comments: All solvents were dried by standard methods
and all reactions were carried out under an inert atmosphere. To
record 1H and 13C NMR spectra the deuteriated solvents indicated
were used. Mass spectroscopic (MS) data were obtained by electron
ionization (EI, 70 eV), chemical ionization (CI, H2O) or by electro-
spray ionization (ESI). For preparative-scale chromatography silica
gel (60–200 mesh) was used. Melting points are uncorrected.
Methyl 2-Bromo-2-[3-bromo-4,5-dihydrofuran-2(3H)-ylidene]acetate
(E-4a): 1H NMR (CDCl3, 300 MHz): δ = 2.43–2.49 (m, 1 H, CH2),
2.53–2.61 (m, 1 H, CH2), 3.80 (s, 3 H, OCH3), 4.74–4.76 (m, 1 H,
OCH2), 4.78–4.79 (m, 1 H, OCH2), 5.20 (d, J = 5.4 Hz, 1 H, CH–
Br) ppm. 13C NMR (CDCl3, 75 MHz): δ = 34.7, 48.4, 52.1, 73.8,
Synthesis of Ethyl 2-[5-Vinyl-4,5-dihydrofuran-2(3H)-ylidene]acetate
(2i): A THF solution of lithium diisopropylamide (LDA) was pre-
pared by addition of nBuLi (78.51 mL, 15% in n-hexane,
87.1, 162.0, 167.0 ppm. IR (KBr): 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) cm–1. MS (EI, 70 eV): m/z (%) = 302 ([2×81Br],
17) [M]+, 300 ([81Br 79Br], 34) [M]+, 298 ([2×79Br], 17) [M]+, 271
(9), 269 (19), 267 (10), 241 (2), 221 (98), 219 (100), 189 (22), 187
(21), 161 (18), 159 (17), 133 (12), 131 (13), 81 (6), 79 (10).
C7H8Br2O3 (299.946): calcd. C 28.03, H 2.69; found C 28.88, H
2.85.
125.0 mmol) to
a solution of diisopropylamine (17.57 mL,
125.0 mmol) in THF (200 mL) at 0 °C. After stirring the mixture
for 20 min, ethyl acetoacetate (1b) (6.32 mL, 50.0 mmol) was added
at 0 °C. The mixture was stirred for 1 h at 0 °C and then this solu-
tion was slowly added to a solution of trans-1,4-dibromo-2-butene
(12.834 g, 60.0 mmol) in THF (100 mL) at –78 °C. The temperature
was allowed to rise to 20 °C over 14 h and the solution was stirred
at room temperature for 24 h. The reaction mixture was poured
into an aqueous solution of HCl (10%) and extracted with diethyl
ether several times. The combined organic extracts were dried over
Na2SO4, filtered and the filtrate was concentrated in vacuo. The
residue was purified by column chromatography (silica gel, n-hex-
ane/EtOAc = 100:1 Ǟ 1:1) to give E-2i (3.633 g, 40%) and Z-2i
(3.213 g, 35%) as yellowish oils (combined yield: 75%). Spectro-
Compounds 3b and 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 Ǟ 1:1) as
slightly yellowish and yellowish solids and as a yellowish oil,
respectively.
Compound Z-4b: 1H NMR (CDCl3, 300 MHz): δ = 1.36 (t, J =
7.2 Hz, 3 H, CH3), 2.55–2.63 (m, 2 H, CH2), 4.29 (dq, J = 2.1,
7.2 Hz, 2 H, OCH2CH3), 4.56–4.66 (m, 2 H, OCH2), 5.81 (dd, J =
4.5, 1.5 Hz, 1 H, CH–Br) ppm. 13C NMR (CDCl3, 75 MHz): δ =
1
scopic data of E-2i: H NMR (CDCl3, 300 MHz): δ = 1.26 (t, J =
7.2 Hz, 3 H, CH3), 1.82–1.91 (m, 1 H, CH2), 2.22–2.31 (m, 1 H,
CH2), 2.99–3.08 (m, 1 H, CH2), 3.21–3.32 (m, 1 H, CH2), 4.13 (q,
J = 7.2 Hz, 2 H, OCH2), 4.80 (q, J = 7.5 Hz, 1 H, OCH), 5.23 (dt,
J = 10.5, 1.2 Hz, 1 H, CH2=CH), 5.31 (dt, J = 9.9, 1.2 Hz, 1 H,
CH2=CH), 5.36 (t, J = 1.2 Hz, 1 H, CH=C), 5.80–5.91 (m, 1 H,
CH=CH2) ppm. 13C NMR (CDCl3, 75 MHz): δ = 14.1, 29.4, 29.8,
13.9, 36.8, 44.1, 61.7, 70.6, 87.1, 162.5, 168.5 ppm. IR (KBr): 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) cm–1. MS (EI, 70 eV): m/z (%) = 315 ([2×81Br], 11) [M]+, 313
([81Br 79Br], 33) [M]+, 311 ([2×79Br], 12) [M]+, 271 (2), 269 (11),
267 (3), 235 (65), 233 (60), 207 (90), 205 (100), 189 (29), 187 (25),
161 (23), 159 (18), 148 (12), 146 (11), 133 (16), 131 (16).
C8H10Br2O3 (313.973): calcd. C 30.60, H 3.21; found C 30.32, H
3.51.
58.7, 83.4, 89.3, 116.9, 135.7, 168.0, 175.6 ppm. IR (neat): ν = 2983
˜
(s), 2941 (m), 2903 (w), 1707 (s), 1644 (s), 1459 (m), 129 (m), 1392
(m), 1372 (s), 1348 (s), 1321 (m), 1284 (m), 1239 (m), 1164 (s), 1111
(s), 1047 (s), 1007 (s), 993 (s), 934 (m), 886 (s), 854 (w), 825 (s) cm–1.
MS (EI, 70 eV): m/z (%) = 182 (58) [M]+, 153 (4), 137 (100), 108
(27), 95 (24). C10H14O3 (182.219): calcd. C 65.92, H 7.74; found C
65.30, H 7.88. The synthesis of Z-2i has been reported previously.[9]
Ethyl 2-Bromo-2-[4,5-dihydrofuran-2(3H)-ylidene]acetate (Z-3b): 1H
NMR (CDCl3, 300 MHz): δ = 1.32 (t, J = 7.2 Hz, 3 H, CH3), 2.23
(quint, J = 7.5 Hz, CH2), 3.18 (t, J = 7.8 Hz, 2 H, CH2), 4.23 (q,
J = 7.2 Hz, 2 H, OCH2CH3), 4.40 (t, J = 7.2 Hz, 2 H, OCH2) ppm.
13C NMR (CDCl3, 150 MHz): δ = 14.0, 24.6, 32.2, 60.8, 72.7, 83.0,
General Procedure for the Reaction of 2-Alkylidene-tetrahydrofurans
or 2-Alkylidene-pyrrolidines with N-Bromosuccinimide (NBS): N-
Bromosuccinimide (1.1–3.0 equiv., see Table 1) was added to a CCl4
solution (5 mLmmol–1) of the 2-alkylidene-tetrahydrofuran or
-pyrrolidine (2) (1 equiv.) at 20 °C. The reaction mixture was heated
and stirred under reflux for 3 h. The reaction mixture was 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 brominated 2-alkylidene-tetra-
hydrofuran or -pyrrolidine (3–6).
163.7, 171.7 ppm. IR (KBr): ν = 2995 (w), 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) cm–1.
MS (EI, 70 eV): m/z (%) = 236 ([81Br], 75) [M]+, 234 ([79Br], 76)
[M]+, 207 (44), 205 (43), 190 (100), 188 (93), 164 (11), 162 (11), 148
(45), 146 (45), 110 (40), 81 (12), 79 (9). C8H11BrO3 (235.077): calcd.
C 40.88, H 4.72; found C 41.04, H 4.61.
Compound E-4b: 1H NMR (CDCl3, 300 MHz): δ = 1.32 (t, J =
7.2 Hz, 3 H, CH3), 2.43–2.48 (m, 1 H, CH2), 2.52–2.61 (m, 1 H,
CH2), 4.27 (q, J = 7.2 Hz, 2 H, OCH2CH3), 4.76 (dt, J = 8.7,
0.9 Hz, 2 H, OCH2), 5.20 (d, J = 5.4 Hz, 1 H, CH–Br) ppm. 13C
NMR (CDCl3, 150 MHz): δ = 14.1, 35.2, 48.7, 61.5, 74.0, 87.9,
Compounds 3a and 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 chromatography (silica
gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as yellowish and colorless sol-
ids, respectively.
162.0, 167.1 ppm. IR (neat): ν = 2983 (m), 2938 (w), 2905 (m), 1737
˜
Methyl 2-Bromo-2-[4,5-dihydrofuran-2(3H)-ylidene]acetate (Z-3a): (s), 1703 (s), 1660 (m), 1616 (s), 1471 (m), 1440 (m), 1371 (s), 1316
1H NMR (CDCl3, 300 MHz): δ = 2.23 (quint, J = 7.2 Hz, 2 H,
CH2), 3.19 (t, J = 7.8 Hz, 2 H, CH2), 3.78 (s, 3 H, OCH3), 4.41 (t,
(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
J = 7.2 Hz, 2 H, OCH2) ppm. 13C NMR (CDCl3, 75 MHz): δ = (w) cm–1. MS (EI, 70 eV): m/z (%) = 316 ([2×81Br], 17) [M]+, 314
24.8, 32.3, 52.2, 73.0, 82.7, 164.7, 172.2 ppm. IR (KBr): ν = 2951
([81Br 79Br], 37) [M]+, 312 ([2×79Br], 18) [M]+, 271 (14), 269 (29),
267 (14), 241 (3), 235 (63), 233 (69), 207 (96), 205 (100), 189 (35),
187 (27), 161 (23), 159 (18), 148 (15), 146 (13), 133 (17), 131 (15),
˜
(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) cm–1. MS (EI,
4820
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 4815–4828

Synthesis of Functionalized Alkylidene-tetrahydrofurans
FULL PAPER
81 (8), 79 (13). The exact molecular mass, m/z = 311.8997 2 ppm
Compounds 3c, 4c, and 5c: Starting with 2c (0.936 g, 5.5 mmol) and
NBS (1.077 g, 6.05 mmol) in CCl4 (20 mL), E-5c (0.281 g, 21%),
Z-3c (0.888 g, 65%) and E-4c (0.219 g, 12%) were isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as yel-
lowish oils.
[M]+, for C8H10Br2O3 was confirmed by HRMS (EI, 70 eV).
Ethyl 2-Bromo-2-[3-bromo-4,5-dihydrofuran-2(3H)-ylidene]acetate
(4b): Starting with 2b (0.300 g, 1.9 mmol) and NBS (1.026 g,
5.8 mmol) in CCl4 (10 mL), Z-4b (0.423 g, 70%) and E-4b (0.138 g,
23%) were isolated after chromatography (silica gel, n-hexane/
EtOAc = 100:1 Ǟ 1:1) as a slightly yellowish solid and a yellowish
oil, respectively (combined yield: 93%).
Isopropyl 2-[3-Bromo-4,5-dihydrofuran-2(3H)-ylidene]acetate (E-
5c): 1H NMR (CDCl3, 300 MHz): δ = 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,
CH–Br) ppm. 13C NMR (CDCl3, 75 MHz): δ = 21.9, 22.0, 36.0,
Compounds 3c and 4c: Starting with 2c (0.888 g, 5.22 mmol) and
NBS (1.208 g, 6.79 mmol) in CCl4 (20mL), Z-4c (0.463 g, 27%),
Z-3c (0.252 g, 19%) and E-4c (0.442 g, 26%) were isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a
yellowish solid, yellowish oil and brownish oil, respectively.
43.0, 67.1, 69.6, 91.9, 166.3, 172.8 ppm. IR (neat): ν = 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. MS (EI, 70 eV): m/z (%) = 250 ([81Br],
6) [M]+, 248 ([79Br], 6) [M]+, 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). C9H13BrO3
(249.104): calcd. C 43.40, H 5.26; found C 43.28, H 5.48.
Isopropyl 2-Bromo-2-[3-bromo-4,5-dihydrofuran-2(3H)-ylidene]ace-
tate (Z-4c): 1H NMR (CDCl3, 300 MHz): δ = 1.34 (dd, J = 6.3,
1.5 Hz, 6 H, 2×CH3), 2.55–2.63 (m, 2 H, CH2), 4.57–4.65 (m, 2
H, OCH2), 5.13 (quint, J = 6.3 Hz, 1 H, CH), 5.79 (dt, J = 4.5,
0.9 Hz, 1 H, CH–Br) ppm. 13C NMR (CDCl3, 150 MHz): δ = 21.8,
37.1, 44.4, 69.7, 70.7, 88.2, 162.1, 168.3 ppm. IR (neat): ν = 2983
˜
(w), 1694 (w), 1678 (m), 1616 (s), 1276 (s), 1217 (s), 1179 (m), 1109
(m), 1071 (s) cm–1. MS (EI, 70 eV): m/z (%) = 329 ([2×81Br], 12)
[M]+, 327 ([81Br 79Br], 26) [M]+, 325 ([2×79Br], 12) [M]+, 287 (29),
285 (57), 283 (29), 268 (18), 240 (1), 206 (99), 204 (100), 190 (9),
188 (29), 186 (19), 163 (4), 161 (18), 159 (14), 148 (10), 146 (9), 133
(11), 131 (11), 127 (2), 120 (2), 108 (3), 106 (3), 104 (3), 81 (3), 70
(8). The exact molecular mass, m/z = 325.9153 2 ppm [M]+, for
C9H12Br2O3 was confirmed by HRMS (EI, 70 eV).
tert-Butyl 2-Bromo-2-[4,5-dihydrofuran-2(3H)-ylidene]acetate (Z-
3d): Starting with 2d (0.700 g, 3.8 mmol) and NBS (0.879 g,
4.9 mmol) in CCl4 (40 mL), Z-3d was isolated after chromatog-
raphy (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a white solid
(0.732 g, 73%). 1H NMR (CDCl3, 300 MHz): δ = 1.51 (s, 9 H,
OtBu), 2.21 (quint, J = 7.2 Hz, 2 H, CH2), 3.13 (t, J = 7.8 Hz, 2
H, CH2), 4.37 (t, J = 7.2 Hz, 2 H, OCH2) ppm. 13C NMR (CDCl3,
150 MHz): δ = 25.1, 28.5, 32.5, 72.8, 81.7, 85.8, 163.4, 170.8 ppm.
IR (KBr): ν = 2975 (w), 1694 (s), 1613 (s), 1370 (m), 1295 (s), 1250
˜
Isopropyl 2-Bromo-2-[4,5-dihydrofuran-2(3H)-ylidene]acetate (Z-
3c): 1H NMR (CDCl3, 300 MHz): δ = 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) ppm. 13C NMR (CDCl3, 150 MHz): δ = 22.0, 25.0, 32.5,
(w), 1243 (w), 1210 (m), 1170 (s), 1067 (s), 1039 (w), 1023 (w), 955
(w), 934 (w), 864 (w) cm–1. MS (EI, 70 eV): m/z (%) = 265 ([81Br],
18) [M]+, 263 ([79Br], 19) [M]+, 208 (98), 206 (100), 191 (48), 190
(92), 189 (54), 188 (93), 166 (9), 164 (10), 148 (26), 146 (26), 70
(12), 58 (57). The exact molecular mass, m/z = 262.0205 2 ppm
[M]+, for C10H15BrO3 was confirmed by HRMS (EI, 70 eV).
C10H15BrO3 (263.131): calcd. C 45.65, H 5.75; found C 45.38, H
6.03.
68.9, 72.9, 84.2, 163.8, 171.6 ppm. IR (neat): ν = 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. MS (EI, 70 eV): m/z
(%) = 249 ([81Br], 26) [M]+, 247 ([79Br], 26) [M]+, 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). The exact
molecular mass, m/z = 248.0048 2 ppm [M]+, for C9H13BrO3 was
confirmed by HRMS (EI, 70 eV). C9H13BrO3 (249.104): calcd. C
43.40, H 5.26; found C 43.28, H 5.48.
2-Bromo-2-[3-bromo-4,5-dihydrofuran-2(3H)-ylidene]-1-phenyl-
ethanone (Z-4e): Starting with 2e (0.600 g, 3.19 mmol), and NBS
(0.738 g, 4.14 mmol) in CCl4 (20 mL), Z-4e was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a
yellowish oil (0.692 g, 63%). 1H NMR (CDCl3, 300 MHz): δ =
2.51–2.72 (m, 2 H, CH2), 4.60–4.71 (m, 2 H, OCH2), 5.60 (d, J =
5.4 Hz, 1 H, CH–Br), 7.41–7.55 (m, 3 H, 3×CH of Ph), 7.75 (d, J
= 3.9 Hz, 2 H, 2×CH of Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ
=
36.8, 43.6, 70.5, 92.8, 127.7, 128.7, 132.0, 137.7, 166.9,
Compound E-4c: 1H NMR (CDCl3, 300 MHz): δ = 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, CH–Br) ppm. 13C NMR (CDCl3,
150 MHz): δ = 21.8, 35.3, 48.8, 69.2, 74.0, 88.3, 161.7, 166.9 ppm.
191.0 ppm. IR (neat): 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) cm–1. MS (EI, 70 eV): m/z (%) = 348 ([2×81Br], 7) [M]+, 346
([81Br 79Br], 15) [M]+, 344 ([2×79Br], 7) [M]+, 267 (36), 265 (36),
186 (100), 129 (11), 105 (68), 89 (6), 77 (76). C12H10Br2O2
(346.018): calcd. C 41.65, H 2.91; found C 41.35, H 3.60.
IR (neat): ν = 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. MS (EI, 70 eV): m/z (%) = 330 ([2×81Br], 12)
[M]+, 328 ([81Br 79Br], 26) [M]+, 326 ([2×79Br], 13) [M]+, 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),
Compounds 5f and 6f: Starting with 2f (0.100 g, 0.59 mmol) and
NBS (0.115 g, 0.65 mmol) in CCl4 (5 mL), 5f (0.082 g, 56%) and
6f (0.023 g, 12%) were isolated after chromatography (silica gel, n-
hexane/EtOAc = 100:1 Ǟ 5:1) as slightly yellowish oils.
106 (3), 87 (17), 70 (16), 43 (70). The exact molecular mass, m/z = Ethyl 2-[3-Bromo-4,5-dihydrofuran-2(3H)-ylidene]propionate (5f):
325.9153 2 ppm [M]+, for C9H12Br2O3 was confirmed by HRMS
(EI, 70 eV).
1H NMR (CDCl3, 300 MHz): δ = 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,
Eur. J. Org. Chem. 2005, 4815–4828
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4821

E. Bellur, P. Langer
FULL PAPER
2.7 Hz, 2 H, OCH2CH3), 4.39–4.54 (m, 2 H, OCH2), 5.81 (m, 1 H, 3,3-Dibromo-4,4Ј,5,5Ј-tetrahydro-2,3Ј-bifuranyliden-2Ј-one (6h): 1H
CH–Br) ppm. 13C NMR (CDCl3, 75 MHz): δ = 11.6, 14.3, 36.7, NMR (CDCl3, 300 MHz): δ = 3.26 (t, J = 6.5 Hz, 2 H, CH2), 3.33
45.1, 60.1, 69.1, 100.4, 167.1, 167.6 ppm. IR (neat): ν = 2984 (m),
2930 (w), 2904 (w), 1699 (s), 1644 (s), 1469 (w), 1441 (m), 1390 (w),
(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) ppm. 13C NMR (CDCl3, 150 MHz): δ =
˜
1369 (m), 1288 (s), 1212 (m), 1185 (m), 1170 (m), 1107 (s), 1082 26.2, 50.3, 51.0, 65.7, 70.5, 98.2, 163.0, 170.3 ppm. IR (KBr): ν =
˜
(s), 1024 (m), 972 (w), 933 (w), 880 (w), 767 (w), 704 (w) cm–1. MS 2908 (w), 1738 (s), 1663 (s), 1224 (w), 1197 (w), 1149 (s), 1134 (m),
(EI, 70 eV): m/z (%) = 250 ([81Br], 29) [M]+, 248 ([79Br], 34) [M]+, 1070 (w), 1029 (m), 991 (w), 728 (w) cm–1. MS (EI, 70 eV): m/z (%)
205 (14), 203 (16), 169 (83), 141 (100), 123 (54), 99 (3), 97 (3), 95
(32), 83 (49), 68 (33). HRMS (ESI): calcd. for C9H13BrO3 [M]+:
250.00276 (81Br), 248.00481 (79Br); found 250.00210 (81Br),
= 314 ([2×81Br], 2) [M+], 312 ([81Br 79Br], 6) [M]+, 310 ([2×79Br],
3) [M]+, 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
248.00485 (79Br). C9H13BrO3 (249.104): calcd. C 43.40, H 5.26; (20), 173 (6), 153 (14), 150 (13), 148 (9), 123 (7), 121 (5), 112 (5),
found C 42.74, H 4.87.
107 (12), 95 (14), 81 (10), 79 (15), 77 (10), 68 (13), 66 (16). The
exact molecular mass, m/z = 309.8840 2 ppm [M]+, for C8H8BrO3
was confirmed by HRMS (EI, 70 eV).
Ethyl
2-[3,3-Dibromo-4,5-dihydrofuran-2(3H)-ylidene]propionate
(6f): 1H NMR (CDCl3, 300 MHz): δ = 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) ppm.
13C NMR (CDCl3, 75 MHz): δ = 14.2, 14.6, 50.4, 51.7, 60.5, 68.7,
Ethyl
2-Bromo-2-[3-bromo-5-vinyl-4,5-dihydrofuran-2(3H)-ylid-
ene]acetate (4i): Starting with 2i (1.500 g, 8.23 mmol) and NBS
(2.344 g, 13.17 mmol) in CCl4 (30 mL), Z-4i (1.392 g, 50%) and E-
4i (0.736 g, 26%) were isolated, each as a 10:1 mixture of cis/trans
diastereomers, after chromatography (silica gel, n-hexane/EtOAc =
100:1 Ǟ 1:1) as a colorless solid and a yellowish oil (combined
yield: 76%), respectively.
103.2, 162.1, 167.2 ppm. IR (neat): ν = 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. MS (EI, 70 eV): m/z (%) = 328 ([81Br 79Br], 11)
[M]+, 326 ([2×79Br], 2) [M]+, 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).
HRMS (ESI): calcd. for C9H12Br2O3 [M]+: 329.91127 (2×81Br),
327.91327 (81Br79Br), 325.91532 (2×79Br); found 329.90904
(2×81Br), 327.91240 (81Br79Br), 325.91549 (2×79Br).
Compound Z-4i: 1H NMR (CDCl3, 300 MHz): major diastereomer:
δ = 1.36 (t, J = 7.2 Hz, 3 H, CH3), 2.30–2.40 (m, 1 H, CH2), 2.67
(dd, J = 14.4, 4.5 Hz, 1 H, CH2), 4.29 (dq, J = 7.2, 2.4 Hz, 2 H,
OCH2), 5.29–5.35 (m, 1 H, CH), 5.38 (dt, J = 10.5, 0.9 Hz, 1 H,
CH2=CH), 5.53 (dt, J = 17.1, 1.2 Hz, 1 H, CH2=CH), 5.83 (d, J =
5.4 Hz, 1 H, CH–Br), 5.89–6.00 (m, 1 H, CH=CH2) ppm; minor
diastereomer: δ = 1.29 (t, J = 7.2 Hz, 3 H, CH3), 2.19–2.28 (m, 1
H, CH2), 2.58 (dd, J = 15.0, 4.5 Hz, 1 H, CH2), 4.18 (dq, J = 7.2,
2.1 Hz, 2 H, OCH2), 5.14–5.24 (m, 1 H, CH), 5.31–5.35 (d, 1 H,
CH2=CH), 5.40–5.42 (d, 1 H, CH2=CH), 5.80 (d, J = 5.4 Hz, 1 H,
CH–Br), 5.81–5.88 (m, 1 H, CH=CH2) ppm. 13C NMR (CDCl3,
75 MHz): major diastereomer: δ = 14.2, 43.1, 44.5, 61.9, 83.6, 87.4,
120.1, 133.6, 162.9, 168.2 ppm; minor diastereomer: δ = 14.3, 42.1,
Ethyl 2-[3-Bromo-4,5-dihydrofuran-2(3H)-ylidene]butyrate (5g):
Starting with 2-[4,5-dihydro-furan-2(3H)-ylidene]butyric acid ethyl
ester (2g) (1.000 g, 5.43 mmol) and NBS (1.063 g, 5.97 mmol) in
CCl4 (30 mL), 5g was isolated after chromatography (silica gel, n-
hexane/EtOAc = 100:1 Ǟ 1:1) as a yellowish oil (1.140 g, 80%). 1H
NMR (CDCl3, 300 MHz): δ = 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, CH–Br) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 12.7, 13.9, 19.2, 36.3, 45.1, 59.6, 68.8, 106.3, 166.8, 166.9 ppm.
43.4, 59.8, 82.5, 87.4, 119.7, 134.2, 162.9, 166.8 ppm. IR (KBr): ν
˜
= 2983 (w), 1698 (s), 1651 (w), 1614 (s), 1445 (w), 1369 (w), 1323
(w), 1277 (s), 1234 (w), 1215 (s), 1186 (m), 1120 (m), 1067 (s), 992
(m), 958 (m), 939 (m), 927 (m), 864 (m), 847 (m), 756 (w) cm–1.
MS (EI, 70 eV): m/z (%) = 342 ([2×81Br], 32) [M]+, 340 ([81Br 79Br],
69) [M]+, 338 ([2×79Br], 34) [M]+, 297 (7), 295 (12), 293 (6), 261
(29), 259 (74), 233 (45), 231 (50), 215 (100), 213 (100), 195 (25),
193 (27), 187 (28), 185 (26), 167 (28), 165 (29), 159 (17), 157 (16),
148 (23), 146 (29), 135 (9), 134 (15), 133 (14), 108 (10), 107 (17),
106 (21), 105 (9), 95 (11), 79 (52). The exact molecular mass, m/z
= 337.9153 2 ppm [M]+, for C10H12Br2O3 was confirmed by
HRMS (EI, 70 eV).
IR (neat): ν = 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. MS
(EI, 70 eV): m/z (%) = 264 ([81Br], 21) [M]+, 262 ([79Br], 23) [M]+,
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). C10H15BrO3
(263.131): calcd. C 45.65, H 5.75; found C 45.05, H 5.55.
Compounds 5h and 6h: Starting with tetrahydro-2,3Ј-bifuranyliden-
2Ј-one (2h) (0.200 g, 1.30 mmol) and NBS (0.277 g, 1.56 mmol) in
CCl4 (10 mL), 5h (0.229 g, 76%) and 6h (0.089 g, 22%) were iso-
lated after chromatography (silica gel, n-hexane/EtOAc = 20:1 Ǟ
1:1) as slightly yellowish solids.
Compound E-4i: 1H NMR (CDCl3, 300 MHz): major diastereomer:
δ = 1.31 (t, J = 7.2 Hz, 3 H, CH3), 2.30–2.40 (m, 1 H, CH2), 2.56–
2.62 (dd, J = 4.8, 14.4 Hz, 1 H, CH2), 4.19–4.28 (m, 2 H, OCH2),
5.22 (d, J = 5.7 Hz, 1 H, CH), 5.34–5.46 (m, 2 H, CH2=CH), 5.51
3-Bromo-4,4Ј,5,5Ј-tetrahydro-2,3Ј-bifuranyliden-2Ј-one (5h): 1H (d, J = 17.1 Hz, 1 H, CH), 5.91–6.02 (m, CH=CH2) ppm. 13C
NMR (CDCl3, 300 MHz): δ = 2.46–2.52 (m, 2 H, CH2), 2.75–3.02 NMR (CDCl3, 75 MHz): major diastereomer: δ = 14.0, 41.2, 48.7,
(m, 2 H, CH2), 4.31–4.39 (m, 2 H, OCH2), 4.47–4.58 (m, 2 H,
61.5, 86.5, 88.3, 119.3, 133.7, 162.0, 166.2 ppm; minor dia-
OCH2), 5.82–5.84 (m, 1 H, CH–Br) ppm. 13C NMR (CDCl3, stereomer: δ = 14.1, 41.2, 48.7, 61.0, 84.8, 88.3, 117.6, 135.0, 164.0,
150 MHz): δ = 25.0, 36.1, 41.8, 65.3, 70.4, 95.7, 166.3, 171.1 ppm.
171.0 ppm. IR (neat): ν = 2984 (m), 2935 (w), 2907 (w), 1705 (s),
˜
IR (KBr): ν = 2910 (w), 1737 (s), 1683 (s), 1366 (m), 1254 (s), 1222
1653 (m), 1616 (s), 1461 (w), 1430 (m), 1392 (w), 1369 (m), 1330
(s), 1299 (s), 1269 (s), 1194 (s), 1097 (m), 1056 (s), 1011 (s), 991 (s),
˜
(m), 1184 (m), 1166 (m), 1080 (m), 1051 (s), 1029 (s), 993 (w), 931
(w), 670 (w) cm–1. MS (EI, 70 eV): m/z (%) = 234 ([81Br], 92) [M] 962 (m), 940 (s), 863 (w), 846 (w), 763 (m), 696 (w) cm–1. MS (EI,
+, 232 ([79Br], 86) [M]+, 153 (100), 125 (14), 123 (20), 107 (32), 97
(23), 95 (39), 85 (14), 81 (23), 79 (34), 70 (35), 68 (40). The exact
molecular mass, m/z = 231.9735 2 ppm [M]+, for C8H9BrO3 was
confirmed by HRMS (EI, 70 eV).
70 eV): m/z (%) = 342 ([2×81Br], 18) [M]+, 340 ([81Br 79Br], 52) [M]
+, 338 ([2×79Br], 19) [M]+, 297 (9), 295 (24), 293 (8), 262 (11), 261
(44), 260 (12), 259 (31), 233 (26), 231 (28), 215 (100), 213 (69), 195
(23), 193 (28), 189 (11), 187 (34), 185 (22), 173 (9), 171 (11), 167
4822
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4815–4828

Synthesis of Functionalized Alkylidene-tetrahydrofurans
FULL PAPER
(36), 165 (37), 159 (17), 157 (14), 148 (22), 146 (28), 135 (38), 134
NMR (CDCl3, 75 MHz): (E) isomer: δ = 21.6, 22.1, 35.6, 48.7,
(15), 133 (13), 108 (11), 107 (22), 106 (17), 105 (8), 95 (13), 85 (25), 67.5, 72.0, 165.3, 166.5 ppm; (Z) isomer: δ = 22.2, 23.3, 32.3, 45.8,
79 (43). The exact molecular mass, m/z = 337.9153 2 ppm [M]+,
for C10H12Br2O3 was confirmed by HRMS (EI, 70 eV).
C10H12Br2O3 (340.011): calcd. C 35.33, H 3.56; found C 35.32, H
3.64.
67.6, 76.8, 162.1, 164.2 ppm. IR (KBr): ν = 3377 (br), 3350 (w),
˜
3338 (w), 2975 (m), 2934 (w), 2882 (w), 1681 (w), 1639 (s), 1592
(s), 1465 (w), 1454 (w), 1439 (w), 1418 (w), 1384 (w), 1374 (w),
1348 (w), 1337 (w), 1311 (w), 1280 (s), 1240 (s), 1197 (w), 1180 (m),
1155 (w), 1144 (w), 1110 (s), 1077 (w), 1066 (w), 1034 (m), 985 (w),
762 (m) cm–1. MS (EI, 70 eV): m/z (%) = 249 ([81Br], 62) [M]+, 247
([79Br], 100) [M]+, 207 (73), 205 (75), 190 (31), 189 (91), 188 (56),
187 (92), 161 (12), 134 (9), 132 (12), 109 (44), 80 (54). The exact
molecular mass, m/z = 247.0208 2 ppm [M]+, for C9H14BrNO2
was confirmed by HRMS (EI, 70 eV).
Compounds 3j and 4j: Starting with Z-2j (0.290 g, 1.87 mmol) and
NBS (0.432 g, 2.43 mmol) in CCl4 (10 mL), 3j [0.287 g, 66%, (E)/
(Z) = 4:1] and 4j [0.174 g, 30%, (E)/(Z) = 7:2] were isolated after
chromatography (silica gel, n-hexane/EtOAc = 50:1 Ǟ 1:1) as
slightly brownish solids.
Ethyl 2-Bromo-2-(pyrrolidin-2-ylidene)acetate (3j): 1H NMR
(CDCl3, 300 MHz): (E) isomer: δ = 1.31 (t, J = 7.2 Hz, 3 H, CH3),
2.03 (quint, J = 7.5 Hz, 2 H, CH2), 2.82 (t, J = 7.8 Hz, 2 H, CH2),
3.64 (t, J = 6.9 Hz, 2 H, CH2–NH), 4.21 (q, J = 7.2 Hz, 2 H,
OCH2), 8.16 (br. s, 1 H, NH) ppm; (Z) isomer: δ = 1.31 (t, J =
7.2 Hz, 3 H, CH3), 2.17 (quint, J = 7.5 Hz, 2 H, CH2), 3.10 (t, J =
7.8 Hz, 2 H, CH2), 3.48 (t, J = 7.5 Hz, 2 H, CH2–NH), 4.21 (q, J =
7.2 Hz, 2 H, OCH2), 5.49 (br. s, 1 H, NH) ppm. 13C NMR (CDCl3,
75 MHz): (E) isomer: δ = 14.3, 21.3, 35.3, 48.6, 60.0, 71.1, 165.3,
166.5 ppm; (Z) isomer: δ = 14.2, 23.9, 32.2, 45.7, 60.5, 75.5, 162.3,
Isopropyl 2-Bromo-2-(3-bromopyrrolidin-2-ylidene)acetate (4k): 1H
NMR (CDCl3, 300 MHz): (E) isomer: δ = 1.21 (dd, J = 7.0, 2.8 Hz,
6 H, 2×CH3), 2.40–2.53 (m, 2 H, CH2), 3.47–3.57 (m, 1 H, CH2–
NH), 3.65–3.73 (m, 1 H, CH2–NH), 5.01 (quint, J = 6.3 Hz, 1 H,
CH), 5.10 (d, J = 6.3 Hz, 1 H, CH–Br), 7.75 (br., 1 H, NH) ppm;
(Z) isomer: δ = 1.31 (dd, J = 6.2, 3.1 Hz, 6 H, 2×CH3), 2.27–2.34
(m, 2 H, CH2), 3.47–3.78 (m, 2 H, CH2–NH), 5.04 (sept, J =
6.3 Hz, 1 H, CH), 5.41 (br. s, 1 H, NH), 5.80 (d, J = 5.1 Hz, 1 H,
CH–Br) ppm. 13C NMR (CDCl3, 75 MHz): (E) isomer: δ = 22.0,
34.7, 46.6, 50.7, 68.3, 73.7, 162.8, 166.5 ppm; (Z) isomer: δ = 22.1,
164.3 ppm. IR (KBr): ν = 3346 (br), 2985 (w), 2903 (w), 1634 (s),
˜
37.0, 43.7, 46.5, 68.5, 80.2, 159.4, 162.0 ppm. IR (KBr): ν = 3376
˜
1588 (s), 1477 (w), 1455 (w), 1442 (m), 1419 (m), 1368 (w), 1320
(m), 1282 (m), 1239 (s), 1069 (s), 1056 (m), 765 (m), 719 (w) cm–1.
MS (EI, 70 eV): m/z (%) = 236 ([81Br], 18) [M]+, 234 ([79Br], 16)
[M]+, 207 (2), 205 (2), 190 (15), 189 (21), 188 (29), 187 (18), 163
(5), 161 (8), 159 (3), 126 (2), 110 (100), 80 (36). The exact molecular
mass, m/z = 233.0052 2 ppm [M]+, for C8H12BrNO2was con-
firmed by HRMS (EI, 70 eV).
Ethyl 2-Bromo-2-(3-bromopyrrolidin-2-ylidene)acetate (4j): 1H
NMR (CDCl3, 300 MHz): (E) isomer: δ = 1.32 (t, J = 7.2 Hz, 3 H,
CH3), 2.39–2.55 (m, 2 H, CH2), 3.64–3.90 (m, 2 H, CH2–NH), 4.21
(q, J = 7.2 Hz, 2 H, OCH2), 5.10 (d, J = 5.7 Hz, 1 H, CH–Br),
8.07 (br. s, 1 H, NH) ppm; (Z) isomer: δ = 1.32 (t, J = 7.2 Hz, 3
H, CH3), 2.35–2.47 (m, 2 H, CH2), 3.47–3.79 (m, 2 H, CH2–NH),
4.21 (q, J = 7.2 Hz, 2 H, OCH2), 5.45 (br. s, 1 H, NH), 5.83 (d, J
= 5.4 Hz, 1 H, CH–Br) ppm. 13C NMR (CDCl3, 75 MHz): (E) iso-
mer: δ = 14.6, 34.9, 46.9, 50.8, 61.1, 73.4, 162.5, 167.1 ppm; (Z)
isomer: δ = 14.6, 37.2, 44.0, 46.6, 61.1, 79.3, 160.0, 163.7 ppm. IR
(br), 2977 (w), 1641 (s), 1598 (s), 1443 (w), 1421 (w), 1376 (w), 1334
(m), 1310 (w), 1276 (s), 1255 (s), 1236 (s), 1197 (m), 1180 (m), 1105
(s), 1064 (w), 1034 (m), 762 (w), 675 (w) cm–1. MS (EI, 70 eV):
m/z (%) = 329 ([2×81Br], 2) [M]+, 327 ([81Br 79Br], 6) [M]+, 325
([2×79Br], 2) [M]+, 287 (9), 285 (20), 283 (10), 267 (4), 249 (10),
247 (10), 207 (16), 206 (12), 205 (18), 204 (11), 190 (17), 189 (19),
188 (36), 187 (17), 186 (18), 163 (18), 161 (20), 126 (19), 107 (100),
80 (52), 69 (11). The exact molecular mass, m/z (%)
=
324.9313 2 ppm [M]+, for C9H13Br2NO2 was confirmed by
HRMS (EI, 70 eV).
General Procedure for the Suzuki Reaction of 2-Alkylidene-tetra-
hydrofurans and 2-Alkylidene-pyrrolidines with Arylboronic Acids:
Potassium phosphate (K3PO4, 6 equiv.), the boronic acid Ar-
B(OH)2 (3 equiv.) and tetrakis(triphenylphosphane)palladium(0)
[Pd(PPh3)4] (0.03 equiv.) were added to a 1,4-dioxane solution
(3 mLmmol–1) of the starting material 3, 4 or 5 (1 equiv.) at 20 °C
under argon. The reaction mixture was stirred under reflux for 6 h,
and then cooled to 20 °C. Diethyl ether (10 mLmmol–1) was added,
and the resulting precipitate was filtered off and washed with di-
ethyl ether. After concentration of the filtrate in vacuo, the residue
was purified by chromatography (silica gel, n-hexane/EtOAc) to
give products 7, 8 and 9, or 10.
(KBr): ν = 3375 (br), 2990 (w), 2974 (w), 1639 (s), 1592 (s), 1473
˜
(w), 1464 (w), 1440 (m), 1422 (m), 1388 (w), 1367 (w), 1328 (m),
1317 (m), 1260 (s), 1231 (s), 1194 (m), 1182 (m), 1158 (w), 1093
(w), 1062 (s), 1043 (m), 1014 (w), 763 (m), 718 (w), 657 (w) cm–1.
MS (EI, 70 eV): m/z (%) = 315 ([2×81Br], 21) [M]+, 313 ([81Br 79Br],
47) [M]+, 311 ([2×79Br], 23) [M]+, 298 (8), 296 (8), 269 (8), 267
(14), 265 (6), 234 (15), 232 (15), 206 (21), 204 (26), 202 (4), 190
(55), 188 (100), 186 (51), 162 (4), 160 (15), 158 (11). The exact
molecular mass, m/z = 310.9157 2 ppm [M]+, for C8H11Br2NO2
was confirmed by HRMS (EI, 70 eV).
Methyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]2-phenylacetate (7a):
Starting with 3a (0.100 g, 0.45 mmol), phenylboronic acid (0.169 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 Ǟ 5:1) as a
slightly yellowish solid (0.077 g, 79%). 1H NMR (CDCl3,
300 MHz): δ = 2.13 (quint, J = 7.2 Hz, 2 H, CH2), 3.28 (t, J =
7.8 Hz, 2 H, CH2), 3.66 (s, 3 H, OCH3), 4.20 (t, J = 7.2 Hz, 2 H,
OCH2), 7.23–7.28 (m, 3 H, 3×CH of Ph), 7.32–7.37 (m, 2 H,
2×CH of Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ = 24.0, 31.6,
51.2, 72.1, 104.4, 126.6, 127.7, 130.5, 135.4, 168.7, 172.2 ppm. IR
Compounds 3k and 4k: Starting with Z-2k (0.550 g, 3.25 mmol) and
NBS (0.752 g, 4.23 mmol) in CCl4 (10 mL), 3k [0.603 g, 75%, (E)/
(Z) = 3:1] and 4k [0.206 g, 19%, (E)/(Z) = 10:3] were isolated after
chromatography (silica gel, n-hexane/EtOAc = 50:1 Ǟ 1:1) as
brownish solids.
Isopropyl 2-Bromo-2-(pyrrolidin-2-ylidene)acetate (3k): 1H NMR
(CDCl3, 300 MHz): (E) isomer: δ = 1.32 (d, J = 7.5 Hz, 6 H,
2×CH3), 2.02 (quint, J = 7.5 Hz, 2 H, CH2), 2.81 (t, J = 7.8 Hz,
(KBr): ν = 2955 (w), 1693 (s), 1616 (s), 1492 (w), 1437 (w), 1378
˜
2 H, CH2), 3.63 (t, J = 7.2 Hz, 2 H, CH2–NH), 5.01 (sept, J = (w), 1318 (w), 1299 (s), 1274 (m), 1256 (w), 1230 (m), 1185 (s), 1116
6.3 Hz, 1 H, CH), 8.12 (br. s, 1 H, NH) ppm; (Z) isomer: δ = 1.32 (w), 1076 (s), 1017 (w), 974 (m), 931 (m), 903 (w), 784 (m), 766
(d, J = 7.5 Hz, 6 H, 2×CH3), 2.17 (quint, J = 7.5 Hz, 2 H, CH2), (m), 702 (m) cm–1. MS (EI, 70 eV): m/z (%) = 218 (100) [M]+, 186
3.09 (t, J = 7.8 Hz, 2 H, CH2), 3.47 (t, J = 6.9 Hz, 2 H, CH2–NH), (80), 159 (3). The exact molecular mass, m/z = 218.0943 2 ppm
5.01 (sept, J = 6.3 Hz, 1 H, CH), 5.48 (br. s, 1 H, NH) ppm. 13C
[M]+, for C13H14O3 was confirmed by HRMS (EI, 70 eV).
Eur. J. Org. Chem. 2005, 4815–4828
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4823

E. Bellur, P. Langer
FULL PAPER
Methyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(p-tolyl)acetate (7b):
Starting with 3a (0.100 g, 0.45 mmol), 4-tolylboronic acid (0.191 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), 7b was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 5:1) as a
126.1, 127.1, 136.1, 168.2, 172.7 ppm. IR (neat):ν = 2952 (w), 1703
˜
(s), 1610 (s), 1435 (m), 1377 (w), 1281 (s), 1231 (m), 1212 (m), 1184
(s), 1148 (w), 1121 (w), 1073 (s), 1025 (w), 975 (w), 928 (w), 877
(w), 765 (m) cm–1. MS (EI, 70 eV): m/z (%) = 224 (100) [M]+, 192
(49), 164 (18). The exact molecular mass, m/z = 224.0507 2 ppm
[M]+, for C11H12O3S was confirmed by HRMS (EI, 70 eV).
1
yellowish solid (0.095 g, 91%). H NMR (CDCl3, 300 MHz): δ =
2.12 (quint, J = 7.5 Hz, 2 H, CH2), 2.35 (s, 3 H, CH3), 3.26 (t, J =
7.8 Hz, 2 H, CH2), 3.65 (s, 3 H, OCH3), 4.19 (t, J = 7.2 Hz, 2
H, OCH2), 7.12–7.16 (m, 4 H, 4×CH) ppm. 13C NMR (CDCl3,
75 MHz): δ = 21.1, 23.9, 31.4, 51.0, 72.0, 104.1, 128.4, 130.2, 132.3,
tert-Butyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-phenylacetate (7f):
Starting with 3d (0.150 g, 0.57 mmol), phenylboronic acid (0.209 g,
1.71 mmol), K3PO4 (0.726 g, 3.42 mmol) and Pd(PPh3)4 (0.20 g,
0.017 mmol) in 1,4-dioxane (5 mL), 7f was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 30:1) as a
slightly yellowish oil (0.128 g, 87%). 1H NMR (CDCl3, 300 MHz):
δ = 1.44 (s, 9 H, OtBu), 2.11 (quint, J = 7.2 Hz, 2 H, CH2), 3.21
(t, J = 7.8 Hz, 2 H, CH2), 4.17 (t, J = 6.9 Hz, 2 H, OCH2), 7.20–
7.34 (m, 5 H, 5×CH of Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ =
24.4, 28.5, 31.7, 71.9, 79.8, 106.4, 126.4, 127.6, 130.6, 136.2, 167.9,
136.0, 168.7, 172.1 ppm. IR (KBr): ν = 2990 (w), 1699 (s), 1614 (s),
˜
1514 (w), 1436 (w), 1301 (m), 1274 (w), 1252 (w), 1184 (s), 1074
(s), 981 (w), 931 (w), 818 (w) cm–1. MS (EI, 70 eV): m/z (%) = 232
(100) [M]+, 200 (73), 173 (6), 159 (9). C14H16O3 (232.279): calcd. C
72.39, H 6.94; found C 73.04, H 7.09.
Methyl
2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(4-methoxyphenyl)-
170.7 ppm. IR (neat): ν = 3079 (w), 2974 (m), 2921 (w), 2907 (w),
˜
acetate (7c): Starting with 3a (0.100 g, 0.45 mmol), 4-methoxyphen-
ylboronic acid (0.213 g, 1.36 mmol), K3PO4 (0.575 g, 2.71 mmol)
and Pd(PPh3)4 (0.016 g, 0.015 mmol) in 1,4-dioxane (5 mL), 7c was
isolated after chromatography (silica gel, n-hexane/EtOAc = 100:1
Ǟ 1:1) as a slightly yellowish oil (0.102 g, 91%). 1H NMR (CDCl3,
300 MHz): δ = 2.13 (quint, J = 7.2 Hz, 2 H, CH2), 3.26 (t, J =
7.8 Hz, 2 H, CH2), 3.66 (s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 4.20
(t, J = 7.2 Hz, 2 H, OCH2), 6.89 (d, J = 11.7 Hz, 2 H, 2×CH), 7.17
(d, J = 9.0 Hz, 2 H, 2×CH) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 24.0, 31.5, 51.2, 55.0, 72.0, 103.7, 113.2, 127.5, 131.4, 158.0,
1687 (s), 1608 (s), 1492 (m), 1474 (m), 1452 (m), 1420 (w), 1384
(m), 1368 (m), 1321 (m), 1301 (m), 1269 (m), 1251 (m), 1231 (m),
1157 (s), 1113 (m), 1063 (s), 1038 (s), 956 (m), 930 (m), 880 (w),
839 (m), 812 (m), 778 (m), 756 (m), 697 (m), 654 (w), 508 (w) cm–1.
MS (EI, 70 eV): m/z (%) = 260 (23) [M]+, 203 (100), 186 (79), 169
(4), 157 (1). The exact molecular mass, m/z = 260.1412 2 ppm
[M]+, for C16H20O3 was confirmed by HRMS (EI, 70 eV).
tert-Butyl
2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(p-tolyl)acetate
(7g): Starting with 3d (0.100 g, 0.38 mmol), tolylboronic acid
(0.160 g, 1.14 mmol), K3PO4 (0.484 g, 2.28 mmol) and Pd(PPh3)4
(0.013 g, 0.014 mmol) in 1,4-dioxane (3 mL), 7g was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 30:1) as
a yellowish solid (0.091 g, 88%). M.p. 56 °C. 1H NMR (CDCl3,
300 MHz): δ = 1.45 (s, 9 H, OtBu), 1.97 (quint, J = 6.6 Hz, 2 H,
CH2), 2.09 (s, 3 H, CH3), 3.20 (t, J = 7.8 Hz, 2 H, CH2), 4.17 (t, J
= 6.9 Hz, 2 H, OCH2), 7.12–7.17 (m, 4 H, 4×CH) ppm. 13C NMR
(CDCl3, 150 MHz): δ = 23.0, 24.4, 28.5, 30.4, 72.0, 79.8, 106.3,
169.1, 172.3 ppm. IR (neat): ν = 2992 (w), 2951 (m), 2904 (w), 2837
˜
(w), 1700 (s), 1613 (s), 1511 (s), 1460 (m), 1438 (m), 1376 (w), 1317
(m), 1300 (m), 1275 (m), 1241 (s), 1184 (s), 1105 (w), 1074 (s), 1035
(m), 981 (m), 934 (w), 831 (m), 800 (w), 775 (w), 734 (w), 593 (w),
533 (w) cm–1. MS (EI, 70 eV): m/z (%) = 248 (100) [M]+, 232 (35),
216 (50), 200 (28), 188 (28), 173 (4), 159 (16). C14H16O4 (248.278):
calcd. C 67.73, H 6.50; found C 67.99, H 7.11.
Methyl 2-(4-Chlorophenyl)-2-[4,5-dihydrofuran-2(3H)-ylidene]ace-
tate (7d): Starting with 3a (0.100 g, 0.45 mmol), 4-chlorophenylbo-
ronic acid (0.219 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), 7d was iso-
lated after chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ
5:1) as a slightly yellowish solid (0.105 g, 92%). 1H NMR (CDCl3,
300 MHz): δ = 2.14 (quint, J = 7.5 Hz, 2 H, CH2), 3.27 (t, J =
7.8 Hz, 2 H, CH2), 3.66 (s, 3 H, OCH3), 4.22 (t, J = 7.2 Hz, 2 H,
OCH2), 7.19 (d, J = 10.8 Hz, 2 H, 2×CH), 7.30 (d, J = 13.5 Hz, 2
H, 2×CH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 23.9, 31.6, 51.2,
72.3, 103.2, 127.8, 132.2, 133.8, 155.0, 168.4, 172.8 ppm. IR (KBr):
128.4, 130.5, 133.1, 135.9, 168.1, 170.4 ppm. IR (neat): ν = 2977
˜
(m), 2936 (m), 2865 (w), 1693 (s), 1616 (s), 1515 (m), 1453 (m),
1428 (w), 1368 (m), 1320 (m), 1300 (m), 1251 (w), 1231 (w), 1162
(s), 1113 (w), 1067 (s), 1038 (w), 1017 (w), 960 (w), 934 (w), 822
(w), 806 (w) cm–1. MS (EI, 70 eV): m/z (%) = 274 (22) [M]+, 218
(100), 200 (61), 184 (4), 172 (4), 159 (5). The exact molecular mass,
m/z = 274.1569 2 ppm [M]+, for C17H22O3 was confirmed by
HRMS (EI, 70 eV).
tert-Butyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(4-methoxyphenyl)-
acetate (7h): Starting with 3d (0.100 g, 0.38 mmol), 4-methoxy-
phenylboronic acid (0.179 g, 1.14 mmol), K3PO4 (0.484 g,
2.28 mmol) and Pd(PPh3)4 (0.013 g, 0.014 mmol) in 1,4-dioxane
(3 mL), 7h was isolated after chromatography (silica gel, n-hexane/
EtOAc = 100:1 Ǟ 10:1) as a slightly yellowish solid (0.085 g, 77%).
1H NMR (CDCl3, 300 MHz): δ = 1.45 (s, 9 H, OtBu), 2.10 (quint,
J = 7.2 Hz, 2 H, CH2), 3.19 (t, J = 7.8 Hz, 2 H, CH2), 3.80 (s, 3
H, OCH3), 4.17 (t, J = 7.2 Hz, 2 H, OCH2), 6.86 (d, J = 6.6 Hz, 2
H, 2×CH), 7.19 (d, J = 6.9 Hz, 2 H, 2×CH) ppm. 13C NMR
(CDCl3, 150 MHz): δ = 24.5, 28.6, 31.8, 55.3, 71.9, 79.8, 105.9,
ν = 2951 (w), 1704 (s), 1614 (s), 1492 (m), 1436 (w), 1378 (w), 1310
˜
(m), 1277 (w), 1256 (w), 1227 (w), 1187 (s), 1073 (s), 1014 (w), 981
(m), 933 (w), 829 (m), 783 (w) cm–1. MS (EI, 70 eV): m/z (%) = 254
([37Cl], 31) [M]+, 252 ([35Cl], 100) [M]+, 223 (9), 222 (31), 221 (32),
220 (98), 193 (5), 191 (3), 189 (4), 181 (5), 179 (17), 139 (24), 137
(28), 129 (51), 125 (10), 123 (15), 101 (88). C13H13ClO3 (252.697):
calcd. C 61.79, H 5.19; found C 61.84, H 5.69.
Methyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(thiophen-2-yl)acetate
(7e): Starting with 3a (0.100 g, 0.45 mmol), 2-thienylboronic acid
(0.179 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), 7e was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 5:1) as a
yellowish oil (0.063 g, 62%). M.p. 80 °C. 1H NMR (CDCl3,
300 MHz): δ = 2.16 (quint, J = 7.2 Hz, 2 H, CH2), 3.26 (t, J =
7.8 Hz, 2 H, CH2), 3.74 (s, 3 H, OCH3), 4.34 (t, J = 7.2 Hz, 2 H,
OCH2), 7.01 (dd, J = 3.6, 1.2 Hz, 1 H, CH), 7.12 (dd, J = 3.6,
1.2 Hz, 1 H, CH), 7.27 (dd, J = 3.6, 1.2 Hz, 1 H, CH) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 24.0, 32.2, 51.4, 72.7, 98.2, 124.6,
113.2, 128.6, 131.7, 158.0, 168.1, 170.3 ppm. IR (KBr): ν = 2982
˜
(w), 2934 (w), 2906 (w), 1686 (s), 1612 (s), 1511 (s), 1457 (w), 1370
(m), 1316 (m), 1281 (m), 1240 (s), 1178 (s), 1160 (s), 1109 (w), 1066
(s), 1038 (m), 1016 (w), 959 (w), 935 (w), 838 (w), 806 (w), 783 (w),
593 (w), 537 (w) cm–1. MS (EI, 70 eV): m/z (%) = 290 (27) [M]+,
234 (100), 216 (36), 200 (6), 188 (19), 159 (5). The exact molecular
mass, m/z = 290.1518 2 ppm [M]+, for C17H22O4 was confirmed
by HRMS (EI, 70 eV).
tert-Butyl
2-(4-Chlorophenyl)-2-[4,5-dihydrofuran-2(3H)-ylid-
ene]acetate (7i): Starting with 3d (0.100 g, 0.38 mmol), 4-chloro-
4824
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4815–4828

Synthesis of Functionalized Alkylidene-tetrahydrofurans
FULL PAPER
phenylboronic acid (0.184 g, 1.14 mmol), K3PO4 (0.484 g,
2.28 mmol) and Pd(PPh3)4 (0.013 g, 0.014 mmol) in 1,4-dioxane
(3 mL), 7i was isolated after chromatography (silica gel, n-hexane/
EtOAc = 100:1 Ǟ 30:1) as a slightly yellowish solid (0.097 g, 87%).
176 (40), 161 (5), 93 (6), 77 (20). The exact molecular mass, m/z =
220.0736 2 ppm [M]+, for C12H12O4 was confirmed by HRMS
(EI, 70 eV).
Isopropyl 2-(4-Chlorophenyl)-2-(pyrrolidin-2-ylidene)acetate (7l):
Starting with 3k (0.150 g, 0.605 mmol), 4-chlorophenylboronic acid
(0.292 g, 1.81 mmol), K3PO4 (0.771 g, 3.63 mmol) and Pd(PPh3)4
(0.021 g, 0.061 mmol) in 1,4-dioxane (5 mL), 7l was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 5:1) as a
brownish oil (0.147 g, 87%). 1H NMR (CDCl3, 300 MHz): δ = 1.23
(d, J = 6.3 Hz, 6 H, 2×CH3), 1.97 (quint, J = 7.5 Hz, 2 H, CH2),
2.57 (t, J = 7.8 Hz, 2 H, CH2), 3.44 (t, J = 7.2 Hz, 2 H, CH2NH),
5.00 (sept, J = 6.3 Hz, 1 H, CH), 6.77 (d, J = 6.9 Hz, 2 H, 2×CH),
7.17 (J = 6.6 Hz, 2 H, 2×CH), 7.87 (br. s, 1 H, NH) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 22.2, 22.3, 32.3, 47.1, 65.4, 80.2,
1
M.p. 75 °C. H NMR (CDCl3, 300 MHz): δ = 1.44 (s, 9 H, OtBu),
2.11 (quint, J = 7.5 Hz, 2 H, CH2), 3.21 (t, J = 7.8 Hz, 2 H, CH2),
4.18 (t, J = 7.2 Hz, 2 H, OCH2), 7.19 (d, J = 6.6 Hz, 2 H, 2×CH),
7.27 (d, J = 8.4 Hz, 2 H, 2×CH) ppm. 13C NMR (CDCl3,
150 MHz): δ = 24.4, 28.5, 31.9, 72.2, 80.2, 105.3, 127.9, 132.1,
132.4, 134.7, 167.6, 171.1 ppm. IR (KBr): ν = 2972 (m), 1693 (s),
˜
1623 (s), 1491 (m), 1391 (w), 1369 (m), 1313 (m), 1257 (m), 1232
(w), 1162 (s), 1071 (s), 1037 (m), 1015 (m), 959 (w), 932 (w), 838
(m), 805 (m) cm–1. MS (EI, 70 eV): m/z (%) = 296 ([37Cl], 6) [M]+,
294 ([35Cl], 18) [M]+, 240 (34), 238 (100), 223 (6), 222 (23), 221
(23), 220 (68), 204 (6), 192 (2), 181 (2), 179 (2), 151 (16), 139 (10),
116.7, 125.1, 129.4, 154.7, 166.6, 170.6 ppm. IR (neat): ν = 3374
˜
137 (15), 129 (20). The exact molecular mass, m/z
=
(br), 2980 (s), 2936 (m), 2874 (w), 1731 (m), 1666 (s), 1605 (s), 1592
(s), 1489 (s), 1449 (m), 1438 (m), 1369 (s), 1340 (m), 1262 (s), 1222
(s), 1180 (m), 1163 (m), 1139 (m), 1105 (s), 1053 (m), 1002 (w), 081
(w), 829 (m), 773 (w), 661 (w), 641 (w), 507 (w).
294.1023 2 ppm [M]+, for C16H19ClO3 was confirmed by HRMS
(EI, 70 eV).
tert-Butyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(thiophen-2-yl)ace-
tate (7j): Starting with 3d (0.100 g, 0.38 mmol), 2-thienylboronic
acid (0.150 g, 1.14 mmol), K3PO4 (0.484 g, 2.28 mmol) and
Pd(PPh3)4 (0.013 g, 0.014 mmol) in 1,4-dioxane (3 mL), 7j was iso-
lated after chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ
30:1) as a yellowish solid (1:1 mixture of 7j/3d, calcd. yield of 7j:
Compounds 8a and 9a: Starting with E-4a (0.300 g, 1.0 mmol),
phenylboronic acid (0.374 g, 3.0 mmol), K3PO4 (1.273 g, 6.0 mmol)
and Pd(PPh3)4 (0.035 g, 0.030 mmol) in 1,4-dioxane (5 mL), 8a
(0.045 g, 21%) and 9a (0.120 g, 41%) were isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 10:1) as a
colorless oil and a slightly yellowish solid, respectively.
1
0.048 g, 48%). M.p. 99 °C. H NMR (CDCl3, 300 MHz): δ = 1.51
(s, 9 H, OtBu), 2.13 (quint, J = 7.5 Hz, 2 H, CH2), 3.13 (t, J =
7.8 Hz, 2 H, CH2), 4.32 (t, J = 6.9 Hz, 2 H, OCH2), 6.98 (t, J =
4.5 Hz, 1 H, CH), 7.21 (s, 1 H, CH), 7.22 (d, J = 4.2 Hz, 1 H,
CH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 25.0, 28.3, 32.3, 72.4,
80.6, 100.5, 124.0, 125.7, 126.6, 136.7, 167.0, 170.0 ppm. IR (neat):
Methyl 2-(Furan-2-yl)-2-phenylacetate (8a): 1H NMR (CDCl3,
300 MHz): δ = 3.74 (s, 3 H, OCH3), 5.03 (s, 1 H, CH), 6.19 (dd, J
= 4.2, 0.75 Hz, 1 H, CH), 6.32 (dd, J = 3.3, 1.8 Hz, 1 H, CH),
7.29–7.38 (m, 6 H, 5×CH of Ph, CH) ppm. 13C NMR (CDCl3,
75 MHz): δ = 51.3, 52.6, 108.1, 110.3, 127.8, 128.5, 128.7, 136.0,
ν = 2977 (m), 1695 (s), 1613 (m), 1454 (w), 1370 (m), 1297 (m),
˜
142.3, 151.6, 171.0 ppm. IR (neat): ν = 2992 (w), 2961 (w), 2936
˜
1253 (w), 1237 (w), 1208 (w), 1173 (s), 1151 (s), 1118 (m), 1070 (s),
1041 (w) cm–1. MS (EI, eV): m/z (%) = 266 (24) [M]+, 210 (100),
193 (16), 176 (8), 164 (25). The exact molecular mass, m/z =
266.0977 2 ppm [M]+, for C14H18O3S was confirmed by HRMS
(EI, 70 eV).
(w), 2912 (w), 2839 (w), 1736 (s), 1646 (w), 1612 (m), 1586 (w),
1513 (s), 1463 (m), 1447 (w), 1392 (w), 1369 (w), 1325 (w), 1301
(m), 1249 (s), 1201 (m), 1177 (s), 1155 (s), 1100 (m), 1075 (w), 1033
(s), 932 (w), 880 (w), 822 (m), 742 (w), 532 (w) cm–1. MS (EI,
70 eV): m/z (%) = 216 (19) [M]+, 187 (3), 157 (100), 102 (4), 77
(7). The exact molecular mass, m/z = 216.0786 2 ppm [M]+, for
C13H12O3 was confirmed by HRMS (EI, 70 eV).
2-[4,5-Dihydrofuran-2(3H)-ylidene]-2-(4-hydroxyphenyl)acetic Acid
(7k): BBr3 (0.525 g, 2.1 mmol) was added to a CH2Cl2 solution
(5 mL) of 7c (0.130 g, 0.5 mmol) at 0 °C. The reaction mixture was
allowed to warm to 20 °C over 12 h and was then stirred at this
temperature for 6 h. Methanol (5 mL) was slowly added to the re-
action mixture and the solvents were removed in vacuo. An aque-
ous solution of KOH (0.069 g, 1.25 mmol in 7 mL H2O) was added
to a THF solution (7 mL) of the residue at 20 °C. The reaction
mixture was refluxed for 4 h and cooled to 20 °C. An aqueous solu-
tion of HCl (10%, 10 mL) was added to the reaction mixture and
the latter was extracted first with diethyl ether and then with
dichloromethane. The combined organic layers were dried with
Na2SO4, filtered and the filtrate was concentrated in vacuo. The
residue was purified by chromatography (silica gel, n-hexane/
EtOAc = 3:1 Ǟ 1:1) to give 7k as a slightly yellowish solid (0.088 g,
80%). 1H NMR (CDCl3/[D6]DMSO = 5:1, 300 MHz): δ = 2.10
(quint, J = 7.5 Hz, 2 H, CH2), 3.21 (t, J = 7.8 Hz, 2 H, CH2), 4.17
(t, J = 7.2 Hz, 2 H, OCH2), 6.79 (d, J = 8.7 Hz, 2 H, 2×CH), 7.10
(d, J = 8.7 Hz, 2 H, 2×CH), 8.45 (s, 1 H, OH), 11.25 (br. s, 1 H,
O=C–OH) ppm. 13C NMR (CDCl3/[D6]DMSO = 1:1, 75 MHz): δ
= 23.1, 30.5, 70.7, 103.3, 113.6, 125.3, 130.5, 154.7, 170.2,
Methyl 2-Phenyl-2-[3-phenyl-4,5-dihydrofuran-2(3H)-ylidene]acetate
1
(9a): H NMR (CDCl3, 300 MHz): δ = 2.08–2.13 (m, 1 H, CH2),
2.49–2.63 (m, 1 H, CH2), 3.48 (s, 3 H, OCH3), 4.16–4.25 (m, 1 H,
OCH2), 4.31 (dt, J = 1.8, 8.7 Hz, 1 H, OCH2), 5.12 (dd, J = 1.2,
8.7 Hz, 1 H, CH–Ph), 7.22–7.41 (m, 10 H, 10×CH of 2×Ph) ppm.
13C NMR (CDCl3, 75 MHz): δ = 34.1, 48.1, 51.1, 69.9, 106.0,
126.5, 126.76, 126.79, 127.8, 128.6, 130.4, 135.4, 142.0, 167.6,
172.5 ppm. IR (KBr): ν = 3026 (w), 2995 (w), 2951 (w), 2901 (w),
˜
1703 (s), 1622 (s), 1603 (w), 1495 (w), 1450 (w), 1432 (w), 1376 (w),
1317 (w), 1299 (m), 1273 (w), 1254 (w), 1238 (w), 1201 (m), 1173
(s), 1075 (s), 1064 (s), 1029 (w), 1014 (w), 976 (m), 930 (w), 785
(m), 756 (w), 734 (w), 700 (m), 540 (w) cm–1. MS (EI, 70 eV): m/z
(%) = 294 (82) [M]+, 279 (12), 262 (100), 247 (18), 235 (4), 216 (13),
139 (19), 77 (68). The exact molecular mass, m/z
=
294.1256 2 ppm [M]+, for C19H18O3 was confirmed by HRMS
(EI, 70 eV).
Ethyl
(4-Methoxyphenyl)[3-(4-methoxyphenyl)-4,5-dihydrofuran-
2(3H)-ylidene]acetate (9b): Starting with Z-4b (0.250 g,
170.2 ppm. IR (KBr): ν = 3389 (br), 3138 (w), 3059 (w), 3018 (w),
0.796 mmol), 4-methoxyphenylboronic acid (0.749 g, 4.78 mmol),
˜
2958 (m), 2912 (m), 2855 (w), 2830 (w), 2724 (w), 2632 (w), 2612 K3PO4 (0.015 g, 4.78 mmol) and Pd(PPh3)4 (0.046 g, 0.040 mmol)
(w), 2559 (w), 1700 (m), 1674 (m), 1638 (s), 1608 (s), 1591 (s), 1516
(s), 1440 (m), 1375 (m), 1319 (s), 1237 (s), 1189 (s), 1102 (w), 1073
in 1,4-dioxane (5 mL), 9b was isolated after chromatography (silica
gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a slightly yellowish oil
(s), 1025 (w), 955 (w), 931 (m), 829 (m), 769 (w), 597 (w), 531 (w), (0.184 g, 66%). 1H NMR (CDCl3, 300 MHz): δ = 1.03 (t, J =
467 (w) cm–1. MS (EI, 70 eV): m/z (%) = 220 (100) [M]+, 202 (37),
7.2 Hz, 3 H, CH3), 2.02–2.08 (m, 1 H, CH2), 2.45–2.58 (m, 1 H,
Eur. J. Org. Chem. 2005, 4815–4828
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4825

E. Bellur, P. Langer
FULL PAPER
1
CH2), 3.79 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3), 3.93–4.01 (dq, J 100:1 Ǟ 1:1) as a slightly yellowish oil (0.170 g, 76%). H NMR
= 7.2, 3.0 Hz, 2 H, OCH2CH3), 4.11–4.21 (m, 1 H, OCH2), 4.26–
(CDCl3, 300 MHz): δ = 1.08 (t, J = 7.2 Hz, 3 H, CH3), 1.28 (t, J
4.32 (dt, J = 8.4, 1.8 Hz, 1 H, OCH2), 5.04 (d, J = 7.8 Hz, 1 H, = 7.2 Hz, 3 H, CH3), 2.00 (ddt, J = 12.4, 5.7, 1.3 Hz, 2 H, CH2),
CH), 6.85–6.93 (m, 2 H, 2×CH), 7.17–7.20 (m, 1 H, CH), 7.24–
7.28 (m, 1 H, CH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 14.1,
34.3, 47.2, 55.05, 55.14, 59.8, 69.7, 105.8, 113.2, 113.9, 127.7, 127.9,
2.42 (q, J = 7.2 Hz, 2 H, CH2), 4.09–4.24 (m, 3 H, 2×OCH2), 4.34
(dt, J = 8.7, 1.4 Hz, 1 H, OCH2), 4.86 (d, J = 8.3 Hz, 1 H, CH–
Ar), 7.09 (d, J = 8.4 Hz, 2 H, 2×CH of Ar), 7.26 (d, J = 8.4 Hz,
2 H, 2×CH of Ar) ppm. 13C NMR (CDCl3, 50 MHz): δ = 13.6,
131.5, 134.0, 158.05, 158.10, 167.5, 172.0 ppm. IR (neat): ν = 3033
˜
(w), 2983 (m), 2937 (m), 2908 (m), 2937 (w), 1734 (w), 1695 (s), 14.1, 19.6, 34.3, 46.9, 59.3, 68.8, 106.6, 128.1 (2 C), 128.7 (2 C),
1609 (s), 1512 (s), 1462 (m), 1447 (m), 1371 (m), 1278 (s), 1245 (s), 129.3, 140.9, 169.9 ppm. IR (neat): ν = 2975 (s), 2934 (m), 2902
˜
1219 (s), 1175 (s), 1069 (s), 1033 (m), 956 (w), 933 (w), 879 (w), (m), 2875 (w), 1737 (m), 1694 (s), 1635 (s), 1489 (m), 1454 (m),
832 (m), 809 (w), 789 (w), 760 (w), 735 (w), 591 (w), 543 (w) cm–1. 1400 (w), 1371 (m), 1310 (m), 1254 (s), 1215 (m), 1174 (s), 1099 (s),
MS (EI, 70 eV): m/z (%) = 368 (69) [M]+, 322 (100), 307 (29), 295
1068 (m), 1036 (m), 1023 (m), 991 (w), 948 (w), 882 (w), 828 (w),
(16), 278 (38), 262 (10), 232 (12). The exact molecular mass, m/z = 781 (w) cm–1. MS (EI, 70 eV): m/z (%) = 296 ([37Cl], 12) [M]+, 294
368.1624 2 ppm [M]+, for C22H24O5 was confirmed by HRMS
(EI, 70 eV).
([35Cl], 77) [M]+, 250 (18), 249 (34), 248 (100), 247 (81), 235 (6),
233 (35), 223 (15), 221 (18), 213 (64), 205 (20), 183 (3), 181 (17),
150 (4), 148 (37), 141 (10), 139 (9), 114 (25), 70 (42). C16H19ClO3
(294.777): calcd. C 65.19, H 6.50; found C 64.50, H 6.33.
1,2-Diphenyl-2-[3-phenyl-4,5-dihydrofuran-2(3H)-ylidene]ethanone
(9c): Starting with 4e (0.150 g, 0.434 mmol), phenylboronic acid
(0.159 g, 1.302 mmol), K3PO4 (0.553 g, 2.60 mmol) and Pd(PPh3)4
(0.015 g, 0.013 mmol) in 1,4-dioxane (5 mL), 9c was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a
3-Phenyl-4,4Ј,5,5Ј-tetrahydro-2,3Ј-bifuranyliden-2Ј-one (10c): Start-
ing with 5h (0.100 g, 0.43 mmol), phenylboronic acid (0.157 g,
1.29 mmol), K3PO4 (0.547 g, 2.57 mmol) and Pd(PPh3)4 (0.015 g,
0.013 mmol) in 1,4-dioxane (5 mL), 10c was isolated after
1
yellowish solid (0.091 g, 62%). H NMR (CDCl3, 300 MHz): δ =
2.09–2.17 (m, 1 H, CH2), 2.54–2.66 (m, 1 H, CH2), 4.36–4.41 (dd, chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 3:1) as a
1
J = 9.0, 4.8 Hz, 2 H, OCH2), 4.77–4.81 (dd, J = 8.4, 3.3 Hz, 1 H,
CH–Ph), 7.07–7.45 (m, 15 H, 15×CH of Ph) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 29.7, 47.7, 70.3, 113.8, 126.4, 126.5, 127.3,
127.6, 128.1, 128.5, 129.3, 129.9, 131.1, 136.8, 139.3, 141.8, 169.1,
yellowish solid (0.054 g, 55%). H NMR (CDCl3, 300 MHz): δ =
2.11–2.18 (m, 1 H, CH2), 2.46–2.60 (m, 1 H, CH2), 2.97 (t, J =
7.8 Hz, 2 H, CH2), 4.29 (t, J = 7.8 Hz, 2 H, OCH2), 4.32–4.37 (m,
1 H, OCH2), 4.45 (dt, J = 9.0, 1.5 Hz, 1 H, OCH2), 4.97 (d, J =
8.4 Hz, 1 H, CH), 7.18–7.32 (m, 5 H, 5×CH of Ph) ppm. 13C
195.8 ppm. IR (KBr): ν = 3055 (w), 3026 (w), 2982 (w), 2957 (w),
˜
2922 (w), 2896 (w), 2852 (w), 1648 (s), 1598 (m), 1577 (w), 1553 NMR (CDCl3, 75 MHz): δ = 25.2, 33.7, 45.7, 65.0, 70.6, 94.6,
(s), 1493 (w), 1448 (w), 1320 (w), 1291 (m), 1271 (w), 1203 (m), 126.7, 126.9 (2 C), 128.6 (2 C), 141.1, 170.5, 171.8 ppm. IR (KBr):
1174 (s), 1113 (w), 1023 (w), 968 (s), 930 (m), 889 (s), 765 (w), 748 ν = 2999 (w), 2981 (w), 2913 (w), 1736 (s), 1675 (s), 1497 (w), 1482
˜
(w), 720 (w), 699 (s) cm–1. MS (EI, 70 eV): m/z = 340 (100) [M]+,
(w), 1449 (w), 1370 (m), 1312 (w), 1253 (s), 1224 (m), 1191 (m),
1173 (m), 1028 (s), 990 (m), 942 (w), 758 (m), 702 (m) cm–1. MS
(EI, 70 eV): m/z (%) = 230 (100) [M]+. HRMS (FTICR): calcd. for
C14H14O3 ([M + 1]+): 231.10212; found 231.10148.
263 (12), 235 (36). The exact molecular mass, m/z
=
340.1463 2 ppm [M]+, for C24H20O2 was confirmed by HRMS
(EI, 70 eV).
Ethyl 2-[3-(4-Chlorophenyl)-4,5-dihydrofuran-2(3H)-ylidene]propion- General Procedure for the Heck Reaction of 2-Alkylidene-tetra-
ate (10a): Starting with 5f (0.200 g, 0.80 mmol), 4-chlorophenyl- hydrofurans: Triethylamine (NEt3, 2 equiv.), the alkene (2 equiv.)
boronic acid (0.377 g, 2.41 mmol), K3PO4 (1.023 g, 4.82 mmol) and tetrakis(triphenylphosphane)palladium(0) [Pd(PPh3)4]
and Pd(PPh3)4 (0.028 g, 0.024 mmol) in 1,4-dioxane (10 mL), 10a (0.03 equiv.) were added to a DMF solution (5 mLmmol–1) of 3
was isolated after chromatography (silica gel, n-hexane/EtOAc =
100:1 Ǟ 3:1) as a slightly yellowish solid (0.117 g, 52%). H NMR
(1 equiv.) at 20 °C. The reaction mixture was heated and stirred at
100 °C for 25 h. The reaction mixture was allowed to cool to 20 °C
1
(CDCl3, 300 MHz): δ = 1.08 (t, J = 7.2 Hz, 3 H, CH3), 1.92 (d, J and then poured into diethyl ether. The mixture was washed several
= 0.6 Hz, 3 H, CH3), 2.01 (ddt, J = 12.4, 5.7, 1.2 Hz, 1 H, CH2), times with water and the combined aqueous layers were extracted
2.43–2.57 (m, 1 H, CH2), 3.98 (q, J = 7.2 Hz, 2 H, OCH2), 4.11–
4.21 (m, 1 H, OCH2), 4.35 (dt, J = 8.5, 1.2 Hz, 1 H, OCH2), 4.86
(d, J = 8.5 Hz, 1 H, CH), 7.10 (dd, J = 6.6, 1.8 Hz, 2 H, 2×CH
of Ar), 7.26 (dd, J = 6.6, 1.8 Hz, 2 H, 2×CH of Ar) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 11.5, 14.2, 34.4, 47.0, 59.6, 68.8, 99.8,
128.3 (2 C), 128.6 (2 C), 132.0, 140.9, 168.2, 170.1 ppm. IR (neat):
with diethyl ether. The combined organic layers were dried
(Na2SO4), filtered and the filtrate was concentrated in vacuo. The
residue was purified by chromatography (silica gel, n-hexane/
EtOAc) to give the products 11.
1-tert-Butyl 5-Methyl 4-[4,5-Dihydrofuran-2(3H)-ylidene]pent-2-
enedioate (11a): Starting with 3a (0.050 g, 0.226 mmol), tert-butyl
acrylate (0.05 mL, 0.34 mmol), NEt3 (0.06 mL, 0.45 mmol),
Pd(PPh3)4 (0.008 g, 0.007 mmol) in DMF (3 mL), 11a was isolated
after chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1)
ν = 2982 (w), 2930 (w), 1737 (w), 1696 (s), 1641 (s), 1488 (w), 1452
˜
(w), 1399 (w), 1390 (w), 1371 (w), 1289 (m), 1251 (w), 1216 (w),
1172 (m), 1089 (s), 1020 (w), 976 (w) cm–1. MS (EI, 70 eV): m/z
(%) = 282 ([37Cl], 27) [M]+, 280 ([35Cl], 100) [M]+, 236 (19), 235
(38), 234 (61), 233 (13), 219 (6), 209 (18), 208 (5), 207 (43), 205
(23), 199 (89), 181 (5), 179 (6), 172 (23), 170 (15), 151 (17), 141
1
as a yellowish oil (0.052 g, 85%). H NMR (CDCl3, 300 MHz): δ
= 1.50 (s, 9 H, OtBu), 2.14 (quint, J = 7.5 Hz, 2 H, CH2), 3.25 (t,
J = 7.8 Hz, 2 H, CH2), 3.76 (s, 3 H, OCH3), 4.44 (t, J = 7.2 Hz, 2
H, OCH2), 6.41 (d, J = 16.2 Hz, 1 H, CH), 7.70 (d, J = 16.2 Hz, 1
H, CH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 23.4, 28.2, 33.2,
51.3, 73.6, 79.6, 101.0, 119.1, 136.2, 167.8, 167.9, 177.8 ppm. IR
(18), 139 (16), 128 (38), 117 (21), 116 (20), 114 (48), 83 (36). HRMS
+
(ESI): calcd. for C15H17ClO3 ([M
1]+): 283.09150 (37Cl),
281.09445 (35Cl); found 283.09119 (37Cl), 281.09405 (35Cl).
Ethyl 2-[3-(4-Chlorophenyl)-4,5-dihydrofuran-2(3H)-ylidene]butyr-
ate (10b): Starting with 5g (0.200 g, 0.76 mmol), 4-chlorophenyl-
(neat): ν = 2978 (m), 2934 (w), 1727 (s), 1711 (s), 1641 (w), 1622
(m), 1583 (m), 1477 (w), 1455 (m), 1440 (m), 1389 (m), 1369 (m),
˜
boronic acid (0.368 g, 2.28 mmol), K3PO4 (0.968 g, 4.56 mmol) 1333 (w), 1305 (m), 1255 (s), 1242 (m), 1151 (s), 1124 (s), 1076 (m),
and Pd(PPh3)4 (0.026 g, 0.023 mmol) in 1,4-dioxane (10 mL), 10b 1052 (w), 993 (w), 976 (w), 847 (w) cm–1. MS (EI, 70 eV): m/z (%)
was isolated after chromatography (silica gel, n-hexane/EtOAc =
= 268 (5) [M]+, 237 (6), 212 (44), 195 (26), 180 (100). The exact
4826
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 4815–4828

Synthesis of Functionalized Alkylidene-tetrahydrofurans
FULL PAPER
molecular mass, m/z = 268.1311 2 ppm [M]+, for C14H20O5 was
confirmed by HRMS (EI, 70 eV).
= 7.2 Hz, 2 H, OCH2CH3), 4.44 (t, J = 7.2 Hz, 2 H, OCH2), 6.43
(d, J = 16.1 Hz, 1 H, CH=CH), 7.70 (d, J = 16.1 Hz, 1 H,
CH=CH) ppm. 13C NMR (CDCl3, 75 MHz): δ = 14.4, 23.5, 28.2,
33.2, 60.2, 73.5, 79.5, 101.2, 119.1, 136.3, 167.3, 167.9, 177.5 ppm.
Methyl
4-Cyano-2-[4,5-dihydrofuran-2(3H)-ylidene]but-3-enoate
(11b): Starting with 3a (0.150 g, 0.68 mmol), acrylonitrile (0.09 mL,
1.36 mmol), NEt3 (0.19 mL, 1.36 mmol) and Pd(PPh3)4 (0.039 g,
0.034 mmol) in DMF (3 mL), 11b was isolated after chromatog-
raphy (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a yellowish oil
IR (neat): ν = 2978 (s), 2934 (m), 2872 (m), 1728 (s), 1640 (m),
˜
1623 (m), 1583 (w), 1477 (w), 1454 (m), 1423 (w), 1390 (m), 1370
(s), 1334 (m), 1302 (m), 1254 (s), 1151 (s), 1119 (s), 1072 (m), 1054
(m), 1026 (m), 868 (w), 846 (m) cm–1. MS (EI, 70 eV): m/z (%) =
282 (2) [M]+, 237 (6), 226 (25), 209 (16), 180 (100), 151 (22), 136
(3), 107 (10). The exact molecular mass, m/z = 282.1467 2 ppm
[M]+, for C15H22O5 was confirmed by HRMS (EI, 70 eV).
1
(0.061 g, 47%). H NMR (CDCl3, 300 MHz): δ = 2.18 (quint, J =
7.1 Hz, 2 H, CH2), 3.28 (t, J = 7.8 Hz, 2 H, CH2), 3.77 (s, 3 H,
OCH3), 4.48 (t, J = 7.2 Hz, 2 H, OCH2), 6.04 (d, J = 16.8 Hz, 1
H, CH=CH), 7.44 (d, J = 16.8 Hz, 1 H, CH=CH) ppm. IR (neat):
ν = 2957 (w), 2906 (w), 2230 (w), 1603 (s), 1442 (m), 1287 (s), 1236
˜
Isopropyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-3-(4-methoxyphenyl)-
but-3-enoate (11f): Starting with 3c (0.100 g, 0.40 mmol), 4-meth-
oxystyrene (0.112 g, 0.80 mmol), NEt3 (0.11 mL, 0.80 mmol) and
Pd(PPh3)4 (0.014 g, 0.012 mmol) in DMF (3 mL), 11f was isolated
after chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1)
(w), 1212 (s), 1186 (s), 1075 (s), 1027 (w), 970 (w), 877 (m), 765
(w) cm–1. MS (EI, 70 eV): m/z (%) = 193 (1) [M]+, 163 (73), 154
(76), 141 (45), 132 (10), 122 (64), 109 (13), 96 (96), 69 (100). The
exact molecular mass, m/z
C10H11NO3 was confirmed by HRMS (EI, 70 eV).
=
193.0739 2 ppm [M]+, for
1
as a yellowish oil (0.070 g, 58%). H NMR (CDCl3, 300 MHz): δ
= 1.03 (d, J = 6.3 Hz, 6 H, 2×CH3), 2.12 (quint, J = 7.5 Hz, 2 H,
CH2), 3.24 (t, J = 7.8 Hz, 2 H, CH2), 3.79 (s, 3 H, OCH3), 4.21 (t,
J = 7.2 Hz, 2 H, OCH2), 4.90 (sept, J = 6.3 Hz, 1 H, OCH), 5.11
(d, J = 1.5 Hz, 1 H, CH2=C), 5.63 (d, J = 1.5 Hz, 1 H, CH2=C),
6.80 (d, J = 9.0 Hz, 2 H, 2×CH of Ar), 7.31 (d, J = 9.0 Hz, 2 H,
2×CH of Ar) ppm. 13C NMR (CDCl3, 75 MHz): δ = 21.8, 24.2,
31.2, 55.3, 66.8, 72.0, 104.9, 113.4, 114.5, 127.1, 133.9, 142.0, 158.9,
Methyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-3-phenylbut-3-enoate
(11c): Starting with 3a (0.100 g, 0.45 mmol), styrene (0.095 g,
0.91 mmol), NEt3 (0.13 mL, 0.91 mmol) and Pd(PPh3)4 (0.027 g,
0.023 mmol) in DMF (3 mL), 11c was isolated after chromatog-
raphy (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a yellowish oil
1
(0.062 g, 56%). H NMR (CDCl3, 300 MHz): δ = 2.13 (quint, J =
7.8 Hz, 2 H, CH2), 3.28 (t, J = 7.8 Hz, 2 H, CH2), 3.78 (s, 3 H,
OCH3), 4.19 (t, J = 7.2 Hz, 2 H, OCH2), 5.20 (d, J = 1.5 Hz, 1 H,
CH2=C), 5.79 (d, J = 1.5 Hz, 1 H, CH2=C), 6.95–7.39 (m, 5 H,
167.9, 171.7 ppm. IR (neat): ν = 2978 (m), 2931 (m), 2859 (w), 1694
˜
(s), 1611 (s), 1510 (s), 1461 (m), 1376 (m), 1251 (s), 1178 (s), 1141
(m), 1108 (s), 1073 (s), 1035 (s), 984 (m), 961 (w), 934 (w), 896 (w),
837 (m), 807 (w), 794 (w) cm–1. MS (EI, 70 eV): m/z (%) = 302 (41)
[M]+, 259 (100), 243 (6), 231 (82), 227 (2), 215 (13), 201 (35), 185
(3), 148 (79), 135 (75). HRMS (ESI): calcd. for C18H22O4 [M]+:
302.15179; found 302.15236.
5×CH of Ph) ppm. IR (neat): ν = 3079 (w), 3060 (w), 3027 (m),
˜
2976 (s), 2927 (s), 2858 (m), 1703 (s), 1639 (s), 1492 (m), 1446 (s),
1378 (m), 1350 (m), 1281 (m), 1239 (m), 1211 (m), 1185 (s), 1156
(m), 1119 (s), 1075 (s), 1049 (m), 980 (m), 927 (w), 829 (w), 760
(m), 701 (s) cm–1. MS (EI, 70 eV): m/z (%) = 244 (100) [M]+, 229
(10), 213 (14), 197 (11), 185 (34), 171 (35), 158 (16),142 (39), 131
(9), 127 (29), 114 (49), 110 (14), 103 (19), 91 (19), 81 (8), 77 (24),
70 (70). HRMS (ESI): calcd. for C15H16O3 ([M + 1]+): 245.11777;
found 245.11711.
Acknowledgments
We thank Dr. Ilia Freifeld for his experimental contribution. Finan-
cial support from the DAAD (scholarship for E. B.), the Deutsche
Forschungsgemeinschaft and the state of Mecklenburg-Vorpom-
mern (Landesforschungsschwerpunkt “Neue Wirkstoffe und
Screeningverfahren”) is gratefully acknowledged.
Methyl 2-[4,5-Dihydrofuran-2(3H)-ylidene]-3-(4-methoxyphenyl)but-
3-enoate (11d): Starting with 3a (0.100 g, 0.45 mmol), 4-meth-
oxystyrene (0.127 g, 0.91 mmol), NEt3 (0.13 mL, 0.91 mmol) and
Pd(PPh3)4 (0.016 g, 0.014 mmol) in DMF (3 mL), 11d was isolated
after chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1)
1
as a yellowish oil (0.055 g, 45%). H NMR (CDCl3, 300 MHz): δ
[1] For cycloaddition reactions, see: a) A. Weichert, H. M. R.
Hoffmann, J. Org. Chem. 1991, 56, 4098; b) P. Tchelitcheff,
Bull. Soc. Chim. Fr. 1954, 672; c) R. E. Ireland, D. Haebich,
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Khanna, A. P. Bhaduri, Bioorg. Med. Chem. 2000, 8, 2195; for
cyclopropanation reactions, see: g) W. Kirmse, K. Rode, Chem.
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Tanaka, Y. Yamamoto, H. Akita, Tetrahedron Lett. 2002, 43,
1511; for hydrogenation reactions, see: k) T. Ohta, T. Miyake,
N. Seido, H. Kumobayashi, H. Takaya, J. Org. Chem. 1995, 60,
= 2.13 (quint, J = 7.5 Hz, 2 H, CH2), 3.27 (t, J = 7.8 Hz, 2 H,
CH2), 3.58 (s, 3 H, OCH3), 3.80 (s, 3 H, OCH3), 4.21 (t, J = 7.2 Hz,
2 H, OCH2), 5.09 (d, J = 1.5 Hz, 1 H, CH2=C), 5.71 (d, J = 1.5 Hz,
1 H, CH2=C), 6.82 (d, J = 9.0 Hz, 2 H, 2×CH of Ar), 7.34 (d, J
= 9.0 Hz, 2 H, 2×CH of Ar) ppm. IR (neat): ν = 2976 (s), 2934
˜
(m), 2895 (w), 2866 (m), 1705 (s), 1638 (m), 1609 (m), 1512 (s),
1460 (w), 1441 (m), 1381 (m), 1351 (w), 1297 (m), 1251 (s), 1216
(w), 1179 (s), 1151 (m), 1118 (s), 1078 (s), 1037 (s), 834 (w) cm–1.
MS (EI, 70 eV): m/z (%) = 274 (100) [M]+, 258 (42), 242 (18), 226
(36), 214 (45), 200 (35), 183 (9), 158 (40), 144 (25), 134 (47), 121
(14), 108 (7), 77 (21), 70 (21). The exact molecular mass, m/z =
274.1205 2 ppm [M]+, for C16H18O4 was confirmed by HRMS
(EI, 70 eV).
1-tert-Butyl 5-Ethyl 4-[4,5-Dihydrofuran-2(3H)-ylidene]pent-2-ene-
dioate (11e): Starting with 3b (0.200 g, 0.85 mmol), tert-butyl acry-
late (0.19 mL, 1.28 mmol), NEt3 (0.24 mL, 1.70 mmol), Pd(PPh3)4
(0.050 g, 0.043 mmol) in DMF (3 mL), 11e was isolated after
chromatography (silica gel, n-hexane/EtOAc = 100:1 Ǟ 1:1) as a
yellowish oil (0.123 g, 51%). 1H NMR (CDCl3, 300 MHz): δ = 1.31
(t, J = 7.2 Hz, 3 H, OCH2CH3), 1.39 (s, 9 H, OtBu), 2.13 (quint,
J = 7.5 Hz, 2 H, CH2), 3.25 (t, J = 7.8 Hz, 2 H, CH2), 4.23 (q, J
357; see also ref.[2]
.
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Org. Synth. 1994, 1, 287; f) H. Gerlach, H. Wetter, Helv. Chim.
Acta 1974, 57, 2306; g) U. Schmidt, J. Gombos, E. Haslinger,
H. Zak, Chem. Ber. 1976, 109, 2628; h) P. A. Bartlett, J. D.
Eur. J. Org. Chem. 2005, 4815–4828
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4827

E. Bellur, P. Langer
FULL PAPER
Meadows, E. Ottow, J. Am. Chem. Soc. 1984, 106, 5304; i) B.
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Received: June 10, 2005
Published Online: October 4, 2005
4828
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4815–4828