Synthesis of functionalized 2-alkylidenetetrahydrofurans by cyclization of 1,3-Bis(trimethylsilyloxy)-1,3-butadienes with epoxides

Article abstract of DOI:10.1002/1521-3765(20020315)8:6<1443::AID-CHEM1443>3.0.CO;2-0

The Lewis acid mediated cyclization of epoxides with 1,3-bis(trimethylsilyloxy)-1,3-butadienes, electroneutral equivalents of 1,3-dicarbonyl dianions, results in the formation of 2-alkylidenetetrahydrofurans with a great variety of substitution patterns and functional groups. This includes the synthesis of 2,3′-bifuranylidenes and 7-oxabicyclo[4.3.0]nonanes. The cyclization of dienes with functionalized epoxides containing base-labile groups proceeds with good chemoselectivity. In all reactions, good regio- and E diastereoselectivities are observed. Based on the stereoselectivities observed for reactions of 1,2-disubstituted epoxides, a working hypothesis for the mechanism of the reaction is suggested.

Full text of DOI:10.1002/1521-3765(20020315)8:6<1443::AID-CHEM1443>3.0.CO;2-0

FULL PAPER
Synthesis of Functionalized 2-Alkylidenetetrahydrofurans by Cyclization of
1,3-Bis(trimethylsilyloxy)-1,3-butadienes with Epoxides
Peter Langer,*[a,c] Holger Armbrust,[a] Tobias Eckardt,[a] and Jˆrg Magull[b]
Abstract: The Lewis acid mediated cy-
clization of epoxides with 1,3-bis(tri-
methylsilyloxy)-1,3-butadienes, electro-
neutral equivalents of 1,3-dicarbonyl
dianions, results in the formation of
the synthesis of 2,3'-bifuranylidenes
and 7-oxabicyclo[4.3.0]nonanes. The
cyclization of dienes with functionalized
epoxides containing base-labile groups
proceeds with good chemoselectivity. In
all reactions, good regio- and E diaste-
reoselectivities are observed. Based on
the stereoselectivities observed for re-
actions of 1,2-disubstituted epoxides, a
working hypothesis for the mechanism
of the reaction is suggested.
Keywords: cyclization ¥ epoxides ¥
2-alkylidenetetrahydrofurans with
a
heterocycles
¥
Lewis acids
¥
great variety of substitution patterns
and functional groups. This includes
stereoselective syntheses
Cyclization reactions of free or masked dianions with
epoxides are relatively rare: for example, the cyclization of
1,3-dicarbonyl dianions with epoxides, which was first report-
ed by Bryson.[11] Cyclizations of carbohydrate-derived epoxy-
triflates with 1,3-dicarbonyl dianions have been reported by
Voelter and co-workers.[12] Recently, we have reported the
synthesis of 2-alkylidene-5-hydroxymethyltetrahydrofurans
by reaction of 1,3-dicarbonyl dianions with epibromohy-
drin.[13] Molander and co-worker have reported the SnF2-
mediated cyclization of epoxyaldehydes with 3-iodo-2-[(tri-
methylsilyl)methyl]propene (an electroneutral equivalent of
the trimethylenemethane dianion).[14] This reaction proceeds
by regioselective attack of the dianion on the aldehyde and
subsequent cyclization through the terminal carbon of the
epoxide to give cyclohexane derivatives.
The reaction of 1,3-dicarbonyl dianions with epoxides
suffers from several drawbacks. The preparative scope of
these reactions is limited to epoxides containing no sterically
hindered substituents or base-labile functional groups. As a
result of the basic conditions, the cyclizations have to be
carried out in two steps rather than as one-pot reactions
(addition of the dianion onto the epoxide and subsequent
acid-mediated cyclization of the open-chain product). To
overcome these problems, we have recently developed the
first Lewis acid mediated cyclizations of 1,3-bis(trimethylsilyl-
oxy)-1,3-butadienes with epoxides.[15, 16] These reactions allow
an efficient synthesis of a great variety of 2-alkylidenetetra-
hydrofurans, which can be transformed into functionalized
tetrahydrofurans by hydrogenation. Herein, we wish to report
full details of this cyclization reaction and studies related to
the mechanism. With regard to our preliminary report, the
scope of the reaction was significantly extended and now
includes the synthesis of 2,3'-bifuranylidenes and 7-oxabicy-
clo[4.3.0]nonanes. In addition, the regiochemical influence of
the substituents of the epoxide was studied.
Introduction
Despite their potential synthetic usefulness, cyclization reac-
tions of dianions[1, 2] with 1,2-dielectrophiles are problematic
since they can suffer from various side reactions, such as
polymerization, decomposition,[3] formation of open-chain
products,[4] elimination,[5] or SET (Single-Electron Transfer)
reactions.[6] These problems result from the fact that both
dianions and 1,2-dielectrophiles are highly reactive com-
pounds (low reactivity matching). In addition, a number of
1,2-dielectrophiles are rather unstable in reactions with strong
nucleophiles. To overcome these problems, Lewis acid
mediated reactions of electroneutral dianion equivalents
(masked dianions) have been developed. During the past
years, we have developed a number of cyclization[7] and
multicomponent reactions[8] of dianions with a variety of 1,2-
dielectrophiles. In this context, we have also developed Lewis
acid mediated cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-
butadienes, masked 1,3-dicarbonyl dianions,[9] with oxalyl
chloride, a-chloroacetic chloride, chloroacetic aldehyde di-
methylacetal, 1,2-diketones, and phthalic dialdehyde.[10]
[a] Priv.-Doz. Dr. P. Langer, Dipl.-Chem. H. Armbrust
Dipl.-Chem. T. Eckardt
Institut f¸r Organische Chemie
der Georg-August-Universit‰t Gˆttingen
Tammannstrasse2, 37077 Gˆttingen (Germany)
Fax : (‡49)551-399475
E-mail: planger@uni-goettingen.de
[b] Prof. Dr. J. Magull
Institut f¸r Anorganische Chemie
der Georg-August-Universit‰t Gˆttingen
Tammannstrasse2, 37077 Gˆttingen (Germany)
[c] Priv.-Doz. Dr. P. Langer
New address:
Institut f¸r Chemie und Biochemie
der Ernst-Moritz-Arndt Universit‰t Greifswald
Soldmannstrasse 16, 17487 Greifswald (Germany)
Chem. Eur. J. 2002, 8, No. 6
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1443

P. Langer et al.
FULL PAPER
(stirring at À78 208C for 5 h and at 208C for 12h) and the
choice of the Lewis acid (TiCl4, 2.0 equiv) proved important
parameters for the optimization of the reaction (Table 1). The
cyclization proceeded by attack of the terminal carbon of the
diene on the sterically less hindered carbon atom of the
Table 1. Optimization of the cyclization of 1a with 2a.
Lewis acid [equiv]
2a [equiv]
t [h][a]
[%][b]
1
2Me
BF3 ¥ Et2O (2.0)
3SiOTf (2.0)
ZnCl2 (2.0)
TiCl4 (2.0)
TiCl4 (2.0)
TiCl4 (2.0)
TiCl4 (2.0)
TiCl4 (2.0)
TiCl4 (1.0)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
1.0
5 ‡ 120
5 ‡ 120
0 ‡ 120
0 ‡ 12[c]
5 ‡ 0
3
4
5
6
7
8
9
0
12
57
5 ‡ 5
5 ‡ 1270
5 ‡ 1262
4 5 ‡ 122
The 2-alkylidenetetrahydrofurans available by our method-
ology are direct precursors of biologically relevant tetrahy-
drofurans. We have recently reported the application of our
methodology to the synthesis of methyl 8-epi-homononac-
tate.[15] (Æ)-Methyl homononactate and methyl 8-epi-homo-
nonactate are subunits of the nactins, a class of macrotetrolide
antibiotics isolated from a variety of Streptomyces cul-
tures.[17, 18] The 2,3'-bifuranylidenes are also present in a
number of natural products. This includes, for example,
charlic acid, charolic acid, and terrestric acid, which are
metabolites of Penicillium charlesii and Penicillium terrestre,
respectively.[19]
[a] Reaction time at À78 208C and at 208C. [b] Isolated yields. [c] The
reaction was started at 08C.
epoxide and subsequent regioselective cyclization through the
oxygen atom. The exocyclic double bond was formed with
excellent E diastereoselectivity.
Preparative scope: To study the preparative scope of the
cyclization, the substituents of the 1,3-bis(trimethylsilyloxy)-
1,3-butadiene and of the epoxide were systematically varied
(Scheme 2, Table 2). The reaction of diene 1a with 1,2-
propenoxide, 1,2-butenoxide, 1,2-hexenoxide, 5,6-epoxy-1-
hexene, and 1-benzyloxy-2,3-propenoxide afforded the 2-al-
kylidenetetrahydrofurans 3a e with good regio- and E dia-
stereoselectivities.
The reaction of 1a with epichloro- and epibromohydrin
afforded the chloro- and bromo-substituted 2-alkylidenetet-
rahydrofurans 3 f and 3g, respectively, in acceptable yields
and with good regio- and E diastereoselectivities. Interest-
ingly, the reaction proceeded with good chemoselectivity with
exclusive attack of the silyl enol ether on the epoxide rather
than on the alkyl halide function. In contrast, the reaction of
the dianion of ethyl acetoacetate with epibromohydrin
resulted in the formation of a 5-hydroxymethyl-2-alkylidene-
tetrahydrofuran (Scheme 3).[13] The reaction of bis-silyl enol
ether 1a with threo-3-bromo-1,2-butenoxide gave the diaste-
reomerically pure 2-alkylidenetetrahydrofuran 3h with again
good E diastereoselectivity and without epimerization at the
carbon attached to the bromine atom. Tetrahydrofurans
containing chloro or bromo substituents in the side chain
Results and Discussion
Optimization: The reaction of 1,2-propenoxide (2a) with
1-ethoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene (1a), which
is available from ethyl acetoacetate in two steps,[9] afforded
the 2-alkylidenetetrahydrofuran 3a in up to 70% yield
(Scheme 1). Proper tuning of the reaction temperature
Scheme 1. Cyclization of 1,3-bis(trimethylsilyloxy)-1,3-diene 1a with
1,2-butenoxide.
Abstract in German: Die TiCl4-vermittelte Cyclisierung von
Epoxiden mit 1,3-Bis(trimethylsilyloxy)-1,3-butadienen, elek-
troneutralen æquivalenten von 1,3-Dicarbonyldianionen, er-
laubt einen effizienten Zugang zu einer gro˚en Bandbreite von
2-Alkylidentetrahydrofuranen. Dies schlie˚t die Synthese von
2,3'-Bifuranylidenen und 7-Oxabicyclo[4.3.0]nonanen ein. Die
Cyclisierung funktionalisierter Epoxide,die basenlabile Grup-
pen tragen,verl‰uft mit guter Chemoselektivit‰t. Alle Produkte
wurden mit guter Regio- und E-Diastereoselektivit‰t gebildet.
Eine experimentell begr¸ndete Arbeitshypothese f¸r den
Mechanismus der Cyclisierung wird vorgeschlagen.
Scheme 2. Cyclization of 1,3-bis(trimethylsilyloxy)-1,3-dienes 1 with epox-
ides 2 (for R1 R5 see Table 2).
1444
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Chem. Eur. J. 2002, 8, No. 6

Functionalized 2-Alkylidenetetrahydrofurans
1443 1455
Table 2. Synthesis of 2-alkylidenetetrahydrofurans 3a v.
methyl group at the exocyclic double bond, with again good
E diastereoselectivity. Diene 1d was prepared from ethyl
2-ethylacetoacetate. The cyclization of 1d with 1,2-propen-
oxide and epibromohydrin gave the ethyl-substituted 2-alkyl-
idenetetrahydrofurans 3n and 3o, respectively.
1
3
R1
R2
R3
R4
R5
d[a]
d[b]
[%][c, d]
a
a
a
a
a
a
a
a
c
b
b
b
b
d
d
e
f
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OMe
H
Me
Pr
H
H
H
H
H
H
H
5.25 168.7 70
5.23 168.7 62
5.22 168.7 44
5.23 168.6 30
5.33 168.5 58
5.31 168.252
ˆ
CH2CH CH2
OBn
Cl
Br
Br
CH2CO2Et
CO2Et
Me
CH2CH CH2
Cl
H
Br
Me
Me
Cl
The reaction of 1,2-butenoxide with the diene of methyl
3-oxopentanoate 1e afforded the 2-alkylidenetetrahydro-
furan 3p as a mixture of diastereomers. Despite the steric
influence of the substituent R1 ˆ Me, the product was formed
with good E diastereoselectivity. The cyclization of 1,2-
butenoxide with diene 1 f, which was prepared from benzoyl-
acetone, afforded the 2-alkylidenetetrahydrofuran 3q. Sim-
ilarly, the chloro-, bromo-, and ethoxycarbonyl-substituted
2-alkylidenetetrahydrofurans 3r t were prepared with good
chemo-, regio-, and E diastereoselectivity. The reaction of
epichlorohydrin and 1,2-butenoxide with 2,4-bis(trimethylsi-
lyloxy)-5-methoxy-1,3-pentadiene (1g) afforded the 2-alkyli-
denetetrahydrofurans 3u and 3v.
The configuration of 2-alkylidenetetrahydrofurans 3b and
3q was proven by NOESY experiments. For 3b, a NOE was
observed between the ester and the C(3)H2 group. In contrast,
no NOE was detected between the latter and the CH group of
the exocyclic double bond. For tetrahydrofuran 3q, a NOE
was observed between the phenyl and the C(3)H2 group.
5.31 168.3 48
Me 5.19 167.4 41
H
H
H
H
H
H
H
H
H
H
H
H
H
H
5.24 169.0 51
169.0 50
Me OEt
Me OEt
Me OEt
Me OEt
Et
Et
H
H
H
H
H
H
H
169.5 58
169.4 32
168.8 45
169.250
ˆ
OEt
OEt
OMe
Ph
Ph
Ph
168.7 44
5.15 168.3 46
6.50 190.262
6.58 190.1 51
6.55 190.1 44
6.53 190.3 41
5.94 197.1 45
5.92197.240
f
f
f
g
g
s
t
u
v
Br
CO2Et
Ph
CH2OMe Cl
CH2OMe Me
[a] Chemical shift (1H NMR) of the hydrogen atoms of the exocyclic double bond.
[b] Chemical shift (13C NMR) of the exocyclic carbonyl group. [c] Isolated yields.
For 3a o and 3q v: E/Z > 98:2; for 3p: E/Z ˆ 5:1. [d] Diastereoselectivity for 3h:
ds > 98:2in favor of the drawn isomer ( ds ˆ diastereoselectivity). For 3p: ds ˆ 4:1.
Comparison of the chemical shifts of the hydrogen atoms of
the exocyclic double bond (Table 2) with those of related
compounds allowed an independent confirmation of the
E configuration of the 2-alkylidenetetrahydrofurans.[7, 10, 19]
As expected, chemical shifts in the range of d ˆ 5.15 5.31
were observed for ester-derived, E configured tetrahydro-
furans. For benzoylacetone-derived tetrahydrofurans, chem-
ical shifts in the typical range of d ˆ 6.50 6.58 were found.
The configuration of 2-alkylidenetetrahydrofurans 3j o, con-
taining a tetrasubstituted exocyclic double bond, was estab-
lished by analysis of the 13C NMR chemical shifts (Table 2) of
the carbonyl carbon atoms.[7, 10, 19] Additional evidence was
obtained by NOESY experiments, for example, of tetrahy-
drofuran 3n, and by a crystal structure analysis of a related
compound (vide infra).
Scheme 3. Chemoselectivity of the cyclization of epibromohydrin with bis-
silyl enol ethers and 1,3-dicarbonyl dianions.
have demonstrated considerable synthetic utility in function-
alization reactions during natural product syntheses.[20] In
addition, halogenated tetrahydrofurans are interesting in
their own right as they occur in biologically relevant marine
natural products.[21]
The reaction of ethyl 4,5-epoxypentanoate with bis-silyl
enol ether 1c, prepared from methyl acetoacetate, afforded
the 2-alkylidenetetrahydrofuran 3i. The cyclization of ethyl
3,4-epoxybutanoate with bis-silyl enol ether 1b, which was
prepared from ethyl 2-methylacetoacetate, afforded the
2-alkylidenetetrahydrofuran 3j. The formation of 3i,j pro-
ceeded again with good chemoselectivity with exclusive
attack of the diene on the epoxide rather than on the ester
function. In contrast, complex mixtures were obtained in the
reaction of ester-substituted epoxides with the dianion of
ethyl acetoacetate. Despite the presence of a methyl group at
the exocyclic double bond, product 3j was formed with good
E diastereoselectivity. The cyclization of diene 1b with 1,2-
butenoxide, 5,6-epoxy-1-hexene, and epichlorohydrin afford-
ed the 2-alkylidenetetrahydrofurans 3k m, containing a
Synthesis of 2,3'-bifuranylidenes: The extension of our
methodology to the preparation of dinuclear 2-alkylidenete-
trahydrofurans (2,3'-bifuranylidenes) was of special interest
since these compounds are present in a number of natural
products (see Introduction).[19] In addition, these compounds
represent versatile building blocks for the synthesis of
naturally occurring spiroketals such as chalcogran.[22] Silyla-
tion of g-butyrolactones 4a,b with Me3SiCl/NEt3 afforded the
silyl enol ethers 5a,b, which were transformed in high yields
into the bis-silyl enol ethers 6a,b by treatment with LDA
(lithium diisopropylamide) and Me3SiCl (Scheme 4).[23]
Chem. Eur. J. 2002, 8, No. 6
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1445

P. Langer et al.
FULL PAPER
Scheme 4. Cyclization of the g-lactone-derived dienes 6a,b with epoxides
(for R1, R2 see Table 3).
Scheme 5. Cyclization of bis-silyl enol ethers with 1,2-disubstituted
epoxides.
To our satisfaction, the TiCl4-mediated reaction of 6a with
1,2-propenoxide and 1,2-butenoxide afforded the 2,3'-bifuran-
ylidenes 7a,b with good regio- and E diastereoselectivity
(Scheme 4, Table 3). The E-configured tetrahydrofurans 7c
and 7d were prepared by reaction of 6a with 1,2-hexenoxide
and 5,6-epoxy-1-hexene, respectively. The reaction of 6a with
epichlorohydrin and epibromohydrin afforded the chloro-
ilarly, tetrahydrofuran 9c was prepared from diene 1b with
good E and cis diastereoselectivity.
The configuration of tetrahydrofurans 9a c was proven by
NOESY measurements and by analysis of the coupling
constants. As expected, the value of the J5-H,4-H coupling
constant is significantly higher for the cis-configured tetrahy-
drofuran 9b than for the trans-configured isomer 9a. This
observation was independently confirmed by comparison of
the 1H NMR data of products 9a c (chemical shifts and
coupling constants) with those of related compounds with
known configuration.[24] The E configuration of the exocyclic
double bond was established by comparison of the chemical
shifts of the CH signals of the exocyclic double bond with
those of tetrahydrofurans 3.
Table 3. Synthesis of the 2,3'-bifuranylidenes 7a h.
7
R1
R2
[%][a]
d[b]
E/Z
a
b
c
d
e
f
H
H
H
H
H
H
Et
Et
H
Me
Pr
42169.1
34
37
36
46
62167.8
57
82167.6
> 98:2
> 98:2
> 98:2
> 98:2
> 98:2
> 98:2
> 98:2
> 98:2
169.2
169.2
168.9
168.1
ˆ
CH2CH CH2
Cl
Br
Me
Br
g
h
168.7
[a] Isolated yields. [b] Chemical shift (13C NMR) of the exocyclic
carbonyl group.
and bromo-substituted 2,3'-bifuranylidenes 7e,f with again
good chemo-, regio-, and E diastereoselectivity. Starting with
the ethyl-substituted bis-silyl enol ether 6b, the 2,3'-bifuranyl-
idenes 7g,h were obtained with good regio- and E diastereo-
selectivity but, as expected, without any remote diastereo-
The observed stereoselectivity suggested that the formation
of 2-alkylidenetetrahydrofurans 3a v, 7a h, and 9a c can
be explained by the following mechanism: regioselective
attack of the terminal carbon of the diene on the epoxide
afforded intermediate A with inversion of the configuration.
The retention of the configuration of the carbon attached to
the oxygen atom suggests that the cyclization proceeded by
TiCl4-mediated conjugate addition of the epoxide-derived
hydroxy group onto the a,b-unsaturated ester moiety to give
intermediate B. In contrast, attack of the silyl enol ether
derived oxygen atom of A on the carbon attached to the
hydroxy group would have resulted in an inversion of the
configuration. The final product was formed by elimination of
silanolate. The presence of the Lewis acid seems to be
important for both the initial condensation and the subse-
quent cyclization and elimination. The stereoselectivity can be
explained by the higher thermodynamic stability of the
products containing E-configured exocyclic double bonds
control. The E configuration of 2,3'-bifuranylidenes 7a
h
was established by comparison of the 13C NMR chemical
shifts (Table 3) with those of tetrahydrofurans 3 (Table 2) and
related compounds.[7, 10, 19] In addition, a crystal structure
analysis of a related product was obtained (vide infra).
Cyclization reactions of 1,2-disubstituted epoxides: To get
some insight into the mechanism of the reaction, we have
studied the reaction of 1,3-bis(trimethylsilyloxy)-1,3-diene 1a
with 1,2-disubstituted epoxides (Scheme 5): the reaction of 1a
with cis-2,3-butenoxide (8a) afforded the E-configured 2-al-
kylidenetetrahydrofuran 9a containing two trans-configured
methyl groups in good yield. In contrast, reaction of 1a with
trans-2,3-butenoxide (8b) gave the 2-alkylidenetetrahydro-
furan 9b containing two cis-configured methyl groups. Sim-
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Chem. Eur. J. 2002, 8, No. 6

Functionalized 2-Alkylidenetetrahydrofurans
1443 1455
(minimization of the dipole dipole repulsion of the oxygen
atoms).[25, 26]
Synthesis of 7-oxabicyclo[4.3.0]nonanes: Based on the stereo-
chemical observations outlined in the preceeding paragraph,
we reasoned that the reaction of bis-silyl enol ethers with cis-
configured cyclic epoxides should result in the formation of
trans-configured bicyclic 2-alkylidenetetrahydrofurans. In
fact, the reaction of diene 1a with cyclohexenoxide 10 afford-
ed the 7-oxabicyclo[4.3.0]nonane 11a with high regioselectiv-
ity and with good E and trans diastereoselectivity (Scheme 6,
Table 4). The cyclization of 10 with dienes 1c, 1h, 1i, and 1 f,
prepared from methyl acetoacetate, isopropyl acetoacetate,
isobutyl acetoacetate, and benzoylacetone, respectively,
Figure 1. ORTEP plot of 11 f. The thermal ellipsoids of 50% probability
are shown for the non-hydrogen atoms. Selected bond lengths [ä] and
À
À
À
angles [8]: C(1A) C(6A) 1.501(6), C(1A) C(9) 1.549(4), O(7) C(8)
À
À
À
136.0(2), O(1') C(2') 1.362(2), O(1') C(5') 1.454(2), C(2') C(3') 1.453(3),
À
À
À
À
C(3') C(4') 1.502(2), C(6A) O(7) 1.536(4); C(6A) C(1A) C(2) 107.7(3),
C(6A) C(1A) C(9) 100.6(3), C(1A) C(2) C(3A) 104.6(2), C(1A)
C(6A) O(7) 97.6(3), C(8) O(7) C(6A) 105.78(18), C(3') C(8) O(7)
120.02(16), C(2') O(1') C(5') 110.75(14), O(1') C(2') C(3') 109.26(15).
À
À
À
À
À
À
À
À
À
À
À
À
À
À
ide 12a resulted in a change of the regioselectivity and
formation of the E-configured 2-alkylidenetetrahydro-
furan 13a containing the phenyl substituent at carbon C-4
rather than C-5 (Scheme 7, Table 5). Similarly, the reaction of
Scheme 6. Cyclization of bis-silyl enol ethers with cyclic epoxides (for R1,
R2 see Table 4).
Table 4. Synthesis of 7-oxabicyclo[4.3.0]nonanes 11a f.
1
11
R1
R2
Yield [%][a]
d[b]
a
c
h
i
f
6a
a
b
c
d
e
f
H
H
H
H
H
OEt
OMe
OiP6r
OiBu
Ph
26
30
325.2
31[c]
24
5.40
5.27
5.32
6.52
Scheme 7. Influence of the substituents of the epoxide on the regioselec-
tivity (for R1, R2 see Table 5).
CH2CH2O
2
6
[a] Isolated yields. For all products: E/Z > 98:2. [b] Chemical shift
(1H NMR) of the hydrogen atoms of the exocyclic double bond.
[c] Impurities could not be completely removed.
Table 5. Synthesis of 2-alkylidenetetrahydrofurans 13a f.
1
13
R1
R2
Yield [%][a]
d[d]
a
f
f
g
j
j
a
b
c
d
e
f
OEt
Ph
Ph
CH2OMe
Me
Me
Ph
CH CH2
Me
Me
Me
30
38
45
425.95
36[b]
15 ‡ 6[c]
5.40
6.54
6.52
ˆ
resulted in diastereoselective formation of the 7-oxabicy-
clo[4.3.0]nonanes 11b e. The dinuclear 7-oxabicyclo[4.3.0]-
nonane 11 f was prepared from diene 6a with good E and
trans diastereoselectivity. Complex mixtures were obtained in
the reaction of 1a with cyclopentenoxide, cyclooctenoxide,
and cyclododecenoxide.
The configuration of 11a f was established by analysis of
the chemical shifts of the hydrogen atoms located at the
exocyclic double bond and by analogy to the stereoselectivity
observed in the formation of tetrahydrofurans 9a c. The
structure of 11 f was independently confirmed by crystal
structure analysis (Figure 1). Compound 11 f possesses an E-
configured exocyclic double bond. The 7-oxabicyclo[4.3.0]no-
nane system exhibits a trans configuration. A chair confor-
mation is observed for the cyclohexane moiety. The two
heterocyclic moieties of the bifuranylidene system of 11 f are
nearly in plane.
5.75, 5.78
5.74, 5.75
Et
[a] Isolated yields. For all products: E/Z > 98:2. [b] Inseparable mixture of
regioisomers. For the main isomer, the methyl group is located at carbon
C-5. [c] Isolated yields of regioisomers. For the main isomer, the ethyl
group is located at carbon C-4. [d] Chemical shift (1H NMR) of the
hydrogen atoms of the exocyclic double bond.
1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene with 3,4-ep-
oxy-1-butene 12b afforded the vinyl-substituted tetrahydro-
furan 13b.
The cyclization of ester-derived dienes with 1,2-propen-
oxide afforded tetrahydrofurans 3a and 3n containing a
methyl group at carbon C-5. In contrast, the reaction of 1,2-
propenoxide with bis-silyl enol ethers 1 f and 1g afforded
tetrahydrofurans 13c and 13d, respectively, containing the
methyl group at carbon C-4 rather than C-5. The reaction of
2,4-bis(trimethylsilyloxy)-1,3-pentadiene (1j) with 1,2-pro-
penoxide and 1,2-butenoxide resulted in the formation of
tetrahydrofurans 13e and 13 f, respectively, which were each
obtained as mixtures of regioisomers. The structure of
Influence of the epoxide on the regioselectivity: To study the
parameters which direct the regioselectivity of cyclization, we
have studied reactions of bis-silyl enol ethers with styrenoxide
and 3,4-epoxy-1-butene. The reaction of 1a with styrenox-
Chem. Eur. J. 2002, 8, No. 6
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0806-1447 $ 17.50+.50/0
1447

P. Langer et al.
FULL PAPER
tetrahydrofurans 13a f was established by DEPT experi-
ments. The E configuration of the exocyclic double bond was
again proven by comparison of the chemical shifts of the
respective CH signals with those of tetrahydrofurans 3.
The change of the regioselectivity can be explained as
follows: bis-silyl enol ethers prepared from 1,3-diketones are
less reactive than those derived from b-ketoesters. The
nucleophilic attack of a bis-silyl enol ether on an epoxide is
slower for ketone- than for ester-derived dienes. Therefore,
the TiCl4-mediated ring opening of the epoxide and formation
of a carbocation is faster than nucleophilic attack of the diene
on the epoxide. The change in the regioselectivity observed
for styrenoxide and 3,4-epoxy-1-butene can be explained by
the fact that the phenyl and vinyl group efficiently stabilize a
carbocation. In contrast, alkyl groups stabilize a carbocation
less efficiently. For reactions of bis-silyl enol ethers with alkyl-
substituted epoxides, a change in the regioselectivity is most
likely for reactions of ketone-derived dienes with 1,2-propen-
oxide due to the low reactivity of the diene and the low steric
hindrance of the methyl group of the epoxide.
by-products, which were formed by hydrolysis of the bis-silyl
enol ethers and epoxides, respectively. The purification of 3b
was again greatly improved by the use of Ambersep900-OH,
which efficiently scavenged the relatively acidic by-prod-
ucts 15 and 16 (Scheme 9). The isolated yield of 3b was similar
to that obtained by the more tedious conventional purification
procedure.
Scheme 9. Purification of 3b by Ambersep900-OH.
In summary, we have reported the, to our knowledge, first
cyclizations
of
1,3-bis(trimethylsilyloxy)-1,3-butadienes,
Optimization of the isolation and purification procedure:
During our synthetic studies, we have developed a new
method, which greatly simplified the purification and isola-
tion of 2-alkylidenetetrahydrofurans. Herein, we wish to
report the results of our efforts. Analysis of the crude product
of the reaction of cyclohexenoxide 10 with 1-methoxy-1,3-
bis(trimethylsilyloxy)-1,3-butadiene indicated that, besides
the desired product 11b, significant amounts of the 1:1 con-
densation product 14 had been formed. Similar by-products
were formed in all cyclization reactions of bis-silyl enol ethers
with 10. As a result of the presence of a hydroxy and a 1,3-
dicarbonyl group, 14 was expected to be considerably more
acidic than 11b. Therefore, a solution of the mixture in diethyl
ether was treated with the basic ion-exchange resin Amber-
sep900-OH (Scheme 8). After stirring for 2h, the resin was
masked 1,3-dicarbonyl dianions, with epoxides. These reac-
tions allow an efficient, chemo-, regio-, and diastereoselective
synthesis of a variety of functionalized 2-alkylidenetetrahy-
drofurans, 2,3'-bifuranylidenes, and 7-oxabicyclo[4.3.0]no-
nanes, which represent useful precursors to biologically
relevant tetrahydrofurans and natural products. Reactions of
1,2-disubstituted epoxides with bis-silyl enol ethers proceeded
with good stereoselectivity and suggest that in all cyclizations
the dienes react as 1,2-nucleophiles/electrophiles rather than
1,3-dinucleophiles; the epoxides can be regarded as 1,3-
electrophiles/nucleophiles rather than 1,2-dielectrophiles.
Further studies relating to the application of our methodology
for the synthesis of natural products are in progress.
Experimental Section
General: All solvents were dried by standard methods, and all reactions
were carried out under an inert atmosphere. For the 1H and 13C NMR
spectra (1H NMR: 250 and 300 MHz, 208C; 13C NMR: 62.5 and 75 MHz,
208C), the deuterated solvents indicated were used. BrukerAM250
(250 MHz), VarianVXR-200 (200 MHz), Varian Mercury200 (200 MHz),
Varian Unity300 (300 MHz), BrukerAMX300 (300 MHz), and Varian
Inova500 (500 MHz) were used. Mass spectrometric data (MS) were
obtained by using electron ionization (EI, 70 eV, FinniganMAT95),
chemical ionization (CI, 200 eV, H2O), or electrospray ionization (Finni-
ganLC-Q, ESI). FT-IR: Bruker Vector22 and BrukerIFS-66 were used.
For preparative scale chromatography, Merck silica gel60 (0.063
0.200 mm, 230 400 mesh) or Macherey-Nagel silica gel60 (0.040
0.063 mm, 200 400 mesh) was used. Thin-layer chromatography (TLC):
Macherey-Nagel silica gel60F254 was used. Melting points were uncorrect-
ed. Elemental analyses were performed at the microanalytical laboratory
Scheme 8. Purification of 11b by Ambersep900-OH.
filtered off, and the filtrate was concentrated in vacuo. This
procedure was repeated one time. Much to our satisfaction,
the major impurity was selectively removed. The pure product
was isolated by column chromatography, which was easy to
carry out as a result of the absence of 14. In contrast, two
tedious chromatographic separations were required during
the conventional purification procedure. The isolated yields of
11b were comparable for either purification method.
of the University of Gˆttingen.
A LECOCHN2000 analyzer with
combined HERAEUS combustion apparatus MikroU/D was used. All
starting materials were used as purchased. Bis-silyl enol ethers 1 were
prepared according to literature procedures.[9c] Ethyl 3,4-epoxybuta-
noate was prepared in three steps from ethyl 4-chloroacetoacetate.[27]
Ethyl 4,5-epoxypentanoate was prepared in three steps from diethyl
2-allylmalonate.[28]
General procedure for the cyclization of epoxides with 1,3-bis(trimethylsi-
lyloxy)-1,3-butadienes: Compound 1,2-butenoxide (130 mg, 0.15 mL,
1.8 mmol, d ˆ 0.837 gcmÀ3) at 2 08C was added to a solution (30 mL) of
In the case of the synthesis of 2-alkylidenetetrahydro-
furans 3, 1,3-dicarbonyl compounds and diols were common
1448
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0947-6539/02/0806-1448 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 6

Functionalized 2-Alkylidenetetrahydrofurans
1443 1455
1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene (1.8 mmol, 0.5 g) in
CH2Cl2 and molecular sieves (4 ä). The solution was cooled to À788C,
and subsequently TiCl4 (3.6 mmol, 0.40 mL, d ˆ 1.726 gcmÀ3) was added.
After warming of the solution to 208C over 6 h, the solution was stirred for
12h. A saturated aqueous solution of NaCl (150 mL) was added, and the
organic layer was separated. The aqueous layer was extracted with diethyl
ether (4 Â 150 mL). The organic layer was dried (MgSO4), filtered, and the
filtrate was concentrated in vacuo. The residue was purified by chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:3) to give 3b as a
colorless oil (205 mg, 62%). In some cases, two chromatographic purifi-
cations were required.
7.1 Hz, 3H; OCH2CH3), 1.58 1.84 (m, 4H; CH2), 2.09 2.23 (m, 2H;
4-H), 2.91 (dddd, J ˆ 18.3, 9.2, 9.2, 2.0 Hz, 1H; 3-H), 3.27 (dddd, J ˆ 18.4,
9.1, 4.1, 1.4 Hz, 1H; 3-H), 4.09 (q, J ˆ 7.1 Hz, 2H ; OC H2CH3), 4.32 4.38
ˆ
(m, 1H; 5-H), 4.94 5.07 (m, 2H; CH CH2), 5.22 5.24 (m, 1H;
CHCO2Et), 5.70 5.84 (m, 1H; CH CH2); 13C NMR (62.9 MHz, CDCl3):
ˆ
d ˆ 14.37 (OCH2CH3), 29.23, 29.70, 30.43, 33.96 (CH2, C-3, C-4, C-1', C-2'),
ˆ
ˆ
58.98 (OCH2CH3), 83.31 (C-5), 89.15 (CH CO2), 115.18 (CH CH2), 137.27
ˆ
ˆ
(CH CH2), 168.57 (C O), 176.22 (C-2); MS (70 eV, EI): m/z (%): 210 (89)
‡
[M ], 170 (45), 106 (60), 89 (66), 43 (100); the exact molecular mass for
‡
C12H18O3: m/z (%): 210.1256 Æ 2mD [ M ] was confirmed by HRMS (EI,
70 eV).
2-(E)-(Ethoxycarbonylmethylidene)-5-(benzyloxymethyl)tetrahydrofuran
(3e): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
(0.97 g, 3.5 mmol), 1-(benzyloxy)-2-propenoxide (0.57 g, 3.5 mmol), and
TiCl4 (0.77 mL, d ˆ 1.726 gcmÀ3, 7.0 mmol), 3e was isolated after chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:3) as a colorless oil
(560 mg, 58%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.26 (t, J ˆ
7.1 Hz, 3H; OCH2CH3), 1.85 1.94 (m, 1H; 4-H), 2.10 2.16 (m, 1H; 4-H),
2.97 3.08 (m, 1H; 3-H), 3.20 3.27 (m, 1H; 3-H), 3.50 3.66 (m, 2H;
CH2OCH2Ph), 4.12(q, J ˆ 7.1 Hz, 2H; OCH2CH3), 4.54 4.62(m, 3H; 5-H,
Purification of 3b by ion-exchange resins: A solution (20 mL) of the crude
product mixture of 3b in diethyl ether was treated with the basic ion-
exchange resin Ambersep900-OH. After stirring for 2h, the resin was
filtered off, and the filtrate was concentrated in vacuo. This procedure was
repeated one time. After evaporation of the solvent, the residue was
purified by chromatography to give 3b as a colorless oil (210 mg, 63%).
2-(E)-(Ethoxycarbonylmethylidene)-5-methyltetrahydrofuran (3a): Start-
ing
with
1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
(0.50 g,
1.8 mmol), 1,2-propenoxide (0.13 mL, d ˆ 0.829 gcmÀ3, 1.8 mmol), and
TiCl4 (0.40 mL, d ˆ 1.726 gcmÀ3, 3.6 mmol), 3a was isolated after chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:3) as a colorless oil
(216 mg, 70%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.25 (t, J ˆ
7.1 Hz, 3H; OCH2CH3), 1.35 (d, J ˆ 5.3 Hz, 3H; CHCH3), 1.51 1.72(m,
1H; 4-H), 2.15 2.27 (m, 1H; 4-H), 2.95 (dddd, J ˆ 18.3, 9.1, 9.1, 2.0 Hz,
1H; 3-H), 3.31 (dddd, J ˆ 18.4, 8.9, 4.0, 1.5 Hz, 1H; 3-H), 4.11 (q, J ˆ 7.1 Hz,
2H; OCH2CH3), 4.47 4.56 (m, 1H; 5-H), 5.25 (t, J ˆ 1.7 Hz, 1H;
CHCO2Et); 13C NMR (62.9 MHz, CDCl3): d ˆ 14.43 (OCH2CH3), 20.33
(CH3), 30.74, 31.00 (C-3, C-4), 59.07 (OCH2CH3), 80.23 (C-5), 89.16
CH2OCH2Ph), 5.33 5.34 (m, 1H; CHC O), 7.35 (m, 5H; Ph); 13C NMR
ˆ
(62.9 MHz, CDCl3): d ˆ 14.36 (OCH2CH3), 25.59, 30.15 (C-3, C-4), 59.07
(OCH2CH3), 71.21, 73.34 (CH2OCH2Ph, CH2OCH2Ph), 82.46, 89.59 (C-5,
ˆ
ˆ
CHC O), 127.56, 127.61, 128.32 (CH, Ph), 137.64 (C, Ph), 168.49 (C O),
176.32(C-2); IR (neat): nÄ ˆ 3088 (w), 3064 (w), 3031 (w), 2980 (m), 2937
(m), 2871 (m), 1722 (s), 1641 (m), 1453 (m), 1393 (m), 1372 (m), 1274 (s),
1113 (s), 1070 (m), 1048 cmÀ1 (m); MS (70 eV, EI): m/z (%): 276 (25) [M ],
‡
231 (36), 91 (100); the exact molecular mass for C16H20O4: m/z (%):
‡
276.1361 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
2-(E)-(Ethoxycarbonylmethylidene)-5-(chloromethyl)tetrahydrofuran
(3 f): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
ˆ
(CHCO2Et), 168.67 (C O), 176.42(C-2); MS (70 eV, EI): m/z (%): 170 (66)
‡
[M ], 142 (29), 125 (100), 69 (68); the exact molecular mass for C9H14O3:
(0.99 g, 3.6 mmol), epichlorohydrin (0.39 g, 0.33 mL, d ˆ 1.180 gcmÀ3
,
‡
m/z (%): 170.0943 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
3.6 mmol), and TiCl4 (0.79 mL, d ˆ 1.726 gcmÀ3, 7.2mmol), 3 f was isolated
after chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a
2-(E)-(Ethoxycarbonylmethylidene)-5-ethyltetrahydrofuran (3b): Starting
with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene (0.50 g, 1.8 mmol),
1
colorless oil (378 mg, 52%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
1,2-butenoxide (0.15 mL, 1.8 mmol), and TiCl4 (0.40 mL, d ˆ 1.726 gcmÀ3
,
1.23 (t, J ˆ 7.1 Hz, 3H; OCH2CH3), 1.89 2.04 (m, 1H; 4-H), 2.15 2.33 (m,
1H; 4-H), 2.93 3.11 (m, 1H; 3-H), 3.02 (dddd, J ˆ 18.5 Hz, 9.1, 4.1, 1.5 Hz,
1H; 3-H), 3.62(d, J ˆ 5.1 Hz, 2H; CH2Cl), 4.09 (q, J ˆ 7.1 Hz, 2H;
OCH2CH3), 4.56 4.71 (m, 1H; 5-H), 5.31 (m, 1H; CHCO2Et); 13C NMR
(62.9 MHz, CDCl3): d ˆ 14.28 (OCH2CH3), 26.67, 29.88 (C-3, C-4), 45.38
3.6 mmol), 3b was isolated after chromatography (silica gel, diethyl ether/
petroleum etherˆ 1:3) as a colorless oil (205 mg, 62%, E/Z > 98:2).
1H NMR (200 MHz, CDCl3): d ˆ 0.95 (t, J ˆ 7.4 Hz, 3H; CH2CH3), 1.23
(t, J ˆ 7.1 Hz, 3H; OCH2CH3), 1.51 1.80 (m, 3H; 4-H, CH2CH3), 2.09
2.22 (m, 1H; 4-H), 2.92 (dddd, J ˆ 18.4, 9.1, 9.1, 2.0 Hz, 1H; 3-H), 3.27
(dddd, J ˆ 18.4, 9.1, 4.0, 1.5 Hz, 1H; 3-H), 4.09 (q, J ˆ 7.1 Hz, 2H;
ˆ
(CH2Cl), 59.15 (OCH2CH3), 81.91 (C-5), 90.17 (CHCO2Et), 168.15 (C O,
175.30 (C-2); IR (neat): nÄ ˆ 2961 (s), 2938 (s), 1778 (s), 1713 (s), 1643 (s),
ˆ
OCH2CH3), 4.23 4.35 (m, 1H; 5-H), 5.23 5.24 (m, 1H; CHC O);
1461 (m), 1445 (m), 1428 (m), 1372 (s), 1331 (m), 1301 (m), 1174 (m), 1117
13C NMR (62.9 MHz, CDCl3): d ˆ 9.72(CH 2CH3), 14.44 (OCH2CH3),
‡
(s), 1048 cmÀ1 (s); MS (70 eV, EI): m/z (%): 204 (44) [M ], 176 (13), 161
27.81, 28.71, 30.54 (C-3, C-4, C-1), 59.06 (OCH2CH3), 85.35 (C-5), 89.03
(34), 159 (100); the exact molecular mass for C9H13O3Cl: m/z (%):
ˆ
(CHCO2Et), 168.74 (C O), 176.55 (C-2); MS (70 eV, EI): m/z (%): 184 (71)
‡
204.0553 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
‡
[M ], 179 (4), 166 (4), 155 (10), 139 (100), 112(24); the exact molecular
2-(E)-(Ethoxycarbonylmethylidene)-5-(bromomethyl)tetrahydrofuran
(3g): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
(0.60 g, 2.2 mmol), epibromohydrin (0.20 mL, d ˆ 1.655 gcmÀ3, 2.2 mmol),
and TiCl4 (0.44 mL, d ˆ 1.726 gcmÀ3, 4.4 mmol), 3g was isolated after
‡
mass for C10H16O3: m/z (%): 184.1099 Æ 2mD [ M ] was confirmed by
HRMS (EI, 70 eV).
2-(E)-(Ethoxycarbonylmethylidene)-5-butyltetrahydrofuran (3c): Starting
with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene (3.1 mmol, 0.87 g),
1,2-hexenoxide (0.31 g, 0.38 mL, d ˆ 0.831 gcmÀ3, 3.1 mmol), and TiCl4
(6.2mmol, 0.68 mL, d ˆ 1.726 gcmÀ3), 3c was isolated after chromatogra-
phy (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a colorless oil
(286 mg, 44%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 0.85 0.91
(m, 3H; CH2CH2CH3), 1.19 1.41 (m, 7H; OCH2CH3, CH2CH2CH3),
1.46 1.68 (m, 3H; 4-H, CH2 to C-5), 2.09 2.26 (m, 1H; 4-H), 2.90 (dddd,
J ˆ 18.3, 9.2, 9.2, 1.9 Hz, 1H; 3-H), 3.26 (dddd, J ˆ 18.4, 9.2, 4.0, 1.4 Hz, 1H;
3-H), 4.09 (q, 2H; OCH2CH3), 4.26 4.41 (m, 1H; 5-H), 5.21 5.22 (m, 1H;
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as
a
colorless oil (260 mg, 48%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.22 (t, J ˆ 7.1 Hz, 3H; OCH2CH3), 1.83 2.01 (m, 1H; 4-H), 2.21 2.39
(m, 1H; 4-H), 2.94 3.05 (m, 1H; 3-H), 3.21 3.52 (m, 3H; 3-H, CH2Br),
4.10 (q, J ˆ 7.1 Hz, 2H; OCH2CH3), 4.55 4.65 (m, 1H; 5-H), 5.31 (m, 1H;
CHC O); 13C NMR (62.9 MHz, CDCl3): d ˆ 14.28 (OCH2CH3), 27.70,
ˆ
29.91 (C-3, C-4), 33.61 (CH2Br), 59.15 (OCH2CH3), 82.01 (C-5), 90.18
ˆ
(CHCO2Et), 168.25 (C O), 176.130 (C-2); MS (70 eV, EI): m/z (%): 248
‡
(60) [M ], 203 (94), 176 (23), 69 (100); the exact molecular mass for
CHC O); 13C NMR (62.9 MHz, CDCl3): d ˆ 13.85, 14.40 (OCH2CH3,
‡
ˆ
C9H13O3Br: m/z (%): 248.0048 Æ 2mD [ M ] was confirmed by HRMS (EI,
CH3), 22.47, 27.67, 29.12, 30.52, 34.55 (C-3, C-4, 3 Â CH2), 59.00
70 eV).
ˆ
ˆ
(OCH2CH3), 84.16, 89.00 (CHC O, C-5), 168.69 (C O), 176.47 (C-2);
MS (70 eV, EI): m/z (%): 212 (89) [M ], 167 (100), 103 (60), 85 (66), 43
threo-2-(E)-(Ethoxycarbonylmethylidene)-5-(bromoethyl)tetrahydro-
furan (3h): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
(0.41 g, 1.5 mmol), threo-2-bromo-3,4-butenoxide (0.25 g, 1.5 mmol), and
TiCl4 (0.33 mL, d ˆ 1.726 gcmÀ3, 3.0 mmol), 3h was isolated after chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:3) as a colorless oil
‡
(89); the exact molecular mass for C12H20O3: m/z (%): 212.1412 Æ 2mD
‡
[M ] was confirmed by HRMS (EI, 70 eV).
2-(E)-(Ethoxycarbonylmethylidene)-5-(3-butenyl)tetrahydrofuran (3d):
Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene (0.97 g,
3.5 mmol), 5,6-epoxy-1-hexene (0.39 mL, d ˆ 0.870 gcmÀ3, 3.5 mmol), and
TiCl4 (0.77 mL, d ˆ 1.726 gcmÀ3, 7.0 mmol), 3d was isolated after chroma-
tography (silica gel, diethyl ether/petroleum ether 1:3) as a colorless oil
(220 mg, 30%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.22 (t, J ˆ
1
(161 mg, 41%, E/Z > 98:2). H NMR (250 MHz, [D6]acetone): d ˆ 1.19 (t,
J ˆ 7.1 Hz, 3H; OCH2CH3), 1.70 (d, J ˆ 6.9 Hz, 3H; CHBrCH3), 1.88 2.01
(m, 1H; 4-H), 2.24 2.39 (m, 1H; 4-H), 2.97 (dddd, J ˆ 18.5, 9.8, 9.8, 1.8 Hz,
1H; 3-H), 3.31 (dddd, J ˆ 18.5, 9.8, 4.3, 1.6 Hz, 1H; 3-H), 3.05 (q, J ˆ 7.1 Hz,
2H; OCH2CH3), 4.28 4.38 (m, 1H; CHBrCH3), 4.52 4.60 (m, 1H; 5-H),
Chem. Eur. J. 2002, 8, No. 6
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0806-1449 $ 17.50+.50/0
1449

P. Langer et al.
FULL PAPER
5.19 (dd, J ˆ 1.7, 1.7 Hz, 1H; CHCO2Et); 13C NMR (62.9 MHz, CDCl3):
d ˆ 13.94 (OCH2CH3), 21.42 (CHBrCH3), 26.80, 30.29 (C-3, C-4), 51.06
(C CO2Et), 115.81 (CH CH2), 137.60 (CH CH2), 168.88 (C O), 170.02
ˆ
ˆ
ˆ
ˆ
‡
(C-2); MS (70 eV, EI): m/z (%): 224 (58) [M ], 195 (42), 179 (100); the
‡
ˆ
(CHBrCH3), 58.58 (OCH2CH3), 86.43 (C-5), 89.04 (CHC O), 167.44
exact molecular mass for C13H20O3: m/z (%): 224.1412 Æ 2mD [ M ] was
‡
ˆ
(C O), 176.18 (C-2); MS (70 eV, EI): m/z (%): 262 (50) [M ], 217 (66), 155
(26), 137 (88), 109 (30), 87 (36), 69 (100).
confirmed by HRMS (EI, 70 eV).
2-(E)-[1-(Ethoxycarbonyl)ethylidene]-5-(chloromethyl)tetrahydrofuran
(3m): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-2-methyl-1,3-buta-
2-(E)-[1-(Methoxycarbonyl)methylidene]-5-(ethoxycarbonylethyl)tetra-
hydrofuran (3i): Starting with 1,3-bis(trimethylsilyloxy)-1-methoxy-1,3-
butadiene (0.83 g, 3.2mmol), ethyl 4,5-epoxypentanoate (0.47 g,
3.2mmol), and TiCl 4 (0.70 mL, d ˆ 1.726 gcmÀ3, 6.2mmol), 3i was isolated
after chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a
diene (0.75 g, 2.6 mmol), epichlorohydrin (0.20 mL, d ˆ 1.180 gcmÀ3
,
2.6 mmol), and TiCl4 (0.57 mL, d ˆ 1.726 gcmÀ3
, 5.2mmol), 3m was
isolated after chromatography (silica gel, diethyl ether/petroleum etherˆ
1:3) as a colorless oil (250 mg, 45%, E/Z > 98:2). 1H NMR (250 MHz,
CDCl3): d ˆ 1.25 (t, J ˆ 7.1 Hz, 3H; OCH2CH3), 1.79 (t, J ˆ 1.6 Hz, 3H;
CH3), 1.82 2.02 (m, 1H; 4-H), 2.16 2.30 (m, 1H; 4-H), 2.92 3.07 (m, 1H;
3-H), 3.14 3.27 (m, 1H; 3-H), 3.54 3.69 (m, 2H; CH2Cl), 4.12(q, J ˆ
7.1 Hz, 2H; OCH2CH3), 4.55 4.64 (m, 1H; 5-H); 13C NMR (62.9 MHz,
CDCl3): d ˆ 11.02(CH ), 14.12(OCH CH3), 27.18, 30.31 (C-3, C-4), 45.39
1
colorless oil (418 mg, 51%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
ˆ
1.24 (t, J ˆ 7.1 Hz, 3H; OCH2CH3), 1.61 2.01 (m, 3H; CH2CH2C O, 4-H),
ˆ
2.13 2.26 (m, 1H; 4-H), 2.33 2.51 (m, 2H; CH2CH2C O), 2.92 (dddd, J ˆ
18.2, 9.0, 9.0, 2.0 Hz, 1H; 3-H), 3.27 (dddd, J ˆ 18.5, 9.1, 4.2, 1.5 Hz, 1H;
3-H), 3.63 (s, 3H; OCH3), 4.12(q, J ˆ 7.1 Hz, 2H; OCH2CH3), 4.35 4.45
3
2
(m, 1H; 5-H), 5.22 5.25 (m, 1H; CHC O); 13C NMR (75 MHz, CDCl3):
ˆ
(CH2Cl), 59.29 (OCH2CH3), 81.13 (C-5), 97.12( CCO2Et), 168.83, 168.99
(C-2, C O); MS (70 eV, EI): m/z (%): 218 (80) [M ], 172(100), 146 (24),
137 (48), 83 (94); the exact molecular mass for C10H15O3Cl: m/z (%):
218.0710 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
2-(E)-[1-(Ethoxycarbonyl)propylidene]-5-methyltetrahydrofuran
ˆ
d ˆ 14.15 (OCH2CH3), 29.02, 29.10, 29.97 (C-3, C-4, CH2CH2C O), 49.85
‡
ˆ
ˆ
(CH2CH2C O), 50.60 (OCH3), 60.53 (OCH2CH3), 82.88 (C-5), 89.11
ˆ
ˆ
‡
(CHC O), 168.97, 172.76 (2 Â C O), 176.18 (C-2); MS (70 eV, EI): m/z
‡
(%): 242 (22) [M ], 210 (70), 169 (23), 122 (100), 118 (58); the exact
‡
(3n):
molecular mass for C12H18O5: m/z (%): 242.1154 Æ 2mD [ M ] was
Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-2-ethyl-1,3-butadiene
(0.70 g, 2.3 mmol), 1,2-propenoxide (0.17 mL, d ˆ 0.829 gcmÀ3, 2.3 mmol),
and TiCl4 (0.51 mL, d ˆ 1.726 gcmÀ3, 4.6 mmol), 3n was isolated after
confirmed by HRMS (EI, 70 eV).
2-(E)-[1-(Ethoxycarbonyl)ethylidene]-5-(ethoxycarbonylmethyl)tetrahy-
drofuran (3j): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-2-methyl-
1,3-butadiene (0.43 g, 1.5 mmol), ethyl 3,4-epoxybutanoate (0.16 g,
1.2mmol), and TiCl 4 (0.27 mL, d ˆ 1.726 gcmÀ3, 2.4 mmol), 3j was isolated
after chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as
a
colorless oil (228 mg, 50%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 0.97 (t, J ˆ 7.4 Hz, 3H; CH2CH3), 1.26 (t, J ˆ 7.1 Hz, 3H; OCH2CH3),
1.33 (d, J ˆ 6.4 Hz, 3H; CH3 to C-5), 1.37 1.69 (m, 1H; 4-H), 2.11 2.23
(m, 1H; 4-H), 2.30 (q, J ˆ 7.4 Hz, 2H; CH2CH3), 2.93 (ddd, J ˆ 9.0, 9.0,
9.0 Hz, 1H; 3-H), 3.21 (ddd, J ˆ 18.4, 9.1, 4.6 Hz, 1H; 3-H), 4.13 (q, J ˆ
7.1 Hz, 2H; OCH2CH3), 4.42 4.55 (m, 1H; 5-H); 13C NMR (62.9 MHz,
CDCl3): d ˆ 13.80, 14.47, 20.57 (3  CH3), 19.38 (CH2CH3), 31.47, 31.53 (C-
1
colorless oil (154 mg, 50%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
1.22 (t, J ˆ 7.1 Hz, 6H; 2  OCH2CH3), 1.64 1.79 (m, 4H; 4-H, CCH3),
2.18 2.31 (m, 1H; 4-H'), AB signal (dA ˆ 2.51, dB ˆ 2.69, JA,B ˆ 15.6 Hz,
ˆ
JA,X ˆ 6.4, JB,X ˆ 6.0 Hz, 2H; CH2C O), 2.91 (dddd, J ˆ 18.2, 9.0, 9.0, 1.7 Hz,
1H; 3-H), 3.16 (dddd, J ˆ 18.2, 7.4, 4.4, 1.3 Hz, 1H; 3-H'), 4.19 (m, 4H; 2 Â
OCH2CH3), 4.87 (quint, J ˆ 7.0 Hz, 1H; 2-H); 13C NMR (50 MHz, CDCl3):
d ˆ 11.19 (CCH3), 14.06, 14.35 (2  OCH2CH3), 29.73, 30.66 (C-3, C-4),
ˆ
ˆ
3, C-4), 59.22 (OCH2CH3), 79.38 (C-5), 103.97 (CC O), 169.25, (C O),
170.16 (C-2); MS (70 eV, EI): m/z (%): 198 (60) [M ], 171 (49), 149 (100),
‡
73 (88); the exact molecular mass for C11H18O3: m/z (%): 198.1256 Æ 2mD
ˆ
39.94 (CH2C O), 59.37, 60.61 (2 Â OCH2CH3), 78.77 (C-5), 97.94
‡
[M ] was confirmed by HRMS (EI, 70 eV).
ˆ
ˆ
(CH3CC O), 169.04, 169.13, 170.03 (C-2, 2  C O); IR (neat): nÄ ˆ 3466
(br), 2984 (s), 2941 (m), 1778 (s), 1733 (s), 1643 (w), 1448 (m), 1371 (s), 1300
(s), 1260 (s), 1176 (s), 1113 (s), 1026 cmÀ1 (s); MS (70 eV, EI): m/z (%): 256
2-(E)-[1-(Ethoxycarbonyl)propylidene]-5-(bromomethyl)tetrahydrofuran
(3o): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-2-ethyl-1,3-buta-
diene (0.91 g, 3.0 mmol), epibromohydrin (0.27 mL, 3.0 mmol, d ˆ
1.655 gcmÀ3), and TiCl4 (0.66 mL, d ˆ 1.726 gcmÀ3, 6.0 mmol), 3o was
isolated after chromatography (silica gel, diethyl ether/petroleum etherˆ
1:3) as an orange solid (366 mg, 44%, E/Z > 98:2). 1H NMR (250 MHz,
CDCl3): d ˆ 0.94 (t, J ˆ 7.3 Hz, 3H; CH2CH3), 1.23 (t, J ˆ 7.2Hz, 3H;
OCH2CH3), 1.84 1.99 (m, 1H; 3-H), 2.15 2.31 (m, 3H; CH2CH3, 3-H'),
2.89 3.04 (m, 1H; 4-H), 3.18 (ddd, J ˆ 18.4, 9.5, 5.3 Hz, 1H; 4-H'),
AB signal (dA ˆ 3.41, dB ˆ 3.47, JAB ˆ 10.4, JA,X ˆ 6.2, JB,X ˆ 4.9 Hz, 2H;
CH2Br), 4.10 (q, J ˆ 7.2Hz, 2H; OC H2CH3), 4.52 4.62 (m, 1H; 5-H);
13C NMR (62.9 MHz, CDCl3): d ˆ 13.60 (CH2CH3), 14.32(OCH 2CH3),
19.32( CH2CH3), 28.27, 30.58 (C-3, C-4), 33.77 (CH2Br), 59.31 (OCH2CH3),
‡
(20) [M ], 210 (72), 122 (100); the exact molecular mass for C13H20O5: m/z
‡
(%): 256.1310 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV);
elemental analysis calcd (%) for C13H20O5 (256.3): C 60.92, H 7.87; found:
C 60.74, H 7.77.
2-(E)-[1-(Ethoxycarbonyl)ethylidene]-5-ethyltetrahydrofuran (3k): Start-
ing
with
1,3-bis(trimethylsilyloxy)-1-ethoxy-2-methyl-1,3-butadiene
(0.75 g, 2.6 mmol), butenoxide (0.20 mL, d ˆ 1.180 gcmÀ3, 2.6 mmol). and
TiCl4 (0.57 mL, d ˆ 1.726gcmÀ3, 5.2mmol), 3k was isolated after chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:3) as a colorless oil
(298 mg, 58%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 0.96 (t, J ˆ
7.0 Hz, 3H; CH2CH3), 1.23 (t, J ˆ 7.1 Hz, 3H; OCH2CH3), 1.50 1.76 (m,
3H; CH2CH3, 4-H), 1.79 (t, J ˆ 1.5 Hz, 3H; CH3), 2.05 2.20 (m, 1H; 4-H),
2.92 (dddd, J ˆ 18.1, 9.1, 9.1, 1.6 Hz, 1H; 3-H), 3.20 (dddd, J ˆ 18.1, 7.4, 4.4,
1.3 Hz, 1H; 3-H'), 4.12(q, J ˆ 7.0 Hz, 2H; OCH2CH3), 4.26 (quint, J ˆ
6.8 Hz, 1H; 5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 9.83, 11.25 (CH3),
14.45 (OCH2CH3), 28.02, 29.41, 31.16 (C-3, C-4, CCH2CH3), 59.32
ˆ
ˆ
80.85 (C-5), 105.02( CHC O), 168.70, 168.90 (C-2, C O); IR (neat): nÄ ˆ
2975 (s), 2937 (m), 1781 (m), 1731 (s), 1698 (s), 1634 (s), 1461 (m), 1445 (m),
1370 (m), 1298 (m), 1254 (s), 1189 (s), 1166 (m), 1099 cmÀ1 (s); MS (70 eV,
‡
EI): m/z (%): 276 (36) [M ], 231 (42), 197 (50), 151 (100); the exact
‡
molecular mass for C11H17O3Br: m/z (%): 276.0361 Æ 2mD [ M ] was
confirmed by HRMS (EI, 70 eV); elemental analysis calcd (%) for
C11H17O3Br (277.2): C 47.67, H 6.18; found: C 47.82, H 6.03.
ˆ
(OCH2CH3), 84.51 (C-5), 96.94 (CCO2Et), 169.49, 170.26 (C-2, C O);
‡
MS (70 eV, EI): m/z (%): 198 (74) [M ], 169 (12), 153 (100); the exact
‡
molecular mass for C11H18O3: m/z (%): 198.1256 Æ 2mD [ M ] was
2-(E)-(Methoxycarbonylmethylidene)-3-methyl-5-ethyltetrahydrofuran
(3p): Starting with 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-pentadiene
(0.52 g, 2.0 mmol), 1,2-butenoxide (0.17 mL, d ˆ 0.837 gcmÀ3, 2.0 mmol),
and TiCl4 (0.44 mL, d ˆ 1.726 gcmÀ3, 4.0 mmol), 3p was isolated after
confirmed by HRMS (EI, 70 eV).
2-(E)-[1-(Ethoxycarbonyl)ethylidene]-5-(3-butenyl)tetrahydrofuran (3l):
Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-2-methyl-1,3-butadiene
(0.75 g, 2.6 mmol), 5,6-epoxy-1-hexene (0.29 mL, d ˆ 0.870 gcmÀ3
,
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as
a
3.5 mmol), and TiCl4 (0.57 mL, d ˆ 1.726gcmÀ3, 5.2mmol), 3l was isolated
colorless oil (169 mg, 46%, E/Z ˆ 5:1, ds ˆ 4:1). 1H NMR (250 MHz,
CDCl3): d ˆ 0.96 (t, J ˆ 7.5 Hz, 3H; CH2CH3), 1.22 (d, J ˆ 7.2Hz, 3H;
CHCH3), 1.33 1.88 (m, 4H; CH2CH3, 4-H), 3.62(s, 3H; OCH 3), 3.63 3.76
after chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a
1
colorless oil (186 mg, 32%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
ˆ
1.26 (t, J ˆ 7.0 Hz, 3H; OCH2CH3), 1.20 1.40 (m, 2H; CH2), 1.60 1.80 (m,
2H; CH2), 1.84 (t, J ˆ 1.5 Hz, 3H; CH2), 2.10 2.30 (m, 2H; CH2), 2.93
(dddd, J ˆ 18.2, 9.2, 9.2, 1.9 Hz, 1H; 3-H), 3.24 (dddd, J ˆ 18.4, 9.2, 4.1,
1.4 Hz, 1H; 3-H), 4.15 (q, J ˆ 7.0 Hz, 2H; OCH2CH3), 4.30 4.42(m, 1H;
(m, 1H; 3-H), 4.33 4.42(m, 1H; 5-H), 5.15, 5.21 (2 Â m, 1H; CHC O,
both diastereomers); 13C NMR (62.9 MHz, CDCl3): d ˆ 9.72(CH 2CH3),
18.67 (CH3 to C-3), 27.86 (CH2CH3), 37.02(C-3), 37.41 (C-4), 50.49 (OCH 3),
ˆ
ˆ
83.37, 87.80 (CHC O, C-5), 168.32(C-2), 181.10 (C O); MS (70 eV, EI):
m/z (%): 184 (68) [M ], 179 (4), 166 (9), 155 (10), 139 (100); the exact
‡
ˆ
ˆ
5-H), 4.95 5.10 (m, 2H; CH CH2), 5.74 5.95 (m, 1H; CH CH2);
13C NMR (62.9 MHz, CDCl3): d ˆ 12.32, 15.61 (CH3), 30.01, 30.12, 31.89,
35.02(CH 2, C-3, C-4, C-1', C-2'), 59.60 (OCH2CH3), 83.22 (C-5), 97.60
‡
molecular mass for C10H16O3: m/z (%): 184.1099 Æ 2mD [ M ] was
confirmed by HRMS (EI, 70 eV).
1450
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0806-1450 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 6

Functionalized 2-Alkylidenetetrahydrofurans
1443 1455
‡
2-(E)-(Phenylcarbonylmethylidene)-5-ethyltetrahydrofuran (3q): Starting
with 1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene (0.58 g, 1.9 mmol),
1,2-butenoxide (0.16 mL, d ˆ 0.837gcmÀ3, 1.9 mmol), and TiCl4 (0.42mL,
d ˆ 1.726gcmÀ3, 3.8 mmol), 3q was isolated after chromatography (silica
gel, diethyl ether/petroleum etherˆ 1:3) as an orange oil (255 mg, 62%,
E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.02(t, J ˆ 7.3 Hz, 3H;
CH2CH3), 1.59 1.83 (m, 3H; 4-H, CH2CH3), 2.19 2.32 (m, 1H; 4-H), 3.14
(dddd, J ˆ 14.3, 9.2, 9.2, 1.9 Hz, 1H; 3-H), 3.49 (dddd, J ˆ 17.9, 9.8, 4.4,
molecular mass for C16H18O4: m/z (%): 274.1205 Æ 2mD [ M ] was
confirmed by HRMS (EI, 70 eV); elemental analysis calcd (%) for
C16H18O4 (274.3): C 70.06, H 6.61; found: C 69.72, H 6.63.
2-(E)-(3-Methoxy-2-oxopropylidene)-5-(chloromethyl)tetrahydrofuran
(3u): Starting with 2,4-bis(trimethylsilyloxy)-1-methoxy-2,4-pentadiene
(0.49 g, 1.8 mmol), epichlorohydrin (0.14 mL, d ˆ 1.180 gcmÀ3, 1.8 mmol),
and TiCl4 (0.40 mL, d ˆ 1.726 gcmÀ3, 3.6 mmol), 3u was isolated after
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as
a
ˆ
1.5 Hz, 1H; 3-H), 4.35 4.46 (m, 1H; 5-H), 6.50 6.51 (m, 1H; CHC O),
colorless oil (165 mg, 45%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.82 2.03 (m, 1H; 4-H), 2.10 2.31 (m, 1H; 4-H'), 2.92 3.10 (m, 1H;
3-H), 3.17 3.44 (m, 1H; 3-H), 3.31 (s, 3H; OCH3), 3.55 3.70 (m, 2H;
CH2Cl), 3.88 (s, 2H; CH2OCH3), 4.55 4.73 (m, 1H; 5-H), 5.94 (m, 1H;
CHCO2Et); 13C NMR (62.9 MHz, CDCl3): d ˆ 26.37, 31.05 (C-3, C-4), 45.33
(CH2Cl), 58.93 (OCH3), 77.58 (CH2OCH3), 82.08 (C-5), 94.14 (CHCOCH2),
7.30 7.53 (m, 3H; Ph), 7.88 7.92(m, 2H; Ph);
13C NMR (62.9 MHz,
CDCl3): d ˆ 9.72(CH CH3), 27.79, 28.59, 31.79 (C-3, C-4, CH2CH3), 85.62
2
ˆ
(C-5), 94.61 (CHC O), 127.41, 128.17, 131.51 (CH, Ph), 139.76 (C, Ph),
ˆ
179.13 (C-2), 190.24 (C O); IR (neat): nÄ ˆ 3084 (w), 3061 (w), 3030 (w),
2966 (s), 2933 (s), 2879 (m), 2855 (m), 1654 (s), 1587 (s), 1571 (m), 1456 (m),
1447 (m), 1386 (s), 1167 cmÀ1 (s); MS (70 eV, EI): m/z (%): 216 (70) [M ],
‡
‡
177.14 (C-2), 197.08 (COCH2); MS (70 eV, EI): m/z (%): 204 (67) [M ], 176
201 (100), 176 (13), 161 (20), 139 (22), 119 (45); the exact molecular mass
(34), 161 (27), 159 (100); the exact molecular mass for C9H13O3Cl: m/z (%):
‡
for C14H16O2: m/z (%): 216.1150 Æ 2mD [ M ] was confirmed by HRMS
‡
204.0553 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
(EI, 70 eV); elemental analysis calcd (%) for C14H16O2 (216.3): C 77.75, H
7.46; found: C 76.88, H 7.60.
2-(E)-(3-Methoxy-2-oxopropylidene)-5-ethyltetrahydrofuran (3v): Start-
ing with 2,4-bis(trimethylsilyloxy)-1-methoxy-2,4-pentadiene (0.96 g,
3.5 mmol), 1,2-butenoxide (0.30 mL, 3.5 mmol, d ˆ 0.837 gcmÀ3), and TiCl4
(0.77 mL, d ˆ 1.726gcmÀ3, 7.0 mmol), 3v was isolated after chromatogra-
phy (silica gel, diethyl ether/petroleum etherˆ 1:3) as a colorless oil
(258 mg, 40%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 0.96 (t, J ˆ
7.5 Hz, 3H; CH2CH3), 1.53 1.77 (m, 3H; 4-H, CH2CH3), 2.12 2.25 (m,
1H; 4-H), 2.99 (dddd, J ˆ 18.3, 9.1, 9.1, 1.8 Hz, 1H; 3-H), 3.27 3.42 (m,
4H; OCH3, 3-H), 3.92(s, 2H; C H2OCH3), 4.32 4.38 (m, 1H; 5-H), 5.92(s,
2-(E)-(Phenylcarbonylmethylidene)-5-(chloromethyl)tetrahydrofuran
(3r): Starting with 1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene
(0.67 g, 2.2 mmol), epichlorohydrin (0.17 mL, d ˆ 1.180gcmÀ3, 2.2 mmol),
and TiCl4 (0.48 mL, d ˆ 1.726 gcmÀ3, 4.4 mmol), 3r was isolated after
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as
a
colorless oil (265 mg, 51%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.98 2.13 (m, 1H; 4-H), 2.26 2.37 (m, 1H; 4-H), 3.16 3.31 (m, 1H;
3-H), 3.42 3.56 (m, 1H; 3-H), 3.69 (dd, J ˆ 5.1, 0.9 Hz, 2H; CH2Cl), 4.68
4.78 (m, 1H; 5-H), 6.58 (t, J ˆ 1.7 Hz, 1H; CHCO2Et), 7.39 7.53 (m, 3H;
Ph), 7.88 7.93 (m, 2H; Ph); 13C NMR (62.9 MHz, CDCl3): d ˆ 26.59, 31.16
(C-3, C-4), 45.44 (CH2Cl), 82.10 (C-5), 95.29 (CHCOPh), 127.40, 128.22,
131.71 (CH, Ph), 139.37 (C, Ph), 177.69 (C-2), 190.06 (COPh); IR (KBr):
nÄ ˆ 3099 (w), 3083 (w), 3055 (w), 2984 (w), 2919 (w), 1663 (s), 1598 (s), 1583
(s), 1566 (s), 1383 (m), 1374 (m), 1167 cmÀ1 (s); MS (70 eV, EI): m/z (%):
1H; CHC OCH2); 13C NMR (50 MHz, CDCl3): d ˆ 9.73 (CH2CH3), 27.82,
ˆ
28.54, 31.77 (CH2CH3, C-3, C-4), 59.12(OCH 3), 77.79 (CH2OCH3), 85.75
ˆ
ˆ
(C-5), 93.53 (CHC O), 178.59 (C-2), 197.23 (C O); MS (70 eV, DCI, NH3):
‡
‡
m/z (%): 185 (100) [M‡1 ], 202 (82) [M‡18 ].
2-Oxo-3-(1-trimethylsilyloxy)ethenyl-4,5-dihydrofuran (5a): Triethylamine
(11.36 mL, 81.9 mmol, d ˆ 0.73 gcmÀ3) was added to a solution (250 mL) of
3-acetyl-2-oxo-4,5-dihydrofuran (7.0 g, 54.6 mmol, d ˆ 1.19gcmÀ3) in ben-
zene at 08C. The solution was stirred for 30 min, and subsequently
trimethylchlorosilane (12.42 mL, 98.3 mmol, d ˆ 0.83 gcmÀ3) was slowly
added. The solution was warmed to ambient temperature over 6 h and
subsequently stirred for 18 h. The solvent was removed in vacuo, and
pentane was added to the residue (100 mL). The suspension was filtered
under nitrogen, and the filtrate was concentrated in vacuo to give 5a as a
slightly yellow oil (10.06 g, 92%). 1H NMR (250 MHz, CDCl3): d ˆ 0.20 (s,
9H; Si(CH3)3), 2.25 (t, J ˆ 1.5 Hz, 3H; CCH3), 2.77 (tt, J ˆ 7.5, 1.5 Hz, 2H;
4-H), 4.15 (t, J ˆ 7.5 Hz, 2H; 5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 0.87
(Si(CH3)3), 18.47 (CCH3), 25.99 (C-4), 64.22 (C-5), 104.55 (C-3), 162.39
‡
236 (100) [M ], 159 (52), 105 (46), 77 (33), 69 (48); the exact molecular
‡
mass for C13H13O2Cl: m/z (%): 236.0604 Æ 2mD [ M ] was confirmed by
HRMS (EI, 70 eV); elemental analysis calcd (%) for C13H13O2Cl (236.7): C
65.97, H 5.54; found: C 66.10, H 5.61.
2-(E)-(Phenylcarbonylmethylidene)-5-(bromomethyl)tetrahydrofuran
(3s): Starting with 1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene
(0.74 g, 2.4 mmol), epibromohydrin (0.21 mL, d ˆ 1.655 gcmÀ3, 2.4 mmol),
and TiCl4 (0.53 mL, d ˆ 1.726 gcmÀ3, 4.8 mmol), 3s was isolated after
chromatography (silica gel, diethyl ether/petroleum etherˆ 1:3) as an
orange solid (298 mg, 44%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ
1.92 2.04 (m, 1H; 4-H), 2.25 2.33 (m, 1H; 4-H), 3.14 3.26 (m, 1H; 3-H),
3.40 3.54 (m, 3H; 3-H, CH2Br), 4.64 4.70 (m, 1H; 5-H), 6.54 6.56 (m,
‡
(Me3SiOC), 172.31 (C-2); MS (70 eV, EI): m/z (%): 200 (23) [M ], 185
(100), 141 (19), 110 (9), 73 (47); the exact molecular mass for C9H16O3Si:
m/z (%): 200.0868 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
1H; CHC O), 7.36 7.50 (m, 3H; Ph), 7.86 7.90 (m, 2H; Ph); 13C NMR
ˆ
‡
(62.9 MHz, CDCl3): d ˆ 27.78, 31.24 (C-3, C-4), 33.43 (CH2Br), 81.85 (C-5),
ˆ
5-Ethyl-2-oxo-3-(1-trimethylsilyloxy)ethenyl-4,5-dihydrofuran (5b): Tri-
ethylamine (2.56 mL, 18.5 mmol, d ˆ 0.73 gcmÀ3) and trimethylchlorosi-
lane (2.81 mL, 22.5 mmol, d ˆ 0.83gcmÀ3) at 08C were slowly added to a
solution (50 mL) of 3-acetyl-5-ethyl-2-oxo-4,5-dihydrofuran (1.93 g,
12.36 mmol) in benzene. The solution was stirred for 30 min, warmed to
ambient temperature over 6 h, and subsequently stirred at 208C for 48 h.
The solvent was removed in vacuo, and pentane (20 mL) was added to the
residue. The suspension was filtered under nitrogen, and the filtrate was
concentrated in vacuo to give 5b as a slightly yellow oil (2.57 g, 91%).
1H NMR (250 MHz, CDCl3): d ˆ 0.23 (s, 9H; Si(CH3)3), 0.94 (t, J ˆ 6.9 Hz,
3H; CH2CH3), 1.62(dq, J ˆ 6.9, 7.3 Hz, 2H; CH2CH3), 2.28 (t, J ˆ 1.9 Hz,
3H; CH3), 2.25 2.35 (m, 1H; 4-H), 2.88 (dq, J ˆ 7.3, 1.9 Hz, 1H; 4-H),
4.22 4.33 (m, 1H; 5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 0.93 (Si(CH3)3),
18.63 (CH3), 29.29 (CH2CH3), 31.57 (C-4), 77.36 (C-5), 105.78 (C-3), 162.06
95.34 (CHC O), 127.42, 128.23, 131.73 (CH, Ph), 139.36 (C, Ph), 177.64 (C-
ˆ
2) 190.09 (C O); IR (KBr): nÄ ˆ 3098 (w), 3054 (w), 3026 (w), 2981 (w), 2945
(w), 2917 (w), 1660 (s), 1596 (s), 1567 (s), 1457 (m), 1433 (m), 1380 (s),
‡
1165 cmÀ1 (s); MS (70 eV, EI): m/z (%): 280 (60) [M ], 203 (24), 180 (18),
147 (35), 122 (33), 105 (100); the exact molecular mass for C13H13O2Br: m/z
‡
(%): 280.0099 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV);
elemental analysis calcd (%) for C13H13O2Br (281.1): C 55.54, H 4.66;
found: C 55.32, H 4.46.
2-(E)-[1-(Phenylcarbonyl)methylidene]-5-(ethoxycarbonylmethyl)tetra-
hydrofuran (3t): Starting with 1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-bu-
tadiene (0.18 g, 0.6 mmol), 3,4-ethyl epoxybutanoate (0.08 g, 0.6 mmol),
and TiCl4 (0.13 mL, d ˆ 1.726 gcmÀ3, 1.2mmol), 3t was isolated after
chromatography (silica gel, ether/petroleum etherˆ 1:3) as a colorless oil
(68 mg, 41%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.28 (t, J ˆ
7.1 Hz, 3H; OCH2CH3), 1.76 1.91 (m, 1H; 4-H), 2.31 2.44 (m, 1H; 4-H),
AB signal (dA ˆ 2.61, dB ˆ 2.74, JAB ˆ 16.0, JA,X ˆ 6.0, JB,X ˆ 7.2Hz, 2H;
‡
(R3SiOC), 172.01 (C-2); MS (70 eV, EI): m/z (%): 228 (15) [M ], 213 (100),
171 (79), 147 (44), 127 (50); the exact molecular mass for C11H20O3Si: m/z
‡
(%): 228.1182 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
ˆ
CH2C O), 3.16 (dddd, J ˆ 18.0, 9.1, 9.1, 1.9 Hz, 1H; 3-H), 3.48 (dddd, J ˆ
19.2, 9.1, 4.3, 1.4 Hz, 1H; 3-H), 4.19 (q, J ˆ 7.1 Hz, 2H; OCH2CH3), 4.87
2,1'-Bis(trimethylsilyloxy)-(3-ethylene)-4,5-dihydrofuran (6a): n-Butyl-
lithium (7.25 mL, 17.15 mmol, 2.36m solution in n-hexane) was added to a
solution (20 mL) of diisopropylamine (2.25 mL, 16.00 mmol, d ˆ
0.72gcm À3) in THF, and the solution was stirred for 30 min. This solution
was added to a solution (50 mL) of 2-oxo-3-(1-trimethylsilyloxy)ethenyl-
4,5-dihydrofuran 5a (1.93 g, 12.36 mmol) in THF at À788C. The solution
was stirred for 25 min, and subsequently trimethylchlorosilane (2.31 mL,
ˆ
(quint, J ˆ 7.0 Hz, 1H; 2-H), 6.53 (t, J ˆ 1.7 Hz, 1H; CHC O), 7.38 7.52
(m, 3H; Ph), 7.87 7.91 (m, 2H; Ph); 13C NMR (62.9 MHz, CDCl3): d ˆ
ˆ
14.12(OCH 2CH3), 29.09, 31.38 (C-3, C-4), 39.73 (CHCH2C O), 60.90
ˆ
(OCH2CH3), 79.73 (C-5), 95.41 (CHC O), 127.52, 128.30, 131.73 (CH, Ph),
ˆ
ˆ
139.63 (C, Ph), 169.91 (C O), 177.89 (C-2), 190.29 (C O); MS (70 eV, EI):
m/z (%): 274 (40) [M ], 186 (100), 122 (22), 117 (34), 105 (64); the exact
‡
Chem. Eur. J. 2002, 8, No. 6
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0806-1451 $ 17.50+.50/0
1451

P. Langer et al.
FULL PAPER
18.29 mmol, d ˆ 0.83 gcmÀ3) was added. After stirring for 10 min at À788C,
the solution was warmed to 208C over 45 min. The solvent was removed in
vacuo, and pentane (20 mL) was added to the residue. The suspension was
filtered under nitrogen, and the filtrate was concentrated in vacuo to give
6a as a yellow oil (2.96 g, 95%). 1H NMR (250 MHz, CDCl3): d ˆ 0.20, 0.24
(2  s, 2  9H; Si(CH3)3), 2.75 (t, J ˆ 7.5 Hz, 2H; 4-H), 3.88 (s, 1H; cis,
(E)-5-Butyl-2'-oxotetrahydro-[2,3']-bifuranylidene (7c): Starting with 2,1'-
bis(trimethylsilyloxy)-3-ethylene-4,5-dihydrofuran 6a (0.65 g, 2.4 mmol),
1,2-hexenoxide (0.287 mL, d ˆ 0.83 gcmÀ3
,
2.4 mmol), and TiCl4
(0.525 mL, d ˆ 1.726 gcmÀ3, 4.7 mmol), 7c was isolated by chromatography
(silica gel, diethyl ether/petroleum etherˆ 1:1) as a colorless oil (185 mg,
37%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 0.85 (t, J ˆ 6.6 Hz, 3H;
(CH2)2CH3), 1.18 1.39 (m, 4H; (CH2)2CH3), 1.39 1.70 (m, 3H; 4-H,
CHCH2(CH2)2), 2.10 2.20 (m, 1H; 4-H), 2.80 (dt, J ˆ 7.6, 1.7 Hz, 2H; 4'-
H), 2.85 2.93 (m, 1H; 3-H), 3.25 (dddd, J ˆ 17.7, 8.9, 4.6, 1.9 Hz, 1H; 3-H),
4.22 (t, J ˆ 7.6 Hz, 5'-H), 4.34 4.40 (m, 1H; 5-H); 13C NMR (62.9 MHz,
CDCl3): d ˆ 13.74 ((CH2)2CH3), 22.31 (CH2CH3), 24.93 (CH2CH2CH3),
29.08, 29.27 (C-3, C-4'), 34.43 (CHCH2(CH2)2), 65.00 (C-5'), 84.88 (C-5),
H2C C), 3.98 (s, 1H; trans, H2C C), 4.24 (t, J ˆ 7.5 Hz, 2H; 5-H); 13C NMR
(62.9 MHz, CDCl3): d ˆ 0.53, 0.93 (Si(CH3)3), 30.18 (C-4), 66.04 (C-5), 81.66
ˆ
ˆ
ˆ
(C CH2), 86.83 (C-3), 153.26 (Me3SiOC), 155.05 (C-2); MS (70 eV, EI): m/z
(%): 273 (18) [M ], 257 (20), 245 (16), 185 (100), 158 (77).
‡
2,1'-Bis(trimethylsilyloxy)-5-ethyl-3-ethylene-4,5-dihydrofuran (6b): n-Bu-
tyllithium (3.71 mL, 2.36m solution in n-hexane, 8.77 mmol) was added to a
ˆ
92.20 (C-3'), 169.17 (C O), 173.07 (C-2); IR (KBr): nÄ ˆ 2958 (s), 2933 (s),
solution (20 mL) of diisopropylamine (1.32 mL, 9.39 mmol, d ˆ 0.72gcm À3
)
2873 (s), 1774 (s), 1658 (m), 1640 (m), 1382 (m), 1219 (s), 1190 (s), 1083 (w),
in THF, and the solution was stirred for 30 min. This solution was added to
‡
1025 cmÀ1 (s); MS (70 eV, EI): m/z (%): 210 (41) [M ], 143 (16), 128 (29),
a
solution (50 mL) of 5-ethyl-2-oxo-3-(1-trimethylsilyloxy)ethenyl-4,5-
113 (57), 85 (100); the exact molecular mass for C12H18O3: m/z (%):
dihydrofuran 5b (1.43 g, 6.26 mmol) in THF at À788C. The solution was
stirred for 25 min, and subsequently trimethylchlorosilane (1.34 mL,
10.65 mmol, d ˆ 0.83 gcmÀ3) was slowly added. After stirring for 10 min
at À788C, the solution was warmed to 208C over 45 min. The solvent was
removed in vacuo, and pentane (20 mL) was added to the residue. The
suspension was filtered under nitrogen, and the filtrate was concentrated in
vacuo to give 6b as a yellow oil (1.77 g, 94%). 1H NMR (250 MHz, CDCl3):
d ˆ 0.20, 0.26 (2  s, 2  9H; Si(CH3)3), 0.95 (t, J ˆ 7.5 Hz, 3H; CH2CH3),
1.57 1.69 (m, 2H; CH2CH3), 2.32 2.40 (m, 1H; 4-H), 2.72 2.83 (m, 1H;
‡
210.1255 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV).
(E)-5-(3-Butylene)-2'-oxotetrahydro-[2,3']-bifuranylidene (7d): Starting
with 4-(1-trimethylsilyloxy)ethenyl-5-trimethylsiloxy-2,3-dihydrofuran 6a
(0.6 g, 2.2 mmol), 1,5-hexenmonoxide (0.25 mL, d ˆ 0.87 gcmÀ3, 1.5 mmol),
and TiCl4 (0.35 mL, d ˆ 1.726 gcmÀ3, 3.15 mmol), 7d was isolated by
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:2) as
a
colorless oil (163 mg, 36%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.58 1.75 (m, 3H; 4-H, CH2CH), 2.08 2.18 (m, 3H; 4-H,
ˆ
H2C CHCH2), 2.80 (dt, J ˆ 7.6, 1.6 Hz, 2H; 4'-H), 2.84 2.95 (m, 1H;
ˆ
ˆ
4-H), 3.82(s, 1H; cis, H2C C), 3.92(s, 1H; trans, H2C C), 4.20 4.35 (m,
1H; 5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 0.10, 0.51 (Si(CH3)3), 9.38
3-H), 3.18 3.25 (m, 1H; 3-H), 4.19 (t, J ˆ 7.6 Hz, 2H; 5'-H), 4.37 (q, J ˆ
ˆ
6.8 Hz, 1H; 5-H), 4.90 (d, J ˆ 10.2Hz, 1H; trans, H2C C), 4.95 (d, J ˆ
ˆ
(CH3), 29.24 (CH2CH3), 35.38 (C-4), 78.96 (C-5), 81.22 (C CH2), 86.41 (C-
3), 153.44 (Me3SiOC), 158.32(C-2); MS (70 eV, EI): m/z (%): 299 (11)
[M ], 213 (32), 171 (30), 147 (100), 73 (77).
16.8 Hz, 1H; cis, H2C C); 13C NMR (62.9 MHz, CDCl3): d ˆ 24.82 (C-4),
ˆ
ˆ
‡
28.94, 29.11, 29.53 (C4', C3, CH2C CHCH2), 24.82 (C-4, CH2CH), 64.92(C-
5'), 83.96 (C-5), 92.29 (C-3'), 115.00 (H2C CH), 137.03 (H2C CH), 168.88
ˆ
ˆ
General procedure for the synthesis of 2-alkylidenetetrahydrofurans (7):
The compound 1,2-butenoxide (0.135 mL, d ˆ 0.837 gcmÀ3, 1.5 mmol) at
208C in the presence of molecular sieves (4 ä) was added to a solution
(30 mL) of 6a (0.42g, 1.5 mmol) in CH 2Cl2. The solution was cooled to
À788C, and TiCl4 (3.6 mmol, 0.40 mL, d ˆ 1.726 gcmÀ3) was slowly added.
After warming of the solution to 208C over 6 h, the solution was stirred for
12h. A saturated aqueous solution of NaCl (150 mL) was added, and the
organic layer was separated. The aqueous layer was extracted with diethyl
ether (4 Â 150 mL). The organic layer was dried (MgSO4), filtered, and the
filtrate was concentrated in vacuo. The residue was purified by chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:2) to give 7b as a
colorless oil (90 mg, 34%).
ˆ
(C O), 172.92 (C-2); IR (KBr): nÄ ˆ 3078 (m), 2937 (s), 1770 (s), 1664 (m),
1642(m), 1382(m), 1189 (s), 1054 (s), 1025 (s), 918 (m), 723 cm À1 (w); MS
‡
(70 eV, EI): m/z (%): 208 (93) [M ], 167 (21), 153 (33), 128 (52), 113 (100);
‡
the exact molecular mass for C12H16O3: m/z (%): 208.1099 Æ 2mD [ M ]
was confirmed by HRMS (EI, 70 eV).
(E)-5-Chloromethyl-2'-oxotetrahydro-[2,3']-bifuranylidene (7e): Starting
with 4-(1-trimethylsilyloxy)ethenyl-5-trimethylsilyloxy-2,3-dihydrofuran
6a (0.6 g, 2.2 mmol), epichlorohydrin (0.173 mL, d ˆ 1.183 gcmÀ3
,
2.2 mmol), and TiCl4 (0.49 mL, d ˆ 1.726 gcmÀ3, 4.4 mmol, 7e was isolated
by chromatography (silica gel, diethyl ether/petroleum etherˆ 1:2) as a
1
colorless oil (205 mg, 46%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
1.96 (ddt, J ˆ 8.5, 5.9, 2.1 Hz, 1H; 4-H), 2.16 2.31 (m, 1H; 4-H), 2.81 (dt,
J ˆ 7.7, 1.9 Hz, 2H; 4'-H), 2.91 3.05 (m, 1H; 3-H), 3.23 (dddd, J ˆ 18.8, 9.4,
4.2, 1.8 Hz, 1H; 3-H), 3.61 (dd, J ˆ 5.1, 1.8 Hz, 2H; CH2Cl), 4.23 (t, J ˆ
7.7 Hz, 2H; 5'-H), 4.66 (q, J ˆ 6.0 Hz, 1H; 5-H); 13C NMR (62.9 MHz,
CDCl3): d ˆ 24.79 (C-4), 26.69 (C-4'), 28.56 (C-3), 45.36 (CH2Cl), 65.07 (C-
(E)-5-Ethyltetrahydro-[2,3']-bifuranyliden-2'-one
(7b):
1H
NMR
(250 MHz, CDCl3): d ˆ 0.92(t, J ˆ 7.4 Hz, 3H; CH2CH3), 1.52 1.71 (m,
3H; 4-H, CH2CH3), 2.14 2.18 (m, 1H; 4-H), 2.84 (dt, J ˆ 7.5, 1.9 Hz, 2H;
4'-H), 2.90 2.98 (m, 1H; 3'-H), 3.18 3.31 (m, 1H; 3-H), 4.19 4.26 (t, J ˆ
7.5 Hz, 2H; 5'-H), 4.30 4.36 (m, 1H; 5-H); 13C NMR (62.9 MHz, CDCl3):
d ˆ 9.60 (CH2CH3), 24.92 (C-4), 27.68 (CH2CH3), 28.75, 29.07 (C-3, C-4'),
ˆ
5'), 82.51 (C-5), 93.48 (C-3'), 168.09 (C O), 172.68 (C-2); IR (KBr): nÄ ˆ
2975 (s), 2933 (s), 1772 (s), 1656 (m), 1458 (m), 1385 (s), 1261 (m), 1199 (s),
65.02(C-5 '), 85.99 (C-5), 92.20 (C-3'), 169.20 (C O), 173.09 (C-2); IR
1181 (m), 1077 (m), 1053 (m), 1023 cmÀ1 (m); MS (70 eV, EI): m/z (%): 202
ˆ
‡
(KBr): nÄ ˆ 2963 (s), 2925 (s), 2879 (m), 1761 (s), 1652 (m), 1456 (m), 1378
(40) [M ], 167 (17), 144 (13), 113 (26), 85 (100); the exact molecular mass
‡
(m), 1188 (s), 1080 (s), 1020 (s), 953 (m), 790 cmÀ1 (w); MS (70 eV, EI): m/z
for C9H11ClO3: m/z (%): 202.0396 Æ 2mD [ M ] was confirmed by HRMS
‡
(%): 182(27) [ M ], 113 (29), 85 (100), 57 (17), 55 (19); the exact molecular
(EI, 70 eV).
‡
mass for C10H14O3: m/z (%): 182.0942 Æ 2mD [ M ] was confirmed by
(E)-5-Bromomethyl-2'-oxotetrahydro-[2,3']-bifuranylidene (7 f): Starting
with 2,1'-bis(trimethylsilyloxy)-(3-ethylene)-4,5-dihydrofuran 6a (0.65 g,
2.4 mmol), epibromohydrin (0.204 mL, d ˆ 0.83 gcmÀ3, 2.4 mmol), and
TiCl4 (0.525 mL, d ˆ 1.726 gcmÀ3, 4.7 mmol), 7 f was isolated by chroma-
tography (silica gel, diethyl ether/petroleum etherˆ 1:1) as a colorless oil
(365 mg, 62%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.94 2.05 (m,
1H; 4-H), 2.88 (dt, J ˆ 7.6, 2.0 Hz, 2H; 4'-H), 3.01 (ddt, J ˆ 17.6, 1.5 Hz, 1H;
3-H), 3.29 (dddd, J ˆ 17.5, 9.3, 4.7, 2.4 Hz, 1H; 3-H), 3.50 (dd, J ˆ 6.4,
1.8 Hz, 2H; CH2Br), 4.30 (t, J ˆ 7.6 Hz, 2H; 5'-H), 4.70 (q, J ˆ 5.9 Hz, 1H;
5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 24.58 (C-4), 27.62 (C-4'), 28.42 (C-
HRMS (EI, 70 eV).
(E)-5-Methyltetrahydro-[2,3']-bifuranyliden-2'-one (7a): Starting with
4-(1-trimethylsilyloxy)ethenyl-5-trimethylsilyloxy-2,3-dihydrofuran 6a
(0.42g, 1.5 mmol), 1,2-propenoxide (0.109 mL, d ˆ 0.829 gcmÀ3, 1.5 mmol),
and TiCl4 (0.35 mL, d ˆ 1.726 gcmÀ3
, 3.0 mmol), 7a was isolated by
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:2) as
a
colorless solid (112mg, 42%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.00 (d, J ˆ 6.6 Hz, 3H; CHCH3), 1.50 1.64 (m, 1H; 4-H), 2.09 2.21
(m, 1H; 4-H), 2.76 (t, J ˆ 7.0 Hz, 2H; 4'-H) 2.82 2.91 (m, 1H; 3'-H), 3.16
3.25 (dddd, J ˆ 18.6, 8.8, 3.9, 1.6 Hz, 1H; 3-H), 4.19 (t, J ˆ 7.5 Hz, 5'-H),
4.46 4.54 (m, 1H; 5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 20.16
(CHCH3), 24.82 (C-4), 29.21, 30.93 (C-3, C-4'), 64.92(C-5 '), 80.87 (C-5),
ˆ
3), 33.45 (CH2Br), 64.85 (C-5'), 82.02 (C-5), 93.22 (C-3'), 167.84 (C O),
172.37 (C-2); IR (KBr): nÄ ˆ 2965 (w), 2926 (w), 1766 (s), 1672 (s), 1383 (m),
1259 (w), 1222 (s), 1199 (s), 1091 (w), 1024 (s), 863 cmÀ1 (w); MS (70 eV,
‡
EI): m/z (%): 246 (39) [M ], 188 (7), 167 (23), 113 (46), 85 (100); the exact
ˆ
92.18 (C-3'), 169.07 (C O), 172.93 (C-2); IR (KBr): nÄ ˆ 2960 (s), 2930 (s),
‡
molecular mass for C9H11BrO3: m/z (%): 245.9891 Æ 2mD [ M ] was
1768 (s), 1671 (m), 1430 (w), 1381 (m), 1259 (m), 1185 (s), 1025 (s), 752 (m),
‡
confirmed by HRMS (EI, 70 eV).
694 cmÀ1 (w); MS (70 eV, EI): m/z (%): 168 (100) [M ], 139 (23), 113 (68),
110 (20), 95 (13); the exact molecular mass for C9H12O3: m/z (%):
(E)-5-Ethyl-5'-methyl-2'-oxotetrahydro-[2,3']-bifuranylidene (7g): Starting
with 2-ethyl-4-(1-trimethylsilyloxy)ethenyl-5-trimethylsilyloxy-2,3-dihy-
‡
168.0786 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV); elemental
analysis calcd (%) for C9H12O3: C 64.28, H 7.20; found: C 63.99, H 6.94.
drofuran 6b (0.42g, 1.4 mmol), 1,2-propenoxide (0.096 mL,
d ˆ
1452
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 0947-6539/02/0806-1452 $ 17.50+.50/0 Chem. Eur. J. 2002, 8, No. 6

Functionalized 2-Alkylidenetetrahydrofurans
1443 1455
0.829 gcmÀ3, 1.4 mmol), and TiCl4 (0.308 mL, d ˆ 1.726 gcmÀ3, 2.8 mmol),
7g was isolated by chromatography (silica gel, diethyl ether/petroleum
etherˆ 1:2) as a colorless solid (156 mg, 57%, E/Z > 98:2). 1H NMR
(250 MHz, CDCl3): d ˆ 0.97 (t, J ˆ 7.3 Hz, 3H; CH2CH3), 1.35 (d, J ˆ
6.2Hz, 3H; CHC H3), 1.55 1.76 (m, 2H; CH2CH3, 4-H), 2.16 2.24 (m,
1H; 4-H), 2.37 2.53 (m, 1H; 3-H), 2.87 2.98 (m, 2H; 3-H, 4'-H), 3.24
3.38 (m, 1H; 4'-H), 4.33 4.40 (m, 1H; 5'-H), 4.51 4.57 (m, 1H; 5-H);
13C NMR (62.9 MHz, CDCl3): d ˆ 8.87 (CH2CH3), 20.15 (CHCH3), 29.24,
29.28 (CH2CH3, C-4), 30.40, 30.98 (C-3, C-4'), 78.04 (C-5'), 80.76 (C-5),
(250 MHz, CDCl3): d ˆ 0.94 (d, J ˆ 7.0 Hz, 3H; CH3 to C-4), 1.21 (d, J ˆ
6.6 Hz, 3H; CH3 to C-5), 1.27 (t, J ˆ 7.0 Hz, 3H; OCH2CH3), 1.79 (t, J ˆ
ˆ
1.5 Hz, 3H; CCH3), 2.17 2.45 (m, 1H; 4-H), 2.83 (ddd, J ˆ 17.9, 5.4,
1.4 Hz, 1H; 3-H), 3.14 (ddd, J ˆ 17.9, 7.7, 1.6 Hz, 1H; 3-H'), 4.13 (q,
J ˆ 7.1 Hz, 2H; OCH2CH3), 4.48 (dt, J ˆ 6.5, 6.5 Hz, 1H; 5-H); 13C NMR
(62.9 MHz, CDCl3): d ˆ 11.18, 13.70, 14.49, 15.32(CH 3), 34.82(C-4), 39.19
ˆ
(C-3), 59.39 (OCH2CH3), 81.27 (C-5), 97.52 (C-2), 169.57 (C O).
trans-2-(E)-(Ethoxycarbonylmethylidene)-7-oxabicyclo[4.3.0]nonane
(11a): Following the general procedure, 1,3-bis(trimethylsilyloxy)-1-
ethoxy-1,3-butadiene (0.50 g, 1.8 mmol), 1,2-cyclohexenoxide 10 (0.18 mL,
ˆ
93.22 (C-3'), 168.70 (C O), 172.49 (C-2); IR (KBr): nÄ ˆ 2975 (s), 2933 (s),
1772(s), 1656 (m), 1458 (m), 1385 (s), 1621 (m), 1199 (s), 1181 (m),
d ˆ 0.971 gcmÀ3
,
1.8 mmol), and TiCl4 (0.40 mL, d ˆ 1.726 gcmÀ3
,
1077 (m), 1053 (m), 1023 cmÀ1 (m); MS (70 eV, EI): m/z (%): 196 (100)
3.6 mmol) were allowed to react. Chromatographic purification (silica
gel, diethyl ether/petroleum etherˆ 1:3) afforded 11a as a colorless solid
(98 mg, 26%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.14 2.18 (m,
11H; CH2CH3, 1-H, CH2), 2.22 2.36 (m, 1H; CH2), 3.40 3.50 (m, 3H;
6-H, 9-H), 4.06 (q, J ˆ 7.1 Hz, 2H; OCH2CH3), 5.23 5.25 (m, 1H;
‡
[M ], 167 (33), 154 (21), 114 (37), 110 (57); the exact molecular mass for
‡
C11H16O3: m/z (%): 196.1099 Æ 2mD [ M ] was confirmed by HRMS (EI,
70 eV).
(E)-5-Bromomethyl-2'-oxotetrahydro-[2,3']-bifuranylidene (7h): Starting
with 2-ethyl-4-(1-trimethylsilyloxy)ethenyl-5-trimethylsilyloxy-2,3-dihy-
drofuran 6b (0.38 g, 1.3 mmol), epibromohydrin (0.99 mL, d ˆ
0.829 gcmÀ3, 1.3 mmol), and TiCl4 (0.26 mL, d ˆ 1.726 gcmÀ3, 2.6 mmol),
7h was isolated by chromatography (silica gel, diethyl ether/petroleum
CHC O); 13C NMR (62.9 MHz, CDCl3): d ˆ 14.32(OCH 2CH3), 23.97,
ˆ
25.22, 28.23, 30.23, 36.20 (C-9, CH2), 44.31 (CH, C-1), 59.03 (OCH2CH3),
ˆ
ˆ
86.66, 90.84 (CHC O, C-6), 168.27 (C O), 175.51 (C-8); MS (70 eV, EI):
‡
m/z (%): 210 (100) [M ], 165 (96), 122 (84), 115 (58), 81 (56); the exact
a
colorless oil (289 mg, 82%, E/Z > 98:2). 1H NMR
‡
etherˆ 1:1) as
molecular mass for C12H18O3: m/z (%): 210.1255 Æ 2mD [ M ] was
(250 MHz, CDCl3): d ˆ 0.87 (t, J ˆ 7.3 Hz, 3H; CH2CH3), 1.58 (dq, J ˆ 7.3,
7.1 Hz, 2H; CH2CH3), 1.82 1.99 (m, 1H; 4-H), 2.17 2.32 (m, 1H; 4-H),
2.34 2.47 (m, 1H; 4'-H), 2.83 2.93 (m, 2H; 3-H, 4'-H), 3.18 3.31 (m, 1H;
3-H), 3.43 (d, J ˆ 5.2Hz, 2H), 4.27 4.34 (m, 1H; 5 '-H), 4.59 4.64 (m, 1H;
5-H); 13C NMR (62.9 MHz, CDCl3): d ˆ 8.84 (CH2CH3), 28.61 (CH2CH3),
29.08 (C-4), 30.05, 30.28 (C-3, C-4'), 33.42(CH 2Br), 78.16 (C-5'), 82.00 (C-
confirmed by HRMS (EI, 70 eV); elemental analysis calcd (%) for
C12H18O3 (210.3): C 68.55, H 8.63; found: C 68.24, H 8.35.
trans-2-(E)-(Methoxycarbonylmethylidene)-7-oxabicyclo[4.3.0]nonane
(11b): Starting with 1,3-bis(trimethylsilyloxy)-1-methoxy-1,3-butadiene
(1.30 g, 5 mmol), 1,2-cyclohexenoxide (0.51 mL, d ˆ 0.971 gcmÀ3, 5 mmol),
and TiCl4 (1.10 mL, d ˆ 1.726 gcmÀ3, 10.0 mmol), 11b was isolated by
ˆ
5), 94.56 (C-3'), 167.58 (C O), 172.12 (C-2); IR (KBr): nÄ ˆ 2963 (w), 2933
chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:2) as
a
(w), 1759 (s), 1667 (s), 1512(m), 1460 (w), 1354 (m), 1257 (m), 1197 (s),
colorless oil (282 mg, 30%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.15 1.58 (m, 9H; CH2CH2, 4-H), 2.24 2.37 (m, 2H; 1-H, 9-H), 3.41
3.53 (m, 2H; 6-H, 9-H), 3.60 (s, 3H; OCH3), 5.27 (t, J ˆ 1.1 Hz, 1H;
‡
1087 (w), 1021 (s), 799 cmÀ1 (s); MS (70 eV, EI): m/z (%): 274 (36) [M ],
190 (23), 130 (27), 114 (55), 85 (100); the exact molecular mass for
‡
C11H15BrO3: m/z (%): 274.0204 Æ 2mD [ M ] was confirmed by HRMS
C CH); 13C NMR (62.9 MHz, CDCl3): d ˆ 23.93, 25.28, 28.28, 30.27
ˆ
(EI, 70 eV).
(CH2CH2), 36.28 (C-9), 44.35 (C-1), 50.60 (OCH3), 86.85 (C-6), 90.48
(Æ)-2-(E)-(Ethoxycarbonylmethylidene)-(4S,5R)-dimethyltetrahydrofur-
an (9a): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
ˆ
ˆ
(C CH), 168.81 (C O), 175.90 (C-8); IR (KBr): nÄ ˆ 2949 (s), 2863 (m),
1639 (s), 1436 (m), 1351 (m), 1236 (w), 1187 (w), 1140 (m), 1113 (m), 1076
(0.89 g, 3.2mmol),
cis-2,3-butenoxide (0.28 mL, d ˆ 0.827 gcmÀ3
,
À1
(m), 1045 (m), 942(m), 821 cm
(s); MS (70 eV, EI): m/z (%): 196 (100)
3.2mmol), and TiCl 4 (0.68 mL, d ˆ 1.726 gcmÀ3, 6.2mmol), 9a was isolated
after chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a
‡
[M ], 165 (41), 122 (53), 101 (57), 81 (45); the exact molecular mass for
‡
C11H16O3: m/z (%): 196.1099 Æ 2mD [ M ] was confirmed by HRMS (EI,
1
colorless oil (265 mg, 45%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
70 eV).
1.03 (d, J ˆ 6.6 Hz, 3H; CH3 to C-4), 1.18 (t, J ˆ 7.1 Hz, 3H; OCH2CH3),
1.27 (d, J ˆ 6.2Hz, 3H; CH 3 to C-5), 1.82 1.95 (m, 1H; 4-H), 2.47 (ddd, J ˆ
18.1, 9.8, 2.1 Hz, 1H; 3-H), 3.44 (ddd, J ˆ 18.0, 7.8, 1.3 Hz, 1H; 3-H), 3.91
(qd, J ˆ 6.2, 2.1 Hz, 1H; 5-H), 4.04 (q, J ˆ 7.1 Hz, 2H; OCH2CH3), 5.15
5.16 (m, 1H; CHCO2Et); 13C NMR (62.9 MHz, CDCl3): d ˆ 14.31
(OCH2CH3), 16.03, 18.50 (2 Â CH3), 38.83 (C-3), 39.01 (C-4), 58.93
Purification of 11b by ion-exchange resins: A solution (20 mL) of the crude
product mixture of 11b in ether was treated with the basic ion-exchange
resin Ambersep900-OH. After stirring for 2h, the resin was filtered off,
and the filtrate was concentrated in vacuo. This procedure was repeated
one time. After evaporation of the solvent, the residue was purified by
chromatography to give 11b as a colorless oil (330 mg, 36%).
ˆ
(OCH2CH3), 85.71, 89.30 (C-5, CHCO2Et), 168.48 (C O), 175.59 (C-2);
‡
MS (70 eV, EI): m/z (%): 184 (56) [M ], 169 (100), 139 (66), 123 (32), 69
trans-2-(E)-(Isopropyloxycarbonylmethylidene)-7-oxabicyclo[4.3.0]no-
nane (11c): Starting with 1,3-bis(trimethylsilyloxy)-1-isopropyloxy-1,3-
(44); the exact molecular mass for C10H16O3 m/z (%): 184.1099 Æ 2mD
‡
[M ] was confirmed by HRMS (EI, 70 eV).
butadiene (0.52g, 1.8 mmol), 1,2-cyclohexenoxide (0.18 mL,
d ˆ
0.971 gcmÀ3, 1.8 mmol), and TiCl4 (0.40 mL, d ˆ 1.726 gcmÀ3, 3.6 mmol),
11c was isolated by chromatography (silica gel, diethyl ether/petroleum
etherˆ 1:3) as a colorless solid (129 mg, 32%, E/Z > 98:2). 1H NMR
(250 MHz, CDCl3): d ˆ 1.15 1.25 (d, J ˆ 8.0 Hz, 6H; CH3), 2.68 2.08 (m,
6H; 1-H, CH2), 2.18 2.40 (m, 3H; CH2), 3.38 3.58 (m, 3H; 6-H, 9-H),
(Æ)-2-(E)-(Ethoxycarbonylmethylidene)-(4S,5S)-dimethyltetrahydrofuran
(9b): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene
(0.89 g, 3.2mmol), trans-2,3-butenoxide (0.28 mL, d ˆ 0.804 gcmÀ3
,
3.2mmol), and TiCl 4 (0.68 mL, d ˆ 1.726 gcmÀ3, 6.2mmol), 9b was isolated
after chromatography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a
1
ˆ
4.97 (sept, J ˆ 8.0 Hz, 1H; CH(CH3)2), 5.26 (t, J ˆ 1.3 Hz, 1H; C CH);
colorless oil (247 mg, 42%, E/Z > 98:2). H NMR (250 MHz, CDCl3): d ˆ
13C NMR (62.9 MHz, CDCl3): d ˆ 22.00, 22.01 (CH(CH3)2), 24.03, 25.29,
28.30, 30.30, 36.26 (C-9, CH2), 44.37 (CH, C-1), 66.09 (OCH(CH3)2), 86.64,
0.93 (d, J ˆ 7.0 Hz, 3H; CH3 to C-4), 1.21 (d, J ˆ 6.5 Hz, 3H; CH3 to C-5),
1.24 (t, J ˆ 7.0 Hz, 3H; OCH2CH3), 2.36 2.45 (m, 1H; 4-H), 2.85 2.94 (m,
1H; 3-H), 3.15 (ddd, J ˆ 18.0, 7.7, 1.4 Hz, 1H; 3-H), 4.10 (q, J ˆ 7.0 Hz, 2H;
OCH2CH3), 4.49 (dq, J ˆ 6.4, 6.4 Hz, 1H; 5-H), 5.23 5.24 (m, 1H;
CHCO2Et); 13C NMR (62.9 MHz, CDCl3): d ˆ 13.55, 14.44, 15.05
(OCH2CH3, 2 Â CH3), 34.31 (C-4), 38.42(C-3), 59.09 (O CH2CH3), 82.03,
ˆ
ˆ
91.41 (CHC O, C-6), 167.94 (C O), 175.33 (C-8); MS (70 eV, EI): m/z (%):
224 (100) [M ], 165 (40).
‡
trans-2-(E)-[(2'-Methyl)propyloxycarbonylmethylidene]-7-oxabicyclo-
[4.3.0]nonane (11d): Starting with 1,3-bis(trimethylsilyloxy)-1-(2'-methyl)-
propyloxy-1,3-butadiene (0.91 g, 3.0 mmol), 1,2-cyclohexenoxide (0.30 mL,
ˆ
89.69 (C-5, CHCO2Et), 168.75 (C O), 175.79 (C-2); MS (70 eV, EI): m/z
‡
(%): 184 (59) [M ], 169 (100), 139 (58), 123 (27), 69 (48); the exact
d ˆ 0.971 gcmÀ3
,
3.0 mmol), and TiCl4 (0.66 mL, d ˆ 1.726 gcmÀ3
,
‡
molecular mass for C10H16O3: m/z (%): 184.1099 Æ 2mD [ M ] was
6.0 mmol), 11d was isolated by chromatography (silica gel, diethyl ether/
petroleum etherˆ 1:2) as a colorless oil (220 mg, 31%, E/Z > 98:2).
Impurities could not be completely removed. 1H NMR (250 MHz, CDCl3):
d ˆ 0.92(d, J ˆ 6.7 Hz, 6H; CH3), 1.01 2.03 (m, 11H; 1-H, CH2,
CH(CH3)2), 2.16 2.45 (m, 1H; 9-H), 3.44 3.56 (m, 2H; 6-H, 9-H),
confirmed by HRMS (EI, 70 eV).
(Æ)-2-(E)-[1-(Ethoxycarbonyl)ethylidene]-(4S,5S)-dimethyltetrahydrofu-
ran (9c): Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-2-methyl-1,3-
butadiene (0.80 g, 2.8 mmol), trans-2,3-butenoxide (0.25 mL, d ˆ
0.804 gcmÀ3, 2.8 mmol), and TiCl4 (0.62mL, d ˆ 1.726 gcmÀ3, 5.6 mmol),
9c was isolated after chromatography (silica gel, diethyl ether/petroleum
3.82 3.92 (m, 2H; OCH 2), 5.32(t, J ˆ 1.2Hz, 1H; C CH); 13C NMR
ˆ
(62.9 MHz, CDCl3): d ˆ 18.99 (CH3), 24.07, 25.33, 27.82, 28.34 (CH2CH2),
30.34 (OCH2CH), 36.34 (C-9), 44.43 (C-1), 69.56 (OCH2), 86.79 (C-6), 91.02
etherˆ 1:3) as
a
colorless oil (205 mg, 37%, E/Z > 98:2). 1H NMR
Chem. Eur. J. 2002, 8, No. 6
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0806-1453 $ 17.50+.50/0
1453

P. Langer et al.
FULL PAPER
ˆ
ˆ
(C CH), 168.55 (C O), 175.56 (C-8); MS (70 eV, EI): m/z (%): 238 (37)
[M ], 182(51), 165 (100), 158 (44), 138 (47), 81 (45).
TiCl4 (0.55 mL, d ˆ 1.726 gcmÀ3, 5.0 mmol), 13c was isolated after chro-
matography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a colorless
oil (228 mg, 45%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.11 (d,
J ˆ 6.4 Hz, 3H; CH3), 2.47 2.61 (m, 1H; 4-H), 2.88 (ddd, J ˆ 18.7, 6.8,
1.7 Hz, 1H; 3-H), 3.46 (ddd, J ˆ 18.7, 8.0, 1.6 Hz, 1H; 3-H), 3.82(dd, J ˆ 8.6,
6.6 Hz, 1H; 5-H), 4.33 (dd, J ˆ 8.6, 6.9 Hz, 1H; 5-H), 6.52(t, J ˆ 1.7 Hz,
‡
trans-2-(E)-(Phenylcarbonylmethylidene)-7-oxabicyclo[4.3.0]nonane
(11e): Starting with 1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene
(1.53 g, 5 mmol), 1,2-cyclohexenoxide (0.51 mL, d ˆ 0.971 gcmÀ3
,
5.0 mmol), and TiCl4 (1.10 mL, d ˆ 1.726 gcmÀ3, 10.0 mmol), 11e was
isolated by chromatography (silica gel, diethyl ether/petroleum etherˆ 1:2)
as an orange solid (290 mg, 24%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3):
d ˆ 1.15 2.24 (m, 11H; CH2CH2, 9-H, 1-H), 3.34 3.49 (m, 2H; 6-H, 9-H),
1H; CHC O), 7.37 7.51 (m, 3H; Ph), 7.87 7.92(m, 2H; Ph); 13C NMR
ˆ
(62.9 MHz, CDCl3): d ˆ 17.38 (CH3), 31.70 (C-4), 39.43 (C-3), 77.71 (C-5),
ˆ
95.42( CHC O), 127.59, 128.22, 131.60 (CH, Ph), 139.68 (C, Ph), 179.05 (C-
‡
ˆ
2), 190.15 (C O); MS (70 eV, EI): m/z (%): 202 (70) [M ], 187 (100), 162
ˆ
6.52(t, J ˆ 2.1 Hz, 1H; C CH), 7.31 7.54 (m, 3H; Ph), 7.85 7.95 (m, 2H;
(13), 147 (20), 125 (22), 105 (45); elemental analysis calcd (%) for
C13H14O2: C 77.20, H 6.98; found: C 76.86, H 7.09.
Ph); 13C NMR (62.9 MHz, CDCl3): d ˆ 24.12, 25.32, 28.34, 29.66 (CH2CH2),
ˆ
37.50 (C-9), 44.55 (C-1), 87.05 (C-6), 96.45 (C CH), 127.58, 128.31, 131.73
2-(E)-(3-Methoxy-2-oxopropylidene)-4-methyltetrahydrofuran
(13d):
ˆ
(CH, Ph), 134.60 (C, Ph), 178.18 (C O), 190.47 (C-8); MS (70 eV, EI): m/z
(%): 242 (27) [M ], 163 (95), 147 (67), 105 (100), 98 (39); the exact
‡
Starting with 2,4-bis(trimethylsilyloxy)-1-methoxy-2,4-pentadiene (0.55 g,
2.0 mmol), 1,2-propenoxide (0.14 mL, d ˆ 0.829 gcmÀ3, 2.0 mmol), and
TiCl4 (0.44 mL, d ˆ 1.726 gcmÀ3, 4.0 mmol), 13d was isolated after chro-
matography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a colorless
oil (143 mg, 42%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.09 (d,
J ˆ 7.0 Hz, 3H; CH3 on C-4), 2.47 2.58 (m, 1H; 4-H), 2.70 2.81 (m, 1H;
3-H), 3.29 3.48 (m, 4H; 3-H, OCH3), 3.80 (dd, J ˆ 8.6, 6.7 Hz, 1H; 5-H),
3.94 (s, 2H; CH2OCH3), 4.32(dd, J ˆ 8.6, 6.9 Hz, 1H; 5-H), 5.94 5.96 (m,
‡
molecular mass for C16H18O2: m/z (%): 242.1307 Æ 2mD [ M ] was
confirmed by HRMS (EI, 70 eV).
trans-2,3'-(E)-(2'-Oxofuranylidene)-7-oxabicyclo[4.3.0]nonane
(11 f):
Starting with 2,1'-bis(trimethylsilyloxy)-(3-ethylene)-4,5-dihydrofuran
(0.71 g, 2.6 mmol), 1,2-cyclohexenoxide (0.26 mL, d ˆ 0.971 gcmÀ3
,
2.6 mmol), and TiCl4 (0.57 mL, d ˆ 1.726 gcmÀ3
, 5.2mmol), 11 f was
isolated by chromatography (silica gel, diethyl ether/petroleum ether ˆ
1:2) as a colorless solid (141 mg, 26%, E/Z > 98:2). 1H NMR (250 MHz,
CDCl3): d ˆ 1.15 1.58 (m, 6H; CH2CH2), 1.71 1.99 (m, 3H; CH2), 2.18
2.34 (m, 2H; 1-H, 9-H), 2.82 (dt, J ˆ 7.6, 2.8 Hz, 2H; 4'-H), 3.45 3.59 (m,
2H; 6-H, 9-H), 4.24 (t, J ˆ 7.7 Hz, 2H; 5'-H); 13C NMR (62.9 MHz, CDCl3):
d ˆ 24.08, 25.02, 25.23, 28.31 (CH2CH2), 34.95 (C-3), 44.60 (C-4), 65.18 (C-
1H; CHC O); 13C NMR (62.9 MHz, CDCl3): d ˆ 17.37 (CH3), 31.68, 39.39
ˆ
ˆ
(C-3, C-4), 59.13 (OCH3), 77.80, 77.87 (C-5, CH2OCH3), 94.38 (CHC O),
ˆ
178.64 (C-2), 197.25 (C O); MS (70 eV, DCI, NH3): m/z (%): 171 (100)
[M‡1 ], 188 (82) [M‡18 ], 358 (2) [2M‡18 ].
‡
‡
‡
2-(E)-(2-Oxopropylidene)-5-methyltetrahydrofuran (13e-1) and 2-(E)-(2-
oxopropylidene)-4-methyltetrahydrofuran (13e-2): Starting with 2,4-bis-
(trimethylsilyloxy)-1,3-pentadiene (0.49 g, 2.0 mmol), 1,2-butenoxide
ˆ
5'), 87.49 (C-5), 94.16 (C-3'), 168.62(C O), 172.99 (C-2); IR (KBr): nÄ ˆ
2942 (s), 2687 (s), 1734 (s), 1684 (s), 1457 (s), 1373 (m), 1266 (s), 1220 (m),
(0.17 mL, d ˆ 0.837 gcmÀ3
,
2.0 mmol), and TiCl4 (0.44 mL, d ˆ
1069 (m), 1019 cmÀ1 (s); MS (70 eV, EI): m/z (%): 208 (70) [M ], 162(11),
‡
1.726 gcmÀ3, 4.0 mmol), 13e was isolated by chromatography (silica gel,
diethyl ether/petroleum ether ˆ 1:3) as a colorless oil. The product was
obtained as an inseparable 3:1 mixture of the regioisomers 13e-1 and 13e-2
(100 mg, 36%, E/Z > 98:2). 13e-1: 1H NMR (250 MHz, CDCl3): d ˆ 1.35
(d, J ˆ 6.3 Hz, 3H; CHCH3), 1.55 1.77 (m, 1H; 4-H), 2.10 (s, 3H; COCH3),
2.10 2.28 (m, 1H; 4-H), 2.85 3.05 (dddd, J ˆ 18.8, 9.0, 9.0, 2.0 Hz, 1H;
3-H), 3.25 3.40 (dddd, J ˆ 18.8, 9.0, 4.1, 1.4 Hz, 1H; 3-H), 4.48 4.58 (m,
128 (14), 113 (100), 81 (26); the exact molecular mass for C12H16O3: m/z
‡
(%): 208.1099 Æ 2mD [ M ] was confirmed by HRMS (EI, 70 eV);
elemental analysis calcd (%) for C12H16O3: C 69.21, H 7.74; found: C
68.87, H 7.77.
2-(E)-(Ethoxycarbonylmethylidene)-4-phenyltetrahydrofuran
(13a):
Starting with 1,3-bis(trimethylsilyloxy)-1-ethoxy-1,3-butadiene (0.50 g,
1.8 mmol), styrenoxide (0.21 mL, d ˆ 1.051 gcmÀ3, 1.8 mmol), and TiCl4
(0.40 mL, d ˆ 1.726 gcmÀ3, 3.6 mmol), 13a was isolated after chromatog-
raphy (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a colorless oil
(125 mg, 30%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 1.27 (t, J ˆ
7.1 Hz, 3H; OCH2CH3), 3.13 3.26 (m, 1H; 3-H), 3.56 3.67 (m, 2H; 3-H,
4-H), 4.09 4.22 (m, 3H; OCH2CH3, 5-H), 4.52 4.59 (m, 1H; 5-H), 5.39
1H; 5-H), 5.74 (m, 1H; CHC O); 13C NMR (62.9 MHz, CDCl3): d ˆ 20.36
ˆ
ˆ
(CH2CH3), 30.91, 31.13, 31.52(C-3, C-4, CH 3, C OCH3), 80.21 (C-5), 98.28
(CHC O), 176.56 (C-2), 197.60 (C O); 13e-2: 1H NMR (250 MHz,
ˆ
ˆ
ˆ
CDCl3): d ˆ 1.08 (d, J ˆ 6.3 Hz, 3H; CHCH3), 2.11 (s, 3H; C OCH3),
2.12 2.38 (m, 1H; 4-H), 2.40 2.58 (ddd, J ˆ 18.5, 7.4, 1.7 Hz, 1H; 3-H),
3.25 3.42 (ddd, J ˆ 18.5, 8.3, 1.5 Hz, 1H; 3-H), 3.75 (dd, J ˆ 8.6, 7.3 Hz, 1H;
5.40 (m, 1H; CHC O), 7.15 7.45 (m, 5H; Ph); 13C NMR (62.9 MHz,
ˆ
ˆ
5-H), 4.28 (dd, J ˆ 8.6, 7.3 Hz, 1H; 5-H), 5.77 (t, J ˆ 1.5 Hz, 1H; CHC O);
CDCl3): d ˆ 14.36 (OCH2CH3), 37.89 (C-3), 42.57 (C-4), 59.22 (OCH2CH3),
13C NMR (62.9 MHz, CDCl3): d ˆ 17.38, 31.76, 32.65, 38.98 (C-3, C-4, CH3,
ˆ
76.99 (C-5), 90.35 (CHC O), 126.78, 127.10, 128.78 (CH, Ph), 140.26 (C,
ˆ
ˆ
ˆ
C OCH3), 77.20 (C-5), 98.98 (CHC O), 176.58 (C-2), 197.60 (C O); MS
ˆ
Ph), 168.28 (C O), 175.69 (C-2); IR (neat): nÄ ˆ 3466 (br), 3086 (w), 3063
‡
(70 eV, EI): m/z (%): 140 (18) [M ], 125 (25); the exact molecular mass for
(w), 2980 (m), 2932 (m), 2901 (m), 1701 (s), 1643 (s), 1604 (m), 1495 (m),
1454 (m), 1371 (s), 1339 (s), 1238 (m), 1115 (s), 1047 cmÀ1 (s); MS (70 eV,
‡
C8H12O2: m/z (%): 140.0837 Æ 2mD [ M ] was confirmed by HRMS (EI,
70 eV).
‡
EI): m/z (%): 232 (52) [M ], 187 (26), 156 (26), 125 (100); the exact
2-(E)-(2-Oxopropylidene)-5-ethyltetrahydrofuran (13 f-1) and 2-(E)-(2-
oxopropylidene)-4-ethyltetrahydrofuran (13 f-2): Starting with 2,4-bis(tri-
‡
molecular mass for C14H16O3: m/z (%): 232.1099 Æ 2mD [ M ] was
confirmed by HRMS (EI, 70 eV).
methylsilyloxy)-1,3-pentadiene
(0.49 g,
2.0 mmol),
1,2-butenoxide
(0.17 mL, d ˆ 0.837 gcmÀ3
,
2.0 mmol), and TiCl4 (0.44 mL, d ˆ
2-(E)-(Phenylcarbonylmethylidene)-4-vinyltetrahydrofuran (13b): Start-
ing
1.726 gcmÀ3, 4.0 mmol), the regioisomers 13 f-1 (18 mg, 6%, E/Z > 98:2)
and 13 f-2 (46 mg, 15%, E/Z > 98:2) were isolated by chromatography
(silica gel, diethyl ether/petroleum etherˆ 1:3) as colorless oils. 13 f-1:
1H NMR (250 MHz, CDCl3): d ˆ 0.97 (t, J ˆ 7.5 Hz, 3H; CH2CH3), 1.53
with
1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene
(1.07 g,
3.5 mmol), 3,4-epoxy-1-butene (0.28 mL, d ˆ 0.870 gcmÀ3, 3.5 mmol), and
TiCl4 (0.77 mL, d ˆ 1.726 gcmÀ3, 7.0 mmol), 13b was isolated after chro-
matography (silica gel, diethyl ether/petroleum ether ˆ 1:3) as a colorless
oil (285 mg, 38%, E/Z > 98:2). 1H NMR (250 MHz, CDCl3): d ˆ 2.96 3.19
(m, 2H; 3-H), 3.40 3.62(m, 1H; 4-H), 4.00 (t, J ˆ 7.9 Hz, 1H; 5-H), 4.39 (t,
ˆ
1.77 (m, 3H; 4-H, CH2CH3), 2.02 2.24 (m, 4H; 4-H, C OCH3), 2.94 (dddd,
J ˆ 18.9, 9.1, 9.1, 1.9 Hz, 1H; 3-H), 3.30 (dddd, J ˆ 18.9, 9.2, 4.1, 1.4 Hz, 1H;
ˆ
J ˆ 7.9 Hz, 1H; 5-H), 5.11 5.23 (m, 2H; CH CH2), 5.73 5.87 (m, 1H;
ˆ
3-H), 4.26 4.34 (m, 1H; 5-H), 5.73 5.76 (m, 1H; CHC O); 13 f-2:
1H NMR (250 MHz, CDCl3): d ˆ 0.92(t, J ˆ 7.4 Hz, 3H; CH2CH3), 1.42
ˆ
ˆ
CH CH2), 6.54 (m, 1H; CHC O), 7.40 7.53 (m, 3H; Ph), 7.88 7.93 (m,
2H; Ph); 13C NMR (62.9 MHz, CDCl3): d ˆ 37.50 (C-3), 41.30 (C-4), 75.27
ˆ
(quint, J ˆ 7.4 Hz, 2H; CH2CH3), 2.09 (s, 3H; C OCH3), 2.12 2.38 (m,
ˆ
ˆ
(C-5), 95.55 (CHC O), 116.83 (CH CH2), 127.52, 128.27, 131.71 (CH, Ph),
1H; 4-H), 2.68 (ddd, J ˆ 18.6, 7.3, 1.7 Hz, 1H; 3-H), 3.29 (ddd, J ˆ 18.6, 8.4,
1.5 Hz, 1H; 3-H), 3.32(dd, J ˆ 8.7, 7.2Hz, 1H; 5-H), 3.81 (dd, J ˆ 8.7,
ˆ
ˆ
136.20 (CH CH2) 139.58 (C, Ph), 178.13 (C-2), 190.12 (C O); IR (KBr):
nÄ ˆ 3081 (w), 3067 (w), 3028 (w), 2987 (w), 2954 (w), 2889 (w), 1647 (s),
7.1 Hz, 1H; 5-H), 5.73 5.75 (m, 1H; CHC O); 13C NMR (62.9 MHz,
ˆ
À1
1587 (s), 1567 (s), 1392(m), 1175 cm (s); MS (70 eV, EI): m/z (%): 214
CDCl3): d ˆ 12.14 (CH2CH3), 25.56, 31.08, 37.01, 38.82 (C-3, C-4, CH2CH3,
‡
(28) [M ], 147 (69), 105 (65), 77 (52), 69 (100); the exact molecular mass for
ˆ
ˆ
ˆ
C OCH3), 75.95 (C-5), 98.76 (CHC O), 176.88 (C-2), 197.53 (C O); MS
‡
‡
C14H14O2: m/z (%): 214.0994 Æ 2mD [ M ] was confirmed by HRMS (EI,
(70 eV, EI): m/z (%): 154 (16) [M ], 139 (28), 125 (56), 111 (16), 71 (24), 69
70 eV).
(100); the exact molecular mass for C9H14O2: m/z (%): 154.0994 Æ 2mD
‡
[M ] was confirmed by HRMS (EI, 70 eV).
2-(E)-(Phenylcarbonylmethylidene)-4-methyltetrahydrofuran (13c): Start-
ing
with
1,3-bis(trimethylsilyloxy)-1-phenyl-1,3-butadiene
(0.79 g,
Crystal structure analysis:[29] For the data collection a StoeIPDSII area
detector system using graphite-monochromated MoKa radiation was used.
2.5 mmol), 1,2-propenoxide (0.18 mL, d ˆ 0.829 gcmÀ3, 2.5 mmol), and
1454
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Chem. Eur. J. 2002, 8, No. 6

Functionalized 2-Alkylidenetetrahydrofurans
1443 1455
No absorption corrections were made. The structures were solved by direct
methods (SHELXS)[30] and refined by the full-matrix least squares
techniques against F 2 (SHELXL-93).[31] The hydrogen atoms were included
at calculated positions with fixed thermal parameters. All non-hydrogen
atoms were refined anisotropically.
[11] a) T. A. Bryson, J. Org. Chem. 1973, 38, 3428; b) M. Yamaguchi, I.
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been reported: a) M. F. Semmelhack, A. Zask, J. Am. Chem. Soc.
1983, 105, 2034; for intermolecular reactions, see: b) G. Lalic, Z.
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therein; b) A. G. M. Barrett, H. G. Sheth, J. Org. Chem. 1983, 48,
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2628; h) P. A. Bartlett, J. D. Meadows, E. Ottow, J. Am. Chem. Soc.
1984, 106, 5304.
Crystallographic data of 11 f: Empirical formula: C12H16O3; formula
weight: 208.25; temperature: 133(2) K; wavelength: 0.71073 ä; crystal
system: monoclinic; space group: P21/n; unit cell dimensions: a ˆ
6.6306(7) ä, b ˆ 7.5994(11) ä, b ˆ 98.199(9)8, c ˆ 21.512(3) ä, Vˆ
1072.9(2) ä3, Z ˆ 4, 1calcd
:
1.289 mgmÀ3
;
absorption coefficient:
0.092mm À1; F(000): 448; theta range for data collection: 1.91 to 24.718;
index ranges: À7 ꢀ h ꢀ 7, À8 ꢀ k ꢀ 8, À23 ꢀ l ꢀ 25; reflections collected/
unique: 6337/1784 [R(int) ˆ 0.0491]; observed reflections: [I > 2s(I)]: 1433;
completeness to q ˆ 24.71: 98.3%; refinement method: full-matrix least-
squares method on F 2; data/restraints/parameters: 1784/0/145; goodness-
of-fit on F 2: 1.037; final R indices [I > 2s(I)] R1 ˆ 0.0457, wR2 ˆ 0.1162,
R indices (all data): R1 ˆ 0.0573, wR2 ˆ 0.1211; largest diff. peak and hole:
0.312and À0.202 eäÀ3
.
Acknowledgements
P.L. thanks Prof. Dr. A. de Meijere for his support. Financial support by the
Fonds der Chemischen Industrie (Liebig scholarship and funds for P.L.) and
by the Deutsche Forschungsgemeinschaft (Heisenberg scholarship and
funds to P.L.) is gratefully acknowledged.
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[20] See for example: J. Hartung, R. Kneuer, Eur. J. Org. Chem. 2000, 1677.
[21] See for example: H. Kikuchi, T. Suzuki, E. Kurosawa, M. Suzuki, Bull.
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Int. Ed. 1999, 38, 1803; b) P. Langer, E. Holtz, Angew. Chem. 2000,
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[22] K. Mori, M. Sasaki, S. Tamada, T. Suguro, S. Masuda, Tetrahedron
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[23] For the synthesis of 6a, see: J. P. Sestelo, M. del Mar Real, A.
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cyclizations, see: J. E. Baldwin, L. I. Kruse, J. Chem. Soc. Chem.
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[29] Crystallographic data for the structure 11 f reported in this paper have
been deposited with the Cambridge Crystallographic Data Centre.
CCDC-171287 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge via www.ccdc.ca-
m.ac.uk/conts/retrieving.html (or from the Cambridge Crystallo-
graphic Data Centre, 12Union Road, Cambridge CB21EZ, UK;
fax: (‡44)1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk).
[30] G. M. Sheldrick, Acta Crystallogr. Sect. A 1990, 46, 467.
[31] G. M. Sheldrick, SHELXL-93, University of Gˆttingen, 1993.
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Krummel, Chem. Eur. J. 2001, 7, 1720.
Received: October 5, 2001 [F3596]
Chem. Eur. J. 2002, 8, No. 6
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0806-1455 $ 17.50+.50/0
1455