Regio- and diastereoselective synthesis of 2-alkylidenetetrahydrofurans by domino SN/SN′ and SN/SN reactions of 1,3-dicarbonyl dianions

Article abstract of DOI:10.1021/jo010303r

The domino C,O-cyclodialkylation reaction of dilithiated 1,3-dicarbonyl compounds with 1,4-dibromo-2-butene resulted in regio- and diastereoselective formation of 2-alkylidene-5-vinyltetrahydrofurans. The cyclization of 1,3-dicarbonyl dianions with 1-brom

Full text of DOI:10.1021/jo010303r

J . Org. Chem. 2001, 66, 6057-6063
6057
Regio- a n d Dia ster eoselective Syn th esis of
2-Alk ylid en etetr a h yd r ofu r a n s by Dom in o SN/SN′ a n d SN/SN
Rea ction s of 1,3-Dica r bon yl Dia n ion s
Peter Langer,* Edith Holtz, Inass Karime´, and Nehad N. R. Saleh
Institut fu¨r Organische Chemie, Georg-August-Universita¨t, Go¨ttingen, Tammannstrasse 2,
37077 Go¨ttingen, Germany
planger@uni-goettingen.de
Received March 20, 2001
The domino C,O-cyclodialkylation reaction of dilithiated 1,3-dicarbonyl compounds with 1,4-dibromo-
2-butene resulted in regio- and diastereoselective formation of 2-alkylidene-5-vinyltetrahydrofurans.
The cyclization of 1,3-dicarbonyl dianions with 1-bromo-2-chloroethane regio- and diastereoselec-
tively afforded 2-alkylidenetetrahydrofurans under thermodynamic reaction control.
In tr od u ction
amounts of CuCl open-chain products were obtained,
however, in only 25-33% yield.11 Employment of 1,2-
dichloroethane resulted in elimination rather than nu-
cleophilic substitution.11 In the course of our interest12
in the development of cyclization reactions of dianions
we have recently shown13 that 2-alkylidenetetrahydro-
furans could be efficiently prepared by domino SN/SN
reactions of 1,3-dicarbonyl dianions with 1-bromo-2-
chloroethane.14,15 Herein, we wish to report full details
of this methodology.
Despite their potential simplicity, cyclization reactions
of dianions1 with 1,2-difunctional alkylhalides can suffer
from various side reactions such as polymerization,
elimination, monoalkylation, or reduction of the dielec-
trophile.2 Recently, the two-step synthesis of annelated
imidazoles by cyclization of dilithiated 2-methylbenzimi-
dazole with 1-bromo-2-chloroethane has been reported.3
As a result of a competing elimination pathway, relatively
low yields were obtained compared with the formation
of six-membered rings. Katritzky and co-workers have
reported the cyclization of 1-bromo-2-chloroethane with
the dianion of 2-methylindole, generated by the use of
Lochmann-Schlosser- base.4 Despite the simplicity of the
idea, cyclization reactions of 1,3-dicarbonyl dianions5,6
with 1,2-dihalides have, to the best of our knowledge, not
been reported so far.7 The reaction of 1,3-dicarbonyl
dianions with 1,n-dibromoalkanes (n ) 3 or higher) was
reported to give mixtures of open-chain monoalkylated
products and of 2:1-condensation products.8 Not even
open-chain products could be isolated in the reaction of
1,3-dicarbonyl dianions with 1,2-dibromo- or 1,2-diiodo-
ethane, because of a competing SET-process.9 In fact, 1,2-
dibromoethane has been used as a reagent for the
oxidation of dianions.10 In the presence of catalytic
The reaction of 1,3-dicarbonyl dianions with 1,4-
dichloro-2-butene has been reported to result only in
formation of mixtures of open-chain products in low
yields.8 Recently, the K2CO3-mediated cyclization of
dimethyl acetone-1,3-dicarboxylate with 1,4-dibromo-2-
butene has been reported by Rodriguez16a and co-workers.
We have recently reported the first, to our knowledge,
(10) Barry, C. E., III; Bates, R. B.; Beavers, W. A.; Camou, F. A.;
Gordon, B., III; Hsu, H. F.-J .; Mills, N. S.; Ogle, C. A.; Siahaan, T. J .;
Suvannachut, K.; Taylor, S. R.; White, J . J .; Yager, K. M. Synlett 1991,
207.
(11) Hampton, K. G.; Christie, J . J . J . Org. Chem. 1976, 41, 2772.
(12) For recent cyclization reactions of dianions and dianion equiva-
lents from our laboratory, see: (a) Langer, P.; Stoll, M. Angew. Chem.
1999, 111, 1919; Angew. Chem., Int. Ed. Engl. 1999, 38, 1803. (b)
Langer, P.; Schneider, T.; Stoll, M. Chem. Eur. J . 2000, 6, 3204. (c)
Langer, P.; Holtz, E. Angew. Chem. 2000, 112, 3208; Angew. Chem.,
Int. Ed. 2000, 39, 3086. (d) Langer, P.; Eckardt, T. Angew. Chem. 2000,
112, 4503; Angew. Chem., Int. Ed. 2000, 39, 4343. (e) Langer, P.;
Krummel, T. Chem. Commun. 2000, 967. (f) Langer, P.; Eckardt, T.
Synlett 2000, 844. (g) Langer, P.; Schneider, T. Synlett 2000, 497. (h)
Langer, P.; Wuckelt, J .; Do¨ring, M.; Go¨rls, H. J . Org. Chem. 2000, 65,
3603. (i) Langer, P.; Karime´, I. Synlett 2000, 743. (j) Langer, P.; Ko¨hler,
V. Org. Lett. 2000, 1597. (k) Langer, P.; Ko¨hler, V. Chem. Commun.
2000, 1653. (l) Langer, P.; Kracke, B. Tetrahedron Lett. 2000, 4545.
(m) Langer, P.; Do¨ring, M. Chem. Commun. 1999, 2439. (n) Langer,
P. Chem. Commun. 1999, 1217. (o) Langer, P.; Wuckelt, J .; Do¨ring,
M.; Beckert, R. Eur. J . Org. Chem. 1998, 1467. (p) Langer, P.; Do¨ring,
M. Synlett 1998, 396. (q) Langer, P.; Freifeld, I. Synlett 2001, 523. (r)
Langer, P.; Albrecht, U. Synlett 2001, 526. (s) Langer, P.; Krummel,
T. Chem. Eur. J . 2001, 1720. (t) Langer, P.; Wuckelt, J .; Do¨ring, M.;
Schreiner, P. R.; Go¨rls, H. Eur. J . Org. Chem. 2001, 2245.
(13) Langer, P.; Karime´, I. Synlett 2000, 743.
* Fax: (+49) 551-399475.
(1) For reviews of dianions, see: (a) Maercker, A. Methoden der
organischen Chemie (Houben-Weyl) 4; G. Thieme: Stuttgart, New York,
1993; Bd. E19d, p 448. (b) Thompson, C. M.; Green, D. Tetrahedron
1991, 47, 4223.
(2) For cyclization reactions of dianions with difunctional alkyl
halides, see: (a) Bahl, J . J .; Bates, R. B.; Beavers, W. A.; Mills, N. S.
J . Org. Chem. 1976, 41, 1620. (b) Hirai, K.; Iwano, Y. Tetrahedron
Lett. 1979, 2031. (c) Bilyard, K. G.; Garratt, P. J .; Hunter, R.; Lete, E.
J . Org. Chem. 1982, 47, 4731.
(3) McClure, J . R.; Custer, J . H.; Schwarz, H. D.; Lill, D. A. Synlett
2000, 710.
(4) Katritzky, A. R.; Fali, C. N.; Li, J . J . Org. Chem. 1997, 62, 4148.
(5) Weiler, L. J . Am. Chem. Soc. 1970, 92, 6702. (b) Seebach, D.;
Ehrig, V. Angew. Chem. 1974, 86, 446; Angew. Chem., Int. Ed. Engl.
1974, 13, 401.
(6) For a review of cyclization reactions of free and masked 1,3-
dicarbonyl dianions with 1,2-dielectrophiles, see: Langer, P, Chem.
Eur. J . 2001, in press.
(14) For the synthesis of open-chain products, see: Lambert, P. H.;
Vaultier, M.; Carrie´, R. J . Org. Chem. 1985, 50, 5352.
(15) For a review of domino reactions, see: Tietze, L. F.; Beifuss,
U., Angew. Chem. 1993, 105, 137; Angew. Chem., Int. Ed. Engl. 1993,
32, 131.
(16) Lavoisier, T.; Rodriguez, J . Synlett 1996, 339. For a related
reaction, see: (b) Wang, T.; Chen, J .; Zhao, K., J . Org. Chem. 1995,
60, 2668.
(7) Branda¨nge, S.; Lindqvist, B. Acta Chem. Scand. 1989, 43, 807.
(8) Sum, P.-E.; Weiler, L., Can. J . Chem. 1977, 55, 996.
(9) Hampton, K. G.; Light, R. J .; Hauser, C. R. J . Org. Chem. 1965,
30, 1413.
10.1021/jo010303r CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/14/2001

6058 J . Org. Chem., Vol. 66, No. 18, 2001
Langer et al.
Sch em e 1. Cycliza tion of 1,3-Dica r bon yl Dia n ion s
w ith 1-Br om o-2-ch lor oeth a n e
domino SN/SN′ reactions of 1,3-dicarbonyl dianions with
1,4-dibromo-2-butene. Herein, we wish to report full
details of this cyclization reaction, which allows for a
direct transformation of unsymmetrical and nonactivated
1,3-dicarbonyl compounds into 2-alkylidene-5-vinyltet-
rahydrofurans. Functionalized 2-alkylidenetetrahydro-
furans represent important intermediates for the syn-
thesis of biologically relevant tetrahydrofurans and natural
products.17
Resu lts a n d Discu ssion
Dom in o SN/SN Rea ction s. After much experimenta-
tion14 we have recently developed conditions for the
cyclization of the dianion of ethyl acetoacetate 1a with
1,2-dihalides (Scheme 1). The following parameters were
crucial to induce a cyclization and to prepare 2-alky-
lidenetetrahydrofuran 3a in acceptable yield: (a) the use
of 1-bromo-2-chloroethane 2 as the dielectrophile and (b)
a proper tuning of the reaction temperature. At low
temperature (-78 f 20 °C) the terminal carbon atom of
the dianion chemo- and regioselectively attacked the
alkyl bromide function of 2. To induce the cyclization
step, which proceeded regioselectively via the oxygen
atom,18 the reaction mixture was refluxed for 12-14 h.
The exocyclic double bond was formed with high E-
diastereoselectivity which can be explained by (a) mini-
mization of the dipole-dipole repulsion of the oxygen
atoms in the W-shaped intermediate A19 and (b) the
higher thermodynamic stability of the E-diastereomer.
To study the preparative scope of the cyclization, the
substituents of the 1,3-dicarbonyl compounds were sys-
tematically varied (Table 1). Reaction of 1-bromo-2-
choroethane 2 with the dianions of ethyl, methyl, tert-
butyl, isobutyl, methoxyethyl, and benzyl acetoacetate
afforded the 2-alkylidenetetrahydrofurans 3a -f in good
yields and with very good regio- and E-diastereoselec-
tivities. Starting with the dianion of N,N-diethylacetyl-
acetic amide the E-configured 2-alkylidenetetrahydrofu-
ran 3g was prepared. Reaction of 2 with the dianions of
ethyl 2-methylacetoacetate, ethyl 2-ethylacetoacetate,
and ethyl 2-butylacetoacetate afforded the tetrahydro-
furans 3h -j containing a methyl, ethyl, and butyl group
at the exocyclic double bond, respectively. All products
were formed with very good regio- and E-diastereoselec-
tivities. The reaction of 1-bromo-2-chloroethane with
methyl 3-oxopentanoate and ethyl 3-oxohexanoate af-
forded the 2-alkylidenetetrahydrofurans 3k ,l with again
very good E-diastereoselectivities (despite the steric
influence of the substituents R1). Reaction of 2 with the
Ta ble 1. Syn th esis of 2-Alk ylid en etetr a h yd r ofu r a n s 3
c
3
R1
R2
R3
δa
δb
%
E/Z
a
H
H
H
H
H
H
H
H
H
H
Me
Et
H
H
H
H
H
H
H
H
H
Me
Et
Bu
H
OEt
OMe
O(t-Bu)
O(i-Bu)
5.30
168.1 75 >98:2
10:1
b
c
d
e
f
g
h
i
j
k
l
m
n
5.32, 4.85 168.7 63
5.25 167.2 74 >98:2
5.30, 4.85 168.7 63
10:1
10:1
10:1
O(CH2)2OMe 5.33, 4.85 168.5 70
OCH2Ph
NEt2
OEt
OEt
OEt
5.37, 4.92 167.8 60
5.62
166.7 80 >98:2
169.4 70 >98:2
169.1 68 >98:2
169.1 60 >98:2
168.4 68 >98:2
168.0 80 >98:2
169.4 40 >98:2
168.8 62 >98:2
OMe
OEt
5.23
5.20
H
CH2CH2O
CH2CH(Et)O
a
Chemical shifts (1H NMR) of the hydrogen atoms of the
b
exocyclic double bond (major and minor isomer). Chemical shifts
(
13C NMR) of the carbonyl group. c Isolated yields
Sch em e 2 Cycliza tion of th e Dia n ion of
r-Cya n oa ceton e w ith 1-Br om o-2-ch lor oeth a n e
dianions of the 2-acetyl-γ-butyrolactones 1m ,n afforded
the interesting 2-alkylidenetetrahydrofurans 3m ,n with
very good E-diastereoselectivities.
Treatment of 3-methylisoxazole with 2 equiv of LDA
afforded the dianion of R-cyanoacetone.20 Reaction of the
latter with 2 afforded the E-configured 2-alkylidene-
tetrahydrofuran 3o with very good diastereoselectivity
(Scheme 2).
(17) Barrett, A. G. M.; Sheth, H. G. J . Org. Chem. 1983, 48, 5017.
(b) Rao, Y. S. Chem. Rev. 1976, 76, 625. (c) Pattenden, G. Prog. Chem.
Nat. Prod. 1978, 35, 133. (d) Knight, D. W. Contemp. Org. Synth. 1994,
1, 287. (e) Gerlach, H.; Wetter, H. Helv. Chim. Acta 1974, 57, 2306. (f)
Schmidt, U.; Gombos, J .; Haslinger, E.; Zak, H. Chem. Ber. 1976, 109,
2628. (g) Bartlett, P. A.; Meadows, J . D.; Ottow, E. J . Am. Chem. Soc.
1984, 106, 5304. (h) Oivin, T. L. B. Tetrahedron 1987, 43, 3309 and
references therein.
The geometry of the exocyclic double bond of 2-alkyl-
idenetetrahydrofurans 3a -o was established by NOESY
experiments and by comparison of the chemical shifts of
the hydrogen atoms of the exocyclic double bond (Table
1) with those of related compounds.12,21 As expected, the
chemical shifts strongly depend on the configuration of
the double bond (for E-configured, ester-derived tetrahy-
(18) For stereoelectronic considerations related to the regioselectivity
of cyclizations, see: Baldwin, J . E.; Kruse, L. I. J . Chem. Soc., Chem.
Commun. 1977, 233.
(19) For the configuration of monoanions of 1,3-dicarbonyl com-
pounds, see: (a) Rhoads, S. J .; Holder, R. W. Tetrahedron 1969, 25,
5443. (b) Miller, B.; Margulies, H.; Drabb, T., J r.; Wayne, R. Tetrahe-
dron Lett. 1970, 3801. (c) Miller, B.; Margulies, H.; Drabb, T., J r.;
Wayne, R. Tetrahedron Lett. 1970, 3805. (d) Entenmann, G. Tetrahe-
dron Lett. 1975, 4241. (e) Cambillau, C.; Sarthou, P.; Bram, G.
Tetrahedron Lett. 1976, 281. For a review of the structure of lithium
enolates, see: (f) Seebach, D. Angew. Chem. 1988, 100, 1685; Angew.
Chem., Int. Ed. Engl. 1988, 27, 1624.
(20) Vinick, F. J .; Pan, Y.; Gschwend, H. W. Tetrahedron Lett. 1978,
44, 4221.

Synthesis of 2-Alkylidenetetrahydrofurans
J . Org. Chem., Vol. 66, No. 18, 2001 6059
Ta ble 2. Syn th esis of
2-Alk ylid en e-5-vin yltetr a h yd r ofu r a n s 5a -k
Sch em e 3 Cycliza tion of 1,3-Dica r bon yl Dia n ion s
w ith 1,4-Dibr om o-2-bu ten e
c
5
R1
R2
R3
δ (CH)a δ (CdO)b
Z/E
%
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
H
H
H
H
Me
Et
Bu
OEt
O(t-Bu)
Me
NEt2
OEt
OEt
4.75
164.5
164.2
200.1
164.3
166.6
167.9
166.4
168.3
187.9
167.5
164.4
>98:2 60
>98:2 58
>98:2 47
>98:2 73d
>98:2 64
>98:2 61
>98:2 32
<2:98 32
<2:98 46
8:1 61
4.68
4.96
4.97
OEt
-CH2CH2O-
H
Me
Et
-CH2CH2(C6H4)-
H
H
j
k
OMe
OEt
4.70, 4.75
4.70, 4.75
>98:2 53
a
Chemical shifts (1H NMR) of the hydrogen atoms of the
b
exocyclic double bond (major and minor isomer). Chemical shifts
(
13C NMR) of the carbonyl group. c Isolated yields. The diastereo-
selectivities for 5j and 5k are 45:55 and 65:35, respectively. The
configuration of the isomers could not be unambigiously assigned.
d
The starting material could not be completely separated.
drofurans δ ) 5.30-5.40; for Z-isomers δ ) 4.80-4.90).
The configuration of 3h -j and 3m ,n , containing tetra-
substituted exocyclic double bonds, was established by
analysis of the 13C NMR chemical shifts of the carbonyl
carbons.12,21 Additional evidence was obtained based on
NOESY experiments.
Sch em e 4. Cycliza tion of th e Dia n ion of
r-Cya n oa ceton e w ith 1,4-Dibr om o-2-bu ten e
Dom in o SN/SN′ Rea ction s. The following parameters
proved to be important for the cyclization of the dianion
of ethyl acetoacetate 1a with 1,4-dihalo-2-butenes: (a)
the use of 1,4-dibromo-2-butene 4 rather than 1,4-
dichloro-2-butene as the dielectrophile and (b) a proper
tuning of the temperature to avoid the formation of open-
chain products.22 The reaction of a THF solution of 4 with
the dianion of 1a afforded the 2-alkylidene-5-vinyltet-
rahydrofuran 5a in up to 60% yield. Formation of 5a can
be explained by a domino SN/SN′ reaction, which involves
regioselective attack of the terminal carbon of the dianion
onto 4 and subsequent cyclization via the oxygen atom
of the dianion (Scheme 3). The exocyclic double bond of
5a was formed with very good Z-diastereoselectivity,
which can be explained by chelation of a lithium ion by
two oxygen atoms (intermediate A). In contrast to the
synthesis of tetrahydrofurans 3, the cyclization step was
carried out at low temperature (kinetic reaction control).
Therefore, no isomerization of the product to the ther-
modynamically more stable E-configured isomer oc-
curred. However, a slow rearrangement (accompagnied
by significant decomposition) was observed upon standing
at room temperature for several days.
To study the preparative scope of our methodology, the
substituents of the 1,3-dicarbonyl compounds were sys-
tematically varied (Scheme 3, Table 2). The reaction of
4 with the dianions of ethyl acetoacetate, tert-butyl
acetoacetate, acetylacetone, and N,N-diethylacetylacetic
amide afforded the Z-configured 2-alkylidene-5-vinyl-
tetrahydrofurans 5a -d in good yields and with very good
stereoselectivities. Treatment of 1,4-dibromo-2-butene
with the dianions of ethyl 2-methylacetoacetate, ethyl
2-ethylacetoacetate, and ethyl 2-butylacetoacetate re-
sulted in formation of tetrahydrofurans 5e-g with very
good Z-diastereoselectivities. Reaction of 4 with the
dianions of 2-acetyl-γ-butyrolactone and R-acetyltetralone
afforded the 2-alkylidene-5-vinyltetrahydrofurans 5h and
5i, respectively. During the tedious purification of these
products a complete isomerization into the more stable
E-diastereomers occurred. The reaction of 1,4-dibromo-
2-butene with the dianions of methyl 3-oxopentanoate
and ethyl 3-oxohexanoate afforded the 2-alkylidene-5-
vinyltetrahydrofurans 5j,k in good yields and with very
good Z-diastereoselectivities. The cyclization of 1,4-di-
bromo-2-butene with the dianion of R-cyanoacetone
(Scheme 4) afforded the cyano-substituted 2-alkylidene-
5-vinyltetrahydrofuran 5l with very good regio- and
E-diastereoselectivity (for comparison, see Scheme 2). The
change from Z- to E-configuration of the exocyclic double
bond can be explained by the fact that no chelation can
occur, a result of the absence of a second carbonyl group.
The geometry of the exocyclic double bond of 2-alky-
lidenetetrahydrofurans 5a -l was established by NOESY
experiments, crystal structure analyses,23 and compari-
son of the chemical shifts of the hydrogen atoms of the
exocyclic double bond (Table 2) with those of tetrahydro-
furans 3 and related compounds (Table 1).12,21 For
example, the chemical shifts of the Z-configured, ester-
derived 2-alkylidenetetrahydrofurans 5a ,b,j,k appear in
the range of δ ) 4.65-4.80. The configuration of tetrahy-
drofurans 5e-i was established by comparison of the 13
C
NMR chemical shifts of the carbonyl carbons with those
of 3h -j and 3m ,n .
From a methodology viewpoint, we have reported
domino C,O-cyclodialkylation reactions of 1,3-dicarbonyl
dianions. Very good regio- and E/Z-diastereoselectivities
were observed giving rise to the formation of function-
alized 2-alkylidenetetrahydrofurans, which are of biologi-
cal relevance and of importance for natural product
syntheses.
(21) For the relationship between the chemical shift of the CH
hydrogen atom and the configuration of the exocyclic double bond of
γ-alkylidenebutenolides, see for example: (a) Siegel, K.; Bru¨ckner, R.
Chem. Eur. J . 1998, 4, 1116. For 2-alkylidenetetrahydrofurans, see
for example: (b) Al-Tel, T. H.; Voelter, W. J . Chem. Soc., Chem.
Commun. 1995, 239. (c) Al-Tel, T. H.; Meisenbach, M.; Voelter, W.
Liebigs Ann. 1995, 689.
(22) For the formation of an open-chain condensation product, see:
Hoye, T. R.; Suhadolnik, J . C. Tetrahedron 1986, 42, 2855.
(23) Langer, P.; Holtz, E.; Ko¨nig, V., unpublished results.

6060 J . Org. Chem., Vol. 66, No. 18, 2001
Langer et al.
2-(E)-[(2-Meth oxyeth oxyca r bon yl)m eth ylid en e]tetr a -
h yd r ofu r a n (3e). Starting with 2-methoxyethyl acetoacetate
(0.32 g, d ) 1.090 g/cm3, 0.29 mL, 2.0 mmol) and 1-bromo-2-
chloroethane (0.18 mL, 2.2 mmol, 1.1 equiv.), 3e was isolated
by chromatography (silica gel, ether/petroleum ether 1:3) as a
colorless oil (261 mg, 70%, E/Z ) 10:1). The starting material
could not be completely removed from the product. 1H NMR
(CDCl3, 250 MHz) δ 2.09 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.07
(dt, J ) 6.5 Hz, J ) 1.5 Hz, 2 H, 3-H), 3.36 (s, 3 H, OCH3),
3.55-3.60 (m, 2 H, OCH2CH2OMe), 4.17-4.29 (m, 4 H, OCH2-
CH2OMe, 5-H), 5.33 (t, J ) 1.5 Hz, 1 H, CHCdO); Z-isomer δ
(dCH-) 4.85; 13C NMR (CDCl3, 50 MHz) δC 23.79, 30.28 (C-3,
C-4), 58.96 (OCH3), 62.34, 70.82, 71.84 (OCH2), 89.30 (CdCH),
168.50 (CdO), 177.14 (C-2); MS (70 eV, EI) m/z 186 (M+, 20).
The exact molecular mass for C9H14O4 m/z 186.0892 ( 2 mDa
was confirmed by HRMS (70 eV, EI).
2-(E)-[(Ben zyloxyca r b on yl)m et h ylid en e]t et r a h yd r o-
fu r a n (3f). Starting with benzyl acetoacetate (0.38 g, 0.35 mL,
d ) 1.112 g/cm3, 2.0 mmol) and 1-bromo-2-chloroethane (2.2
mmol, 0.18 mL, 1.1 equiv), 3f was isolated by chromatography
(silica gel, ether/petroleum ether 1:5) as a colorless oil (262
mg, 60%, E/Z ) 10:1). The starting material could not be
completely removed from the product. 1H NMR (CDCl3, 250
MHz) δ 2.09 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.13 (dt, J ) 6.5
Hz, J ) 1.5 Hz, 2 H, 3-H), 4.23 (t, J ) 6.5 Hz, 2 H, 5-H), 5.18
(s, 2 H, OCH2Ph), 5.37 (t, J ) 6.5 Hz, 1 H, CHCO2), 7.26-
7.36 (m, 5 H, Ph); Z-isomer δ 4.92 (dCH-); 13C NMR (CDCl3,
50 MHz) δC 23.33, 29.62 (C-3, C-4), 64.62 (OCH2Ph), 71.49 (C-
5), 88.78 (CHCO2CH2), 127.44, 127.55, 128.01, 128.20 (Ph),
167.82 (CdO), 176.97 (C-2).
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Cycliza tion of 1-Br om o-2-
ch lor oet h a n e w it h 1,3-Dica r b on yl Dia n ion s. To a THF
solution of LDA (prepared by addition of 5.0 mmol of n-BuLi,
1.6 M in hexane, to a solution of diisopropylamine (0.57 mL,
5.0 mmol) in 50 mL of THF) was added ethyl acetoacetate (0.25
mL, 2.0 mmol) at 0 °C. The deep yellow, clear solution was
stirred at 0 °C for 45 min. To this solution was added 1-bromo-
2-chloroethane (0.18 mL, 2.2 mmol) at -78 °C. The tempera-
ture was allowed to rise to ambient during 14 h, and the
solution was subsequently refluxed for 14 h. To the solution
was added hydrochloric acid (200 mL, 0.1 M), and the mixture
was extracted with ether (4 × 150 mL). The organic layers
were dried and filtered, the solvent of the filtrate was removed
in vacuo, and the residue was purified by chromatography
(silica gel, ether/petroleum ether 1:20 f 1:3) to give 3a (234
mg, 75%, E/Z > 98:2) as a colorless oil. The diastereomeric
1
ratios were determined by integration of the H NMR spectra
of the products.
2-(E)-(E t h oxyca r b on ylm et h ylid en e)t et r a h yd r ofu r a n
(3a ). 1H NMR (CDCl3, 250 MHz) δ 1.25 (t, J ) 7 Hz, 3 H,
OCH2CH3), 2.08 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.10 (dt, J )
6.5 Hz, J ) 1.5 Hz, 2 H, 3-H), 4.15 (q, J ) 7 Hz, 2 H, OCH2-
CH3), 4.23 (t, J ) 6.5 Hz, 2 H, H-5), 5.30 (t, J ) 1.5, 1 H, CHCd
O); 13C NMR (CDCl3, 50 MHz) δC 14.02 (OCH2CH3), 23.44,
29.82 (C-3, C-4), 58.68 (OCH2CH3), 71.33 (C-5), 89.04 (CHCO2-
Et), 168.08 (CdO), 176.29 (C-2); MS (70 eV, EI) m/z 156 (M+,
38), 111 (100), 69 (72). Anal. Calcd for C8H12O3: C 61.52, H
7.74. Found: C 61.48, H 7.90.
2-(E )-(1-Me t h oxyca r b on ylm e t h ylid e n e )t e t r a h yd r o-
fu r a n (3b). Starting with methyl acetoacetate (0.23 g, d )
1.077 g/cm3, 0.22 mL, 2.1 mmol) and 1-bromo-2-chloroethane
(0.18 mL, 2.2 mmol, 1.1 equiv.), 3b was isolated by chroma-
tography (silica gel, ether/petroleum ether 1:1) as a colorless
oil (185 mg, 63%, E/Z ) 10:1): 1H NMR (CDCl3, 250 MHz) δ
2.09 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.11 (dt, J ) 6.5 Hz, J )
1.5 Hz, 2 H, 3-H), 3.66 (s, 3 H, OCH3), 4.23 (t, J ) 6.5 Hz, 2 H,
5-H), 5.32 (t, J ) 1.5 Hz, 1 H, CHCO2Me); Z-isomer: δ (d
CH-) 4.85; 13C NMR (CDCl3, 50 MHz) δC 23.55, 29.96 (C-3,
C-4), 50.26 (OCH3), 71.55 (C-5), 88.82 (CHCO2CH3), 168.65
(CdO), 176.62 (C-2); IR (neat) ν˜ 3383 (br), 3030 (w), 2993 (m),
2959 (m), 2912 (m), 1703 (s), 1648 (s), 1432 (m), 1352 (s), 1121
(s) cm-1; MS (70 eV, EI) m/z 142 (M+, 60). The exact molecular
mass for C7H10O3 m/z 142.0630 ( 2 mDa was confirmed by
HRMS (70 eV, EI).
2-(E)-(2-Dieth yla m in o-2-oxoeth ylid en e)tetr a h yd r ofu -
r a n (3g). Starting with N,N-diethylacetylacetic amide (0.31
g, 2.0 mmol) and 1-bromo-2-chloroethane (2.2 mmol, 0.18 mL,
1.1 equiv), 3g was isolated by chromatography (silica gel, ether/
petroleum ether 1:3) as a colorless oil (293 mg, 80%, E/Z >
98:2): 1H NMR (CDCl3, 250 MHz) δ 1.25 [br, 6 H, N(CH2CH3)2],
2.08 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.15 (dt, J ) 6.5 Hz, J )
1.5 Hz, 2 H, 3-H), 3.20-3.50 [m, 4 H, N(CH2CH3)2], 4.16 (t, J
) 6.5 Hz, 2 H, 5-H), 5.62 (t, J ) 1.5 Hz, 1 H, CHCdO); 13C
NMR (CDCl3, 50 MHz) δC 12.92, 13.93 (CH3), 23.60, 29.23 (C-
4, C-3), 39.63, 41.59 [N(CH2CH3)2], 70.13 (C-5), 88.32 (CHCd
O), 166.65 (CdO), 173.30 (C-2); IR (neat) ν˜ 3458 (br), 2976 (m),
2933 (m), 2897 (m), 1662 (s), 1600 (s), 1482 (m), 1429 (m), 1182
(m), 1114 (s) cm-1; MS (70 eV, EI) m/z 183 (M+, 35), 111 (100),
69 (38). Anal. Calcd for C10H17NO2: C 65.54, H, 9.35. Found:
C 65.27, H, 9.11.
2-(E)-(ter t-Bu t oxyca r b on ylm et h ylid en e)t et r a h yd r o-
fu r a n (3c). Starting with tert-butyl acetoacetate (2.0 mmol,
0.32 g) and 1-bromo-2-chloroethane (0.18 mL, 2.2 mmol, 1.1
equiv), 3c was isolated by chromatography (silica gel, ether/
petroleum ether 1:1) as a colorless oil (273 mg, 74%, E/Z >
98:2): 1H NMR (CDCl3, 250 MHz) δ 1.50 [s, 9 H, C(CH3)3],
2.08 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.10 (dt, J ) 6.5 Hz, J )
1.5 Hz, 2 H, 3-H), 4.20 (t, J ) 6.5 Hz, 2 H, 5-H), 5.25 (t, J )
1.5 Hz, 1 H, CHCdO); 13C NMR (CDCl3, 50 MHz) δC 27.74
[C(CH3)3], 23.44, 29.82 (C-3, C-4), 71.31 (C-5), 77.84 (C(CH3)3),
90.45 (CHCO2t-Bu), 167.16 (CdO), 175.94 (C-2); MS (70 eV,
EI) m/z 184 (M+, 1), 128 (65), 69 (96). Anal. Calcd for
2-(E )-[1-(E t h o x y c a r b o n y l)e t h y lid e n e ]t e t r a h y d r o -
fu r a n (3h ). Starting with ethyl 2-methylacetoacetate (0.29 g,
2.0 mmol) and 1-bromo-2-chloroethane (0.18 mL, 2.2 mmol,
1.1 equiv), 3h was isolated by chromatography (silica gel,
ether/petroleum ether 1:3) as a colorless oil (238 mg, 70%, E/Z
> 98:2): 1H NMR (CDCl3, 250 MHz) δ 1.25 (t, J ) 7 Hz, 3 H,
OCH2CH3), 1.80 (s, 3 H, CH3), 2.25 (quint, J ) 6.5 Hz, 2 H,
4-H), 3.05 (m, 2 H, 3-H), 4.20 (t, J ) 6.5 Hz, 2 H, 5-H), 4.17 (t,
J ) 7 Hz, 2 H, OCH2CH3); 13C NMR (CDCl3, 50 MHz) δC 11.24
(OCH2CH3), 14.45 (CH3), 24.52, 30.84 (C-3, C-4), 59.42 (OCH2-
CH3), 71.18 (C-5), 97.52 (CCO2Et), 169.36 (CdO), 170.25
(C-2); MS (70 eV, EI) m/z 170 (M+, 70), 125 (100), 83 (81), 42
(71). Anal. Calcd for C9H14O3: C 63.51, H 8.29. Found: C 63.80,
H 7.99.
C
10H16O3: C 65.19, H 8.75. Found: C 65.19, H 8.97.
2-(E)-(Isob u t yloxyca r b on ylm et h ylid en e)t et r a h yd r o-
fu r a n (3d ). Starting with isobutyl acetoacetate (2.0 mmol, 0.32
g, d ) 0.980 g/cm3, 0.32 mL) and 1-bromo-2-chloroethane (0.18
mL, 2.2 mmol, 1.1 equiv), 3d was isolated by chromatography
(silica gel, ether/petroleum ether 1:5) as a colorless oil (232
mg, 63%, E/Z ) 10:1): 1H NMR (CDCl3, 250 MHz) δ 0.93 (d,
J ) 6.5 Hz, 6 H, CH3), 2.07 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.09
[m, 1 H, OCH2CH(CH3)2], 3.82 [m, 4 H, 3-H, OCH2CH(CH3)2],
4.20 (t, J ) 6.5 Hz, 2 H, 5-H), 5.30 (t, J ) 1.5 Hz, 1 H, CHCd
O); Z-isomer δ (dCH-) 4.85; 13C NMR (CDCl3, 50 MHz) δC
19.16 [CH(CH3)2], 23.84 (C-4), 27.83 [CH(CH3)2], 30.20 (C-3),
69.54 [OCH2CH(CH3)2] 71.69 (C-5), 89.62 (CHCdO), 168.68
(CdO), 176.49 (C-2); IR (neat) ν˜ 2962 (m), 2876 (w), 1704 (s),
1646 (s), 1381 (m), 1112 (s), 1046 (s) cm-1; MS (70 eV, EI) m/z
184 (M+, 19), 129 (17), 128 (30), 111 (100), 69 (61). Anal. Calcd
for C10H16O3: C 65.19, H 8.75. Found: C 65.40, H 8.62.
2-(E )-[1-(E t h oxyca r b on yl)p r op ylid e n e ]t e t r a h yd r o-
fu r a n (3i). Starting with ethyl 2-ethylacetoacetate (2.0 mmol,
0.32 g) and 1-bromo-2-chloroethane (0.18 mL, 2.2 mmol, 1.1
equiv), 3i was isolated by chromatography (silica gel, ether/
petroleum ether 1:3) as a colorless oil (251 mg, 68%, E/Z >
98:2): 1H NMR (CDCl3, 250 MHz) δ 0.90 (t, J ) 7 Hz, 3 H,
CH2CH3), 1.25 (t, J ) 7 Hz, 3 H, OCH2CH3), 2.05 (quint, J )
7 Hz, 2 H, 4-H), 2.30 (q, J ) 7 Hz, 2 H, CH2CH3), 3.04 (t, J )
7 Hz, 2 H, 3-H), 4.01-4.30 (m, 4 H, 5-H, OCH2CH3); 13C NMR
(CDCl3, 50 MHz) δC 13.77, 14.43 (CH3), 19.39, 24.38 (C-4, C-3),
30.95 (CCH2CH3), 59.27 (OCH2CH3), 71.18 (C-5), 104.36 (CCO2-
Et), 169.10, 170.19 (C-2, CdO); IR (neat) ν˜ 29962 (s), 2928 (s),
2961 (s), 1734 (m), 1655 (s), 1602 (m), 1457 (m), 1261 (s), 1076
(s) cm-1; MS (70 eV, EI) m/z 184 (25). Anal. Calcd for
C
10H16O3: C 65.19, H 8.75. Found: C 64.90, H 8.47.

Synthesis of 2-Alkylidenetetrahydrofurans
J . Org. Chem., Vol. 66, No. 18, 2001 6061
2-(E )-[1-(E t h oxyca r b on yl)p e n t ylid e n e ]t e t r a h yd r o-
fu r a n (3j). To a suspension of sodium hydride (0.50 g) in THF
(50 mL) was added ethyl 2-butylacetoacetate (0.75 g, 4.0 mmol)
at 0 °C, and the solution was stirred at 0 °C (1 h) and at 20 °C
(1h). To the solution was added n-butyllithium (2.03 mL, 4.8
mmol, 2.35 M Lo¨sung in n-hexane). After stirring for 1 h at 0
°C the solution was cooled to -78 °C, and 1-bromo-2-chloro-
ethane (0.37 mL, 4.4 mmol, 1.1 equiv) was added. After
warming to 20 °C during 14 h the solution was refluxed for
14 h. The solution was poured into an aqueous solution of
hydrochloric acid (200 mL, 0.1 M), and the aqueous layer was
extracted with ether (4 × 150 mL). The combined organic
layers were dried (MgSO4) and filtered, and the filtrate was
concentrated in vacuo. The residue was purified by chroma-
tography (silica gel, ether/petroleum ether 1:10 f 1:3) to give
3j as a colorless oil (509 mg, 60%, E/Z > 98:2). The starting
material could not be completely removed from the product.
1H NMR (CDCl3, 200 MHz) δ 0.80 (t, J ) 7 Hz, 3 H, CH2CH3),
1.20 (t, J ) 7 Hz, 3 H, OCH2CH3), 1.40-1.62 [m, 6 H, (CH2)3],
1.95 (quint, J ) 6.5 Hz, 2 H, 4-H), 3.00 (t, J ) 7 Hz, 2 H, 3-H),
4.02-4.20 (m, 4 H, 5-H, OCH2CH3); 13C NMR (CDCl3, 50 MHz)
δC 13.91, 14.28 (CH2CH3), 22.26, 22.44, 24.28, 27.73, 30.86
(CH2CH2CH2CH3, C-4, C-3), 61.05 (OCH2CH3), 71.69 (C-5),
102.84 (CCO2Et), 169.10, 170.32 (C-2, CdO); MS (70 eV, EI)
m/z 212 (M+, 100), 185 (22), 167 (50), 111 (28), 97 (55). The
exact molecular mass for C12H20O3 m/z 212.1412 ( 2 mDa was
confirmed by HRMS (70 eV, EI).
gel, ether/petroleum ether 1:1) as a colorless oil (225 mg, 62%,
E/Z > 98:2): 1H NMR (CDCl3, 200 MHz) δ 0.90 (t, J ) 7 Hz,
3 H, CH3), 1.46-1.84 (m, 2 H, CH2CH3), 2.04 (quint, J ) 6.5
Hz, 2 H, 4-H), 2.32-2.40 (m, 2 H, CH2CHO), 2.98-3.06 (m, 2
H, 3-H), 4.21 (t, J ) 6.5 Hz, 2 H, 5-H), 4.27 (m, 1 H, OCHCH2);
13C NMR (CDCl3, 50 MHz) δC 8.61 (CH3), 23.58, 28.51, 28.90,
30.09 (C-4, CH2CHO, C-3, CH2CH3), 71.94 (C-5), 77.84
(OCHCH2CH3), 93.45 (CdCCO2), 168.79 (CdO), 172.21 (C-2);
IR (neat) ν˜ 2968 (m), 2938 (m), 1739 (s), 1668 (s), 1457 (w),
1351 (m), 1254 (s), 1036 (s) cm-1; MS (70 eV, EI) m/z 182 (M+,
100), 153 (35), 125 (63), 96 (77), 43 (49). Anal. Calcd for
C
10H14O3: C 65.91, H 7.74. Found: C 65.71, H 7.49.
2-(E)-(Cya n om eth ylid en e)tetr a h yd r ofu r a n (3o). Start-
ing with 5-methylisoxazole (2.0 mmol, 0.17 g) and 1-bromo-2-
chloroethane (2.2 mmol, 0.18 mL, 1.1 equiv), 3o was isolated
by chromatography (silica gel, ether/petroleum ether 1:3) as a
colorless oil (87 mg, 40%, E/Z > 98:2): 1H NMR (CDCl3, 250
MHz) δ 2.11 (quint, J ) 7 Hz, 2 H, 4-H), 2.70 (dt, J ) 6.5 Hz,
J ) 1.5 Hz, 2 H, 3-H), 4.27 (t, J ) 1.5 Hz, 1 H, CHCN), 4.37
(t, J ) 7 Hz, 2 H, 5-H); 13C NMR (CDCl3, 50 MHz) δC 23.96,
30.79 (C-4, C-3), 65.09 (C-5), 73.88 (CHCN), 116.66 (CN),
176.85 (C-2); IR (neat) ν˜ 3327 (br), 3088 (w), 2968 (m), 2912
(m), 2213 (s, CN), 1651 (s), 1391 (m), 1187 (s), 1200 (s), 1112
(s) cm-1; MS (70 eV, EI) m/z 109 (M+, 81), 68 (100), 42 (81).
The exact molecular mass for C6H7NO m/z 109.0527 ( 2 mDa
was confirmed by HRMS (70 eV, EI). Anal. Calcd for C6H7-
NO: C 66.04, H 6.47. Found: C 65.41, H 7.40.
2-(Z)-[(Me t h o x y c a r b o n y l)m e t h y lid e n e ]-3-m e t h y l-
tetr a h yd r ofu r a n (3k ). Starting with methyl 3-oxopentanoate
(2.0 mmol, 0.26 g) and 1-bromo-2-chloroethane (2.2 mmol, 0.18
mL, 1.1 equiv), 3k was isolated by chromatography (silica gel,
ether/petroleum ether 1:3) as a colorless oil (212 mg, 68%, E/Z
> 98:2): 1H NMR (CDCl3, 250 MHz) δ 1.25 (d, J ) 7 Hz, 3 H,
CH3), 2.18-2.31 (m, 2 H, 4-H), 2.59 (q, J ) 7 Hz, 1 H, 3-H),
3.65 (s, 3 H, OCH3), 4.20-4.40 (m, 2 H, 5-H), 5.23 (s, 1 H,
CHCdO); 13C NMR (CDCl3, 50 MHz) δC 17.53 (CH3), 31.52,
35.88 (C-3, C-4), 50.43 (OCH3), 69.74 (C-5), 88.30 (CHCdO),
168.35 (CdO), 181.51 (C-2); IR (neat) ν˜ 3344 (br), 3076 (m),
2961 (s), 1627 (s), 1441 (s), 1308 (s), 1268 (s), 1200 (s), 1112
(s) cm-1; MS (70 eV, EI) m/z 156 (M+, 50), 139 (27), 125 (89),
111 (45), 69 (100). Anal. Calcd for C8H12O3: C 61.52, H 7.74.
Found: C 61.41, H, 7.40.
2-(Z)-[(Eth oxyca r bon yl)m eth ylid en e]-3-eth yltetr a h y-
d r ofu r a n (3l). Starting with ethyl 3-oxohexanoate (2.0 mmol,
0.31 g) and 1-bromo-2-chloroethane (0.18 mL, 2.2 mmol, 1.1
equiv), 3l was isolated by chromatography (silica gel, ether/
petroleum ether 1:3) as a colorless oil (293 mg, 80%, E/Z >
98:2): 1H NMR (CDCl3, 250 MHz) δ 1.0 (t, J ) 7 Hz, 3 H,
CH3), 1.23 (t, J ) 7 Hz, 3 H, OCH2CH3), 1.62-1.83 (m, 2 H,
CH2CH3), 1.84-2.20 (m, 2 H, 4-H), 3.42-3.61 (m, 1 H, 3-H),
3.99-4.16 (m, 2 H, 5-H), 4.25 (q, J ) 7 Hz, 2 H, OCH2CH3),
5.20 (s, 1 H, CHCdO); 13C NMR (CDCl3, 50 MHz) δC 12.37
(CHCH2CH3), 14.38 (OCH2CH3), 24.94, 28.06, 42.92 (C-3, C-4,
CCH2CH3), 59.08 (OCH2CH3), 69.99 (C-5), 89.16 (CHCdO),
167.99 (CdO), 180.67 (C-2); IR (neat) ν˜ 2964 (s), 2903 (s), 1741
(s), 1714 (s), 1646 (s), 1463 (m), 1384 (m), 1151 (s), 1113 (s)
cm-1; MS (70 eV, EI) m/z 184 (M+, 35), 111 (100), 69 (38). Anal.
Calcd for C10H16O3: C 65.19, H 8.75. Found: C 65.27, H 9.11.
2-(E )-(2-Oxot e t r a h yd r ofu r a n -3-ylid e n e )t e t r a h yd r o-
fu r a n (3m ). Starting with 2-acetyl-γ-butyrolactone (0.26 g, 2.0
mmol) and 1-bromo-2-chloroethane (2.2 mmol, 0.18 mL, 1.1
equiv), 3m was isolated by chromatography (silica gel, ether/
petroleum ether 1:3) as a colorless oil (123 mg, 40%, E/Z >
98:2): 1H NMR (CDCl3, 250 MHz) δ 2.10 (quint, J ) 6.5 Hz, 2
H, 4-H), 2.87 (m, 2 H, (CH2CH2O), 3.09 (t, J ) 6.5 Hz, 2 H,
3-H), 4.30 (2 x t, J ) 6.5 Hz, 4 H, OCH2CH2, 5-H); 13C NMR
(CDCl3, 50 MHz) δC 23.96, 24.96, 28.84 [C-3, C-4, CH2(CdC)],
65.12, 72.39 (C-5, OCH2), 92.84 (CdCCO2), 169.40 (CdO),
173.00 (C-2); MS (70 eV, EI) m/z 154 (M+, 20). The exact
molecular mass for C8H10O3 m/z 154.0630 ( 2 mDa was
confirmed by HRMS (70 eV, EI).
Gen er a l P r oced u r e for th e Cycliza tion of 1,3-Dica r -
bon yl Dia n ion s w ith 1,4-Dibr om o-2-bu ten e. A THF solu-
tion of LDA (4.7 mmol) was prepared by addition of n-BuLi
(8.0 mL, 18.4 mmol, 2.3 M solution in n-hexane) to a THF
solution (50 mL) of diisopropylamine (2.6 mL, 18.4 mmol) at
0 °C. After the solution stirred for 20 min, ethyl acetoacetate
(1.04 g, 8.0 mmol) was added at 0 °C. After stirring for 60 min,
to the solution was added a THF solution (25 mL) of 1,4-
dibromo-2-butene 4 (1.712 g, 8.0 mmol) at -78 °C. The
employment of an inverse addition protocol was advantageous
in many cases. The temperature was allowed to rise to ambient
during 4-12 h, and the solution was stirred at 20 °C for 2 h.
The reaction mixture was poured into an aqueous solution of
hydrochloric acid (0.1 M) and was extracted with ether. The
combined organic layers were dried (MgSO4), filtered, and the
filtrate was concentrated in vacuo. The residue was purified
by column chromatography (silica gel, petroleum ether/ether
3:2) to give 5a (875 mg, 60%, Z/E > 98:2) as a colorless oil.
2-(E t h oxyca r b on ylm et h ylid en e)-5-vin ylt et r a h yd r o-
fu r a n (5a ). Starting with ethyl acetoacetate (1.04 g, 8.0 mmol),
diisopropylamine (2.6 mL, 18.4 mmol), n-BuLi (8.0 mL, 18.4
mmol, 2.3 M solution in n-hexane), and 1,4-dibromo-2-butene
(1.712 g, 8.0 mmol), 875 mg (60%, Z/E > 98:2) of 5a was
obtained as a colorless solid. The purification was effected by
chromatography (silica gel, petroleum ether/ether 3:2). 1H
3
NMR (250 MHz, acetone-d6) δ 1.18 (t, J ) 7 Hz, 3 H, CH3),
3
1.69-1.86 (m, 1 H, 4-H), 2.15-2.34 (m, 1 H, 4-H), 2.75 (t, J
) 8 Hz, 2 H, 3-H), 4.01 (q, 3J ) 7 Hz, 2 H, OCH2), 4.75 (s, 1 H,
3
3
OdCCH), 4.98 (dt, J ) 3J ) 6 Hz, 1 H, 5-H), 5.19 [d, J (Z) )
11 Hz, 1 H, CdCH], 5.36 [d, 3J (E) ) 18 Hz, 1 H, H2CdCH],
3
3
3
5.94 [ddd, J ) 6 Hz, J (Z) ) 11 Hz, J (E) ) 18 Hz, 1 H, CHd
CH2]; 13C NMR (62.9 MHz, acetone-d6) δ 13.98 (CH3), 28.91,
31.53 (CH2), 58.06 (OCH2), 85.98, 87.33 (C-5, OdCCH), 116.23
(CHdCH2), 136.63 (CHdCH2), 164.47 (CdO), 171.63 (C-2); MS
(70 eV, EI) m/z 182 (73) [M]+, 137 (100), 87 (85), 69 (100), 43
(55). The exact molecular mass for C10H14O3 m/z 182.0943 (
2 mD (M+) was confirmed by HRMS (EI, 70 eV).
2-(1,1-Dim eth yleth oxyca r bon ylm eth ylid en e)-5-vin yl-
tetr a h yd r ofu r a n (5b). Starting with tert-butyl acetoacetate
(1.73 g, 10.95 mmol), diisopropylamine (3.55 mL, 25.0 mmol),
n-BuLi (25.0 mmol, solution in n-hexane), and 1,4-dibromo-
2-butene (2.58 g, 12.05 mmol), 1.33 g of 5b (58%, Z/E > 98:2)
was isolated as a colorless solid. The purification was effected
1
by chromatography (silica gel, petroleum ether/ether 3:2). H
2-(E)-(5-Eth yl-2-oxotetr ah ydr ofu r an -3-yliden e)tetr ah y-
d r ofu r a n (3n ). Starting with R-acetyl-γ-ethyl-γ-butyrolactone
(2.0 mmol, 0.31 g) and 1-bromo-2-chloroethane (0.18 mL, 2.2
mmol, 1.1 equiv), 3n was isolated by chromatography (silica
NMR (250 MHz, CDCl3) δ 1.40 (s, 9 H, CH3), 1.68-1.84 (m, 1
H, 4-H), 2.13-2.29 (m, 1 H, 4-H), 2.71 (t, 3J ) 8 Hz, 2 H, 3-H),
4.68 (s, 1 H, OdCCH), 4.94 (dt, 3J ) 3J ) 6 Hz, 1 H, 5-H),
5.18 [d, 3J (Z) ) 11 Hz, 1 H, H2CdCH], 5.36 [d, 3J (E) ) 18 Hz,

6062 J . Org. Chem., Vol. 66, No. 18, 2001
Langer et al.
3
3
3
3
1 H, H2CdCH], 5.93 [ddd, J ) 6 Hz, J (Z) ) 11 Hz, J (E) )
18 Hz, 1 H, CHdCH2]; 13C NMR (62.9 MHz, acetone-d6) δ 27.72
(CH3), 28.93, 31.46 (CH2), 77.31 [OC(CH3)3], 85.70, 89.04 (C-
5, OdCCH), 116.10 (CHdCH2), 136.70 (CHdCH2), 164.16 (Cd
O), 170.68 (C-2); MS (70 eV, EI) m/z 210 (23) [M]+, 154 (83),
137 (100), 87 (91), 69 (65), 68 (51), 57 (40). The exact molecular
mass for C12H18O3 m/z 210.1256 ( 2 mD (M+) was confirmed
by HRMS (EI, 70 eV).
NMR (250 MHz, CDCl3) δ 0.96 (t, J ) 7 Hz, 3 H, CCH2CH3),
3
1.23 (t, J ) 6 Hz, 3 H, OCH2CH3), 1.79-1.90 (m, 1 H, 4-H),
2.19-2.36 (m, 1 H, 4-H), partly overlaped by 2.32 (q, 3J ) 7
Hz, 2 H, CH2CH3), 2.87-3.05 (m, 1 H, 3-H), 3.05-3.21 (m, 1
3
3
3
H, 3-H), 4.10 (q, J ) 6 Hz, 2 H, OCH2CH3), 4.87 (dt, J ) J
) 6 Hz, 1 H, 5-H), 5.18 [d, 3J (Z) ) 11 Hz, 1 H, CHdCH2], 5.31
[d, 3J (E) ) 17 Hz, 1 H, CHdCH-H2], 5.94 [ddd, 3J ) 6 Hz,
3J (Z) ) 11 Hz, J (E) ) 17 Hz, 1 H, CHdCH2]; 13C NMR (62.9
3
2-(2-Oxopr opyliden e)-5-vin yltetr ah ydr ofu r an (5c). Start-
ing with acetylacetone (1.60 g, 15.97 mmol), diisopropylamine
(5.20 mL, 36.7 mmol), n-BuLi (36.7 mmol, solution in n-
hexane), and 1,4-dibromo-2-butene (3.76 g, 17.57 mmol), 5c
was isolated as a colorless solid (1.14 g, 47%, Z/E > 98:2). The
purification was effected by chromatography (silica gel, pe-
troleum ether/ether 5:1). 1H NMR (250 MHz, acetone-d6) δ
1.73-1.91 (m, 1 H, 4-H), 2.18-2.35 (m, 1 H, 4-H), partly
MHz, acetone-d6) δ 13.37, 13.96 (CH3), 19.24, 30.03, 30.62
(CH2), 58.79 (O-CH2), 83.13 (O-CH), 103.83 (C, OCdC),
115.80 (CHdCH2), 137.17 (CHdCH2), 167.89 (CdO), 169.72
(C-2); MS (70 eV, EI) m/z 210 (100) [M]+, 165 (78), 157 (45),
149 (46), 143 (41), 115 (72), 97 (87). The exact molecular mass
for C12H18O3 m/z 210.1256 ( 2 mD (M+) was confirmed by
HRMS (EI, 70 eV).
2-(1-E t h oxyca r b on ylp en t ylid en e)-5-vin ylt et r a h yd r o-
fu r a n (5g). Starting with 2-acetylhexanoic acid ethylester (560
mg, 3.0 mmol), diisopropylamine (0.98 mL, 6.9 mmol), n-BuLi
(6.9 mmol, solution in n-hexane) and 1,4-dibromo-2-butene
(705 mg, 3.3 mmol), 5g was isolated as a colorless oil (224 mg,
32%, Z/E > 98:2). The purification was effected by chroma-
tography (silica gel, petroleum ether/ether 3:2). 1H NMR (250
3
overlaped by 2.22 (s, 3 H, CH3), 2.78 (t, J ) 8 Hz, 2 H, 3-H),
4.96 (s, 1 H, OdCCH), 5.06 (dt, 3J ) 3J ) 6 Hz, 1 H, 5-H),
5.23 [d, 3J (Z) ) 11 Hz, 1 H, H2CdCH], 5.37 [d, 3J (E) ) 18 Hz,
3
3
3
1 H, H2CdCH], 5.98 [ddd, J ) 6 Hz, J (Z) ) 11 Hz, J (E) )
18 Hz, 1 H, CHdCH2]; 13C NMR (62.9 MHz, MeOH-d4) δ 30.01,
33.25 (CH2), 30.53 (CH3), 88.80 (C-5), 100.81 (OdCCH), 117.87
(CHdCH2), 137.23 (CHdCH2), 175.37 (C-2), 200.06 (CdO); MS
(70 eV, EI) m/z 152 (24) [M]+, 137 (27), 85 (54), 69 (100), 43
(70). The exact molecular mass for C9H12O2 m/z 152.0837 ( 2
mD (M+) was confirmed by HRMS (EI, 70 eV).
3
3
MHz, acetone-d6) δ 0.88 (t, J ) 6 Hz, 3 H, CH3), 1.18 (t, J )
6 Hz, 3 H, CH3), partly overlaped by 1.17-1.44 (m, 4 H, CH2),
1.66-1.86 (m, 1 H, CH2), 2.10-2.31 (m, 3 H, CH2), 2.71-2.85
(m, 2 H, CH2), 4.08 (q, 3J ) 6 Hz, 2 H, OCH2CH3), 4.88 [ddddd,
2-(2-Diet h yla m in o-2-oxoet h ylid en e)-5-vin ylt et r a h y-
d r ofu r a n (5d ). Starting with N,N-diethylacetyl acetic amide
(314 mg, 2.0 mmol), diisopropylamine (0.65 mL, 4.6 mmol),
n-BuLi (2.0 mL, 4.6 mmol, 2.3 M solution in n-hexane), and
1,4-dibromo-2-butene (424 mg, 11.3 mmol), 5d was isolated
as a colorless oil (305 mg, 73%, Z/E > 98:2). The purification
was effected by chromatography (silica gel, petroleum ether/
ether 5:1). The starting material could not be completely
removed. 1H NMR (250 MHz, acetone-d6) δ 0.95-1.26 (m, 6
H, CH3), 1.73 (ddt, 3J ) 3J ) 9 Hz, 2J ) 13 Hz, 1 H, 4-H),
2.10-2.29 (m, 1 H, 4-H), 2.57-2.75 (m, 2 H, 3-H2), 3.26-3.47
3
J ) 3J ) 3J ) 6 Hz, 4J (E) ) 4J (Z) ) 1 Hz, 1 H, H-5], 5.14
2 4 3
[ddd, J ) J (Z) ) 1 Hz, J (Z) ) 10 Hz, 1 H, HCdCH2], 5.35
2
4
3
[ddd, J ) J (E) ) 1 Hz, J (E) ) 18 Hz, 1 H, HCdCH2], 5.92
[ddd, 3J ) 6 Hz, 3J (Z) ) 10 Hz, 3J (E) ) 18 Hz, 1 H, HCdCH-
H]; 13C NMR (62.9 MHz, CDCl3) δ 13.90, 14.31 (CH3), 22.48,
28.95, 29.06, 29.84, 31.76 (CH2), 59.38 (O-CH2), 84.67 (O-
CH), 100.95 (C, O-CdC), 116.70 (CHdCH2), 136.20 (CHd
CH2), 166.41 (CdO), 167.12 (C-2); MS (70 eV, EI) m/z 238 (48)
[M]+, 195 (58), 193 (49), 149 (100), 85 (56), 57 (46). The exact
molecular mass for C14H22O3 m/z 238.1569 ( 2 mD (M+) was
confirmed by HRMS (EI, 70 eV).
3
(m, 4 H, NCH2), 4.83 (dt, J ) 3J ) 6 Hz, 1 H, 5-H), 4.97 (s, 1
2-(2-γ-Bu t yr ola ct on ylid en e)-5-vin ylt et r a h yd r ofu r a n
(5h ): Starting with 2-acetyl-γ-butyrolactone (384 mg, 3.0
mmol), diisopropylamine (0.97 mL, 6.9 mmol), n-BuLi (2.9 mL,
6.9 mmol, 2.38 M solution in n-hexane), and 1,4-dibromo-2-
butene (708 mg, 3.3 mmol), 5h was isolated as a colorless solid
(175 mg, E/Z > 98:2, 32%). The product was purified two times
3
H, OdCCH), 5.15 [d, J (Z) ) 11 Hz, 1 H, CHdCH2], 5.35 [d,
3
3
3J (E) ) 17 Hz, 1 H, CHdCH2], 5.90 [ddd, J ) 6 Hz, J (Z) )
11 Hz, 3J (E) ) 17 Hz, 1 H, CHdCH2]; 13C NMR (62.9 MHz,
acetone-d6) δ 12.40, 26.09 (CH3), 29.12, 29.21, 35.25, 35.32
(CH2), 39.26, 41.46, 41.87 (NCH2), 84.40 (C-5), 88.58, 115.72
(CHdCH2), 129.16, 129.40 (CH, OdCCH), 136.99 (CHdCH2),
164.33, 164.69 (CdO, C-2); MS (70 eV, EI) m/z 209 (43) [M]+,
137 (100), 72 (28), 69 (72). The exact molecular mass for
C12H19O2N m/z 209.1416 ( 2 mD (M+) was confirmed by HRMS
(EI, 70 eV).
1
by chromatography (silica gel, petroleum ether/ether 4:1). H
NMR (250 MHz, acetone-d6) δ 1.78-1.96 (m, 1 H, O-CH-
CH-H), 2.24-2.41 (m, 1 H, 4-H), 2.60-3.01 (m, 4 H, CdC-
3
3
3
3
CH2), 4.25 (t, J ) 8 Hz, 2 H, OCH2), 4.96 (ddd, J ) J ) J
) 7 Hz, 1 H, 5-H), 5.23 [d, 3J (Z) ) 10 Hz, 1 H, HCdCH2], 5.36
2-(1-E t h oxyca r b on ylet h ylid en e)-5-vin ylt et r a h yd r o-
fu r a n (5e). Starting with 2-acetylpropanoic acid ethylester
(0.60 g, 4.16 mmol), diisopropylamine (1.34 mL, 9.5 mmol),
n-BuLi (9.5 mmol, solution in n-hexane), and 1,4-dibromo-2-
butene (0.98 g, 4.58 mmol), 5e was isolated as a colorless oil
(524 mg, 64%, Z/E > 98:2). The purification was effected by
chromatography (silica gel, petroleum ether/ether 3:2). 1H
3
3
3
[d, J (E) ) 17 Hz, 1 H, HCdCH2], 5.95 [ddd, J ) 7 Hz, J (Z)
) 10 Hz, J (E) ) 17 Hz, 1 H, HCdCH2]; 13C NMR (62.9 MHz,
3
acetone-d6) δ 24.79, 28.48, 29.74 (CH2), 64.61 (O-CH2), 84.49
(O-CH), 93.00 (C, O-CdC), 116.63 (CHdCH2), 136.62 (CHd
CH2), 168.33 (CdO), 171.91 (C-2); MS (70 eV, EI) m/z 180 (38)
[M + H] +, 139 (49), 113 (100), 43 (71). The exact molecular
mass for C10H12O3 m/z 180.0786 ( 2 mD (M+) was confirmed
by HRMS (EI, 70 eV).
3
NMR (250 MHz, acetone-d6) δ 1.21 (t, J ) 6 Hz, 3 H, CH3),
1.71 (s, 3 H, CH3), 1.73-1.96 (m, 1 H, 4-H), 2.14-2.31 (m, 1
H, 4-H), 2.68-2.81 (m, 2 H, 3-H), 4.07 (q, 3J ) 6 Hz, 2 H,
2-(1-Oxo-1,2,3,4-t et r a h yd r on a p h t -2-ylid en e)-5-vin yl-
tetr a h yd r ofu r a n (5i). Starting with R-acetyltetralone (372
mg, 2 mmol), diisopropylamine (0.65 mL, 4.6 mmol), n-BuLi
(2.0 mL, 4.6 mmol, solution in n-hexane), and 1,4-dibromo-2-
butene (468 mg, 2.2 mmol)), 5i was isolated as a colorless oil
(220 mg, 46%, E/Z > 98:2). The purification was effected by
chromatography (silica gel, petroleum ether/ether 4:1). 1H
NMR (250 MHz, acetone-d6) δ 1.80-1.98 (m, 1 H, CH2), 2.22-
2.47 (m, 1 H, CH2), 2.70-2.97 (m, 4 H, CH2), 2.98-3.22 (m, 1
3
3
OCH2), 4.89 (dt, J ) 3J ) 6 Hz, 1 H, 5-H), 5.14 [d, J (Z) ) 11
Hz, 1 H, CHdCH2], 5.34 [d, 3J (E) ) 17 Hz, 1 H, CHdCH2],
3
3
3
5.91 [ddd, J ) 6 Hz, J (Z) ) 11 Hz, J (E) ) 17 Hz, 1 H, CHd
CH2]; 13C NMR (62.9 MHz, acetone-d6) δ 13.96, 14.09 (CH3),
29.00, 30.23 (CH2), 58.70 (OCH2), 84.75 (C-5), 94.33 (CdC-
CH3), 115.48 (CHdCH2), 137.26 (CHdCH2), 166.60, 166.62
(CdO, C-2); MS (70 eV, EI) m/z 196 (77) [M]+, 151 (93), 129
(38), 101 (84), 83 (100). The exact molecular mass for C11H16O3
m/z 196.1099 ( 2 mD (M+) was confirmed by HRMS (EI,
70 eV).
3
3
H, CH2), 3.27-3.43 (m, 1 H, CH2), 4.95 (dt, J ) J ) 7 Hz, 1
3
3
H, 5-H), 5.23 [d, J (Z) ) 10 Hz, 1 H, HCdCH2], 5.38 [d, J (E)
3
3
) 17 Hz, 1 H, HCdCH2], 5.89 [ddd, J ) 7 Hz, J (Z) ) 10 Hz,
3J (E) ) 17 Hz, 1 H, HCdCH2], 7.22-7.48 (m, 3 H, Ar-H), 7.92
(d, 3J ) 8 Hz, 1 H, Ar-H); 13C NMR (62.9 MHz, CDCl3) δ 23.84,
28.58, 30.27, 31.62 (CH2), 83.60 (O-CH), 106.58 (O-CdC),
117.36 (CHdCH2), 126.54, 127.05, 127.83, 131.91 (Ar-CH),
135.08, 142.98 (Ar-C), 136.29 (CHdCH2), 170.89 (C-2), 187.87
(CdO); MS (70 eV, EI) m/z 240 (100) [M]+, 199 (25), 173 (79).
2-(1-E t h oxyca r b on ylp r op ylid en e)-5-vin ylt et r a h yd r o-
fu r a n (5f). Starting with 2-acetylbutanoic acid ethylester (593
mg, 3.75 mmol), diisopropylamine (1.22 mL, 8.62 mmol),
n-BuLi (8.62 mmol, solution in n-hexane) and 1,4-dibromo-2-
butene (882 mg, 4.12 mmol), 5f was isolated as a colorless oil
(480 mg, 61%, Z/E > 98:2). The purification was effected by
chromatography (silica gel, petroleum ether/ether 3:2). 1H

Synthesis of 2-Alkylidenetetrahydrofurans
J . Org. Chem., Vol. 66, No. 18, 2001 6063
The exact molecular mass for C16H16O2 m/z 240.1150 ( 2 mD
(M+) was confirmed by HRMS (EI, 70 eV).
OCH2, both isomers), 4.70 (s, 1 H, CdCHCdO), 4.75 (s, 1 H,
CdCHCdO), 4.84 (ddd, 3J ) 3J ) 6 Hz, 3J ) 11 Hz, 1 H, 5-H),
3
2-(Met h oxyca r b on ylm et h ylid en e)-3-m et h yl-5-vin yl-
tetr a h yd r ofu r a n (5j). Starting with 3-oxopentanoic acid
methylester (1.85 g, 14.2 mmol), diisopropylamine (4.64 mL,
32.7 mmol), n-BuLi (32.7 mmol, solution in hexane), and 1,4-
dibromo-2-butene (3.35 g, 15.7 mmol), 5j was isolated as a
colorless oil (1.58 g, 61%, Z/E ) 8:1, ds ) 55:45). The
purification was effected by chromatography (silica gel, pe-
troleum ether/ether 5:1). 1H NMR (250 MHz, acetone-d6]) δ
1.06 (d, 3J ) 6 Hz, 3 H, CCH3), 1.21 (d, 3J ) 6 Hz, 3 H, C-CH3),
5.05 (ddd, J 1 ) 3J 2 ) 3J 3 ) 6 Hz, 1 H, 5-H), 5.17, 5.21 [2 × d,
3J (Z) ) 11 Hz, 2 × 1 H, CHdCH2, both isomers], 5.33, 5.42 [d,
3J (E) ) 18 Hz, 2 × 1 H, CHdCH2, both isomers], 5.84-6.04
(m, 2 × 1 H, CHdCH2, both isomers); 13C NMR (62.9 MHz,
acetone-d6) δ 11.04, 11.15 (CH2CH3), 13.96, 13.97 (OCH2CH3),
24.62, 25.70, 33.91, 35.20 (C-4, CCH2CH3), 44.54, 45.37 (C-3),
58.00, 58.01 (OCH2), 83.65, 84.01, 86.54, 87.22 (C-5, CdCHCd
O), 115.66, 116.52 (CHdCH2), 136.71, 136.74 (CHdCH2),
164.42, 164.43 (CdO) 174.23, 174.49 (C-2); MS (70 eV, EI) m/z
210 (65) [M]+, 182 (54), 165 (100), 115 (52), 94 (46), 87 (71),
69 (83). The exact molecular mass for C12H18O3 m/z 210.1256
( 2 mD (M+) was confirmed by HRMS (EI, 70 eV).
2
3
3
1.43 (ddd, J ) J ) J ) 11 Hz, 1 H, CH2), 1.82-2.01 (m, 1
H, CH2), 2.29-2.50 (m, 2 × 1 H, CH2, both isomers), 2.66-
2.81 (m, 1 H, CH), 2.92-3.09 (m, 1 H, CH), 3.55 (s, 3 H, OCH3),
3.65 (s, 3 H, OCH3), 4.70, 4.75 (2 x s, 2 H, OdCCH), 4.86 (dt,
2-Cyan om eth yliden e-5-vin yltetr ah ydr ofu r an (5l). Start-
ing with 5-methylisoxazole (166 mg, 2.0 mmol), diisopropy-
lamine (0.65 mL, 4.6 mmol), n-BuLi (2.0 mL, 4.6 mmol,
solution in n-hexane), and 1,4-dibromo-2-butene (470 mg, 2.2
mmol) 5l was isolated as a colorless oil (135 mg, 50%, E/Z >
98:2). The purification was effected by chromatography (silica
3
3
3
3J ) 11 Hz, J ) 6 Hz, 1 H, 5-H), 5.06 (dt, J ) J ) 6 Hz, 1
H, 5-H), 5.11-5.48 (m, 2 × 2 H, HCdCH2, both isomers), 5.83-
6.04 (m, 2 H, HCdCH2, both isomers); 13C NMR (62.9 MHz,
acetone-d6) δ 16.16, 17.50 (C-CH3), 35.15, 36.25 (CH2), 37.47,
38.78 (CH-CH3), 49.43, 51.26 (OCH3), 83.51, 84.07, 85.89,
86.23 (C-5, CdCHCdO), 115.84, 116.86 (CHdCH2), 136.57,
136.66 (CHdCH2), 165.11, 167.47 (CdO), 175.74, 175.75 (C-
2); MS (70 eV, EI) m/z 182 (54) [M]+, 151 (50), 101 (100), 81
(29), 69 (98), 41 (32). The exact molecular mass for C10H14O3
m/z 182.0943 ( 2 mD (M+) was confirmed by HRMS (EI, 70
eV).
1
gel, petroleum ether/ether 5:1). H NMR (250 MHz, CDCl3) δ
3
1.80-2.00 (m, 1 H, H-4), 2.20-2.40 (m, 1 H, H-4), 2.74 (t, J
) 6 Hz, 2 H, H-3), 4.27 (s, 1 H, CdCHCN), 4.99 (ddd, 3J 1
)
3
3J 2 ) 3J 3 ) 6 Hz, 1 H, H-5), 5.27 [d, J (Z) ) 11 Hz, 1 H, HCd
3
3
CH2], 5.37 [d, J (E) ) 17 Hz, 1 H, HCdCH2], 5.87 [ddd, J )
3
3
6 Hz, J (Z) ) 11 Hz, J (E) ) 17 Hz, 1 H, HCdCH2]; 13C NMR
(62.9 MHz, CDCl3) δ 29.83, 30.66 (CH2), 65.36, 86.08 (CH,
O-CdC, O-CH), 116.55 (C, CN), 117.97 (CHdCH2), 135.04
(CHdCH2), 176.11 (C, O-CdC); MS (70 eV, EI) m/z 135 (100)
[M]+, 134 (87), 120 (50), 67 (87), 53 (56). The exact molecular
mass for C8H9NO m/z 135.0684 ( 2 mD (M+) was confirmed
by HRMS (EI, 70 eV).
2-(Eth oxycar bon ylm eth yliden e)-3-eth yl-5-vin yltetr ah y-
d r ofu r a n (5k ). Starting with 3-oxohexanoic acid ethylester
(316 mg, 2.0 mmol), diisopropylamine (0.65 mL, 4.6 mmol),
n-BuLi (2.0 mL, 4.6 mmol, 2.36 M solution in n-hexane), and
1,4-dibromo-2-butene (426 mg, 2.0 mmol (petroleum ether/
ether 5:1), 5k was isolated as a colorless solid (224 mg, 53%,
Z/E > 98:2, ds ) 65:35). The purification was effected by
chromatography (silica gel, petroleum ether/ether 5:1). 1H
NMR (250 MHz, acetone-d6) δ 0.95 (t, 3J ) 7 Hz, 2 × 3 H,
CH3, beide isomere), 1.18 (t, 3J ) 7 Hz, 2 × 3 H, CH3, both
isomers), 1.30-1.59 (m, 2 × 2 H, CH2), 1.61-1.76 (m, 2 × 1
H, 4-H, both isomers), partly overlaped by 1.73-1.93 (m, 2 ×
Ack n ow led gm en t. P.L. thanks Professor A. de
Meijere for his support. Financial support from the
Fonds der Chemischen Industrie (Liebig-scholarship
and funds for P.L.) and the Deutsche Forschungsge-
meinschaft is gratefully acknowledged.
3
3
2
1 H, 4-H), 2.43 (ddd, J ) 6 Hz, J ) 8 Hz, J ) 13 Hz, 1 H,
3-H), 2.75-2.97 (m, 1 H, 3-H), 4.03 (q, 3J ) 7 Hz, 2 × 2 H,
J O010303R