Synthesis of 2-Alkenyl-3-(alkoxycarbonyl)furans Based on

Feist-Benary Cyclocondensation of
(2,4-Dioxobutylidene)phosphoranes with r-Haloketones and
r-Chloracetaldehyde
Gerson Mross, Edith Holtz, and Peter Langer*,,
Institut fur Chemie, UniVersitat Rostock, Albert-Einstein-Strasse 3a, 18059 Rostock, Germany, Institut fur
Organische und Biomolekulare Chemie, Georg-August-UniVersitat Gottingen, Tammannstrasse 2,
37077 Gottingen, Germany, and Leibniz-Institut fur Katalyse e. V. an der UniVersitat Rostock,
Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
[email protected].
ReceiVed June 6, 2006

3-Acyl-2-alkenylfurans were prepared by Feist-Benary cyclocondensation of (2,4-dioxobutylidene)phosphoranes with chloracetaldehyde and R-haloketones and subsequent Wittig reactions.

Functionalized furans are present in a great variety of

pharmacologically relevant natural products.1,2 3-Acylfurans,
such as (-)-myodesmone and 7-hydroxymyoporone, constitute
a large and important subgroup of naturally occurring furans.3
Likewise, 2-alkenylfurans are widespread in nature.4 In addition,
they are of considerable pharmacological relevance and have
been used as synthetic building blocks. Although a number of
Institut fur Chemie, Universitat Rostock. Fax: +381 4986412.
Institut fur Organische und Biomolekulare Chemie, Georg-August-Universitat Gottingen.
Leibniz-Institut fu
r Katalyse e. V. an der Universitat Rostock.

(1) For reviews of furan syntheses, see: (a) Friedrichsen, W. in

ComprehensiVe Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Elsevier: New York, 1996; Vol. 2, pp 359-363
and references therein. (b) Konig, B. In Science of Synthesis; Thieme:
Stuttgart, Germany, 2001; Vol. 9, pp 183-285.
(2) (a) Marshall, J. A.; Robinson, E. D. J. Org. Chem. 1990, 55, 3450.
(b) Marshall, J. A.; Wang, X. J. Org. Chem. 1991, 56, 960. (c) Marshall,
J. A.; Wang, X. J. Org. Chem. 1992, 57, 3387. (d) Marshall, J. A.; DuBay,
W. J. J. Org. Chem. 1993, 58, 3602. (e) Marshall, J. A.; Bartley, G. S. J.
Org. Chem. 1994, 59, 7169. (e) Marshall, J. A.; Sehon, C. A. J. Org. Chem.
1995, 60, 5966. (f) Hashmi, A. S. K.; Ruppero, T. L.; Knofel, T.; Bats, J.
W. J. Org. Chem. 1997, 62, 7295. (g) Gabriele, B.; Salerno, G.; De Pascali,
F.; Costa, M.; Chiusoli, G. P. J. Org. Chem. 1999, 64, 7693. (h) Sperry, J.
B.; Whitehead, C. R.; Ghiviriga, I.; Walczak, R. M.; Wright, D. L. J. Org.
Chem. 2004, 69, 3726. (i) Aso, M.; Ojida, A.; Yang, G.; Cha, O.-J.; Osawa,
E.; Kanematsu, K. J. Org. Chem. 1993, 58, 3960. (j) Bach, T.; Kruger, L.
Eur. J. Org. Chem. 1999, 2045.

synthetic approaches to furans have been reported,1,2 the

development of new and more efficient strategies is of ongoing
interest. New synthetic approaches to furans should allow a
facile assembly of substitution patterns which are not readily
available by other methods. In recent years, we have reported
a number of synthetic approaches to (furan-2-yl)acetates based
on cyclization reactions of 1,3-dicarbonyl dianions or 1,3-bis(silyl enol ethers) with 1,2-dielectrophiles.5 The Feist-Benary
cyclocondensation of 1,3-dicarbonyl compounds with haloketones represents a classical method for the synthesis of furans
containing an ester or ketone substituent at carbon C-3.1
Recently, we reported6 the synthesis of 2-alkenyl-3-(alkoxycarbonyl)furans by Feist-Benary cyclocondensation of (2,4dioxobutylidene)phosphoranes7 with chloracetaldehyde to give
(furylmethyl)phosphonium chlorides8 and subsequent Wittig
reactions. Herein, we report full details of this methodology.
With respect to our preliminary communication,6 the preparative
scope was significantly extended. An improved procedure was
developed which allows, for the first time, the employment of
(3) (a) Sutherland, M. D.; Rodwell, J. L. Aust. J. Chem. 1989, 42, 1995.
(b) Reich, H. J.; Shah, S. K.; Gold P. M.; Olson R. E. J. Am. Chem. Soc.
1981, 103, 3112. (c) Zdero, C.; Bohlmann, F.; Niemeyer, H. M. Phytochemistry 1991, 30, 1597. (d) Williams, D. H.; Faulkner, D. J. Tetrahedron 1996,
52, 4245.

10.1021/jo061153t CCC: $33.50 2006 American Chemical Society

Published on Web 09/14/2006

J. Org. Chem. 2006, 71, 8045-8049

8045

Mross et al.

R-haloketones as starting materials and the synthesis of a great

variety of novel 3-acyl-2-alkenylfurans. Notably, 3-acyl-2alkenylfurans have been shown to be of considerable pharmacological relevance.9

SCHEME 1. Cyclization of
(2,4-Dioxobutylidene)phosphorane 1a with
Chloracetaldehyde (2a)a

Results and Discussion

The reaction of chloracetaldehyde (2) with (2,4-dioxobutylidene)phosphorane (1a), prepared by reaction of triphenylphosphane with ethyl 4-chloroacetoacetate, afforded the (2furylmethyl)phosphonium chloride 3a (Scheme 1). The formation
of 3a can be explained by tautomerization of 1a to give
intermediate A, attack of the central carbon atom of the latter
onto the aldehyde (intermediate B), 1,3-prototropic shift (intermediate C), cyclization by attack of the carbonyl oxygen atom
onto the chloride (intermediate D), and subsequent elimination
of water.
The cyclization of 2a with phosphoranes 1b-g afforded the
alkoxycarbonyl-, carbamoyl-, and benzoyl-substituted (2-furyl)methylphosphonium chlorides 3b-g (Scheme 2, Table 1). The
(4) (a) Bowden, B. F.; Coll, J. C.; de Silva, E. D.; de Costa, M. S. L.;
Djura, P. J. Aust. J. Chem. 1983, 36, 371. (b) Subba R. G. S. R.;
Ravindranath, B.; Sashi K. V. P. Phytochemistry 1984, 23, 399. (c) Lam,
J.; Bildsoe, H.; Christensen, L. P.; Thomasen, T. Acta Chem. Scand. 1989,
43, 799. (d) Teresa, J. P.; Bellido, I. S.; Gonzalez, M. S.; Vicente, S.
Phytochemistry 1986, 25, 185. (e) Shun, A. L. K. S.; Tykwinski, R. R. J.
Org. Chem. 2003, 68, 6810. (f) Schoedel, R.; Spiteller, G. Liebigs Ann.
Chem. 1987, 459. (g) Bauer, S.; Spiteller, G. HelV. Chim. Acta 1985, 68,
1635. (h) Zechlin, L.; Wolf, M.; Steglich, W.; Anke, T. Liebigs Ann. Chem.
1981, 12, 2099. (i) Tsuge, O.; Kanemasa, S.; Suga, H. Bull. Chem. Soc.
Jpn. 1988, 61, 2133. (j) Williams, D. H.; Faulkner, D. J. Tetrahedron 1996,
52, 4245. (k) Lam, J.; Bildsoe, H.; Christensen, L. P.; Thomasen, T. Acta
Chem. Scand. 1989, 43, 799. (l) Fraga, B. M.; Terrero, D. Phytochemistry
1996, 41, 229. (m) Previtera, L.; Merola, D.; Monaco, P. Phytochemistry
1985, 24, 1838. (n) Bohlmann, F.; Zdero, C. Phytochemistry 1982, 21, 1989.
(o) Mansfield, J. W.; Porter, A. E. A.; Smallman, R. V. Phytochemistry
1980, 19, 1057. (p) Fraga, B. M.; Terrero, D. Phytochemistry 1996, 41,
229. (q) Schulz, S.; Steffensky, M.; Roisin, Y. Liebigs Ann. Chem. 1996,
941. (r) Leclerq, S.; Braekman, J. C.; Kaisin, M.; Daloze, D.; Detrain, C.
J. Nat. Prod. 1997, 60, 1143. (s) Hu, J.-F.; Wunderlich, D.; Sattler, I.; Haertl,
A.; Papastavrou, I.; Grond, S.; Grabley, S.; Feng, X.-Z.; Thiericke, R. J.
Antibiot. 2000, 53, 94. (t) Hoffmann, L.; Grond, S. Eur. J. Org. Chem.
2004, 4771. (u) Resch, M.; Heilmann, J.; Steigel, A.; Bauer, R. Planta Med.
2001, 67, 437.
(5) For the synthesis of furans by sequential [3 + 2] cyclization/
bromination/elimination reactions, see: Bellur, E.; Langer, P. Synthesis
2006, 480. (b) For sequential [3 + 2] cyclization/elimination reactions,
see: Bellur, E.; Gorls, H.; Langer, P. Eur. J. Org. Chem. 2005, 2074. (c)
For the synthesis of benzofurans by reaction of 2-alkylidenetetrahydrofurans
with BBr3, see: Bellur, E.; Langer, P. J. Org. Chem. 2005, 70, 7686. (d)
For sequential [3 + 2] cyclization/dehydrogenation reactions, see: Bellur,
E.; Langer, P. J. Org. Chem. 2005, 70, 10013.
(6) Holtz, E.; Langer, P. Synlett 2004, 1805.
(7) For reactions of (2,4-dioxobutylidene)phosphoranes, see for example: (a) Hatanaka, M.; Tanaka, Y.; Ueda, I. Tetrahedron Lett. 1995,
3719. (b) Banwell, M. G.; Cameron, J. M. Tetrahedron Lett. 1996, 525. (c)
Hatanaka, M.; Ishida, A.; Tanaka, Y.; Ueda, I. Tetrahedron Lett. 1996, 401.
(d) Ceccarelli, S.; Piarulli, U.; Gennari, C. Tetrahedron Lett. 1999, 153.
(e) Langer, P.; Holtz, E. Synlett 2003, 402 and references therein. (f) Langer,
P.; Kracke, B. Synlett 2001, 1790.
(8) For synthetic applications of (furylmethylidene)phosphoranes, see:
(a) Cooper, J. A.; Cornwall, P.; Dell, C. P.; Knight, D. W. Tetrahedron
Lett. 1988, 29, 2107 and refernces cited therein. (b) Krapivin, G. D.; Valter,
N. I.; Zavodnik, V. E.; Kaklyugina, T. Ya.; Kulnevich, V. G. Chem.
Heterocycl. Compd. (Engl. Transl.) 1994, 30, 296; Khim. Geterotsikl. Soedin.
1994, 3, 335. (c) Brittain, J. M.; Jones, R. A. Tetrahedron, 1979, 35, 1139.
(d) Schweizer, E. E.; Creasy, W. S.; Light, K. K.; Schaffer, E. T. J. Org.
Chem. 1969, 34, 212. (e) Markl, G.; Stiegler, J.; Kreitmeier, P.; Burgemeister, T.; Kastner, F.; Dove, S. HelV. Chim. Acta 1997, 80, 14. (f) Tsuboi,
S.; Mimura, S.; Ono, S.; Watanabe, K.; Takeda, A. Bull. Chem. Soc. Jpn.
1987, 60, 1807.
(9) (a) Vuligonda, V.; Garst, M. E.; Chandraratna, R. A. S. Bioorg. Med.
Chem. Lett. 1999, 9, 589. (b) Rivalle, C.; Andre-Louisfert, J.; Bisangni, E.
Tetrahedron, 1976, 32, 829.

8046 J. Org. Chem., Vol. 71, No. 21, 2006

Key for step i: CH2Cl2, reflux 24 h.

SCHEME 2. Cyclization of
(2,4-Dioxobutylidene)phosphoranes 1a-g with r-Haloketones
and Aldehydes 2a-ka

a Key for step i: procedure A: CH Cl , reflux 24 h; procedure B: neat,

2 2
80 C, 1 h; procedure C: neat, 80 C, 1 h, 10-2 bar.

reactions of ester-derived phosphoranes 1a-c proceeded in good

yield. During the optimization, it proved to be important to carry
out the reaction in the absence of base and under reflux
conditions (procedure A, CH2Cl2, 24 h). No product could be
isolated in the reaction of 1c with 2a when NaOiPr/iPrOH or
pyridine was employed which might be explained by nucleophilic attack of the base onto 2a. The water had to be removed
from the commercially available aqueous solution (45%) of 2a.
The protocol for purification of the phosphonium salt (silica
gel chromatography; eluents, acetone and then MeOH) also
played an important role (Table 1). The synthesis of 3c was
successfully scaled up from 1.1 to 11.0 mmol (Table 2). A
change of the concentration of 1c (0.02 versus 0.05 M) had no
major influence on the yield.
Relatively low yields were obtained for benzoylacetone and
ketoamide derived phosphoranes 1d-g (Scheme 2). The low
yields can be explained by the reduced acidity of the ketoamides
(due to steric reasons) which results in a smaller amount of
intermediate A present in the equilibrium. This assumption is
supported by the fact that, in the case of the synthesis 3e, the
open-chained side-product 3e was isolated. The yields could
not be improved by extension of the reaction time. However,
the yields could be successfully improved by employment of

2-Alkenyl-3-(alkoxycarbonyl)furans
SCHEME 3. Synthesis of Furans 5a-aga

TABLE 1. Products and Yields

3

R1

R2

R3

% 3a

procedurec

a
b
c
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
t

OMe
OEt
OiPr
OiPr
NH2
N(CH2)4
N(CH2)5
Ph
OMe
OEt
OiPr
Ph
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt

H
H
H
H
H
H
H
H
Me
Me
Me
Me
CH2Cl
tBu
CH2CO2Et
Ph
Ph
4-MeC6H4
4-BrC6H4
4-(O2N)C6H4
4-ClC6H4

H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
H
H
H
H

Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Cl
Br
Br
Br
Cl
Br
Br

43
41
27
72
71b
37
53
50
52b
49
56
43
35
75
63
53
46
80
71
80
52

Ad,g
Ad,g
Ad
Ae
B
Ae,f
B
B
B
B
B
B
Ag
C
C
Ag
C
C
C
C
C

a Isolated yields. b Unstable products. c Procedure A: CH Cl , reflux, 24

2 2
h. Procedure B: neat, 80 C, 1 h. Procedure C: neat, 80 C, 1 h, 10-2 bar.
d Workup: washing of the crude product with acetone. e Workup: flash
chromatography (silica gel; acetone and then MeOH). f In addition, 3e was
isolated in 32% yield. g Experiments using procedures B or C have not been
carried out.

TABLE 2. Scale-Up of the Synthesis of 3c

entry

1c (mmol)

c (mol/L)

yield (%)a

1
2
3

1.1
5.1
11.0

0.02
0.05
0.05

72
65
69

Isolated yields.

TABLE 3. Optimization of the Synthesis of 3d,f,g

3

R1

%a,b

%a,c

%a,d

g
d
f

Ph
NH2
N(CH2)5

28
10
22

33
47
35

50
71
53

a Isolated yields. b Conditions: CH Cl , 40 C, 24 h (procedure A).

2 2
Conditions: (CH2Cl)2, 60 C, 48 h. d Conditions: neat, 80 C, 1 h
(procedure B).

dichloroethane rather than dichloromethane as the solvent which

allows an increase of the reaction temperature from 40 to 60
C (Table 3). The best yields were obtained when the reactions
were carried out at 80 C without any solvent (procedure B).
Notably, the application of this procedure allowed one to
significantly shorten the reaction time to only 1 h.

The application of procedure A to the reaction of (2,4dioxobutylidene)phosphoranes with R-haloketones gave unsatisfactory results (low conversion, decomposition). Eventually,
optimal yields were obtained when the transformations were
carried out following procedure B (vide supra) or procedure C
(with repeated removal of water at 10-2 bar). Procedure C was
applied for all cyclizations of nonvolatile R-haloketones and

a Key for step i: (1) nBuLi, THF, 0 C, 0.5 h; (2) 4, THF, 0 C, 0.5 h
and then 20 C, 4-72 h.

allowed the removal of water during the reaction. In case of

solid starting materials, the melting was stirred at 80 C. The
most important factors responsible for the success of procedures
B and C are presumably the reaction temperature of 80 C and
the high concentration of the starting materials (neat). The
reaction of 1a-c,g with 2-chloroacetone (2b) afforded the
methyl-substituted (2-furyl)methylphosphonium chlorides 3hk. The cyclocondensation of 1b with 1,3-dichloroacetone (2c),
1-bromo-3,3-dimethylbutan-2-one (2d), and ethyl 4-chloroacetoacetate (2e) afforded the corresponding (2-furyl)methylphosphonium chlorides 3l-n. The aryl-substituted (2-furyl)methylphosphonium halides 3o-t were prepared by cyclization
of 1b with phenacyl bromide (2f), desyl bromide (2g), 4-(bromoacetyl)toluene (2h), 4-(chloroacetyl)-1-bromobenzene (2i),
4-(bromoacetyl)-1-nitrobenzene (2j), and 4-(bromoacetyl)-1chlorobenzene (2k).
The (2-furyl)methylphosphonium salts were formed in moderate to very good yields. The lowest yields were obtained for
difuncational 1,3-dichloroacetone and for reactions of amidederived phosphoranes (vide supra). The best yields were
obtained for reactions of phenacyl halides. There was no
significant difference between phenacyl chlorides and bromides.
The Wittig reaction of (2-furyl)methylphosphonium halides
3 with various aldehydes was next studied (Scheme 3, Table
4). The reaction of 3c with various aliphatic and aromatic
aldehydes (4a-l) afforded the 2-alkenyl-3-(isopropoxycarbonyl)furans 5a-l in moderate to good yields. The reaction of 3g
with butan-1-al and benzaldehyde afforded the furans 5m,n,
respectively. Furan 5o was prepared from 3d, albeit, in low
yield. The reaction of 3h-k with butan-1-al and benzaldehyde
gave the furans 5p-t. The furans 5u,v were prepared by reaction
of (2-furyl)methylphosphonium bromide 3m with butan-1-al and
benzaldehyde, respectively. The reaction of 3l with butan-1-al
and 4-methoxybenzaldehyde gave the 3-acyl-2-alkenyl-4-(chloromethyl)furans 5w,x, respectively. The diesters 5y,z were
prepared from phosphonium salt 3n. Wittig reactions of arylsubstituted (2-furyl)methylphosphonium halides 3o-t afforded
the 4-aryl-2-vinylfurans 5aa-ag.
Optimization studies showed that the best yields were
obtained when nBuLi/THF was employed (reaction time 0.5 h,
0 C). The yield of 5e dramatically decreased (to 15%) when
NaOEt/EtOH or NaOiPr/iPrOH were used. Most of the Wittig
reactions of (2-furyl)methylphosphonium salts with aldehydes
proceeded in good yields. The products were formed with good
to excellent E-diastereoselectivity which can be explained by
the presence of lithium chloride in the reaction mixture (salt
conditions). Product 5c was isolated in low yield, presumably
due to conjugate addition of the phosphorane to crotonaldehyde.
The yields of 5o and 5af were low, due to side reactions of
nBuLi with the amino and the nitro group, respectively. The
yield of 5o could be improved to 30% by use of triethylamine
rather than nBuLi. The low yields of 5t,u,aa remain unclear at
J. Org. Chem, Vol. 71, No. 21, 2006 8047

Mross et al.
TABLE 4. Products and Yields

Isolated yields. b Unstable products.

present. In fact, some products tend to be unstable during

chromatographic purification. The Wittig reactions of aromatic
aldehydes generally proceeded with better E-diastereoselectivity
than those of aliphatic aldehydes which might be explained by
steric reasons.
In conclusion, a variety of 3-acyl-2-alkenylfurans were
prepared by Feist-Benary cyclocondensation of (2,4-dioxobutylidene)phosphoranes with chloracetaldehyde or R-haloketones
and subsequent E-diastereoselective Wittig reactions.
8048 J. Org. Chem., Vol. 71, No. 21, 2006

Experimental Section
General Comments. All solvents were dried by standard
methods, and all reactions were carried out under an inert
atmosphere. For 1H and 13C NMR spectra the deuterated solvents
indicated were used. Mass spectrometric data (MS) were obtained
by electron ionization (EI, 70 eV), chemical ionization (CI, H2O),
or electrospray ionization (ESI). For preparative scale chromatography, silica gel (60-200 mesh) was used. Melting points are
uncorrected.
General Procedure for the Synthesis of Phosphonium Halides
3. Procedure A. To a CH2Cl2 solution (20 mL) of chloracetaldehyde (45%, aqueous solution) was added MgSO4. The solution was
filtered, and the MgSO4 was washed with CH2Cl2. The filtrate (50
mL) was added to phosphorane 1, and the solution was refluxed
for 24 h. The solvent was removed in vacuo. For 3a,b, the residue
was washed with acetone. For 3c,e, the residue was purified by
column chromatography (silica gel; acetone and then MeOH, i.d.
) 2.0 cm).
Procedure B. To chloracetaldehyde (55%, aqueous solution) was
added MgSO4. The mixture was filtered to give neat chloracetaldehyde. To neat chloracetaldehyde or R-chloroacetone was added
phosphorane 1, and the mixture was vigorously stirred at 80 C
for 1 h. After being cooled to room temperature, the mixture was
dissolved in CH2Cl2 (10 mL), and the solution was poured into
hexane (500 mL). The oil layer was separated from hexane and
was subsequently dissolved in CH2Cl2 (5 mL). The solution was
filtered, and the solvent of the filtrate was removed in vacuo to
give the (furylmethyl)phosphonium chloride 3.
Procedure C. The neat anhydrous haloketone 2 and phosphorane
1 were vigorously stirred at 80 C for 1 h. The reaction vessel was
repeatedly evacuated (10-2 bar). After being cooled to room
temperature, the mixture was dissolved in CH2Cl2 (10 mL), and
the solution was poured into hexane (500 mL). The oil layer was
separated from hexane and was subsequently dissolved in CH2Cl2
(5 mL). The solution was filtered, and the solvent of the filtrate
was removed in vacuo to give the (furylmethyl)phosphonium halide
3.
(3-(Methoxycarbonyl)furan-2-ylmethyl)triphenylphosphonium Chloride (3a). Following procedure A, the starting materials
4-(triphenylphosphanylidene)acetic acid methyl ester (1a) (372 mg,
0.99 mmol) and chloracetaldehyde (2a) (85 mg, 1.1 mmol) yielded
3a as a colorless solid (186 mg, 43%). 1H NMR (250 MHz,
CDCl3): ) 3.25 (s, 3H, OCH3), 6.11 (d, 2JH-P ) 15 Hz, 2H,
PCH2), 6.48 (d, 3J ) 2 Hz, 1H, H-4, Hetar) 7.25 (d 3J ) 2 Hz, 1H,
H-5, Hetar), 7.45-7.60 (m, 6H, Ph), 7.65-7.85 (m, 9H, Ph). 13C
NMR (50.3 MHz, CDCl3): ) 24.4, 51.6, 110.7, 117.4, 118.4,
130.0, 133.9, 135.0, 143.4, 148.5, 162.9. IR (KBr, cm-1): )
3005 (w), 2850 (w), 1702 (s), 1602 (m), 1439 (s), 1321 (s), 1207
(m), 1112 (s), 766 (s), 741 (s), 691 (m), 527 (m), 500 (m). MS [EI,
70 eV; m/z (%)]: 400 ([M - HCl]+, 100), 262 (46), 183 (44). MS
[CI, NH3; m/z (%)]: 401 ([M - Cl]+, 5) 263 (100). Anal. Calcd
for C25H22ClO3P (Mr ) 436.87): C, 69.26; H, 5.36. Found: C,
69.00; H, 5.25.
General Procedure for the Synthesis of 2-Alkenylfurans 5.
Procedure A. To a THF solution (5 mL; in the case solid aldehydes,
2.5 mL) of the phosphonium halide 3 was added nBuLi (1.0 equiv)
at 0 C. After the solution was stirring for 0.5 h at 0 C, aldehyde
4 (1.0 equiv) was added; solid aldehydes were added as a THF
solution or suspension (2.5 mL). The solution was stirred for 0.5 h
at 0 C and at 20 C until the reaction was completed (4-25 h,
TLC control). The mixture was poured into ice water (40 mL),
and ether (100 mL) was added. The organic and the aqueous layer
were separated, and the latter was extracted with ether (50 mL).
The combined organic layers were dried (MgSO4) and filtered, and
the solvent of the filtrate was removed in vacuo. The residue was
purified by column chromatography (silica gel, column i.d. ) 2.0
cm). The starting materials were separated by elution with acetone,
and the product was subsequently isolated by elution with methanol.

2-Alkenyl-3-(alkoxycarbonyl)furans
Procedure B. To a THF solution (10 mL) of the phosphonium
halide 3 was added nBuLi (1.1 equiv) at 0 C. After the solution
was stirred for 0.5 h at 0 C, aldehyde 4 (1.1-2.0 equiv) was added,
and the solution was stirred for 72 h at 20 C. The mixture was
poured into ice water (40 mL), and ether (25 mL) was added. The
organic and the aqueous layers were separated, and the latter was
extracted with ether (5 25 mL). The combined organic layers
were dried (MgSO4) and filtered, and the solvent of the filtrate
was removed in vacuo. The residue was purified by column
chromatography (silica gel, 40:1 n-hexane/ethyl acetate; column,
i.d. ) 8.0 cm, height ) 10 cm) and, subsequently, by HPLC
(Lichrosorb 60, 7 m, i.d. ) 3.0 cm, l ) 20 cm; eluent CH2Cl2).
Isopropyl 2-(Prop-1-enyl)furan-3-carboxylate (5a). The reaction of 3c (503 mg, 1.12 mmol) with nBuLi (1.12 mmol) and
acetaldehyde (4a) (49 mg, 1.12 mmol) was carried out as described
in procedure A (reaction time 23 h). After purification by column
chromatography (50:1 n-pentane/diethyl ether), 5a was isolated as
a yellow oil (130 mg, 62%, E/Z ) 4:1); Rf ) 0.35. 1H NMR (250
MHz, CDCl3, isomeric mixture): ) 1.33 (d, 3J ) 6 Hz, 6H, 2
CH3), 1.92 (dd, 3J ) 7 Hz, 4J ) 2 Hz, 3H, CH3, E-isomer), 2.10
(dd, 3J ) 7 Hz, 4J ) 2 Hz, 3H, CH3, Z-isomer), 5.17 (sept, 3J ) 6
Hz, 1H, OCH(CH3)2), 5.92 (dq, 3J ) 12 Hz, 3J ) 7 Hz, 1H, CHd
CH, Z-isomer), 6.49 (dq, 3J ) 16 Hz, 3J ) 7 Hz, 1H, CHdCH,
E-isomer), 6.65 (d, 3J ) 2 Hz, 1H, H-4, Hetar, E-isomer), 6.71 (d,

) 2 Hz, 1H, H-4, Hetar, Z-isomer), 6.91 (dd, 3J ) 12 Hz, 4J )

2 Hz, 1 H, CHdCH, Z-Isomer), 6.97 (dd, 3J ) 16 Hz, 4J ) 2 Hz,
1H, CHdCH, E-isomer), 7.21 (d, 3J ) 2 Hz, 1H, H-5, Hetar,
E-isomer), 7.33 (d, 3J ) 2 Hz, 1H, H-5, Hetar, Z-isomer). 13C (50.3
MHz, CDCl3, E-isomer): ) 18.6, 21.9, 67.6, 111.3, 112.5, 119.1
130.7, 140.4, 156.7, 163.2. IR (neat, cm-1): ) 2983 (m), 2936
(w), 1716 (s), 1453 (m), 1412 (m), 1378 (m), 1302 (m), 1183 (m),
1107 (s), 1025 (m), 840 (w), 756 (m), 605 (w). MS [EI, 70 eV;
m/z (%)]: 194 (M+, 35), 152 (100), 137 (60), 135 (42). Anal. Calcd
for C11H14O3 (Mr ) 194.23): C, 68.02; H, 7.27. Found: C, 67.85;
H, 6.94.

3J

Acknowledgment. We are grateful to Dr. H. Feist for his

help during the preparation of this manuscript and to Dr. D.
Michalik for NMR studies. Financial support from the state of
Mecklenburg-Vorpommern (Landesforschungsschwerpunkt Neue
Wirkstoffe und Screeningverfahren) is gratefully acknowledged.
Supporting Information Available: Experimental procedures
and compound characterization. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO061153T

J. Org. Chem, Vol. 71, No. 21, 2006 8049