Synthesis of γ-alkylidenebutenolides by formal [3+2] cyclizations of 1,5- and 2,4-bis(trimethylsilyloxy)-1,3,5-hexatrienes with oxalyl chloride

Article abstract of DOI:10.1002/ejoc.200600398

Lewis acid-catalyzed cyclizations of 1,5-bis(trimethylsilyloxy)-1,3,5- hexatrienes and 1,3,5-tris(trimethylsilyloxy)-1,3,5-hexatrienes with oxalyl chloride resulted in the formation of polyunsaturated γ- alkylidenebutenolides, while the cyclization of a 2

Full text of DOI:10.1002/ejoc.200600398

FULL PAPER
DOI: 10.1002/ejoc.200600398
Synthesis of γ-Alkylidenebutenolides by Formal [3+2] Cyclizations of 1,5- and
2,4-Bis(trimethylsilyloxy)-1,3,5-hexatrienes with Oxalyl Chloride
Ilia Freifeld,[a] Gopal Bose,[a] Tobias Eckardt,[b] and Peter Langer*[c,d]
Keywords: Butenolides / Cyclizations / O-Heterocycles / Regioselectivity / Silyl enol ethers
Lewis acid-catalyzed cyclizations of 1,5-bis(trimethylsilyl-
oxy)-1,3,5-hexatrienes and 1,3,5-tris(trimethylsilyloxy)-1,3,5-
hexatrienes with oxalyl chloride resulted in the formation of
polyunsaturated γ-alkylidenebutenolides, while the cycliza-
tion of a 2,4-bis(trimethylsilyloxy)-1,3,5-hexatriene with oxal-
yl chloride afforded a γ-(2-oxobut-3-en-1-ylidene)butenol-
ide, permitting a formal synthesis of the natural product lu-
cidone.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
1,5-Bis(trimethylsilyloxy)-1,3,5-hexatrienes
1,5-Bis(trimethylsilyloxy)-1,3,5-hexatrienes were pre-
pared as follows. The acetals 1a–e were prepared from the
corresponding β-keto esters (Scheme 1, Table 1); reduction
of the ester groups afforded the alcohols 2a–e, which were
oxidized to the aldehydes 3a–e by use of the Swern reaction.
Subsequent Wittig treatment of 3a–e with the correspond-
ing phosphoranes afforded 4a–e. Cleavage of the acetal
groups then gave the 1,5-keto esters 5a–e,[5] which were
transformed into 6a–e by treatment with Me3SiCl/NEt3.
Deprotonation of 6a–e with LDA/HMPA at –78 °C and
subsequent addition of Me3SiCl afforded the 1,5-bis-
(trimethylsilyloxy)-1,3,5-hexatrienes 7a–e. The use of
HMPA (1.0 equiv.) proved to be essential. The synthesis of
7a–c and 7e required the use of a spiroketal protective
group. In the case of 7d, all attempts to cleave the spiroketal
resulted in decomposition of the molecule, a problem
eventually solved through the preparation of a dimethyl
acetal.
1,3-Bis-silyl enol ethers represent important synthetic
building blocks that have been used in a variety of synthetic
transformations, including one-pot cyclizations,[1] while re-
actions between the 1,3,5-tris-silyl enol ether B (R = OMe)
and acid chlorides have been reported to result in [5+1] cyc-
lizations.[2] Some years ago, we reported the first synthesis
of the 1,5-bis(trimethylsilyloxy)-1,3,5-hexatrienes C, which
can be regarded as vinylogous bis-silyl enol ethers,[3] while
recently we have reported a formal synthesis of the acylcy-
clopentenediones linderone and lucidone based on cycliza-
tion reactions of the 2,4-bis(trimethylsilyloxy)-1,3,5-hexatri-
enes D.[4] Here we wish to report full details of the synthesis
of silyl enol ethers B, C, and D and their cyclizations with
oxalyl chloride.
Treatment of the 1,5-bis(trimethylsilyloxy)-1,3,5-hexatri-
enes 7a–d with oxalyl chloride in the presence of 0.5 equiv.
of Me3SiOTf afforded the γ-(4-oxobut-2-en-1-ylidene)but-
enolides 8a–d (Scheme 1, Table 1). Like the cyclization of
1,3-bis-silyl enol ethers A with oxalyl chloride, the cycliza-
tion proceeds through the terminal carbon atom and the
neighboring oxygen atom of the silyl enol ether. In the cases
of butenolides 8a, 8b, and 8d the products containing (Z)-
configured exocyclic double bonds were formed selectively,
due to the steric influence of the substituent R1. The config-
urations of the products were determined by spectroscopic
methods.[3,6]
[a] Institut für Biochemie, Universität Greifswald,
Soldmannstr. 16, 17487 Greifswald, Germany
[b] Institut für Organische Chemie, Georg-August-Universität
Göttingen,
Tammannstr. 2, 37077 Göttingen, Germany
[c] Institut für Chemie, Universität Rostock,
Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax: +381-4986412
1-Methoxy-1,3,5-tris(trimethylsilyloxy)-1,3,5-
hexatriene
The Me3SiOTf-catalyzed cyclization of the 1,3,5-tris(tri-
methylsilyloxy)-1,3,5-hexatriene 9 with oxalyl chloride was
E-mail: peter.langer@uni-rostock.de
[d] Leibniz-Institut für Katalyse e. V. an der Universität Rostock,
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2007, 351–355
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
351

I. Freifeld, G. Bose, T. Eckardt, P. Langer
FULL PAPER
Table 1. Synthesis of γ-[3-(alkoxycarbonyl)prop-3-enylidene]butenolides 8a–d.
1–7
R1
R2
R3
% (1)[a]
% (2)[a]
% (3)[a]
% (4)[a]
% (5)[a]
% (6)[a]
% (7)[a]
% (8)[a] (Z)/(E)[b]
a
b
c
d
e
Me
Et
H
H
H
H
H
Me
Et
Me
Et
77
82
32
84
93
92
74
78
85
60
42
62
72
68
81
84
59
95
81
98
77
70
81
80
91
95
98
70
95
55
41
50
32
0
Ͼ 98:2
Ͼ 98:2
2:1
10:1
–
OMe
62
60
73
–(CH2)3–
Et
1
[a] Isolated yield. [b] By H NMR of the products.
by cyclization via the terminal carbon and the neighboring
oxygen atom of the silyl enol ether. Butenolides 10 and 8c
contain no substituent at carbon atom C-4 of the butenol-
ide and, notably, butenolide 10 (in contrast to 8c) was
formed with excellent (E) diastereoselectivity. Likewise, the
cyclization of 1,3-bis-silyl enol ethers A with oxalyl chloride
has been reported to give γ-(2-oxoeth-1-ylidene)butenolides
with very (E) diastereoselectivity. The selective formation of
10 can be explained by the presence of the additional car-
bonyl group located at the exocyclic double bond, which
is essential for observation of good (E)/(Z) diastereoselec-
tivity.
Scheme 2. Synthesis of γ-(2,4-dioxobut-1-ylidene)butenolide 10.
a) Oxalyl chloride, Me3SiOTf (0.3 equiv.), CH2Cl2, –78Ǟ20 °C,
12 h, 55%.
Scheme 1. Synthesis of 1,5-bis(trimethylsilyloxy)-1,3,5-hexatrienes
7a–e and butenolides 8a–d. a) 1a–c,e: (CH2OH)2, pTosOH, toluene,
Dean–Stark trap, reflux, 12 h, 77–80%; 1d: (MeO)3CH, Amberlist
IR-120+, 20 °C, 62 %. b) (iBu)2AlH, CH2Cl2, –78Ǟ20 °C, 2 h, 20°,
1 h, 60–92%. c) Oxalyl chloride, DMSO, NEt3, –78Ǟ20 °C, 78–
95%. d) Ph3P=CHCO2R3, THF, 20 °C, 1 h, 42–72%. e) 5a–c,e:
pTsOH, acetone, reflux, 12 h, 65–84%; 5d: TFA, CH2Cl2, 95%.
f) Me3SiCl, NEt3, C6H6, 20 °C, 24 h, 77–98%. g) 1) 1.5 equiv.
LDA, HMPA, THF, –78 °C, 1 h, 2) Me3SiCl, –78Ǟ20 °C, 4 h,
70–93%. h) Oxalyl chloride, 0.5 equiv. Me3SiOTf, CH2Cl2,
–78Ǟ20 °C.
Scheme 3. Formal synthesis of lucidone: i) TiCl4 (1.0 equiv.),
CH2Cl2, –78Ǟ20 °C. ii) Me3SiOTf (2.0 equiv.), NEt3, Et2O,
0Ǟ20 °C. iii) Oxalyl chloride, Me3SiOTf (0.5 equiv.), CH2Cl2,
–78Ǟ20 °C. iv) Me2SO4, K2CO3, acetone, 20 °C. v) NaOMe,
studied next, and afforded the γ-(2,4-dioxobut-1-ylidene)-
butenolide 10 as a 2:1 mixture of keto and enol tautomers
(in [D6]acetone) (Scheme 2). The product was again formed MeOH (ref.[8]).
352
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Eur. J. Org. Chem. 2007, 351–355

Synthesis of γ-Alkylidenebutenolides by formal [3+2] Cyclizations
FULL PAPER
Transformation of 2a into 3a: A dichloromethane solution (15 mL)
of oxalyl chloride (1.186 g, 0.0094 mol) was added at –78 °C to a
dichloromethane solution (3 mL) of DMSO (1.60 g, 0.02 mol). Af-
ter this system had been stirred for 10 min, a dichloromethane solu-
tion (5 mL) of 2a (1.25 g, 8.55 mmol) was added. After this system
had in turn been stirred for 15 min, triethylamine (4.3 g, 43 mmol)
was slowly added and the solution was allowed to warm to 20 °C
over 30 min. Water (20 mL) was added, the solution was stirred for
20 min, the organic and the aqueous layer were separated, and the
latter was extracted with dichloromethane (50 mL). The combined
organic layers were then washed with an aqueous solution of HCl
(10%, 30 mL), with H2O (30 mL), with a dilute aqueous solution
of Na2CO3 (30 mL), and with H2O (30 mL), the solution was dried
(Na2SO4) and filtered, and the filtrate was concentrated in vacuo
to give 3a as a yellow liquid (1.15 g, 93%). The spectroscopic data
are identical with those reported.[10] 3a: 1H NMR (CDCl3,
250 MHz): δ = 0.97 (t, J = 7 Hz, 3 H, CH3), 1.71 (q, J = 7 Hz, 2
H, CH3CH2), 2.68 (m, 2 H, CH2), 3.98 [m, 4 H, O(CH2)2O], 9.72
(t, 1 H, OCH) ppm.
2,4-Bis(trimethylsilyloxy)-1,3,5-hexatrienes
The 2,4-bis(trimethylsilyloxy)-1,3,5-hexatriene 14 was
prepared by silylation of the 1,3-diketone 13, available by
condensation of the 1,3-bis-silyl enol ether 12 with benzal-
dehyde (Scheme 3). The Me3SiOTf-catalyzed cyclization of
14 with oxalyl chloride afforded the (E)-configured γ-(2-
oxobut-3-en-1-ylidene)butenolide 15, the (E) configuration
of the exocyclic double bond of 15 being established by
comparison of the spectroscopic data with those reported
in the literature.[7] Methylation of 15 (Me2SO4/K2CO3, ace-
tone) afforded 16, which had previously been transformed
into the natural acylcyclopentenedione lucidone by treat-
ment with NaOMe/MeOH.[8]
The synthetic precursor 16 of lucidone was prepared
from 13 via 14 in four steps and in 25% overall yield, which
compares well with known syntheses.[7,8]
Methyl
4-(2-Ethyl-1,3-dioxolan-2-yl)-2-butenoate
(4a):
Conclusion
Ph3P=CHCO2Me (3.85 g, 11.5 mmol) was added to a THF solu-
tion (10 mL) of 3a (1.66 g, 11.5 mmol) and the solution was stirred
for 2 h at 20 °C. The solvent was removed in vacuo and the residue
was purified by chromatography (silica gel, ether/petroleum ether
In summary, we report the synthesis of 1,5-bis(trimethyl-
silyloxy)-1,3,5-hexatrienes,
1,3,5-hexatrienes, and 2,4-bis(trimethylsilyloxy)-1,3,5-hexa-
trienes and their cyclization with oxalyl chloride.
1,3,5-tris(trimethylsilyloxy)-
1
1:3) to give 4a as a yellow liquid (1.39 g, 60%). H NMR (CDCl3,
250 MHz): δ = 0.92 (t, J = 7 Hz, 3 H, CH3), 1.66 (q, J = 7 Hz, 2
H, CH2CH3), 2.53 (d, J = 8 Hz, 2 H, CH2), 3.62 (s, 3 H, OCH3),
3.96 [s, 4 H, O(CH2)2O], 5.88 (d, J = 15 Hz, 1 H, CHCOOMe),
6.93 (dt, J = 15 Hz, J = 8 Hz, 1 H, CHCHCOOMe) ppm.
Experimental Section
Methyl (E)-5-Oxohept-2-enoate and Methyl (E)-5-Oxohept-3-enoate
(5a): An acetone solution (35 mL) of 4a (1.5 g, 7.5 mmol) and
pTsOH·H2O (120 mg) was stirred under reflux for 12 h. NaHCO3
(9 g) was added to the solution at 20 °C and the suspension was
vigorously stirred for 20 min. The suspension was filtered and the
filtrate was concentrated in vacuo to give 5a as a yellow liquid
(0.95 g, 81%, 1:1 mixture of positional isomers). 1H NMR (CDCl3,
250 MHz): δ = 1.06, 1.09 (2ϫt, J = 7 Hz, 1ϫ1.5 H, CH3), 2.49,
2.59 (2ϫq, J = 7 Hz, 2ϫ1 H, CH2), 3.24, 3.33 (2ϫd, J = 7 Hz,
2ϫ1 H, H-4), 3.72 (s, 3 H, OCH3), 5.87, 6.17 (2ϫd, J = 16 Hz,
2ϫ0.5 H, H-2), 6.86, 7.03 (2ϫdt, J = 16 Hz, J = 7 Hz, 2ϫ0.5 H,
H-3) ppm.
General Comments: All solvents were dried by standard methods
and all reactions were carried out under inert atmosphere. For H
1
and 13C NMR spectra, the deuterated solvents indicated were used.
Mass spectrometric data (MS) were obtained by electron ionization
(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.
Methyl 2-(2-Ethyl-1,3-dioxolan-2-yl)acetate (1a):[9] A toluene solu-
tion (100 mL) of methyl 3-oxopentanoate (15.0 g, 0.115 mol), eth-
ane-1,2-diol (14.3 g, 0.230 mol), and p-toluenesulfonic acid mono-
hydrate (0.3 g) was stirred for 14 h under a Dean–Stark trap.
NaHCO3 (5%, 50 mL) was added to the cooled solution, the aque-
ous and the organic layer were separated, and the latter layer was
dried (Na2SO4). The solution was filtered, the solvent was removed
from the filtrate in vacuo, and the residue was distilled in vacuo
(bp. 110 °C/20 Torr) to give 1a as a colorless liquid (15.5 g, 77%).
The spectroscopic data are identical with those reported.[9] 1H
NMR (CDCl3, 250 MHz): δ = 0.95 (t, J = 7 Hz, 3 H, CH3), 1.83
(q, J = 7 Hz, 2 H, CH3CH2), 2.66 (s, 2 H, CH2), 3.69 (s, 3 H,
OCH3), 3.98 [m, 4 H, O(CH2)2O] ppm.
2-(2-Ethyl-1,3-dioxolan-2-yl)ethanal (3a):[10] DiBAlH (21 mL, 1 
solution in toluene) was slowly added at –78 °C to a dichlorometh-
ane solution (40 mL) of 1a (5.0 g, 0.029 mol) and the mixture was
stirred for 1 h. Water (50 mL) was slowly added, the mixture was
allowed to warm to 20 °C, and an aqueous solution of HCl (4 ,
40 mL) was slowly added. The organic and the aqueous layer were
separated, the latter was extracted with dichloromethane
(2ϫ30 mL), the combined organic layers were dried (Na2SO4) and
filtered, and the filtrate was concentrated in vacuo to give a 1:1
mixture of 3a (1.38 g, 32%) and 2a. 2a:[9] 1H NMR (CDCl3,
200 MHz): δ = 0.95 (t, J = 7 Hz, 3 H, CH3), 1.67 (q, J = 7 Hz, 2
Methyl 5-(Trimethylsilyloxy)hepta-2,4-dienoate (6a): Triethylamine
(0.68 g, 6.7 mmol) and Me3SiCl (0.73 g, 6.7 mmol) were added to
a benzene solution (25 mL) of 5a (0.70 g, 4.49 mmol) and the reac-
tion mixture was stirred for 2 d at 20 °C under inert atmosphere
(N2). The solution was filtered and the filtrate was concentrated in
vacuo to give 6a as a brownish oil (0.97 mg, 98%). 1H NMR
(CDCl3, 250 MHz): δ = 0.27 [s, 9 H, Si(CH3)3], 1.09 (m, 3 H, CH3),
2.17 (q, J = 7 Hz, 2 H, CH2), 3.73 (s, 3 H, OCH3), 5.24 (d, J =
12 Hz, 1 H, CHCOOMe), 5.68 (d, J = 15 Hz, 1 H, TMSOCCH),
7.59 (dd, J = 15 Hz, J = 12 Hz, 1 H, CH) ppm. 13C NMR (CDCl3,
50 MHz): δ = 0.6 [(CH3)3], 11.2 (CH3), 30.0 (CH2), 51.1 (OCH3),
106.7 (C-2), 114.9 (C-4), 140.4 (C-3), 163.1, 168.2 (C) ppm.
1-Methoxy-1,5-bis(trimethylsilyloxy)hepta-1,3,5-triene (7a): nBuLi
(0.63 mL, 15% solution in n-hexane) and HMPA (0.17 g,
0.95 mmol) were added at 0 °C to a THF solution (5 mL) of diiso-
propylamine (0.098 g, 0.97 mmol) and the solution was stirred for
15 min. Compound 6a (150 mg, 0.66 mmol) was added to the solu-
tion at –78 °C and the system was stirred at –78 °C for 1.5 h. Chlo-
rotrimethylsilane (0.127 g, 1.17 mmol) was added and the solution
H, CH3CH2), 1.93 (t, J = 4 Hz, 2 H, CH2CH2OH), 3.75 (t, J = was allowed to warm to 20 °C over 3 h, the solvent was removed
4 Hz, 2 H, CH2CH2OH), 3.98 [m, 4 H, O(CH2)2O] ppm. in vacuo, and n-pentane was added to the residue. The suspension
Eur. J. Org. Chem. 2007, 351–355
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353

I. Freifeld, G. Bose, T. Eckardt, P. Langer
FULL PAPER
was filtered under inert atmosphere (N2) and the solvent was re-
moved from the filtrate in vacuo to give 7a as a brownish oil
(0.18 g, 91%). 1H NMR (CDCl3, 250 MHz): δ = 0.19 [m, 18 H,
2ϫSi(CH3)3], 1.64 (d, J = 6 Hz, 3 H, CH3), 3.14 (m, 1 H, CHCH3),
3.68 (s, 3 H, OCH3), 4.85 (m, 1 H, CHCOMe), 5.97 [m, 1 H,
C(OTMS)CH], 6.32 (d, J = 12 Hz, 1 H, CH) ppm.
16.0 Hz, 1 H, =CH), 5.65 (s, 1 H, =CH), 2.16 (s, 3 H, CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 197.8, 176.9 (C), 139.7 (CH),
135.0 (C), 129.8, 128.3 (2 C), 127.8 (2 C), 122.7, 101.1 (CH), 27.0
(CH3) ppm. MS (EI, 70 eV): m/z (%) = 188.1 (100), 173.0 (31),
144.8 (83), 131.1 (47), 102.8 (50), 85.1 (62), 43.1 (64); elemental
analysis: calcd. (%) for C12H12O2: C 76.57, H 6.42; found: C 76.75,
H 6.62.
(5Z)-3-Hydroxy-5-[(2E)-3-methoxycarbonyl-prop-2-enylidene]-4-
methyl-2(5H)-furanone (8a): Oxalyl chloride (0.08 g, 0.62 mmol)
and TMSOTf (0.07 g, 0.31 mmol) were added at –78 °C to a dichlo-
romethane solution (10 mL) of 7a (0.15 g, 0.50 mmol) and the mix-
ture was allowed to warm to 20 °C over 12 h. The solution was
extracted with brine (20 mL) and aqueous HCl (10%, 20 mL), the
aqueous layer was extracted with dichloromethane (2ϫ20 mL), the
combined organic layers were dried (MgSO4) and filtered, and the
filtrate was concentrated in vacuo. The residue was purified by
chromatography (silica gel, ether/petroleum ether 1:2Ǟ2:1) to give
6-Phenyl-2,4-bis(trimethysilyloxy)hexa-1,3,5-triene (14): Triethyl-
amine (1.21 mL, 8.75 mL) was added to a diethyl ether solution
(10 mL) of 13 (0.750 g, 4.0 mmol) and the solution was stirred for
30 min at 0 °C. TMSOTf (1.52 mL, 8.35 mL) was added and the
solution was stirred for 12 h at 20 °C. To the solution was added
an aqueous solution of HCl (10%, 100 mL). The ether layer was
separated from the liquid salt layer by syringe under inert atmo-
sphere, ether (10 mL) was added to the liquid salt layer, and the
mixture was stirred. The ether layer was again separated from the
liquid salt layer by syringe under inert atmosphere, this procedure
was repeated, and the combined organic layers were concentrated
in vacuo to give 14 (1.250 g, 94 %) as a yellow oil. 1H NMR
(300 MHz, CDCl3/TMS): δ = 7.63, 6.70 (d, J = 15.6 Hz, 1 H, =CH)
1
8a as a yellow solid (58 mg, 55%). H NMR (CDCl3, 250 MHz): δ
= 2.03 (s, 3 H, CH3), 3.78 (s, 3 H, OCH3), 5.81 (d, J = 12 Hz, 1
H, 1Ј-H), 6.00 (d, J = 14 Hz, 1 H, 3Ј-H), 7.76 (dd, J = 14 Hz, J =
12 Hz, 1 H, 2Ј-H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 7.2
(CH3), 52.8 (OCH3), 105.5 (C-1Ј), 120.9 (C), 122.2 (C-3Ј), 136.2 [(E)/(Z) isomer], 7.41–7.17 (m, 10 H, ArH) [(E)/(Z) isomer], 6.80,
(C-2Ј), 141.9, 152.6, 164.4, 166.9 (C) ppm. MS (EI, 70 eV): m/z (%) 6.50 (d, J = 15.6 Hz, 1 H, =CH) [(E)/(Z) isomer], 5.36, 5.19 (s, 1
= 210 [M]+ (66), 179 (43), 95 (100), 83 (43), 57 (40). The exact H, =CH) [(E)/(Z) isomer], 4.78, 4.25 (s, 1 H, =CH2) [(E)/(Z) iso-
molecular mass for C11H12O5 m/z = 210.0528Ϯ2 ppm (M+) was
confirmed by HRMS (70 eV, EI).
mer], 4.43, 4.23 (s, 1 H, =CH2) [(E)/(Z) isomer] ppm. 13C NMR
(75 MHz, CDCl3/TMS): δ = 154.5, 152.8 [(E)/(Z) isomer], 150.6,
150.0 [(E)/(Z) isomer], 137.3, 136.7 [(E)/(Z) isomer] (C), 130.1,
129.7 [(E)/(Z) isomer], 128.6, 128.6 (2 C) [(E)/(Z) isomer], 127.7,
126.6 [(E)/(Z) isomer], 127.6, 127.5 [(E)/(Z) isomer], 126.9, 123.5
(2 C) [(E)/(Z) isomer], 113.6, 112.1 (CH) [(E)/(Z) isomer], 97.0, 96.0
(CH2) [(E)/(Z) isomer], 1.3, 0.3 (3C) [(E)/(Z) isomer], 0.9, 0.2 (3C,
CH3) [(E)/(Z) isomer] ppm.
(5E)-5-[1-(Methoxycarbonyl)-2-oxopropylidene]-3-hydroxy-2-furan-
one (10): TMSOTf (0.5 mmol, 0.09 mL) was added at –78 °C to a
CH2Cl2 solution (20 mL) of oxalyl chloride (1.5 mmol, 0.13 mL)
and 9 (1.5 mmol, 0.65 g). The solution was allowed to warm to
20 °C over 6 h. After the system had been stirred for 3 h at 20 °C,
a saturated aqueous solution of NaCl (100 mL) was added, the
organic and the aqueous layer were separated, the latter was ex-
tracted with diethyl ether (4ϫ100 mL), the combined organic lay-
3-Hydroxy-5-(2-oxo-4-phenylbut-3-enylidene)-5H-furan-2-one (15):
The reaction was carried out according to the procedure given for
ers were dried (MgSO4) and filtered, and the filtrate was concen- the synthesis of 10. Starting with 14 (0.332 g, 1.00 mmol), oxalyl
trated in vacuo. The residue was purified by chromatography (silica
gel) to give 10 (174 mg, 55%) as a yellow solid. 1H NMR ([D6]
acetone, 250 MHz, keto/enol 1:3): δ = 3.62 (s, 2 H, keto, CH2, 3Ј-
chloride (0.090 mL, 1.03 mmol), and Me3SiOTf (0.11 mL,
0.50 mmol; in 1 mL CH2Cl2), 15 was isolated (0.155 g, 64%) as a
yellow solid; m.p. 128–129 °C; Rf = 0.47 (hexane/ethyl acetate 3:1).
H), 3.64 (s, 3 H, enol, OCH3), 3.72 (3 H, keto, OCH3), 5.33 (s, 1 1H NMR (300 MHz, CDCl3): δ = 7.74–7.67 (m, 3 H, ArH, =CH),
H, enol, CH, 3Ј-H), 5.85 (s, 1 H, keto, CH, 1Ј-H), 6.14 (s, 1 H, 7.46–7.42 (m, 3 H, ArH), 7.12–7.03 (m, 2 H, =CH), 6.59 (s, 1 H,
enol, 3Ј-H), 7.02 and 7.04 (2ϫs, 1 H, keto, 1 H, enol, 4-H), 12.21
=CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 188.3, 163.7, 159.3,
151.4 (C), 152.3 (CH), 134.4 (C), 130.5, 128.9 (2 C), 128.5 (2 C),
(br., 1 H, OH) ppm. 13C NMR ([D6]acetone, 50 MHz): δC = 50.8
(CH2), 51.8, 52.2 (OCH3), 94.2, 103.7, 104.4, 108.9, 110.2 (CH, C- 128.2, 107.7, 103.6 (CH) ppm. IR (KBr): ν = 3002 (br), 1800 (s),
˜
4, C-1Ј, C-3Ј, keto, enol), 149.1, 152.3, 154.9, 160.4, 161.4, 164.3,
168.3, 169.7, 173.9 (C), 192.5 (C-2Ј, keto). MS (70 eV, EI): m/z (%)
1628 (s), 1612 (s), 1552 (s), 1398 (m), 1267 (s), 1213 (m), 1045 (s),
979 (m), 767 (w) cm–1. MS (EI, 70 eV): m/z (%) = 242 [M]+ (1), 226
= 212 [M]+ (48), 194 (8), 181 (8), 156 (26), 139 (100). The exact (2), 214 (3), 131 (1), 103 (1), 77 (1), 44 (7), 28 (100); elemental
molecular mass for C9H8O6 m/z = 212.0321Ϯ2 ppm (M+) was con-
firmed by HRMS (70 eV, EI).
analysis: calcd. (%) for C14H10O4: C 69.41, H 4.16; found: C 69.17,
H 4.49.
6-Phenylhex-5-ene-2,4-dione (13): Benzaldehyde (3.1 g, 29.3 mmol)
was added at –78 °C to a stirred solution of 2,4-bis(trimethysilyl-
oxy)penta-1,3-diene (7.0 g, 28.7 mmol) in CH2Cl2 (300 mL), which
was followed by dropwise addition of TiCl4 (3.1 mL, 28.2 mmol;
dissolved in 10 mL of CH2Cl2). The temperature was allowed to
rise to 20 °C over 6 h, the solution was stirred for an additional 6 h
at 20 °C, and an aqueous solution of HCl (10 %, 100 mL) was
added. The organic and the aqueous layer were separated, the latter
was extracted with CH2Cl2 (2ϫ100 mL), the combined organic
layers were dried (Na2SO4) and filtered, and the filtrate was con-
centrated in vacuo. The residue was purified by column chromatog-
raphy (EtOAc/hexane 1:9) to give 13 (3.3 g, 62%) as yellow crystals,
mp. 84–85 °C; Rf = 0.62 (EtOAc/hexane 1:9). 1H NMR (300 MHz,
3-Hydroxy-5-(2-oxo-4-phenylbut-3-enylidene)-5H-furan-2-one (16):
K2CO3 (0.051 g, 0.37 mmol) was added at 20 °C to an acetone solu-
tion of 15 (0.060 g, 0.025 mmol). After the mixture had been stirred
for 30 min, Me2SO4 (0.042 g, 0.33 mmol) was added dropwise and
the solution was stirred for 12 h. The reaction mixture was filtered,
the residue was washed with acetone (2ϫ15 mL), and the filtrate
was concentrated in vacuo. The residue was purified by column
chromatography (silica gel, hexane/EtOAc 4:1) to give 16 (0.042 g,
66%) as a yellow solid. Rf = 0.17 (hexane/ethyl acetate 4:1). 1H
NMR (300 MHz, CDCl3): δ = 7.64 (d, J = 16.2 Hz, 1 H, =CH),
7.60–7.55 (m, 2 H, ArH), 7.43–7.39 (m, 4 H, ArH, =CH), 6.87 (d,
J = 16.2 Hz, 1 H, =CH), 6.41 (s, 1 H, =CH), 3.99 (s, 3 H,
OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 188.6, 162.4, 158.6,
CDCl3): δ = 15.34 (brs, 1 H, OH), 7.59 (d, J = 16.0 Hz, 1 H, =CH), 153.1 (C), 143.5 (CH), 134.3 (C), 130.9, 129.0 (2 C), 128.5 (2 C),
7.55–7.49 (m, 2 H, ArH), 7.41–7.34 (m, 3 H, ArH), 6.46 (d, J = 127.7, 108.1, 105.2 (CH), 59.4 (CH ) ppm. IR (KBr): ν = 1792 (s),
˜
3
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Eur. J. Org. Chem. 2007, 351–355

Synthesis of γ-Alkylidenebutenolides by formal [3+2] Cyclizations
FULL PAPER
[5] For the preparation of keto ester 5c, see: A. G. M. Barrett,
R. A. E. Carr, M. A. W. Finch, J.-C. Florent, G. Richardson,
N. D. A. Walshe, J. Org. Chem. 1986, 51, 4254.
1652 (w), 1617 (s), 1449 (w), 1334 (w), 1223 (m), 1067 (s), 986
(m) cm–1. MS (EI, 70 eV): m/z (%) = 256 [M]+ (31), 228 (5), 213
(13), 185 (15), 152 (13), 131 (13), 103 (25), 77 (22), 70 (38), 28 (100).
[6] For the synthesis of polyunsaturated butenolides, see for exam-
ple: a) K. Siegel, R. Brückner, Chem. Eur. J. 1998, 4, 1116; b)
F. C. Görth, R. Brückner, Synthesis 1999, 1520; for butenolides
containing only one double bond in the γ-alkylidene side chain,
see for example: c) D. W. Knight, G. Pattenden, J. Chem. Soc.,
Perkin Trans. 1 1979, 62; d) C. F. Ingham, R. A. Massy-Wes-
tropp, G. D. Reynolds, W. D. Thorpe, Aust. J. Chem. 1975, 28,
2499; review: e) R. Brückner, Curr. Org. Chem. 2001, 5, 679.
[7] H.-H. Lee, Y.-T. Que, J. Chem. Soc., Perkin Trans. 1 1985, 453.
[8] N. G. Clemo, D. R. Gedge, G. Pattenden, J. Chem. Soc., Perkin
Trans. 1 1981, 1448.
Acknowledgments
Financial support from the Deutsche Forschungsgemeinschaft is
gratefully acknowledged.
[1] a) T. H. Chan, P. Brownbridge, J. Chem. Soc., Chem. Commun.
1979, 578; b) T. H. Chan, P. Brownbridge, J. Am. Chem. Soc.
1980, 102, 3534; c) G. A. Molander, K. O. Cameron, J. Am.
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[9] S. R. Hitchcock, R. Shawn, F. Perron, V. A. Martin, K. F. Albi-
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[10] Y. Vankar, M. V. Reddy, N. C. Chaudhuri, Tetrahedron 1994,
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[2] P. Langer, Synthesis 2002, 441.
[3] P. Langer, I. Freifeld, Synlett 2001, 523.
Received: May 5, 2006
Published Online: November 13, 2006
[4] G. Bose, P. Langer, Synlett 2005, 1021.
Eur. J. Org. Chem. 2007, 351–355
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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