α-Amino-α-vinyl-γ-butyrolactone derivatives from α-{[(trimethylsilyl)-methyl]alkylidene}-γ-butyrolactones

Article abstract of DOI:10.1002/ejoc.200600540

N-Protected α-amino-α-vinyl-γ-butyrolactones 1 are obtained by the aza-Michael-type addition of NsONHCO₂Et to novel silylated α-ylidene-γ-butyrolactones 2, through ring opening of the intermediate aziridine and loss of the trimethylsilyl group.

Full text of DOI:10.1002/ejoc.200600540

FULL PAPER
DOI: 10.1002/ejoc.200600540
α-Amino-α-vinyl-γ-butyrolactone Derivatives from α-{[(Trimethylsilyl)-
methyl]alkylidene}-γ-butyrolactones
Marinella Capuzzi,[a,b] Augusto Gambacorta, Tecla Gasperi,
[c]
[a,b]
M. Antonietta Loreto,*[a,b]
and P. Antonio Tardella[
a]
Keywords: α-Amino lactones / Aza-Michael reactions / Allylsilanes / Vinyl triflates / Cross-coupling / Palladium
N-Protected α-amino-α-vinyl-γ-butyrolactones 1 are obtained
by the aza-Michael-type addition of NsONHCO Et to novel
silylated α-ylidene-γ-butyrolactones 2, through ring opening
of the intermediate aziridine and loss of the trimethylsilyl
group. The stereoselective synthesis of compounds 2, by
cross-coupling reactions between α-[(triflyloxy)ylidene]-γ-
butyrolactones 3 and tris[(trimethylsilyl)methyl]aluminum, is
also described.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
2
Introduction
finic β-carbon atom by an aza-Michael-type reaction, fol-
lowed by ring closure and the expulsion of the NsO group.
–
In the past years, significant attention has been focused Particularly, this reaction sequence on α-ylidene-γ-butyrol-
[
1]
on the synthesis of α-amino-γ-butyrolactone derivatives.
actones afforded spiroaziridines, precursors of α-amino-γ-
[
6]
The biological interest in this class of compounds is linked butyrolactone derivatives, while the same aminating rea-
to the presence of the α-amino-γ-lactone skeleton in several gent, when allowed to react with α,β-unsaturated esters and
compounds with antiallergic and antineoplastic proper- ketones, carrying a (trimethylsilyl)methyl group at the
ties.[ Furthermore, N-acylhomoserine lactones control the double bond, gave α-amino-α-vinyl derivatives through azi-
transcription of specific genes in Gram-negative bacteria ridination and subsequent loss of the trialkylsilyl group.[
2]
7]
[
3]
and have been used as quorum-sensing autoinducers.
On these grounds, faced with the synthesis of both α-
From the synthetic point of view, α-amino-γ-lactone deriva- amino-γ-butyrolactone derivatives and α-vinyl amino acids,
tives constitute valuable precursors for the synthesis of bio- we planned the preparation of the novel α-{[N-(ethoxycar-
logically important compounds. In particular, α-amino-α- bonyl)]amino}-α-vinyl-γ-butyrolactones 1 according to the
vinyl-γ-lactones have been successfully used by Berkowitz retrosynthetic analysis depicted in Scheme 1. Thus, the
et al. as intermediates in the preparation of α-vinyl amino novel
acids, which are mechanism-based inhibitors for enzymes tones 2, obtained in turn from the triflates 3, could undergo
of the amino acid decarboxylase class. Recently, Smith et an aza-Michael-type addition of NsONHCO Et to afford
α-{[(trimethylsilyl)methyl]alkylidene}-γ-butyrolac-
[
4]
2
al. have published an interesting synthetic route to obtain intermediate aziridines. Subsequent loss of the trialkylsilyl
polypyrrolinone nonpeptidomimetics starting from α-alkyl- group and concomitant aziridine ring opening, could give
[
5]
α-aminolactones.
the expected α-{[N-(ethoxycarbonyl)]amino}-α-vinyl-γ-bu-
For several years, our research group has been
interested in studying the reactivity of electron-poor olefins
towards ethyl N-{[(4-nitrobenzyl)sulfonyl]oxy}carbamate
(
NsONHCO Et) in order to obtain N-(ethoxycarbonyl)-
2
aziridines, which can be opened to obtain new amino deriv-
[
6,7]
atives.
In the presence of a base, the anion of
NsONHCO Et carries out a nucleophilic attack at the ole-
2
[
a] Dipartimento di Chimica, Università “La Sapienza”,
Piazzale Aldo Moro 5, Rome 00185, Italy
Fax: +39-06-490631
E-mail: mariaantonietta.loreto@uniroma1.it
b] Istituto C.N.R. di Chimica Biomolecolare, Dipartimento di
Chimica, Università “La Sapienza”,
[
[
Piazzale Aldo Moro 5, Rome 00185, Italy
c] CISDiC, Dipartimento di Ingegneria Meccanica e Industriale,
Università “Roma Tre”,
Scheme 1. Retrosynthetic analysis for the synthesis of α-{[N-
(ethoxycarbonyl)]amino}-α-vinyl-γ-butyrolactones 1.
Via della Vasca Navale 79, Rome 00146, Italy
5076
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5076–5082

α-Amino-α-vinyl-γ-butyrolactone Derivatives
FULL PAPER
tyrolactones 1. We report here the synthesis of triflates 3, Table 1. Synthesis of triflates 3.
their conversion into the allylsilanes 2 and the amination of
the latter to afford the α-{[N-(ethoxycarbonyl)]amino}-α-
vinyl-γ-butyrolactones 1.
Substrate R1 R2 R3 Base Solvent T [°C]/Time [h] Product Yield [%]
4a
4b
4b
4b
H
H
H
H
H
CH
H
H
3
H
H
H
H
H
H
nBuLi THF
nBuLi THF
LDA THF
–78/1
–78/1
–40/6
–40 to 25/7
–78/2
Z-3a
68
–
–
50
75
70
62
[a]
–
–
[a]
[b]
H
–
DME
E-3b
Z-3c
Z-3d
Z-3e
4
4d
c
Ph
Ph CH3
CH
nBuLi THF
nBuLi THF
Ph nBuLi THF
Results and Discussion
–78/3
–78/3
4e
H
3
Allylsilanes with a carbonyl group at the β- or γ-position,
or their equivalents, represent a powerful synthetic tool in
organic synthesis, since they can formally react either as
nucleophiles or as electrophiles.[ Though several prepara-
tions of this class of functionalized allylsilanes are known
[
a] Unreacted substrate was recovered. [b] The sodium salt of 4b
was directly used without any additional base.
8]
With the triflates 3 in hand, we performed the synthesis
of the allylsilanes 2 (Scheme 3).
[
9]
in the literature, to the best of our knowledge, no exam-
ples of allylsilanes carrying a γ-butyrolactone moiety at the
double bond, as in 2, have been reported. In order to obtain
these challenging substrates, we have chosen to perform a
Pd-catalyzed cross-coupling reaction between α-[(triflyl-
oxy)ylidene]-γ-butyrolactones 3 and tris[(trimethylsilyl)-
methyl]aluminum, according to the route previously de-
scribed for the synthesis of [γ-(methoxycarbonyl)allyl]si-
Scheme 3. Synthesis of α-{[(trimethylsilyl)methyl]alkylidene}-γ-bu-
[
7c]
lanes.
Actually, cross-coupling reactions provide one of tyrolactones 2a–d.
the most useful synthetic ways for stereoselective carbon–
carbon bond formation.[
10]
The cross-coupling reaction was initially performed on
a, as a model substrate, according to the same procedure
The α-[(triflyloxy)ylidene]-γ-butyrolactones 3a–e were
synthesized from the corresponding and previously de-
scribed α-acyl-γ-butyrolactones 4a–e (Scheme 2), obtained
in turn either by cross-Claisen acylation of commercial γ-
3
reported for the synthesis of [γ-(methoxycarbonyl)allyl]si-
[
7c]
lanes, but initial results were quite disappointing. In fact,
through the in situ generation of the catalytic species,
Pd(PPh ) , by reduction of Pd(OAc) by the nBuLi/PPh
[
11]
butyrolactones or by the enolate-promoted ring-opening
reaction of styrene oxide followed by intramolecular trans-
3
4
2
3
[
12]
system, the addition of the vinyl triflate 3a and transmetal-
esterification.
lation with (Me SiCH ) Al, formed in situ from AlCl and
3
2 3
3
Me SiCH Li, we did not observe the formation of the ex-
3
2
pected allylsilane 2a, even after 24 h at reflux. Only the ad-
dition of a second equiv. of (Me SiCH ) Al allowed us to
3
2 3
isolate the product 2a in 33% yield. In an effort to improve
the reaction efficiency, several different combinations of sol-
vents, bases and alkylating agent ratios were evaluated, but
Scheme 2. Synthesis of α-[(triflyloxy)ylidene]-γ-butyrolactones only low yields of product could be obtained.
3a–e.
Finally, the use of a large excess of (Me SiCH ) Al at
3 2 3
50 °C, in the absence of nBuLi, afforded the desired allylsi-
According to the procedure reported for the preparation lane 2a in 95% yield with a (Z) configuration. Therefore,
[
13]
of 3a,
we treated the α-acyl-γ-butyrolactones 4a–e with the cross coupling proceeds with retention of the double
trifluoromethanesulfonic anhydride in the presence of a bond configuration, as confirmed by the deshielding of the
suitable base to afford the corresponding triflates in the CH -TMS protons compared to the methyl protons in the
2
1
yields and under the conditions reported in Table 1. In the
H NMR spectrum.
case of substrate 4b, isolated as the sodium salt, the corre-
Presumably, the excess of (Me SiCH ) Al or the tri-
3
2 3
[
17]
sponding known vinyl triflate 3b was directly obtained phenylphosphane itself acts as a reducing agent towards
without employing any additional base.[ It is noteworthy the palladium acetate. The above optimized protocol for the
that vinyl triflates 3a–e were easily purified by crystalli- vinyl triflate 3a was successfully extended to the other tri-
zation from diethyl ether.[ The (Z) selectivity for the novel flates 3b–e by adjusting the reaction time and the tempera-
compounds 3c–e is consistent with the behaviour reported tures to enhance the reactivity on a case-by-case basis
14]
15]
by Jacobi et al. for the vinyl triflate 3a. Presumably, Li+ (Table 2).
[
13]
coordination with both the exocyclic and endocyclic car-
In all experiments, the cross coupling proceeded with re-
bonyl groups forces the enolate into the less stable (Z) con- tention of the double bond configuration in the parent tri-
figuration. Accordingly, the use of the sodium enolate in flates, and the best results were obtained in the synthesis of
the case of 4b results in the more stable (E)-enolate and allylsilanes 2a–c, while minor conversion was observed with
affords (E) selectivity for the vinyl triflate 3b.[
11a,16]
the allylsilane 2d, substituted with a phenyl group on the
Eur. J. Org. Chem. 2006, 5076–5082
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5077

M. Capuzzi, A. Gambacorta, T. Gasperi, M. A. Loreto, P. A. Tardella
Table 2. Pd-cross-coupling reaction between compounds 3 and and characterized by NMR and GC-MS analyses, and the
FULL PAPER
(
3 2 3
Me SiCH ) Al.
spectroscopic data are in agreement with the reported struc-
tures.
Substrate[a]
R1
R2
R3
T [°C]/Time [h] Product Yield [%]
Z-3a
E-3b
Z-3c
Z-3d
Z-3e
Z-3e
H
H
H
Ph
H
H
CH
H
Ph
3
H
H
H
H
Ph
Ph
50/4
50/5
70/4
50/4
50/4
70/24
Z-2a
E-2b
95
71
83
62
–
Table 3. Amination reaction on allylsilanes 2.
Substrate R1 R2 2/NsONHCO Et/CaO Time [h] Product Yield [%][a]
2
Z-2c[
b]
CH
CH
CH
3
3
3
Z-2d
Z-2a
E-2b
Z-2c
Z-2d
H
H
H
CH
H
Ph
3
1:5:5
1:5:5
1:8:8
1:6:6
6
6
9
7
1a
1b
1c
1d
73
70
55
52
[
c]
–
[c]
–
–
Ph CH
3
[
1
a] The molar ratio of 3a–e/(Me
:2.5:0.09:0.36. [b] In this case, a larger excess of (Me
was used. [c] Unreacted substrate was recovered.
3
SiCH
2
)
3
Al/Pd(OAc)
2
/PPh
3
=
Al
3
SiCH
2
)
3
[
a] Isolated yields of the crude mixtures obtained after treatment
with AcOH, as determined by HPLC chromatography.
ring. The triflate 3e did not react, possibly because steric
hindrance of the phenyl group in the β-position made the
transmetallation step in the catalytic cycle unfavourable.
With the α-{[(trimethylsilyl)methyl]alkylidene}-γ-butyro-
lactones 2 in hand, and on the basis of our previous re-
It is noteworthy that, starting from the allylsilane 2d,
substituted on the ring, we isolated the α-amino-α-vinyllac-
tone 1d as single diastereomer, as shown by HPLC analysis
1
and the H NMR spectrum. Probably, the bulky phenyl
group in the γ-position of the lactone ring drives the amin-
ating agent approach from the less hindered face of the
double bond, anti to the substituent, affording diastereo-
selectively the formation of 1d, analogous to the behaviour
previously observed in the aziridination of α-ylidene-γ-bu-
[
6,7]
sults,
we extended the amination reaction to these com-
pounds. First attempts were carried out on the substrate 2a
by adding to it 5 equiv. of an NsONHCO Et/CaO mixture
2
(1:1 molar ratio) portionwise at room temperature. After
the usual workup, it was not possible to find the expected
spiroaziridine intermediate, but we obtained two new com-
pounds. The major product was the desired unsaturated α-
amino-γ-lactone 1a (64% yield) (Figure 1), derived from the
ring opening of the intermediate spiroaziridine with the
concomitant loss of the silyl group (Scheme 4). The minor
product was the unexpected compound 5a (10% yield) (Fig-
ure 1), generated by the loss of a proton instead of the tri-
[6b]
tyrolactones.
Conclusions
In summary, we have described an efficient three-step
synthesis of the novel α-{[N-(ethoxycarbonyl)]amino}-α-vi-
nyl-γ-lactones 1a–d by the aza-Michael-type aziridination
of the new silylated α-ylidene-γ-butyrolactones 2a–d. The
latter, due to the versatility of both the allylsilane and enone
systems, are valuable building blocks and have been stereo-
selectively obtained by Pd-catalyzed cross coupling between
the easy accessible α-[(triflyloxy)ylidene]-γ-butyrolactones
[
18]
methylsilyl group. Fortunately, it was possible to convert,
almost quantitatively, 5a into 1a through the known acid-
catalysed protodesilylation of vinylsilanes.[19] Therefore, di-
rect treatment of the crude reaction mixture with acetic acid
resulted in the formation of 1a as the only product in higher
yield.
3
1
a–d and tris[(trimethylsilyl)methyl]aluminum. Compounds
a–d are interesting intermediates in the preparation of α-
vinyl amino acids and direct precursors of quaternary α-
aminolactones having in the α-position all functionalities
obtainable by chemical elaboration of the vinyl group.
2
Figure 1. Products obtained by reaction of 2a with NsONHCO Et
and CaO, without treatment with AcOH.
Experimental Section
General: All reactions were performed under argon with standard
air-free manipulation techniques. Solvents and common reagents
were purchased from commercial sources and used without further
purification. All reactions were monitored by GC-MS analysis and
by thin layer chromatography (TLC) carried out on Merck F-254
The above amination protocol, followed by treatment
with acetic acid, was performed on the silylated compounds
2a–d and provided the α-{[N-(ethoxycarbonyl)]amino}-γ-
lactones 1a–d (Scheme 4), in the yields and under the condi- silica glass plates and visualized with UV light and I . Chromato-
2
tions reported in Table 3. Compounds 1a–d were isolated graphic separations were performed on Merck silica gel 60 (230–
2
Scheme 4. Amination reaction performed on 2a–d with NsONHCO Et and CaO, followed by treatment of the crude mixtures with
AcOH.
5078
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Eur. J. Org. Chem. 2006, 5076–5082

α-Amino-α-vinyl-γ-butyrolactone Derivatives
00 mesh). Purifications by HPLC were performed with an instru-
FULL PAPER
separated, the aqueous layer was extracted with diethyl ether, and
4
ment equipped with a differential refractometer and an analytical
2 4
the combined organic phases were dried (Na SO ). Solvent was
1
column (3.9×300 mm, flow rate 1.3 mL/min). H (200 MHz) and
removed under vacuum, and the crude residue was purified by flash
chromatography (hexane/AcOEt, 9:1) to give 4d (5.020 g, 32%
yield, 1:1 cis/trans mixture) and 4e as only the trans stereoisomer
(9.098 g, 58% yield). The characterization data are in agreement
13
C NMR (50 MHz) spectra were recorded with a Varian Gemini
200 spectrometer; chemical shifts are expressed in ppm (δ) and are
referenced to the carbon and residual proton signals of the solvent
1
13
(
CHCl
unless otherwise indicated. IR spectra were recorded in CHCl
a Perkin–Elmer 1600 instrument (FT-IR); data are presented in
3
: δ = 7.26 ppm for H NMR, δ = 77.0 ppm for C NMR), with literature data.
3
with
Synthesis of α-[(Triflyloxy)alkylidene]-γ-butyrolactones 3a–e
–1
(1Z)-1-(2-Oxodihydrofuran-3-ylidene)ethyl Trifluoromethanesulfon-
wavenumbers (cm ). MS data were obtained by GC-MS coupling
with an HP 5890 apparatus, equipped with a phenylmethylsilicon
capillary column (15 m, 0.25 mm i.d.). HRMS data were recorded
with a Micromass Q-TOF micro Mass Spectrometer (Waters). All
melting points were determined with a Mel-Temp apparatus and
are uncorrected.
ate (3a):[
13]
A solution of commercial α-acetyl-γ-butyrolactone
(
0.76 mL, 7.09 mmol) in anhydrous THF (30 mL) was cooled to
–78 °C under argon. nBuLi (2.5  solution in hexane, 2.84 mL,
7.09 mmol) was added dropwise, under efficient stirring, over a
period of 10 min, and the resulting mixture was stirred at –78 °C
for an additional 30 min. Trifluoromethanesulfonic anhydride
Synthesis of α-Acyl-γ-butyrolactones 4b–e
(
1.19 mL, 7.09 mmol) was added over a period of 5 min. The re-
sulting solution was stirred at –78 °C for an additional 20 min,
quenched by the careful addition of ice-cold saturated NaHCO3/
Sodium (E)-(2-oxodihydrofuran-3-ylidene)methoxide (E-4b sodium
[
11a]
salt):
To a stirred suspension of NaH (580 mg, 14.5 mmol, 60%
brine (1:1) (24 mL) and extracted with diethyl ether. The combined
organic extracts were dried (Na SO ), concentrated under reduced
2 4
pressure, and the residue was crystallized from diethyl ether to ob-
suspension in mineral oil) in anhydrous DME (60 mL), a mixture
of commercial γ-butyrolactone (1.14 mL, 15 mmol) and ethyl for-
mate (1.21 mL, 15 mmol) in anhydrous DME (8 mL) was added.
After the addition of absolute ethanol (0.1 mL), the mixture was
heated to 40 °C for 22 h. The reaction mixture was directly filtered
through a Büchner funnel under vacuum and washed several times
with anhydrous diethyl ether to obtain the E-4b sodium salt as a
tain 3a as a white crystalline solid (1.253 g, 68% yield). M.p. 64–
13]
+
6
5 °C (ref.[ 65–66 °C). MS: m/z (%) = 260 (24) [M] , 43 (100).
Other spectroscopic data are in agreement with literature data.
(
(
E)-(2-Oxodihydrofuran-3-ylidene)methyl Trifluoromethanesulfonate
fine, powdery, white solid (1.990 g, 97% yield). M.p. 116–118 °C.
[14]
3b):
A stirred suspension of the sodium salt of 4b (1.900 g,
1
H NMR (D
CH O), 4.16 (t, J = 8.4 Hz, 2 H, CH
C=CH) ppm. C NMR (D
2
O, 200 MHz, 25 °C): δ = 2.60 (t, J = 8.4 Hz, 2 H,
CH O), 8.26 (s, 1 H,
O, 50 MHz): δ = 23.8 (CH CH O),
O), 93.4 (C=CH), 172.2 (C=CH), 180.3 (C=O) ppm.
-Benzoyldihydrofuran-2-one (4c):[11b] To a stirred suspension of
13.97 mmol) in anhydrous DME (28 mL) was cooled to –40 °C,
CH
2
2
2
2
and trifluoromethanesulfonic anhydride (2.35 mL, 13.97 mmol)
was added dropwise. The reaction mixture was stirred at –40 °C for
an additional 1 h and at room temp. for a further 3 h. The solvent
was removed by evaporation under vacuum, and the residue was
filtered and washed with diethyl ether. The organic phase was
13
2
2
2
6
6.8 (CH
2
3
NaH (1.309 g, 30 mmol, 60% suspension in mineral oil) in anhy-
drous DME (50 mL), methyl benzoate (3.73 mL, 30 mmol) was
added. The reaction mixture was heated to 50 °C, and then a solu-
tion of γ-butyrolactone (1.280 g, 15 mmol) in anhydrous DME
treated with a saturated solution of NaHCO
layer was extracted with diethyl ether. The combined organic
phases were dried with Na SO , concentrated under vacuum, and
3
, and the aqueous
2
4
the crude product was purified by flash chromatography (hexane/
(7 mL) was added dropwise. After the addition of anhydrous meth-
diethyl ether, 1:1) to give 3b as a white crystalline solid (1.718 g,
anol (0.1 mL), the resulting yellow solution was stirred at reflux for
an additional 5 h. After cooling the mixture to room temp., the
reaction was quenched by the cautious addition of H O (20 mL)
2
followed by acidification with 1  HCl to pH = 4. The organic layer
was separated, and the aqueous layer was extracted with diethyl
5
5
0% yield). M.p. 41–42 °C (ref.[ 41–42 °C). C NMR (CDCl
14]
13
3
,
0 MHz, 25 °C): δ = 24.2 (CH
2
CH
2
O), 65.9 (CH
2 2
CH O), 117.0
(
(
C=C-OTf), 118.4 (q, J = 321 Hz, CF
C=O) ppm. MS: m/z (%) = 246 (13.1) [M] , 69 (100). The
3
), 142.6 (C=C-OTf), 168.5
+
1
H
NMR spectrum is in agreement with literature data.
2 4
ether. The combined organic phases were dried (Na SO ), concen-
trated under vacuum, and the crude mixture was purified by flash
(Z)-(2-Oxodihydrofuran-3-ylidene)(phenyl)methyl Trifluoromethane-
sulfonate (3c): This compound was prepared from 4c (1.800 g,
9.47 mmol), according to the procedure described for 3a. After the
addition of trifluoromethanesulfonic anhydride, the resulting solu-
chromatography (hexane/AcOEt, 9:1) to obtain pure 4c (2.052 g,
1
3
7
(
2% yield). C NMR (CDCl
3
, 50 MHz, 25 °C): δ = 25.8
CH O), 128.5 (CHarom.),
CH CH O), 47.7 (CH-C=O), 67.5 (CH
2
2
2
2
129.1 (CHarom.), 133.8 (CHarom.), 135.0 (Carom.), 172.9 (O-C=O), tion was stirred at –78 °C for an additional 3 h. The crude mixture
1
93.2 (Ph–C=O) ppm. R
f
+
0.49 (silica gel, hexane/AcOEt, 7:3). MS:
was purified by crystallization from diethyl ether and by flash
chromatography of the crystallization mother liquor to obtain 3c
1
m/z (%) = 190 (2.4) [M] , 105 (100). The H NMR spectrum is in
agreement with literature data.
(2.287 g, 75% total yield). M.p. 134–136 °C. IR (CHCl ): ν˜
3
max
=
–
1 1
1
750, 1685 cm . H NMR (CDCl
J = 7.1 Hz, 2 H, CH CH O), 4.38 (t, J = 7.1 Hz, 2 H, CH
.40–7.62 (m, 5 H, CHarom.) ppm. C NMR (CDCl
5 °C): δ = 29.3 (CH CH O), 64.7 (CH CH O), 118.1 (q, J =
09 Hz, CF ), 118.6 (C=C-OTf), 127.8 (CHarom.), 128.7 (CHarom.),
31.2 (CHarom.), 131.5 (Carom.), 149.0 (C-OTf), 165.2 (C=O) ppm.
= 0.17 (silica gel, hexane/AcOEt, 8:2). MS: m/z (%) = 322 (0.8)
3
, 200 MHz, 25 °C): δ = 3.21 (t,
CH O),
, 50 MHz,
trans- and cis-3-Acetyl-5-phenyldihydrofuran-2-one (4d) and trans-3-
Acetyl-4-phenyldihydrofuran-2-one (4e):[
12]
2
2
2
2
A solution of EtONa
1
3
7
2
3
1
3
was prepared from absolute ethanol (28.8 mL, 494.6 mmol) and
sodium (1.474 g, 64.1 mmol). The flask was then cooled with ice,
and ethyl acetoacetate (9.8 mL, 76.9 mmol) was added rapidly. The
reaction mixture was stirred at room temp. for 1 h, and styrene
oxide (8.77 mL, 76.9 mmol) was added dropwise at 0 °C over a
period of 30 min. The mixture was warmed to room temperature
and stirred for an additional 72 h. The alcohol was removed under
reduced pressure, below 50 °C, and glacial acetic acid (8.8 mL,
2
2
2
2
3
R
f
+
[M] , 105 (100). HRMS: calcd. for C12
H
9
F
3
NaO
5
S [M] 345.0020;
found 345.0029.
(1Z)-1-(2-Oxo-5-phenyldihydrofuran-3-ylidene)ethyl
Trifluorome-
6
7.3 mmol) and ice were added to the syrupy residue. The excess
thanesulfonate (3d): This compound was prepared from 4d (900 mg,
2.94 mmol), according to the procedure described for 3a. After the
of acetic acid was neutralized with NaHCO . The oily layer was
3
Eur. J. Org. Chem. 2006, 5076–5082
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5079

M. Capuzzi, A. Gambacorta, T. Gasperi, M. A. Loreto, P. A. Tardella
FULL PAPER
0
addition of trifluoromethanesulfonic anhydride, the resulting solu-
tion was stirred at –78 °C for an additional 3 h. The crude mixture
was purified by crystallization from diethyl ether and by flash
chromatography of the crystallization mother liquor to obtain 3d
as a white crystalline solid (691 mg, 70% yield). M.p. 86–88 °C.
lactone 3b solution to the Pd catalyst, the reaction mixture was
stirred at 50 °C for 5 h. Purification by flash chromatography on
silica gel (hexane/AcOEt, 9:1) afforded 2b as a light yellow oil
–
1 1
(74 mg, 71% yield). IR (CHCl
(CDCl , 200 MHz, 25 °C): δ = 0.08 [s, 9 H, Si(CH
= 9.3 Hz, J = 1.4 Hz, 2 H, CH SiMe ), 2.75–2.85 (m, 2 H,
CH CH O), 4.36 (t, J = 7.5 Hz, 2 H, CH O), 6.89 (dt, J = 9.3 Hz,
J = 16.9 Hz, J = 6.2 Hz, J = 2.0 Hz, 1 H, CHH-C=C), 3.46 (ddq, J = 2.8 Hz, 1 H, C=CH) ppm. C NMR (CDCl , 50 MHz, 25 °C):
J = 16.9 Hz, J = 8.2 Hz, J = 1.9 Hz, 1 H, CHH-C=C), 5.55 (dd, J δ = –1.4 [Si(CH ], 23.7 (CH SiMe ), 25.3 (CH CH O), 65.1
8.2 Hz, J = 6.2 Hz, 1 H, CHPh), 7.29–7.46 (m, 5 H, CHarom. (CH O), 122.1 (C-C=O), 139.7 (C=CH), 171.4 (C=O) ppm. R
), 0.45 (silica gel, hexane/AcOEt, 8:2). MS: m/z (%) = 184 (13.3)
3
): ν˜ max = 1755, 1690 cm . H NMR
3
3 3
)
], 1.73 (dt, J
–
1 1
IR (CHCl
3
): ν˜ max = 1752, 1695 cm . H NMR (CDCl
3
, 200 MHz,
), 2.96 (ddq,
2
3
25 °C): δ = 2.18 (dd, J = 1.9 Hz, J = 2.0 Hz, 3 H, CH
3
2
2
2
1
3
3
3
)
3
2
3
2
2
=
)
2
f
=
13
ppm. C NMR (CDCl
5.5(CH ), 77.2 (CHPh), 118.3 (C=C-OTf), 118.4 (q, J = 320 Hz, [M] , 73 (100). HRMS: calcd for C
CF ), 125.3 (CHarom.), 128.9 (CHarom.), 129.0 (CHarom.), 139.1 found 207.0825.
arom.), 149.5 (C-OTf), 165.1(C=O) ppm. R = 0.47 (silica gel, hex-
3 3
, 50 MHz, 25 °C): δ = 19.6 (CH
+
3
2
9 2
H16NaO Si [M] 207.0817;
3
(C
f
(
Z)-3-[1-Phenyl-2-(trimethylsilyl)ethylidene]dihydrofuran-2-one (2c):
+
ane/AcOEt, 7:3). MS: m/z (%) = 336 (0.3) [M] , 97 (100). HRMS:
This compound was prepared from 3b (322 mg, 1 mmol), according
to the procedure described for 2a. An excess of 4 equiv. of
calcd. for C13 NaO S [M] 359.0177; found 359.0183.
H
11
F
3
5
(
1Z)-1-(2-Oxo-4-phenyldihydrofuran-3-ylidene)ethyl Trifluorome-
thanesulfonate (3e): This compound was prepared from 4e (1.419 g,
.96 mmol), according to the procedure described for 3a. After the
3 2 3
(Me SiCH ) Al, generated in situ, was required for a good conver-
sion. After the addition of the triflate lactone 3c solution to the
0
6
Pd catalyst, the reaction mixture was stirred at 70 °C for 3 h. Puri-
addition of trifluoromethanesulfonic anhydride, the resulting solu-
tion was stirred at –78 °C for an additional 3 h. The crude mixture
was purified by crystallization from diethyl ether and by flash
chromatography of the crystallization mother liquor to obtain 3e
as a white crystalline solid (1.450 g, 62% yield). M.p. 124–126 °C.
fication by flash chromatography on silica gel (hexane/AcOEt, 9:1)
afforded 2c as a colourless oil (216 mg, 83% yield). IR (CHCl
3
):
, 200 MHz, 25 °C): δ =
], 2.77–3.09 (m, 4 H, CH CH O, CH SiMe ),
4.16–4.46 (m, 2 H, CH O), 7.27–7.64 (m, 5 H, CHarom.) ppm.
NMR (CDCl 50 MHz, 25 °C): –1.2 [Si(CH ], 26.9
(CH SiMe ), 29.6 (CH CH O), 64.6 (CH O), 116.1 (C=CPh),
.5 Hz, 1 H, CHPh), 7.20–7.44 (m, 5 H, CHarom.) ppm. 13C NMR 127.1 (CHarom.), 128.1(CHarom.), 128.3 (CHarom.), 142.8 (Carom.),
, 50 MHz, 25 °C): δ = 19.6 (CH ), 44.6 (CHPh), 72.7
155.9 (C=CPh), 171.2 (C=O) ppm. R = 0.70 (silica gel, hexane/
O), 118.3 (q, J = 320 Hz, CF
), 121.9 (C=C-OTf), 127.0 AcOEt, 8:2). MS: m/z (%) = 260 (36) [M] , 130 (100). HRMS:
CHarom.), 128.2 (CHarom.), 129.7 (CHarom.), 139.5 (Carom.), 152.8 calcd. for C15 20NaO Si [M] 283.1130; found 283.1140.
C-OTf), 165.6 (C=O) ppm. R = 0.25 (silica gel, hexane/AcOEt,
–
1 1
ν˜ max = 1750, 1685 cm . H NMR (CDCl
0.00 [s, 9 H, Si(CH
3
3
)
3
2
2
2
3
1
3
2
C
–1 1
IR (CHCl
2
8
3
): ν˜ max = 1751, 1692 cm . H NMR (CDCl
3
, 200 MHz,
3
,
δ
=
3 3
)
5 °C): δ = 1.90 (s, 3 H, CH ), 4.19–4.30 (m, 2 H, CH ), 4.72 (t, J =
3
2
2
3
2
2
2
(
(
(
(
CDCl
CH
3
3
f
+
2
3
H
2
f
(
Z)-3-[1-Methyl-2-(trimethylsilyl)ethylidene]-5-phenyldihydrofuran-
+
7
:3). MS: m/z (%) = 336 (0.5) [M] , 43 (100). HRMS: calcd. for
2-one (2d): This compound was prepared from 3d (202 mg,
13 11 3 5
C H F NaO S [M] 359.0177; found 359.0183.
0.6 mmol), according to the procedure described for 2a. Purifica-
tion by flash chromatography on silica gel (hexane/AcOEt, 9:1) af-
forded 2d as a light yellow oil (102 mg, 62% yield). IR (CHCl ):
, 200 MHz, 25 °C): δ =
], 1.84 (t, J = 1.4 Hz 3 H, C=C-CH ), 2.53 (dt,
J = 11.2 Hz, J = 1.4 Hz, 1 H, CHHSiMe ), 2.61 (dt, J = 11.2 Hz, J
1.4 Hz, 1 H, CHHSiMe ), 2.77 (m, 1 H, CHH), 3.31 (m, 1 H,
CHH), 5.42 (dd, J = 8.6 Hz, J = 6.4 Hz, 1 H, CHPh), 7.30–7.41
Synthesis of α-{[(Trimethylsilyl)methyl]alkylidene}-γ-butyrolactones
a–d
2
3
–
1 1
ν˜ max = 1748, 1688 cm . H NMR (CDCl
.08 [s, 9 H, Si(CH
3
(Z)-3-[1-Methyl-2-(trimethylsilyl)ethylidene]dihydrofuran-2-one (2a):
0
3
)
3
3
A solution of tris[(trimethylsilyl)methyl]aluminum was prepared by
adding [(trimethylsilyl)methyl]lithium (1.0  solution in pentane,
3
=
3
1
8.7 mL, 18.75 mmol) to a magnetically stirred suspension of AlCl
3
(834 mg, 6.25 mmol) in dry 1,2-dichloroethane (25 mL) under ar-
13
(
–
(
1
1
m, 5 H, CHarom.) ppm. C NMR (CDCl
0.9 [Si(CH ], 25.0 (C=C-CH ), 27.4 (CH
CH CH O), 76.3 (CHPh), 114.7 (C=C-CH ), 125.3 (CHarom.),
28.0 (CHarom.), 128.6 (CHarom.), 141.3 (Carom.), 154.7 (C=C-CH ),
70.3 (C=O) ppm. R = 0.59 (silica gel, hexane/AcOEt, 8:2). MS:
3
, 50 MHz, 25 °C): δ =
gon and at room temp. for 30 min. Triflate 3a (650 mg, 2.5 mmol)
in dry benzene (4 mL) was added under argon to a solution of
Pd(OAc) (50 mg, 0.22 mmol) and PPh (236 mg, 0.90 mmol) in
2 3
dry benzene (2 mL). The resulting mixture was immediately trans-
ferred by cannula into the tris[(trimethylsilyl)methyl]aluminum
solution and stirred at 50 °C for 4 h. The workup consisted of di-
3
)
3
3
2
SiMe ), 36.7
3
2
2
3
3
f
+
m/z (%) 274 (4.7) [M] , 73 (100). HRMS: calcd. for
=
C
16
H
22NaO Si [M] 297.1287; found 297.1292.
2
lution with CH
2
Cl
2
, washing with 0.2  HCl, H
2
O and brine. The
Representative Amination Procedures
combined organic extracts were dried (Na
2
SO ) and concentrated
4
under reduced pressure. Purification by flash chromatography on
silica gel afforded 2a as a light yellow oil (471 mg, 95% yield).
Method A: To a stirred solution of the silylated α-ylidene-γ-butyro-
lactone 2 (1 mmol) in CH Cl (1 mL), NsONHCO Et (290 mg,
1 mmol) and CaO (56 mg, 1 mmol) were added portionwise at
room temp. every hour, until the molar ratio of substrate/
2
2
2
–
1 1
IR (CHCl
2
3
): ν˜ max = 1755, 1690 cm . H NMR (CDCl
5 °C): δ = 0.08 [s, 9 H, Si(CH ], 1.87 (t, J = 1.4 Hz, 3 H, C=C-
), 2.54 (t, J = 1.4 Hz, 2 H, CH SiMe ), 2.88 (m, 2 H,
CH O), 4.29 (t, J = 7.7 Hz, 2 H, CH CH
, 50 MHz, 25 °C): δ = –1.0 [Si(CH
7.1 (CH SiMe ), 27.7 (CH CH O), 63.9 (CH
SiMe ), 167.1 (C=O) ppm. R
gel, hexane/AcOEt, 8:2). MS: m/z (%) = 198 (18.3) [M] , 73 (100).
HRMS: calcd. for C10 18NaO Si [M] 221.0974; found 221.0980.
3
, 200 MHz,
3 3
)
CH
CH
3
2
3
NsONHCO Et/CaO reported in Table 3 was reached. As the reac-
2
O) ppm. 13C NMR tion was exothermic, during every addition the flask was cooled in
2
2
2
2
(CDCl
3
3
)
3
], 25.0 (C=C-CH
3
),
2
an H O bath to avoid overheating. After the time reported in
2
2
3
2
2
2
CH O), 114.2 (C- Table 3, the reaction was quenched by adding a pentane/CH Cl
2
2
2
C=O), 154.1 (C-CH
2
3
f
= 0.52 (silica
solution (8:2). The resulting solid by-product was filtered and
+
washed with the same solution. The organic phase was concen-
trated under reduced pressure and dried (Na SO ). The crude mix-
H
2
2
4
ture was purified by HPLC chromatography (hexane/AcOEt, 8:2).
(E)-3-[2-(Trimethylsilyl)ethylidene]dihydrofuran-2-one (2b): This
compound was prepared from 3b (140 mg, 0.57 mmol), according
to the procedure described for 2a. After the addition of the triflate
Method B: To a stirred solution of the silylated α-ylidene-γ-butyro-
lactone 2 (1 mmol) in CH Cl (1 mL), NsONHCO Et (290 mg,
2 2 2
5080
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5076–5082

α-Amino-α-vinyl-γ-butyrolactone Derivatives
FULL PAPER
1
mmol) and CaO (56 mg, 1 mmol) were added portionwise at
room temp. every hour, until the molar ratio of substrate/
NsONHCO
tion was exothermic, during every addition the flask was cooled in
an H O bath to avoid overheating. After the time reported in
Table 3, the reaction was quenched by adding a pentane/CH Cl
ing to amination method B and purified by HPLC chromatography
(hexane/AcOEt, 8:2) to afford 1c as a colourless oil (159 mg, 55%
–
1
1
2
Et/CaO reported in Table 3 was reached. As the reac- yield). IR (CHCl
(CDCl , 200 MHz, 25 °C): δ = 1.23 (t, J = 7.1 Hz, 3 H, CH
2.61–2.80 (m, 1 H, CHHCH O), 2.89–3.16 (m, 1 H, CHHCH
3.80–4.00 (m, 1 H, CH CHHO), 4.11 (q, J = 7.1 Hz, 2 H,
CH CH ), 4.40 (m, 1 H, CH CHHO), 5.34 (br. s, 1 H, NH), 5.43
(s, 1 H, CH=CHH), 5.50 (s, 1 H, CH=CHH), 7.28–7.51 (m, 5 H,
3
): ν˜ max = 3430, 1770, 1722 cm . H NMR
CH ),
O),
3
3
2
2
2
2
2
2
2
solution (8:2). The resulting solid by-product was filtered and
washed with the same solution. The organic phase was concen-
trated under reduced pressure and stirred with AcOH (0.56 mL,
3
2
2
1
3
CHarom.) ppm. C NMR (CDCl
3
, 50 MHz, 25 °C): δ = 14.4
O), 61.4 (C-NH), 63.3 (CH CH ), 65.5
), 128.3(CHarom.), 128.4 (CHarom.), 128.5
), 155.1 (CO Et), 175.3
f
= 0.25 (silica gel, hexane/AcOEt, 7:3). MS:
1
0 mmol) for 48 h at room temp. The mixture was washed with
saturated NaHCO , extracted with CH Cl , and the combined or-
ganic phases were dried (Na SO ) and concentrated under reduced
(CH
3
CH
2
), 33.7 (CH
O), 118.2 (C=CH
(CHarom.), 137.7 (Carom.), 145.6 (C=CH
(lactone C=O) ppm. R
m/z (%) 275 (0.6) [M] , 202 (100). HRMS: calcd. for
17NNaO [M] 298.1055; found 298.1060.
2
CH
2
3
2
3
2
2
(CH
2
2
2
4
2
2
pressure. Reaction products were isolated by HPLC chromatog-
raphy (hexane/AcOEt, 8:2).
+
=
C
15
H
4
Ethyl (3-Isopropenyl-2-oxotetrahydrofuran-3yl)carbamate (1a) and
Ethyl {3-[1-Methyl-2-(trimethylsilyl)vinyl]-2-oxotetrahydrofuran-3-
yl}carbamate (5a): These compounds were prepared from 2a
Ethyl (3-Isopropenyl-2-oxo-5-phenyltetrahydrofuran-3-yl)carbamate
1d): This compound was prepared from 2d (96 mg, 0.35 mmol),
(
(198 mg, 1 mmol), according to amination method A. HPLC puri-
according to amination method B. Purification by HPLC
chromatography (hexane/AcOEt, 8:2) afforded 1d as a single dia-
fication (hexane/AcOEt, 8:2) afforded 1a (136 mg, 64% yield) and
5
a (29 mg, 10%) as colourless oils. 1a: IR (CHCl
3
): ν˜ max = 3430,
, 200 MHz, 25 °C): δ = 1.24 (t,
), 1.87 (s, 3 H, CH C=C), 2.69–2.93 (m,
O), 4.11 (q, J = 7.1 Hz, 2 H, CH CH ), 4.17–4.25
CHHO), 4.40–4.50 (m, 1 H, CH CHHO), 5.12–5.16
m, 2 H, C=CH
), 5.34 (br. s, 1 H, NH) ppm. 13C NMR (CDCl
0 MHz, 25 °C): δ = 14.4 (CH CH ), 18.5 (CH C=C), 33.2
CH CH O), 61.3 (C-NH), 63.1 (CH CH ), 65.8 (CH O), 114.9
), 139.7 (C=CH ), 155.2 (CO Et), 175.0 (lactone C=O)
= 0.09 (silica gel, hexane/AcOEt, 8:2). MS: m/z (%) = 213
stereomer (colourless oil, 52 mg, 52% yield). IR (CHCl
3
): ν˜ max
, 200 MHz, 25 °C): δ =
), 1.80 (dd, J = 1.4 Hz, J = 0.7 Hz,
C=C), 2.57 (dd, J = 14.0 Hz, J = 6.1 Hz, 1 H,
=
–1 1
1774, 1723 cm . H NMR (CDCl
3
–1 1
3
1
3
430, 1771, 1723 cm . H NMR (CDCl
.25 (t, J = 7.1 Hz, 3 H, CH CH
H, CH
3
J = 7.1 Hz, 3 H, CH
H, CH CH
m, 1 H, CH
3
CH
2
3
3
2
2
(
(
2
2
3
2
3
2
2
CHHCHPh), 3.31 (dd, J = 14.0 Hz, J = 8.6 Hz, 1 H, CHHCHPh),
.12 (q, J = 7.1 Hz, 2 H, CH CH ), 5.04 (q, J = 1.4 Hz, 1 H,
CHH=C), 5.09 (br. s, 1 H, CHH=C), 5.25 (br. s, 1 H, NH), 5.81
dd, J = 8.6 Hz, J = 6.1 Hz, 1 H, CHPh), 7.31–7.42 (m, 5 H,
2
3
,
4
3
2
5
3
2
3
(
(
2
2
3
2
2
(
C=CH
2
2
2
13
CHarom.) ppm. C NMR (CDCl
CH CH ), 19.0 (CH =CCH ), 40.8 (CH
4.4 (CH CH O), 78.2 (CHPh), 115.2 (C=CH
28.2 (CHarom.), 128.7 (CHarom.), 139.7 (Carom.), 141.3 (C=CH
55.7 (CO Et), 174.9 (lactone C=O.) ppm. R
3
, 50 MHz, 25 °C): δ = 14.5
ppm. R
f
(
3
2
2
3
2
CH
2
O), 61.6 (CH
3
CH
2
),
+
(
2
1
2.3) [M] , 96 (100). HRMS: calcd. for C10
H
15NNaO
): ν˜ max = 3430, 1772,
, 200 MHz, 25 °C): δ = 0.13 [s, 9 H,
], 1.24 (t, J = 7.1 Hz, 3 H, CH CH ), 1.92 (s, 3 H,
C=C), 2.61–2.97 (m, 2 H, CH CH O), 4.11 (q, J = 7.1 Hz, 2
H, CH CH ), 4.16 (t, J = 8.8 Hz, 1 H, CHHO), 4.43 (t, J = 8.9 Hz,
H, CHHO), 5.28 (s, 1 H, NH), 5.61 (s, 1 H, C=CH) ppm.
4
[M]
6
1
1
2
2
2
), 125.2 (CHarom.),
36.0899; found 236.0904. 5a: IR (CHCl
3
2
),
–1 1
719 cm . H NMR (CDCl
3
2
f
= 0.19 (silica gel,
Si(CH
CH
3
)
3
3
2
+
hexane/AcOEt, 7:3). MS: m/z (%) = 289 (0.9) [M] , 216 (100).
HRMS: calcd. for C16 19NNaO [M] 312.1212; found 312.1220.
3
2
2
H
4
3
2
1
3
1
C
NMR (CDCl
CH CH ), 17.4 (CH
5.6 (CH
CO Et), 175.4 (lactone C=O) ppm. R
3
,
50 MHz, 25 °C):
δ
=
–0.3 [Si(CH
3
)
3
], 14.6 Acknowledgments
(
6
(
3
2
3
C=C), 33.1 (CH
2
CH O), 61.2 (CH CH ),
2
3 2
2
O), 98.0 (C-NH), 128.3 (C=CH), 146.8 (C=CH), 155.2
= 0.16 (silica gel, hexane/
We thank the Italian Ministero dell’Istruzione dell’Università e
della Ricerca (MIUR), and the University “La Sapienza” of Rome
2
f
+
AcOEt, 8:2). MS: m/z (%) = 285 (2.6) [M] , 73 (100). HRMS: calcd. (National Project “Stereoselezione in Sintesi Organica. Metodolo-
for C13 23NNaO Si [M] 308.1294; found 308.1290. Compound 1a
gie ed Applicazioni”) for financial support.
H
4
was also prepared from 2a (198 mg, 1 mmol), according to amin-
ation method B. Purification by HPLC chromatography (hexane/
AcOEt, 8:2) afforded 1a as a colourless oil (155 mg, 73% yield).
[
1] a) D. Ma, W. Zhu, J. Org. Chem. 2001, 66, 348–350; b) R.
Cannella, F. Clerici, M. L. Gelmi, M. Penso, D. Pocar, J. Org.
Chem. 1996, 61, 1854–1856; c) U. Kazmaier, Tetrahedron Lett.
1996, 37, 5351–5354.
Ethyl (2-Oxo-3-vinyltetrahydrofuran-3-yl)carbamate (1b): This com-
pound was prepared from 2b (74 mg, 0.4 mmol), according to am-
ination method B and purified by HPLC chromatography (hexane/
AcOEt, 8:2) to give 1b as a colourless oil (56 mg, 70% yield). IR
[2] S. J. deSolms, E. A. Giuliani, S. L. Graham, K. S. Koblan,
N. E. Kohl, S. D. Mosser, A. I. Oliff, D. L. Pompiliano, E.
Rands, T. H. Scholz, C. M. Wiscount, J. B. Gibbs, R. L. Smith,
J. Med. Chem. 1998, 41, 2651–2656.
–1
1
(
2
2
CHCl
3
): ν˜ max = 3430, 1774, 1720 cm . H NMR (CDCl
00 MHz, 25 °C): δ = 1.25 (t, J = 7.1 Hz, 3 H, CH CH ), 2.63–
.88 (m, 2 H, CH CH O), 4.12 (q, J = 7.1 Hz, 2 H, CH CH ), 4.22
3
,
3
2
[
3] a) Z.-Q. Luo, S. Su, S. K. Farrand, J. Bacteriol. 2003, 185,
665–5672; b) J. A. Olsen, R. Severinsen, T. B. Rasmussen, M.
Hentzer, M. Givskov, J. Nielsen, Bioorg. Med. Chem. Lett.
2
2
3
2
5
(
5
(
t, J = 8.5 Hz, 1 H, CHHO), 4.48 (t, J = 8.5 Hz, 1 H, CHHO),
.25 (br. s, 1 H, NH), 5.40 (d, J = 10.4 Hz, 1 H, CH=CHH), 5.40
d, J = 17.4 Hz, 1 H, CH=CHH), 5.97 (dd, J = 10.4 Hz, J =
2002, 12, 325–328.
[
4] M. L. Pedersen, D. B. Berkowitz, J. Org. Chem. 1993, 58, 6966–
1
2
7.4 Hz, 1 H, CH=CHH) ppm. 13C NMR (CDCl
5 °C): δ = 14.4 (CH CH ), 34.3 (CH CH
CH ), 65.5 (CH O), 118.1 (CH=CH
55.1 (CO Et), 175.1 (lactone C=O) ppm. R
3
, 50 MHz,
6975.
O), 60.7 (C-NH), 61.3 [5] A. B. Smith, III, H. Liu, R. Hirschmann, Org. Lett. 2000, 2,
3
2
2
2
(CH
3
2
2
2
), 133.6 (CH=CH
2
),
2037–2040.
[
6] a) T. Gasperi, M. A. Loreto, P. A. Tardella, E. Veri, Tetrahe-
dron Lett. 2003, 44, 4953–4956; b) T. Gasperi, M. A. Loreto,
A. Migliorini, P. A. Tardella, Heterocycles 2005, 65, 1447–1454.
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1
2
f
= 0.32 (silica gel,
+
hexane/AcOEt, 7:3). MS: m/z (%) = 199 (2.3) [M] , 82 (100).
HRMS: calcd. for C 13NNaO [M] 222.0742; found 222.0746.
9
H
4
[
Ethyl [2-Oxo-3-(1-phenylvinyl)tetrahydrofuran-3-yl]carbamate (1c):
This compound was prepared from 2c (208 mg, 0.8 mmol), accord-
Eur. J. Org. Chem. 2006, 5076–5082
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5081

M. Capuzzi, A. Gambacorta, T. Gasperi, M. A. Loreto, P. A. Tardella
FULL PAPER
8
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[
7c]
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Received: June 21, 2006
Published Online: September 7, 2006
5082
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 5076–5082