Epoxidation of 4-alkylidenecyclopentenones: A route to the 1-oxaspiro[2.4]hept-6-en-5-one framework

Article abstract of DOI:10.1002/ejoc.201201030

Thanks to their lack of polarity, the exocyclic double bonds of 4-alkylidenecyclopentenones 4 are selectively epoxidized by MCPBA to give spiroepoxycyclopentenones 7, which feature the nonclassical 1-oxaspiro[2.4]hept- 6-en-5-one framework. Under acidic c

Full text of DOI:10.1002/ejoc.201201030

FULL PAPER
DOI: 10.1002/ejoc.201201030
Epoxidation of 4-Alkylidenecyclopentenones: A Route to the
1-Oxaspiro[2.4]hept-6-en-5-one Framework
Mohammed Ahmar,[a] Stéphane Thomé,[a] and Bernard Cazes*[a]
Keywords: Synthetic methods / Epoxidation / Spiro compounds
Thanks to their lack of polarity, the exocyclic double bonds
work. Under acidic conditions, compounds 7 undergo ring-
of 4-alkylidenecyclopentenones 4 are selectively epoxidized
opening to afford 4-hydroxy-4-(1-hydroxyalkyl)cyclopen-
by MCPBA to give spiroepoxycyclopentenones 7, which fea- tenones 10.
ture the nonclassical 1-oxaspiro[2.4]hept-6-en-5-one frame-
Introduction
4-Alkylidenecyclopentenones are rare unsaturated cyclic
enones, the chemistry of which has been only little studied,
unquestionably because of their very small number of syn-
thesis procedures.[1] We recently developed a straightfor-
ward route to these cyclopentenones 4 (Scheme 1), as well
as the cyclopentenone minor products 5 and 6, through co-
balt-mediated intermolecular Pauson–Khand reactions
(PKRs) between alkynes 1 and allenes 3.[2,3] Consequently,
studies on their chemical reactivities and potential utility
became possible.[4,5]
In another context, the 1-oxaspiro[2.4]hept-6-en-5-one
(spiroepoxycyclopentenone) framework forms the struc-
tural core of several natural products such as strepta-
zone A[6] and guaianolides related to cyclotagitinin C[7] or
arborescin,[8] and also of an antitumor agent.[9] Spiroepoxy-
cyclopentenones are also useful intermediates for the syn-
thesis of plant-derived leads for drug discovery.[10] Conse-
quently, we focused our attention on the epoxidation of the
Scheme 1. Pauson–Khand reactions of allenic compounds.
doubly unsaturated systems of 4-alkylidenecyclopentenones
4. Basic epoxidation conditions (H2O2 + NaOH), as classi-
cally used for enones,[11] were inappropriate for these cyclo-
pentenones 4, which turned out to be very sensitive to basic
media because of their very easy enolisation.[4] Epoxidation
of α,β-enones with peroxy acids is often difficult because
competitive Baeyer–Villiger oxidation leads mostly to enol
esters and acyloxyoxiranes.[12] However, the exocyclic
double bonds in 4-alkylidenecyclopentenones 4 did not ap-
pear to be polarized, with poor conjugation with the α,β-
double bonds. Indeed, analysis of the 13C NMR spectra of
these compounds showed the chemical shifts of the carbon
atoms of these exocyclic double bonds to be very close to-
gether.[2c,5] Consequently, because of the differences in po-
larity between the two double bond types, the selective
epoxidation of the exocyclic double bonds in cyclopen-
tenones 4 by use of peroxy acids seemed possible. We had
already disclosed in a preliminary note that treatment of
4-alkylidenecyclopentenones 4 with a peracid does lead to
spiroepoxycyclopentenones 7 (Scheme 1),[5] and not to enol
lactones 8 as previously published.[13] These methodologies
(PKRs of allenes, selective epoxidation) might represent
valuable synthetic transformations for the preparation of
cyclopentanoid natural products,[6–10,14] or for the synthesis
of functionalized butenolide-type steroidal systems, which
are of great medicinal therapeutic potential.[15] We therefore
report here a full account of the selective epoxidation of the
[a] Université LYON 1, CNRS UMR 5246-ICBMS, Laboratoire
COSMO, Bât. Curien,
43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France
E-mail: bj.cazes@gmail.com
Homepage: http://www.icbms.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201030
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exocyclic double bonds in cyclopentenones 4 and the acid- the silicon atom has been demonstrated to induce a negative
catalyzed ring-opening of the obtained spiro compounds 7, γ-effect.[17] The shielding positive cis γ-effect of the allylic
which leads to dihydroxylated cyclopentenones 10 (Table 3). methyl group (C-4)=C(CH3)SiX(CH3)2 is now more influ-
ential for the chemical shifts of both C-3 and C-5, so signal
of C-5 of cyclopentenones (E)-4l and (E)-4m (δ = 40.9 and
Results and Discussion
41.1 ppm, respectively) is observed downfield, whereas for
isomers (Z)-4l and (Z)-4m it is found upfield (δ = 39.1 and
39.4 ppm). Similarly, the C-3 carbon atoms are shielded in
cyclopentenones (E)-4l and (E)-4m, because of the positive
γ-effect of the allylic methyl group, and deshielded in iso-
mers (Z)-4l and (Z)-4m (Figure 1).
Synthesis of 4-Alkylidenecyclopentenones
We have already described most of the starting 4-alkyl-
idenecyclopentenones 4 (and 5) used in this study.[2c] Some
new ones were prepared by the same Pauson–Khand meth-
odology. In particular, the functionalized 4-alkylidenecyclo-
pentenones 4j–m (shown in Table 2, below) were obtained
as (E + Z) mixtures through PKRs between acetylene and
the α-allenic alcohol 3d (further acetylation of cyclopen-
tenone 4i gave 4j) or the silylated allenes 3c, 3e and 3f.
Previously, the E or Z configurations of the alkyl-substi-
tuted 4-alkylidenecyclopentenones 4 had been easily as-
signed by comparison of the 13C NMR spectra of the two
isomers, with both their C-3 and their C-5 carbon nuclei
depending on the configurations of the exocyclic double
bonds.[2c] Thus, for the new cyclopentenone 4k (Figure 1),
the C-5 carbon of isomer (E)-4k resonates at high field (δ
= 37.6 ppm) relative to the analogous C signal of isomer
(Z)-4k (δ = 40.5 ppm) because of the shielding due to a
positive cis γ-effect from the allylic carbon atom (C-4)=C–
CH2.[2c,16] A similar shielding effect is observed for the C-3
(δ = 154.9 ppm) of the isomer (Z)-4k, whereas for isomer
(E)-4k this C-3 signal is shifted downfield (δ = 160.9 ppm)
.
Epoxidation of 4-Alkylidenecyclopentenones 4
The 4-alkylidenecyclopentenones 4 (and 5) were each
treated with two equivalents of meta-chloroperbenzoic acid
(MCPBA) under classical conditions in toluene at 0–20 °C.
They all gave 7 or 9 (Table 1) with unoptimized 50–86%
yields. As would be expected, the (E)-4-alkylidenecyclopen-
tenones (E)-4c–h gave trans-7c–h (Entries 3–8) whereas the
cyclopentenone (Z)-4h afforded cis-7h (Entry 9). The 5-
alkyl-substituted cyclopentenone 5h furnished a 90:10 mix-
ture of the two isomers trans-9i and cis-9i (Entry 10). As
anticipated, the epoxidation mainly occurred on the less
hindered side of the exocyclic double bond, anti to the hexyl
group at C-5.
We next looked at the epoxidation of functionalized 4-
alkylidenecyclopentenones 4j–m (Table 2). They gave the
corresponding spiroepoxycyclopentenones 7j–m as trans +
cis mixtures of isomers with trans/cis ratios similar to the
E/Z ratios of the starting cyclopentenones (Entries 1–4).
Structures and Stereochemical Assignments of
Spiroepoxycyclopentenones 7
The chemical structures of compounds 7 had to be eluci-
dated. The literature had provided one example of a reac-
tion between a peracid and an 4-alkylidenecyclopentenone:
cyclopentenone 4j (Scheme 2) was reported to afford the
enol lactone 8j resulting from a Baeyer–Villiger reaction.[13]
1
The published IR and H NMR spectroscopic data for
this compound 8j do not, however, fit an enol lactone struc-
ture such as the model lactone 8n (Figure 2), also found in
the literature.[18] Compounds 7j and 8j displayed similar IR
absorptions [7j: 1718 (C=O acetate) and 1685 cm–1 (C=O
ketone); 8j: 1722 cm–1], whereas the enol lactone 8n showed
an absorption at 1755 cm–1. A comparison of the 1H NMR
spectroscopic data for 7j and for the enol lactones 8j (sup-
posed) and 8n is provided in Figure 2. There is a significant
discrepancy between the NMR spectroscopic data pub-
lished for compound 8j and those for the model enol lac-
tone 8n. In particular, the chemical shifts corresponding to
the vinylic protons of compound 8j, at δ = 6.43 and
7.34 ppm, are inconsistent with an enol ester function, and
the triplet (δ = 2.69 ppm) and quartet (δ = 4.24 ppm) corre-
Figure 1. 13C NMR data for cyclopentenones (E)- and (Z)-4k–m.
A reverse situation is observed with the silylated cyclo- sponding to the CH2 groups are unrealistic. In contrast,
pentenones (E)- and (Z)-4l and (E)- and (Z)-4m, because these data [chemical shifts and coupling constants (J)], ex-
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Epoxidation of 4-Alkylidenecyclopentenones
Table 1. Epoxidation of 4-alkylidenecyclopentenones 4–5.
Table 2. Epoxidation of functionalized 4-alkylidenecyclopen-
tenones 4.
[a] Epoxidations were carried out with MCPBA (2 equiv.) in tolu-
ene at 0–20 °C on 1–5 mmol scales. [b] trans/cis ratios were deter-
1
mined from H NMR spectra. [c] Yields of isolated epoxides (mix-
tures of trans + cis stereoisomers) after flash chromatography, ex-
cept for 7m, for which the cis and trans stereoisomers were sepa-
rated.
Scheme 2. Reported reaction between MCPBA and 4-alkylidenecy-
clopentenone 4j.
lactone had been given erroneously to compound 8j and
that it should in fact be considered identical with 7j.
With regard to the 13C NMR spectra of compounds 7a–
m, the chemical shifts of the five carbon atoms (C-n) of the
cyclopentenone rings and the carbon atoms of the epoxy
[a] Epoxidation reactions were carried out with MCPBA (2 equiv.)
in toluene at 0–20 °C on 1–5 mmol scales. [b] Yields of isolated
product(s) after flash chromatography. [c] Ratio of isomers was ob-
1
tained by H NMR spectroscopy.
cept for the given multiplicities, match those for our com- functions are consistent for the proposed spiro structures 7.
pound 7j. We thus concluded that the structure of an enol Treatment of 4-alkylidenecyclopentenones 4 with MCPBA
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dominating positive cis γ-effect of the C(CH3)SiX(CH3)2
methyl groups. The C-5 carbon atoms of trans-7l and trans-
7m are deshielded, whereas those of stereoisomers cis-7l
and cis-7m are shifted upfield. Similarly, the C-3 carbon
atoms are deshielded for cis-7l and cis-7m but shifted up-
field for trans-7l and trans-7m (Figure 4).
1
Figure 2. Comparison of the H NMR spectra for structures 7j, 8j
and 8n.
does therefore indeed result in the selective epoxidation of
their exocyclic double bonds.
Figure 4. 13C NMR data for trans- and cis-7l and trans- and cis-
7m.
The trans or cis configuration of the epoxide function of
7 is the result of the E or Z configuration in the original 4-
alkylidenecyclopentenone 4. As in the parent cyclopen-
tenones (E)- and (Z)-4, however, the two isomers trans- and
cis-7 can easily be recognized thanks to their different 13C
NMR spectra. In particular, the C-5 signals of trans-7h and
trans-7k are shifted upfield (δ = 37.9 and 37.5 ppm, respec-
tively, Figure 3) because of the positive cis γ-effects of the
first methylene groups of the R substituents, whereas for
isomers cis-7h and cis-7k they are shifted downfield (δ =
39.8 and 40.9 ppm, respectively, Δ = 2–3 ppm). Alterna-
tively, the C-3 signals are shifted downfield for trans-7h and
trans-7k and upfield for isomers cis-7h and cis-7k.
Acid-Catalyzed Ring-Opening of
Spiroepoxycyclopentenones 7
Epoxides are valuable synthetic intermediates, due to
their reactivity with numerous reagents to give addition
products.[19] Ring-opening of 7 was thus expected to give
interesting dihydroxylated cyclopentenones 10 (Table 3), the
structures of which are related to several natural products
such as pentenocine B, an interleukine inhibitor.[20] We
therefore examined the ring-opening of 7 under acidic con-
ditions as reported in Table 3. Compounds 7 reacted with
sulfuric acid (0.75 m) to give the 4-hydroxy-4-(1-hy-
droxyalkyl)cyclopentenones 10. Spiroepoxycyclopentenone
7b gave the dihydroxylated cyclopentenone 10b (Table 3,
Entry 1). The cyclopentenones (E)-7c and (E)-7d both af-
forded mixtures of the two syn and anti diastereomers of
dihydroxylated cyclopentenones 10c and 10d, respectively.
The diastereomers anti-10c and anti-10d were the major
ones in both cases (Entries 2 and 3). The phenyl-substituted
compound 7e did not react under the above conditions, un-
doubtedly because of its low solubility. However, addition
of a solvent such as tBuOH or THF allowed the ring-open-
ing of the epoxide bridge to occur (Entries 4 and 5). The
diastereoselectivity was then dependent on the nature of
this solvent. The diastereomer anti-10e was still the major
diastereomer produced when the reaction was carried out
with added tBuOH, but an equal mixture of syn- and anti-
10e diastereomers was obtained when THF was added.
In order to determine the configurations of the major
Figure 3. 13C NMR data for spiroepoxycyclopentenones trans and
cis-7h and trans and cis-7k.
The cases of the silylated compounds trans- and cis-7l
and trans- and cis-7m (Figure 4) are also worth some com- diastereomers 10c–e, these diastereomers were transformed
ment. As in the cases of the parent silylated cyclopen- into the cyclic acetals 11c–e (Scheme 3), with which several
tenones (E)- and (Z)-4l and (E)- and (Z)-4m, opposite NOE 1D NMR experiments were carried out. With acetal
chemical shifts are observed for C-3 and C-5, because of 11c, irradiation of the diastereomeric proton Ha of the
the above-mentioned negative γ-effect of silicon and the methylene (C-5)H2 group at δ = 2.94 ppm (d, part A of an
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Epoxidation of 4-Alkylidenecyclopentenones
Table 3. Acid-catalyzed ring-opening of spiroepoxycyclopentenones 7.
[a] Yields of isolated products after flash chromatography. [b] Reaction carried out with added tBuOH. [c] The reaction was carried out
with added THF. [d] syn/anti ratios were obtained from isolated pure diastereomers syn- and anti-10c–e.
AB system, 2J = 18.3 Hz) resulted in the enhancement
(21%) of proton Hb (δ = 2.53 ppm, part B of an AB system,
2J = 18.3 Hz) together with a small increase (0.5%) for the
acetal proton Hd at δ = 6.00 ppm (Figure 5). This irradia-
tion had no effect on the dioxolane proton Hc, which is too
far away. On the other hand, irradiation of the dia-
stereomeric proton Hb (δ = 2.53 ppm) resulted in the en-
hancement (21%) of proton Ha (δ = 2.94 ppm) and of the
dioxolane proton Hc (6.3%) at δ = 4.14 ppm (dd, 3J =
Scheme 3. Synthesis of acetals 11c–e from the major diastereomers
3.4 Hz and 3J = 9.0 Hz). From these two NMR experiments
of dihydroxylated cyclopentenones 10c–e.
we can infer that the methylene (C-5)H2 group and the Hc
proton of acetal 11c are cis, so that the (C-5)H2/nC6H13
relationship for this acetal 11c is trans (trans-11c). Had such
For acetals 11d and 11e, irradiation of proton Hc (at δ =
a NOE experiment been performed with the other dia- 4.15 and 5.40 ppm, respectively) resulted in the enhance-
stereomer of acetal 11c (cis-11c), the signal of proton Hc ment of both protons Hb and Hd (Figure 6), which also
would not have been increased. Consequently, the relative confirms the anti relationships of the two OH groups of the
stereochemistry of the two hydroxy groups of the major dia- major dihydroxylated cyclopentenone products anti-10c and
stereomer 10c is anti.
anti-10d.
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M. Ahmar, S. Thomé, B. Cazes
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group, which should stabilize the carbocation 13, which
would explain why 7e (R = Ph) gave an about equal mixture
of syn- and anti-dihydroxylated cyclopentenones 10e.
Conclusions
In summary, this study demonstrates that epoxidation of
4-alkylidenecyclopentenones 4 occurs regioselectively on
their exocyclic double bonds to afford spiroepoxycyclopen-
tenones 7. The acidic ring-opening of these epoxides dia-
stereoselectively gives dihydroxylated cyclopentenones 10,
which might be interesting dihydroxylated synthons for the
synthesis of cyclopentanoid targets.[14]
Figure 5. NOE 1D experiments (500 MHz) with acetal trans-11c.
Experimental Section
General: All reactions were carried out under nitrogen in oven-
dried glassware with use of standard syringe, cannula and septa
techniques. Tetrahydrofuran was distilled from deep-purple so-
dium-benzophenone dianion and stored under nitrogen. Dichloro-
methane was distilled from calcium hydride and stored under nitro-
gen. Thin-layer chromatography (TLC) was performed with pre-
coated Kieselgel 60 F254 plates (Merck). Detection was achieved by
UV (254 nm) followed by charring with p-anisaldehyde (4%), acetic
acid (5%) and sulfuric acid (5%) in ethanol (86%). Flash
chromatography was performed on silica gel 60 (40–63 μm, Merck)
by Still’s procedure.[21] IR spectra were recorded with a Perkin–
Elmer 298 spectrophotometer or a Perkin–Elmer Spectrum One
FT-IR instrument; they were recorded from thin films on NaCl
plates for oils or from KBr discs for solids. 1H and 13C NMR spec-
tra were recorded at 300 MHz and 75 MHz, respectively, with
Bruker DRX 300 or ALS 300 instruments. NOE 1D experiments
were recorded at 500 MHz with a Bruker DRX 500 instrument. 1H
NMR chemical shifts were measured in CDCl3 and are reported
in ppm relative to the solvent shift of residual chloroform at δ =
7.26 ppm. Multiplicities are described as s (singlet), d (doublet), dd,
ddd, etc. (doublet of doublets, doublet of doublets of doublets,
etc.), t (triplet), q (quartet), m (multiplet), and further qualified as
br (broad), app (apparent); coupling constants (nJ) are reported in
Hz. 13C NMR chemical shifts were obtained in CDCl3 and are
reported in ppm relative to CHCl3 at δ = 77.16 ppm. All the car-
bons were assigned with the aid of Dept 135 experiments. Low-
and high-resolution mass spectra were obtained with a ThermoFin-
nigan MAT 95 XL spectrometer in the Electron Impact (EI, ioniza-
tion potential of 70 eV) mode or Chemical Ionisation (CI, isobut-
ane as the reagent gas) modes. Low-resolution mass spectra were
also obtained with the ElectroSpray Ionisation (ESI) mode and
a ThermoFinnigan LCQ Advantage spectrometer. GC–MS were
obtained with a Focus DSQ ThermoElectron spectrometer. Micro-
analyses were carried out by the “Service Central d’analyse du
CNRS”, Solaize, France. Melting points (m.p.s) were not corrected.
PE refers to petroleum ether with a boiling range of 40–60 °C.
Figure 6. NOE 1D experiments (500 MHz) with acetals trans-11d
and trans-11e.
From a mechanistic point of view, the major dia-
stereomers anti-10c and anti-10d should mainly be the re-
sults of favoured SN2 ring-opening of the protonated epox-
ide bridges of cations 12 (Scheme 4), whereas syn-10c and
syn-10d should be produced from carbocations 13 through
SN1 substitution reactions. This last substitution route
should be more significant when the R group is a phenyl
Starting Materials: Octacarbonyldicobalt was purchased from
Strem Chemicals, Inc. as a solid stabilized with hexane (1–5%). It
was used as received and stored under nitrogen at 0 °C. Acetylene
(1a, dissolved) was purchased from Air Liquide. But-2-yne (1b),
hex-3-yne (1c) and 3-(trimethylsilyl)buta-1,2-diene (3e) were com-
mercially available from Aldrich. 3-Methylbuta-1,2-diene (3a),[22]
phenylallene (3b),[23] 4-(trimethylsilyl)buta-1,2-diene (3c)[24] and 2-
methylbuta-2,3-dien-1-ol (3d)[25] were prepared as reported in the
literature.
Scheme 4. Ring-opening mechanism for spiroepoxycyclopen-
tenones.
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Epoxidation of 4-Alkylidenecyclopentenones
3-[Dimethyl(phenyl)silyl]buta-1,2-diene (3f): A solution of 1-(tosyl- the cobalt clusters. The crude product was purified by flash
oxy)but-2-yne (11 g, 49 mmol) in THF (20 mL) was added drop-
wise under nitrogen at –30 °C to a solution of dimethyl(phenyl)silyl
cuprate, previously prepared at –10 °C from a THF solution of
dimethyl(phenyl)silyllithium (1.1 m, 150 mL) and a suspension of
copper cyanide (6.6 g, 73 mmol) in THF (50 mL).[26] After having
been stirred at –30 °C for 1 h, the mixture was allowed to warm
to room temperature. The reaction mixture was quenched with a
saturated ammonium chloride solution (70 mL), and extracted with
diethyl ether (3ϫ 60 mL). The combined organic extracts were
dried (Na2SO4) and concentrated under reduced pressure. Purifica-
tion by distillation gave allene 3f (4.1 g, 31%) containing disilane
Me2PhSi–SiPhMe2 (about 5 mol-%), which can be recognized by
chromatography (PE/Et2O mixtures as eluents) to afford the corre-
sponding 4-alkylidenecyclopentenone 4.
4-Isopropylidene-2,3-dimethylcyclopent-2-enone (4a): The cycload-
dition between (but-2-yne)dicobalthexacarbonyl complex (2b,
605 mg, 1.78 mmol) and 3-methylbuta-1,2-diene (3a, 332 mg,
2.67 mmol) by the General Procedure, promoted by NMO (1.251 g,
10.68 mmol) in CH2Cl2/THF (1:1, 10 mL), gave the cyclopentenone
4a (283 mg, 77%) after flash chromatography (PE/Et2O 90:10). Yel-
1
low oil; Rf = 0.33 (PE/Et2O 50:50). H NMR (CDCl3, 300 MHz):
δ = 2.90 (s, 2 H, 5-H), 2.27 [s, 3 H, (C-3)CH3], 2.06 [s, 3 H, (C-
4)=CCH3-trans], 1.83 [s, 3 H, (C-4)=CCH3-cis], 1.77 [s, 3 H, (C-2)-
CH3] ppm. 13C NMR (CDCl3, 75 MHz): δ = 204.6 (C-1, C=O),
163.7 [C-3, C=C(C=O)], 139.7 [C-2, C=C(C=O)], 130.8 and 130.5
[2ϫ Cq, C-4 and (C-4)=Cq], 40.7 [C-5, (C=O)CH2], 24.9 [(C-
1
its H and 13C NMR spectra and GC–MS analysis.[27]
Compound 3f: Colourless liquid, b.p. 65 °C (14 Torr). 1H NMR
(300 MHz, CDCl3): δ = 7.54 (m, 2 H, Har), 7.3 (m, 3 H, Har), 4.34 4)=C(CH3-cis)], 21.3 [(C-4)=C(CH3-trans)], 17.2 [(C-3)CH3], 8.2 [(C-
5
5
(q, J = 3.2 Hz, 2 H, H2C=C=C), 1.67 (t, J = 3.2 Hz, 3 H, CH3), 2)CH3] ppm. IR (thin film): ν˜ = 2970, 2910, 2850, 1685 (C=O),
0.38 (s, 6 H, 2ϫ SiCH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
1640, 1390, 1340, 1280, 1200, 945, 770, 670 cm–1. MS (EI): m/z (%)
210.0 (C=C=C), 137.9 [Cq, C(Ph)i], 133.9 [2ϫ CH(Ph)o], 129.4 = 150 (71) [M]+, 135 (11) [M – CH3]+, 122 (29), 107 (65), 91 (20),
[CH(Ph)p], 127.9 [2ϫ CH(Ph)m], 88.2 [C=C=C(Si)], 68.0 79 (26), 77 (19), 65 (17), 53 (43), 51 (32), 41 (67), 39 (100), 28 (58),
(H2C=C=C), 15.7 [C=C=C(Si)CH3], –3.3 [2ϫ SiCH3] ppm. IR 27 (50). C10H14O (150.22): calcd. C 79.96, H 9.39; found C 79.99,
(thin film): ν = 1960 (allene), 1225(SiMe), 1105(SiPh) cm–1. GC–
H 9.23.
˜
MS (EI): m/z (%) = 188 (12) [M]+, 173 (7) [M – CH3]+, 135 (100)
[SiPh(CH3)2]+, 105 (11). HRMS (EI): calcd. for C12H16Si [M]+
188.1021; found 188.1030.
(E)-4-Benzylidene-2,3-diethylcyclopent-2-enone (4e): The cycload-
dition between (hex-3-yne)hexacarbonyldicobalt complex (2c,
13.1 g, 35.6 mmol) and phenylallene (3b, 4.96 g, 42.7 mmol) by the
General Procedure, promoted by NMO (13.1 g, 35.61 mmol) in
CH2Cl2/THF (1:1), gave the cyclopentenone (E)-4e (3.4 g, 35%)
after flash chromatography (PE/Et2O 85:15). Yellow solid; m.p.
1,2-Dimethyl-1,2-diphenyldisilane:[25] 1H NMR (300 MHz, CDCl3):
δ = 7.53–7.56 (m, 4 H, Har), 7.38 (m, 6 H, Har), 0.34 (s, 12 H, 4ϫ
SiCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 139.9 [2ϫ C(Ph)i],
133.1 [4ϫ CH(Ph)o], 129.4 [2ϫ CH(Ph)p], 129.3 [4ϫ CH(Ph)m],
1.0 [4ϫ SiCH3] ppm. GC–MS (EI): m/z (%) = 270 (9) [M]+, 255
(2) [M – CH3]+, 197 (14), 135 (100) [SiPh(CH3)2]+, 105 (6).
1
95 °C; Rf = 0.33 (PE/Et2O 80:20). H NMR (300 MHz, CDCl3): δ
= 7.43 (m, 5 H, Har), 6.67 [s, 1 H, (C-4)=CH], 3.26 (s, 2 H, 5-H),
2.68 [q, 3J = 7.5 Hz, 2 H, (C-3)CH2], 2.36 [q, 3J = 7.5 Hz, 2 H, (C-
3
3
2)CH2], 1.25 (t, J = 7.5 Hz, 3 H, CH3), 1.10 (t, J = 7.5 Hz, 3 H,
CH3) ppm. 13C NMR (75 Mz, CDCl3): δ = 205.4 (C-1, C=O), 169.5
(C-3), 136.9 (C-2), 136.2 [2ϫ Cq, C-4 and C(Ph)i], 129.0 and 128.8
[2ϫ CH(Ph)o and 2ϫ CH(Ph)m], 127.7 [CH(Ph)p], 123.3 [(C-
4)=CH(Ph)], 40.0 (C-5), 19.8 [(C-3)CH2], 17.4 [(C-2)CH2], 14.5
Synthesis of 4-Alkylidenecyclopentenones 4 and 5: Cyclopentenones
4b–d, 4g, 4h and 5h, prepared by our PKR methodology, are al-
ready described.[2c] New cyclopentenones 4a, 4e, 4f and 4i–m were
similarly synthesized as follows.
Synthesis of 4-Alkylidenecyclopentenones 4
(CH ), 13.9 (CH ) ppm. IR (KBr): ν = 3060, 2960, 2930, 2870,
˜
3
3
1680, 1600, 1450, 755, 690 cm–1. MS (EI): m/z (%) = 226 (100)
[M]+, 211 (55) [M – CH3]+, 197 (27), 169 (27), 141 (17), 115 (16),
91 (11).
General Procedure for the Preparation of (Alkyne)hexacarbonyldico-
balt Complexes 2a–c:[2c] An alkyne 1 (1.2 mmol) was added at 0 °C
to a stirred solution of Co2(CO)8 (1 mmol) in CH2Cl2 [2.5 mL per
mmol of Co2(CO)8], and the mixture was stirred at this temperature
for 30 min. The reaction was complete when the emission of carbon
monoxide stopped. In the case of complex 2a, acetylene gas (after
condensation of acetone through a cooled trap) was bubbled
through the solution of Co2(CO)8 for 1 h. The mixture was allowed
to warm to room temperature and stirred until all Co2(CO)8 was
consumed (ca. 2–3 h). The mixture was then filtered through a
short plug of Celite®. Washing with dichloromethane and evapora-
tion of solvent under vacuum with a rotary evaporator (without
heating) gave the crude dicobalt complex 2 as a purple viscous
precipitate; yields ranged from 95 to 100%.
(E)-2,3-Diethyl-4-[2-(trimethylsilyl)ethylidene]cyclopent-2-enone
(4f): The cycloaddition between (hex-3-yne)hexacarbonyldicobalt
complex (2c, 1.53 g, 4 mmol) and 4-(trimethylsilyl)buta-1,2-diene
(3c, 0.66 g, 4 mmol) by the General Procedure, promoted by NMO
(2.8 g, 24 mmol) in CH2Cl2/THF (1:1, 30 mL), gave the cyclopen-
tenone (E)-4f (527 mg, 56%) after flash chromatography (PE/Et2O
80:20). Yellow oil; Rf = 0.33 (PE/Et2O 80:20). 1H NMR (300 MHz,
3
CDCl3): δ = 5.83 [t, J = 8.9 Hz, 1 H, (C-4)=CHCH2SiMe3], 2.82
3
3
(s, 2 H, 5-H), 2.51 [q, J = 7.7 Hz, 2 H, (C-3)CH2], 2.26 [q, J =
7.5 Hz, 8.9 Hz, H, (C-
2
H, (C-2)CH2], 1.62 [d, 3J
=
2
4)=CHCH2SiMe3], 1.14 (t, 3J = 7.7 Hz, 3 H, CH3), 1.03 (t, 3J =
7.5 Hz, 3 H, CH3), 0.04 [s, 9 H, 3ϫ SiCH3] ppm. 13C NMR (75
Mz, CDCl3): δ = 205.4 (C-1, C=O), 168.9 (C-3), 142.3 (C-4), 133.6
(C-2), 122.3 [(C-4)=CHCH2SiMe3], 37.7 (C-5), 22.1 (CH2SiMe3),
19.3 [(C-3)CH2], 16.7 [(C-2)CH2], 14.1 (CH3), 13.5 (CH3), –1.5 (3ϫ
General Procedure for the Synthesis of 4-Alkylidenecyclopent-2-en-
ones 4:[2c] A solution of an allene 3 (1.5 mmol) in CH2Cl2 (1 mL)
was added at –78 °C (or –40 °C) to a stirred solution of an (alkyne)-
hexacarbonyldicobalt complex 2 (1 mmol) in a CH2Cl2/THF mix-
ture (1:1, 10 mL). Solid NMO (6 mmol) was then added over 5 min.
After 15 min at this temperature, the mixture was allowed to warm
to room temperature by removal of the cold bath (1 h) and stirred
until the starting complex had disappeared (1 to 3 h). The solution
was filtered through a small plug of silica gel (washing of the pre-
cipitate with ether) and concentrated under vacuum. This opera-
tion was repeated several times if necessary, to eliminate most of
SiCH ) ppm. IR (thin film): ν = 2968, 2878, 1693 (C=O), 1247
˜
3
(C=C), 1247 and 838 (Si–Me) cm–1. MS (EI): m/z (%) = 236 (29)
[M]+, 221 (34) [M – CH3]+, 207 (10) [M – C2H5]+, 91 (6), 75 (13),
73 (100) [SiMe3]+. HRMS (EI): calcd. for C14H24OSi [M]+
236.1596; found 236.1605.
4-[2-Hydroxy-1-(methyl)ethylidene]cyclopent-2-enone (4i): Gaseous
acetylene (1a) was bubbled for 1.5 h through a solution of octacar-
Eur. J. Org. Chem. 2012, 7093–7105
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7099

M. Ahmar, S. Thomé, B. Cazes
FULL PAPER
bonylcobalt complex Co2(CO)8 (13 mmol, 1.1 equiv.) in CH2Cl2 (d, 3J = 5.3 Hz, 1 H, 2-H), 5.75 [t, 3J = 9.2 Hz, 1 H, (C-
3
(16 mL per g of complex) at room temperature in order to obtain
4)=CHCH2], 2.96 (s, 2 H, 5-H), 1.79 (d, J = 9.2 Hz, 2 H, CH2Si),
a solution of (acetylene)hexacarbonylcobalt complex (2a). 2-Meth- 0.05 (s, 9 H, 3ϫ SiCH3) ppm. 13C NMR (75 Mz, CDCl3): (E)-4k:
ylbuta-2,3-dien-1-ol (3d, 1 g, 11.9 mmol) was then added together
with anhydrous THF (35 mL). The mixture was cooled down to
–40 °C, N-methylmorpholine oxide (1 equiv.) was added, and the
mixture was allowed to warm to –30 °C. Then the mixture was
cooled down to –40 °C again, and the remaining 5 equiv. of N-
methylmorpholine oxide were added portionwise. The reaction
mixture was stirred at room temperature for 18 h and was then
filtered through a silica gel plug with washing with diethyl ether.
The filtrate was concentrated under vacuum and the crude product
was purified by flash chromatography (gradient from PE/Et2O
10:90 to pure Et2O as the eluent) to afford cyclopentenone (E + Z)-
4i (632 mg, 38%, E/Z 53:47). Rf = 0.18 (Et2O). 1H NMR (300 MHz
δ = 206.7 (C-1, C=O), 160.9 (C-3), 135.8 (Cq, C-4), 131.3 (C-2),
129.7 [(C-4)=CH], 37.6 (C-5), 22.9 (SiCH2), –1.5 (3ϫ SiCH3) ppm.
(Z)-4k: δ = 207.5 (C-1), 154.9 (C-3), 133.6 (Cq, C-4), 132.9 (C-2),
127.8 [(C-4)=CH], 40.5 (C-5), 20.9 (SiCH2), –1.7 (3ϫ SiCH3) ppm.
IR (KBr): ν = 2955, 2886, 1699 (C=O), 1645, 1537, 1247 and 834
˜
(SiCH3) cm–1. MS (EI): m/z (%) = 180 (34) [M]+, 165 (8) [M –
CH3]+, 91 (15) [M – H – SiMe3]+, 73 (100) [SiMe3]+. HRMS (EI):
calcd. for C10H16OSi [M]+ 180.0970; found 180.0974.
4-[1-(Trimethylsilyl)ethylidene]cyclopent-2-enone (4l): Treatment of
3-(trimethylsilyl)buta-1,2-diene (3e, 1 g, 7.9 mmol), (acetylene)-
hexacarbonyldicobalt complex (2a, 2.97 g, 9.5 mmol) and NMO
(6.7 g, 57 mmol) by the General Procedure at –40 °C gave the cyclo-
pentenone 4l as a mixture of E and Z stereoisomers (570 mg, 40%,
E/Z 64:36) after purification by flash chromatography (PE/Et2O
3
CDCl3): (E)-4i: δ = 8.04 (d, J = 5.8 Hz, 1 H, 3-H, HC=CHCO),
6.24 (d, 3J = 5.8 Hz, 1 H, 2-H, HC=CHCO), 4.21 (s, 2 H, CH2OH),
2.94 (s, 2 H, 5-H), 2.45 (s, 1 H, OH), 2.00 (s, 3 H, CH3) ppm. (Z)-
4i: δ = 8.13 (d, 3J = 5.7 Hz, 1 H, HC=CHCO), 6.19 (d, 3J = 5.7 Hz,
1 H, HC=CHCO), 4.35 (s, 2 H, CH2OH), 2.89 (s, 2 H, 5-H), 2.45
(br. s, 1 H, OH), 1.90 (s, 3 H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): (E)-4i: δ = 207.0 (C=O), 156.7 (C-3), 135.8 (C-2), 134.2
(Cq), 133.5 (Cq), 64.7 (CH2OH), 38.2 [C-5, (C=O)CH2], 15.6
(CH3) ppm. (Z)-4i: δ = 206.7 (C=O), 155.4 (C-3), 136.0 (C-2), 133.9
(Cq), 132.8 (Cq), 62.7 (CH2OH), 38.9 (C-5), 18.4 (CH3) ppm. IR
1
75:25). Rf = 0.21 (PE/Et2O 75:25). H NMR (300 MHz, CDCl3):
(E)-4l: δ = 8.14 [d, 3J = 5.6 Hz, 1 H, HC=CH(C=O)], 6.25 [d, 1 H,
3J = 5.6 Hz, HC=CH(C=O)], 2.96 [s, 2 H, (C=O)CH2], 1.99 [s, 3
H, (C-4)=CCH3], 0.17 (s, 9 H, 3ϫ SiCH3) ppm. (Z)-4l: δ = 7.96
[d, 3J = 5.6 Hz, 1 H, HC=CH(C=O)], 6.24 [d, 3J = 5.6 Hz, 1 H,
HC=CH(C=O)], 2.92 [s, 2 H, (C=O)CH2], 1.88 [s, 3 H, (C-
4)=CCH3], 0.23 (s, 9 H, 3ϫ SiCH3) ppm. 13C NMR (75 MHz,
CDCl3): (E)-4l: δ = 207.5 (C=O), 154.6 (C-3), 143.7 (C-2), 139.1
(C-4, Cq=CSiMe3), 132.9 [(C-4)=CqSiMe3], 40.9 [(C=O)CH2], 17.7
[(C-4)=CCH3], –0.8 (3ϫ SiCH3) ppm. (Z)-4l: δ = 205.7 (C=O),
157.9 (C-3), 146.1 (C-2), 141.3 (C-4), 133.6 [(C-4)=CqSi], 39.1
[(C=O)CH2], 20.4 [C-(4)=CCH3], 0.12 (3ϫ SiCH3) ppm. GC–MS
(EI): m/z (%) = 180 (32) [M]+, 165 (37) [M – CH3]+, 135 (6), 109
(7), 106 (11), 97 (17), 91 (83), 73 (100) [SiMe3]+, 75 (27). HRMS
(EI): calcd. for C10H16OSi [M]+ 180.0970; found 180.0971.
(thin film): ν = 3400, 2970, 2920, 2860, 2240, 1700, 1670, 1530,
˜
1440, 1385 cm–1. MS (CI): m/z (%) = 139 [M + H]+.
4-[2-Acetoxy-1-(methyl)ethylidene]cyclopent-2-enone (4j): Triethyl-
amine (0.1 mL, 1.24 mmol) and 4-(dimethylamino)pyridine
(13.7 mg, 10 mol-%) were added under nitrogen to a solution of
cyclopentenone (E + Z)-4i (155 mg, 1.13 mmol) in CH2Cl2 (5 mL).
The mixture was cooled to 5 °C, and acetic anhydride (0.2 mL,
2 mmol) was added. The reaction mixture was stirred at room tem-
perature for 1 h and was then quenched with water (5 mL) with a
few drops of a saturated solution of NaHCO3 and extracted with
CH2Cl2 (3ϫ 5 mL). The organic layers were collected, washed with
water (5 mL), dried with Na2SO4, filtered and concentrated in
vacuo. The crude product was purified by flash chromatography
(PE/Et2O 2:3, then 1:3) to afford acetate (E + Z)-4j (167 mg, 83%,
E/Z 53:47). Rf = 0.20 (PE/Et2O 40:60). 1H NMR (300 MHz,
4-[1-(Dimethylphenylsilyl)ethylidene]cyclopent-2-enone (4m): Treat-
ment of 3-(dimethylphenylsilyl)buta-1,2-diene (3f, 1.5 g, 8 mmol),
(acetylene)dicobalt complex 2a (3 g, 9.6 mmol) and NMO (6.75 g,
58 mmol) by the General Procedure at –40 °C gave the cyclopen-
tenone 4m as a mixture of E and Z isomers (602 mg, 31%, E/Z
60:40) after purification by flash chromatography (PE/Et2O 75:25).
1
Rf = 0.32 (PE/Et2O 70:30). H NMR (300 MHz, CDCl3): (E)-4m:
δ = 8.18 (d, 3J = 5.6 Hz, 1 H, 3-H), 7.62 (br. s, 1 H, Har), 7.52–
3
CDCl3): (E)-4j: δ = 8.02 (d, J = 5.8 Hz, 1 H, HC=CHCO), 6.30
3
3
7.39 (br. s, 4 H, Har), 6.28 (d, J = 5.6 Hz, 1 H, 2-H), 2.79 [s, 2 H,
(d, J = 5.8 Hz, 1 H, HC=CHCO), 4.63 (s, 2 H, CH2–OAc), 3.01
(C=O)CH2], 2.08 [s, 3 H, (C-4)=CCH3], 0.48 (s, 6 H, 2ϫ
[s, 2 H, (C=O)CH2], 2.08 [s, 3 H, O(C=O)CH3], 1.96 (s, 3 H,
3
CH3) ppm. (Z)-4j: δ = 8.10 (d, 3J = 5.7 Hz, 1 H, HC=CHCO), 6.27
SiCH3) ppm. (Z)-4m: δ = 7.72 (d, J = 5.5 Hz, 1 H, 3-H), 7.62 (br.
3
3
s, 1 H, Har), 7.52–7.39 (m, 4 H, Har), 6.17 (d, J = 5.5 Hz, 1 H, 2-
(d, J = 5.7 Hz, 1 H, HC=CHCO), 4.78 (s, 2 H, CH2–OAc), 2.93
H), 2.99 [s, 2 H, (C=O)CH2], 1.96 [s, 3 H, (C-4)=CCH3], 0.43 (s, 6
H, 2ϫ SiCH3) ppm. 13C NMR (75 MHz, CDCl3): (E)-4m: δ =
207.7 (C-1, C=O), 154.7 (C-3), 145.3 (Cq, C-4), 139.4 [(C-
4)=C(SiPhMe2)], 137.6 [C(Ph)i], 133.8 [2ϫ CH(Ph)o], 129.5 (C-2),
128.2 [C(Ph)p], 127.9 [2ϫ CH(Ph)met], 41.1 [(C=O)CH2], 18.5 [(C-
4)=CCH3], –1.9 (2ϫ SiCH3) ppm. (Z)-4m: δ = 206.2 (C=O), 158.2
(C-3), 147.5 (C-4), 139.2 [(C-4)=C(SiPhMe2)], 137.3 [C(Ph)i], 133.8
[2ϫ CH(Ph)o], 129.6 (C-2), 128.2 [C(Ph)p], 127.9 [2ϫ CH(Ph)met],
39.4 [(C=O)CH2], 20.9 [(C-4)=CCH3], 0.1 (2ϫ SiCH3) ppm. GC–
MS (EI): m/z (%) = 242 (73) [M]+, 227 (26) [M – CH3]+, 168 (27),
135 (100) [SiPhMe2]+, 105 (36), 75 (42). HRMS (EI): calcd. for
C15H18OSi [M]+ 242.1127; found 242.1131.
[s, 2 H, (C=O)CH2], 2.08 [s, 3 H, O(C=O)CH3], 1.89 (s, 3 H,
CH ) ppm. IR (thin film): ν = 2975, 2920, 2860, 2240, 1730, 1700,
˜
3
1670, 1530, 1440, 1385 cm–1.
4-[2-(Trimethylsilyl)ethylidene]cyclopent-2-enone (4k): As described
in the General Procedure NMO (13.1 g, 35.61 mmol) was added
portionwise at –40 °C over 30 min to a solution of 4-(trimethyl-
silyl)buta-1,2-diene (3c, 4 g, 31.8 mmol) and (acetylene)hexa-
carbonyldicobalt complex (2a, 6.6 g, 21.2 mmol), prepared as for
4i from Co2(CO)8 (8.06 g, 23.6 mmol) and acetylene, in CH2Cl2/
THF (1:1, 100 mL) stirred at –40 °C. After warming up, dilution
with ethyl ether, stirring at room temperature for 18 h and workup,
purification by flash chromatography (PE/Et2O 80:20) gave the cy-
clopentenone (E + Z)-4k (2.36 g, 62%, E/Z 80:20). Rf = 0.32 (PE/
General Procedure for Epoxidation of 4-Alkylidenecyclopentenones
Et2O 75:25). H NMR (300 MHz, CDCl3): (E)-4k: δ = 7.70 (d, J 4 (or 5): m-Chloroperbenzoic acid (4 mmol) was added at 0 °C to
a solution of a cyclopentenone 4 (or 5, 2 mmol) in toluene (10 mL).
The reaction mixture was stirred until completion (2–18 h) and
5-H, (C=O)CH2], 1.66 (d, J = 8.9 Hz, 2 H, SiCH2), 0.05 (s, 9 H, then concentrated in vacuo. Filtration on silica gel with petroleum
1
3
= 5.1 Hz, 1 H, 3-H, CH=CCO), 6.12 (d, 3J = 5.1 Hz, 1 H, 2-H,
C=CHCO), 5.90 [t, 3J = 8.9 Hz, 1 H, (C-4)=CHCH2], 2.84 [s, 2 H,
3
3
3ϫ SiCH3) ppm. (Z)-4k: δ = 7.98 (d, J = 5.3 Hz, 1 H, 3-H), 6.21
ether/ether 95:5 as eluent, followed by purification by flash
7100
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 7093–7105

Epoxidation of 4-Alkylidenecyclopentenones
chromatography, gave 7 (or 9). If m-chlorobenzoic acid remained,
the epoxide 7 (or 9) was dissolved in CH2Cl2, which was washed
with water to which few drops of a saturated NaHCO3 solution
had been added. The organic layer was washed again with water,
dried with Na2SO4, filtered and concentrated in vacuo.
[(C-4)-O-CH], 37.8 [(C=O)CH2], 31.8, 30.9, 29.3, 26.4 and 22.7
(5ϫ CH2), 17.9 (CH2CH3), 17.0 (CH2CH3), 14.2, 14.0 and 13.2
(3ϫ CH ) ppm. IR (thin film): ν = 2860, 2820, 1660, 1650, 1400,
˜
3
1375, 1250, 1165, 915, 790 cm–1. MS (EI): m/z (%) = 250 (6) [M]+,
221 (8), 179 (12), 152 (100), 137 (13), 108 (31), 57 (25). HRMS
(CI): calcd. for C16H26O2 [M + H]+ 251.1933; found 251.1931.
Spiroepoxycyclopentenone 7a: Epoxidation of cyclopentenone 4a
(300 mg, 2 mmol) by the General Procedure (Table 1, Entry 1) gave
the spiroepoxycyclopentenone 7a (253 mg, 76%) after flash
chromatography (PE/Et2O 70:30). Yellow oil; Rf = 0.18 (PE/Et2O
Spiroepoxycyclopentenone trans-7e: Epoxidation of cyclopentenone
(E)-4e (226 mg, 1 mmol) by the General Procedure (Table 1, En-
try 5) gave trans-7e (169 mg, 70%) after flash chromatography (PE/
1
2
70:30). H NMR (300 MHz, CDCl3): δ = 2.66 [d, J = 18.8 Hz, 1 Et2O 80:20). Yellow solid; m.p = 60–61 °C; Rf = 0.22 (PE/Et2O
2
H, (C=O)CHaHb], 2.43 [d, J = 18.8 Hz, 1 H, (C=O)CHaHb], 1.96
80:20). 1H NMR (300 MHz, CDCl3): δ = 7.31 (m, 5 H, 5ϫ CHar),
[s, 3 H, (C-3)CH3], 1.78 [s, 3 H, (C-2)CH3], 1.54 [s, 3 H, (C-4)-O- 4.34 (s, 1 H, O–CHPh), 2.45 [d, 2J = 19.0 Hz, 1 H, (C=O)CHaHb],
CCH3CH3], 1.40 [s, 3 H, (C-4)-O-CH3CH3] ppm. 13C NMR
(75 MHz, CDCl3): δ = 204.0 (C-1, C=O), 165.2 (C-3), 143.3 (C-2),
2.29 [m, 4 H, (C-3)CH2 and (C-2)CH2], 2.15 [d, J = 19.0 Hz, 1 H,
2
(C=O)CHaHb], 1.21 (t, 3J = 7.7 Hz, 3 H, CH3), 1.07 (t, 3J = 7.5 Hz,
70.1 (C-4, Cq–O), 64.2 [(C-4)-O-C(CH3)2], 40.6 (C-5), 25.5 [(C-4)- 3 H, CH3) ppm. 13C NMR (CDCl3): δ = 209.9 (C=O), 168.0 (C-
O-CCH3], 20.7 [(C-4)-O-CCH3], 14.6 [(C-3)CH3], 8.8 [(C-2)-
CH ] ppm. IR (thin film): ν = 3332, 2986, 2907, 1669, 1589, 1392,
3), 147.6 (C-2), 135.5 (Cq-ar), 128.6 (2ϫ CHar), 128.4 (CHar), 126.2
(2ϫ CHar), 68.5 (C-4, Cq-O-CH), 61.5 [(C-4)-O-CH], 37.9 [(C=O)-
˜
3
1368, 1200, 1076, 915, 891 cm–1. MS (EI): m/z (%) = 166 (6) [M]+, CH2], 18.0 [(C-3)CH2], 17.0 [(C-2)CH2], 14.0 (CH3), 13.1
124 (40) [M – C(CH3)2]+, 80 (100), 77 (20), 43 (36). HRMS (EI):
calcd. for C10H14O2 [M]+ 166.0994; found 166.0992.
(CH ) ppm. IR (thin film): ν = 3060, 3040, 2960, 2930, 2870, 1700,
˜
3
1630, 1495, 1460, 1450, 1380, 1240, 905, 810, 760 cm–1. MS (EI):
m/z (%) = 242 (45) [M]+, 215 (37), 185 (18), 136 (24), 108 (100), 91
(52), 77 (32), 43 (60).
Spiroepoxycyclopentenone 7b: Epoxidation of cyclopentenone 4b
(130 mg, 0.6 mmol) by the General Procedure (Table 1, Entry 2)
gave 7b (80 mg, 57%) after flash chromatography (PE/Et2O 80:20).
Yellowish oil; Rf = 0.22 (PE/Et2O 80:20). 1H NMR (300 MHz,
Spiroepoxycyclopentenone trans-7f: Epoxidation of cyclopentenone
4f (237 mg, 1 mmol) by the General Procedure (Table 1, Entry 6)
gave trans-7f (212 mg, 84%) after flash chromatography (PE/Et2O
2
2
CDCl3): δ = 2.65 [d, J = 18.5 Hz, 1 H, (C=O)CHaHb], 2.43 [d, J
= 18.5 Hz, 1 H, (C=O)CHaHb], 2.48–2.33 [m, 2 H, (C-3)CH2], 2.28
[qd, 3J = 7.5, 5J = 2.3 Hz, 2 H, (C-2)CH2], 1.90–1.45 (m, 10 H, 5ϫ
1
80:20). Rf = 0.30 (PE/Et2O 80:20). H NMR (300 MHz, CDCl3): δ
3
3
2
= 3.36 (dd, J = 7.7, J = 7.5 Hz, 1 H, O–CHCH2Si), 2.53 [d, J =
CH2), 1.11 (t, J = 7.5 Hz, 3 H, CH3), 1.06 (t, 3J = 7.5 Hz, 3 H,
18.8 Hz, 1 H, (C=O)CHaHb], 2.44 [d, J = 18.8 Hz, 1 H, (C=O)-
3
2
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.2 (C-1, C=O),
169.7 (C-3), 148.6 (C-2), 70.3 (C-4, C–O), 68.9 [(C-4)-O-Cq], 40.9
[(C=O)CH2], 35.2, 30.5, 25.5, 25.4 and 24.9 (5ϫ CH2), 20.7 and
17.1 (2ϫ CH2CH3), 13.0 and 12.9 (2ϫ CH3) ppm. IR (thin film):
CHaHb], 2.27 [q, 3J = 7.5 Hz, 2 H, (C-3)CH2], 2.15 [q, 3J = 7.7 Hz,
2 H, (C-2)CH2], 1.18–1.07 (m, 1 H, CHaHbSi), 1.09 (t, 3J = 7.7 Hz,
3
2
3
3 H, CH3), 1.05 (t, J = 7.5 Hz, 3 H, CH3), 0.80 (dd, J = 14.3, J
= 7.7 Hz, 1 H, CHaHbSi), 0.08 (s, 9 H, 3ϫ SiCH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 204.3 (C=O), 169.6 (C-3), 146.8 (C-2), 65.8
(C-4, Cq–O), 58.8 (O–CH), 38.0 [(C=O)CH2], 18.9 (CH2SiMe3),
17.8 and 17.3 (2ϫ CH2CH3), 13.9 and 13.2 (2ϫ CH2CH3), –1.1
ν = 2960, 2920, 2850, 1705, 1620, 1450, 1380, 1240, 960, 835 cm–1.
˜
MS (EI): m/z (%) = 234 (7) [M]+, 152 (100), 136 (13), 108 (33), 93
(20), 67 (24). HRMS (EI): calcd. for C15H22O2 [M]+ 234.1620;
found 234.1621.
(3ϫ SiCH ) ppm. IR (thin film): ν = 2969, 2878, 1705, 1663, 1464,
˜
3
1381, 1249, 1186, 1059, 963, 846 cm–1. MS (EI): m/z (%) = 252 (1)
[M]+, 251 (2), 237 (6) [M – CH3]+, 225 (6), 223 (5) [M – C2H5]+,
209 (2), 195 (2). 73, (100) [Si(CH3)3]+. HRMS (ESI): calcd. for
C14H24O2SiNa [M + Na]+ 275.1441; found 275.1443.
Spiroepoxycyclopentenone trans-7c: Epoxidation of cyclopentenone
(E)-4c (207 mg, 1 mmol) by the General Procedure (Table 1, En-
try 3) gave trans-7c (203 mg, 81%) after flash chromatography (PE/
Et2O 80:20). Yellow oil; Rf = 0.33 (PE/Et2O 70:30). 1H NMR
(300 MHz, CDCl3): δ = 3.26 [t, 3J = 5.6 Hz, 1 H, (C-4)-O-CH], Spiroepoxycyclopentenone trans-7g: Epoxidation of cyclopentenone
2
2
2.56 [d, J = 19.0 Hz, 1 H, (C=O)CHaHb], 2.41 [d, J = 19.0 Hz, 1
(E)-4g (600 mg, 2.5 mmol) by the General Procedure (Table 1, En-
H, (C=O)CHaHb], 1.80 (s, 3 H, CH3), 1.78 (s, 3 H, CH3), 1.60– try 7) gave trans-7g (535 mg, 86%) after flash chromatography (PE/
1.20 (m, 10 H, 5ϫ CH2), 0.88 (t, 3J = 6.6 Hz, 3 H, CH2CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 204.5 (C=O), 165.4 (C-3), 141.8
(C-2), 66.0 (C-4, Cq-O-CH), 60.5 [(C-4)-O-CH], 37.6 [(C=O)CH2],
32.1, 31.1, 29.5, 26.6 and 22.9 (5ϫ CH2), 14.4 (CH2CH3), 10.7 [(C-
Et2O 80:20). Yellow oil; Rf = 0.55 (PE/Et2O 50:50). 1H NMR
3
(300 MHz, CDCl3): δ = 3.25 (t, J = 5.6 Hz, 1 H, O–CH), 2.55 [d,
2J = 19.2 Hz, 1 H, (C=O)CHaHb], 2.35 [d, 2J = 19.2 Hz, 1 H,
(C=O)CHaHb], 2.22 [t, 3J = 7.5 Hz, 2 H, (C-2)CH2], 1.8 [s, 3 H,
3
3)CH ], 8.83 [(C-2)CH ] ppm. IR (thin film): ν = 2936, 1685, 1670, (C-3)CH3], 1.58 (m, 2 H, CH2), 1.45 [quint, J = 7.5 Hz, 2 H, (C-
˜
3
3
1376, 1220, 1163, 1040, 965, 848, 813 cm–1. MS (ESI): m/z (%) =
2)CH2CH2CH3], 1.38 (m, 8 H, 4ϫ CH2), 1.05 (t, 3J = 6.8 Hz, 3 H,
223 (100) [M + H]+, 254.9 (22) [M + H + CH3OH]+, 277.2 (51) [M CH3), 0.9 (t, 3J = 7.5 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz,
+ Na + CH3OH]+, 445.1 (49) [2M + H]+.
CDCl3): δ = 204.0 (C=O), 165.2 (C-3), 145.6 (C-2), 65.7 (C-4), 60.3
(O–CH), 37.5 [(C=O)CH2], 31.8 [(C-3)CH3], 30.8 [(C-2)CH3], 29.2
(O–CHCH2), 26.4, 25.5, 22.6 and 21.5 (4ϫ CH2), 14.2 [(C-2)-
Spiroepoxycyclopentenone trans-7d: Epoxidation of cyclopentenone
(E)-4d (234 mg, 1 mmol) (Table 1, Entry 4) by the General Pro-
cedure gave trans-7d (173 mg, 69%) after flash chromatography
CH CH ], 14.0 and 13.2 (2ϫ CH ) ppm. IR (thin film): ν = 2958,
˜
2
2
3
2928, 2858, 1707 (C=O), 1457, 1387, 1267, 1228, 1082, 960,
812 cm–1. MS (CI): m/z (%) = 251 (100) [M + H]+, 235 (19), 154
(19), 93 (15), 81 (21), 69 (35). HRMS (CI): calcd. for C16H27O2 [M
+ H]+ 251.2011; found 251.2007.
1
(PE/Et2O 90:10). Yellow oil; Rf = 0.28 (PE/Et2O 80:20). H NMR
3
(300 MHz, CDCl3): δ = 3.26 (t, J = 5.5 Hz, 1 H, Cq-O-CH), 2.55
2
2
[d, J = 19.2 Hz, 1 H, (C=O)CHaHb], 2.41 [d, J = 19.2 Hz, 1 H,
3
3
(C=O)CHaHb], 2.27 [q, J = 7.5 Hz, 2 H, (C-3)CH2], 2.14 [qd, J
5
= 7.5, J = 2.5 Hz, 2 H, (C-2)CH2], 1.43 (m, 10 H, 5ϫ CH2), 1.08
Spiroepoxycyclopentenone trans-7h: Epoxidation of cyclopentenone
(E)-4h (300 mg, 1 mmol) by the General Procedure (Table 1, En-
(t, 3J = 7.5 Hz, 3 H, CH3), 1.05 (t, J = 7.5 Hz, 3 H, CH3), 0.88 (t,
3
3J = 6.8 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = try 8) gave trans-7h (162 mg, 50%) after flash chromatography (PE/
204.5 (C=O), 169.5 (C-3), 146.9 (C-2), 65.2 (C-4, Cq-O-CH), 60.6 Et2O 80:20). Yellow oil; Rf = 0.44 (PE/Et2O 70:30). 1H NMR
Eur. J. Org. Chem. 2012, 7093–7105
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7101

M. Ahmar, S. Thomé, B. Cazes
FULL PAPER
(300 MHz, CDCl3): δ = 6.73 [s, 1 H, CH=C(C=O)], 3.21 [dd (tapp),
HaHb], 2.44 [d, 2J = 19.2 Hz, 1 H, (C=O)HaHb], 2.09 (s, 3 H, CH3),
1.45 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.1
(C=O), 170.5 (C=O), 158.3 (C-3), 139.4 (C-2), 69.7 (Cq–O), 65.8
2
2
2J = 6.0, J = 5.8 Hz, 1 H, (C-4)-O-CH], 2.63 [d, J = 19.2 Hz, 1
2
H, (C=O)CHaHb], 2.46 [d, J = 19.2 Hz, 1 H, (C=O)CHaHb], 2.21
[t, 3J = 7.5 Hz, 2 H, (C-2)CH2], 1.60–1.45 (m, 2 H, O–CHCH2), (Cq–O), 63.7 (CH2–OAc), 38.6 [(C=O)CH2], 20.8 (CH3), 18.5
3
1.52 [quint, J = 7.5 Hz, 2 H, (C-2)CH2CH2], 1.45–1.15 (m, 10 H,
(CH3) ppm.
3
3
4ϫ CH2), 0.94 (t, J = 7.3 Hz, 3 H, CH3), 0.89 (t, J = 6.8 Hz, 3
H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.0 (C=O),
154.7 (C-3), 151.0 (C-2), 64.6 (C-4, Cq-O-CH), 63.1 [(C-4)-O-CH],
38.0 [(C=O)CH2], 31.8, 30.9, 29.2, 26.9, 26.2, 22.6 and 20.8 (7ϫ
3
Isomer (minor) cis-7j: 1H NMR (300 MHz, CDCl3): δ = 7.29 [d, J
= 5.8 Hz, 1 H, HC=CH(C=O)], 6.46 [d, 3J = 5.8 Hz, 1 H,
HC=CH(C=O)], 4.14 (d, 2J = 12.5 Hz, 1 H, HaHbC–OAc), 4.09
(d,2J=12.5 Hz,1H,HaHbC–OAc),2.71[d,2J=19.2 Hz,1H,(C=O)-
HaHb], 2.47 [d, 2J = 19.2 Hz, 1 H, (C=O)HaHb], 2.09 (s, 3 H, CH3),
1.49 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.1
(C=O), 170.6 (C=O), 158.4 (C-3), 139.5 (C-2), 69.4 (Cq–O), 67.3
(Cq–O), 63.9 (CH2–OAc), 38.1 [(C=O)CH2], 20.8 (CH3), 16.2
(CH3) ppm.
CH ), 14.2 and 14.0 (2ϫ CH ) ppm. IR (thin film): ν = 2958, 2927,
˜
2
3
2858, 1714 (CO), 1458, 1379, 1254, 1045, 968 cm–1. HRMS (CI):
calcd. for C15H25O2: [M + H]+ 237.1855; found 237.1853.
Spiroepoxycyclopentenone cis-7h: Epoxidation of cyclopentenone
(Z)-4h (230 mg, 1.05 mmol) by the General Procedure (Table 1, En-
try 9) gave cis-7h (177.4 mg, 72%) after flash chromatography (PE/
Et2O 80:20). Yellow oil; Rf = 0.36 (PE/Et2O 70:30). 1H NMR
Spiroepoxycyclopentenone (7k): Epoxidation of cyclopentenone (E
+ Z)-4k (220 mg, 1.22 mmol) by the General Procedure (Table 2,
Entry 2) gave (trans + cis)-7k (157 mg, 66%, trans/cis = 80:20) after
flash chromatography (PE/Et2O 80:20.
4
(300 MHz, CDCl3): δ = 6.85 [d, J = 1.2 Hz, 1 H, CH=C(C=O)],
3.36 [dd (tapp), 2J = 6.2, 2J = 6.0 Hz, 1 H, O–CH], 2.69 [d, 2J =
2
19.2 Hz, 1 H, (C=O)CHaHb], 2.58 [d, J = 19.2 Hz, 1 H, (C=O)-
3
4
Isomers (trans + cis)-7k: Rf = 0.21 (PE/Et2O 80:20). IR (thin film):
CHaHb], 2.24 [td, J = 7.5, J = 1.2 Hz, 2 H, (C-2)CH2], 1.80–1.60
ν = 2955, 2884, 1719 (C=O), 1350, 1248, 1118, 1165, 969, 840 cm–1.
(m, 2 H, O–CHCH2), 1.53 [quint, 3J = 7.5 Hz, 2 H, (C-2)CH2CH2],
˜
3
Isomer (major) trans-7k: 1H NMR (300 MHz, CDCl3): δ = 7.13
[d, 3J = 5.7 Hz, 1 H, CH=CH(C=O)], 6.31 [d, 3J = 5.7 Hz, 1 H,
1.60–1.20 (m, 8 H, 4ϫ CH2), 0.94 (t, J = 7.5 Hz, 3 H, CH3), 0.89
(t, J = 6.8 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
3
3
204.5 (C=O), 154.2 (C-3), 150.8 (C-2), 64.4 (C-4, Cq-O-CH), 65.3
[(C-4)-O-CH], 39.8 [(C=O)CH2], 32.2, 30.9, 29.1, 26.3, 25.2, 22.6
and 20.8 (7ϫ CH2), 14.1 and 13.9 (2ϫ CH3) ppm. IR (thin film):
CH=CH(C=O)], 3.31 (tapp, Japp = 6.8 Hz, 1 H, O-CH-CHaHbSi),
2
2
2.53 [d, J = 19.2 Hz, 1 H, (C=O)CHaHb], 2.37 [d, J = 19.2 Hz, 1
H, (C=O)CHaHb], 0.97 (dd, 2J = 14.5, 3J = 6.6 Hz, 1 H, CHaHbSi),
2
3
ν = 2958, 2928, 2858, 1707 (C=O), 1457, 1387, 1267, 1228, 1082,
˜
0.83 (dd, J = 14.5, J = 6.8 Hz, 1 H, CHaHbSi), 0.06 (s, 9 H, 3ϫ
SiCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.1 (C=O), 162.5
(C-3), 137.7 (C-2), 66.6 (C-4, Cq-O-CH), 61.5 (O-CH-CH2Si), 37.5
[(C=O)CH2], 18.9 [CH2Si(CH3)3], –1.1 (3ϫ SiCH3) ppm.
960, 812 cm–1. MS (CI): m/z (%) = 237 (100) [M + H]+, 222 (11),
208 (41), 190 (47).
Spiroepoxycyclopentenone 9h: Epoxidation of cyclopentenone 5h
(221 mg, 0.93 mmol) by the General Procedure (Table 1, Entry 10)
gave a mixture of trans-9h and cis-9h (112 mg, 47%, trans-9h/cis-
9h 90:10) after flash chromatography (PE/Et2O 95:5).
Isomer (minor) cis-7k: 1H NMR (300 MHz, CDCl3): δ = 7.26 [d,
3J = 5.8 Hz, 1 H, CH=CH(CO)], 6.43 [d, 3J = 5.8 Hz, 1 H,
CH=CH(C=O)], 3.46 (m, 1 H, O-CH-CH2Si), 2.62 [d, 2J =
2
19.2 Hz, 1 H, (C=O)CHaHb], 2.51 [d, J = 19.2 Hz, 1 H, (C=O)-
Isomers (trans + cis)-9h: Yellow oil; Rf = 0.34 (PE/Et2O 90:10). IR
CHaHb], 1.10–1.25 (m, 2 H, CH2Si), 0.06 (s, 9 H, 3ϫ SiCH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 204.9 (C=O), 159.4 (C-3), 139.2
(C-2), 65.9 (C-4, Cq-O-CH), 62.6 (O-CH-CH2Si), 40.9 [(C=O)-
CH2], 17.5 [CH2Si(CH3)3], –1.1 (3ϫ SiCH3) ppm. MS (CI): m/z
(%) = 197 (100) [M + H]+, 154 (9), 125 (7), 107 (18), 81 (25), 69
(36). HRMS (CI): calcd. for C10H17O2Si: [M + H]+ 197.0998; found
197.1009.
(thin film): ν = 2960, 2930, 2860, 1700 (C=O), 1460, 1386, 1270,
˜
1229, 1082, 960, 812 cm–1.
Isomer trans-9h: 1H NMR (300 MHz, CDCl3): δ = 6.70 [s, 1 H,
CH=C(C=O)], 3.29 [d, 2J = 4.3 Hz, 1 H, (C-4)-O-CHaHb], 3.09
[d,2J=4.3 Hz,1H,(C-4)-O-CHaHb],2.53[t, 3J=5.3 Hz,1H,(C=O)-
CH], 2.23 [t, 3J = 6.8 Hz, 2 H, (C-2)CH2], 1.51 [m, 2 H, (C-2)-
3
CH2CH2], 1.2–1.4 (m, 10 H, 5ϫ CH2), 0.96 (t, J = 7.3 Hz, CH3),
Spiroepoxycyclopentenone 7l: Epoxidation of cyclopentenone (E +
Z)-4l (180.4 mg, 1 mmol) by the General Procedure (Table 2, En-
try 3) gave (trans + cis)-7l (162 mg, 82%, trans/cis = 64:36) after
flash chromatography (PE/Et2O 80:20).
0.84 (t, 3J = 6.8 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 207.3 (C=O), 153.1 (C-3), 151.6 (C-2), 64.8 (C-4, Cq–O), 51.8
[(C-4)-O-CH2], 48.4 [(C=O)CH], 31.7 [(C-2)CH2], 31.7, 29.7, 27.1,
26.0, 22.8 and 20.9 (6ϫ CH2), 14.2 and 14.0 (2ϫ CH3) ppm.
Isomers (trans + cis)-7l: Rf = 0.46 (PE/Et2O 80:20).
Isomer cis-9h: 1H NMR (300 MHz, CDCl3): δ = 6.92 (s, 1 H,
CH=CCO), 3.29 [d, 2J = 4.3 Hz, 1 H, (C-4)-O-CHaHb], 3.08 [d, J Isomer (major) trans-7l: H NMR (300 MHz, CDCl3): δ = 7.43 [d,
2
1
3
= 4.3 Hz, 1 H, (C-4)-O-CHaHb], 2.44 [t, J = 5.3 Hz, 1 H, (C=O)-
3J = 5.9 Hz, 1 H, HC=CH(C=O)], 6.63 [d, 3J = 5.9 Hz, 1 H,
CH=CH(C=O)], 2.63 [d, 2J = 19.0 Hz, 1 H, (C=O)CHaHb], 2.45
[d, 2J = 19.0 Hz, 1 H, (C=O)CHaHb], 1.40 (s, 3 H, O–CCH3), 0.14
(s, 9 H, 3ϫ SiCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.3
(C=O), 161.2 (C-3), 138.0 (C-2), 68.3 (C-4, Cq–O), 62.0 (O-C-Si),
40.4 [(C=O)CH2], 17.1 (O-CCH3), –2.6 (3ϫ SiCH3) ppm.
CH], 2.22 [t, 3J = 6.8 Hz, 2 H, (C-2)CH2], 1.50 [m, 2 H, (C-2)-
3
CH2CH2], 1.2–1.4 (m, 10 H, 5ϫ CH2), 1.25 (t, J = 7.3 Hz, CH3),
3
0.85 (t, J = 6.8 Hz, CH3) ppm.
Spiroepoxycyclopentenone 7j: Epoxidation of cyclopentenone (E +
Z)-4j (160 mg, 0.89 mmol) by the General Procedure (Table 2, En-
try 1) gave (trans + cis)-7j (117 mg, 67%, trans/cis 53:46) after flash
chromatography (PE/Et2O 80:20).
Isomer (minor) cis-7l: 1H NMR (300 MHz, CDCl3): δ = 7.30 [d, J
3
= 5.9 Hz, 1 H, HC=CH(C=O)], 6.34 [d, 3J = 5.9 Hz, 1 H,
2
C=CH(C=O)], 2.68 [d, J = 19.0 Hz, 1 H, (C=O)CHaHb], 2.46 [d,
Isomers (trans + cis)-7j: Yellow oil; Rf = 0.24 (PE/Et2O 70:30).
2J = 19.0 Hz, 1 H, (C=O)CHaHb], 1.33 (s, 3 H, OCCH3), 0.18 (s,
1
Isomer (major) trans-7j: H NMR (300 MHz, CDCl3): δ = 7.34 [d, 9 H, 3ϫ SiCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.13
3J = 6.0 Hz, 1 H, HC=CH(C=O)], 6.43 [d, 3J = 6.0 Hz, 1 H,
HC=CH(C=O)], 4.27 (d, 2J = 12.0 Hz, 1 H, HaHbC–OAc), 4.20 (d, [(C=O)CH2], 20.3 (O–CCH3), –1.9 (3ϫ SiCH3) ppm. GC–MS (EI):
2J = 12.0 Hz, 1 H, HaHbC–OAc), 2.67 [d, 2J = 19.2 Hz,1 H, (C=O)- m/z (%) = 196 (6) [M]+, 181 (5), 154 (4), 153 (11), 116 (4), 101 (4),
(C=O), 161.7 (C-3), 137.4 (C-2), 66.6 (C-4), 61.6 (O-C-Si), 38.8
7102
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 7093–7105

Epoxidation of 4-Alkylidenecyclopentenones
2
85 (13)75 (20), 73 (100). HRMS (EI): calcd. for C10H16O2Si: [M]+
196.0919; found 196.0920.
CHaHb], 2.37 [d, J = 18.1 Hz, 1 H, (C=O)CHaHb], 2.05 (s, 3 H,
CH3), 1.70 (s, 3 H, CH3), 1.20–1.40 (m, 10 H, 5ϫ CH2), 0.87 (t,
3J = 6.8 Hz, 3 H, CH2CH3) ppm.
Spiroepoxycyclopentenone 7m: Epoxidation of cyclopentenone (E
+ Z)-4m (300 mg, 1.23 mmol) by the General Procedure (Table 2,
Entry 4) gave trans-7m (168 mg, 53%) and its isomer cis-7m
(108 mg, 34%) after flash chromatography (PE/Et2O 80:20).
Isomer syn-10c: Colourless oil; Rf = 0.22 (Et2O). 1H NMR
3
(300 MHz, CDCl3): δ = 3.84 [br. d, J = 10.2 Hz, 1 H, CH(OH)],
3.20–2.60 (m, 2 H, 2ϫ OH), 2.79 [d, 2J = 18.8 Hz, 1 H, (C=O)-
2
CHaHb], 2.20 [d, J = 18.8 Hz, 2 H, (C=O)CHaHb], 1.98 (s, 3 H,
Isomer (major) trans-7m: Rf = 0.33 (PE/Et2O 60:40). 1H NMR
CH3), 1.72 (s, 3 H, CH3), 1.30–1.05 (m, 10 H, 5ϫ CH2), 0.87 (t,
3
(300 MHz, CDCl3): δ = 8.01 [d, J = 5.9 Hz, 1 H, HC=C(C=O)],
3J = 6.8 Hz, 3 H, CH2CH3) ppm.
7.60–7.50 (m, 2 H, Har), 7.41–7.36 (m, 3 Har), 6.41 [d, 3J = 5.9 Hz,
2
1 H, CH=CH(C=O)], 2.53 [d, J = 19.0 Hz, 1 H, (C=O)CHaHb],
2,3-Diethyl-4-hydroxy-4-(1-hydroxyheptyl)cyclopent-2-enone (10d):
Ring-opening of epoxide 7d (72 mg, 0.29 mmol) by the General
Procedure (Table 3, Entry 3) gave anti-10d (30.5 mg, 36%) and its
diastereomer syn-10d (10 mg, 12%) after flash chromatography.
2.24 [d, 2J = 19.0 Hz, 1 H, (C=O)CHaHb], 1.43 (s, 3 H, CH3), 0.43
and 0.40 (2ϫ CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.6
(C=O), 161.1 (C-3), 138.4 (C-2), 135.5 [C(Ph)i], 134.1 [2ϫ CH-
(Ph)o], 129.9 [CH(Ph)p], 128.3 [2ϫ CH(Ph)m], 68.6 (C-4, Cq–O),
61.9 (O-C-Si), 40.5 [(C=O)CH2], 17.9 (CH3), –3.6 and –3.9 (2ϫ
SiCH3) ppm. GC–MS (EI): m/z (%) = 258 (4) [M]+, 243 (5), 162
(11), 136 (13), 135 (100), 105 (12). HRMS (EI): calcd. for
C15H18O2Si: [M]+ 258.1076; found 258.1066.
1
Isomer anti-10d: White solid; Rf = 0.39 (PE/Et2O 20:80). H NMR
(300 MHz, CDCl3): δ = 3.79 [br. d, 3J = 9.4 Hz, 1 H, CH(OH)],
3.10–2.70 (br. s, 2 H, 2ϫ OH), 2.50 [m, 2 H, (C-3)CH2], 2.49 [d,
2J = 18.1 Hz, 1 H, (C=O)CHaHb], 2.35 [d, 2J = 18.1 Hz, 1 H,
(C=O)CHaHb], 2.20 [q, 3J = 7.7 Hz, 2 H, (C-2)CH2], 1.42–1.10 (m,
10 H, 5ϫ CH2), 1.21 (t, 3J = 7.6 Hz, 3 H, CH3), 1.02 (t, 3J =
7.7 Hz, 3 H, CH3), 0.86 (t, 3J = 6.8 Hz, 3 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 205.5 (C=O), 173.3 (C-3), 144.7 (C-2), 81.4
(C-4, Cq–O), 75.9 [CH(OH)], 46.7 [(C=O)CH2], 31.9 [(C-3)CH2],
31.7 [(C-2)CH2], 29.3, 26.7, 22.7, 20.5 and 16.6 (5ϫ CH2), 14.2,
Isomer (minor) cis-7m: Rf = 0.40 (PE /Et2O 60:40). 1H NMR
(300 MHz, CDCl3): δ = 7.60–7.50 (m, 2 H, Hortho), 7.41–7.36 (m,
3
3 H, Hmeta + Hpara), 6.94 [d, J = 5.9 Hz, 1 H, HC=C(C=O)], 6.20
3
2
[d, J = 5.9 Hz, 1 H, CH=CH(C=O)], 2.68 [d, J = 19.2 Hz, 1 H,
2
(C=O)CHaHb], 2.45 [d, J = 19.2 Hz, 1 H, (C=O)CHaHb], 1.25 (s,
3 H, CH3), 0.48 and 0.46 (2ϫ CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 205.4 (C=O), 161.7 (C-3), 137.4 (C-2), 135.8 [C(Ph)i],
134.1 [2ϫ CH(Ph)o], 129.8 [CH(Ph)p], 128.3 [2ϫ CH(Ph)m], 69.9
(C-4, Cq–O), 61.5 (O-Cq-Si), 39.0 [(C=O)CH2], 20.9 (CH3), –3.2
and –3.4 (2ϫ SiCH3) ppm.
14.0 and 13.2 (3ϫ CH ) ppm. IR (thin film): ν = 3360, 2960, 2920,
˜
3
2870, 2855, 1680, 1640, 1460, 1375, 1195, 1150, 1130 cm–1. MS
(CI): m/z (%) = 269 [M + H]+. HRMS (EI): calcd. for C16H28O3
[M]+ 268.2039; found 268.2115.
Isomer syn-10d: White solid; m.p 76–77 °C; Rf = 0.14 (PE/Et2O
20:80). H NMR (300 MHz, CDCl3): δ = 3.84 [dd, J = 7.9, J =
1
3
3
General Procedure for the Acidic Ring-Opening of Spiroepoxycyclo-
pentenones 7: A spiroepoxycyclopentenone 7 (1 mmol) was mixed
with H2SO4 (0.75 m, 7.2 mL, 5.5 mmol, 11 equiv.). The mixture was
stirred at room temperature overnight (15 h). A solution of
NaHCO3 (1 m, 11 mL, 11 mmol) was added, and the mixture was
extracted with CH2Cl2 (2ϫ 10 mL) and ether (10 mL). The organic
layers were collected, dried with Na2SO4, and then concentrated in
vacuo. Flash chromatography on silica gel yielded a dihydroxylated
cyclopentenone 10.
2
3.4 Hz, 1 H, CH(OH)], 3.20–2.50 (br. s, 2 H, 2ϫ OH), 2.78 [d, J
= 18.1 Hz, 1 H, (C=O)CHaHb], 2.21 [d, 2J = 18.1 Hz, 1 H, (C=O)-
3
CHaHb], 2.55–2.20 [m, 2 H, (C-3)CH2], 2.22 [q, J = 7.6 Hz, 2 H,
3
(C-2)CH2], 1.45–1.10 (m, 10 H, 5ϫ CH2), 1.19 (t, J = 7.5 Hz, 3
3
3
H, CH3), 1.03 (t, J = 7.6 Hz, 3 H, CH3), 0.86 (t, J = 6.8 Hz, 3
H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 206.4 (C=O),
172.6 (C-3), 144.5 (C-2), 82.6 (C-4, Cq–O), 75.3 [CH(OH)], 45.1
[(C=O)CH2], 31.8 [(C-3)CH2], 31.3 [(C-2)CH2], 29.2, 26.3, 22.6,
19.9 and 16.6 (5ϫ CH2), 14.1, 13.7 and 12.9 (3ϫ CH3) ppm. IR
2,3-Diethyl-4-hydroxy-4-(1-hydroxycyclohexyl)cyclopentenone (10b):
Ring-opening of epoxide 7b (80 mg, 0.34 mmol) by the General
Procedure (Table 3, Entry 1) gave 10b (55 mg, 64%) after flash
(thin film): ν = 3420, 2920, 2850, 1685, 1640, 1455, 1380 cm–1. MS
˜
(CI): m/z (%) = 269 [M + H]+.
1
chromatography. Yellow oil; Rf = 0.24 (PE/Et2O 75:25). H NMR
2,3-Diethyl-4-hydroxy-4-(1-hydroxy-1-phenylmethyl)cyclopent-2-
enone (10e): Ring-opening of epoxide 7e (43 mg, 0.18 mmol) by the
General Procedure (Table 3, Entry 4) but with addition of tBuOH
as solvent (2 mL) gave anti-10e (12 mg, 26%) and its diastereomer
syn-10e (9 mg, 20%) after flash chromatography. In a second ex-
periment (Table 3, Entry 5), by the General Procedure but with ad-
dition of THF as solvent (5 mL), ring-opening of epoxide 7e
(120 mg, 0.5 mmol) gave cyclopentenone anti-10e (36 mg, 28%)
and its diastereomer syn-10e (36 mg, 28%) after flash chromatog-
raphy.
(300 MHz, CDCl3): δ = 3.20–2.60 (br. s, 2 H, 2ϫ OH), 2.67 [dq, 2J
= 13.3, 3J = 7.6 Hz, 1 H, (C-3)CHaHbCH3], 2.64 [d, 2J = 18.2 Hz, 1
H, (C=O)CHaHb], 2.50 [dq, 2J = 13.3, 3J = 7.6 Hz, 1 H, (C-3)
2
CHaHbCH3], 2.35 [d, J = 18.2 Hz, 1 H, (C=O)CHaHb], 2.22 [dq,
3
2J = 13.6, J = 7.6 Hz, 1 H, (C-2)CHaHbCH3], 2.16 [dq, 2J = 13.6,
3J = 7.5 Hz, 1 H, (C-2)CHaHbCH3], 1.70–1.00 (m, 10 H, 5ϫ CH2),
1.19 (t, 3J = 7.6 Hz, 3 H, CH3), 1.01 (t, 3J = 7.5 Hz, 3 H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.7 (C-1, C=O),
175.0 (C-3, C=C-CO), 144.6 (C-2, C=C-CO), 84.2 (C-4, Cq–O),
76.5 (Cq–O), 47.5 [C-5, (C=O)CH2], 32.4 [(C-3)CH2], 31.5 [(C-2)-
CH2], 25.6, 21.6, 21.5, 21.4 and 16.7 (5ϫ CH2), 14.1 (CH3), 13.1
1
Isomer anti-10e: Yellow oil; Rf = 0.20 (PE/Et2O 80:20). H NMR
(300 MHz, CDCl3): δ = 7.34 (m, 5 H, Har), 4.87 [s, 1 H, CH(OH)],
(CH ) ppm. IR (thin film): ν = 3520, 3340, 2920, 2870, 1685, 1630,
˜
3
2
2
3
1450, 1380, 1160 cm–1. MS (CI): m/z (%) = 253 [M + H]+.
2.84 [d, J = 17.7 Hz, 1 H, (C=O)CHaHb], 2.50 [dq, J = 14.0, J
= 7.5 Hz, 1 H, (C-3)CHaHb], 2.44 [dq, J = 14.0, 3J = 7.5 Hz, 1 H,
2
4-Hydroxy-4-(1-hydroxyheptyl)-2,3-dimethylcyclopent-2-enone
(10c): Ring-opening of 7c (90 mg, 0.40 mmol) by the General Pro-
cedure (Table 3, Entry 2) gave anti-10c (58 mg, 59%) and its dia-
stereomer syn-10c (8 mg, 8%) after flash chromatography.
(C-3)CHaHb], 2.90–2.20 (br. s, 2 H, 2ϫ OH), 2.25–2.05 [m, 2 H,
(C-2)CH2], 2.13 [d, J = 17.7 Hz, 1 H, (C=O)CHaHb], 1.22 (t, 3J =
2
7.5 Hz, 3 H, CH3), 0.95 (t, 3J = 7.5 Hz, 3 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 205.0 (C=O), 172.4 (C-3), 145.0 (C-2), 139.2
Isomer anti-10c: Colourless oil; Rf = 0.43 (Et2O). 1H NMR [C(Ph)i], 128.7 [CH(Ph)p], 128.5 [2ϫ CH(Ph)m], 127.4 [2ϫ CH-
(300 MHz, CDCl3): δ = 3.79 [br. d, 3J = 9.4 Hz, 1 H, CH(OH)], (Ph)o], 81.8 [C-4, Cq(OH)], 77.4 [CH(OH)], 46.3 [(C=O)CH2], 20.2
3.30–2.80 (m, 2 H, 2ϫ OH), 2.49 [d, 2J = 18.1 Hz, 1 H, (C=O)-
[(C-3)CH2], 16.7 [(C-2)CH2], 14.1 (CH3), 12.9 (CH3) ppm. IR (thin
Eur. J. Org. Chem. 2012, 7093–7105
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7103

M. Ahmar, S. Thomé, B. Cazes
FULL PAPER
film): ν = 3400, 3050, 2970, 2935, 2885, 1695, 1640, 1450, 1380,
Procedure gave trans-11e (25 mg, 47%) after flash chromatography
˜
1
735, 705 cm–1. HRMS (EI): calcd. for C16H20O3 [M]+ 260.1413; (PE/Et2O 75:25). Yellow oil; Rf = 0.16 (PE/Et2O 75:25). H NMR
found 260.1424.
(300 MHz, CDCl3): δ = 7.65–7.75 (m, 2 H, Har), 7.40–7.50 (m, 3
H, Har), 7.20–7.35 (m, 5 H, Har), 6.20 [s, 1 H, O-CH(Ph)-O], 5.39
[s, 1 H, O-Cq-CH(Ph)-O], 3.10 [d, 2J = 18.0 Hz, 1 H, (C=O)-
Isomer syn-10e: Yellow oil; Rf = 0.16 (PE/Et2O 80:20). 1H NMR
(300 MHz, CDCl3): δ = 7.21 (m, 5 H, Har), 4.99 [s, 1 H, CH(OH)],
2
CHaHb], 2.95 [d, J = 18.0 Hz, 1 H, (C=O)CHaHb], 1.73–2.33 (m,
2
3.90–2.40 (br. s, 2 H, 2ϫ OH), 2.85 [d, J = 18.1 Hz, 1 H, (C=O)-
3
3
4 H, 2ϫ CH2CH3), 0.84 (t, J = 7.5 Hz, 3 H, CH2CH3), 0.75 (t, J
= 7.5 Hz, 3 H, CH2CH3) ppm. At 500 MHz, irradiation of proton
CH(Ph)–O at δ = 5.40 ppm resulted in the enhancement of proton
(C=O)CHaHb at δ = 2.97 ppm (5% nOe), of the acetal proton O-
CH(Ph)-O at δ = 6.20 ppm (4% nOe) and of the ortho-protons of
the phenyl group CHc(Ph)–O at δ = 7.27 ppm (3.6% nOe).
CHaHb], 2.57 [q, 3J = 7.5 Hz, 2 H, (C-3)CH2], 2.20 [d, 2J = 18.1 Hz,
2
3
1 H, (C=O)CHaHb], 2.06 [dq, J = 13.4, J = 7.5 Hz, 1 H, (C-2)-
2
3
CHaHb], 1.96 [dq, J = 13.4, J = 7.5 Hz, 1 H, (C-2)CHaHb], 1.28
2
3
(t, J = 7.5 Hz, 3 H, CH3), 0.75 (t, J = 7.5 Hz, 3 H, CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 204.8 (C=O), 171.6 (C-3), 144.9
(C-2), 138.5 [C(Ph)i], 128.3 [C(Ph)p], 128.1 [2ϫ C(Ph)m], 126.8 [2ϫ
C(Ph)o], 82.9 [C-4, Cq(OH)], 77.4 [CH(OH)], 45.0 [C-5, (C=O)-
CH2], 20.9 [(C-3)CH2], 16.4 [(C-2)CH2], 14.3 (CH3), 12.3
Supporting Information (see footnote on the first page of this
1
article): The H and 13C NMR spectra of cyclopentenones 10 and
(CH ) ppm. IR (thin film): ν = 3400, 3060, 3030, 2965, 2935, 2875,
˜
3
acetals 11 are provided.
1690, 1635, 1490, 1460, 1450, 1375, 1195, 735, 700 cm–1. HRMS
(CI): calcd. for C16H21O3 [M + H]+ 261.1491; found 261.1488.
Acknowledgments
General Procedure for Acetalization of Dihydroxylated Cyclopen-
tenones 10: A crystal of para-toluenesulfonic acid was added to a
solution of a dihydroxylated cyclopentenone 10 (0.15 mmol) and
distilled benzaldehyde (15.5 mg, 0.15 mmol) in benzene (2.5 mL)
under a Dean–Stark apparatus. The mixture was heated at reflux
for 1–2 h. After cooling, the mixture was filtered over neutral alu-
mina (grade III), which was further eluted with ether. Evaporation
of the solvents followed by flash chromatography gave the acetal
11. In order to prevent the hydrolysis of the acetal 11 on the silica
gel column, the column was prepared with a 1% triethylamine PE/
Et2O mixture of solvents and then eluted with this solvent mixture.
The authors thank B. Fenet for helpful assistance with the nuclear
Overhauser effect experiments.
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Acetal trans-11c: Acetalization of the major isomer of dihydrox-
ylated cyclopentenone anti-10c (35 mg, 0.15 mmol) by the General
Procedure gave trans-11c (10 mg, 21%) after flash chromatography
(PE/Et2O gradient 95:5 to 40:60). Yellow oil; Rf = 0.33 (PE/Et2O
1
80:20). H NMR (300 MHz, CDCl3): δ = 7.54 (m, 2 H, Har), 7.40
3
3
(m, 3 H, Har), 5.98 [s, 1 H, O-CH(Ph)-O], 4.14 (dd, J = 9.1, J =
3.4 Hz, 1 H, CH–O), 2.92 [d, 2J = 18.5 Hz, 1 H, (C=O)CHaHb],
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the acetal proton O-CH(Ph)-O at δ = 6.00 ppm (0.5% nOe). Irradi-
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ylated cyclopentenone anti-10d (27 mg, 0.1 mmol) by the General
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1
90:10). H NMR (300 MHz, CDCl3): δ = 7.55 (m, 2 H, Har), 7.40
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3
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3.4 Hz, 1 H, CH(nC6H13)-O], 2.94 [d, J = 18.5 Hz, 1 H, (C=O)-
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2.51 ppm (7% nOe) and of the acetal proton O-CH(Ph)-O at δ =
5.97 ppm (6.8% nOe).
2
3
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7104
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Received: August 1, 2012
Published Online: October 30, 2012
1744–1747.
Eur. J. Org. Chem. 2012, 7093–7105
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7105