Synthesis of functionalized bicyclo[3.2.0]heptanes - A study of the [2+2] photocycloaddition reactions of 4-hydroxycyclopent-2-enone derivatives

Article abstract of DOI:10.1002/ejoc.200900749

A selection of 4-hydraxycyclopent-2-enone derivatives were prepared in enantiomerically pure form, and their photochemical [2+2] cycloaddition reactions with a variety of alkenes were studied, with a view to providing diversely functionalized bicyclo[3.2.0]heptanes. Intermolecular reactions provided the target structures in reasonable yields as a mixture of exo and endo adducts, in proportions which varied very little as a. function of the steric bulk of the reactants or the reaction conditions, The system was suitably adapted for an intramolecular reaction, which provided a single, stereochemically pure product, the convenient precursor of a rigid, concave, trioxygenated skeleton.

Full text of DOI:10.1002/ejoc.200900749

FULL PAPER
DOI: 10.1002/ejoc.200900749
Synthesis of Functionalized Bicyclo[3.2.0]heptanes – a Study of the [2+2]
Photocycloaddition Reactions of 4-Hydroxycyclopent-2-enone Derivatives
Matthieu Le Liepvre,[a] Jean Ollivier,[a] and David J. Aitken*[a]
Keywords: Cycloaddition / Carbocycles / Enones / Photochemistry
A selection of 4-hydroxycyclopent-2-enone derivatives were
prepared in enantiomerically pure form, and their photo-
very little as a function of the steric bulk of the reactants or
the reaction conditions. The system was suitably adapted for
chemical [2+2] cycloaddition reactions with a variety of al- an intramolecular reaction, which provided a single, stereo-
kenes were studied, with a view to providing diversely func-
tionalized bicyclo[3.2.0]heptanes. Intermolecular reactions
provided the target structures in reasonable yields as a mix-
ture of exo and endo adducts, in proportions which varied
chemically pure product, the convenient precursor of a rigid,
concave, trioxygenated skeleton.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
intramolecular cycloadditions of bis(enones) have also been
described, as have gold(I)-catalyzed cycloisomerizations of
enynes.[6b] Two-component construction strategies are also
known, involving Lewis-acid-catalyzed intermolecular [2+2]
cycloadditions between appropriately functionalized cyclo-
pentenes and alkenes[6c,16] or alkynes.[17] A number of other
approaches have been investigated.[18]
Introduction
The bicyclo[3.2.0]heptane skeleton (Figure 1) attracts
considerable interest in organic chemistry. The structural
system is a core feature in a range of natural products[1]
and some therapeutic agents,[2,3] and the inherent ring strain
provides the driving force for a diversity of ring-expan-
sion[4,5] or skeletal isomerization reactions,[6] leading to
other cyclic or bicyclic systems. Various synthetic ap-
proaches for the construction of bicyclo[3.2.0]heptanes have
been established, and in a good number of cases, they pro-
ceed with a significant degree of stereoselectivity. Starting
from acyclic precursors, intramolecular [2+2] cycload-
ditions have been described under a variety of conditions:
copper(I)-catalyzed photocycloaddition of nonconjugated
1,6-heptadienes,[7] Lewis-acid-catalyzed thermal cycload-
dition,[8] gold(I)-catalyzed cycloaddition of allene–al-
kenes,[9] and thermal cyclization of ketene–alkenes,[10] ke-
teneiminium–alkenes,[5c,11] and ketene–allenes.[12] The pho-
tochemical,[13] electrochemical,[14] and cobalt-catalyzed[15]
In principle, one of the most attractive entries into bi-
cyclo[3.2.0]heptanes is the photochemical [2+2] cycload-
dition between a cyclopent-2-enone and an alkene.[19] Intra-
molecular reactions generally proceed with good regio- and
stereochemical control, but selectivity is rather more diffi-
cult to achieve in intermolecular versions. Several applica-
tions of intermolecular [2+2] photochemical cycloaddition
reactions have been described using cyclopent-2-enones and
asymmetrical alkene partners.[20] Some studies have in-
cluded 2- and 3-substituted cyclopent-2-enones,[21] but work
on 4-substituted derivatives, and in particular the chiral
compound 4-hydroxycyclopent-2-enone and derivatives
thereof, is much more scarce (Figure 1). This seemed rather
curious, since these materials have been otherwise widely
employed in synthesis,[22] particularly in the preparation
of prostaglandins.[23] Indeed, some synthetically useful
[4+2][24] and [3+2][25] cycloadditions as well as cyclopropan-
ations[26] have been described for this cyclic enone. In con-
trast, the rare literature on photochemical [2+2] cycload-
ditions involving these compounds deals only with acetyl-
ene,[27] allene,[28] and a small selection of vinyl acetates[29]
as intermolecular olefin partners, whereas a very limited
number of intramolecular cases have been examined.[6f,30,31]
No studies have hitherto been described concerning the
scope of photochemical reactivity of the 4-oxycyclopen-
tenones. Given their privileged status as building blocks in
organic synthesis, we undertook an investigation of the pre-
parative utility of their [2+2] photocycloaddition reactions
Figure 1. Target bicyclic skeleton and photochemical approach to
its construction.
[a] Laboratoire de Synthèse Organique et Méthodologie, ICMMO
(UMR 8182), Bât. 420, Université Paris-Sud 11,
15 rue Georges Clemenceau, 91405 Orsay, France
Fax: +33-1-69156278
E-mail: david.aitken@u-psud.fr
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M. Le Liepvre, J. Ollivier, D. J. Aitken
FULL PAPER
with a view to the elaboration of new diversely function-
With the substrates 2a–e in hand, we began our explora-
alized bicyclo[3.2.0]heptanes. The results of these studies tion of the photochemical [2+2] photocycloaddition reac-
are presented and discussed in this paper.
tions. We designed the first series of experiments to estab-
lish the impact of the nature and the steric bulk of the O-
bound group on the yield and diastereoselectivity of the
reaction. One of the most challenging alkene partners (in
terms of diastereoselectivity) is ethene, due to its small size.
We carried out the [2+2] photocycloaddition reactions on
each of the cyclopentenones 2a–e in turn, using a medium-
pressure Hg lamp (400 W) in a water-cooled immersion re-
actor fitted with a Pyrex filter. We allowed the substrates
to react at 5 m, and acetone served as both solvent and
photosensitizer under these conditions (Table 2).
Results and Discussion
We first prepared 4-hydroxycyclopenten-2-one (2a) and a
selection of O-functionalized derivatives in enantiomerically
pure form. We prepared the (+)-(1R,3S) antipode of cy-
clopent-2-ene-1,3-diol monoacetate (1) according to the lit-
erature[32] in Ͼ99% ee (Scheme 1) and oxidized it smoothly
to (R)-4-acetoxycyclopenten-2-one (2b) using PDC.[33]
However, as anticipated,[34] the hydrolytic conversion of 2b
into the parent alcohol 2a was complicated by the loss of
enantiomeric integrity.
Table 2. Photochemical [2+2] cycloadditions of ethene with (S)-4-
hydroxycyclopent-2-enone derivatives 2a–e.
Entry
Enone
2
R
Yield 5 + 6
Ratio
[%]
5/6[a]
1
2
3
4
5
2a
2b[b]
2c
H
Ac
TBS
tBuCO
MOM
49
43
50
49
48
70:30
63:37
68:32
60:40
70:30
2d
2e
Scheme 1. Approaches for the synthesis of 4-hydroxycyclopent-2-
enone (2a) in enantiomerically pure form.
[a] Ratios were determined by GC analysis of the crude reaction
products. [b] The (R) enantiomer was used.
We adopted a slightly longer but more reliable approach
(Table 1). Using adaptations of literature procedures, we
functionalized the hydroxy group of 1 as required by apply-
ing the appropriate electrophilic halide to give 3c–e and
then removed the acetate under basic conditions to provide
4c–e, from which we obtained the target derivatives 2c–e
with an (S) configuration by PDC oxidation. These reac-
tions all proceeded smoothly and in good yield, and we
verified the product enones as having Ͼ99% ee. Finally, we
obtained the (S) enantiomer of the parent alcohol 2a by the
mildly acidic cleavage of silyl ether 2c (Scheme 1).
In all cases, the starting material was consumed (Ͼ90%)
within only 15 min. We stopped irradiating after this time,
and isolated the cyclobutane adducts by chromatography
after evaporation of the solvent. We obtained the expected
bicyclo[3.2.0]heptanes in reasonable and fairly uniform
yields (approximately 50%), exclusively with a cis ring junc-
tion and as a mixture of exo and endo stereoisomers. We
easily distinguished these two isomeric forms in each case,
1
since the H NMR spectrum of one isomer (invariably the
major component) showed a clean doublet (J = 4.8–6.8 Hz)
at δ = 4.20–5.20 ppm for 4-H, whereas this proton appeared
in the same chemical shift range as a more complex signal
in the spectrum of the other (minor) isomer. We tentatively
designated the major isomer as exo (5a–e) and the minor
isomer as endo (6a–e) in each case, on the basis of steric
arguments; we obtained subsequent evidence conclusively
in support of this attribution (vide infra). The general selec-
tivity trend was rather disappointing, since the exo/endo
diastereoselectivity ratio (dr) remained around 70:30
throughout the series. The bulky O-TBS substituent of 2c
induced a dr which was comparable with that observed for
the O-unsubstituted substrate 2a, whereas the pivaloate 2d
provided no more selectivity than the diminutive acetate 2b.
Interestingly, in the only previous comparative study of 2a
and a few of its O-functionalized derivatives, Sydnes and
co-workers reported that the unsensitized [2+2] photocy-
Table 1. Preparation of enantiomerically pure derivatives 2.
Entry Derivative
RCl
Yield 3
[%]
Yield 4
[%]
Yield 2
[%]
1
2
3
c
d
e
TBSCl
tBuCOCl
MOMCl
98
80
78
98[a]
77[b]
83[a]
96
96
79
[a] Base used for hydrolysis: NaOMe. [b] Base used for hydrolysis:
K2CO3.
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Synthesis of Bicyclo[3.2.0]heptanes by [2+2] Photocycloaddition
cloadditions of these compounds with allene generally pro- rex). Although conversion was not always complete, longer
ceeded with low dr but with a slight preference for the for- reaction times tended to produce more complex mixtures
mation of the endo isomer.[28]
(by GC analysis) without increasing the yield of the desired
We next varied the experimental conditions, using the bicyclo[3.2.0]heptanes. In general, the yields of these prod-
TBS ether derivative 2c as the standard substrate. The re- ucts were comparable with those of the reaction involving
sults are presented in Table 3, and several trends emerge. ethene. We performed the analysis of isomeric mixtures on
First, using acetone as the standard solvent, we observed crude material using NMR and GC techniques, but prepar-
no temperature or concentration effects (Table 3, Entries 1– ative chromatographic separation was generally not conve-
3). We then examined different solvents, with appropriate nient. The results are summarized in Table 4.
adaptation of the reaction time to provide for Ͼ90% con-
sumption of 2c. These sensitized reactions were slower than
the reaction run in acetone, requiring up to 50 min in the
Table 4. [2+2] Photocycloaddition reaction of cyclopentenone 2c
with alkenes 7a–g.
cases of CH2Cl2 or acetonitrile (Table 3, Entries 4 and 5) to
achieve near completion (conversion Ͼ90%), by which time
other products had begun to appear (detected by GC analy-
sis). Isolated product yields remained similar to those ob-
served in acetone. The consumption of 2c was somewhat
faster in methanol or hexane, requiring around 30 min, but
we observed more significant amounts of secondary prod-
ucts in these cases, resulting in lower isolated yields of the
target bicyclic materials (Table 3, Entries 6 and 7). Overall,
acetone proved to be the most convenient solvent, but we
note that the exo/endo ratio remained remarkably uniform,
whatever the nature of the solvent. In their study of the
[2+2] photocycloaddition of 2c with allene, Sydnes and co-
workers noted a solvent effect, with higher product yields
being obtained in less polar solvents. This trend was in-
verted for 2a, which gave a higher yield in more polar sol-
vents.[28]
[a] The exo/endo ratios were determined for the crude reaction
1
products by GC analysis or from H NMR spectra. [b] Expressed
Table 3. [2+2] Photocycloaddition reaction of cyclopentenone 2c
with ethene.[a]
in terms of quantity of material isolated after chromatography; the
exo component (8d) consisted of two stereoisomers (78:22) with
undetermined configurations at the chlorine-bearing carbon atoms.
[c] Four unidentified stereoisomers were observed in a ratio of
47:29:18:6. [d] Four unidentified stereoisomers were observed in a
ratio of 33:25:22:20.
The completely symmetrical alkene components, tetra-
methylethylene (7a) and acetylene (7b), gave yields and
exo/endo ratios comparable to those observed above for eth-
ene. The results obtained with 7b are comparable to those
in the literature.[27] We were disappointed by the lack of
improvement in the dr with the sterically hindered 7a. We
obtained only two adducts with cyclopentene (7c). The
exo/endo ratio remained near parity, which meant we ob-
tained isomers 8c and 9c in a single form, which we propose
to be cis-anti-cis on the basis of steric and geometric argu-
ments. This encouraging development was not sustained
with other symmetrical alkenes, however. 1,2-Dichloroeth-
ene (7d) furnished three stereoisomeric adducts, in which
Entry Solvent Time
Sensitizer
Yield 5c + 6c
Ratio
[min] [0.1 equiv.]
[%]
5c/6c[b]
[c]
1
2
3
4
5
6
7
acetone
15
50
40
48
41
46
13
18
68:32
71:29
68:32
70:30
68:32
68:32
69:31
acetone 15[d]
[c]
[c]
acetone
CH2Cl2
MeCN
MeOH
hexane
15[e]
50
50
35
25
PhCOMe
PhCOMe
PhCOMe
PhCOMe
[a] 20 °C, 5 m enone solution, Pyrex filter, unless stated otherwise.
[b] Ratios were determined by GC analysis of the crude reaction
products. [c] The solvent served as a sensitizer. [d] Reaction carried
out at –30 °C. [e] The enone concentration was 1 m.
We then turned our attention to photocycloaddition re- the possible cis/trans isomerization of the chlorine substitu-
actions involving more elaborate alkene partners, with a ents[31b,35] we could neither verify nor rule out due to the
view to obtaining bicyclo[3.2.0]heptanes substituted on intractable nature of the product mixture. 2,3-Dihydro-2,4-
both the four- and five-membered rings. We again selected dioxine (7e) also provided a mixture of four isomeric prod-
silyl ether 2c as the representative cyclopentenone, and ucts in which we could only evaluate the isomeric ratio (but
studied a range of diversely substituted alkenes 7a–g under not the isomer identities). Finally, we tested two nonsym-
standard conditions (5 m 2c in acetone as solvent/sensi- metrical alkene partners, 1,1-dimethoxyethylene (7f) and
tizer, excess alkene, 15–30 min irradiation, room temp., Py- isobutene (7g). The former, with a strong electronic effect,
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M. Le Liepvre, J. Ollivier, D. J. Aitken
FULL PAPER
produced only the head-to-tail regioisomer with a slightly
improved exo/endo ratio, but the latter yielded four isomers
whose identity was difficult to assess.
The intermolecular cycloadditions studied up to this
point had provided a diversity of bicyclo[3.2.0]heptanes in
acceptable yields, but the low selectivities limit the potential
utility in preparative work, which requires single-stereoiso-
mer materials. Therefore, we decided to investigate the reac-
tion in an intramolecular mode. We anticipated that the al-
kene moiety could be introduced conveniently as an allyl
alcohol derivative and attached to the core 4-hydroxycy-
clopenten-2-one by an acetal linkage (Scheme 2). This
should allow for the facile liberation of the hydroxy groups
after the cycloaddition.[36] We prepared the appropriate tar-
get substrate 12 as follows. Treatment of 2a with allyl chlo-
romethyl ether[37] gave acetal 10 in 80% yield. Basic hydrol-
ysis liberated alcohol 11, which we oxidized with PDC to
give 12 in 57% yield over 3 steps. The irradiation of 12 in
acetone for 15 min resulted in the consumption of all the
stating material and the formation of a single new product
(by GC analysis). We isolated this material in 60% yield
and, from NMR spectral analysis, deduced it to be the tri-
cyclic adduct 13. A single-crystal X-ray diffraction analysis
provided confirmation of this structure (Figure 2).[38] The
1H NMR spectrum of 13, with its imposed endo configura-
tion, showed a complex 7a-H signal (apparently a tt) at δ =
4.58 ppm. This characteristic signal provided confirmation
that the minor components in the 5/6 mixtures described
above (Table 1) were the endo isomers. Finally, the careful
acid hydrolysis of 13 furnished the enantiomerically pure,
highly functionalized, dihydroxy ketone 14, without skeletal
rearrangement (Scheme 2).
Figure 2. Crystal structure of tricyclic acetal 13. Displacement el-
lipsoids are drawn at the 50% probability level.
Conclusions
We have prepared a range of new, highly functionalized
bicyclo[3.2.0]heptanes from chiral nonracemic 4-hydroxycy-
clopentenone derivatives. The scope of the intermolecular
[2+2] photocycloaddition reaction is quite large, but the
stereoselectivity is low. Changing to the intramolecular
mode allows complete control of all selectivity aspects and
furnishes a rigid, concave, trioxygenated manifold 14. Such
materials are of interest in the context of chiral bidentate
ligands[5b] and are potential candidates for controlled ring-
rearrangement or -enlargement reactions. Given the relative
simplicity of the procedures, the photochemical [2+2] as-
sembly of complex bicyclo[3.2.0]heptanes should retain
interest in the future. Studies of the synthetic applications
and reactivity of 14 and its derivatives is currently underway
in our laboratory.
Experimental Section
General Remarks: Melting points (uncorrected) were measured
with a Büchi B-545 apparatus. Optical rotations were measured
with a Perkin–Elmer 241 polarimeter. Fourier transform IR spectra
were recorded with a Perkin–Elmer Spectrum One spectrophotom-
eter. 1H NMR spectra were recorded with Bruker AM 300
(300 MHz) or AV 360 (360 MHz) instruments; chemical shifts are
expressed with respect to residual protonated solvent (δ = 7.27 ppm
for CHCl3), which served as an internal standard. 13C NMR spec-
tra were recorded with a Bruker AV 360 (90 MHz) instrument;
chemical shifts are expressed with respect to the deuterated solvent
(δ = 77.0 ppm for CDCl3). DEPT-135 pulses were used for the de-
termination of 13C NMR signal types. Diastereomeric ratios (dr)
were determined by GC with a Fisons GC 8000 Top instrument
fitted with a dimethylpolysiloxane column (12 mϫ0.22 mmϫ
Scheme 2. Intramolecular mode of the reaction providing a single
product.
We note that the final product 14 is formally a [2+2] ad-
duct from allyl alcohol and enone 2a. In the intermolecular
mode, allyl alcohol gives notoriously poor regio- and
stereoselectivities in photocycloadditions with related cyclo-
pentenones;[39] the isolation of one single isomer in this
work underlines the usefulness of the temporary tether ap-
proach for selectivity control.
1
0.2 µm) or from H NMR integration data. Enantiomeric excesses
(ees) were determined with the GC instrument described above,
fitted with
a β-cyclodextrin DM column (40 mϫ0.25 mmϫ
0.25 µm). Chemical-ionization mass spectra (MS) were recorded
with a Nermag R-10 instrument by using ammonia as the vector
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Synthesis of Bicyclo[3.2.0]heptanes by [2+2] Photocycloaddition
gas. High-resolution mass spectra (HRMS) were recorded with a
Finningan MAT 95S in positive electrospray mode. Elemental
analyses were performed by the Microanalysis Service, ICSN-
CNRS, Gif-sur-Yvette, France. Reaction solvents were dried ac-
cording to standard procedures prior to use. All reactions requiring
anhydrous conditions were performed under argon. Acetates 1,[32]
3c,[40] 3d,[41] and 3e,[42] and the alcohols 4c[43] and 4e[44] were pre-
pared according to the literature, and their spectroscopic data are
comparable to those previously reported.
guished, and the reaction mixture was concentrated. The residue
was purified by flash chromatography to provide the bicyclic prod-
ucts.
General Method for the Irradiation of Cyclopentenones in the Pres-
ence of a Nongaseous Alkene Partner (Method B): A solution of the
enone 2c (1 mmol) and the given alkene 7 (10 mmol) in acetone
(200 mL) was saturated with argon for 15 min and then irradiated
with a 400 W medium-pressure mercury vapor lamp fitted with a
Pyrex filter for 15 or 30 min (see Table 4). At the end of the reaction
time, the lamp was extinguished, and the reaction mixture was con-
centrated. The residue was purified by flash chromatography to
give the polycyclic products.
(–)-(1S,4R)-4-Hydroxy-2-cyclopenten-1-yl Pivalate (4d): To a solu-
tion of diester 3d (560 mg, 2.5 mmol) in MeOH (5 mL) under ar-
gon, was added K2CO3 (342 mg, 2.5 mmol). The solution was
stirred at room temp. for 20 min and then quenched with a mixture
of aq. HCl (5%, 12 mL) and Et2O (12 mL). The mixture was stirred
until the aq. layer was clear. This layer was then extracted with
Et2O (2ϫ10 mL), and the combined organic phases were dried
with MgSO4 and filtered. The solvents were evaporated, and the
residue was purified by flash chromatography (Et2O/EtOAc, 80:20)
to give 4d as a colorless oil (350 mg, 77%). [α]2D3 = –59.5 (c = 2.30,
(4S)-4-Hydroxybicyclo[3.2.0]heptan-2-one [exo-5a (1R,5S) and
endo-6a (1S,5R)]: By using 2a and ethene, according to Pro-
cedure A, flash chromatography (Et2O/EtOAc, 95:5) gave an in-
separable mixture of bicyclic products exo-5a and endo-6a as a col-
orless oil (49%; 70:30 dr, by 1H NMR). 1H NMR (300 MHz,
CDCl3): δ = 4.56 (dd, J = 17.7, J = 7.7 Hz, 1 H, 4-H, major), 4.36
(d, J = 4.9 Hz, 1 H, 4-H, minor), 3.25–3.10 (m, 1 H, 1-H, minor),
3.10–2.60 (m, 5 H, major + minor), 2.60–2.00 (m, 3 H, major +
minor), 1.95–1.65 (m, 4 H, major + minor) ppm. 13C NMR
(90 MHz, CDCl3): δ = 222.4 (major), 220.1 (minor), 73.4 (major),
69.4 (minor), 47.0 (minor), 45.6 (major), 43.8 (major), 44.3 (minor),
43.7 (major), 39.7 (minor), 22.4 (minor), 21.6 (major), 21.5 (major),
1
CH2Cl2). H NMR (300 MHz, CDCl3): δ = 6.11 (ddd, J = 5.6, J
= 1.9, J = 1.3 Hz, 1 H, 2-H), 5.98 (ddd, J = 5.6, J = 2.0, J = 1.1 Hz,
1 H, 3-H), 5.51–5.45 (m, 1 H, 4-H), 4.69–4.78 (m, 1 H, 1-H), 2.83
(dt, J = 14.6, J = 7.3 Hz, 1 H, 5-H), 1.76 (br. s, 1 H, OH), 1.61
(dt, J = 14.5, J = 4.0 Hz, 1 H, 5-H), 1.20 (s, 9 H, tBu) ppm. 13C
NMR (90 MHz, CDCl3): δ = 178.1, 138.1, 131.6, 76.7, 73.8, 40.0,
17.5 (minor) ppm. IR (neat): ν = 3422, 2948, 1732 cm–1. MS: m/z
˜
38.1, 26.7 ppm. IR (neat): ν = 3425, 2976, 1726, 1708, 1284, 1160
˜
= 144 [M + NH4]+. C7H10O2 (126.15): calcd. C 66.65, H 7.99;
found C 66.24, H 7.83.
cm–1. MS: m/z = 202 [M + NH4]+. C10H16O3 (184.23): calcd. C
65.19, H 8.75; found C 64.92, H 8.60.
(2R)-4-Oxobicyclo[3.2.0]hept-2-yl Acetate [exo-5b (1R,5S) and
endo-6b (1S,5R)]: By using 2b and ethene, according to Pro-
cedure A, flash chromatography (hexanes/Et2O, 70:30) gave an in-
separable mixture of bicyclic products exo-5b and endo-6b as a col-
orless oil (43%; 63:37 dr, by 1H NMR). 1H NMR (300 MHz,
CDCl3): δ = 5.29 (dt, J = 9.0, J = 7.4 Hz, 1 H, 4-H, minor), 5.17
(d, J = 5.7 Hz, 1 H, 4-H, major), 3.40–3.28 (m, 1 H, 3-H, minor),
3.10–2.70 (m, 3 H, major + minor), 2.60–2.30 (m, 3 H, major +
minor), 2.07 (s, 3 H, CH3, minor), 2.01 (s, 3 H, CH3, major), 1.95–
1.80 (m, 2 H, major + minor) ppm. 13C NMR (90 MHz, CDCl3):
δ = 219.0 (major), 216.8 (minor), 170.3 (minor), 170.1 (major), 75.7
(major), 71.2 (minor), 45.8 (minor), 43.9 (major), 42.8 (major), 41.8
(minor), 40.8 (major), 37.6 (minor), 22.1 (minor), 21.7 (major), 21.6
(major), 20.8 (major), 20.6 (minor), 18.2 (minor) ppm. IR (neat):
General Method for the Preparation of Cyclopentenones from Their
Alcohol Precursors: To a solution of the given alcohol 1 or 4c–e
(1 mmol) in CH2Cl2 (5 mL), PDC (1.5 mmol) was added under ar-
gon. The solution was stirred at room temp. for 16 h and then
filtered, the solid was washed with CH2Cl2 (2ϫ2 mL), and the
combined organic phases were dried with MgSO4, filtered, and
concentrated. The crude residue was then purified by flash
chromatography on silica gel to give the expected enones 2b–e.
(+)-(4R)-4-Acetoxycyclopent-2-enone (2b):[33] Eluent: Et2O/EtOAc
(80:20). Colorless oil. Yield: 80%. [α]2D0 = +95 (c = 0.1, CHCl3).
(–)-(4S)-4-(tert-Butyldimethylsiloxy)cyclopent-2-enol (2c):[33] Elu-
ent: hexanes/EtOAc (90:10). Colorless oil. Yield: 96%. [α]2D0 = –68
(c = 0.94, MeOH).
ν = 2948, 1753 cm–1. MS: m/z = 186 [M + NH ]+. C H O
˜
4
9
12
3
(–)-(1S)-4-Oxo-2-cyclopenten-1-yl Pivalate (2d):[24c] Eluent: Et2O/
EtOAc (80:20). Colorless oil. Yield: 96%. [α]2D0 = –111 (c = 1.0,
MeOH).
(168.19): calcd. C 64.27, H 7.19; found C 63.94, H 7.09.
(4S)-4-(tert-Butyldimethylsilyloxy)bicyclo[3.2.0]heptan-2-one [exo-
5c (1R,5S) and endo-6c (1S,5R)]: By using 2c and ethene according
to Procedure A, flash chromatography (hexanes/Et2O, 90:10) gave
an inseparable mixture of bicyclic products exo-5c and endo-6c as
a colorless oil (50%; 68:32 dr, by GC). 1H NMR (300 MHz,
CDCl3): δ = 4.47 (dt, J = 9.9, J = 7.5 Hz, 1 H, 4-H, major), 4.25
(dt, J = 4.8, J = 1.0 Hz, 1 H, 4-H, minor), 3.10–2.70 (m, 6 H, major
+ minor), 2.60–2.20 (m, 6 H, major + minor), 2.20–1.70 (m, 4 H,
major + minor), 0.89 (s, 9 H, SitBu, major), 0.86 (s, 9 H, SitBu,
minor), 0.06 (s, 6 H, SiMe2, minor), 0.05 (s, 6 H, SiMe2, major)
ppm. 13C NMR (90 MHz, CDCl3): δ = 220.9 (major), 218.5
(minor), 74.0 (major), 69.8 (minor), 46.4 (minor), 46.2 (major), 45.1
(minor), 44.4 (major), 43.9 (major), 40.3 (minor), 25.6 (major +
minor), 22.4 (minor), 21.5 (2 C major + minor), 17.9 (minor), 17.6
(major), –4.8 (major + minor), –4.9 (major + minor) ppm. IR
(–)-(4S)-4-(Methoxymethoxy)cyclopent-2-enone (2e): Eluent: hex-
anes/Et2O (50:50). Colorless oil. Yield: 79%. [α]2D0 = –16 (c = 1.0,
1
CH2Cl2). H NMR (360 MHz, CDCl3): δ = 7.61 (dd, J = 5.7, J =
2.3 Hz, 1 H, 3-H), 6.26 (d, J = 5.7 Hz, 1 H, 2-H), 4.89–4.85 (m, 1
H, 4-H), 4.80–4.72 (m, 2 H, OCH2O), 3.42 (s, 3 H, OCH3), 2.74
(dd, J = 18.4, J = 6.1 Hz, 1 H, 5-H), 2.33 (dd, J = 18.4, J = 2.5 Hz,
1 H, 5-H) ppm. 13C NMR (90 MHz, CDCl3): δ = 205.4, 161.4,
135.0, 95.7, 75.1, 55.0, 41.5 ppm. IR (neat): ν = 3075, 2949, 2893,
˜
1721 cm–1. MS: m/z = 160 [M + NH4]+. C7H10O3 (142.15): calcd.
C 59.14, H 7.09; found C 58.86, H 7.01.
General Method for the Irradiation of Cyclopentenones in the Pres-
ence of a Gaseous Alkene Partner (Method A): A solution of the
enone 2 (0.90 mmol) in acetone (180 mL) was presaturated with the
gaseous alkene. After 15 min, the mixture was irradiated with a
400 W medium-pressure mercury vapor lamp fitted with a Pyrex
(neat): ν = 2954, 1740 cm–1. MS: m/z = 258 [M + NH ]+. HRMS:
˜
4
calcd. for C13H24O2SiNa 263.1443; found 263.1437.
filter for 15 min; the passage of a slow stream of alkene gas was (2S)-4-Oxobicyclo[3.2.0]hept-2-yl Pivalate [exo-5d (1S,5R) and
maintained. At the end of the reaction time, the lamp was extin- endo-6d (1R,5S)]: By using 2d and ethene, according to Pro-
Eur. J. Org. Chem. 2009, 5953–5962
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5957

M. Le Liepvre, J. Ollivier, D. J. Aitken
FULL PAPER
cedure A, flash chromatography (CH2Cl2/MeOH, 98:2) gave an in-
separable mixture of bicyclic products exo-5d and endo-6d as a col-
orless oil (49%; dr 60:40, by 1H NMR). 1H NMR (360 MHz,
CDCl3): δ = 5.21 (dd, J = 16.4, J = 8.5 Hz, 1 H, 4-H, minor), 5.17
(d, J = 5.6 Hz, 1 H, 4-H, major), 3.45–3.20 (m, 1 H, 1-H, minor),
3.15–2.96 (m, 2 H, 1-H, 3-H, major), 2.90–2.60 (m, 4 H, major +
minor), 2.50–2.00 (m, 6 H, major + minor), 2.00–1.60 (m, 3 H,
inseparable mixture of the bicyclic exo-8b and endo-9b as a color-
less solid (41 %; 53:47 dr, by 1H NMR). 1H NMR (360 MHz,
CDCl3): δ = 6.46 (d, J = 2.5 Hz, 1 H, 6-H or 7-H, minor), 6.40 (d,
J = 2.5 Hz, 1 H, 6-H or 7-H, major), 6.25 (d, J = 2.5 Hz, 1 H, 6-
H or 7-H, minor), 6.20 (d, J = 2.5 Hz, 1 H, 6-H or 7-H, major),
4.40–4.30 (m, 2 H, 4-H, major + minor), 3.50 (dd, J = 7.3, J =
2.9 Hz, 1 H, 1-H, minor), 3.38–3.30 (m, 2 H, 1-H, 5-H, major),
major + minor), 1.21 (s, 9 H, tBu, minor), 1.00 (s, 9 H, tBu, major) 3.26–3.23 (m, 1 H, 5-H, minor), 3.21 (ddd, J = 15.5, J = 4.7, J =
ppm. 13C NMR (90 MHz, CDCl3): δ = 218.9 (major), 216.8
(minor), 177.5 (major + minor), 75.4 (major), 70.9 (minor), 45.9
(minor), 43.8 (major), 42.8 (major), 42.0 (minor), 40.9 (major), 37.7
(minor), 26.9 (minor), 26.8 (major), 23.1 (major), 22.3 (minor), 21.8
(major), 21.7 (major), 19.7 (minor), 18.1 (minor) ppm. IR (neat):
0.7 Hz, 1 H, 3-H, major), 3.05 (ddd, J = 17.4, J = 10.0, J = 1.2 Hz,
1 H, 3-H, minor), 2.35 (ddd, J = 17.3, J = 7.8, J = 1.5 Hz, 1 H, 3-
H, minor), 2.13–2.05 (m, 1 H, 3-H, major), 0.91 (s, 9 H, SitBu,
major), 0.88 (s, 9 H, SitBu, minor), 0.10 (s, 3 H, SiMe, minor), 0.08
(s, 3 H, SiMe, major), 0.07 (s, 6 H, SiMe, major + minor) ppm.
13C NMR (90 MHz, CDCl3): δ = 220.9 (major), 214.5 (minor),
141.8 (major), 141.2 (minor), 137.2 (minor), 131.8 (major), 68.1
(major), 66.1 (minor), 55.9 (minor), 53.9 (major), 53.7 (major), 49.0
(minor), 44.1 (major), 42.4 (minor), 25.6 (major + minor), 17.9
(major + minor), –4.8 (major + minor), –4.9 (major + minor) ppm.
ν = 2976, 1752 cm–1. MS: m/z = 200 [M + NH ]+. C H O
˜
4
11 18
2
(182.26): calcd. C 72.49, H 9.95; found C 72.13, H 9.86.
(4S)-4-(Methoxymethoxy)bicyclo[3.2.0]heptan-2-one
[exo-5e
(1R,5S) and endo-6e (1S,5R)]: By using 2e and ethene, according
to Procedure A, flash chromatography (hexanes/Et2O, 60:40) gave
an inseparable mixture of bicyclic products exo-5e and endo-6e as
IR (neat): ν = 3053, 1741 cm–1. HRMS: calcd. for C H O SiNa
˜
13 22
2
261.1287; found 261.1283.
1
1
a colorless oil (48%; 70:30 dr, by H NMR). H NMR (360 MHz,
CDCl3): δ = 4.66 (d, J = 3.0 Hz, 1 H, OCH2O, major), 4.64 (s, 2
H, OCH2O, minor), 4.60 (d, J = 3.0 Hz, 1 H, OCH2O, major), 4.35
(dt, J = 10.4, J = 7.9 Hz, 1 H, 4-H, minor), 4.21 (d, J = 5.4 Hz, 1
H, 4-H, major), 3.38 (s, 3 H, OCH3, minor), 3.35 (s, 3 H, OCH3,
major), 3.30–3.20 (m, 1 H, 1-H, minor), 3.17–3.07 (m, 1 H, 1-H,
major), 2.96 (dd, J = 18.4, J = 5.4 Hz, 1 H, 3-H, major), 2.90–2.73
(m, 2 H, major + minor), 2.68 (ddd, J = 18.0, J = 8.2, J = 1.2 Hz,
1 H, 3-H, minor), 2.60–2.10 (m, 6 H, major + minor), 1.95–1.75
(m, 4 H, major + minor) ppm. 13C NMR (90 MHz, CDCl3): δ =
220.3 (major), 217.9 (minor), 95.6 (minor), 94.5 (major), 77.9
(major), 74.4 (minor), 55.4 (major + minor), 46.4 (minor), 43.9
(major), 43.5 (major), 42.5 (minor), 41.1 (major), 38.4 (minor), 22.4
(3S)-3-(tert-Butyldimethylsilyloxy)octahydrocyclopenta[3,4]cyclobuta-
[1,2]cyclopenten-1(2H)-one [exo-8c (3aS,6bR) and endo-9c
(3aR,6bS)]: By using 7c, according to Procedure B, flash
chromatography (hexanes/Et2O, 95:5) gave two separate bicyclic
products (54:46 dr, by 1H NMR) as a colorless oil for exo-8c (22%)
and as colorless needles for endo-9c (19%). exo-8c: [α]2D0 = +215 (c
= 0.6, CHCl3). 1H NMR (360 MHz, CDCl3): δ = 4.47 (dt, J = 11.1,
J = 7.6 Hz, 1 H, 10-H), 3.12–3.03 (m, 1 H, 7-H), 2.80 (dd, J =
17.0, J = 11.0 Hz, 1 H, 9-H), 2.54–2.39 (m, 2 H, 6-H, 9-H), 2.34–
2.24 (m, 1 H, 1-H), 2.22–2.12 (m, 1 H, 2-H), 1.92–1.54 (m, 6 H, 3-
H, 4-H, 5-H), 0.91 (s, 9 H, SitBu), 0.07 (s, 3 H, SiMe), 0.07 (s, 3
H, SiMe) ppm. 13C NMR (90 MHz, CDCl3): δ = 217.4, 70.0, 51.1,
44.8, 44.1, 41.7, 34.8, 33.2 (2 C), 25.7, 24.6, 18.0, –4.8 ppm. IR
(minor), 21.8 (2C, major), 18.2 (minor) ppm. IR (neat): ν = 2947,
˜
(neat): ν = 2953, 1740 cm–1. HRMS: calcd. for C16H28O2SiNa
1736 cm–1. MS: m/z
= 171 [M +
H]+. HRMS: calcd. for
˜
303.1756; found 303.1759. endo-9c: M.p. 45 °C. [α]2D0 = –129 (c =
1.0, CHCl3). 1H NMR (360 MHz, CDCl3): δ = 4.30 (d, J = 4.6 Hz,
1 H, 10-H), 2.92 (dd, J = 17.2, J = 4.6 Hz, 1 H, 9-H), 2.52–2.42
(m, 2 H, 1-H, 7-H), 2.30–2.10 (m, 3 H, 2-H, 6-H, 9-H), 1.95–1.45
(m, 6 H, 3-H, 4-H, 5-H), 0.84 (s, 9 H, SitBu), 0.04 (s, 6 H, SiMe2)
ppm. 13C NMR (90 MHz, CDCl3): δ = 220.0, 74.1, 48.5, 48.0, 45.9,
C9H14O3Na 193.0841; found 193.0845.
(4S)-4-(tert-Butyldimethylsilyloxy)-6,6,7,7-tetramethylbicyclo[3.2.0]-
heptan-2-one [exo-8a (1R,5S) and endo-9a (1S,5R)]: By using 7a,
according to Procedure B, flash chromatography (CH2Cl2/MeOH,
1
9:1) gave two separable bicyclic products (60:40 dr, by H NMR)
as a colorless oil for exo-8a (27%) and as colorless needles for endo-
9a (18%). exo-8a: [α]2D0 = +168 (c = 1.05, CHCl3). 1H NMR
(360 MHz, CDCl3): δ = 4.58 (dt, J = 9.6, J = 7.9 Hz, 1 H, 4-H),
2.74 (t, J = 7.6 Hz, 1 H, 3-H), 2.71 (dd, J = 19.1, J = 10.1 Hz, 1
H, 1-H), 2.58 (ddd, J = 19.6, J = 9.4, J = 1.3 Hz, 1 H, 5-H), 2.31
(d, J = 7.9 Hz, 1 H, 3-H), 1.25 (s, 3 H, CH3), 1.17 (s, 3 H, CH3),
1.10 (s, 3 H, CH3), 0.93 (s, 3 H, CH3), 0.91 (s, 9 H, SitBu), 0.08 (s,
3 H, SiMe), 0.06 (s, 3 H, SiMe) ppm. 13C NMR (90 MHz, CDCl3):
δ = 218.5, 71.3, 56.0, 48.5, 48.1, 41.7, 39.4, 27.7, 27.6, 25.8, 22.6,
40.1, 39.4, 33.1, 32.9, 25.7, 24.6, 18.0, –4.8 ppm. IR (neat): ν =
˜
2951, 1741 cm–1. HRMS: calcd. for C16H28O2SiNa 303.1756; found
303.1754.
(4S)-4-(tert-Butyldimethylsilyloxy)-6,7-dichlorobicyclo[3.2.0]heptan-
2-one [exo-8d (1R,5S) and endo-9d (1S,5R)]: By using 7d, according
to the general Procedure B, flash chromatography (hexanes/Et2O,
90:10) provided two fractions. The first (minor) one, endo-9d, was
obtained as a colorless oil (16%) and was a unique anti or syn
diastereomer. The second (major) one, exo-8d, was obtained as col-
orless needles (33%) and was an inseparable mixture of stereoiso-
20.2, 17.9, –4.9 ppm. IR (neat): ν = 2956, 1735 cm–1. HRMS: calcd.
˜
for C17H32O2SiNa 319.2069; found 319.2075. endo-9a: M.p. 84 °C.
1
1
mers at positions C-6 and C-7 (78:22 dr, by H NMR). exo-8d: H
NMR (360 MHz, CDCl3): δ = 4.79 (ddd, J = 6.5, J = 4.2, J =
2.5 Hz, 1 H, 4-H, major), 4.71 (ddd, J = 9.3, J = 6.5, J = 0.8 Hz,
1 H, 7-H, major), 4.56 (dd, J = 8.2, J = 6.8 Hz, 1 H, 4-H, minor),
4.50 (d, J = 5.0 Hz, 1 H, 7-H, minor), 4.14 (ddd, J = 6.4, J = 5.6,
J = 1.1 Hz, 1 H, 6-H, major), 4.06 (ddd, J = 6.8, J = 5.8, J =
1.1 Hz, 1 H, 6-H, minor), 3.34–3.22 (m, 2 H, 3-H, major + minor),
3.13–3.06 (m, 1 H, 3-H, major), 3.01–2.97 (m, 1 H, 3-H, minor),
2.94 (dd, J = 18.4, J = 6.4 Hz, 1 H, 1-H, major), 2.74 (dd, J =
18.7, J = 4.8 Hz, 1 H, 1-H, minor), 2.48–2.35 (m, 2 H, 5-H, major
+ minor), 0.87 (s, 9 H, SitBu, major), 0.86 (s, 9 H, SitBu, minor),
0.11 (s, 6 H, SiMe, major + minor), 0.09 (s, 6 H, SiMe, major +
minor) ppm. 13C NMR (90 MHz, CDCl3): δ = 214.5 (minor), 211.4
1
[α]2D0 = –145 (c = 1.05, CHCl3). H NMR (360 MHz, CDCl3): δ =
4.52–4.46 (m, 1 H, 4-H), 2.78 (dd, J = 19.5, J = 6.5 Hz, 1 H, 3-H),
2.62–2.55 (m, 1 H, 1-H), 2.46 (d, J = 8.3 Hz, 1 H, 5-H), 2.39–2.29
(m, 1 H, 3-H), 1.13 (s, 3 H, CH3), 1.12 (s, 3 H, CH3), 0.96 (s, 3 H,
CH3), 0.87 (s, 12 H, CH3, SitBu), 0.06 (s, 3 H, SiMe), 0.05 (s, 3 H,
SiMe) ppm. 13C NMR (90 MHz, CDCl3): δ = 220.1, 70.1, 53.8,
53.1, 51.4, 41.7, 39.6, 27.2, 27.0, 25.8, 21.1, 20.8, 17.9, –4.7 ppm.
IR (neat): ν = 2954, 1717 cm–1. HRMS: calcd. for C H O SiNa
˜
17 32
2
319.2069; found 319.2074.
(4S)-4-(tert-Butyldimethylsilyloxy)bicyclo[3.2.0]hept-6-en-2-one
[exo-8b (1R,5S) and endo-9b (1S,5R)]: By using 7b, according to
Procedure A, flash chromatography (hexanes/Et2O, 95:5) gave an
5958
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5953–5962

Synthesis of Bicyclo[3.2.0]heptanes by [2+2] Photocycloaddition
(major), 71.0 (minor), 69.0 (major), 59.9 (major), 59.8 (major), 59.6
(minor), 56.4 (minor), 53.2 (major), 53.1 (minor), 48.5 (major), 47.6
(major + minor), 46.9 (minor), 25.6 (major + minor), 17.9 (major
+ minor), –4.8 (major + minor) ppm. HRMS: calcd. for
C13H22O2Cl2SiNa 331.0678; found 331.0664. endo-9d: [α]2D0 = +85
(c = 0.5, CHCl3). 1H NMR (360 MHz, CDCl3): δ = 4.85 (ddd, J =
6.5, J = 5.3, J = 1.5 Hz, 1 H, 4-H), 4.62 (dd, J = 14.2, J = 7.1 Hz,
1 H, 7-H), 4.55 (ddd, J = 6.2, J = 3.3, J = 0.9 Hz, 1 H, 6-H), 3.42
(dd, J = 13.0, J = 7.7 Hz, 1 H, 3-H), 3.15–3.09 (m, 1 H, 1-H), 2.69
(ddd, J = 18.8, J = 7.7, J = 1.1 Hz, 1 H, 3-H), 2.52 (dd, J = 18.9,
J = 6.4 Hz, 1 H, 5-H), 0.93 (s, 9 H, SitBu), 0.14 (s, 3 H, SiMe),
0.12 (s, 3 H, SiMe) ppm. 13C NMR (90 MHz, CDCl3): δ = 211.8,
7-H), 0.90 (s, 9 H, SitBu), 0.07 (s, 6 H, SiMe2) ppm. 13C NMR
(90 MHz, CDCl3): δ = 217.8 (major), 214.5 (minor), 141.2 (minor),
137.2 (minor), 103.1 (major), 69.4 (major), 66.1 (minor), 55.9
(minor), 52.2 (major), 49.2 (major), 49.0 (minor), 48.4 (major), 46.1
(major), 42.4 (minor), 39.0 (major), 35.5 (major), 25.7 (major), 25.6
(minor), 18.0 (major), 17.9 (minor), –4.9 (major + minor), –4.8
(minor), –4.6 (major) ppm. HRMS: calcd. for C15H28O4SiNa
323.1655; found 323.1670.
(4S)-4-(tert-Butyldimethylsilyloxy)-6,6-dimethylbicyclo[3.2.0]hept-
an-2-one [exo-8g (1R,5S) and endo-9g (1S,5R)]: By using 7g, accord-
ing to Procedure A, flash chromatography (hexanes/EtOAc, 90:10)
gave a colorless oil containing a mixture of four isomers exo-8g
and endo-9g (38%; 33:25:22:20 dr, by 1H NMR). A second flash
chromatography (hexanes/EtOAc, 90:10) allowed for the isolation
and characterization (but not identification) of three of these com-
67.1, 57.7, 54.0 (2 C), 51.1, 47.4, 25.7, 18.0, –4.9 ppm. IR (neat): ν
˜
= 2 9 5 2 , 2 9 2 9 , 2 8 5 7 , 1 7 4 0 c m – 1 . H R M S : c a l c d . f o r
C13H22O2Cl2SiNa 331.0678; found 331.0680.
(7S)-7-(tert-Butyldimethylsilyloxy)octahydro-5H-cyclopenta[3,4]cyclo- pounds. First Compound: 1H NMR (360 MHz, CDCl3): δ = 4.46
buta[1,2-b][1,4]dioxin-5-one [exo-8e (4bS,7aR) and endo-9e (ddd, J = 7.6, J = 2.2, J = 1.4 Hz, 1 H, 4-H), 2.94 (dd, J = 22.0, J
(4bR,7aS)]: By using 7e, according to Procedure B, flash
chromatography (hexanes/Et2O, 50:50) gave a colorless oil, which
was an inseparable mixture of four diastereomers of bicyclic prod-
ucts exo-8e and endo-9e (33%; 47:29:18:6 dr, by 1H NMR). 1H
= 7.6 Hz, 1 H, 3-H), 2.93–2.83 (m, 1 H, 3-H), 2.50–2.40 (m, 1 H,
1-H), 2.30 (ddd, J = 18.3, J = 3.3, J = 1.7 Hz, 1 H, 5-H), 2.13 (ddd,
J = 12.2, J = 10.5, J = 1.5 Hz, 1 H, 7-H), 1.71 (dd, J = 12.6, J =
5.5 Hz, 1 H, 7-H), 1.25 (s, 3 H, CCH3), 1.07 (s, 3 H, CCH3), 0.87
NMR (360 MHz, CDCl3): δ = 4.69 (ddd, J = 7.2, J = 2.0, J = (s, 9 H, SitBu), 0.06 (s, 3 H, SiMe), 0.06 (s, 3 H, SiMe) ppm. 13C
1.4 Hz, 1 H, 7-H, minor a), 4.66 (dd, J = 2.6, J = 2.1 Hz, 1 H, 7-
H, minor b), 4.62 (dd, J = 7.2, J = 2.6 Hz, 1 H, 7-H, major), 4.57
(dd, J = 4.9, J = 1.8 Hz, 1 H, 8-H or 9-H, minor a), 4.49 (ddd, J
= 5.3, J = 5.2, J = 2.8 Hz, 1 H, 8-H or 9-H, minor b), 4.41 (ddd,
J = 5.4, J = 2.9, J = 1.1 Hz, 1 H, 8-H or 9-H, major), 4.33 (ddd,
NMR (90 MHz, CDCl3): δ = 220.6, 70.6, 54.9, 48.0, 39.2, 37.0,
34.3, 32.1, 25.8, 24.6, 18.1, –4.6, –4.9 ppm. HRMS: calcd. for
C15H28O2SiNa 291.1756; found 291.1747. Second Compound: 1H
NMR (360 MHz, CDCl3): δ = 4.25 (d, J = 5 Hz, 1 H, 4-H), 2.90–
2.80 (m, 1 H, 3-H), 2.76 (dd, J = 18.3, J = 4.5 Hz, 1 H, 3-H), 2.53–
J = 4.4, J = 4.3, J = 0.7 Hz, 1 H, 8-H or 9-H, major), 4.32–4.22 2.45 (m, 1 H, 1-H), 2.26 (ddd, J = 17.8, J = 2.5, J = 1.1 Hz, 1 H,
(m, 2 H, 8-H or 9-H, minor a + minor b), 3.97–3.77 (m, 6 H, 1-H,
2-H, major + minor a + minor b), 3.70–3.60 (m, 3 H, 4-H, major
+ minor a + minor b), 3.57–3.44 (m, 3 H, major + minor a +
minor b), 3.38–3.20 (m, 4 H, major + minor a + minor b), 3.15–
3.05 (m, 2 H, major + minor a or minor b), 2.73–2.65 (m, 1 H,
major), 2.64 (dd, J = 8.3, J = 1.4 Hz, 1 H, minor b), 2.60 (ddd, J
= 9.1, J = 1.5, J = 0.5 Hz, 1 H, minor a), 2.58 (dd, J = 7.0, J =
1.1 Hz, 1 H, minor b), 2.44 (ddd, J = 4.3, J = 1.0, J = 0.4 Hz, 1
H, major), 2.41–2.36 (m, 1 H, minor a), 0.91 (s, 9 H, SitBu, minor
a), 0.90 (s, 9 H, SitBu, major), 0.87 (s, 9 H, SitBu, minor b), 0.09
(s, 6 H, SiMe2, minor b), 0.08 (s, 6 H, SiMe2, major), 0.07 (s, 6 H,
SiMe2, minor a) ppm. 13C NMR NMR (90 MHz, CDCl3): δ =
218.8 (minor a or minor b), 216.5 (minor a or minor b), 215.3
(major), 75.6 (minor a or minor b), 73.3 (minor a or minor b), 71.7
(major), 70.5 (major + minor a or minor b), 69.5 (minor a or minor
b), 67.4 (major), 67.3 (minor a + minor b), 63.5 (minor a or minor
b), 63.3 (minor a or minor b), 62.7 (major), 62.1 (major), 61.9
(minor a or minor b), 61.8 (minor a or minor b), 55.6 (minor a or
b), 52.7 (minor a or minor b), 51.8 (minor a or minor b), 50.1
(major), 49.7 (major), 49.0 (minor a or minor b), 45.1 (minor a or
b), 44.3 (major + minor a or minor b), 40.6 (minor a or minor b),
25.7 (minor a + minor b), 25.6 (major), 18.0 (minor a + minor b),
17.9 (major), –4.8 (minor a + minor b), –5.0 (major), –5.1 (minor
5-H), 2.00 (ddd, J = 12.1, J = 9.3, J = 2.7 Hz, 1 H, 7-H), 1.67–
1.55 (m, 1 H, 7-H), 1.28 (s, 3 H, CCH3), 0.94 (s, 3 H, CCH3), 0.86
(s, 9 H, SitBu), 0.05 (s, 3 H, SiMe), 0.04 (s, 3 H, SiMe) ppm. 13C
NMR (90 MHz, CDCl3): δ = 222.3, 73.7, 54.8, 48.0, 39.4, 35.9,
34.8, 31.2, 25.8, 25.7, 18.1, –4.7, –4.8 ppm. HRMS: calcd. for
C
15H28O2SiNa 291.1756; found 291.1753. Third Compound: 1H
NMR (360 MHz, CDCl3): δ = 4.56 (ddd, J = 11.1, J = 8.5, J =
7.6 Hz, 1 H, 4-H), 2.76 (ddd, J = 18.0, J = 11.4, J = 0.6 Hz, 1 H,
3-H), 2.70–2.60 (m, 1 H, 3-H), 2.60–2.45 (m, 1 H, 1-H), 2.40–2.25
(m, 1 H, 5-H), 2.20–2.10 (m, 1 H, 7-H), 1.73 (dd, J = 9.3, J =
3.6 Hz, 1 H, 7-H), 1.31 (s, 3 H, CCH3), 1.22 (s, 3 H, CCH3), 0.91
(s, 9 H, SitBu), 0.07 (s, 3 H, SiMe), 0.06 (s, 3 H, SiMe) ppm.
HRMS: calcd. for C15H28O2SiNa 291.1756; found 291.1750.
(1R,4S)-4-(Allyloxymethoxy)cyclopent-2-enyl Acetate (10): To a
solution of alcohol 2a (568 mg, 4.0 mmol) in CH2Cl2 (5 mL) under
argon were added iPr2NEt (3.10 g, 24.0 mmol), allyl chloromethyl
ether (1.28 g, 12.0 mmol) and Bu4NI (148 mg, 0.4 mmol). The solu-
tion was stirred at room temp. for 72 h and then washed with aq.
HCl (2 , 2 ϫ5 mL), saturated aq. NaHCO3 (5 mL), and brine
(5 mL). The organic phase was dried with MgSO4, filtered, and
concentrated. The residue was purified by flash chromatography
(hexanes/Et2O, 80:20) to give 10 as a colorless oil (678 mg, 80%).
[α]2D0 = +33 (c = 1.2, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
6.13 (dt, J = 5.8, J = 1.4 Hz, 1 H, 2-H), 6.01 (dt, J = 5.8, J =
1.4 Hz, 1 H, 3-H), 5.93 (ddt, J = 16.9, J = 10.8, J = 5.8 Hz, 1 H,
a + minor b) ppm. IR (neat): ν = 2956, 1735 cm–1. MS: m/z = 316
˜
[M + NH4]+.
(4S)-4-(tert-Butyldimethylsilyloxy)-6,6-dimethoxybicyclo[3.2.0]hep- CHallyl), 5.54–5.48 (m, 1 H, 1-H), 5.31 (ddd, J = 17.3, J = 3.2, J =
tan-2-one [exo-8f (1R,5S) and endo-9f (1S,5R)]: By using 7f, accord-
ing to Procedure B, flash chromatography (hexanes/EtOAc, 90:10)
gave an inseparable mixture of the bicyclic exo-8f and endo-9f as a
1.8 Hz, 1 H, CH2allyl), 5.21 (ddd, J = 10.4, J = 2.8, J = 1.4 Hz, 1
H, CH2allyl), 4.79 (s, 2 H, OCH2O), 4.65–4.58 (m, 1 H, 4-H), 4.17–
4.05 (m, 2 H, OCH2), 2.81 (dt, J = 14.7, J = 7.4 Hz, 1 H, 5-H),
colorless oil (40%; 73:27 dr, by GC). For the 1H NMR signals, 2.06 (s, 3 H, OAc), 1.74 (dt, J = 14.5, J = 4.2 Hz, 1 H, 5-H) ppm.
only those of the major product could be interpreted. 1H NMR
(360 MHz, CDCl3): δ = 4.46 (ddd, J = 10.8, J = 8.2, J = 7.0 Hz, 1
H, 4-H), 3.25 (s, 3 H, OMe), 3.15 (s, 3 H, OMe), 3.05 (t, J = 7.2 Hz,
1 H, 1-H), 2.98 (dd, J = 17.7, J = 10.9 Hz, 1 H, 3-H), 2.60–2.50
13C NMR (90 MHz, CDCl3): δ = 170.6, 136.5, 134.1, 132.7, 116.9,
93.8, 79.9, 76.6, 68.2, 37.9, 21.0 ppm. IR (neat): ν = 3076, 2944,
˜
2887, 1736 cm–1. MS: m/z = 230 [M + NH4]+. HRMS: calcd. for
C11H16O4Na 235.0946; found 235.0941. C11H16O4 (212.24): calcd.
(m, 1 H, 5-H), 2.50–2.35 (m, 2 H, 3-H, 7-H), 2.30–2.23 (m, 1 H, C 62.25, H 7.60; found C 61.94, H 7.71.
Eur. J. Org. Chem. 2009, 5953–5962
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5959

M. Le Liepvre, J. Ollivier, D. J. Aitken
FULL PAPER
(1R,4S)-4-(Allyloxymethoxy)cyclopent-2-enol (11): To a solution of
ester 10 (623 mg, 2.9 mmol) in MeOH (16 mL) under argon was
added sodium methoxide (317 mg, 5.9 mmol), and the solution was
stirred at room temp. for 14 h. Most of the MeOH was then evapo-
rated, and CH2Cl2 was added (25 mL). The mixture was washed
with H2O (3ϫ10 mL), dried with MgSO4, filtered, and concen-
H), 3.09–2.98 (m, 1 H, 6-H), 2.74–2.60 (m, 3 H, 1-H, 3-H, 7-H),
2.47 (dd, J = 18.0, J = 4.9 Hz, 1 H, 3-H), 1.95–1.60 (m, 2 H, 7-H,
OH) ppm. 13C NMR (90 MHz, CDCl3): δ = 219.7, 78.8, 74.1, 47.3,
44.7, 38.6, 36.3, 27.1 ppm. IR (neat): ν = 3455, 2975, 2931, 2852,
˜
1735 cm–1. MS: m/z = 174 [M + NH4]+. C8H12O3 (156.18): calcd.
C 61.52, H 7.74; found C 61.31, H 7.71.
trated to afford 11 as a colorless oil (456 mg, 91% yield). [α]2D0
=
+10 (c = 1.65, CHCl3). 1H NMR (360 MHz, CDCl3): δ = 6.08
(ddd, J = 5.8, J = 1.4, J = 1.1 Hz, 1 H, 2-H), 6.03 (ddd, J = 5.8, J
= 1.4, J = 1.1 Hz, 1 H, 3-H), 5.93 (ddt, J = 17.3, J = 10.4, J =
5.4 Hz, 1 H, CHallyl), 5.32 (ddd, J = 17.3, J = 3.2, J = 1.8 Hz, 1
H, CH2allyl), 5.21 (ddd, J = 10.4, J = 2.9, J = 1.4 Hz, 1 H, CH2allyl),
4.79 (q, J = 7.0 Hz, 2 H, OCH2O), 4.69–4.61 (m, 1 H, 4-H), 4.61–
4.56 (m, 1 H, 1-H), 4.18–4.05 (m, 2 H, OCH2), 2.70 (dt, J = 14.3,
J = 7.2 Hz, 1 H, 5-H), 1.76 (d, J = 9.0 Hz, 1 H, OH), 1.66 (dt, J
= 14.2, J = 3.9 Hz, 1 H, 5-H) ppm. 13C NMR (90 MHz, CDCl3):
δ = 137.3, 134.2 (2 C), 117.1, 93.5, 80.2, 76.6, 68.3, 41.4 ppm. IR
Acknowledgments
We thank the French Ministère de la Recherche for a PhD grant
to M. L. L. We are grateful to Dr. Régis Guillot, ICMMO, for
performing the X-ray structural analysis. We are also indebted to
both Mr. Bertrand Perrin and Dr. Christian Girard (now both re-
tired) for their kind technical assistance with the photochemical
equipment.
(neat): ν = 3402, 3063, 2941, 2886, 1648 cm–1. MS: m/z = 188 [M
[1] M. Miesch, Curr. Org. Synth. 2006, 3, 327–340.
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2006; Chem. Abstr. 2006, 145, 606101.
˜
+ NH4]+. C9H14O3 (170.20): calcd. C 63.51, H 8.29; found C 63.24,
H 8.18.
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K. Ohashi, M. Kawai, N. Ninomiya, C. Taylor, Y. Kurebayashi,
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(4S)-4-(Allyloxymethoxy)cyclopent-2-enone (12): To a solution of
alcohol 11 (405 mg, 2.4 mmol) in CH2Cl2 (30 mL) under argon,
was added PDC (600 mg, 3.6 mmol). The mixture was stirred at
room temp. for 72 h and then filtered through Celite. The solid
was washed with CH2Cl2, and the combined organic phases were
concentrated. The obtained residue was purified by flash
chromatography (hexanes/Et2O, 50:50) to give 12 as a colorless oil
(312 mg, 78%). [α]2D0 = –16 (c = 1.0, CHCl3). H NMR (360 MHz,
1
CDCl3): δ = 7.62 (dd, J = 5.7, J = 2.4 Hz, 1 H, 3-H), 6.26 (dd, J
= 5.7, J = 1.0 Hz, 1 H, 2-H), 5.93 (ddt, J = 16.9, J = 10.8, J =
5.4 Hz, 1 H, CHallyl), 5.33 (ddd, J = 17.6, J = 3.2, J = 1.8 Hz, 1
H, CH2allyl), 5.23 (ddd, J = 10.4, J = 2.5, J = 1.4 Hz, 1 H, CH2allyl),
4.94–4.89 (m, 1 H, 4-H), 4.83 (d, J = 1.1 Hz, 1 H, OCH2O), 4.19–
4.06 (m, 2 H, OCH2), 2.75 (dt, J = 18.4, J = 6.1 Hz, 1 H, 5-H),
2.35 (dt, J = 18.4, J = 2.3 Hz, 1 H, 5-H) ppm. 13C NMR (90 MHz,
CDCl3): δ = 205.5, 161.4, 135.2, 133.6, 116.9, 93.9, 75.3, 68.2,
41.7 ppm. IR (neat): ν = 3081, 2944, 2890, 1722 cm–1. HRMS:
˜
calcd. for C9H12O3Na 191.0684; found 191.0678.
(2aS,3aR,7aS,7bR)-Hexahydro-5,7-dioxacyclobuta[cd]azulen-2(1H)-
one (13): A solution of enone 12 (164 mg, 0.98 mmol) in acetone
(195 mL) was saturated with argon for 15 min and then irradiated
with a 400 W high-pressure mercury vapor lamp fitted with a Pyrex
filter for 15 min. The mixture was concentrated, and the residue
was purified by flash chromatography (hexanes/Et2O, 50:50) to give
13 (97 mg, 60%) as white crystals. M.p. 61 °C. [α]2D0 = +112 (c =
1.35, CHCl3). 1H NMR (360 MHz, CDCl3): δ = 5.15 (d, J =
7.5 Hz, 1 H, 6-H), 4.58 (tt, J = 5.4, J = 1.4 Hz, 1 H, 7a-H), 4.55
(d, J = 7.2 Hz, 1 H, 6-H), 3.80 (dd, J = 13.1, J = 3.8 Hz, 1 H, 8-
H), 3.71 (dd, J = 13.1, J = 2.8 Hz, 1 H, 4-H), 3.13–3.04 (m, 1 H,
7b-H), 2.99–2.87 (m, 1 H, 3a-H), 2.82 (dd, J = 17.5, J = 8.3 Hz, 1 [7] a) S. Ghosh, in: CRC Handbook of Organic Photochemistry and
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H, 2a-H), 2.62–2.42 (m, 3 H, 1-H, 1-H, 3-H), 2.41–2.30 (m, 1 H,
3-H) ppm. 13C NMR (90 MHz, CDCl3): δ = 217.5, 97.8, 79.4, 71.4,
48.6, 46.5, 40.3, 37.4, 28.4 ppm. IR (neat): ν = 2942, 1739 cm–1.
˜
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HRMS: calcd. for C9H12O3Na 191.0684; found 191.0677.
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one (14): To a solution of tricyclic acetal 13 (288 mg, 1.7 mmol) in
THF (20 mL) was added concentrated HCl (1 mL). The mixture
was stirred at room temp. for 2 h and then concentrated to give 14
1
(227 mg, 85%) as a colorless oil. [α]2D0 = +77 (c = 1.0, CHCl3). H
NMR (360 MHz, CDCl3): δ = 4.57 (dd, J = 5.8, J = 5.2 Hz, 1 H,
4-H), 3.80 (d, J = 9.3 Hz, 1 H, CH2O), 3.65 (dd, J = 9.3, J =
3.9 Hz, 1 H, CH2O), 3.64 (br. s, 1 H, OH), 3.41–3.32 (m, 1 H, 5-
5960
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5953–5962

Synthesis of Bicyclo[3.2.0]heptanes by [2+2] Photocycloaddition
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Eur. J. Org. Chem. 2009, 5953–5962
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5961

M. Le Liepvre, J. Ollivier, D. J. Aitken
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Received: July 7, 2009
Published Online: October 21, 2009
5962
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5953–5962