Regioselectivity of the intramolecular photocycloaddition of α,β-butenolides to a terminal alkene

Article abstract of DOI:10.1055/s-2001-15058

The intramolecular [2+2] photocycloaddition of α,β-butenolides to a terminal double bond tethered to the lactone through the γ-position and located at a suitable distance has been studied. The regioselectivity of the photoisomerization depends on the substitution pattern of the substrate and can be rationalized by simple theoretical calculations performed on the diradical intermediates.

Full text of DOI:10.1055/s-2001-15058

PAPER
1143
Regioselectivity of the Intramolecular Photocycloaddition of , -Butenolides
to a Terminal Alkene
I
ntramolecular
é
Photocyc
l
l
i
n
of
,
x
-Butenolides to
aB
Terminal Alkeneusqué,a Pedro de March,a Marta Figueredo,*a Josep Font,*a Paul Margaretha,b Javier Rayaa
a
Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
b
Institut für Organische Chemie, Universität Hamburg, 20146 Hamburg, Germany
Fax +34(93)5811265; E-mail: marta.figueredo@uab.es; josep.font@uab.es
Received 1 February 2001; revised 9 March 2001
butenolide 2 with an additional terminal double bond teth-
ered to the -position through a two-carbon chain could be
a suitable precursor for 1, provided that the intramolecular
[2+2] cycloaddition took place with the appropriate regi-
Abstract: The intramolecular [2+2] photocycloaddition of , -
butenolides to a terminal double bond tethered to the lactone
through the -position and located at a suitable distance has been
studied. The regioselectivity of the photoisomerization depends on
the substitution pattern of the substrate and can be rationalized by oselectivity.
simple theoretical calculations performed on the diradical interme-
diates.
O
O
O
O
Key words: intramolecular photochemical cycloaddition
, -
butenolides, alkenes, regioselectivity, intermediate diradicals
1
2
Since the first published studies dealing with the [2+2]
photocycloaddition of enones to alkenes,1–3 this reaction
has found broad application in the synthesis of natural
products as a key step in the preparation of many target
molecules containing a cyclobutane ring in their skele-
ton.4–7 Nevertheless, reports on the use of , -unsaturated
lactones as substrates for [2+2] photocycloadditions are
quite limited.8–16 The synthetic utility of these reactions
relies on both the regio- and stereoselectivity of the pro-
cess. Studies addressed to the issue of facial diastereose-
lectivity in the intermolecular photocycloadditions to
chiral lactones have been performed11,13–15 and, as a result,
successful stereoselective syntheses of (+)- and (–)-
bourbonene13 and (+)- and (–)-grandisol11,14b,15c,f have
been developed.
Scheme 1
The [2+2] photocycloaddition of enones is a triplet pro-
cess and the regioselectivity is recognized to be originated
in the diradical-forming step.29 When cyclization is faster
than reversion of the diradical to the ground-state reac-
tants, the initial bond formation determines the regio-
chemistry of the products. For intramolecular processes,
on the basis of experimental results, it seems to be a pref-
erence for the initial formation of a five-membered ring
(rule of five),21,30,31 although the regioselectivity may be
strongly affected by electronic as well as steric factors.
To evaluate the influence of the substituents at the and
positions on the regioselectivity of the intramolecular
[2+2] cycloaddition of butenolides analogous to 2, we de-
cided to synthesize compounds 4–6 (Scheme 2) and in-
vestigate their photochemical isomerization.
The light induced intramolecular [2+2] cycloaddition of
an enone containing an additional carbon–carbon double
bond was first observed for L-carvone.17,18 More recently,
new examples have been reported,19–22 in which the main
purpose is to understand, and eventually to control, the re-
giochemical outcome of the process. Intramolecular pho-
tocycloadditions to , -unsaturated -lactones have also
been used for the preparation of polycyclic compounds23
and nicely applied to the asymmetric synthesis of stoecho-
spermol.24
O
O
O
O
iv
i-iii
H3C
4
5
O
O
3
O
v,ii-iii
CH3
6
In connection with the synthesis of cyclobutanic phero-
mones, we were interested in the preparation of molecules
with the tricyclic skeleton of 125 (Scheme 1). This lactone
has already been used as a key intermediate in the synthe-
sis of (+)-grandisol26 and several pinane27 and
bergamotane28 derivatives. We envisaged that the , -
Scheme 2 Reagents and conditions: i) PhSeCH2CO2H, LDA (2
equiv), THF, 0 ºC to r. t.; ii) AcOH, reflux; iii) H2O2, AcOH, THF, <
0 ºC, 4: 95% overall; iv) CH2N2, Et2O–THF, –5 ºC to r. t.; then, dioxa-
ne, reflux, 5: 69% overall; v) PhSeCH(Me)CO2H, LDA (2 equiv),
THF, 0 ºC to r. t., 6: 57% overall
Butenolides 4 and 6 were prepared through a three step se-
quence of reactions:32 condensation of 1,2-epoxyhex-5-
ene (3) with the dianion of phenylselenoacetic or 2-phe-
Synthesis 2001, No. 8, 18 06 2001. Article Identifier:
1437-210X,E;2001,0,08,1143,1148,ftx,en;C00901SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1144
F. Busqué et al.
PAPER
able 1 Photoisomerization of Butenolides 4–6
un
Substrate
(nm)
Filter
Solvent
Temp. (°C)
Time (h)
Yield (%)a
Product
Isomers
a:b
1b
2b
3b
4b
5b
6
4
4
4
5
6
4
4
4
5
6
254
Quartz
Pyrex®
Pyrex®
Pyrex®
Pyrex®
Pyrex®
Pyrex®
Pyrex®
Pyrex®
Pyrex®
Et2O
r. t.
r. t.
r. t.
r. t.
r. t.
0
3
5
30
40
40
50
58
–
3:1c
3:1c
3:1c
7:1c
1.6:1c
7:1e
7:1e
7:1e
8:1e
1.7:1e
300
350
300
acetone
acetone
acetone
acetone
acetone
acetone
acetone
acetone
acetone
10
8
300
5
-d
6
-d
-d
-d
-d
7
–15
–25
–15
–15
6
51
–
8
6
9
8
58
55
0
5
Isolated yields after flash chromatography.
Irradiations were performed on a Rayonet® system.
Ratio of isolated products.
Irradiations were performed on a photochemical reactor with a 125 W medium pressure mercury lamp fitted in an immersion cooling jacket.
Ratio determined by GC of the reaction mixture.
nylselenopropionic acid, respectively, acid induced lac-
tonization, and oxidation of the selenide function with
consequent thermal elimination. Total yields were 95%
for 4 and 57% for 6. Introduction of a methyl group at the
-carbonyl position of 4 by treatment with diazomethane
followed by pyrolysis of the corresponding pyrazoline af-
forded 5 in 69% overall yield.
Scheme 3
Preliminary irradiation experiments were performed on a
Rayonet® system at room temperature (Table 1). De-
flash column chromatography, afforded a 7:1 mixture of
8a and 8b in 50% yield. Again we were unable to separate
this mixture, but the structures were assigned by GC/MS
analysis and NMR experiments as above. Irradiation of 6
(run 5) for 5 hours allowed the isolation of a 1.6:1 mixture
of 9a and 9b in 58% yield. The structure of each isomer
was elucidated by GC/MS and NMR analyses of enriched
gassed solutions of lactone 4 were irradiated at 254 nm
(run 1), 300 nm (run 2) and 350 nm (run 3) until full con-
version of the substrate. Purification by flash column
chromatography gave in all three cases a ca 3:1 mixture of
the regioisomers 7a and 7b (Scheme 3), although the iso-
lated ratio of these isomers is not a reliable measure of the
regioselectivity of the cycloaddition due to the high vola-
tility of isomer 7a (see below). We were unable to sepa-
mixtures as in the precedent cases. Tables 2 and 3 summa-
1
13
rize the most significant H and C NMR data observed
rate compounds 7a and 7b, but GC/MS analysis showed
that both reaction products had the same molecular weight
for compounds 7–9.
as the starting butenolide 4. The structure of each isomer Next, the experiments were repeated in a photochemical
1
was assigned by H and 13C NMR analysis of enriched reactor using a 125 W medium pressure mercury lamp, fit-
samples with the help of DEPT, COSY and 1H/13C corre- ted in an immersion Pyrex® cooling jacked, with a careful
lation experiments. For the major isomer, it was observed control of the internal temperature (entries 6–10). For
that the -carbonyl proton in the lactone ring was bonded these runs, the regioisomeric ratio was determined
to three different methine groups, a fact which is compat- through GC analysis of the reaction mixture and it is
ible with H-8 in 7a, but not with H-9 in 7b.
therefore representative of the regioselectivity of the cy-
cloaddition. It was observed that the regioselectivity was
independent of the reaction temperature (compare entries
6, 7 and 8). An experiment parallel to run 7 with a four-
fold diluted solution also gave the same regioisomeric ra-
tio. The straight (head to head) regioisomer always pre-
dominates, but the proportion of the crossed (head to tail)
Since the irradiation of acetone solutions gave cleaner
crude reaction products and the regioselectivity of the cy-
cloaddition did not seem to be affected by the irradiation
frequency, the next experiments with substrates 5 and 6
were performed under the conditions of run 2. Irradiation
of 5 (run 4) took 8 hours to reach full conversion and, after
Synthesis 2001, No. 8, 1143–1148 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Photocycloaddition of , -Butenolides to a Terminal Alkene
1145
Table 2 1H and 13C NMR Data of Compounds 7a–9a, , J (Hz)
Product
H-1
H-4
H-8
C-1
C-4
C-7
C-8
C-9
7a
3.02 (m)
5.02 (dd, J4,8 = 6.6,
J4,5 = 4.1)
3.30 (q, J8,1 J8,4 J8,7 36.4
7.1)
86.5
36.0
44.7
31.6
8a
9a
2.7
4.53 (d, J4,5 = 2.8)
41.3
91.6
84.6
41.5
32.2
52.7
50.2
28.2
39.2
–
4.96 (ddd, J4,8 = 7.2,
J4,5 = 4.5, 1.5)
2.98 (br t, J8,4 J8,7
7.2)
50.1
able 3 1H and 13C NMR Data of Compounds 7b–9b, , J (Hz)
roduct
H-1
H-4
H-9
C-1
C-4
C-7
C-8
C-9
b
2.96 (t, J1,7 J1,9
–
3.09 (dq, J = 7.1,
46.2
82.3
37.3
24.5–23.1 40.9
6.1)
J
5.6)
b
b
2.63 (d, J = 7.0)
4.60 (br t, J4,5
2.2)
–
51.4
42.1
87.9
81.3
34.0
43.1
30.0
–
4.99 (br d,J = 7.0) 2.70 (m)
23.4
44.2
Table 4 Geometrical Data for the Minimum Energy Conformation
of Intermediate Diradicals I–IVa
cycloadduct increases substantially when the starting
butenolide bears a methyl group at the -carbonyl position
and it diminishes slightly when the methyl group is at the
-carbonyl position.
Diradicals
R
R
Energy (kcal IRD (Å)c
mol-1)b
To explain the regioselectivity of these reactions, the in-
termediate diradicals leading to each product have to be
considered. For intermolecular [2+2] photocycloadditions
of enones to monosubstituted olefins, attack at the less
substituted terminus of the olefin is supposed to occur in
the first place,29 but for intramolecular processes steric
constrains may have a decisive influence on the regiose-
lectivity.22 It has been demonstrated that simple molecular
mechanics calculations may be used to analyze the geom-
etry of diradical species and inter-radical distances (IRD)
minor than 3 Å are considered appropriate for ring clos-
ing.33 We have calculated the relative stability and geom-
etry of the four possible intermediate diradicals, I–IV, for
each irradiated substrate (Figure, Table 4). Molecular me-
chanics (MMFF94) was used for assigning the lowest en-
ergy conformer to each intermediate species and its
equilibrium geometry was then optimized applying the
semi-empirical AM1 model. The results are summarized
in Table 4.
I7a/II7a
H
H
19.3/78.9
20.8/84.8
25.0/81.3
35.1/67.9
36.5/74.8
37.8/70.0
2.7/2.8
2.8/2.8
2.7/2.9
2.9/3.8
3.0/3.8
2.9/3.8
I8a/II8a
H
CH3
H
I9a/II9b
CH3
H
III7b/IV7b
III8b/IV8b
III9b/IV9b
H
H
CH3
H
CH3
a The calculations were performed using the PC SPARTAN pro pro-
gram of Wavefunction, Inc.
b Energy of the most stable conformer (MMFF94).
c Inter-radical distance (IRD) in the most stable conformer (AM1).
bon and the internal olefin position, but both I and II gave
suitable inter-radical distances for fast ring closing. For
the intermediates leading to the crossed adducts, III and
IV, those coming from initial formation of the -carbonyl
bond gave also lower energies. In these cases, moreover,
the calculated inter-radical distance for the minimum en-
ergy conformation of the alternative intermediates IV
gave too high values to favor collapse over reversion of
the excited substrate to the ground state. The lower energy
values and shorter inter-radical distances obtained for in-
termediates I in relation to III are in agreement with the
regioselectivity experimentally observed in favor of the
straight cycloadducts. The presence of a methyl group at
the - or -carbonyl position has little influence on the in-
ter-radical distance either on I or III, but the methyl group
at the -position destabilizes I in more extension than III
(compare I9a vs I7a and III9b vs III7b), in qualitative agree-
ment with the lower regioselectivity observed for 6.
O
O
O
O
O
O
O
O
Rβ
Rβ
Rα
Rα
Rα
Rα
Rβ
Rβ
I
II
III
IV
Figure Structures of intermediate diradicals I–IV
Regarding the two kind of diradicals leading to the
straight adducts 7a–9a, those of type I, coming from ini-
tial collapse of the enone -carbon with the olefin terminal
position, gave lower energies than those of type II, in
which the initial bond is formed between the enone -car-
Synthesis 2001, No. 8, 1143–1148 ISSN 0039-7881 © Thieme Stuttgart · New York

1146
F. Busqué et al.
PAPER
was added drop-wise 30% H2O2 (0.80 mL, 7.0 mmol), keeping the
temperature below 0 ºC. The mixture was stirred at 0 ºC for 45 min,
then neutralized with sat. aq NaHCO3 and extracted with Et2O (3
10 mL). The organic extracts were dried (Na2SO4) and the solvent
evaporated under vacuum. The oily residue was distilled on a
Kugelrohr (70–75 ºC, oven temp./0.06 Torr) to afford 4 (127 mg,
98%) as a colorless oil.
In conclusion, the regioselectivity of the intramolecular
[2+2] photocycloaddition of , -butenolides to a terminal
double bond located at a suitable distance depends on the
substitution pattern of the substrate. Very simple theoret-
ical calculations performed on the diradical intermediates,
considering the relative energy and inter-radical distance
of the most stable conformer, are in good qualitative
agreement with the experimental regioselectivity.
IR (film): = 3084, 2927, 1754, 1164, 1105 cm–1.
1H NMR (CDCl3, 250 MHz): = 7.45 (dd, J = 5.6, 1.5 Hz, 1 H), 6.08
(dd, J = 5.6, 2.0 Hz, 1 H), 5.77 (ddt, Jtrans = 17.2 Hz, Jcis = 10.2 Hz,
J = 6.6 Hz, 1 H), 5.06 (m, 3 H), 2.21 (m, 2 H), 1.82 (m, 1 H), 1.77
(m, 1 H).
13C NMR (CDCl3, 62.5 MHz): = 172.9, 156.1, 136.6, 121.5,
116.1, 82.5, 32.3, 29.1.
All solvents were purified and dried by standard techniques just be-
fore use. Diisopropylamine was freshly distilled over NaOH.
Phenylselenoacetic34 and 2-phenylselenopropionic35 acids were
prepared following previously described procedures. Photochemi-
cal reactions at r.t. were performed on a Rayonet® reactor and at
lower temperatures on a standard photochemical reactor for internal
irradiation with a 125 W medium pressure mercury lamp fitted in an
immersion well, equipped with a Pyrex® cooling jacket. Substrate
solutions were degassed by passing an argon stream through. For
analytical TLC, Alugram Sil 0.25 mm thick plates Machery–Nägel
were used. Chromatographic separations were carried out on silica
gel 230–400 mesh activated at 80 ºC under moderated pressure
(flash). GC were performed on a Hewlett-Packard 6890 chromato-
graph with a dimethylsilicone cross linked 12 m capillary column.
GC/HRMS were recorded on a Varian MAT 311A spectrometer.
Mass spectra were performed on a Hewlett-Packard 5989A spec-
trometer. IR spectra were obtained on a Nicolet 5ZDX spectropho-
MS: m/z (%) = 139 (M+ + 1, 1), 138 (M+, 2), 110 (5), 84 (100), 55
(74).
Anal. Calcd for C8H10O2: C, 69.55; H, 7.30; found C, 69.38; H,
7.40.
5-But-3-enyl-4-methylfuran-2(5H)-one (5)
An ethereal solution of diazomethane (ca 3.80 mmol) prepared from
Diazald® (1.09 g, 5.09 mmol) was slowly distilled over to a stirred
solution of 4 (245 mg, 1.8 mmol) in THF (4 mL) at –5 ºC. The mix-
ture was kept in the dark, at r. t. for 24 h, monitoring the reaction by
TLC (eluent: EtOAc–hexane, 1:1). Evaporation of the solvent gave
a white solid identified as 4-(but-3-enyl)-3a,4,6,6a-tetrahydro-3H-
furo[3,4-c]pyrazol-6-one (323 mg, 100%) which was not further
purified:
1H NMR (CDCl3, 400 MHz): = 5.75 (ddt, Jtrans = 17.0 Hz,
Jcis = 10.1 Hz, J = 6.6 Hz, 1 H), 5.50 (td, J = 2.5, 2.2 Hz, 1 H), 4.98
(m, 2 H), 4.82 (dt, Jgem = 18.6 Hz, J = 2.5 Hz, 1 H), 4.67 (ddd,
Jgem = 18.6 Hz, J = 8.2 Hz, J = 1.9 Hz, 1 H), 3.92 (m, 1 H), 2.62 (m,
1 H), 2.16 (m, 2 H), 1.78 (m, 1 H), 1.71 (m, 1 H).
1
tometer. H NMR spectra were recorded on a Brucker AC250,
AM400WB or 500WB instruments. Chemical shifts are given in
ppm values with CHCl3 as reference (set at = 7.24). 13C NMR
spectra were recorded on a Brucker AC-250, AM400WB or 500WB
instruments. Theoretical calculations were performed using the PC
SPARTAN pro program of Wavefunction, Inc.
5-But-3-enylfuran-2(5H)-one (4)
13C NMR (CDCl3, 125 MHz): = 168.0, 136.2, 116.3, 94.3, 85.2,
85.1, 37.9, 35.6, 29.1.
To a stirred solution of diisopropylamine (740 L, 5.3 mmol) in
THF (7 mL) under N2 at 0 ºC was added a 1.6 M solution of BuLi
in hexane (3.3 mL, 5.3 mmol) and the mixture was stirred at 0 ºC for
30 min. Then, a solution of phenylselenoacetic acid (516 mg, 2.4
mmol) in THF (10 mL) was added dropwise. A white precipitate
was immediately formed. Next, a solution of epoxide 3 (225 L, 2.0
mmol) in THF (10 mL) was added drop-wise, the cooling bath was
removed and the reaction mixture was stirred at r. t. for 5 h. The
mixture was acidified with glacial AcOH and the resulting solution
was heated at reflux overnight. After neutralization with sat. aq
NaHCO3, the mixture was extracted with Et2O (3 25 mL). The or-
ganic extracts were dried (Na2SO4) and concentrated to give an oily
residue (662 mg) which purified by flash chromatography (eluent:
EtOAc–hexane, 1:3) afforded a mixture of cis- and trans-5-(but-3-
enyl)-3-phenylseleno-2-oxolanone (572 mg, 97%) as a pale yellow
oil.
This solid was dissolved in freshly distilled 1,4-dioxane (25 mL)
and heated at reflux for 48 h, following the reaction progress by
TLC (eluent: EtOAc–hexane, 1:1). Evaporation of the solvent under
vacuum gave a crude product which was purified by flash chroma-
tography (eluent: EtOAc–hexane, 1:2) affording 5 (185 mg, 69%)
as a colorless oil.
IR (film): = 3079, 2984, 2924, 1751, 1643, 1439, 1296, 1170 cm–1.
1H NMR (CDCl3, 500 MHz): = 5.78 (m, 2 H), 5.03 (m, 2 H), 4.82
(d, J = 7.9 Hz, 1 H), 2.19 (m, 2 H), 2.03 (s, 3 H), 1.97 (m, 1 H), 1.56
(m, 1 H).
13C NMR (CDCl3, 125 MHz): = 173.1, 168.4, 136.7, 117.0, 116.1,
83.8, 31.4, 28.7, 13.8.
HRMS: m/z calcd for C9H12O2 (M+) 152.0837, found 152.0842.
MS: m/z (%) = 153 (M+ + 1, 1), 152 (M+, 2), 110 (12), 98 (100), 69
IR (film): = 3069, 2980, 2931, 1774, 1474, 1442, 1353, 1183,
1021 cm–1.
1H NMR (CDCl3, 250 MHz): = 7.55 (m, 2 H), 7.25 (m, 3 H), 5.65
(m, 1 H), 4.92 (m, 2 H), 4.32 and 4.23 (m, 1 H), 3.94 (t, J = 9.5 Hz)
and 3.86 (dd, J = 6.6, 4.0 Hz) (total 1 H), 2.64 (ddd, J = 13.5, 9.5, 6.4
Hz) and 2.30–1.4 (complex absorption) (total 6 H).
13C NMR (CDCl3, 62.5 MHz): = 175.6, 136.8, 136.7, 135.8,
135.7, 135.6, 135.4, 129.4, 129.3, 129.1, 128.8, 115.7, 115.6, 78.7,
78.4, 77.5, 77.0, 76.5, 37.4, 37.0, 36.7, 36.6, 35.8, 34.6, 34.3, 29.3,
29.2.
(40), 41 (79).
5-But-3-enyl-3-methylfuran-2(5H)-one (6)
To a stirred solution of diisopropylamine (4.2 mL, 30.0 mmol) in
THF (40 mL) under N2 at 0 ºC was added a 1.6 M solution of BuLi
in hexane (18.7 mL, 30.0 mmol) and the mixture was stirred for 30
min. Then, a solution of 2-phenylselenopropionic acid (3.44 g, 15.0
mmol) in THF (10 mL) was added drop-wise and the mixture was
stirred at 0 ºC for 15 min and at 40 ºC for 30 min. Then the reaction
mixture was cooled again to 0 ºC, a solution of epoxide 3 (1.6 mL,
14.2 mmol) in THF (40 mL) was added, the cooling bath removed
and the mixture stirred at r. t. for 4 h. The mixture was acidified with
glacial AcOH and the resulting solution was heated at reflux over-
Anal. Calcd for C14H16O2Se: C, 56.96; H, 5.46; found C, 56.91; H,
5.56.
To a stirred, cold solution of 5-(but-3-enyl)-3-phenylseleno-2-oxol-
anone (276 mg, 0.93 mmol) and AcOH (2 drops) in THF (3 mL)
Synthesis 2001, No. 8, 1143–1148 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Photocycloaddition of , -Butenolides to a Terminal Alkene
1147
night. After neutralization with sat. aq NaHCO3, the mixture was
extracted with Et2O (3 200 mL). The organic extracts were dried
(Na2SO4) and concentrated to give an oily residue which purified by
flash chromatography (eluent: EtOAc–hexane, 1:3) afforded a mix-
ture of the two diastereoisomers of 5-(but-3-enyl)-3-phenylseleno-
3-methyl-2-oxolanone (3.61 g, 80%) as a pale yellow oil:
1H NMR (CDCl3, 400 MHz): = 7.64 (m, 2 H), 7.40 (m, 1 H), 7.32
(m, 2 H), 5.74 (m, 1 H), 5.00 (m, 2 H), 4.40 (m, 1 H), 2.41 (m, 1 H),
2.20–2.05 (complex absorption) and 1.91 (dd, J = 14.0, 10.4 Hz)
(total 3 H), 1.78 (m, 1 H), 1.68–1.50 (complex absorption, 4 H).
Irradiation of 5-But-3-enyl-4-methylfuran-2(5H)-one (5) at
Room Temperature
Irradiation of 5 (105 mg, 0.69 mmol) for 8 h following the general
procedure gave
a
7:1 mixture of 8-methyl-3-oxatricyc-
lo[5.1.1.04,8]nonan-2-one (8a) and of 9-methyl-3-oxatricyc-
lo[5.2.0.04,9]nonan-2-one (8b) (52 mg, 50%); bp 90–95 ºC (oven
temp.)/0.1 Torr.
8a and 8b
IR (film): = 2960, 2930, 2870, 1769, 1451, 1284, 1164, 1044 cm–1.
To a stirred, cool solution of this oil and AcOH (a few drops) in
THF (25 mL) was added drop-wise 30% H2O2 (9.0 mL, 79 mmol),
keeping the temperature below 0 ºC. The mixture was stirred at 0 ºC
for 45 min, then neutralized with sat. aq NaHCO3 and extracted with
Et2O (3 30 mL). The organic extracts were dried (Na2SO4) and the
solvent evaporated under vacuum. The oily residue was purified by
flash chromatography (eluent: EtOAc–hexane, 1:4) to afford 6
(1.23 g, 71%) as a colorless oil; bp 50–55 ºC (oven temp.)/0.7 Torr.
1H NMR (CDCl3, 500 MHz): Signals assigned to 8a; = 4.53 (d,
J4,5 = 2.8 Hz, 1 H, H4), 2.76–2.62 (complex absorption, 2 H, H-1 and
H-9), 2.29 (m, 1 H, H-7), 2.20 (m, 1 H, H-5), 2.14 (m, 1 H, H-6),
1.81–1.64 (complex absorption, 3 H, H-5, H-6 and H-9), 1.28 (s, 3
H, CH3). Signals assigned to 8b; = 4.60 (br t, J4,5 2.2 Hz, 1 H, H-
4), 2.63 (d, J = 7.0 Hz, 1 H, H-1), 1.19 (s, 3 H, CH3).
13C NMR (CDCl3, 125 MHz): Signals assigned to 8a; = 180.8 (C-
2), 91.6 (C-4), 52.7 (C-8), 41.5 (C-7), 41.3 (C-1), 35.0 (C-6), 32.5
(C-5), 28.2 (C-9), 20.5 (CH3). Signals assigned to 8b; = 87.9 (C-
4), 51.4 (C-1), 34.0 (C-7), 30.0 (C-8), 24.6 (C-5), 22.4 (C-6), 22.1
(CH3).
IR (film): = 3083, 2926, 1755, 1647, 1449, 1100, 1058 cm–1.
1H NMR (CDCl3, 500 MHz): = 7.01 (m, 1 H), 5.76 (ddt,
Jtrans = 17.0 Hz, Jcis = 10.1 Hz, J = 6.6 Hz, 1 H), 5.03 (dm, Jtrans = 17.0
Hz, 1 H), 4.98 (dm, Jcis = 10.1 Hz, 1 H), 4.87 (m, 1 H), 2.18 (m, 2
H), 1.87 (s, 3 H), 1.78 (m, 1 H), 1.67 (m, 1 H).
GC (T1 = 60 ºC, t1 = 2 min, T2 = 240 ºC, rate = 10 ºC/min): 8a 10.85
min, 8b 10.93 min.
13C NMR (CDCl3, 125 MHz): = 174.2, 148.6, 136.9, 130.1, 116.0,
80.4, 32.7, 29.3, 10.6.
HRMS: m/z calcd for C9H12O2 (M+) 152.0837, found 8a 152.0850,
8b 152.0850.
HRMS: m/z calcd for C9H12O2 (M+) 152.0837, found 152.0839.
MS: m/z (%) = 152 (M+, 2), 124 (10), 110 (34), 98 (76), 97 (54), 69
MS: m/z (%) 8a = 152 (M+, 6), 124 (5), 110 (11), 98 (100); 8b = 152
(M+, 10), 124 (12), 109 (13), 98 (100), 80 (61), 39 (45).
(46), 55 (92), 41 (100).
Irradiation of 5-But-3-enyl-3-methylfuran-2(5H)-one (6) at
Room Temperature
Irradiation of 5-But-3-enylfuran-2(5H)-one (4) at Room
Temperature; General Procedure
Irradiation of 6 (105 mg, 0.69 mmol) for 5 h following the general
procedure gave
a 1.6:1 mixture of 1-methyl-3-oxatricyc-
A solution of 4 (100 mg, 0.72 mmol) in acetone (10 mL) placed in
a Pyrex® vessel was irradiated on a Rayonet® reactor suited with
300 nm lamps for 5 h. The progress of the reaction was followed by
GC. The solvent was evaporated and the oily residue was purified
by flash chromatography (eluent: CH2Cl2–hexane, 3:2), affording a
3:1 mixture of 3-oxatricyclo[5.1.1.04,8]nonan-2-one (7a) and of
3-oxatricyclo[5.2.0.04,9]nonan-2-one (7b) (40 mg, 0.29 mmol,
40%); bp 70–75 ºC (oven temp.)/0.1 Torr.
lo[5.1.1.04,8]nonan-2-one (9a) and of 1-methyl-3-oxatricyc-
lo[5.2.0.04,9]nonan-2-one (9b) (61 mg, 58%); bp 90–95 ºC (oven
temp.)/0.2 Torr.
9a and 9b
IR (film): = 2962, 2932, 2865, 1770, 1455, 1352, 1231, 1128,
1086 cm–1.
1H NMR (CDCl3, 500 MHz): Signals assigned to 9a; = 4.96 (ddd,
J4,8 = 7.2 Hz, J4,5 = 4.5 Hz, J4,5 = 1.5 Hz, 1 H, H-4), 2.98 (br t, J8,4
J8,7 7.2 Hz, 1 H, H-8), 2.71 (m, 1 H, H-7), 2.34 (dd, Jgem = 12.6 Hz,
J9,7 = 8.8 Hz, 1 H, H-9), 2.25 (m, 1 H, H-5), 2.12 (m, 1 H, H-6), 1.92
(dd, Jgem = 12.6 Hz, J9,7= 3.5 Hz, 1 H, H-9), 1.73–1.58 (complex ab-
sorption, 2 H, H-5 and H-6), 1.34 (s, 3 H, CH3). Signals assigned to
9b; = 4.99 (br d, J 7.0 Hz, 1 H, H-4), 2.70 (m, 1 H, H-9), 2.35
(m, 1 H, H-7), 2.23 (m, 1 H, H-8), 2.00–1.90 (complex absorption,
4 H, 2 H-5 and 2 H-6), 1.34 (s, 3 H, CH3).
13C NMR (CDCl3, 125 MHz): Signals assigned to 9a; = 183.0 (C-
2), 84.6 (C-4), 50.2 (C-8), 50.1 (C-1), 39.2 (C-9), 36.5 (C-5), 32.2
(C-7), 31.5 (C-6), 21.5 (CH3). Signals assigned to 9b; = 180.1 (C-
2), 81.3 (C-4), 44.2 (C-9), 43.1 (C-7), 42.1 (C-1), 23.9 (C-5), 23.6
(C-6), 23.4 (C-8), 16.7 (CH3).
7a and 7b
IR (film): = 2966, 2936, 2870, 1769, 1356, 1170, 1050, 1003 cm–1.
1H NMR (CDCl3, 400 MHz): Signals assigned to 7a; = 5.02 (dd,
J4,8 = 6.6 Hz, J4,5 = 4.1 Hz, 1 H, H-4), 3.30 (q, J8,1 J8,4 J8,7 7.1
Hz, 1 H, H-8), 3.02 (m, 1 H, H-1), 2.85–2.74 (complex absorption,
2 H, H-7 and H-9), 2.31 (m, 1 H, H-5/H-6), 2.26 (m, 1 H, H-5/H-6),
1.76–1.63 (complex absorption, 3 H, H-5, H-6 and H-9). Signals as-
signed to 7b; = 3.09 (dq, J = 7.1 Hz, J 5.6 Hz, 1 H, H-9), 2.96 (t,
J
6.1 Hz, 1 H, H-1).
13C NMR (CDCl3, 125 MHz): Signals assigned to 7a; = 181.0 (C-
2), 86.5 (C-4), 44.7 (C-8), 36.6 (C-5/C-6), 36.4 (C-1), 36.0 (C-7),
31.7 (C-5/C-6), 31.6 (C-9). Signals assigned to 7b; = 178.0 (C-2),
82.3 (C-4), 46.2 (C-1), 40.9 (C-9), 37.3 (C-7), 24.5/23.9/23.1 (C-5/
C-6/C-8).
GC (T1 = 80 ºC, t1 = 1 min, T2 = 240 ºC, rate = 10 ºC/min): 9a 7.72
min, 9b 8.18 min.
HRMS: m/z calcd for C9H12O2 (M+) 152.0837, found 9a 152.0857,
9b 152.0854.
MS: m/z (%) 9a = 152 (M+, 3), 93 (31), 80 (100), 67 (32), 41 (47);
9b = 152 (M+, 10), 124 (23), 110 (41), 98 (100), 96 (85), 55 (78), 41
(74), 39 (75).
GC (T1 = 80 ºC, t1 = 1 min, T2 = 240 ºC, rate = 10 ºC/min): 7a 8.17
min, 7b 8.29 min.
HRMS: m/z calcd for C8H10O2 (M+) 138.0681, found 7a 138.0701,
7b 138.0701.
MS: m/z (%) 7a = 139 (M+ + 1, 1), 138 (M+, 6), 79 (50), 66 (100),
55 (28), 39 (50); 7b = 138 (M+, 4), 110 (20), 84 (96), 83 (44), 79
(60), 66 (60), 55 (42), 39 (100).
Synthesis 2001, No. 8, 1143–1148 ISSN 0039-7881 © Thieme Stuttgart · New York

1148
F. Busqué et al.
PAPER
Irradiation of 5-But-3-enylfuran-2(5H)-one (4) at Low
Temperature; General Procedure
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A solution of 4 (89 mg, 0.65 mmol) in acetone (80 mL) at –15 ºC
was irradiated for 6 h. MeOH was used for refrigeration of the im-
mersion well jacket and an external bath at –50 ºC was also neces-
sary to keep the temperature of the reaction mixture at –15 ºC. The
reaction progress was monitored by GC. After total conversion of 4,
the ratio 7a/7b was 7:1. The solvent was evaporated and the oily
residue was purified by flash chromatography (eluent: CH2Cl2–hex-
ane, 1:1), affording a 6:1 mixture of 7a and 7b (45 mg, 51%). Re-
peated flash chromatography allowed the isolation of a fraction (18
mg) containing a 14:1 mixture (1H NMR analysis) of 7a and 7b.
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Asymmetry 1991, 2, 1391. (b) Alibés, R.; Bourdelande, J.
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Irradiation of 5-But-3-enyl-4-methylfuran-2(5H)-one (5) at
Low Temperature
Irradiation of 5 (80 mg, 0.53 mmol) at –15 ºC following the general
procedure showed total conversion of the substrate after 8 h, giving
a 8:1 mixture (GC) of 8a and 8b. Purification by flash chromatog-
raphy (eluent: CH2Cl2–hexane, 1:1) afforded a 10:1 mixture of 8a
and 8b (46 mg, 58%). A second flash chromatography allowed iso-
lation of 8a (14 mg) of more than 98% purity (1H NMR analysis).
Irradiation of 5-But-3-enyl-3-methylfuran-2(5H)-one (6) at
Low Temperature
Irradiation of 6 (74 mg, 0.49 mmol) at –15 ºC following the general
procedure showed total conversion of the substrate after 5 h, giving
a 1.7:1 mixture (GC) of 9a and 9b. Purification by flash chromatog-
raphy (eluent: CH2Cl2–hexane, 1:1) afforded a 1.5:1 mixture of 9a
and 9b (41 mg, 55%).
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1292. (b) Schröder, C.; Wolff, S.; Agosta, W. C. J. Am.
Chem. Soc. 1987, 109, 5491.
Acknowledgement
We gratefully acknowledge financial support of CIRIT (1997SGR
00003) and DGES (PB97–0215) and grants of Generalitat de Cata-
lunya (to F. B. and J. R.).
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Synthesis 2001, No. 8, 1143–1148 ISSN 0039-7881 © Thieme Stuttgart · New York