Intramolecular butenolide allene photocycloadditions and ensuing retro-ene reactions of some photoadducts

Article abstract of DOI:10.1002/ejoc.201100245

This report describes intramolecular [2+2] photocycloadditions of several butenolides with an allenylmethyl substituent at the 5-position. These photosubstrates were prepared from 2-(silyloxy)furans through silver-mediated reactions with allenylmethyl bromides. Two cases were studied where the lactone was replaced by an N-Boc-lactam. Irradiations of the photosubstrates were carried out with 300 nm UV-light in acetonitrile/acetone mixtures. Crossed cycloadducts were produced in good yields via cycloaddition of the heterocyclic double bond with the allene internal double bond. The products were γ-lactones (γ-lactams) containing the strained 5-methylenebicyclo[2. 1.1]hexane skeleton. In some cases the products were unstable due to remarkably facile retro-ene reactions (1,5-hydrogen shifts) leading to unique α,β-unsaturated γ-lactone derivatives. These reactions occurred only with well-oriented C-H bonds so that strain-releasing four-membered ring opening could take place. This retro-ene reaction was studied in detail for more highly substituted derivatives in order to establish its relevance in connection with the instability of the natural terpenoid solanoeclepin A, the hatching agent of potato cyst nematodes. To this end, the methylenecyclobutane moiety in one of the cycloadducts was converted into a bicyclo[2.1.1]hexan-5-one (cyclobutanone) substructure. Copyright

Full text of DOI:10.1002/ejoc.201100245

FULL PAPER
DOI: 10.1002/ejoc.201100245
Intramolecular Butenolide Allene Photocycloadditions and Ensuing Retro-Ene
Reactions of Some Photoadducts
Ginger Lutteke,[a] Roel A. Kleinnijenhuis,[a] Ivo Jacobs,[a] Pauli J. Wrigstedt,[a]
Ana C. A. Correia,[a] Rowan Nieuwenhuizen,[a] B. T. Buu Hue,[a] Kees Goubitz,[b]
René Peschar,[b] Jan H. van Maarseveen,[a] and Henk Hiemstra*[a]
Keywords: Photochemistry / Cycloaddition / Small ring systems / Cyclobutane / Silver-mediated allylation / Retro-ene
reaction / Solanoeclepin A
This report describes intramolecular [2+2] photocycload- products were unstable due to remarkably facile retro-ene
ditions of several butenolides with an allenylmethyl substitu-
ent at the 5-position. These photosubstrates were prepared
from 2-(silyloxy)furans through silver-mediated reactions
with allenylmethyl bromides. Two cases were studied where
the lactone was replaced by an N-Boc-lactam. Irradiations of
the photosubstrates were carried out with 300 nm UV-light
in acetonitrile/acetone mixtures. Crossed cycloadducts were
produced in good yields via cycloaddition of the heterocyclic
double bond with the allene internal double bond. The prod-
ucts were γ-lactones (γ-lactams) containing the strained 5-
methylenebicyclo[2.1.1]hexane skeleton. In some cases the
reactions (1,5-hydrogen shifts) leading to unique α,β-unsatu-
rated γ-lactone derivatives. These reactions occurred only
with well-oriented C–H bonds so that strain-releasing four-
membered ring opening could take place. This retro-ene re-
action was studied in detail for more highly substituted deriv-
atives in order to establish its relevance in connection with
the instability of the natural terpenoid solanoeclepin A, the
hatching agent of potato cyst nematodes. To this end, the
methylenecyclobutane moiety in one of the cycloadducts was
converted into a bicyclo[2.1.1]hexan-5-one (cyclobutanone)
substructure.
Our strategy was first tested on substrate 2 (Scheme 1).
When we began our study such an intramolecular allene
butenolide photocycloaddition in which the allene and the
butenolide double bond are connected by a two-atom tether
appeared to be unknown in the literature. We were therefore
pleased to observe a smooth acetone-sensitized photocy-
cloaddition of 2 in the desired regiochemical sense to give
the tetracyclic product 3 containing the desired carbocyclic
core of 1 in 70% yield. Apparently, only the allene internal
double bond reacted and the cycloaddition took place in
the crossed fashion.[2]
Introduction
The intramolecular [2+2] photocycloaddion has been fre-
quently used as a key step in the construction of cyclobut-
ane-containing natural products.[1] In connection with our
research toward a total synthesis of solanoeclepin A (1),
the hatching agent of potato cyst nematodes (Figure 1), the
butenolide allene [2+2] photocycloaddition was of special
interest to us. For the construction of the tricyclic core of
the natural product we designed a strategy based on this
process.[2]
Scheme 1. The model intramolecular butenolide allene photocy-
cloaddition.
Figure 1. Structure of solanoeclepin A (1).
The efficiency of this reaction and the relevance of the
product structure stimulated us to study this type of intra-
molecular [2+2] photocycloaddition in more detail by vary-
ing the substitution pattern of the butenolide (R1 and R2)
and the allene (R3) (Scheme 2). Such variations in substitu-
ents can have a significant effect on the course of the [2+2]
photocycloaddition, as was observed in a previous study.[2a]
[a] Laboratory of Organic Chemistry, Van ’t Hoff Institute for
Molecular Sciences, Faculty of Science, University of
Amsterdam,
Science Park 904, 1098 XH Amsterdam, The Netherlands
Fax: +31-20-5255604
E-mail: h.hiemstra@uva.nl
[b] Laboratory of Crystallography, Van ’t Hoff Institute for
Molecular Sciences,
Science Park 904, 1098 XH Amsterdam, The Netherlands
3146
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Intramolecular Butenolide Allene Photocycloadditions
After the cycloaddition these substituents end up at bridge-
The synthesis of the lactam analogues of 7 and 8 com-
head carbon atoms making their introduction at a later menced with the synthesis of 11 according to a literature
stage virtually impossible.
procedure.[6] Silver-mediated coupling with allenic bromides
5 and 6 gave the photosubstrates 12 and 13 in acceptable
yields (see Scheme 4).
Scheme 2. General synthetic approach to the photolysis products.
We herewith report the syntheses of these photosub-
strates (X = O) by using a silver-mediated coupling pro-
cedure of 2-(silyloxy)furan derivatives with the appropriate
allenic bromide (Scheme 2). For the synthesis of the nitro-
gen analogues (X = N-Boc) a similar coupling of N-Boc-2-
(silyloxy)pyrrole was used. Such silver-mediated alkylations
Scheme 4. The N-Boc-2-(silyloxy)pyrrole 11 as starting material.
Irradiation of 12 for 50 min resulted in complete con-
sumption of the starting material according to TLC. Purifi-
cation gave a single crystalline product in 67% yield.
Recrystallization from n-pentane afforded crystals (m.p. 61–
62 °C) suitable for X-ray analysis, which unambiguously
confirmed the formation of the crossed cycloadduct 14
(Figure 2). The n-butyl-substituted photosubstrate 13 also
participated uneventfully in the [2+2] photocycloaddition
to provide 15 in 44% yield after 45 min of irradiation. Re-
lated cycloadditions of allyl-substituted pyrrol-2-ones were
recently reported by Wrobel and Margaretha.[7]
of silyl dienol ethers were pioneered by Jefford and co-
[3]
workers
and were first applied for the introduction of
allenic substituents by us.[2a] The photosubstrates were then
subjected to irradiation with 300 nm UV light providing
interesting cyclic structures, some of which appeared to be
susceptible to remarkably facile retro-ene reactions. The rel-
evance of this rearrangement reaction in connection with
the thermal instability of the natural product 1 itself will be
discussed.
Results and Discussion
We began our studies with the parent commercially avail-
able 2-(trimethylsilyloxy)furan (4) as coupling partner for
two allenic bromides, namely unsubstituted 2,3-butadienyl
bromide 5[4] and its 2-butyl analogue 6, both prepared from
the corresponding alcohols.[5] The silver-mediated couplings
went in moderate yields to provide the photosubstrates 7
and 8, respectively (see Scheme 3). We were pleased to find
that 7 gave smooth photocycloaddition using similar condi-
tions as for 2 requiring only 40 min of irradiation. After
purification cycloadduct 9 was obtained in 53% yield. The
butyl analogue 8 gave full conversion after 1 h of irradiation
according to TLC. Purification provided cycloadduct 10 in
61% yield. The structures of 9 and 10 were assigned by
comparison of their NMR spectra with those of 3. Most
diagnostic are the methylene protons in the 1H NMR spec-
tra as two singlets between 4.60 and 4.55 ppm and the cor-
Figure 2. X-ray crystal structure of photoadduct 14.
The lactam ring of 14 was readily opened by treatment
with sodium methoxide in methanol at 0 °C for 15 min
which furnished 16 in 82% yield (Scheme 5). The strained
bicyclo[2.1.1]hexane skeleton of 16 has aroused consider-
able interest as template for mechanistic studies[8] and as
backbone for novel glutamate receptor agonists.[9]
responding carbon signals at ca. 150 and 94 ppm in the 13
NMR spectra.
C
Scheme 5. Ring opening of the lactam.
Continuing our investigations we directed our attention
to methyl-substituted butenolides. Coupling of the allenic
bromides 5 and 6 with (silyloxy)furan 17[10] gave the ex-
pected substitution products 18 and 19 in ca. 30% yield,
apparently reflecting a steric effect of the methyl group
(Scheme 6). Irradiation of these photosubstrates proceeded
smoothly to give the expected cycloadducts 20 and 21 in
67% and 89% yield, respectively.
Scheme 3. The parent 2-(silyloxy)furan 4 as starting material.
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Scheme 8. Photochemistry of 23.
Scheme 6. 4-Methyl-2-(silyloxy)furan 17 as starting material.
The silver-mediated coupling of (silyloxy)furan 22[10]
with allenic bromides 5 and 6 provided the desired photo-
substrates 23 in 58% and 24 in 49% yield (Scheme 7).
Scheme 9. The two possible modes of the retro-ene reaction.
ene process. The chromatographic separation of this mix-
ture was also tedious, but 27 could be eventually isolated in
30% yield.
Scheme 7. 3-Methyl-2-(silyloxy)furan 22 as starting material.
When photosubstrate 23 was irradiated at 300 nm under
the usual conditions, two products were formed in a ratio
of 72:28 according to 1H NMR (Scheme 8). Both the minor
(25) and the major product (26) showed exocyclic methylene
hydrogens as sharp singlets at δ = 4.73 and 4.68 ppm for
Scheme 10. Photochemistry of 24.
With the pure cycloadduct 27 in hand the anticipated
the minor product and as doublets (J = 2 Hz) at δ = 6.26 retro-ene process could be investigated in more detail.
and 5.69 ppm for the major product. These latter chemical When 27 was heated as a neat sample for 5 h at 70 °C under
shift values of the major product were at unusually low field vacuum a smooth and complete conversion to 28 was ob-
compared to the olefinic data of the previous photoadducts. served. Noteworthy are the mild conditions at which this
Furthermore, this major product showed another olefinic retro-ene reaction occurs. Usually these 1,5-hydrogen shifts
hydrogen as a broad signal at δ = 5.39 ppm, thereby ruling require high temperatures.[11] It was clear that the retro-ene
out the formation of the regioisomeric straight cycload- reaction involves cleavage according to a (see C in
1
duct.[2] On the basis of H NMR spectroscopic data it was Scheme 9), because product 27 showed only two alkene hy-
1
concluded that the minor product was the expected pho- drogen signals in the H NMR (6.21 and 5.65 ppm), indi-
toadduct 25. Chromatographic separation of the mixture cating that the endocyclic alkene is tetrasubstituted.
failed. The major product appeared to be present in all
The question remains how 26 and 28 are formed in the
chromatographic fractions, which indicated that the minor photoreaction. It is unlikely that they only arise via thermal
25 was unstable and slowly turned into the major product. 1,5-hydrogen shift from the [2+2]-cycloaddition products,
This latter product could be eventually obtained pure in because the temperature of the photoreaction is too low
14% yield. After extensive NMR analysis the α-methyl- (Ͻ 45 °C). It is probable that the allylic biradical intermedi-
enelactone structure 26 was assigned to this product. The ate D can ondergo both direct radical coupling to the cyclo-
transformation of 25 into 26 can be viewed as an intramo- butane and hydrogen abstraction (Scheme 11).
lecular thermal retro-ene reaction (see Scheme 8).[11] This
The α-methylene-γ-butyrolactone moiety in the formal
process is shown in more detail in Scheme 9 and is in es- retro-ene products 26 and 28 is a motif that is encountered
sence a 1,5-hydrogen shift of a 3-methyl-1-methylenecy- in numerous terpenoid natural products of which several
clobutane moiety with relief of ring strain as a driving force. display anticancer and antiviral activity.[12] This consecutive
As indicated there are two possible products A and B de- photocycloaddition fragmentation sequence constitutes a
pending on which allylic bond is cleaved. The results with novel and interesting synthetic approach to this important
24 give conclusive evidence on this issue (vide infra).
class of compounds.[13]
The irradiation of 24 also resulted in the formation of
The potential instability of complex cyclobutanes due to
1
two products in a ratio of 66:34 as was determined by H a remarkably facile retro-ene type 1,5-hydrogen shift could
NMR (Scheme 10). However, in this case the major product be pertinent to the chemical properties of solanoeclepin A
was the normal cycloadduct 27 indicating a slower retro- (1). It is known that 1 decomposes at a temperature above
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Intramolecular Butenolide Allene Photocycloadditions
Figure 3. X-ray crystal structure of retro-ene product 29.
The n-butyl analogue of 3 was constructed in a straight-
forward fashion by first coupling of allenyl bromide 6 and
2-(silyloxy)furan 30 to give 31 in 64% yield. A smooth cy-
cloaddition was observed upon irradiation of 31 at 300 nm
for 1.5 h and a single product was detected using 1H NMR,
which was isolated in 70% yield (Scheme 13).
Scheme 11. Possible mechanisms of the photochemical events.
35 °C. However, it not clear which domain of the molecule
is responsible for this instability.[14] Thus, the thermal sensi-
tivity of 3 could provide some insight whether the decom-
position pathway of the natural product has a bearing on
such a retro-ene type rearrangement.
Therefore, the photochemical synthesis of 3 was repeated
and the crude reaction mixture was carefully analyzed with
1H NMR to make sure that the rearranged product had not
escaped identification during the previous study.[2b] In the
event byproducts could not be detected indicating that 3
was considerably less prone to rearrange than 23 or 24. Pre-
sumably this difference is a reflection of the degree of con-
formational change required for the rearrangement to oc-
cur.
Scheme 13. Synthesis and photolysis of 31.
As for 3, on heating a solution of 32 in DMF at 140 °C
for 14 h the rearranged product 33 was obtained along with
a small amount of 31 in a ratio of 90:10 (Scheme 14). The
separation of these two products using standard flash
chromatography was again difficult. However, 33 could be
obtained in pure form in 49% yield via recrystallization of
the combined chromatographic fractions containing both
31 and 33. The structure of 33 was assigned by comparison
This became evident when we heated a sample of 3 in
[D6]DMSO and found that the fragmentation indeed pro-
ceeds on prolonged heating at 140 °C. The formation of the
1
novel tricyclic product 29 was clear from the H NMR of
the crude reaction mixture showing a characteristic triplet
at δ = 6.99 ppm (Ha), a broad signal at δ = 5.43 ppm (Hb)
and a sharp doublet at δ = 4.56 ppm (Hc). In addition to
29 the allene 2 was formed in almost equal amount, which
1
of its H NMR spectroscopic data with those of 29.
is the product of
a formal retro-[2+2]-cycloaddition
(Scheme 12).
Scheme 12. Thermolysis of 3.
The use of other solvents such as DMF and xylenes did
not greatly affect the ratio of 29 and 2, but the reaction in
DMF gave fewer side products and was therefore the sol-
Scheme 14. Thermolysis and reduction of 32.
At this stage it is interesting to return to the thermal
vent of choice for a reaction on a preparative scale sensitivity of solanoeclepin A (1). Structural features of 1
(Scheme 12). After 14 h at 140 °C full conversion of the are the secondary hydroxy group and the bridgehead methyl
starting material was observed according to TLC. However, group, which are positioned on the cyclopentane ring of the
the separation of 29 and 2 using flash chromatography tricyclic core of the natural product. These groups are being
failed. Most gratifyingly, 29 could be obtained in pure form masked in the model substrates 3 and 32 as lactone rings.
by crystallization of the combined chromatographic frac- From molecular models it is clear that this difference in
tions containing both 29 and 2. Recrystallization from hex- backbone structure has a significant effect on the confor-
anes provided suitable crystals (m.p. 69–71 °C) for X-ray mation and therefore on the spatial orientation of the two
analysis, which unambiguously confirmed the proposed reacting groups in the retro-ene rearrangement. Therefore,
structure of 29 (Figure 3).
32 was fully reduced to diol 34 by treatment with LiAlH4
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H. Hiemstra et al.
FULL PAPER
and then heated in DMF. Interestingly this diol did not give might be that the natural product is a cyclobutanone in-
a clean retro-ene reaction. On prolonged heating at 150 °C stead of a methylenecyclobutane. The ketone oxygen could
1
decomposition products were observed in H NMR, which well speed up the retro-ene reaction. Precedent for an easier
did not reveal the typical signals of the spiro compound as retro-ene process in the case of cyclopropyl ketones com-
shown in Scheme 14.
pared with the methylene analogues is available.[11] We
This finding suggests that the thermal 1,5-hydrogen shift could only find one single example in the literature of a
is facilitated through the stereoelectronic effects of the lac- retro-ene reaction of a highly strained 3-alkylcyclobutanone
tone ring. As this structural motif is not present in the natu- in a fashion as expected here.[15] The most usual way in
ral product, we reasoned that it is quite unlikely that the which cyclobutanones decompose at high temperature is via
thermal instability of 1 can be ascribed to the retro-ene re- a ketene olefin [2+2]-cycloreversion.[16]
action. To get experimental proof for this assumption we
Thus, we decided to transform 39 into the cyclobutanone
set out to convert 34 into a compound, which is more natu- 42 according to our previously published method.
ral product like by conversion of the primary alcohol into (Scheme 16)[2b] Thus, dihydroxylation of the double bond
a methyl.
using OsO4 followed by cleavage of the vicinal diol gave the
Silylation of 34 using TBSCl in DMF resulted in the for- desired ketone 42. The heating a sample of 42 in [D6]-
mation of two mono-protected alcohols 35 and 36, which DMSO was carefully studied by 1H NMR spectroscopy.
were isolated in 59% and 25% yield in favor of the desired The temperature was slowly raised. Already at 110 °C a
regioisomer (Scheme 15). After some experimentation it be- rather quick decomposition of 42 into several products was
came clear that the selectivity could not be increased even observed. Unfortunately, attempts to purify the mixture
using protocols for selective protection of primary over sec- failed and none of the products could be obtained in pure
ondary alcohols (TBSCl, DMAP). The isomers could be form. Despite the purification problems, the discovery that
readily separated using flash chromatography and the unde- the cyclobutanone analogue of 39 has a lower thermal sta-
sired isomer could be converted back into 34 upon desi- bility provides some experimental support that the cyclobu-
lylation (TBAF, THF) to ensure material throughput. The tanone may play a role in the decomposition pathway of 1.
alcohol 38 was obtained through protection of the remain-
ing hydroxy group in 35 (BnBr, NaH, THF) followed by
desilylation (CSA, MeOH). Conversion of the hydroxy
group into a tosylate and subsequent reductive removal
using lithium triethylborohydride gave the bridgehead
methyl group and completed the synthesis of 39. With this
substrate in hand the retro-ene reaction could be investi-
gated. Heating a sample in [D6]DMSO showed an increased
Scheme 16. Synthesis of cyclobutanone 42.
stability compared to 34, because at a temperature of
150 °C no decomposition was observed. However, a further
increase of the temperature to 180 °C did cause a slow con-
version into the retro-ene rearrangement product 40. A
Conclusions
Silver-mediated reactions of 2-(silyloxy)furans with allen-
ylmethyl bromides proceeded well to produce several buten-
olides with an allenylmethyl substituent at the 5-position.
These products were excellent substrates for intramolecular
[2+2] photocycloaddion processes (300 nm, acetonitrile/acet-
one, 9:1), giving γ-lactones containing the strained 5-meth-
ylenebicyclo[2.1.1]hexane skeleton. Some of the products
reacted further via a retro-ene reaction (a 1,5-hydrogen
shift) to furnish unique α,β-unsaturated lactone derivatives.
All of these reactions are important in conjunction with our
synthetic approach toward solanoeclepin A, the hatching
agent of potato cyst nematodes. The instability of this natu-
ral product at temperatures above 35 °C might be related to
the inherent vulnerability of 3-alkylcyclobutanones to retro-
ene decomposition.
complete transformation was observed after 6 h of heating
and 40 could be isolated in 45% yield. This example shows
that the lactone ring is not essential for the retro-ene reac-
tion and that this still might be possible in the natural prod-
uct.
Experimental Section
Scheme 15. Synthesis and thermolysis of 39.
General Information: All reactions involving oxygen- or moisture-
sensitive compounds were carried out under a dry nitrogen atmo-
sphere. THF was distilled from sodium/benzophenone and CH2Cl2
The temperatures at which the rearrangements of the
substrates occur are still much higher than the 35 °C at
which the natural product decomposes. An obvious reason and acetonitrile were distilled from CaH2. The acetone used for
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Intramolecular Butenolide Allene Photocycloadditions
the irradiation experiments was of spectrophotometric grade. All
(m, 1 H, H-CH), 2.10–2.08 (m, 1 H, HC-H), 1.80–1.75 (m, 2 H,
commercially available chemicals were used as received. NMR CH2 nBu), 1.25–1.14 (m, 4 H, 2ϫCH2 nBu), 0.72 (t, J = 7.1 Hz, 3
spectra were recorded on a Bruker ARX 400 operating at 400 and
H, CH3 nBu) ppm. 13C NMR: δ = 205.6 (=C=), 172.5 (C-2), 156.4
100 MHz for 1H and 13C. Unless otherwise stated, CDCl3 was used (C-4), 121.0 (C-3), 97.9 (ϾC=), 81.7 (C-5), 76.8 (=CH2), 35.3
as solvent. Chemical shifts are given in ppm (δ) and were referred
to internal solvent signals. IR spectra were measured using a
(CH2), 31.8 (CH2 nBu), 29.2 (CH2 nBu), 21.9 (CH2 nBu), 13.6
(CH ) ppm. IR (neat): ν = 1975, 1748 cm–1. HR-MS: m/z calcd.
˜
3
Bruker IFS 28 FT-spectrometer and wavenumbers (ν) are reported
for C12H17O2 193.1223; found 193.1229 [M + H]+.
˜
in cm–1. Mass spectra and accurate mass determinations were per-
formed on a JEOL JMX SX/SX102A, coupled to a JEOL MS-
MP7000 data system. The photoreactions were carried out in a
quartz reaction vessel with a Rayonet RPR 300 nm. Elemental
analyses were performed by Dornis & Kolbe Microanalytisches La-
boratorium, Mülheim an der Ruhr, Germany.
tert-Butyl
2-(Buta-2,3-dien-1-yl)-5-oxo-2,5-dihydro-1H-pyrrole-1-
carboxylate (12): Prepared according to the general procedure from
(silyloxy)pyrrole 11 (1.0 g, 3.4 mmol).[6] Purification of the residue
by chromatography (hexanes/EtOAc, 1:1) provided 12 as an orange
1
solid (600 mg, 67%); m.p. 66–68 °C. H NMR: δ = 7.15–7.13 (m,
1 H, 4-H), 6.09–6.07 (m, 1 H, 3-H), 4.90–4.85 (m, 1 H, HC=),
4.69–4.63 (m, 3 H, 5-H, =CH2), 2.71–2.66 (m, 1 H, H-CH), 2.45–
2.40 (m, 1 H, HC-H), 1.52 (s, 9 H, Boc) ppm. 13C NMR: δ = 209.5
(=C=), 169.1 (C-2), 149.6 (C-4), 149.1 (C=O, Boc), 126.9 (C-3),
83.1 (HC=), 82.9 (Cq Boc), 75.3 (=CH2), 61.6 (C-5), 30.4 (CH2),
3-(Bromomethyl)hepta-1,2-diene (6): To a solution of 2-vinyl-
idenehexan-1-ol[5] (5.30 g, 42.0 mmol) in CH2Cl2 (50 mL) at 0 °C
was added methanesulfonyl chloride (4.9 mL, 7.29 g, 50.4 mmol).
Then triethylamine (6.8 mL, 5.10 g, 50.4 mmol) was added drop-
wise. The reaction was stirred for 1 h. The mixture was diluted with
CH2Cl2 (50 mL), washed with water (3ϫ), dried with MgSO4 and
27.9 (CH3 Boc) ppm. IR: ν = 2956, 1956, 1774, 1731 cm–1. HR-
˜
MS: m/z calcd. for C13H17NO3 236.1287; found 236.1290 [M +
H]+.
1
concentrated in vacuo. H NMR: δ = 4.91–4.87 (m, 2 H, C=CH2),
4.71–4.69 (m, 2 H, CH2OMs), 3.00 (s, 3 H, SO2CH3), 2.11–2.05
(m, 2 H, CH2 nBu), 1.51–1.40 (m, 2 H, CH2 nBu), 1.40–1.31 (m, 2
H, CH2 nBu), 0.90 (t, J = 7.3 Hz, 3 H, CH3 nBu). This crude
mesylate was used in the next reaction without further purification.
It was dissolved in 20 mL of acetone and then added dropwise to
a suspension of LiBr (14.59 g, 168 mmol) in acetone (80 mL) at
0 °C. The reaction was stirred for 1 h. The mixture was filtered
and concentrated in vacuo. Purification of the residue by column
chromatography (hexanes) afforded 6 (6.41 g, 34.0 mmol, 81% over
tert-Butyl
2-Oxo-5-(2-vinylidenehexyl)-2,5-dihydro-1H-pyrrole-1-
carboxylate (13): Prepared according to the general procedure from
(silyloxy)pyrrole 11[6] (500 mg, 1.7 mmol). Purification of the resi-
due by chromatography (hexanes/EtOAc, 1:1) provided 13 as a yel-
1
low oil (220 mg, 45%). H NMR: δ = 7.20 (dd, J = 6.1, 2.0 Hz, 1
H, 4-H), 6.00 (dd, J = 6.1, 1.4 Hz, 1 H, 3-H), 4.70–4.67 (m, 2 H,
=CH2), 4.64–4.61 (m, 1 H, 5-H) 2.78–2.74 (m, 1 H, H-CH), 2.06–
1.97 (m, 1 H, HC-H), 1.88–1.86 (m, 2 H, CH2 nBu), 1.53 (s, 9 H,
Boc), 1.36–1.18 (m, 4 H, 2ϫCH2 nBu), 0.83 (t, J = 7.1 Hz, 3 H,
CH3 nBu) ppm. 13C NMR: δ = 205.9 (=C=), 168.9 (C-2), 150.5 (C-
4), 149.1 (C=O, Boc), 126.1 (C-3), 98.1 (ϾC=), 82.7 (Cq Boc), 76.5
(=CH2), 61.2 (C-5), 34.4 (CH2), 32.3 (CH2 nBu), 29.4 (CH2 nBu),
1
two steps) as a colorless oil. H NMR: δ = 4.79 (s, 2 H, C=CH2),
4.02 (s, 2 H, CH2Br), 2.12 (m, 2 H, CH2 nBu), 1.46–1.33 (m, 4 H,
2ϫCH2 nBu), 0.92 (t, J = 7 Hz, 3 H, CH3) ppm. 13C NMR: δ =
206.9 (=C=), 101.2 (ϾC=), 76.5 (=CH2), 46.9 (CH2Br), 35.6 (CH2),
27.9 (CH Boc), 22.0 (CH ), 13.7 (CH ) ppm. IR: ν = 1965, 1773,
˜
3
2
3
29.1 (CH ), 22.1 (CH ), 13.7 (CH ) ppm. IR: ν = 2958, 1953 cm–1.
1730 cm–1. HR-MS: m/z calcd. for C17H25NO3Na 314.1732; found
˜
2
2
3
314.1736 [M + Na]+.
General Procedure for the Preparation of the Photosubstrates via
Silver-Mediated Coupling: To a well stirred suspension of dried
powdered 4 Å molecular sieves (same amount in weight as the all-
enic bromide) and silver trifluoroacetate (1.2 equiv.) in CH2Cl2
(0.5 m) at –78 °C was added a solution of the allenic bromide
(1.2 equiv.) in CH2Cl2 (0.4 m). After 5 min, a solution of 2-(silyl-
oxy)furan or 2-(silyloxy)pyrrole (1 equiv.) in CH2Cl2 (0.4 m) was
added. The mixture was well stirred and warmed to room tempera-
ture overnight followed by filtration through Celite. The solvent
was removed in vacuo and the residue purified using flash
chromatography.
5-(Buta-2,3-dien-1-yl)-4-methylfuran-2(5H)-one (18): Prepared ac-
cording to the general procedure from furan 17[10] (1.2 g,
5.7 mmol). Purification of the residue by chromatography (hexanes/
EtOAc, 4:1) provided 18 as a colorless oil (262 mg, 31%). 1H
NMR: δ = 5.79 (t, J = 1.4 Hz, 1 H, 3-H), 4.99–4.89 (m, 1 H, HC=),
4.89 (t, J = 1.0 Hz, 1 H, 5-H), 4.73–4.63 (m, 2 H, =CH2), 2.65–
2.58 (m, 1 H, H-CH), 2.34–2.25 (m, 1 H, HC-H), 2.07 (s, 3 H,
CH3) ppm. 13C NMR: δ = 209.8 (=C=), 173.2 (C-2), 168.2 (C-4),
117.9 (C-3), 83.8 (HC=), 83.3 (C-5), 75.8 (=CH2), 31.2 (CH2), 14.2
(CH ) ppm. IR: ν = 1958, 1753 cm–1. HR-MS: m/z calcd. for
˜
3
C9H10O2 151.0759; found 151.0578 [M + H]+.
5-(Buta-2,3-dien-1-yl)furan-2(5H)-one (7): Prepared according to
the general procedure from 2-(trimethylsiloxy)furan (4) (0.75 mL,
4.48 mmol). Purification of the residue by chromatography (hex-
anes/EtOAc, 2:1) afforded 7 as a light yellow oil (429 mg, 70%).
1H NMR: δ = 7.50 (dd, J = 5.7, 1.4 Hz, 1 H, 4-H), 6.13–6.11 (m,
1 H, 3-H), 5.11–5.03 (m, 2 H, 5-H, CH=), 4.79–4.71 (m, 2 H,
=CH2), 2.51–2.40 (m, 2 H, CH2) ppm. 13C NMR: δ = 209.4 (=C=),
172.7 (C-2), 155.6 (C-4), 121.9 (C-3), 83.5 (HC=), 82.2 (C-5), 75.8
4-Methyl-5-(2-vinylidenehexyl)furan-2(5H)-one (19): Prepared ac-
cording to the general procedure from furan 17[10] (1.0 g,
4.7 mmol). Purification of the residue by chromatography (hexanes/
EtOAc, 4:1) provided 19 as a colorless oil (305 mg, 31%). 1H
NMR: δ = 5.81 (t, J = 1.2 Hz, 1 H, 3-H), 4.99 (t, J = 5.6 Hz, 1 H,
5-H), 4.80–4.66 (m, 2 H, =CH2), 2.50–2.42 (m, 1 H, H-CH), 2.25–
2.17 (m, 1 H, HC-H), 2.08 (s, 3 H, CH3), 2.01–1.91 (m, 2 H, CH2
nBu), 1.42–1.23 (m, 4 H, 2ϫCH2 nBu), 0.86 (t, J = 7.0 Hz, 3 H,
CH3 nBu) ppm. 13C NMR: δ = 206.4 (=C=), 173.7 (C-2), 169.1 (C-
4), 117.5 (C-3), 98.7 (ϾC=), 83.8 (C-5), 77.4 (=CH2), 35.1 (CH2),
32.4 (CH2, nBu), 29.8 (CH2, nBu), 22.5 (CH2, nBu), 14.5 (CH3),
(=CH ), 31.9 (CH ) ppm. IR (neat): ν = 3026, 2924, 1957, 1769,
˜
2
2
1602 cm–1. HR-MS: m/z calcd. for C8H9O2 137.0603; found
137.0604 [M + H]+.
5-(2-Vinylidenehexyl)furan-2(5H)-one (8): Prepared according to
the general procedure from 2-(trimethylsiloxy)furan (4) (0.75 mL,
4.48 mmol). Purification of the residue by chromatography (hex-
anes/EtOAc, 4:1) afforded 8 as a colorless oil (597 mg, 54%). 1H
14.1 (CH , nBu) ppm. IR: ν = 1957, 1745 cm–1. HR-MS: m/z calcd.
˜
3
for C13H18O2 207.1385; found 207.1387 [M + H]+.
5-(Buta-2,3-dien-1-yl)-3-methylfuran-2(5H)-one (23): Prepared ac-
NMR: δ = 7.45 (d, J = 5.0 Hz, 1 H, 4-H), 5.93–5.91 (m, 1 H, 3- cording to the general procedure from 22[10] (200 mg, 0.91 mmol).
H), 5.02–4.99 (m, 1 H, 5-H), 4.62–4.60 (m, 2 H, =CH2), 2.22–2.12
Purification of the residue by chromatography (hexanes/EtOAc,
Eur. J. Org. Chem. 2011, 3146–3155
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3151

H. Hiemstra et al.
FULL PAPER
4:1) provided 23 as a colorless oil (79 mg, 58%). 1H NMR: δ =
1.76 (m, 2 H, CH2 nBu), 1.69 (d, J = 11.9 Hz, 1 H, 6Ј-H), 1.38–
7.08 (q, J = 1.6 Hz, 1 H, 4-H), 5.12–5.04 (m, 1 H, HC=), 5.00–4.93 1.33 (m, 4 H, 2ϫCH2 nBu), 0.94 (t, J = 6.8 Hz, 3 H, CH3) ppm.
(m, 1 H, C-5), 4.79–4.70 (m, 2 H, =CH2), 2.51–2.32 (m, 2 H, CH2),
13C NMR: δ = 174.3 (C-3), 152.2 (C-8), 92.7 (=CH2), 79.8 (C-5),
1.91 (t, J = 1.5 Hz, 3 H, CH3) ppm. 13C NMR: δ = 209.7 (=C=), 59.5 (C-7), 57.1 (C-2), 51.9 (C-1), 38.3 (C-6), 28.5 (CH2), 27.4
174.3 (C-2), 148.4 (C-4), 130.7 (C-3), 84.1 (HC=), 80.4 (C-5), 76.0 (CH ), 22.9 (CH ), 13.8 (CH ) ppm. IR: ν = 1766, 1697 cm–1. HR-
˜
2
2
3
(=CH ), 32.6 (CH ), 10.9 (CH ) ppm. IR: ν = 1957, 1746 cm–1.
MS: m/z calcd. for C12H17O2 193.1229; found 193.1229 [M + H]+.
˜
2
2
3
HR-MS: m/z calcd. for C9H11O2 151.0759; found 151.0758 [M +
tert-Butyl 8-Methylene-3-oxo-4-azatricyclo[3.3.0.02,7]octane-4-carb-
oxylate (14): According to the general procedure a solution of 12
(104 mg, 0.44 mmol) in 30 mL acetonitrile/acetone (9:1) was irradi-
ated for 50 min. The solvent was removed and the residue purified
by chromatography (hexanes/EtOAc, 1:1) to give 14 as a white solid
H]+.
3-Methyl-5-(2-vinylidenehexyl)furan-2(5H)-one (24): Prepared ac-
cording to the general procedure from furan 22[10] (170 mg,
0.81 mmol). Purification of the residue by chromatography (hex-
1
1
anes/EtOAc, 4:1) provided 24 as a colorless oil (82 mg, 49%). H
(70 mg, 67%); m.p. 61–62 °C. H NMR: δ = 4.61–4.60 (m, 1 H, 5-
NMR: δ = 7.12 (q, J = 1.6 Hz, 1 H, 4-H), 5.05–4.97 (m, 1 H, 5- H), 4.58 (s, 1 H, =CHH), 4.53 (s, 1 H, =CHH), 3.28–3.26 (m, 2 H,
H), 4.81–4.73 (m, 2 H, =CH2), 2.48–2.38 (m, 1 H, H-CH), 2.21– 1-H, 7-H), 2.88–2.87 (m, 1 H, 2-H), 2.12 (dd, J = 11.3, 4.5 Hz, 1
2.12 (m, 1 H, HC-H), 2.00–1.93 (m, 2 H, CH2), 1.90 (t, J = 1.6 Hz,
H, 6-H), 1.62 (dd, J = 11.4, 1.9 Hz, 1 H, 6Ј-H), 1.53 (s, 9 H, Boc)
3 H, CH3), 1.45–1.28 (m, 4 H, 2ϫCH2 nBu), 0.88 (t, J = 7.1 Hz, ppm. 13C NMR: δ = 170.7 (C-3), 149.3 (C=O, Boc), 149.0 (C-8),
3 H, CH3 nBu) ppm. 13C NMR: δ = 206.1 (=C=), 174.4 (C-2), 94.4 (=CH2), 83.1 (Cq, Boc), 57.3 (C-5), 55.2 (C-2), 52.3 (C-1), 47.4
149.0 (C-4), 130.2 (C-3), 98.7 (ϾC=), 79.9 (C-5), 77.3 (=CH2), 36.2
(C-7), 35.4 (C-6), 28.1 (CH ) ppm. IR: ν = 1780, 1745, 1701 cm–1.
˜
3
(CH2), 32.5 (CH2, nBu), 29.7 (CH2, nBu), 22.5 (CH2, nBu), 14.2 HR-MS: m/z calcd. for C13H17NO3 236.1287; found 236.1286 [M
(CH , nBu), 10.9 (CH ) ppm. IR: ν = 1956, 1753 cm–1. HR-MS:
+ H]+. C13H17NO3 (235.279): calcd. C 66.36, H 7.28, N 5.95; found
C 66.21, H 7.16, N 5.88.
˜
3
3
m/z calcd. for C13H18O2: 207.1385; found 207.1387 [M + H]+.
3-(2-Vinylidenehexyl)-4,5,6,7-tetrahydroisobenzofuran-1(3H)-one
(31): Prepared according to the general procedure from furan 30[2b]
(2.13 g, 7.25 mmol). Purification of the residue by chromatography
(hexanes/EtOAc, 9:1 to 8:2) gave 31 as a colorless oil (1.14 g, 64%).
X-ray Crystal Structure Analysis of 14: C13H17NO3, M = 235.28, T
= 253 K, λ = 1.5418 Å; triclinic, P1, a = 11.697(14) Å, b =
¯
11.732(14) Å, c = 11.851(2) Å, α = 117.71(4)°, β = 114.89(4)°, γ =
91.24(12)°, V = 1257(3) Å3, Z = 4, Dx = 1.24 gcm–3, 4243 observed
1H NMR: δ = 4.95–4.93 (m, 1 H, 3-H), 4.76–4.68 (m, 2 H, =CH2), unique reflections, R1 = 0.061.
2.44–2.37 (m, 1 H, H-CH), 2.28–2.19 (m, 5 H, HC-H, 2ϫCH2),
CCDC-765944 contains the supplementary crystallographic data
1.99–1.94 (m, 2 H, CH2 nBu), 1.74–1.67 (m, 4 H, 2ϫCH2), 1.41–
1.29 (m, 4 H, 2ϫCH2 nBu), 0.89 (t, J = 7.2 Hz, 3 H, CH3) ppm.
13C NMR: δ = 206.0 (=C=), 173.3 (C-1), 163.4 (C-9), 126.6 (C-8),
98.3 (ϾC=), 81.4 (C-3), 76.6 (=CH2), 34.9 (CH2), 32.1 (CH2, nBu),
29.4 (CH2, nBu), 23.2 (CH2), 22.1 (CH2, nBu), 21.4 (CH2), 21.3
for 14. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Methyl (1S*,2R*,4R*,5S*)-2-[(tert-Butoxycarbonyl)amino]-6-meth-
ylenebicyclo[2.1.1]hexane-5-carboxylate (16): To a solution of 14
(50 mg, 0.17 mmol) in 1 mL MeOH was added at 0 °C a solution
of 152 μL of a 2 m solution of MeONa in MeOH. The mixture was
stirred for 15 min at 0 °C and quenched by the addition of brine.
The resulting mixture was extracted with diethyl ether (3ϫ) and
the combined organics were washed with water and brine and dried
using MgSO4. The solvent was removed and the residue purified
by chromatography (hexanes/EtOAc, 1:1) to give 16 as a colourless
(CH ), 19.7 (CH ), 13.7 (CH ) ppm. IR: ν = 2929, 1957, 1746 cm–1.
˜
2
2
3
HR-MS: m/z calcd. for C16H23O2 247.1698; found 247.1699 [M +
H]+.
General Procedure for the [2+2] Photocycloadditions: A solution of
the photosubstrate in a mixture of acetonitrile/acetone (9:1) was
degassed by bubbling argon through the solution for 30 min. The
solution was kept under argon during the irradiation and the reac-
tion vessel was air-cooled with a fan which kept the temperature
below ca. 45 °C. The irradiation was continued until complete con-
version of the starting material was observed with TLC. The sol-
vent was removed in vacuo and the residue purified.
1
oil (38 mg, 82%). H NMR: δ = 5.39 (br. s, 1 H, NH), 4.47 (s, 2
H, =CH2), 4.08 (m, 1 H, 2-H), 3.69 (s, 3 H, OMe), 3.36–3.37 (m,
1 H, 1-H), 3.13–3.14 (m, 1 H, 2-H), 2.74 (m, 1 H, 5-H), 2.25.2.24
(m, 1 H, 3-H), 1.79–1.76 (m, 1 H, 3Ј-H), 1.45 (s, 9 H, Boc) ppm.
13C NMR: δ = 172.4 (C=O ester), 155.6 (C=O Boc), 150.2 (C-6),
93.6 (=CH2), 79.1 (Cq Boc), 55.3 (C-2), 51.7 (OMe), 49.1 (C-1),
48.8 (C-2), 44.1 (C-5), 33.0 (C-3), 28.4 (CH3) ppm. HR-MS: m/z
calcd. for C14H22NO4 268.1549; found 268.1550 [M + H]+.
8-Methylene-4-oxatricyclo[3.3.0.02,7]octan-3-one (9): According to
the general procedure a solution of 7 (93 mg, 0.68 mmol) in 25 mL
acetonitrile/acetone (9:1) was irradiated for 40 min. The solvent
was removed and the residue purified by chromatography (hexanes/
EtOAc, 2:1) to give 9 as a light yellow oil (49 mg, 53%). 1H NMR:
δ = 4.98–4.97 (m, 1 H, 5-H), 4.60 (s, 1 H, =CHH), 4.55 (s, 1 H,
=CHH), 3.62–3.59 (m, 1 H), 3.29–3.28 (m, 1 H), 2.97–2.96 (m, 1
H), 2.09 (dd, J = 12, 4 Hz, 1 H), 1.78 (dd, J = 12, 2 Hz, 1 H) ppm.
13C NMR: δ = 173.8 (C-3), 148.7 (C-8), 94.8 (=CH2), 78.9 (C-5),
tert-Butyl 7-Butyl-8-methylene-3-oxo-4-azatricyclo[3.3.0.02,7]octane-
4-carboxylate (15): According to the general procedure a solution
of 13 (72 mg, 0.25 mmol) in 20 mL acetonitrile/acetone (9:1) was
irradiated for 45 min. The solvent was removed and the residue
purified by chromatography (hexanes/EtOAc, 2:1) to give 15 as a
colorless oil (31 mg, 44%). 1H NMR: δ = 4.58–4.56 (m, 1 H, 5-H),
4.51 (s, 1 H, =CHH), 4.50 (s, 1 H, =CHH), 3.23–3.21 (m, 1 H, 1-
H), 2.61 (s, 1 H, 2-H), 2.03–1.99 (m, 1 H, 6-H), 1.77–1.73 (m, 2 H,
CH2 nBu), 1.53–1.50 [m, 10 H, C(CH3)3, 6Ј-H], 1.37–1.32 (m, 4 H,
2ϫCH2 nBu), 0.91–0.88 (t, J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR:
δ = 171.2 (C-3), 152.4 (C-8), 149.4 (C=O, Boc), 92.3 (=CH2), 83.0
(Cq, Boc), 60.8 (C-7), 58.4 (C-5), 55.5 (C-1), 53.4 (C-2), 38.7 (C-6),
28.8 (CH2), 28.1 (CH2), 27.6 (CH3, Boc), 23.1 (CH2), 13.4 (CH3)
59.0, 48.8, 46.1, 35.1 (C-6) ppm. IR: ν = 3100, 1766 cm–1. HR-MS:
˜
m/z calcd. for C8H9O2 137.0597; found 137.0612 [M + H]+.
7-Butyl-8-methylene-4-oxatricyclo[3.3.0.02,7]octan-3-one (10): Ac-
cording to the general procedure a solution of 8 (491 mg,
2.56 mmol) in 60 mL acetonitrile/acetone (9:1) was irradiated for
1 h. The solvent was removed and the residue purified by
chromatography (hexanes/EtOAc, 5:1) to give 10 as a light yellow
1
oil (300 mg, 61%). H NMR: δ = 4.97–4.96 (m, 1 H, 5-H), 4.57 (s,
1 H, =CHH), 4.55 (s, 1 H, =CHH), 3.57 (t, J = 4.0 Hz, 1 H, 2-H),
2.74 (s, 1 H, 1-H), 2.00 (ddd, J = 11.9, 4.0, 1.4 Hz, 1 H, 6-H), 1.81–
ppm. IR: ν = 1779, 1743, 1708 cm–1. HR-MS: m/z calcd. for
˜
C17H25NO3 292.1913; found 292.1917 [M + H]+.
3152
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3146–3155

Intramolecular Butenolide Allene Photocycloadditions
1-Methyl-8-methylene-4-oxatricyclo[3.3.0.02,7]octan-3-one (20): Ac-
cord-ing to the general procedure a solution of 18 (192 mg,
1.28 mmol) in 30 mL acetonitrile/acetone (9:1) was irradiated for
2 h. The solvent was removed and the residue purified by
=CHH), 4.62 (d, J = 4.0 Hz, 1 H, CH), 4.55 (s, 1 H, =CHH), 2.05
(dt, J = 13.5, 2.8 Hz, 1 H), 1.99 (dd, J = 11.6, 4.0 Hz, 1 H), 1.93–
1.88 (m, 1 H), 1.72 (d, J = 12.0 Hz, 1 H), 1.64–1.43 (m, 6 H), 1.35–
1.26 (m, 4 H), 1.18–1.15 (m, 1 H), 1.02 (dt, J = 13.5, 3.3 Hz, 1 H),
0.89 (t, J = 7.2 Hz, 3 H, CH3 nBu) ppm. 13C NMR: δ = 175.9
chromatography (n-pentane/Et2O, 2:1) to give 20 as a light yellow
1
oil (128 mg, 67%). H NMR: δ = 4.61–4.55 (m, 2 H, =CH2), 4.49 (C=O), 154.2 (ϾC=), 93.9 (CH2), 80.1 (CH), 64.3 (Cq), 59.4 (Cq),
(s, 1 H, 5-H), 3.26 (s, 1 H, 7-H), 2.68 (t, J = 1.4 Hz, 1 H, 2-H),
2.17–2.09 (m, 1 H, 6-H), 1.77 (dd, J = 12.0, 2.4 Hz, 1 H, 6Ј-H),
55.2 (Cq), 39.1 (CH2), 26.9 (CH2), 25.6 (CH2), 22.8 (CH2), 21.5
(CH ), 20.2 (CH ), 19.3 (CH ), 19.2 (CH ), 13.7 (CH ) ppm. IR: ν
˜
2
2
2
2
3
1.33 (s, 3 H, CH3) ppm. 13C NMR: δ = 173.7 (C-3), 152.4 (C-8), = 2929, 1766, 1690 cm–1. HR-MS: m/z calcd. for C16H23O2
92.3 (=CH2), 82.7 (C-5), 66.8 (C-1), 53.1 (C-2), 44.8 (C-7), 36.2 (C- 247.1698; found 247.1699 [M + H]+. C16H22O2 (246.35): calcd. C
6), 9.9 (CH ) ppm. IR: ν = 1768 cm–1. HR-MS: m/z calcd. for
78.01, H 9.00; found C 78.13, H 9.43.
˜
3
C9H11O2 151.0759; found 151.0755 [M + H]+.
5-Butyl-4-methyl-3-methylene-3,3a,6,6a-tetrahydro-2H-cyclopenta-
[b]furan-2-one (28): Cycloadduct 27 was heated in vacuo at 70 °C
for 5 h to furnish 28 (23 mg, 75%) as a light yellow oil after chro-
matographic purification (hexanes/EtOAc, 9:1). 1H NMR: δ = 6.21
(d, J = 2.0 Hz, 1 H, =CHH), 5.65 (d, J = 1.5 Hz, 1 H, =CHH),
5.02 (t, J = 6.3 Hz, 1 H, 7-H), 3.84–3.76 (m, 1 H, 8-H), 2.83–2.71
(m, 1 H, 6-H), 2.62 (d, J = 18.0 Hz, 1 H, 6Ј-H), 2.07 (t, J = 7.5 Hz,
2 H, CH2 nBu), 1.60 (s, 3 H, CH3), 1.41–1.20 (m, 2 H, CH2 nBu),
1.28 (m, 2 H, CH2 nBu), 0.90 (t, J = 7.3 Hz, 3 H, CH3 nBu) ppm.
13C NMR: δ = 170.7 (C-2), 136.5 (ϾC=), 135.9 (ϾC=), 128.2
(ϾC=), 121.5 (= CH2), 79.8 (C-7), 55.3 (C-8), 42.1 (C-6), 30.1
(CH2), 28.2 (CH2), 22.7 (CH2), 14.2 (CH3, nBu), 10.9 (CH3) ppm.
7-Butyl-1-methyl-8-methylene-4-oxatricyclo[3.3.0.02,7]octan-3-one
(21): According to the general procedure a solution of 19 (58 mg,
0.28 mmol) in 30 mL acetonitrile/acetone (9:1) was irradiated for
30 min. The solvent was removed and the residue purified by
chromatography (n-pentane/Et2O, 1:1) to give 21 as a light yellow
1
oil (39 mg, 67%). H NMR: δ = 4.50 (dd, J = 4.0, 1.4 Hz, 1 H, 5-
H), 4.47 (s, 1 H, =CHH), 4.43 (s, 1 H, =CHH), 2.38 (s, 1 H, 2-H),
1.95 (ddd, J = 11.6, 3.6, 1.2 Hz, 1 H, 6-H), 1.72–1.67 (m, 2 H, CH2
nBu), 1.63 (d, J = 12.0 Hz, 1 H, 6Ј-H), 1.33–1.22 (m, 7 H, 2ϫCH2,
CH3), 0.85 (t, J = 6.8 Hz, 3 H, CH3 nBu) ppm. 13C NMR: δ =
174.2 (C-3), 156.0 (C-8), 90.5 (=CH2), 83.7 (C-5), 64.7 (C-1), 58.3
(C-7), 56.5 (C-2), 39.8 (C-6), 28.5 (CH2), 27.6 (CH2), 22.9 (CH2),
IR: ν = 1759 cm–1. HR-MS: m/z calcd. for C H O 207.1385;
˜
13 19
2
found 207.1387 [M + H]+.
13.8 (CH , nBu), 9.9 (CH ) ppm. IR: ν = 1767 cm–1. HR-MS: m/z
˜
3
3
calcd. for C13H19O2 207.1385; found 207.1387 [M + H]+.
Thermolysis of 3: After heating 3[2b] (450 mg, 2.36 mmol) in 45 mL
of DMF for 14 h at 140 °C, the solvent was removed in vacuo and
the residue was purified by chromatography (hexanes/EtOAc, 9:1)
to provide an inseparable mixture of 2 and 29 (ratio 47:53). The
mixture was allowed to crystallize from hexanes resulting in the
isolation of 29 as a crystalline compound (65 mg, 14%); m.p. 69–
71 °C. 1H NMR: δ = 6.99 (t, J = 3.6 Hz, 1 H, =CH), 5.46–5.40 (m,
1 H, =CH), 4.56 (d, J = 4.8 Hz, 1 H), 2.97–2.68 (m, 1 H), 2.66–
2.54 (m, 1 H), 2.51–2.40 (m, 1 H), 2.39–2.44 (m, 1 H), 1.99–1.81
(m, 3 H), 1.80–1.71 (m, 3 H), 1.69–1.56 (m, 1 H) ppm. 13C NMR:
δ = 169.8 (C=O), 142.1 (=CH), 136.7 (ϾC=), 130.7 (ϾC=), 123.9
(=CH), 89.9 (CH), 56.1 (Cq), 36.2 (CH2), 29.4 (CH2), 24.2 (CH2),
Irradiation of Photosubstrate 23: According to the general pro-
cedure a solution of 23 (100 mg, 0.67 mmol) in 30 mL MeCN/ace-
tone was irradiated for 3 h at 300 nm. The solvent was removed
and the residue (mixture of 25 and 26 in a ratio 28:72 according to
1H NMR) was purified by chromatography (hexanes/EtOAc, 4:1)
to give pure 26 as a light yellow oil (14 mg, 14%). The minor prod-
uct 25 could not be obtained pure due to slow transformation into
26. Data for 4-methyl-3-methylene-3,3a,6,6a-tetrahydro-2H-cy-
1
clopenta[b]furan-2-one (26): H NMR: δ = 6.26 [d, J = 2.0 Hz, 1
H (=CHH)], 5.69 (d, J = 1.6 Hz, 1 H, =CHH), 5.39 (s, 1 H, 5-H),
5.12 (m, 1 H, 7-H), 3.77 (m, 1 H, 8-H), 2.82–2.64 (m, 2 H), 1.72
(m, 3 H) ppm. 13C NMR: δ = 170.3 (C-2), 137.3 (C-4), 135.8 (C-
3), 124.0 (=CH2), 122.0 (C-5), 81.5 (C-7), 54.0 (C-8), 39.3 (C-6),
18.6 (CH ), 14.7 (CH ) ppm. IR: ν = 1745 cm–1. HR-MS: m/z
˜
2
3
calcd. for C12H15O2 191.1072; found 191.1075 [M + H]+.
13.6 (CH ) ppm. IR: ν = 1757 cm–1.
˜
3
X-ray Crystal Structure Analysis of 29: C12H14O2, M = 190.24, T
¯
= 293 K, λ = 1.5418 Å, triclinic, P1, a = 5.8759(4) Å, b =
Irradiation of Photosubstrate 24: According to the general pro-
cedure a solution of 24 (100 mg, 0.7 mmol) in a 9:1 mixture of
acetonitrile/acetone (30 mL) was irradiated for 2 h at 300 nm. The
solvent was removed and the residue (mixture of 27 and 28 in a
ratio 66:34 according to 1H NMR) was purified by chromatography
(hexanes//EtOAc, 4:1) to give 27 as a light yellow oil (30 mg, 30%).
Data for 7-butyl-2-methyl-8-methylene-4-oxatricyclo[3.3.0.02,7]oc-
tan-3-one (27): 1H NMR: δ = 4.94 (dd, J = 4.0, 3.0 Hz, 1 H, 5-H),
4.63 (s, 1 H, =CHH), 4.62 (s, 1 H, =CHH), 3.23 (d, J = 2.5 Hz, 1
H, 1-H), 1.99 (dd, J = 12.0, 4.0 Hz, 1 H, 6-H), 1.70 (d, J = 12.0 Hz,
1 H, 6Ј-H), 1.65–1.53 (m, 2 H, CH2 nBu), 1.34–1.23 (m, 7 H,
2ϫCH2, CH3) 0.86 (t, J = 7.2 Hz, 1 H, CH3 nBu) ppm. 13C NMR:
δ = 177.0 (C-3), 153.9 (C-8), 94.7 (=CH2), 78.3 (C-5), 61.4 (C-1),
60.5 (C-2), 54.9 (C-7), 38.4 (C-6), 26.9 (CH2), 25.8 (CH2), 23.3
7.857(1) Å, c = 11.694(10) Å, α = 74.40(3)°, β = 85.447(16)°, γ =
74.232(8)°, V = 500.4(4) Å3, Z = 2, Dx = 1.26 gcm–3, 1444 observed
unique reflections, R1 = 0.052.
CCDC-773803 contains the supplementary crystallographic data
for 29. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Thermolysis of 32: After heating 32 (700 mg, 2.84 mmol) in 70 mL
of DMF for 14 h provided at 140 °C, the solvent was removed and
the residue purified by chromatography (5% EtOAc in hexanes) to
provide a mixture of 31 and 33 (10:90). The chromatographic frac-
tions containing both products were collected and concentrated in
vacuo. The residue was recrystallized from hexanes resulting in the
isolation of 33 as a crystalline solid (343 mg, 49%); m.p. 52–54 °C.
1H NMR: δ = 6.95 (t, J = 2.0 Hz, 1 H=CH), 4.48 (d, J = 4.8 Hz,
1 H, CH), 2.79–2.69 (m, 1 H, CH), 2.57–2.49 (m, 1 H, CH), 2.49–
2.38 (m, 1 H, CH), 2.37–2.21 (m, 1 H, CH), 2.14–2.06 (m, 2 H,
CH2 nBu), 1.99–1.76 (m, 3 H, CH, CH2), 1.66–1.55 (m, 4 H, CH3,
CH), 1.48–1.23 (m, 4 H, 2ϫCH2 nBu), 0.91 (t, J = 7.2 Hz, 3 H,
CH3 nBu) ppm. 13C NMR: δ = 170.2 (C=O), 136.1 (CH), 135.3
(CH ), 14.1 (CH , nBu), 8.9 ppm. IR: ν = 1763 cm–1. HR-MS: m/z
˜
2
3
calcd. for C13H19O2 207.1385; found 207.1387 [M + H]+.
Irradiation of Photosubstrate 31: According to the general pro-
cedure a solution of 31 (1.47 g, 5.96 mmol) in a 9:1 mixture of
acetonitrile/acetone (150 mL) was irradiated for 1.5 h at 300 nm.
The solvent was removed and the residue purified by chromatog-
raphy (hexanes/EtOAc, 8:2) to give 32 as a colorless crystalline so-
lid (1.03 g, 70%); m.p. 37–39 °C. 1H NMR: δ = 4.70 (s, 1 H, (Cq), 132.9 (Cq), 131.3 (Cq), 88.3 (CH), 57.3 (CH), 39.2 (CH2), 29.8
Eur. J. Org. Chem. 2011, 3146–3155
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3153

H. Hiemstra et al.
(CH2), 29.6 (CH2), 27.9 (CH2), 24.2 (CH2), 22.2 (CH2), 18.6 (CH2), 1 H), 1.90 (m, 2 H), 1.62–1.14 (m, 13 H), 0.88 (m, 12 H), 0.02 [s,
FULL PAPER
13.8 CH , (nBu), 11.9 (CH ) ppm. IR: ν = 1753 cm–1. HR-MS: m/z
calcd. for C16H23O2 247.1698; found 247.1696 [M
C16H22O2: calcd. C 78.01, H 9.00; found C 77.31, H 9.27.
6 H, Si(CH3)2] ppm. 13C NMR: δ = 159.5 (ϾC=), 139.1 (Cq Ph),
129.0 (CH Ph), 128.4 (CH Ph), 127.2 (CH Ph), 92.2 (=CH2), 80.3
(CHOBn), 70.9 (PhCH2O), 60.4 (Cq), 59.9 (Cq), 59.6 (CH2OSi),
47.1 (Cq), 40.4 (CH2), 37.0 (CH2), 27.6 (CH2), 25.8 [SiC(CH3)3],
25.0 (CH2), 23.7 (CH2), 22.1 (CH2), 21.3 (CH2), 20.9 (CH2), 18.2
˜
3
3
+
H]+.
(3S*,7aR*)-1-Butyl-7a-(hydroxymethyl)-8-methyleneoctahydro-1,3a-
methanoinden-3-ol (34): To cooled solution of LiAlH4
a
(CH2), 14.0 (CH3 nBu), –5.4 (SiCH ), –5.6 (CH ) ppm. IR: ν =
˜
3
3
(15.0 mmol) in THF (45 mL) was added dropwise a solution of
lactone 32 (1.170 g, 4.75 mmol) in THF (30 mL). The resulting
mixture was stirred for 1 h. The reaction was quenched by careful
addition of ethyl acetate (10 mL), followed by saturated Na2SO4
solution (5 mL). The mixture was stirring for 30 min, treated with
solid Na2SO4, filtered through Celite, and concentrated in vacuo.
Purification by recrystallization from hexanes/EtOAc afforded diol
21 (0.862 g, 3.34 mmol, 73%) as a colorless solid; m.p. 123–124 °C.
1H NMR: δ = 4.47 (s, 1 H, =CHH), 4.34 (s, 1 H, =CHH), 4.04–
3.98 (m, 2 H, CHOH, HCHOH), 3.79 (d, J = 11.5 Hz, 1 H,
HCHOH) 2.65 (br. s, 1 H, OH), 2.53 (br. s, 1 H, OH), 1.99–1.91
(m, 2 H), 1.81–1.40 (m, 11 H), 1.34–1.22 (m, 3 H), 1.14–1.11 (m,
1 H), 0.89 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR: δ = 159.2 (ϾC=),
92.1 (=CH2), 73.2 (CHOH), 66.0 (CH2OH), 61.3 (Cq), 60.0 (Cq),
46.2 (Cq), 39.9 (CH2), 31.7 (CH2), 27.8 (CH2), 26.7 (CH2), 23.5
2928, 1227, 1027, 834 cm–1. HR-MS: m/z calcd. for C29H47O2Si
455.3345; found 455.3340 [M + H]+.
[(3S*,7aR*)-3-(Benzyloxy)-1-butyl-8-methyleneoctahydro-1,3a-meth-
anoinden-7a-yl]methanol (38): To a stirred solution of 37 (0.847 g,
1.86 mmol) in CH2Cl2/MeOH (12.5 mL, 9:1) was added cam-
phorsulfonic acid (0.173 g, 0.744 mmol). The resulting mixture was
stirred overnight. The reaction was quenched with saturated
NaHCO3 solution. The layers were separated and the aqueous layer
was extracted with ethyl acetate (2ϫ 20 mL). The organic layers
were combined and washed with water (2ϫ 40 mL). The organic
layer was dried with MgSO4 and concentrated in vacuo. Purifica-
tion by column chromatography (hexanes/EtOAc, 20:1) yielded 38
as a light yellow oil (0.446 g, 1.31 mmol, 70%). 1H NMR: δ = 7.37–
7.26 (m, 5 H, Ph), 4.65 [d, J = 12.0 Hz, 1 H (PhHCHO)], 4.50–
4.47 (m, 2 H, =CHH, PhHCHO), 4.35 (s, 1 H, =CHH), 3.98 [d, J
= 12.0 Hz, 1 H, (HCHOH)], 3.78 (dd, J = 7.2, 2.0 Hz, 1 H,
CHOBn), 3.71 (d, J = 12.0 Hz, 1 H, HCHOH), 2.76 (br. s, 1 H,
OH), 2.05 (dd, J = 12.0, 2.4 Hz, 1 H), 1.88–1.12 (m, 15 H), 0.91
(t, J = 6.8 Hz, 3 H, CH3) ppm. 13C NMR: δ = 158.6 (ϾC=), 137.9
(Cq Ph), 128.3 (CH Ph), 127.5 (CH Ph), 127.4 (CH Ph), 92.1
(=CH2), 80.2 (CHOBn), 71.3 (PhCH2O), 65.9 (CH2OSi), 60.6 (Cq),
59.8 (Cq), 46.3 (Cq), 37.0 (CH2), 31.3 (CH2), 27.7 (CH2), 26.6
(CH2), 23.3 (CH2), 21.8 (CH2), 21.5 (CH2), 21.4 (CH2), 13.9 (CH3)
(CH ), 22.0 (CH ), 21.6 (CH ), 21.1 (CH ), 14.0 (CH ) ppm. IR: ν
˜
2
2
2
2
3
= 3300, 2927, 2860 cm–1. HR-MS: m/z calcd. for C16H27O2
251.2011; found 251.2011 [M + H]+. C16H26O2 (250.38): calcd. C
76.75, H 10.47; found C 76.74, H 10.48.
Silyl Ether 35: To a stirred solution of diol 34 (0.830 g, 3.32 mmol)
in DMF (20 mL) was added tert-butyldimethylsilyl chloride
(0.745 g, 4.49 mmol) and imidazole (1.59 g, 23.35 mmol). The re-
sulting mixture was stirred overnight at room temperature and then
diluted with ethyl acetate (10 mL). The layers were separated and
the aqueous layer was extracted with diethyl ether (2ϫ 25 mL).
The organic layers were combined and washed with water (3ϫ
80 mL), dried with MgSO4 and concentrated in vacuo. Purification
by column chromatography (hexanes/EtOAc, 20:1) gave 35 as a col-
orless oil (0.713 g, 1.96 mmol, 59%). 1H NMR: δ = 4.45 (s, 1 H,
=CHH), 4.31 (s, 1 H, =CHH), 3.91–3.83 (m, 3 H), 3.51 (d, J =
7.2 Hz, 1 H, HCHOH), 1.92 (dd, J = 12.0, 7.6 Hz, 1 H), 1.87 (dd,
J = 12.0 2.4 Hz, 1 H), 1.69–1.59 (m, 5 H), 1.53–1.35 (m, 5 H),
1.31–1.12 (m, 4 H), 0.90–0.86 (m, 12 H), 0.86 (s, 3 H, SiCH3), 0.76
(s, 3 H, SiCH3) ppm. 13C NMR: δ = 159.6 (ϾC=), 91.9 (=CH2),
73.3 (CHOH), 65.0 (CH2OH), 61.6 (Cq), 60.2 (Cq), 46.1 (Cq), 40.4
(CH2), 30.3 (CH2), 27.7 (CH2), 26.9 (CH2), 25.8 [CH3 SiC(CH3)3],
23.5 (CH2), 21.9 (CH2), 21.7 (CH2), 20.9 (CH2), 18.1 [SiC(CH3)3],
ppm. IR: ν = 3460, 2926, 1454, 1065, 733 cm–1. HR-MS: m/z calcd.
˜
for C23H33O2 341.2481; found 341.2482 [M + H]+.
(3S*,7aS*)-3-(Benzyloxy)-1-butyl-7a-methyl-8-methyleneoctahydro-
1,3a-methanoindene (39): To a stirred solution of 38 (0.430 g,
1.263 mmol) in pyridine (6.4 mL) was added p-toluenesulfonyl
chloride (0.489 g, 2.57 mmol). The resulting mixture was stirred
overnight at room temperature. The reaction was quenched with
water (2 mL) and stirring was continued for 1 h. The mixture was
further diluted with CH2Cl2 (25 mL). The layers were separated
and the organic layer was washed with 10% KHSO4 solution (3ϫ
20 mL). The organic layer was dried with MgSO4 and then concen-
trated in vacuo to afford the tosylate (0.578 g) as an oil which was
1
used for the next step without further purification. H NMR: δ =
7.72 (d, J = 8.0 Hz, 2 H, 2ϫCH Ts), 7.36–7.21 (m, 7 H, 2ϫCH
Ts, Ph), 4.75 (d, J = 10.5 Hz, 1 H, PhHCHO), 4.56 (s, 1 H, =CHH),
4.44 (d, J = 12.0 Hz, 1 H, PhHCHO), 4.36 (s, 1 H, =CHH), 4.33
(d, J = 14.5 Hz, 1 H, HCHOTs), 3.99 (d, J = 11.0 Hz, 1 H,
HCHOTs), 3.60 (dd, J = 7.0, 2.5 Hz, 1 H, CHOBn), 2.42 (s, 3 H,
SO3CH3), 1.92–1.83 (m, 2 H), 1.56–1.02 (m, 16 H), 0.92 (t, J =
7.5 Hz, 3 H, CH3) ppm. To a solution of crude tosylate in THF
(22 mL) was added lithium triethylborohydride (1 m in THF,
5.05 mL, 5 equiv.). The reaction mixture was refluxed for 18 h and
then cooled to 0 °C. The reaction was quenched with ice water
(6 mL) and the layers were separated. The aqueous layer was ex-
tracted with diethyl ether (3ϫ 25 mL), the combined organic layers
were then washed with water (2ϫ 75 mL). The organic layer was
dried with MgSO4 and concentrated in vacuo. Purification by col-
umn chromatography (hexanes/EtOAc, 20:1) afforded 39 as a col-
14.0 (CH nBu), –5.48 (SiCH ), –5.73 (SiCH ) ppm. IR: ν = 3323,
˜
3
3
3
2928, 2857, 1065, 834 cm–1. HR-MS: m/z calcd. for C22H41O2Si
365.2876; found 365.2870 [M + H]+.
Benzyl Ether 37: To a stirred solution of silyl ether 35 (0.690 g,
1.892 mmol) in THF (12 mL) was added benzyl bromide
(0.450 mL, 0.648 g, 3.79 mmol) and sodium hydride (0.167 g,
4.16 mmol, 60 wt.-% dispersion in mineral oil). The resulting mix-
ture was stirred at room temperature for 30 min. Tetra-n-butylam-
monium iodide was added (catalytic) and stirring was continued
overnight. The reaction was quenched with ice water. The mixture
was extracted with diethyl ether (3ϫ 15 mL). The combined or-
ganic layers were then washed with water (2ϫ 40 mL). The organic
layer was dried with MgSO4 and concentrated in vacuo. Purifica-
tion by column chromatography (hexanes/EtOAc, 50:1) yielded 37
1
1
as a clear oil (0.847 g, 1.86 mmol, 99%). H NMR: δ = 7.34–7.25
orless oil (0.143 g, 0.436 mmol, 43% over two steps). H NMR: δ
(m, 5 H, Ph), 4.56 (d, J = 8 Hz, 1 H, PhHCHO), 4.49 (s, 1 H,
=CHH), 4.43 (d, J = 12.5 Hz, 1 H, PhHCHO), 4.32 (s, 1 H,
= 7.34–7.24 (m, 5 H, Ph), 4.58 (d, J = 12.4 Hz, 1 H, PhHCHO),
4.47–4.44 (m, 2 H, PhHCHO, =CHH), 4.30 (s, 1 H, =CHH), 3.65
=CHH), 4.24 (d, J = 11 Hz, 1 H, HCHOSi), 3.65 (t, J = 5 Hz, 1 (dd, J = 7.2, 2.8 Hz, 1 H, CHOBn), 1.93–1.83 (m, 2 H), 1.73–1.22
H, CHOBn), 3.52 (d, J = 11 Hz, 1 H, HCHOSi), 2.04 (d, J = 12 Hz, (m, 14 H), 1.15 (s, 3 H, CH3), 0.90 (t, J = 6.8 Hz, 3 H, CH3 nBu)
3154
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3146–3155

Intramolecular Butenolide Allene Photocycloadditions
ppm. 13C NMR: δ = 160.4 (ϾC=), 139.3 (Cq Ph), 128.2 (CH Ph),
127.1 (CH Ph), 127.0 (CH Ph), 91.9 (=CH2), 81.4 (CHOBn), 71.0
4.46 (d, J = 12.0 Hz, 1 H, PhHCHO), 3.77 (dd, J = 7.2, 3.6 Hz, 1
H, CHOBn), 2.10–2.00 (m, 2 H) 1.78 (dd, J = 13.2, 3.6 Hz, 1 H),
(PhCH2O), 60.5 (Cq), 59.3 (Cq), 42.4 (Cq), 37.3 (CH2), 32.7 (CH2), 1.63–1.15 (m, 16 H), 0.89 (t, J = 7.2 Hz, 3 H, CH3 nBu) ppm. 13C
27.7 (CH2), 26.5 (CH2), 23.7 (CH2), 22.4 (CH2), 22.8 (CH2), 20.6
NMR: δ = 205.3 (C=O), 138.5 (Cq Ph), 128.3 (CH Ph), 127.5 (CH
Ph), 127.2 (CH Ph), 74.8 (CHOBn), 70.9 (PhCH2O), 69.8 (Cq), 69.1
(Cq), 37.1 (Cq), 34.6 (CH2), 34.4 (CH2), 27.3 (CH2), 23.9 (CH2),
23.4 (CH2), 22.6 (CH2), 21.3 (CH2), 19.7 (CH2), 14.3 (CH3), 13.9
(CH ), 14.1 (CH ), 12.5 (CH nBu) ppm. IR: ν = 2927, 1686, 1454,
˜
2
3
3
1104, 730 cm–1. HR-MS: m/z calcd. for C23H33O 325.2531; found
325.2528 [M + H]+.
(CH3 nBu) ppm. IR: ν = 2930, 1792, 1455, 1101, 733 cm–1. HR-
˜
(4S*,5R*)-4-(Benzyloxy)-2-butyl-1,6-dimethylspiro[4.5]deca-1,6-
diene (40): A sample of 39 (20 mg, 0.062 mmol) was dissolved in
[D6]DMSO. The solution was heated at 180 °C for 4 h, after which
1H NMR showed complete conversion of starting material. The
mixture was then cooled and diluted with diethyl ether (10 mL)
and washed with water (2ϫ 10 mL). The aqueous layers were ex-
tracted with diethyl ether (2ϫ 20 mL). The organic layer was dried
with MgSO4 and concentrated in vacuo to give 40 (9 mg, 45%) 1H
NMR: δ = 7.34–7.26 (m, 5 H, Ph), 5.67 (br. s, 1 H, =CH), 4.60 (d,
J = 12.4 Hz, 1 H, PhHCHO), 4.56 (d, J = 12.4 Hz, 1 H, PhHCHO),
3.80 (dd, J = 7.9, 5.3 Hz, 1 H, CHOBn), 2.60 (dd, J = 16.0, 7.9 Hz,
1 H), 2.35–2.29 (m, 1 H), 2.17–2.11 (m, 1 H), 2.09–1.99 (m, 3 H),
1.71–1.59 (m, 7 H), 1.46 (br. s, 3 H, CH3), 1.41–1.25 (m, 6 H), 0.92
(t, J = 7.2 Hz, 3 H, CH3 nBu) ppm. 13C NMR: δ = 139.4 (Cq Ph),
135.6 (ϾC=), 134.9 (ϾC=), 133.8 (ϾC=), 128.2 (CH Ph), 128.1
(CH Ph), 127.4 (CH Ph), 127.1 (CH Ph), 125.2 (CH=), 86.9
(CHOBn), 71.4 (PhCH2O), 58.3 (Cq), 41.4 (CH2), 34.7 (CH2), 30.0
(CH2), 28.4 (CH2), 25.8 (CH2), 22.5 (CH2), 21.6 (CH3), 19.4 (CH2),
MS (FAB) calcd. for C22H31O2 327.2324; found 327.2323 [M +
H]+.
Acknowledgments
We wish to thank Jan A. J. Geenevasen for his generous help to
analyse many NMR spectra and Lianne M. Jongens and Soraya
N. Sluijter for their synthetic contributions.
[1] For recent reviews, see, for example: a) T. Bach, J. P. Hehn,
Angew. Chem. Int. Ed. 2011, 50, 1000–1045; b) N. Hoffmann,
Chem. Rev. 2008, 108, 1052–1103; c) J. Iriondo-Alberdi, M. F.
Greaney, Eur. J. Org. Chem. 2007, 4801–4815.
[2] a) B. T. B. Hue, J. Dijkink, S. Kuiper, K. K. Larson, F. S. Guz-
iec Jr., K. Goubitz, J. Fraanje, H. Schenk, J. H. van Maarse-
veen, H. Hiemstra, Org. Biomol. Chem. 2003, 1, 4364–4366; b)
B. T. B. Hue, J. Dijkink, S. Kuiper, S. van Schaik, J. H.
van Maarseveen, H. Hiemstra, Eur. J. Org. Chem. 2006, 127–
137; c) for a recent review on [2+2] cycloadditions of allenes,
see: B. Alcaide, P. Almendros, C. Aragoncillo, Chem. Soc. Rev.
2010, 39, 783–816.
[3] a) C. W. Jefford, A. W. Sledeski, J. Boukouvalas, Helv. Chim.
Acta 1989, 72, 1362–1370; b) C. W. Jefford, A. W. Sledeski, J.-
C. Rossier, J. Boukouvalas, Tetrahedron Lett. 1990, 31, 5741–
5744.
[4] J. Pornet, B. Randrianoelina, L. Miginiac, J. Organomet. Chem.
1979, 174, 1–13.
14.0 (CH ), 10.8 (CH nBu) ppm. IR: ν = 2926, 1454, 1095 cm–1.
˜
3
3
(3S*,7aS*)-3-(Benzyloxy)-1-butyl-8-(hydroxymethyl)-7a-methylocta-
hydro-1,3a-methanoinden-8-ol (41): To a stirred mixture of tert-but-
yl alcohol (1.3 mL) and pyridine (90 μL) at 45 °C was added alkene
39 (43.5 mg, 0.134 mmol). To this mixture was added OsO4 (4 wt.-
% in water, 1.23 mL, 0.201 mmol) and stirring was continued for
20 h. The reaction was quenched with 20% sodium bisulfite solu-
tion (2 mL) and stirred for 45 min at room temperature. The mix-
ture was further diluted with water (3 mL) and extracted with
EtOAc (4ϫ 10 mL). The combined organic layers were washed
with water (4ϫ 20 mL). The organic layer was dried with MgSO4
[5] G. Lutteke, R. AlHussainy, P. J. Wrigstedt, B. T. B. Hue, R.
de Gelder, J. H. van Maarseveen, H. Hiemstra, Eur. J. Org.
Chem. 2008, 925–933.
[6] G. Casiraghi, G. Rassu, P. Spanu, L. Pinna, J. Org. Chem. 1992,
and concentrated in vacuo. Column chromatography (EtOAc/hex-
57, 3760–3763.
1
anes, 1:8) yielded 41 as a colorless oil (21.0 mg, 44%) H NMR: δ [7] M. N. Wrobel, P. Margaretha, Helv. Chim. Acta 2003, 86, 515–
521.
= 7.35–7.24 (m, 5 H, Ph), 4.61 (d, J = 12.0 Hz, 1 H, PhHCHO),
4.48 (d, J = 10.0 Hz, 1 H, HCHOH), 4.45 (d, J = 8.8 Hz, 1 H),
4.15–4.09 (m, 2 H), 2.21 (dd, J = 11.2, 7.2 Hz, 1 H), 2.05–1.98 (m,
1 H), 1.82 (dd, J = 11.2, 2.4 Hz, 1 H), 1.66–1.55 (m, 4 H), 1.45–
1.32 (m, 5 H), 1.30–1.21 (m, 6 H), 1.18 (s, 3 H, CH3), 0.88 (t, J =
7.2 Hz, 3 H, CH3 nBu) ppm. 13C NMR: δ = 139.6 (Cq Ph), 128.2
(CH Ph), 127.1 (CH Ph), 127.0 (CH Ph), 82.0 (CHOBn), 81.4 (Cq),
71.6 (PhCH2O), 66.6 (CH2OH), 57.9 (Cq), 57.2 (Cq), 40.6 (Cq), 36.1
[8] a) J. Meinwald, J. K. Crandall, J. Am. Chem. Soc. 1966, 88,
1292–1301; b) G. Mehta, S. R. Singh, V. Gagliardini, U. D. Pri-
yakumar, G. N. Sastry, Tetrahedron Lett. 2001, 42, 8527–8530.
[9] a) P. Conti, A. P. Kozikowski, Tetrahedron Lett. 2000, 41, 4053–
4056; b) N. Jullian, I. Brabet, J.-P. Pin, F. C. Acher, J. Med.
Chem. 1999, 42, 1546–1555.
[10] M. Abe, E. Torii, M. Nojima, J. Org. Chem. 2000, 65, 3426–
3431.
(CH2), 31.6 (CH2), 28.0 (CH2), 26.3 (CH2), 23.7 (CH2), 22.2 (CH2), [11] J.-L. Ripoll, Y. Vallée, Synthesis 1993, 659–677.
[12] J. M. Cassady, S. R. Byrn, I. K. Stamos, S. M. Evans, A. Mc-
Kenzie, J. Med. Chem. 1978, 21, 815–819.
21.1 (CH ), 20.9 (CH ), 20.2 (CH ), 14.0 (CH nBu) ppm. IR: ν =
˜
2
3
2
3
3450, 2915, 1750, 1480 cm–1.
[13] a) H. M. R. Hoffmann, J. Rabe, Angew. Chem. Int. Ed. Engl.
1985, 24, 94–110; b) R. R. A. Kitson, A. Millemaggi, R. J. K.
Taylor, Angew. Chem. Int. Ed. 2009, 48, 9426–9451.
[14] H. Schenk, R. A. J. Driessen, R. de Gelder, K. Goubitz, H.
Nieboer, I. E. M. Brüggemann-Rotgans, P. Diepenhorst, Croat.
Chem. Acta 1999, 72, 593–606.
[15] W. K. Appel, T. J. Greenhough, J. R. Scheffer, J. Trotter, J. Am.
Chem. Soc. 1979, 101, 213–215.
[16] See, e. g.: D. Bellus, B. Ernst, Angew. Chem. Int. Ed. Engl. 1988,
(3S*,7aS*)-3-(Benzyloxy)-1-butyl-7a-methyloctahydro-1,3a-meth-
anoinden-8-one (42): To a solution of diol 41 (18.0 mg, 0.051 mmol)
in acetone/water (1:1 v/v%, 2.25 mL) was added sodium periodate
(23.3 mg, 0.109 mmol). The resulting mixture was stirred for 2 d at
room temperature. Acetone was then removed in vacuo. The re-
sulting suspension was dissolved in EtOAc (10 mL) and washed
with brine (2ϫ 15 mL). The organic layer was dried with MgSO4
and concentrated in vacuo. Column chromatography (EtOAc/hex-
27, 797–827.
1
anes, 1:15) yielded 42 as a colorless oil (14.8 mg, 90%). H NMR:
Received: February 23, 2011
δ = 7.33–7.25 (m, 5 H, Ph), 4.58 (d, J = 12.4 Hz, 1 H, PhHCHO),
Published Online: May 2, 2011
Eur. J. Org. Chem. 2011, 3146–3155
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3155