Short Access to Belt Compounds with Spatially Close C=C Bonds and Their Transannular Reactions

Article abstract of DOI:10.1002/chem.201502351

Two domino Diels-Alder adducts were obtained from 3,7-bis(cyclopenta-2,4-dien-1-ylidene)-cis-bicyclo[3.3.0]octane and dimethyl acetylenedicarboxylate or N-methylmaleimide under microwave irradiation. From the first adduct, a C₂₀H₂₄ diene with C_2v symmetry was obtained by Zn/AcOH reduction, hydrolysis, oxidative decarboxylation, and selective hydrogenation. Photochemical [2+2] cycloaddition of this diene gave a thermally unstable cyclobutane derivative, which reverts to the diene. However, both the diene and the cyclobutane derivatives could be identified by X-ray diffraction analysis upon irradiation of the diene crystal. New six-membered rings are formed upon the transannular addition of bromine or iodine to the diene. The N-type selectivity of the addition was examined by theoretical calculations, which revealed the distinct susceptibility of the doubly bonded carbon atoms to the bromine attack. Short access: A polycyclic C₂₀H₂₄ hydrocarbon with two spatially close C=C bonds that experience photochemical conversion to a thermally unstable cyclobutane derivative and N-type transannular addition of bromine or iodine has been obtained from a domino Diels-Alder adduct of the shown difulvene. The mechanism of the N-type bromination is examined by DFT computations.

Full text of DOI:10.1002/chem.201502351

DOI: 10.1002/chem.201502351
Full Paper
&
Belt Compounds
Short Access to Belt Compounds with Spatially Close C=C Bonds
and Their Transannular Reactions
[a]
[a]
[a]
[b]
[c]
Pelayo Camps,* Tània Gómez, Ane Otermin, Merc› Font-Bardia, Carolina Estarellas,
[c]
and Francisco Javier Luque
In memory of Jean-Paul Picard
Abstract: Two domino Diels–Alder adducts were obtained
from 3,7-bis(cyclopenta-2,4-dien-1-ylidene)-cis-bicy-
derivative, which reverts to the diene. However, both the
diene and the cyclobutane derivatives could be identified by
X-ray diffraction analysis upon irradiation of the diene crys-
tal. New six-membered rings are formed upon the transan-
nular addition of bromine or iodine to the diene. The N-type
selectivity of the addition was examined by theoretical cal-
culations, which revealed the distinct susceptibility of the
doubly bonded carbon atoms to the bromine attack.
clo[3.3.0]octane and dimethyl acetylenedicarboxylate or N-
methylmaleimide under microwave irradiation. From the first
adduct, a C H diene with C2v symmetry was obtained by
20
24
Zn/AcOH reduction, hydrolysis, oxidative decarboxylation,
and selective hydrogenation. Photochemical [2+2] cycload-
dition of this diene gave a thermally unstable cyclobutane
Introduction
Pyramidalized alkenes contain C=C double bonds in which one
or both of the doubly bonded carbon atoms do not lie in the
[1]
same plane as the attached atoms. The degree of pyramidali-
zation of these carbon atoms may be large enough to confer
[
2]
unique structural, spectroscopic, and chemical properties. In
this context, we have reported the generation, trapping as
Diels–Alder (DA) adducts and dimerization of the highly pyr-
3
,7
amidalized alkenes 2, containing the tricyclo[3.3.0.0 ]oct-1(5)-
[3]
ene skeleton (Scheme 1). Of particular interest is the forma-
tion of cyclobutane dimers, which experience a thermal [2+2]
retrocycloaddition to the belt dienes 4 with close parallel C=C
[
3g]
bonds. In turn, these compounds photochemically generate
Scheme 1. Generation and dimerization of the highly pyramidalized alkenes
2
and several transformations of the diene dimers 4.
[
a] Prof. Dr. P. Camps, Dr. T. Gómez, A. Otermin
Laboratori de Química Farmac›utica
the cyclobutane products and experience transannular addi-
tions of electrophiles, such as bromine, iodine, or water.
Because the preparation of the diiodides 1 implies many
synthetic steps, the dienes 4 are not readily available. Herein,
we describe a short synthetic route to the dienes 8 and 9
(
Unitat Associada al CSIC), Facultat de Farmàcia and
Institut de Biomedicina (IBUB), Universitat de Barcelona
Av. Joan XXIII 27–31, 08028 Barcelona (Spain)
E-mail: camps@ub.edu
[
b] Dr. M. Font-Bardia
Departament de Cristallografia
(
Scheme 2), which features a key step consisting of a domino
Mineralogia i Dipòsits Minerals, Universitat de Barcelona
Martí Franqu›s s/n. 08028 Barcelona (Spain) and Unitat de Difracció de RX
Centres Científics i Tecnològics de la Universitat de Barcelona (CCiTUB)
SolØ i Sabarís 1–3, 08028 Barcelona (Spain)
[4]
DA reaction among the known difulvene 7 and dimethyl ace-
tylenedicarboxylate or N-methylmaleimide under microwave ir-
radiation. Furthermore, several transannular and photochemi-
cal transformations of these compounds are also examined.
The preferential formation of N-type halogenated adducts over
the U-type products is investigated by means of theoretical
calculations. Overall, the results support the reliability of the
domino Diels–Alder reaction to yield polycyclic compounds
with belt structures having close parallel C=C bonds.
[
c] Dr. C. Estarellas, Prof. Dr. F. J. Luque
Departament de Fisicoquímica
Facultat de Farmàcia and Institut de Biomedicina (IBUB)
Universitat de Barcelona, Prat de la Riba 171
0
8921 Santa Coloma de Gramenet (Spain)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502351.
Chem. Eur. J. 2015, 21, 14036 – 14046
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Full Paper
methylfulvene and maleic anhydride under microwave irradia-
tion did not give the expected DA addition product, but ad-
ducts from tautomeric derivatives of the fulvene unit. In this
work, the expected DA adducts were formed under conven-
tional thermal conditions.
Results and Discussion
Reaction of equimolar amounts of the difulvene 7 and dimeth-
yl acetylenedicarboxylate in 1,2-dichlorobenzene under micro-
wave irradiation at 1508C for 5 min gave a product mixture,
which after column chromatography and washing with MeOH
yielded the domino DA adduct 8 in 24% yield (Scheme 2).
Longer or shorter reaction times of microwave irradiation led
to lower yields of compound 8.
Hydrogenation of the products 8 and 9 by using 5% Pd on
charcoal led to the selective formation of compounds 10 and
[
6]
11, respectively. The configuration of all of these compounds
was clearly established by spectroscopic studies and, for com-
pounds 8, 9, and 10, confirmed by X-ray diffraction analysis
(
see the Supporting Information). Compound 10 was irradiated
in a quartz reactor by using a 125 W medium-pressure mercury
[
3c]
[7]
lamp in pentane or in a 1:1 benzene/acetone mixture at
different reaction times (till 24 h). Due to solubility problems,
compound 11 was irradiated under similar conditions but only
in a 1:1 benzene/acetone mixture. In both cases, there was no
evidence supporting the formation of cyclobutane derivatives,
even though the starting compounds were degraded.
Because the failure of the intramolecular [2+2] photocy-
cloaddition process might be due to the ester or imide groups,
the tetraene 17 was prepared (Scheme 3). Reduction of the
[
8]
diester 8 with Zn/AcOH under ultrasonic irradiation gave
a stereoisomeric mixture of the esters 12, 13, and 14, in a ratio
Scheme 2. Preparation of the domino DA adducts 8 and 9 and their deriva-
tives.
Similarly, reaction of compound 7 with N-methylmaleimide
under similar conditions and treatment gave adduct 9 in only
11 % yield (Scheme 2). Alternatively, compound 9 was obtained
by microwave irradiation of a mixture of the double DA ad-
ducts of the difulvene 7 and N-methylmaleimide in 1,2-dichlo-
robenzene. The formation of compound 9 under these condi-
tions requires that the above-described double DA adducts ex-
perience a retro-DA reaction to regenerate the fulvene subunit
necessary for the intramolecular DA reaction.
Worthy of note, reaction of compound 7 and maleic anhy-
dride or cis- and trans-1,2-bis(phenylsulfonyl)ethylene, under
microwave irradiation conditions used to prepare compound
8
, did not give any defined product. This agrees with the find-
[
5]
ings by Hong et al. who reported that the reaction of 7,7-di-
Scheme 3. Preparation of the tetraene 17 (d.c.=direct current).
Chem. Eur. J. 2015, 21, 14036 – 14046
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1
1
2/13/14 close to 3:4:1, as confirmed by H NMR spectroscopy,
ture with the diene 18. The thermal conversion of the cyclobu-
tane 19 to the diene 18 was followed by H NMR spectroscopy
1
which could be partially separated by silica gel column chro-
matography, thus obtaining samples of each stereoisomer. As-
signment of the endo,endo-stereoisomer 13 was confirmed
upon hydrogenation, yielding the expected diester 10. Next,
the stereoisomeric mixture of the diesters 12, 13, and 14 was
hydrolyzed to give mainly the corresponding endo,exo-diacid
5, which contains a norbornane substructure. Following Pa-
quette et al., oxidative decarboxylation of the diacid 15, was
in CDCl at 25, 35, and 458C (see Table S1 in the Supporting In-
3
formation), revealing first-order kinetics. The following rate
constant values were obtained: k =0.0030, k =0.0112, and
25
35
À1
k =0.0231 min . By using the Arrhenius equation, an activa-
45
[
7]
À1
tion energy of 19.2 kcalmol and a pre-exponential Arrhenius
11
À1
1
factor of 3.4·10 min were calculated. The activation energy
[
9]
À1
of this process compares with the value of 22.7 kcalmol for
only attempted by using either electrolysis or Cu O oxidation
the conversion of the more stable cyclobutane 3a to the corre-
sponding diene 4a in CDCl3.
2
[
3b]
in quinoline at high temperature. Electrolysis of the diacid 15
was carried out in a 9:1 pyridine/water mixture as solvent in
Irradiation of a crystallographic sample of compound 18
gave a new crystal, containing molecules of the cyclobutane
19 and the diene 18 in a 19/18 ratio of about 1:1. The atom
site occupancy for the olefinic carbon atoms of compound 18
and the cyclobutane carbon atoms of compound 19 was 0.500
for all of them. The X-ray data showed that the monoclinic
crystal state of compound 18 had been retained during the ir-
radiation process. All the atoms, except the olefinic carbon
atoms of compound 18, retained their position in its conver-
sion to compound 19 (see the Supporting Information).
Figure 1 shows the ORTEP representation of the mixture of
[8,10]
the presence of triethylamine.
However, both NMR and X-
ray data (see the Supporting Information) confirmed that the
only defined product isolated from this reaction was the alco-
hol 16 (4%), which might have been formed by hydration of
the tetraene 17. Fortunately, oxidative decarboxylation of the
[9]
diacid 15 by using Cu O gave the high melting point C -sym-
2
2v
metric C H tetraene 17 (16%) together with significant
20
20
amounts of 2-methylnaphthalene and traces of 1-methylnaph-
thalene as byproducts. The structure of compound 17 was
confirmed by X-ray diffraction analysis (see the Supporting In-
formation).
Selective hydrogenation of the tetraene 17 led to the diene
18 (Scheme 4). Irradiation of compound 17 (quartz reactor,
Figure 1. ORTEP representation of the mixture of the cyclobutane 19 and
the diene 18.
Scheme 4. Transannular reactions of compounds 18 and 10.
compounds 19 and 18. The easy thermal opening of the cyclo-
butane 19 to the diene 18, whether during irradiation of the
crystal or during acquisition of the X-ray data, and not the size
of the crystal, might be the reason why no pure cyclobutane
19 was observed in the X-ray experiment.
[3c]
1
25 W medium-pressure mercury lamp in pentane or in a 1:1
[
7]
benzene/acetone mixture) at different reaction times (till 4 h)
led to degradation products in which the olefinic protons had
disappeared. GC-MS showed the presence, among others, of
dihydro and tetrahydro compounds.
Photochemical transformations in the solid state are well
[
11,12]
known, sometimes accompanied by photochromism.
How-
However, irradiation of the diene 18 in pentane with the
same lamp for 3 h led to a mixture of the cyclobutane 19 and
minor amounts of compound 18. The H and C NMR data of
compound 19 could be obtained from the spectra of its mix-
ever, to the best of our knowledge, no intramolecular [2+2]
photocycloaddition of simple alkenes in the solid state and in
the absence of any photosensitizer has been reported before.
1
13
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The olefinic carbon atoms of compounds 8, 9, 10, 17, and
8 are slightly pyramidalized: C4/C9 (13.5–15.88) and C3a/C9a
In the pre-reactant complex (i.e., I in Figure 2), the bromine
1
1
(
atom closest to the molecule is roughly equidistant (2.37–
2.50 Š) from the doubly bonded carbon atoms. Addition of
bromine to the carbon atoms C3a and C4 is concurrent with
[
13]
2.0–5.88).
Also, the C6ÀC7 (1.586–1.589 Š) and C13ÀC14
bonds (1.572–1.588 Š) are somewhat longer than the standard
CÀC bond length (see Table S2 in the Supporting Information).
Reaction of the diene 18 with a slight molar excess of bro-
mine or iodine in CH Cl gave compounds 21 and 22, respec-
the breaking of the bond in the Br molecule and with the for-
2
mation of bonds between the atom pairs C4ÀC9a and C3aÀC9
(distances of 2.48 and 2.12 Š, respectively, in the transition-
state structures (i.e., TS(3a) and TS(4) in Figure 2). The barrier
for the addition to the C3a atom is approximately 3.2 kcal
2
2
13
tively, as the only detected products (Scheme 4). The C NMR
data supported the C symmetry group (N-type addition). U-
s
À1
type additions would have generated a five- and a seven-
membered ring in the halogenated products, leading to prod-
ucts with C2v symmetry. X-ray diffraction analyses further con-
firmed the structures of compounds 21 and 22 (see in Sup-
porting Information).
mol more favorable than the addition to the C4 atom. This
difference can be partly ascribed to the larger electron density
supported by the C3a atom relative to the C4 atom in the
diene (Dq=0.034 e, Figure S1 in the Supporting Information).
This process leads to a N-type-brominated adduct cation,
which is characterized by the presence of internal six-mem-
bered rings leading to a formal positive charge on the carbon
atom C9. Finally, the nucleophilic addition of the bromine
anion to the C9 atom generates compound 21. All attempts to
locate the transition states leading to the U-type bromine addi-
tion were unsuccessful, suggesting that this process induces
a larger structural barrier than the N-type addition. The largest
destabilization of the U-type adduct formed upon addition to
the C4 atom is reflected in the relative free energy compared
to the N-type adducts, because the former is destabilized by
The mechanism of the bromination addition of the diene 18
was examined by combining density functional theory calcula-
tions and the self-consistent reaction field theory to account
for solvation effects. DFT calculations were performed by using
[14]
the M062X/6-31+G(d) level of theory, and solvation effects
in CH Cl were accounted for with the solvation model based
2
2
[15]
on the solute electron density (SMD) method. The geome-
tries were fully optimized and the nature of the stationary
points was verified by determination of the vibrational fre-
quencies (see the Supporting Information). The structural pa-
rameters derived from the optimized geometry of compound
À1
around 15 kcalmol relative to the preferred N-type-brominat-
18 showed a close agreement with the X-ray structure, as
ed cation adduct (i.e., I (3a) in Figure 3). This trend is also
3
noted in the pyramidalization of the C=C carbon atoms (C3a/
C9a: 4.88, C4/C9: 15.68), and the lengths of the C6ÀC7 and
C13ÀC14 bonds (1.581 and 1.582 Š, respectively).
noted in the larger distance between the carbon atoms of the
bond formed between the two C=C bonds, and the lower
value of the electron density at the bond critical point
Figure 2. Mechanistic pathway for the bromination of the diene 18 and formation of the N-type product 21.
Chem. Eur. J. 2015, 21, 14036 – 14046 www.chemeurj.org ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
14039

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and 1400948 (24) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Conclusions
In summary, the domino Diels–Alder reaction of 3,7-bis(cyclo-
penta-2,4-dien-1-ylidene)-cis-bicyclo[3.3.0]octane and dimethyl
acetylenedicarboxylate has been shown to be a short route to
polycyclic compounds with belt structures having close parallel
C=C bonds that experience different transannular processes.
Experimental Section
General information
Melting points were determined in open capillary tubes with
a MFB 595010M Gallenkamp melting-point apparatus. All new
compounds were fully characterized by their analytical (melting
point, elemental analysis, and/or accurate mass measurement,
1
13
spectroscopic data (IR, H NMR, and C NMR) and in much cases X-
ray diffraction analysis. Assignments given for the NMR spectra are
1
13
based on DEPT, COSY, H/ C single quantum correlation (gHSQC
1
13
sequence), and H/ C multiple bond correlation (gHMBC se-
1
13
quence) spectra. H NMR and C NMR spectra were recorded on
1
13
a Varian Mercury 400 (400 MHz for H, 100.6 MHz for C) spectrom-
eter. Unless otherwise stated, NMR measurements have been per-
formed in CDCl . Chemical shifts (d) are reported in parts per mil-
3
lion related to TMS or CDCl as internal standard. Multiplicities are
3
reported by using the following abbreviations: s=singlet, d=dou-
blet, t=triplet, m=multiplet, br=broad or their combinations. IR
spectra were registered on a FTIR Perkin–Elmer Spectrum RX1
spectrometer by using the attenuated total reflectance (ATR) tech-
nique. Absorption values are given as wavenumbers, the intensity
of the absorptions is given as strong (s), medium (m), or weak (w).
High-resolution mass spectrometry (HRMS) were carried out at the
Mass Spectrometry Unity of the Centres Científics i Tecnològics of
the Universitat de Barcelona (CCiTUB) and the results are reported
as m/z. Except for compound 22 a LC/MSD-TOF spectrometer with
electrospray ionization (ESI-TOF-MS) from Agilent Technologies was
used. The HRMS of compound 22 was performed on a LTQ Orbi-
trap Velos mass spectrometer (Thermo Scientific, Bremen, Germa-
ny). The elemental analyses were carried out at the IIQAB (CSIC) of
Barcelona, Spain, in an elemental microanalyzers (A5) model
Flash1112 series from Thermofinnigan for (C, H, and N) determina-
tions, and in a titroprocessor Methrom model808 for the halogen
determination. Microwave irradiation experiments were performed
by using a single-mode discover system from CEM Corporation by
using standard Pyrex vessel (capacity of 10 mL). For the flash
column chromatography, silica gel 60AC (35–70 mm, SDS,
ref. 2000027) was used. The eluents employed are reported as
volume/volume percentages. Thin-layer chromatography (TLC) was
performed on aluminum-backed sheets with silica gel 60F254
Figure 3. Molecular geometry and selected properties of the brominated
cation adducts derived from the diene 18. Representation of the two N-
type-brominated adduct cations and the single U-type addition product ob-
À1
tained from M062X calculations (the relative stability in [kcalmol ] is given
in parenthesis). The length of the central bond (in [Š]) and the electron den-
sity at the bond critical point (in units of electron) is given above/below the
bond, respectively.
(
Figure 3). In addition, all attempts to locate the U-type adduct
originating from bromination at the C3a atom failed.
Bromination of the diene diester 10 was performed under
similar conditions, leading to a mixture of the isomeric dibro-
mides 23 and 24. Samples of these dibromides could be ob-
tained by slow crystallization from EtOAc and were fully char-
acterized by spectroscopic and analytical means including X-
ray diffraction analysis. As before, only N-type addition was ob-
served. Compound 23 was the major species of the reaction
mixture, which contained compounds 23 and 24 in a ratio of
1
3
.5:1 (as obtained by H NMR spectroscopy), an effect that can
(
Merck, ref. 1.05554) and spots were visualized with UV light or
be ascribed to the inductive effect of the ester groups on the
double bond formed by the C3a and C4 atoms.
a 1% aqueous solution of KMnO . X-ray diffraction analyses were
performed in a D8 Venture diffractometer at the CCiTUB of the Uni-
versity of Barcelona. The diketone 6 was prepared as described
from glioxal (40% in water) and dimethyl 1,3-acetonedicarboxylate,
both obtained from Sigma–Aldrich. Dimethyl acetylenedicarboxy-
late, copper(I) oxide, and 2,2’-bipyridyl were purchased from
Sigma–Aldrich, N-methylmaleimide from TCI, zinc powder from
4
The X-ray diffraction data for most compounds described in
this paper have been collected in the Tables S3 and S4 in the
Supporting Information. CCDC 1400938 (8), 1400939 (9),
[
16]
1
400940 (10), 1400941 (16), 1400942 (17), 1400943
(
18),1400944 (19), 1400945 (21), 1400946 (22), 1400947 (23),
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Panreac, neutral aluminum oxide Brockman I (50–200 mm) from
Acros Organics, and 5% Pd/C from Degussa AG. All chemicals were
used without further purification.
double DA adducts (3.75 g, 93% yield) was isolated as white solid.
A part of this mixture (300 mg, 0.66 mmol) in 1,2-dichlorobenzene
(4 mL) was placed in a 10 mL microwave tube, which was closed
and irradiated at 1508C for 5 min. This process was repeated
twelve times more (total amount of the double DA mixture: 3.58 g,
Dimethyl (3R,3aZ,6S,7R,9Z,10S,12aR,13S,13aS,14R)-
7
.78 mmol). The combined solutions were concentrated in vacuum
5,6,7,8,10,12a,13,13a-octahydro-3H-3,10,13-(epimethanetri-
and the yellow brown residue (4.62 g) was subjected to column
chromatography (35–70 mm silica gel (50 g), hexane/EtOAc mix-
tures). On elution with hexane/EtOAc 4:1 and 3:1 the domino DA
adduct 9 (445 mg, 16% yield) was isolated as a white solid. Crystal-
lization of a sample of compound 9 (290 mg) from EtOAc (15 mL)
gave an analytical sample of compound 9 (113 mg) as a white crys-
yl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annulene-1,2-di-
carboxylate (8)
A solution of the difulvene 7 (300 mg, 1.28 mmol) and dimethyl
acetylenedicarboxylate (0.16 mL, 98%, 181 mg, 1.28 mmol) in 1,2-
dichlorobenzene (4 mL) was placed in a 10 mL microwave tube,
which was closed and irradiated at 1508C for 5 min. This process
was repeated seven times more, by using compound 7 (total
amount: 2.44 g, 10.4 mmol). The combined solutions were concen-
trated in vacuum and the yellow brown residue (ꢀ4 g) was sub-
jected to column chromatography (35–70 mm silica gel (96 g),
hexane/EtOAc mixtures). On elution with hexane/EtOAc 85:15,
a mixture of the domino DA adduct 8 and adducts still containing
a fulvene subunit (931 mg) was isolated as yellow solid. After
washing this solid with MeOH (4 mL), compound 8 was obtained
1
talline solid. M.p. 254–2558C (decomp.) (EtOAc); H NMR (400 MHz,
2
CDCl ): d=1.53 (s, 2H; 13(14)-H), 2.05 (d, J(H,H)=12.8 Hz, 2H;
3
2
8
5
2
2
(16)-H ), 2.06 (d, J(H,H)=12.8 Hz, 2H; 5(15)-H ), 2.13–2.21 (m, 4H;
(15)-H , 8(16)-H ), 2.38–2.45 (m, 2H; 6(7)-H), 2.63 (s, 2H; 1(2)-H),
.83 (s, 3H; N-CH ), 2.98 (s, 2H; 3(13a)-H), 3.13 (t, J(H,H)= J(H,H)=
.0 Hz, 2H; 10(12a)-H), 6.30 ppm (t, J(H,H)= J(H,H)=2.0 Hz, 2H;
b
b
a
a
3
4
3
3
4
13
1
1(12)-H); C NMR (100.6 MHz, CDCl ): d=24.5 (CH , N-CH ), 35.6
3 3 3
[
CH, C6(7)], 40.0 [CH , C8(16)], 40.9 [CH , C5(15)], 43.6 [CH,
2 2
C13(14)], 44.6 [CH, C3(13a)], 46.3 [CH, C10(12a)], 49.4 [CH, C1(2)],
24.0 (C, C9), 128.3 (C, C3a), 136.0 (C, C4), 138.6 [CH, C11(12)],
1
as light yellow solid (794 mg, 24% yield). M.p. 185–1868C
1
139.5 (C, C9a), 178.2 ppm (C, CON); IR (ATR): n˜ =2984 (w), 2837 (w),
(
1
decomp.) (MeOH); H NMR (400 MHz, CDCl ): d=1.91 (s, 2H;
3
2
2
1769 (w), 1692 (s), 1435 (m), 1380 (m), 1299 (m), 1281 (m), 1131
3(14)-H), 2.08 (d, J(H,H)=12.8 Hz, 2H) and 2.09 (d, J(H,H)=
2.4 Hz, 2H) (5(15)-Hb and 8(16)-H ), 2.21 (dd, J(H,H)=12.6,
J(H,H)=3.6 Hz, 4H; 5(15)-H , 8(16)-H ), 2.46–2.52 (m, 2H, 6(7)-H),
.07 (t, J(H,H)= J(H,H)=2.0 Hz, 2H; 10(12a)-H), 3.42 (s, 2H, 3(13a)-
H), 3.76 (s, 6H, 2”OCH ), 6.39 ppm (t, J(H,H)= J(H,H)=2.0 Hz, 2H;
1(12)-H); C NMR (100.6 MHz, CDCl ): d=36.3 [CH, C6(7)], 40.2
À1
2
(m), 1111 (m), 971 (m), 738 (m), 687 (m), 646 cm (m); accurate
1
b
+
3
mass measurement: m/z calcd for C23
346.1792; elemental analysis calcd (%) for C23
H 7.13, N 3.67; found: C 72.60, H 6.82, N 3.39.
H
23NO
2
+H : 346.1802; found:
a
a
3
4
H23NO ·2H O: C 72.42,
2 2
3
3
4
3
1
3
1
3
[
[
(
CH , C5(15), C8(16)], 45.3 [CH, C10(12a)], 46.3 [CH, C13(14)], 49.1
2
CH, C3(13a)], 51.9 (CH , OCH ), 124.1 (C, C9), 128.1 (C, C4), 135.8
3
3
C, C3a), 140.3 (C, C9a), 140.3 [CH, C11(12)], 147.8 [C, C1(2)],
1
2
64.9 ppm (C, COOCH ); IR (ATR): n˜ =2992 (w), 2948 (m), 2914 (w),
3
Dimethyl (1R,2S,3R,3aZ,6S,7R,9Z,10R,12aS,13R,13aS,14S)-
2,3,5,6,7,8,10,11,12,12a,13,13a-dodecahydro-1H-3,10,13-(epi-
methanetriyl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annu-
lene-1,2-dicarboxylate (10)
842 (w), 1736 (s), 1714 (s), 1433 (m), 1306 (s), 1287 (m), 1205 (s),
À1
1192 (s), 1168 (s), 1114 (m), 1094 (s), 1026 (s), 803 (m), 693 cm (s);
+
accurate mass measurement: m/z calcd for C H O +H : 377.1747;
found: 377.1742; elemental analysis calcd (%) for C H O ·0.5H O:
2
4
24
4
2
4
24
4
2
C 74.78, H 6.54; found: C 74.57, H 6.54.
A suspension of compound 8 (191 mg, 0.51 mmol) and 5% Pd on
charcoal (50% in water, 19 mg) in EtOAc (20 mL) was hydrogenat-
ed at room temperature and atmospheric pressure for 3 h. The sus-
pension was filtered through a short pad of celite and concentrat-
ed in vacuum to give the crude compound 10 as a white solid
N-Methyl (1R,2S,3R,3aZ,6S,7R,9Z,10S,12aR,13S,13aS,14R)-
,6,7,8,10,12a,13,13a-octahydro-3H-3,10,13-(epimethanetri-
5
yl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annulene-1,2-di-
(
(
177 mg, 96% yield). An analytical sample of compound 10
42 mg) was obtained as a white crystalline solid by crystallization
carboximide (9)
Procedure 1: A solution of the difulvene 7 (300 mg, 1.28 mmol)
and N-methylmaleimide (142 mg, 1.28 mmol) in 1,2-dichloroben-
zene (4 mL) was placed in a 10 mL microwave tube, which was
closed and irradiated at 1508C for 5 min. The solution was concen-
trated in vacuum and the brown residue was subjected to column
chromatography (35–70 mm silica gel (55 g), hexane/EtOAc mix-
tures). On elution with hexane/EtOAc 95:5, the difulvene 7 (31 mg)
was isolated as yellow solid. On elution with hexane/EtOAc 80:20
and 75:25, the domino DA adduct 9 (64 mg) was isolated as
a beige solid. After washing this solid with MeOH (0.7 mL), the
pure compound 9 was obtained as a white solid (48 mg, 11 %
yield).
of a part of this product (114 mg) from EtOAc (2 mL). M.p. 192–
1
1
2
(
2
1
948C (EtOAc); H NMR (400 MHz, CDCl ): d=1.27–1.32 (m, 2H;
3
1(12)-H ), 1.44–1.50 (m, 2H; 11(12)-Hexo), 2.05 (s, 2H; 13(14)-H),
endo
2
2
.18 (d, J(H,H)=12.8 Hz, 2H) and 2.19 (d, J(H,H)=12.4 Hz, 2H)
5(15)-H and 8(16)-H ), 2.23–2.28 (m, 4H; 5(15)-H , 8(16)-H ), 2.40–
b b a a
3
4
.46 (m, 2H; 6(7)-H), 2.42 (t, J(H,H)= J(H,H)=2.2 Hz, 2H; 10(12a)-
3
4
H), 2.83 (dd, J(H,H)=2.4, J(H,H)=2.0 Hz, 2H; 3(13a)-H), 2.91 (dd,
3
4
J(H,H)=2.4, J(H,H)=1.6 Hz, 2H; 1(2)-H), 3.66 ppm (s, 6H; 2 OCH );
3
13
C NMR (100.6 MHz, CDCl ): d=29.3 [CH , C11(12)], 35.3 [CH,
3
2
C6(7)], 40.9 (CH ) and 41.0 (CH ) [C5(15) and C8(16)], 41.1 [CH,
2
2
C13(14)], 41.25 [CH, C10(12a)], 45.3 [CH, C3(13a)], 46.6 [C, C1(2)],
1.4 (CH , OCH ), 127.8 (C, C9), 130.8 (C, C4), 133.25 (C, C3a), 139.1
5
3
3
Procedure 2: A solution of the difulvene 7 (2.07 g, 8.83 mmol) and
N-methylmaleimide (2.94 g, 26.5 mmol) in toluene (40 mL) was
stirred at room temperature for 110 h in a closed flask fitted with
a gas outlet. The solution was concentrated in vacuum and the
yellow brown residue (5.03 g) was subjected to column chroma-
tography (35–70 mm silica gel (100 g), hexane/EtOAc mixtures). On
elution with hexane/EtOAc 2:3, a stereoisomeric mixture of the
(C, C9a), 172.6 ppm (C, COOCH ); IR (ATR): n˜ =2961 (w), 2942 (m),
3
2928 (m), 2839 (w), 1744 (s), 1739 (s), 1429 (m), 1356 (m), 1344 (m),
1181 (s), 1156 (s), 1142 (s), 1111 (m), 1081 (m), 1069 (m), 1052 (s),
À1
921 (m), 821 (m), 761 (m), 743 cm (m); accurate mass measure-
+
ment: m/z calcd for C H O +H : 381.2060; found: 381.2063; ele-
24
28
4
mental analysis calcd (%) for C H O : C 75.76, H 7.42; found: C
24
28
4
75.65, H 7.57.
Chem. Eur. J. 2015, 21, 14036 – 14046
www.chemeurj.org
14041
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
N-Methyl (1R,2S,3S,3aZ,6R,7S,9Z,10S,12aR,13S,13aR,14R)-
,3,5,6,7,8,10,11,12,12a,13,13a-dodecahydro-1H-3,10,13-(epi-
methanetriyl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annu-
On elution with hexane/EtOAc from 97:3 to 95:5, the pure com-
pound 13 (23 mg) was isolated as a white solid. Crystallization of
samples of compounds 13 (28 mg), 12 (22 mg), and 14 (22 mg)
from EtOAc (0.5 mL) gave the corresponding analytical samples
2
lene-1,2-dicarboximide (11)
(
13, 10, and 10 mg, respectively).
A mixture of the imide 9 (424 mg, 1.23 mmol) and 5% Pd on char-
Analytical and spectroscopic data of compound 12: White solid;
coal (50% in water, 45 mg) in CH Cl (40 mL) was hydrogenated at
2
2
m.p. 192–1938C (EtOAc), at 186–1888C the sample of compound
room temperature and atmospheric pressure for 3 h. The mixture
was filtered through a short pad of celite and concentrated in
vacuum to give the product 11 (406 mg, 95% yield) as a white
solid. An analytical sample of compound 11 was obtained by crys-
tallization of a part of the crude product (104 mg) from EtOAc
1
1
2 becomes a paste; H NMR (400 MHz, CDCl ): d=1.34 (d,
3
3
3
J(H,H)=7.6 Hz, 1H; 13-H), 1.52 (d, J(H,H)=7.6 Hz, 1H; 14-H),
2
2
.05–2.28 (m, 8H; 5-H , 5-H , 8-H , 8-H , 15-H , 15-H , 16-H , 16-H ),
a b a b a b a b
3
.40–2.47 (m, 2H; 6-H, 7-H), 2.86 (d, J(H,H)=5.2 Hz, 1H; 2-H), 2.94
3
(
brs, 1H; 3-H), 2.98 (brd, J(H,H)=4.4 Hz, 1H; 13a-H), 3.07–3.09 (m,
(
4.5 mL), thus obtaining compound 11 (54 mg) as a white crystal-
3
1
1H; 12a-H), 3.12–3.14 (m, 1H; 10-H), 3.19 (dd, J(H,H)=5.2,
line solid. M.p. 245–2478C (EtOAc); H NMR (400 MHz, CDCl ): d=
3
3
J(H,H)=4.8 Hz, 1H; 1-H), 3.65 (s, 3H; 2-COOCH ), 3.71 (s, 3H; 1-
3
1
.21–1.26 (m, 2H; 11(12)-H ), 1.48–1.55 (m, 2H; 11(12)-Hexo), 1.60
endo
3
3
4
COOCH ), 6.25–6.26 ppm (pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H;
3
11-H, 12-H]; C NMR (100.6 MHz, CDCl ): d=35.76 (CH) and 35.82
(
s, 2H; 13(14)-H), 2.09 (d, J(H,H)=12.8 Hz, 2H; 5(15)-H ), 2.14 (d,
J(H,H)=12.8 Hz, 2H; 8(16)-H ), 2.14–2.21 (m, 2H; 5(15)-H ), 2.21–
b
13
2
3
b
a
3
(CH) (C6 and C7), 39.6 (CH, C13), 40.1 (CH ) and 40.2 (CH ) (C8 and
2
2
2
2
.26 (m, 2H; 8(16)-H ], 2.38–2.44 [m, 2H; 6(7)-H), 2.50 (dd, J(H,H)=
a
4
C16), 40.7 (CH ) and 41.0 (CH ) (C5 and C15), 43.6 (CH, C14), 44.4
2 2
(CH, C13a), 45.5 (CH, C3), 46.3 (CH, C12a), 46.6 (CH, C10), 49.3 (CH,
.4, J(H,H)=2.0 Hz, 2H; 10(12a)-H), 2.62 (s, 2H; 1(2)-H), 2.82 (s, 3H;
1
3
N-CH ), 2.92 ppm (s, 2H; 3(13a)-H); C NMR (100.6 MHz, CDCl3):
3
C1), 49.6 (CH, C2), 51.97 (1-COOCH ), 51.98 (2-COOCH ), 123.6 (C,
3
3
d=24.5 (CH , N-CH ), 29.3 [CH , C11(12)], 35.1 [CH, C6(7)], 40.8
3
3
2
C9), 132.0 (C, C4), 132.9 (C, C3a), 138.3 (CH, C11), 138.5 (CH, C12),
40.2 (C, C9a), 173.2 (C, 1COOCH ), 173.9 ppm (C, 2-COOCH ); IR
[
CH , C8(16)], 40.9 [CH , C5(15)], 41.1 [CH, C10(12a)], 45.2 [CH,
2 2
1
3
3
C3(13a)], 45.9 [CH, C13(14)], 48.9 [CH, C1(2)], 128.3 (C, C3a), 128.9
C, C9), 136.0 (C, C4), 136.6 (C, C9a), 178.5 ppm (C, CON); IR (ATR):
n˜ =2951 (m), 2914 (w), 2857 (w), 2836 (w), 1767 (w), 1693 (s), 1679
(
(
ATR): n˜ =2954 (w), 2914 (w), 2842 (w), 1723 (s), 1432 (m), 1306
(
À1
m), 1214 (m), 1190 (s), 1176 (s), 1163 (s), 1022 (m), 696 cm (m);
+
accurate mass measurement: m/z calcd for C H O +H :
24
26
4
(
(
s), 1434 (m), 1380 (m), 1300 (m), 1280 (m), 1131 (m), 1108 (m), 972
À1
379.1904; found: 379.1910; elemental analysis calcd (%) for
C H O : C 76.17, H 6.92; found: C 76.11, H 6.93.
m), 643 (m), 630 cm (m); accurate mass measurement: m/z calcd
+
24
26
4
for C H NO +H : 348.1958; found: 348.1949; elemental analysis
2
3
25
2
(
7
%) calcd for C H NO : C 79.51, H 7.25, N 4.03; found: C 79.52, H
23 25 2
.40, N 3.93.
Analytical and spectroscopic data of compound 13: White solid;
m.p. 191–1928C (EtOAc), at 184–1868C the sample of compound
1
1
1
1
3 becomes a paste; H NMR (400 MHz, CDCl ): d=1.93 (s, 2H;
3
2
2
3(14)-H), 2.09 (d, J(H,H)=12.8 Hz, 2H; 8(16)-H ), 2.14 (d, J(H,H)=
2.4 Hz, 2H; 5(15)-H ), 2.14–2.20 (m, 2H; 8(16)-H ), 2.20–2.27 (m,
2H; 5(15)-H ), 2.41–2.47 (m, 2H; 6(7)-H), 2.91 (dd, J(H,H)=2.4,
J(H,H)=1.8 Hz, 2H; 3(13a)-H), 3.00 [dd, J(H,H)=2.4, J(H,H)=
.8 Hz, 2H; 1(2)-H), 3.10 (pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H;
0(12a)-H), 3.64 (s, 6H; 2 OCH ), 6.25 ppm (pseudo t, J(H,H)=
J(H,H)=2.0 Hz, 2H; 11(12)-H); C NMR (100.6 MHz, CDCl ): d=35.8
b
Dimethyl (1RS,2RS,3RS,3aZ,6SR,7RS,9Z,10RS,12aSR,13R-
S,13aSR,14SR)-1,2,5,6,7,8,10,12a,13,13a-decahydro-3H-
b
a
3
a
4
3
4
3
,10,13-(epimethanetriyl)-4,7:6,9-dimethanodicyclopen-
ta[a,d][11]annulene-1,2-dicarboxylate (12),
1R,2S,3R,3aZ,6S,7R,9Z,10R,12aS,13R,13aS,14S)-
,2,5,6,7,8,10,12a,13,13a-decahydro-3H-3,10,13-(epimetha-
3
4
1
3
1
3
(
1
4
13
3
[
CH, C6(7)], 38.1 [CH, C13(14)], 40.2 [CH , C8(16)], 40.9 [CH ,
2
2
netriyl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annulene-1,2-
dicarboxylate (13), and (1R,2S,3S,3aZ,6R,7S,9Z,10S,12aR,13-
S,13aR,14R)-1,2,5,6,7,8,10,12a,13,13a-decahydro-3H-3,10,13-
C5(15)], 44.7 [CH, C3(13a)], 46.6 [CH, C10(12a)], 46.9 [CH, C1(2)],
1.4 (CH , OCH ), 122.8 (C, C9), 130.8 (C, C4), 133.1 (C, C3a), 138.2
5
3
3
[
CH, C11(12)], 141.6 (C, C9a), 172.4 ppm (C, COOCH ); IR (ATR): n˜ =
3
(epimethanetriyl)-4,7:6,9-dimethanodicyclopenta[a,d][11]an-
2947 (w), 2919 (w), 2832 (w), 1746 (s), 1736 (s), 1442 (m), 1430 (m),
nulene-1,2-dicarboxylate (14)
1354 (m), 1344 (m), 1193 (s), 1173 (s), 1159 (s), 1053 (m), 770 (m),
À1
6
91 cm
(m); accurate mass measurement: m/z calcd for
Zn dust (347 mg, 5.31 mmol) was added to a suspension of the
diester 8 (250 mg, 0.66 mmol) in glacial AcOH (3.5 mL), and the
mixture was submitted to ultrasonic irradiation at room tempera-
ture for 2 h in a closed flask fitted with a gas outlet. The reaction
+
C H O +H : 379.1904; found: 379.1907; elemental analysis calcd
24
26
4
(
%) for C H O ·0.25H O: C 75.27, H 6.97; found: C 75.20, H 6.84.
24 26 4 2
Analytical and spectroscopic data of compound 14: White solid;
ꢁ
1
mixture was filtered through a short pad of Celite and concentrat-
m.p. 170–1718C (EtOAc); H NMR (400 MHz, CDCl ): d=1.41 (s, 2H;
3
2
2
ed in vacuum to give a light brown semisolid residue (247 mg),
which was subjected to column chromatography (35–70 mm silica
gel (15 g), hexane/EtOAc mixtures). On elution with hexane/EtOAc
13(14)-H), 2.09 (d, J(H,H)=12.8 Hz, 2H; 8(16)-H ), 2.17 (d, J(H,H)=
b
12.8 Hz, 2H; 5(15)-H ), 2.15–2.21 (m, 2H; 8(16)-H ), 2.32–2.38 (m,
b
a
2H; 5(15)-H ), 2.41–2.48 (m, 2H; 6(7)-H), 2.70 (s, 2H; 1(2)-H), 2.90 (s,
a
3
4
9
7:3, compound 12 (22 mg) was isolated as a white solid. On elu-
2H; 3(13a)-H), 3.13 (pseudo t, J(H,H)= J(H,H)=1.8 Hz, 2H;
3
4
tion with hexane/EtOAc 96.5:3.5, a mixture of compounds 12 and
10(12a)-H), 3.58 (s, 6H; 2”OCH ), 6.28 ppm (t, J(H,H)= J(H,H)=
3
1
13
1
3 (88 mg, ratio 1:1.3 determined by H NMR spectroscopy) and
1.8 Hz, 2H; 11(12)-H); C NMR (100.6 MHz, CDCl ): d=35.9 [CH,
3
the pure compound 13 (28 mg) were isolated, both as white
solids. On elution with hexane/EtOAc 9:1, compound 14 (22 mg)
was isolated as a white solid (global yield, 160 mg, 64%). The mix-
ture of compounds 12 and 13 (88 mg) was subjected to a new
column chromatography (35–70 mm silica gel (15 g), hexane/EtOAc
mixtures). On elution with hexane/EtOAc 97:3, compound 12
C6(7)], 40.2 [CH , C8(16)], 40.9 [CH , C5(15)], 43.7 [CH, C13(14)],
44.5 [CH, C3(13a)], 46.5 [CH, C10(12a)], 51.1 [CH, C1(2)], 51.6 (CH3,
2
2
OCH ), 123.8 (C, C9), 131.7 (C, C3a), 133.6 (C, C4), 138.6 [CH,
3
C11(12)], 139.6 (C, C9a), 172.7 ppm (C, COOCH ); IR (ATR): n˜ =2992
3
(w), 2949 (m), 2919 (m), 2841 (m), 1745 (s), 1722 (s), 1433 (m), 1423
(m), 1347 (m), 1313 (m), 1275 (m), 1259 (s), 1164 (s), 1147 (s), 1023
À1
(
19 mg) and a mixture of compounds 12 and 13 (37 mg, ratio 1:2
(s), 767 (m), 752 (m), 742 (m), 703 cm (m); accurate mass mea-
1
+
determined by H NMR spectroscopy) were isolated as white solids.
surement: m/z calcd for C H O +H : 379.1904; found: 379.1909;
24
26
4
Chem. Eur. J. 2015, 21, 14036 – 14046
www.chemeurj.org 14042
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
elemental analysis calcd (%) for C H O ·0.25H O: C 75.27, H 6.97.
Found: C 75.39, H 6.81.
matography (35–70 mm silica gel (4 g), pentane/EtOAc mixtures).
On elution with pentane and pentane/EtOAc 95:5, the alcohol 16
2
4
26
4
2
(
14 mg, 4% yield) was isolated as a beige solid. An analytical
sample of compound 16 (8 mg) was obtained as a white solid by
crystallization from EtOAc (1.2 mL). M.p. 108–1098C (EtOAc);
Synthesis of the diester 10 from the diester 13
1
A suspension of the diester 13 (13 mg, 35 mmol) and 5% Pd on
charcoal (50% in water, 2 mg) in EtOAc (10 mL) was hydrogenated
at room temperature and atmospheric pressure for 2.5 h. The sus-
pension was filtered through a short pad of celite and concentrat-
ed in vacuum to give the diester 10 (8 mg, 61% yield) as a white
solid.
H NMR (400 MHz, CDCl
3
): d=1.40–1.48 (m, 4H; 1(15)-H
), 1.59 (s, 2H; 9(13)-H), 1.85–1.91 (m, 2H;
), 2.33 (brs, 1H; O-H), 2.37–2.44 (m, 2H; 2(3)-H), 2.46 (m
b a
, 4(14)-H ),
1.55–1.58 (m, 2H; 4(14)-H
1(15)-H
plus overlapped pseudo t, J(H,H)= J(H,H)=2.0 Hz, 3H; 5-H,
9a(12)-H), 2.55 (pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H; 6(8a)-H),
6.02 (pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H; 7(8)-H), 6.17 ppm
b
a
3
4
3
4
3
4
3
4
13
(
pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H; 10(11)-H);
C NMR
(
100.6 MHz, CDCl ): d=37.0 (CH, C5), 37.6 [CH, C2(3)], 40.7 [CH ,
3
2
(1RS,2RS,3RS,3aZ,6SR,7RS,9Z,10RS,12aSR,13RS,13aSR,14SR)-
C1(15)], 41.6 [CH , C4(14)], 48.2 [CH, C9(13)], 48.5 [CH, C6(8a)], 50.4
2
1,2,5,6,7,8,10,12a,13,13a-decahydro-3H-3,10,13-(epimetha-
(
C, C12b), 51.7 [CH, C9a(12)], 66.8 (C, C5a), 90.6 (C, C12a), 136.1
netriyl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annulene-1,2-
[CH, C7(8)], 136.4 ppm [CH, C10(11)]; IR (ATR): n˜ =3500–3000
dicarboxylic acid (15)
(broad band, w), 2950 (m), 2919 (s), 2850 (m), 1731 (m), 1456 (m),
1
376 (m), 1319 (m), 1284 (m), 1274 (m), 1256 (m), 1163 (m), 1081
An aqueous NaOH solution (9.6m, 7 mL) was added dropwise to
a cold (08C, ice/water bath) suspension of a mixture of compounds
À1
(
m), 964 (m), 795 (m), 742 (s), 684 cm (s); accurate mass measure-
+
ment: m/z calcd for C H O+NH : 296.2009; found: 296.2012; el-
emental analysis calcd (%) for C H O ·0.25H O: C 84.91, H 8.02;
20
22
4
1
2, 13, and 14 (223 mg, 0.59 mmol) in 96% EtOH (2.4 mL), and
20
22
2
2
then the mixture was heated at 958C for 4 h. The mixture was al-
lowed to cool to room temperature, was acidified with 1n HCl and
extracted with EtOAc (45 mL). The aqueous phase was extracted
with EtOAc (2”40 mL). The combined organic phases were
washed with water (2”20 mL), dried with anhydrous Na SO , and
found: C 84.92, H 7.98.
(3R,3aZ,6s,7s,9Z,10S,12aR,13r,13aS,14r)-
2
4
5,6,7,8,10,12a,13,13a-Octahydro-3H-3,10,13-(epimethanetri-
concentrated in vacuum to give a beige solid (205 mg, 92% yield),
which was a stereoisomeric mixture, consisting mainly of the hy-
yl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annulene (17)
drated endo,exo-stereoisomer 15. M.p. 192–2018C (decomp.)
Glass powder (42 mg), 2,2’(-bipyridyl (749 mg, 4.80 mmol), and
1
(
washed with hot EtOAc); H NMR (400 MHz, CD OD): d=1.47 (d,
J(H,H)=7.8 Hz, 1H; 13-H), 1.50 (d, J(H,H)=7.8 Hz, 1H; 14-H),
3
9
7% Cu O (708 mg, 4.80 mmol) were added to a solution of the
2
3
3
diacid 15 (561 mg, 1.60 mmol) in quinoline (9.5 mL), and the mix-
ture was heated at 1858C for 18 h. The mixture was allowed to
cool to room temperature, poured onto 2n HCl (50 mL), filtered
through a short pad of celite. and washed with water (15 mL) and
pentane (100 mL). The organic phase was separated from the com-
bined filtrate and the aqueous phase was extracted with pentane
2
2
.15–2.27 (m, 8H; 5-H , 5-H , 8-H , 8-H , 15-H , 15-H , 16-H , 16-H ),
a b a b a b a b
3
.42–2.50 (m, 2H; 6-H, 7-H), 2.78 (d, J(H,H)=5.2 Hz, 1H; 2-H), 2.98
3
(
brs, 1H; 3-H), 3.01 (brd, J(H,H)=4.4 Hz, 1H; 13a-H), 3.08–3.10 (m,
3
3
1
3
2
H; 12a-H), 3.12 (dd, J(H,H)=5.2, J(H,H)=4.4 Hz, 1H; 1-H), 3.14–
3
4
.16 (m, 1H; 10-H), 6.25–6.27 ppm (pseudo t, J(H,H)= J(H,H)=
1
3
.0 Hz, 2H; 11-H, 12-H); C NMR (100.6 MHz, CD OD): d=37.2 (CH)
3
(
3”100 mL). The combined organic phases were washed with 1n
and 37.3 (CH) (C6 and C7), 40.82 (CH ) and 40.86 (CH ) (C8 and
2
2
HCl (2”80 mL) and water (2”80 mL), dried with anhydrous
Na SO , and distilled under atmospheric pressure by using a 10 cm
C16), 40.89 (CH, C13), 41.5 (CH ) and 41.7 (CH ) (C5 and C15), 45.2
2
2
2
4
(
CH, C14), 45.5 (CH, C13a), 47.1 (CH, C3), 47.4 (CH, C12a), 47.8 (CH,
C10), 50.6 (CH, C1), 51.0 (CH, C2), 124.3 (C, C9), 132.8 (C, C4), 134.8
C, C3a), 139.28 (CH) and 139.34 (CH) (C11 and C12), 141.6 (C, C9a),
76.3 (C, 1-COOH), 177.1 ppm (C, 2-COOH); IR (ATR): n˜ =3600–2300
Vigreux column and heating till 508C. The oily residue (59.5 mg)
contained the tetraene 17, 2-methylnaphthalene, and traces of 1-
methylnaphthalene and the alcohol 16. An approximate molar
ratio of 17/2-methylnaphthalene of 1:2 was calculated from the in-
tegration of the signals corresponding to the olefinic protons of
the tetraene 17 (d=6.37 ppm) and the methyl protons of 2-meth-
(
1
(
(
broad band, max. at 2939) (m), 1694 (s), 1408 (m), 1373 (m), 1235
À1
s), 1172 (s), 1042 (m), 717 (m), 687 cm (m); accurate mass mea-
À
surement: m/z calcd for C H O ÀH : 349.1445; found: 349.1437;
1
2
2
22
4
ylnaphthalene (d=2.51 ppm) in the H NMR spectrum of the mix-
elemental analysis calcd (%) for C H O ·1.5H O: C 70.01, H 6.68;
2
2
22
4
2
ture. This residue was placed in a desiccator containing paraffin
wax under vacuum overnight to give the tetraene 17, containing
traces of the alcohol 16 as a white solid (31 mg). The combined
aqueous phases were extracted with EtOAc (3”100 mL) and the
combined organic extracts were washed with 1n HCl (2”80 mL)
and water (2”80 mL). The organic phase was extracted with a satu-
found: C 69.66, H 6.58.
(2R,3S,5s,5ar,6R,8aS,9R,9aR,12S,12as,12bs,13S)-
2
2
,3,4,5,8a,9,9a-Octahydro-1H-6,9,12-(epimethanetriyl)-
,5:3,12b-dimethanocyclohepta[d]-s-indacen-12a(6H)-ol (16)
rated aqueous NaHCO solution (3”80 mL) and water (2”80 mL).
3
A solution of the diacid 15 (415 mg, 1.18 mmol) in pyridine
20 mL), water (2 mL), and Et N (0.66 mL, 478 mg, 4.74 mmol) was
The organic phase was dried with anhydrous Na SO and distilled
2
4
(
under atmospheric pressure by using a 10 cm Vigreux column and
heating till 110–1158C, to give an oily residue (127 mg) containing
the tetraene 17, 2-methylnaphthalene, and traces of 1-methylnaph-
thalene and the alcohol 16 (approximate molar ratio 17/2-methyl-
naphthalene 2:1), which was subjected to column chromatography
(neutral Al O (8 g), pentane/EtOAc mixtures). On elution with pen-
3
2
electrolyzed by using two rectangular Pt electrodes (3.3”1.7 cm )
at a distance of 8 mm at 90 V (d.c., 0.34 A) in an open water-
cooled (208C) 50 mL vessel for 18 h. After 16 h, the current dimin-
ished till 0.06 A. Water (45 mL) and EtOAc (100 mL) were added.
The organic phase was separated and the aqueous phase was ex-
tracted with EtOAc (2”100 mL). The combined organic phase and
extracts were washed with 1n HCl (3”60 mL) and water (2”
2
3
tane a first fraction (16 mg) consisting mainly of a mixture of 2-
methylnaphthalene and the tetraene 17 in an approximate ratio 2-
methylnaphthalene/tetraene 17 of 8:1, and a second fraction
(32 mg) consisting mainly of the tetraene 17 were isolated. The
6
0 mL), dried with anhydrous Na SO , and concentrated in vacuum
2 4
to give a residue (165 mg), which was subjected to column chro-
www.chemeurj.org 14043
Chem. Eur. J. 2015, 21, 14036 – 14046
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
+
second fraction, after elimination of the methylnaphthalenes, as
described before, gave pure the tetraene 17 (27 mg) as a white
solid. On elution with pentane and pentane/EtOAc 9:1, a third frac-
tion (6 mg) containing the impure alcohol 16 was isolated. The
C H +H : 265.1951; found: 265.1941; elemental analysis calcd (%)
20 24
for C H : C 90.85, H 9.15; found: C 90.77, H 9.11.
20
24
aqueous NaHCO extracts were acidified with 1n HCl (120 mL) and
3
extracted with EtOAc (3”120 mL). The combined organic phases
were washed with water (2”80 mL), dried with anhydrous Na SO ,
and concentrated in vacuum to give a solid residue (229 mg),
which consisted mainly of the starting diacid 15. This product was
resubmitted as such to the above-described bis-decarboxylation
process leading to a pentane extract (15 mg) and an EtOAc extract
(
2
1R,3aS,4r,4aR,7S,7ar,9s,10s,11br,12r)-
,3,3a,4,4a,5,6,7,8,9,10,11-Dodecahydro-1H-1,4,7-(epimetha-
2
4
netriyl)-7b,10:9,11a-dimethanobenzo[3,4]cyclobuta[1,2 h]cy-
clopenta[a]pentalene (19)
Procedure a (in pentane): A solution of the diene 18 (10.4 mg,
3
pressure mercury lamp for 3 h. At the end of the irradiation most
of the solvent had been evaporated. The solution was concentrat-
ed to dryness in vacuum at room temperature, the residue was
(
39 mg), both containing the tetraene 17, 2-methylnaphthalene,
and the alcohol 16 in a 2-methylnaphthalene/tetraene 17/alcohol
6 ratio of about 4:2:1. These fractions were combined and sub-
9 mmol) in pentane (25 mL) was irradiated with a 125 W medium-
1
jected to column chromatography (neutral Al O3 (7 g), pentane/
2
EtOAc mixtures). On elution with pentane, a mixture containing
mainly 2-methylnaphthalene and the tetraene 17 (ratio 2-methyl-
naphthalene/tetraene 17 5:2, 6 mg) and the tetraene 17 (10.5 mg)
were isolated. Altogether, the tetraene 17 (68.5 mg, 16% yield)
was obtained as a white solid. A significant amount of 2-methyl-
naphthalene and traces of 1-methylnaphthalene and the alcohol
1
13
taken in CDCl , and the different NMR spectra [ H and C NMR,
3
1
1
1
13
DEPT, H/ H homocorrelation (gCOSY), H/ C heterocorrelation
one bond: gHSQC and long range: gHMBC)] were recorded at
(
2
1
58C. To check the ratio of compounds 18 and 19, several H NMR
spectra were recorded at different times during the registration of
the other spectra.
1
6 were also detected. An analytical sample of the tetraene 17
1
From the spectra of a mixture of compounds 18 and 19, the H
and C NMR data of compound 19 were obtained. H NMR
(400 MHz, CDCl3): d=1.42–1.46 (brd, J(H,H)=8.8 Hz, 4H;
8(11,13,14)-Ha), 1.51–1.53 (overlapped d, J(H,H)=8.8 Hz, 4H;
8(11,13,14)-H ), 1.52–1.56 (m, 8H; 2(3,5,6)-H , 2(3,5,6)-H ), 1.59 (s,
2
2.4 Hz, J(H,H)=1.6 Hz, 4H; 1(3a,4a,7)-H); C NMR (100.6 MHz,
CDCl ): d=25.3 [CH , C2(3,5,6)], 39.4 [CH, C9(10)], 47.9 [CH ,
C8(11,13,14)], 48.4 [C, C7b(11a)], 50.8 [CH, C4(12)], 54.2 [CH,
C1(3a,4a,7)], 59.8 ppm [C, C7a(11b)].
(
(
8 mg) was obtained as a white solid by dissolving a fraction of 17
13
1
11 mg) in pentane (3 mL) and allowing the solution to concentrate
2
1
till a final volume of 0.5 mL. M.p. 164–1658C (pentane); H NMR
(
1
2
2
400 MHz, CDCl ): d=1.63 (s, 2H; 13(14)-H), 2.11 (d, J(H,H)=
3
2
3
b
n
x
2.4 Hz, 4H; 5(8,15,16)-H ), 2.21 (m, J(H,H)=12.4 Hz, J(H,H)=
b
3
H; 4(12)-H), 2.24–2.26 (brs, 2H; 9(10)-H), 2.30 ppm (dd, J(H,H)=
8
.0 Hz, 4H; 5(8,15.16)-H ), 2.43–2.49 (m, 2H; 6(7)-H), 2.97 (pseudo t,
a
4
13
3
4
J(H,H)= J(H,H)=2.0 Hz, 4H; 3(10,12a,13a)-H), 6.37 ppm (pseudo t,
3
4
13
3
2
2
J(H,H)= J(H,H)=2.0 Hz, 4H, 1(2,11,12)-H); C NMR (100.6 MHz,
CDCl ): d=36.6 [CH, C6(7)], 40.3 [CH , C5(8,15,16)], 45.3 [CH,
3
2
C3(10,12a,13a)], 46.2 [CH, C13(14)], 123.7 [C, C4(9)], 140.2 [CH,
C1(2,11,12)], 141.0 ppm [C, C3a(9a)]; IR (ATR): n˜ =2941 (m), 2919 (s),
Procedure b (in the solid state): A crystal of the diene 18 covert
with Fomblin Y was mounted on a cryoloop supported on a gonio-
metric bolster at about 4 cm from a 125 W low-pressure mercury
lamp. The crystal was cooled at À1008C with a stream of cold ni-
trogen flowing from about 2 cm from the upper side of the crystal,
while it was irradiated for 5 h. The crystal was rotated several times
to irradiate it from different sites. After stopping the irradiation,
the crystal was immediately submitted to X-ray diffraction analysis
at 100 K (exposure time: 3.87 h). The X-ray data (see part 1.7 in the
Supporting Information) show that the crystal contains molecules
of the cyclobutane derivative 19 and the diene 18 in a ratio 19/18
of 1:1.
À1
2
848 (m), 1445 (m), 1314 (m), 757 (m), 733 (m), 694 (m), 658 cm
+
(
m); accurate mass measurement: m/z calcd for C H +H :
20 20
2
61.1638; found: 261.1643; elemental analysis calcd (%) for
C H ·0.1H O: C 91.62, H 7.77; found: C 91.56, H 7.85.
20
20
2
(3R,3aZ,6s,7s,9Z,10S,12aR,13r,13aS,14r)-
2,3,5,6,7,8,10,11,12,12a,13,13a-Dodecahydro-1H-3,10,13-(epi-
methanetriyl)-4,7:6,9-dimethanodicyclopenta[a,d][11]annu-
lene (18)
5
% Pd on charcoal (5 mg) was added to a solution of the tetraene
1
7 (13.6 mg, 52 mmol) in EtOAc (15 mL), and the mixture was
stirred at room temperature under a hydrogen atmosphere (1 atm)
for 1 h. The suspension was filtered through a short pad of Celite,
the filtrate was concentrated in vacuum, and the residual beige
solid was crystallized from EtOAc (1 mL) to give the diene 18
Thermal conversion of the cyclobutane 19 to the diene 18
The kinetics of the thermal conversion of compound 19 to com-
1
pound 18 was followed by H NMR spectroscopy in CDCl at 25,
3
(
10.2 mg, 74% yield) as a white solid. M.p. 171–1728C (EtOAc);
35, and 458C. The ratio 19/18 was obtained by integration of the
signals at d=2.30 ppm corresponding to four protons (i.e.,
1(3a,4a,7)-H) of compound 19 and d=2.38–2.44 ppm (complex ab-
sorption) corresponding to six protons (i.e., 6(7)-H and
3(10,12a,13a)-H) of compound 18 (see Table S1 in the Supporting
Information). The plots ln[%19] versus time for each temperature
1
H NMR (400 MHz, CDCl ): d=1.21–1.26 (m, 4H; 1(2,11,12)-H ),
3
x
1
.45–1.51 (m, 4H; 1(2,11,12)-H ), 1.47 (s, 2H; 13(14)-H), 2.20 (d,
n
2
J(H,H)=12.4 Hz, 4H; 5(8,15,16)-H ), 2.26–2.30 (m, 4H; 5(8,15,16)-
b
3
H ), 2.38–2.44 (m, 2H; 6(7)-H), 2.41 ppm (pseudo t, J(H,H)=
a
4
13
J(H,H)=2.0 Hz, 4H; 3(10,12a,13a)-H); C NMR (100.6 MHz, CDCl3):
d=29.6 [CH , C1(2,11,12)], 35.7 [CH, C6(7)], 41.0 [CH , C5(8,15,16)],
2
gave straight lines (first-order kinetics) (r =0.99, n=4 for the pro-
2
2
2
2
4
1
2
9
1.4 [CH, C3(10,12a,13a)], 47.6 [CH, C13(14)], 128.2 [C, C4(9)],
37.7 ppm [C, C3a(9a)]; IR (ATR): n˜ =2951 (s), 2935 (s), 2916 (s),
860 (s), 2833 (s), 1436 (m), 1313 (m), 1298 (m), 1133 (m), 1108 (m),
cess at 258C, r =0.98, n=10 for the process at 358C, and r =0.99,
n=7 for the process at 458C) with rate constant values of k =
2
5
À1
0.0030, k =0.0112, and k =0.0231 min . From these rate con-
35
45
À1
36 (m), 816 (m), 781 (m), 742 (m), 652 cm (m); UV (n-pentane)
stant values, by using the Arrhenius equation, approximate values
À1
3
À1
À1
lmax(e)=207 nm (1740 mol m cm ); UV (CH Cl ) lmax(e)=228 nm
(
for the activation energy (19.2 kcalmol ) and the pre-exponential
2
2
À1
3
À1
11
À1
1750 mol m cm ); accurate mass measurement: m/z calcd for
Arrhenius factor (3.4”10 min ) were calculated.
Chem. Eur. J. 2015, 21, 14036 – 14046
www.chemeurj.org 14044
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
+
(
2R,3S,5s,5as,6S,8aR,9R,9aS,12R,12as,12br,13S)-5,12a-Dibro-
mo-2,3,4,5,6a,7,8,8a,9,9a,10,11,12a,12b-tetradecahydro-1H-
,9,12-(epimethanetriyl)-2,5:3,12b-dimethanocyclohepta[d]-
s-indacene (21)
C
(
H
20
24
I
2
ÀI : 391.0917; found: 391.0904; elemental analysis calcd
%) for C H I ·H O: C 44.80, H 4.89; found: C 44.55, H 4.86.
20 24 2
2
6
Dimethyl (2R,3S,5s,5ar,6R,7S,8R,8aS,9S,9aS,12-
R,12as,12br,13R)-5,12a-dibromo-
,3,4,5,6a,7,8,8a,9,9a,10,11,12a,12b-tetradecahydro-1H-
,9,12-(epimethanetriyl)-2,5:3,12b-dimethanocyclohepta[d]-
s-indacene-7,8-dicarboxylate (23) and dimethyl
2R,3S,5s,5as,6R,8aS,9R,9aS,10S,11R,12R,12ar,12br,13S)-5,12a-
A 0.49m solution of Br [0.1 mL, 49 mmol, prepared by dissolving
Br (50 mL) in CH Cl (2 mL)] was added dropwise to a stirred solu-
tion of the diene 18 (11.1 mg, 42 mmol) in anhydrous CH Cl (2 mL)
under an Ar atmosphere, and the reaction mixture was stirred at
room temperature protected from light for 20 h. The brown solu-
tion was diluted with CH Cl (5 mL), washed with a 10% aqueous
2
2
2
2
2
6
2
2
(
2
2
dibromo-2,3,4,5,6a,7,8,8a,9,9a,10,11,12a,12b-tetradecahy-
dro-1H-6,9,12-(epimethanetriyl)-2,5:3,12b-dimethanocyclo-
hepta[d]-s-indacene-10,11-dicarboxylate (24)
solution of NaHSO3 (1”3 mL plus 2”2.5 mL) and water (3 mL),
dried with anhydrous Na SO , and concentrated in vacuum to give
the crude dibromo derivative 21 as a light brown solid (19.8 mg),
which was crystallized from EtOAc (3 mL) to give compound 21
2
4
Bromine (30 mL, 94 mg, 0.58 mmol) was added to a stirred solution
of the diester 10 (158 mg, 0.41 mmol) in CH Cl (2 mL) under an Ar
2 2
atmosphere, and the solution protected from light was stirred at
room temperature for 21 h. To the brown solution, a 10% aqueous
(
(
16 mg, 89% yield) as a white solid. M.p. 260–2618C (decomp.)
1
EtOAc); H NMR (400 MHz, CDCl ): d=1.03–1.08 (m, 2H; 7(8)-H ),
3
n
1
.17–1.22 (m, 2H; 10(11)-H ), 1.59–1.63 (m, 2H; 1(15)-H ), 1.60
n b
(
(
2
2
4
overlapped s, 2H; 9(13)-H), 1.94–2.00 (m, 2H; 10(11)-H ), 2.17–2.23
x
3
4
Na
phase was separated, washed with a 10% aqueous Na
tion (2”4 mL) and water (2”3 mL), dried with anhydrous Na SO ,
S
2
2
O
3
solution (4 mL) and CH
2
Cl
2
(5 mL) were added. The organic
m, 2H; 1(15)-H ), 2.20 (overlapped pseudo t, J(H,H)= J(H,H)=
a
3
4
S O
2 2 3
solu-
.0 Hz, 2H; 9a(12)-H), 2.23 (overlapped dd, J(H,H)=2.4, J(H,H)=
2
4
.0 Hz, 2H; 6(8a)-H), 2.24–2.30 (m, 2H; 4(14)-H ), 2.33–2.38 (m, 2H;
a
and concentrated in vacuum to give a white residue (211 mg, 95%
(14)-H ), 2.39–2.44 (m, 2H; 2(3)-H), 2.63–2.69 ppm (m, 2H; 7(8)-
b
1
3
yield), which was a mixture of compounds 23 and 24 in a ratio
Hx); C NMR (100.6 MHz, CDCl ): d=29.4 [CH , C10(11)], 30.0 [CH ,
3
2
2
1
close to 3.5:1 (determined by H NMR spectroscopy). Slow crystalli-
C7(8)], 38.9 [CH, C2(3)], 44.26 [CH, C6(8a)], 44.35 [CH , C1(15)], 49.2
2
zation from EtOAc (2 mL) gave the main isomer 23 as colorless
prisms (88 mg). The mother liquors were concentrated to dryness
and the residue, still enriched with the main stereoisomer, was
crystallized from EtOAc (5 mL) to give colorless needles corre-
sponding to the minor stereoisomer 24 (14 mg). Further crystalliza-
tion of the mother liquors gave more compound 24 (11 mg).
[
6
(
1
CH, C9a(12)], 52.1 [CH, C9(13)], 55.6 (C, C12b), 56.2 [CH , C4(14)],
2
5.9 (C, C5a), 67.4 (C, C5), 88.0 ppm (C, C12a); IR (ATR): n˜ =2956
m), 2936 (m), 2883 (w), 2863 (w), 1460 (m), 1442 (w), 1311 (w),
300 (w), 1123 (w), 1098 (w), 988 (w), 954 (s), 923 (m), 899 (m), 839
À1
(
w), 786 (m), 698 cm (s); accurate mass measurement: m/z calcd
7
9
+
for C H Br ÀBr : 343.1055; found: 343.1064; elemental analysis
2
0
24
2
Analytical and spectroscopic data of compound 23: Colorless
calcd (%) for C H Br : C 56.63, H 5.70; found: C 57.15, H 6.05.
2
0
24
2
1
prisms; m.p. 230–2318C (EtOAc); H NMR (400 MHz, CDCl ): d=
3
1
.23–1.28 (m, 2H; 10(11)-H ), 1.58–1.62 (m, 2H; 1(15)-H ), 1.95–1.99
n
b
3
4
(
m, 2H; 10(11)-H ), 2.20 (pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H;
x
9
2
2
a(12)-H), 2.22–2.30 (m, 2H; 1(15)-H ), 2.27 (s, 2H; 9(13)-H), 2.31–
(
2
6
2R,3S,5s,5as,6S,8aR,9R,9aS,12R,12as,12br,13S)-5,12a-Diiodo-
,3,4,5,6a,7,8,8a,9,9a,10,11,12a,12b-tetradecahydro-1H-
,9,12-(epimethanetriyl)-2,5:3,12b-dimethanocyclohepta[d]-
a
2
.37 (m, 2H; 4(14)-H ), 2.41 (d, J(H,H)=10.8 Hz, 2H; 4(14)-H ),
a
b
3
4
.43–2.47 (m, 2H; 2(3)-H), 2.65 (pseudo t, J(H,H)= J(H,H)=2.0 Hz,
3
2
H; 6(8a)-H), 3.65 (s, 6H; 2 OCH ), 4.45 ppm (pseudo t, J(H,H)=
3
s-indacene (22)
4
13
J(H,H)=2.0 Hz, 2H; 7(8)-H); C NMR (100.6 MHz, CDCl ): d=29.3
3
[
CH , C10(11)], 39.0 [CH, C2(3)], 44.3 [CH , C1(15)], 44.4 [CH,
2 2
Iodine (18 mg, 71 mmol) was added to a stirred solution of the
diene 18 (11.3 mg, 43 mmol) in anhydrous CH Cl (2 mL) under an
C9(13)], 44.9 [CH, C7(8)], 47.5 [CH, C6(8a)], 48.7 [CH, C9a(12)], 51.5
CH , OCH ), 56.2 (C, C12b), 56.7 [CH , C4(14)], 66.0 (C, C5a), 67.9 (C,
2
2
(
Ar atmosphere, and the reaction mixture was stirred at room tem-
perature protected from light for 20 h. The brown solution was di-
luted with CH Cl (6 mL), washed with a 10% aqueous solution of
3
3
2
C5), 86.8 (C, C12a), 172.8 ppm (C, COOCH ); IR (ATR): n˜ =2948 (m),
2
1
6
C H Br O +H : 539.0427; found: 539.0437; elemental analysis
calcd (%) for C H Br O : C 53.35, H 5.22, Br 29.58; found: C 53.32,
H 5.33, Br 29.62.
3
875 (w), 1735 (s), 1731 (s), 1460 (m), 1434 (m), 1344 (m), 1204 (s),
2
2
191 (s), 1168 (s), 1098 (m), 1065 (m), 1047 (m), 936 (m), 899 (m),
NaHSO (1”5 mL plus 2”4 mL) and water (4 mL), dried with anhy-
3
À1
99 cm
(s); accurate mass measurement: m/z calcd for
drous Na SO , and concentrated in vacuum to give the crude
2
4
7
9
+
diiodo derivative 22 as a light brown solid (26 mg), which was
treated with hot EtOAc (3 mL) to give compound 22 (14 mg, 61%
yield) as a white solid. M.p. 232–2338C (decomp.), at 1958C the
24 28
2
4
24 28
2
4
1
sample of compound 22 became brown); H NMR (400 MHz,
Analytical and spectroscopic data of compound 24: Colorless
needles; m.p. 251–2528C (EtOAc); H NMR (400 MHz, CDCl ): d=
1
CDCl ): d=1.00–1.05 (m, 2H; 7(8)-H ), 1.17–1.22 (m, 2H; 10(11)-H ),
3
n
n
3
1
1
.54 (s, 2H; 9(13)-H), 1.67–1.72 (m, 2H; 1(15)-H ), 1.90–1.96 (m, 2H;
1.11–1.16 (m, 2H; 7(8)-H ), 1.60–1.63 (m, 2H; 1(15)-H ), 2.17 (s, 2H;
9(13)-H), 2.16–2.23 (m, 2H; 1(15)-H ), 2.24–2.30 (m, 2H; 4(14)-H ),
a a
b
n
b
0(11)-H ), 2.18–2.23 (m, 4H; 2(3)-H, 1(15)-H ), 2.22 (overlapped
x
a
3
4
3
pseudo t, J(H,H)= J(H,H)=2.4 Hz, 2H; 6(8a)-H), 2.28 (dd, J(H,H)=
2
4
2.25 (t, J=2.0 Hz, 2H, 6(8a)-H), 2.35 (d, J=11.2 Hz, 2H, 4(14)-Hb),
2.40–2.45 (m, 2H, 2(3)-H), 2.54 (t, J=2.0 Hz, 2H, 9a(12)-H), 2.64–
4
.4, J(H,H)=1.6 Hz, 2H; 9a(12)-H), 2.53–2.58 (m, 4H; 4(14)-H ,
a
1
3
3
4
(14)-H ), 2.82–2.89 ppm (m, 2H; 7(8)-H ); C NMR (100.6 MHz,
2.71 (m, 2H, 7(8)-H ), 3.60 (pseudo t, J(H,H)= J(H,H)=2.0 Hz, 2H;
x
b
x
13
CDCl ): d=29.2 [CH , C7(8)], 31.4 [CH , C10(11)], 40.6 [CH, C2(3)],
10(11)-H), 3.66 ppm (s, 6H; 2 OCH3); C NMR (100.6 MHz, CDCl3):
3
2
2
4
4.0 [CH, C6(8a)], 44.3 (C, C5), 47.8 [CH , C1(15)], 50.7 [CH,
d=29.9 [CH , C7(8)], 38.9 [CH, C2(3)], 44.1 [CH, C6(8a)], 44.3 [CH ,
2
2
2
C9a(12)], 51.4 [CH, C9(13)], 56.1 (C, C12b), 61.2 [CH , C4(14)], 64.9
C1(15)], 45.9 [CH, C9(13)], 46.4 [CH, C10(11)], 51.6 (CH , OCH ), 52.0
3 3
2
(
(
C, C5a), 82.1 ppm (C, C12a); IR (ATR): n˜ =2951 (m), 2925 (m), 2888
w), 2863 (w), 1454 (m), 1439 (w), 1294 (w), 1192 (w), 1121 (m),
[CH, C9a(12)], 55.3 (C, C12b), 56.1 [CH , C4(14)], 66.4 (C, C5), 66.6
2
(C, C5a), 87.3 (C, C12a), 172.2 ppm (C, COOCH ); IR (ATR): n˜ =2956
3
1
6
114 (m), 949 (m), 927 (w), 914 (w), 892 (m), 835 (w), 783 (m),
(m), 2941 (m), 2886 (w), 1742 (s), 1731 (s), 1435 (m), 1337 (m), 1306
(m), 1205 (s), 1175 (s), 1158 (s), 1134 (m), 1048 (m), 955 (m), 933
À1
81 cm
(s); accurate mass measurement: m/z calcd for
Chem. Eur. J. 2015, 21, 14036 – 14046
www.chemeurj.org 14045
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
À1
(
m), 894 (m), 710 (s), 681 cm (m); accurate mass measurement:
Angew. Chem. Int. Ed. 2014, 53, 8195–8199; Angew. Chem. 2014, 126,
7
9
+
8334–8338.
m/z calcd for C H Br O +H : 539.0427; found: 539.0414; ele-
2
4
28
2
4
[
3] a) P. Camps, M. Font-Bardia, F. PØrez, X. Solans, S. Vµzquez, Angew.
Chem. Int. Ed. Engl. 1995, 34, 912–914; Angew. Chem. 1995, 107, 1011–
mental analysis calcd (%) for C H Br O ·0.25H O: C 52.91, H 5.27,
2
4
28
2
4
2
2
9.58; found: C 52.79, H 5.12, Br 29.28.
1012; b) P. Camps, M. Font-Bardia, F. PØrez, L. Solà, X. Solans, S.
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Luque, M. Orozco, F. PØrez, S. Vµzquez, Tetrahedron Lett. 1996, 37,
Acknowledgements
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We thank the Ministerio de Economía y Competitividad
MINECO) (CTQ2011-22433, SAF2014-57094-R) and the General-
4049–4051; Angew. Chem. 2003, 115, 4183–4185; f) C. Ayats, P. Camps,
(
M. D. Duque, M. Font-Bardia, M. R. MuÇoz, X. Solans, S. Vµzquez, J. Org.
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M. R. MuÇoz, M. A. Pericàs, L. Solà, S. Vµzquez, Tetrahedron 2007, 63,
itat de Catalunya (2014SGR1189) for financial support, the
CCiTUB for NMR spectroscopy and MS facilities, the Institut de
Química AvanÅada de Catalunya for the elemental analyses,
and the Consorci de Serveis Universitaris de Catalunya for com-
putational resources. P.C. thanks Prof. M. A. Miranda (Universi-
tat Polit›cnica de Val›ncia) for helpful comments. C.E. is a fel-
lowship of the MINECO (FPDI-2013-15572). F.J.L. acknowledges
ICREA Academia for financial support.
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Keywords: density functional calculations · domino reactions ·
photochemistry · polycycles · X-ray diffraction
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Received: June 18, 2015
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Published online on August 20, 2015
Chem. Eur. J. 2015, 21, 14036 – 14046
www.chemeurj.org
14046
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim