A convenient approach to polycyclic derivatives with a cis-fused 2,6-dioxabicyclo[4.3.0]nonane system by the sequence ring-opening/intramolecular Ring-closing enyne metathesis/diels-alder reaction

Article abstract of DOI:10.1002/ejoc.200800936

7-Oxanorbornene derivatives functionalized with alkyne appendages undergo intramolecular enyne metathesis reactions to give cis-fused 2,6-dioxabicyclo[4. 3.0]nonane derivatives. These compounds have a diene functionality that allows their reaction with di

Full text of DOI:10.1002/ejoc.200800936

FULL PAPER
DOI: 10.1002/ejoc.200800936
A Convenient Approach to Polycyclic Derivatives with a cis-Fused
2,6-Dioxabicyclo[4.3.0]nonane System by the Sequence Ring-Opening/
Intramolecular Ring-Closing Enyne Metathesis/Diels–Alder Reaction
Ana Aljarilla,[a] Maria C. Murcia,[a] Aurelio G. Csákÿ,[a] and Joaquín Plumet*[a]
Dedicated to Professor Rosa Fernández of the University of Oviedo
Keywords: Metathesis / Cycloaddition / Diels–Alder reaction / Ruthenium / Polycycles
7-Oxanorbornene derivatives functionalized with alkyne
appendages undergo intramolecular enyne metathesis reac-
tions to give cis-fused 2,6-dioxabicyclo[4.3.0]nonane deriva-
tives. These compounds have a diene functionality that
allows their reaction with dienophiles (N-phenylmaleimide)
to yield densely functionalized polycyclic compounds.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
architectures.[8] From a methodological point of view, this
procedure is also a valuable alternative to the transforma-
tion of carbohydrates into carbocycles.[9] Moreover, many
kinds of dienophilic components have been used, including
singlet oxygen[10] and fullerene C60.[11]
Norbornene derivatives have been used as convenient
substrates in metathesis reactions because the release of
ring-strain during the metathesis process (in particular
those that include ROM reactions) makes the reaction es-
sentially irreversible.[12] For this reason norbornene deriva-
tives are valuable monomers in ring-opening metathesis po-
lymerization (ROMP) reactions.[13] Also, bis-propargylic
norbornene derivatives have been used as starting materials
for the construction of pentacyclic ring systems by the IEM/
DA reaction sequence (Scheme 2).[14]
Introduction
Nowadays, olefin metathesis is a standard method for the
formation of C–C bonds.[1] Because the three main types of
metathesis reactions, that is, ring-opening metathesis
(ROM), ring-closing metathesis (RCM) and cross meta-
thesis (CM), allow the synthesis of complex molecules, they
are now widely used in an almost routine fashion.[2]
In the case of intramolecular enyne metathesis reac-
tions[3] (IEM, Scheme 1), the final product is an exocyclic
1,3-diene that can be further transformed into polycyclic
structures through Diels–Alder cycloaddition reactions.
Scheme 1. The intramolecular enyne metathesis (IEM)/Diels–Alder
cycloaddition sequence.
Since the first reports of diene synthesis by enyne meta-
thesis,[4] this methodology has been lavishly applied in or-
ganic synthesis. For instance, the construction of very dif-
ferent types of complex carbo- and heterocyclic compounds
has been reported, including conformational constrained
amino acids,[5] polycyclic β-lactams[6] and C-glycosides or
other sugar derivatives,[7] among many other molecular
Scheme 2. The intramolecular enyne metathesis/Diels–Alder cyclo-
addition sequence for norbornene derivatives.
However, it is surprising that, to the best of our knowl-
edge, in the case of the related 7-oxanorbornene deriva-
tives,[15] with the exception of one isolated report,[16] this
process has not yet been explored. In this case the oxa-
bicyclic amino acid derivative 1 was transformed into bicy-
clic compounds 2 through the IEM protocol. Further reac-
[a] Universidad Complutense, Facultad de Química, Departa-
mento de Química Orgánica,
28040 Madrid, Spain
Fax: 34-91-3944231
E-mail: plumety@quim.ucm.es
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
822
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 822–832

Polycyclic Derivatives with a Dioxabicyclononane System
tion of 2 with N-benzylmaleimide or diethyl azodicarboxyl-
ate afforded tetra- 3 or tricyclic 4 derivatives, respectively
(Scheme 3).
Scheme 4. The intramolecular enyne metathesis/Diels–Alder cyclo-
addition sequence for 2-mono- and 2,3-disubstituted derivatives of
7-oxanorbornenes 5 and 6.
Scheme 3. The intramolecular enyne metathesis/Diels–Alder cyclo-
addition sequence for an oxanorbornene derivative (see ref.[16]).
On the basis of these previous reports, we thought that
the IEM reactions of the mono- and 2,3-disubstituted de-
rivatives of the 7-oxabicyclo[2.2.1]hept-5-ene framework 5
and 6 (Scheme 4) should give bi- and tricyclic dienic com-
pounds 7 and 8, respectively. Subsequent DA reactions of
7 and 8 with the appropriate dienophile should pave the
way for the preparation of the densely functionalized poly-
cyclic compounds 9 and 10.
Note that the central cores of these compounds are a
fused cis-2,6-dioxabicyclo[4.3.0]nonane skeleton, a motif
widely distributed in nature. For instance, compounds such
as dysiherbaine 11a and neodysiherbaine 11b (Figure 1) are
excitatory amino acids with potent convulsant activity.[17]
On the other hand, some pyranonaphthoquinone anti-
biotics,[18] such as kalafungin 12a, frenolicin 12b and arizo-
micin 12c (Figure 1), bear the naphtho[2,3-c]pyran-5,10-di-
one substructure as the basic skeleton. These compounds
exhibit activity against a variety of Gram-positive bacteria,
pathogenic fungi and yeasts as well as antiviral activity. Fi-
nally some furanopyrones of the styryl lactone family,[19]
such as altholactone 13a and isoaltholactone 13b, possess,
among others, interesting antitumour properties. Therefore
Figure 1. Some natural products containing the cis-2,6-dioxabicy-
clo[4.3.0]nonane skeleton.
compounds 9 and 10 may be considered as potentially use- appropriate oxabicyclic compounds 5 and 6 and using an
ful derivatives of this basic skeleton. IEM/DA reaction sequence. Note that, at least in two cases,
In this report we wish to describe our efforts towards the compounds showing the cis-fused 2,6-dioxabicyclo[4.3.0]-
synthesis of compounds 7–10 (Scheme 4) starting from the nonane system have been synthesized by metathesis reac-
Eur. J. Org. Chem. 2009, 822–832
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
823

A. Aljarilla, M. C. Murcia, A. G. Csákÿ, J. Plumet
FULL PAPER
tions[20] and that a part of this report has been published pargyl derivative. The experimental conditions and yields
in a preliminary account.[21]
are summarized in Scheme 6. Unfortunately all efforts to
prepare compound 26 were unsuccessful under a variety of
experimental conditions. Extensive decomposition of the re-
action mixture was observed even at low temperatures (–5
to 0 °C) when the acid chloride or carboxylic acid were used
under the experimental conditions indicated in Scheme 5
and Scheme 6.
Results and Discussion
Synthesis of the General Structures 5 and 6 as Starting
Materials
Racemic compounds have been used in this research. It
should be noted that precursor 7-oxanorbornenone 14
(Scheme 5) has previously been obtained in optically pure
form[22] and thus compounds 16–21 could also be synthe-
sized in optically pure form.
Scheme 6. Synthesis of the propioloyl derivatives of 7-oxanorbor-
nene.
Metathesis Reactions
First we explored the IEM reactions of compounds 16
and 18 by using first-generation Grubb’s ruthenium catalyst
27 in the absence of an ethylene atmosphere (Scheme 7).
The reactions worked well and bicyclic derivatives 28 and
29 were obtained in 88 and 79% yields, respectively.[25]
Scheme 5. Synthesis of 2-propargyl derivatives of 7-oxanorbornene.
Monosubstituted derivatives of the type 5 (Scheme 4)
were prepared by reduction of 14[23] (NaBH4, MeOH, 90%
compound 15) or by addition of the corresponding organo-
lithium or Grignard reagent[24] (compound 20a, 90% with
PhLi, ratio endo/exo 3.6:1, 80% with PhMgBr, only the
endo alcohol; compound 20b, 75% with EtMgI, only the
Scheme 7. Intramolecular enyne metathesis reactions of propargyl
ethers 16 and 18.
On the basis of these results, two comments appear to be
endo alcohol) followed by etherification or esterification of opportune at this point. First, the reactions were satisfacto-
the alcohols with the appropriate propargyl derivative. The rily achieved with both terminal and internal alkynes. Sec-
experimental conditions and yields are summarized in ondly, the reactions were conducted in the absence of an
Scheme 5.
ethylene atmosphere. Regarding the first point, this result is
Disubstituted derivatives of type 6 (Scheme 4) were syn- noteworthy because, in general, alkyne metathesis reactions
thesized from diol 22 by reaction with the appropriate pro- are often limited to internal acetylenic compounds,[26] al-
824
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 822–832

Polycyclic Derivatives with a Dioxabicyclononane System
though some solutions to this problem have been reported:
the use of an appropriate catalyst[27] or the selection of suit-
able experimental conditions.[28] Nevertheless, note also that
IEM reactions involving terminal alkynes have previously
been observed in the norbornene series.[14] Secondly, al-
though the beneficial effect of ethylene in IEM reactions
has previously been reported,[29] we have verified[30] that the
reaction of enyne 30 with catalyst 31 (5%, CH2Cl2, 24 h,
ethylene) afforded tetrahydrofuran 32 as the major product
(60%) together with only 35% of compound 33 arising
from IEM reaction (Scheme 8).
Scheme 10. Intramolecular enyne metathesis reactions of the 2,3-
bis-propargyl ethers 23 and 24.
[32]
´
generation Hoveyda–Grubbs catalyst 43.
On the other
hand, catalyst 31 (Scheme 8) has proven to be very active
in the presence of conjugated electron-deficient olefins[33]
allowing CM reactions between α,β-unsaturated carbonyl
compounds and terminal olefins. For these reasons we de-
cided to use catalyst 31 in the IEM reactions of our 3-meth-
ylpropiolates.
Scheme 8. Metathesis reaction of 3-methylpropiolate 30.
cis-Fused 2,6-dioxabicyclo[4.3.0]non-8-enes with alkenyl
side-chains at C-3 and C-8 and also a quaternary stereo-
genic centre at C-5 was synthesized in the presence of cata-
lyst 27 and 1.0 equiv. of allyl acetate 34 starting from the
compounds 16 and 20a,b (Scheme 9).[21] In this way the bi-
cyclic derivatives 35–37 were prepared in 58, 60 and 55%
yields, respectively. All these compounds were obtained as
1:1 mixtures of the E and Z isomers.
Scheme 11. Metathesis reaction of acrylate 40.
Scheme 9. Metathesis reactions of the propargyl ethers 16 and
20a,b in the presence of allyl acetate 34.
The results were satisfactory in the case of ester 19.
Finally, the tricyclic bis-dienes 38 and 39 were synthe- Treatment of this compound with catalyst 31 (10%,
sized in a similar fashion starting from compounds 23 and CH2Cl2, ethylene) gave 93% of bicycle 44 when the reaction
24, respectively, by using catalyst 27 in the absence of ethyl- was carried out for 75 min. The reaction time appeared to
ene (Scheme 10).
be critical in this process. For instance, after a reaction time
Having successfully completed the IEM reactions of the of 90 min, compounds 45 (59%) and 44 (38%) were isolated
propargyl ethers we turned our attention to related esters. and after 12 h the product distribution was 33% compound
In these cases some previous considerations should be 45 and 50% compound 44. On the other hand, when the
noted. First, the ROM/CM/RCM sequence performed on reaction was conducted in CH2Cl2 (sealed tube, oil bath,
acrylates such as 40 in the presence of catalyst 27 resulted 50–60 °C) a mixture containing 56% of tetrahydrofuran 45
in the formation of tetrahydrofurans 41. No traces of the and 43% of bicycle 44 was isolated. The ratio 45/44 re-
bicyclic compound 42 were observed (Scheme 11).[31] Nev- mained essentially unchanged by the application of longer
ertheless compound 42 was prepared by using the second- reaction times (Scheme 12).
Eur. J. Org. Chem. 2009, 822–832
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
825

A. Aljarilla, M. C. Murcia, A. G. Csákÿ, J. Plumet
FULL PAPER
Table 1. Diels–Alder reaction of compounds 28, 29 and 42 with N-
phenylmaleimide. Reactions times and yields of isolated products
50–52.
Scheme 12. Metathesis reaction of 3-methylpropiolate 19.
Starting material
Reaction time [d] Product Yield [%]
X
R
CH2
CH2 CH3
CO CH3
H
28
29
42
7
5
4
50
51
52
86
81
68
In sharp contrast, compounds 17 and 25 gave disap-
pointing results. In the case of 17 only tetrahydrofuran 46
(44% yield) was obtained with 5% catalyst 31 in CH2Cl2
(2 h, best result). Longer reaction times or the use of cata-
lyst 43 did not improve this result. Compound 47 was never
isolated although total consumption of the starting material
was observed in the presence of 43 (5%, 1 h), resulting in a
complex reaction mixture. Similar results were observed for
compound 25. Thus, reaction of 25 with 10% catalyst 31
gave, under ethylene, 37% of the tetrasubstituted tetra-
hydrofuran 48 (best conditions). Also in this case com-
pound 49 was neither isolated nor observed under different
reaction conditions (Scheme 13).
Table 2. Diels–Alder reaction of compounds 38 and 39 with N-
phenylmaleimide. Reactions times and yields of isolated products
53 and 54.
Starting material
Reaction time [d] Product
Yield [%]
R = H
R = CH3
38
39
4
4
53
54
90
85
The stereochemistries of the cycloadducts 50–54 were es-
tablished as outlined below. In the case of the tetracyclic
derivatives 50–52, the experimental and calculated coupling
3
constants J(H10b–H10c) (AMBER method implemented in
the HyperChem 7.5 package, MNDO-optimized geome-
tries) were compared. For structure I (Figure 2), the calcu-
lated 3J(H10b–H10c
) values lie between 0.41–0.72 Hz,
whereas for structure II the values were estimated to be be-
tween 4.8–6.6 Hz. By comparison with the experimental
values (values between 1.63–1.93 Hz, Table 3), structure I
can be proposed as the most probable structure of the tetra-
cyclic cycloadducts 50–52.
Structure I was further confirmed on consideration of
the long-range coupling constants (NOESY experiments)
observed for compound 50 (I, X = CH2, R = H) as a model.
Correlations H10a–H10c and H10c–H2 are, in this case, par-
ticularly significant and support structure I.
Scheme 13. Metathesis reactions of enynes 17 and 25.
Diels–Alder Reactions
Having synthesized the dienes 28, 29, 38, 39 and 42 these
Structure III (Figure 2) was proposed as the structure of
compounds were subjected to the Diels–Alder reaction the heptacyclic systems 53 and 54 on the basis of the sym-
using N-phenylmaleimide as the dienophilic partner. In all metrical character of these compounds, as deduced from
cases the reactions were performed in CH2Cl2 and gave the their 1H NMR spectra. NOESY experiments carried out on
expected tetra- (50–52) or heptacyclic (53, 54) derivatives in compound 54 (R = CH3) confirmed the proposed stereo-
convenient yields and as a single stereoisomer (see Tables 1 chemistry. The correlations for H1a–H1c, H1b–H5Ј and H4a–
and 2).
H1a clearly support III as the structure of this compound.
826
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 822–832

Polycyclic Derivatives with a Dioxabicyclononane System
AM-300 (300 MHz) NMR spectrometers in deuteriochloroform or
deuteriated benzene. The proton (1H NMR) and carbon (13C
NMR) signals were assigned on the basis of DEPT 135, COSY 45,
HMQC and HMBC experiments. Chemical shifts are expressed as
δ values in ppm and coupling constants are given in Hz. Melting
points were determined by using a Gallenkamp instrument and are
uncorrected. IR spectra were obtained with a Perkin–Elmer 781
apparatus in CHCl3 solution. Elemental analyses were carried out
by using a Perkin–Elmer 2400 CHN apparatus at the Complutense
University, Madrid.
Starting Materials: Compounds 15,[23] 20a,b[24] and 22[20b] have
been described previously.
General Procedure for the Synthesis of Compounds 16 and 18: NaH
(1.2 mmol) and the corresponding bromoalkyne (1.2 mmol) were
added to a solution of compound 15 (1.0 mmol) in anhydrous
DMF (6 mL/mmol) under argon at 0 °C. The reaction mixture was
stirred at room temp. for 24 h. After the reaction was complete, the
reaction mixture was treated with 1  HCl (10 mL) and then ex-
tracted with Et2O (3ϫ5 mL). The combined organic layers were
washed with 5% NaHCO3 (3ϫ10 mL), dried (MgSO4) and con-
centrated in vacuo. The crude product was purified as indicated in
each case.
Figure 2. Proposed structures of the Diels–Alder cycloadducts 50–
54.
Compound 16: NaH (28.3 mg, 1.2 mmol) and 3-bromopropyne
(0.14 mL, 1.2 mmol) were added to a solution of 15 (120.0 mg,
1.07 mmol) in DMF (6.5 mL) at 0 °C. Purification by column
chromatography (SiO2, hexane/AcOEt, 8:2) gave 151.0 mg (94%)
of pure 16 as a colourless oil. 1H NMR (CDCl3, 300 MHz): δ =
6.54 (dd, J = 10.83, 4.00 Hz, 1 H, 2-H), 6.35 (dd, J = 5.90, 1.60 Hz,
1 H, 3-H), 5.06 (dd, J = 4.10, 1.40 Hz, 1 H, 4-H), 4.94 (dd, J =
4.80, 1.60 Hz, 1 H, 1-H), 4.31 (ddd, J = 7.90, 4.40, 2.50 Hz, 1 H,
5-H), 4.14 (ddd, J = 16.00, 12.10, 2.40 Hz, 1 H, HCϵCCH2O),
2.48 (t, J = 2.40 Hz, 1 H, HCϵCCH2O), 2.22 (ddd, J = 12.00, 8.00,
4.90 Hz, 1 H, 6-H), 1.11 (dd, J = 11.70, 2.40 Hz, 1 H, 6Ј-H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 137.38 (C-2), 132.36 (C-3), 79.98
(HCϵCCH2O), 79.36 (C-1), 78.40 (C-4), 76.65 (C-5), 74.86
(HCϵCCH2O), 57.77 (HCϵCCH2O), 33.21 (C-6) ppm. IR
Table 3. Comparison of calculated and experimental values of
3J(H10b-H10c) for compounds 50–52.
3
3
Calcd.3J(H10b–H10c
for I [Hz]
)
Calcd. J(H10b–H10c) for Exp. J
II [Hz]
[Hz]
50
51
52
0.41
0.60–0.70
0.56–0.72
5.8–6.5
6.6
4.8
1.60
1.80
1.90
Conclusions
In this paper the IEM/DA reaction sequence has been
optimized for a series of propargyl derivatives with the 7-
oxabicyclo[2.2.1]hept-5-ene skeleton. In the IEM reaction,
bi- or tricyclic compounds bearing a cis-fused 2,6-dioxa-
bicyclo[4.3.0]nonane subunit with three or four well-defined
stereogenic centres were synthesized. In addition, by selec-
tion of the appropriate starting materials, a quaternary
stereogenic centre may also be created. These compounds
bear dienic or bis-dienic substructures prone to Diels–Alder
(CHCl ): ν = 3282, 3004, 2950, 2857, 2115, 1091, 1024 cm–1.
˜
3
C9H10O2 (150.07): calcd. C 71.98, H 6.71; found C 72.13, H 6.86.
Compound 18: NaH (24.0 mg, 0.98 mmol) and 1-bromobut-2-yne
(0.11 mL, 0.98 mmol) were added to a solution of 15 (100.0 mg,
0.89 mmol) in DMF (5.4 mL) at 0 °C. Purification by column
chromatography (SiO2, hexane/AcOEt, 8:2) gave 126.0 mg (86%)
of pure 18 as a colourless oil. 1H NMR (CDCl3, 300 MHz): δ =
6.52 (dd, J = 5.90, 1.70 Hz, 1 H, 2-H), 6.33 (dd, J = 5.90, 1.70 Hz,
reaction with the appropriate dienophilic agent. In this way 1 H, 3-H), 5.03 (dm, J = 4.20 Hz, 1 H, 4-H), 4.94 (dm, J = 4.70 Hz,
1 H, 1-H), 4.27 (ddd, J = 7.90, 4.30, 2.50 Hz, 1 H, 5-H), 4.07
(dquint., J = 10.60, 2.30 Hz, 2 H, CH3CϵCCH2O), 2.19 (ddd, J =
11.70, 7.90, 5.0 Hz, 1 H, 6-H), 1.85 (t, J = 2.30 Hz, 3 H,
CH3CϵCCH2O), 1.09 (dd, J = 11.70, 2.30 Hz, 1 H, 6Ј-H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 137.60 (C-2), 132.61 (C-3), 83.21
(CH3CϵCCH2O), 79.64 (C-1), 78.77 (C-4), 76.77 (C-5), 75.55
(CH3CϵCCH2O), 58.53 (CH3CϵCCH2O) 33.42 (C-6), 4.05
tetra- and heptacyclic derivatives of the cis-fused 2,6-di-
oxabicyclo[4.3.0]nonane skeleton with five and nine stereo-
genic centres, respectively, were also synthesized. The se-
quence described herein is an atom-economic entry to these
kinds of compounds.
(CH CϵCCH O) ppm. IR (CHCl ): ν = 3392, 2952, 2243, 1713,
˜
3
2
3
1259, 1156, 1082, 1026 cm–1. C10H12O2 (164.08): calcd. C 73.15, H
Experimental Section
7.37; found C 73.29, H 7.48.
General Information: All reactions were carried out under argon
using standard techniques. All solvents were reagent grade. Dichlo-
romethane was freshly distilled from calcium hydride. DMF was
used after distillation. All other reagents and solvents were used as
supplied. Flash chromatography was performed with silica gel 60
(230–400 mesh). Yields refer to chromatographically and spectro-
scopically pure compounds unless otherwise noted. 1H and 13C
NMR spectra were recorded with Bruker AM-200 (200 MHz) and
General Procedure for the Synthesis of Compounds 21a and 21b:
NaH (1.9 mmol) and 1-bromobut-2-yne (2.5 mmol) were added to
a solution of the starting material 20a and 20b (1.0 mmol) in anhy-
drous DMF (6 mL/mmol) under argon at 0 °C. Then the reaction
mixture was stirred at room temp. for 24 h. After the reaction was
complete, the reaction mixture was hydrolysed with H2O (3 mL)
and then extracted with Et2O (3ϫ4 mL). The combined organic
Eur. J. Org. Chem. 2009, 822–832
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
827

A. Aljarilla, M. C. Murcia, A. G. Csákÿ, J. Plumet
FULL PAPER
layers were washed with H2O, dried (MgSO4) and concentrated in
vacuo. The crude product was purified as indicated in each case.
temp. overnight. After this time 1  HCl was added (15 mL) and
then the mixture was extracted with CH2Cl2 (3ϫ12 mL). The reac-
tion mixture was washed with NaHCO3 (saturated solution,
20 mL), and NaCl (saturated solution, 20 mL) and the organic
layer dried with MgSO4. After filtration the solvent was removed
in vacuo and the reaction crude was purified by column
chromatography (SiO2, hexane/AcOEt, 7:3) to give 179.0 mg (75%)
of pure 19 as a colourless oil. 1H NMR (CDCl3, 300 MHz): δ =
6.59 (dd, J = 5.90, 1.80 Hz, 1 H, 5-H), 6.31 (dd, J = 5.98, 1.40 Hz,
1 H, 6-H), 5.17 (ddd, J = 12.10, 4.36, 2.30 Hz, 1 H, 2-H), 5.14 (m,
1 H, 1-H), 4.98 (dd, J = 4.80, 1.70 Hz, 1 H, 4-H), 2.36 (ddd, J =
12.10, 7.60, 4.80 Hz, 1 H, 3-H), 1.98 (s, 3 H, CH3CϵC-CO2), 1.22
(dd, J = 12.10, 2.10 Hz, 1 H, 3Ј-H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 153.93 (CH3CϵC-CO2), 138.45 (C-5), 132.13 (C-6),
86.62 (CH3CϵC-CO), 79.49 (C-4), 78.07 (C-1), 77.59 (CH3CϵC-
CO), 72.44 (C-2), 33.28 (C-3), 4.23 (CH3CϵC-CO) ppm. IR
Compound 21a: NaH (36.0 mg, 0.76 mmol) and 1-bromobut-2-yne
(0.09 mL, 1.0 mmol) were added to a solution of 20a (75.0 mg,
0.4 mmol) in DMF (2.0 mL) at 0 °C. Purification by column
chromatography (SiO2, hexane/AcOEt, 2:1) gave 80.0 mg (83%) of
pure 21a as a colourless oil. 1H NMR (CDCl3, 300 MHz): δ =
7.25–7.60 (m, 5 H, Ar), 6.65 (dd, J = 4.9, 1.5 Hz, 2 H, 2-H, 3-H),
5.15 (d, J = 1.4 Hz, 1 H, 4-H), 4.95 (dd, J = 5.6, 1.5 Hz, 1 H, 1-H),
4.00 (d, J = 12.0 Hz, 1 H, CH3CϵCCH2O), 3.95 (d, J = 12.0 Hz, 1
H, CH3CϵCCH2O), 2.25 (dd, J = 11.8, 4.9 Hz, 1 H, 6-H), 1.85 (s,
3 H, CH3CϵCCH2O), 1.80 (d, J = 11.8 Hz, 1 H, 6Ј-H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 142.1, 138.1, 134.2, 128.6, 127.2,
126.7 (C-Ar), 85.1 (C-5), 83.5 (C-4), 81.4 (CH3CϵCCH2O), 79.3
(C-1), 74.2 (CH3CϵCCH2O), 54.1 (CH3CϵCCH2O), 42.5 (C-6),
3.7 (CH CϵCCH O) ppm. IR (CHCl ): ν = 2220, 1660, 1215 cm–1.
˜
3
2
3
(CHCl ): ν = 3009, 2957, 2920, 2326, 2243, 1707, 1179, 1027 cm–1.
˜
3
C16H16O2 (240.12): calcd. C 79.97, H 6.71; found C 80.15, H 6.92.
C10H10O3 (178.06): calcd. C 67.41, H 5.66; found C 67.53, H 5.79.
Compound 21b: NaH (63.0 mg, 1.3 mmol) and 1-bromobut-2-yne
(0.11 mL, 1.8 mmol) were added under argon to a solution of 20b
(100.0 mg, 0.71 mmol) in DMF (4.3 mL) at 0 °C. Purification by
column chromatography (SiO2, hexane/AcOEt, 3:1) gave 75.0 mg
(55%) of pure 21b as a colourless oil. 1H NMR (CDCl3, 300 MHz):
δ = 6.45 (dd, J = 4.9, 1.5 Hz, 2 H, 2-H, 3-H), 4.85 (dd, J = 5.6,
1.5 Hz, 1 H, 1-H), 4.55 (d, J = 1.4 Hz, 1 H, 4-H), 3.80 (m, 2 H,
CH3CϵCCH2O), 1.95 (dd, J = 11.2, 5.9 Hz, 1 H, 6-H), 1.80 (m, 5
H, CH3CϵCCH2O, CH3CH2), 1.40 (d, J = 11.2 Hz, 1 H, 6Ј-H),
0.90 (t, J = 7.2 Hz, 3 H, CH3CH2) ppm. 13C NMR (CDCl3,
75 MHz): δ = 136.5 (C-2 or C-3), 134.1 (C-2 or C-3), 82.1 (C-5),
80.9 (C-4), 80.4 (CH3CϵCCH2O), 79.3 (C-1), 74.2
(CH3CϵCCH2O), 52.6 (CH3CϵCCH2O), 38.6 (C-6), 28.1
(CH2CH3), 9.5 (CH2CH3), 3.7 (CH3CϵCCH2O) ppm. IR (CHCl3):
General Procedure for the Synthesis of Compounds 23 and 24: NaH
(3.0 mmol) and the corresponding bromoalkyne (3.0 mmol) were
added to a solution of compound 22 (1.0 mmol) in anhydrous
DMF (6 mL/mmol) under argon at 0 °C. Then the reaction mixture
was stirred at room temp. for 24 h. After the reaction was complete,
the reaction mixture was treated with 1  HCl (10 mL) and then
extracted with Et2O (3ϫ5 mL). The combined organic layers were
washed with 5% NaHCO3 (3ϫ10 mL), dried (MgSO4) and con-
centrated in vacuo. The crude product was purified as indicated in
each case.
Compound 23: NaH (164.0 mg, 3.60 mmol) and 3-bromopropyne
(0.32 mL, 3.60 mmol) were added to a solution of diol 22
(150.0 mg, 1.20 mmol) in DMF (7.0 mL) at 0 °C. Purification by
column chromatography (SiO2, hexane/AcOEt, 8:2) gave 217.0 mg
ν = 2225, 1650, 1225 cm–1. C H O (192.12): calcd. C 74.97, H
˜
12 16
2
1
8.39; found C 75.05, H 8.54.
(91%) of pure 23 as a colourless oil. H NMR (C6D6, 300 MHz):
δ = 6.27 (t, J = 0.90 Hz, 2 H, 2-H, 3-H), 4.76 (m, J = 5.90, 1.60 Hz,
2 H, 5-H, 6-H), 3.92 (dd, J = 2.80, 1.50 Hz, 2 H, 1-H, 4-H), 3.79
(qd, J = 16.00, 2.40 Hz, 4 H, 2ϫHCϵCCH2O), 1.92 (t, J =
2.40 Hz, 2 H, 2ϫHCϵCCH2O) ppm. 13C NMR (C6D6, 75 MHz):
δ = 134.85 (C-2, C-3), 80.48 (2ϫHCϵCCH2O), 79.72 (C-5,
C-6), 75.33 (C-1, C-4), 74.66 (2ϫHCϵCCH2O), 57.51
Esterification Reactions of Compound 15. Synthesis of 3-Methylpro-
piolates 17 and 19
Compound 17: Propiolyl chloride (120 mg, 1.35 mmol, freshly pre-
pared from the corresponding acid) and DMPA (5.4 mg,
0.05 mmol) were added to a solution of compound 15 (50.0 mg,
0.45 mmol) in CH2Cl2 (2.2 mL) under argon at 0°°C. The reaction
mixture was stirred at room temp. overnight. After this time 1 
HCl was added (7 mL) and the mixture was then extracted with
CH2Cl2 (3ϫ10 mL). The crude reaction was washed with NaHCO3
(saturated solution, 15 mL) and NaCl (saturated solution, 15 mL)
and the organic layer dried with MgSO4. After filtration the solvent
was removed in vacuo and the reaction crude was purified by col-
umn chromatography (SiO2, hexane/AcOEt, 7:3) to give 52.0 mg
(71%) of pure 17 as a colourless oil. 1H NMR (CDCl3, 300 MHz):
δ = 6.60 (dd, J = 5.90, 1.80 Hz, 1 H, 5-H), 6.32 (dd, J = 5.90,
1.40 Hz, 1 H, 6-H), 5.21 (ddd, J = 8.00, 4.40, 2.30 Hz, 1 H, 2-H),
5.15 (dm, J = 4.30 Hz, 1 H, 1-H), 5.01 (dd, J = 4.70, 1.40 Hz, 1 H,
4-H), 2.89 (s, 1 H, HCϵCCH2O), 2.38 (ddd, J = 13.20, 7.90,
4.70 Hz, 1 H, 3-H), 1.23 (dd, J = 12.30, 2.00 Hz, 1 H, 3Ј-H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 152.85 (HCϵC-CO2), 138.63 (C-
5), 132.05 (C-6), 79.54 (C-4), 78.00 (C-1), 75.59 (HCϵC-CO2),
(2ϫHCϵCCH O) ppm. IR (CHCl ): ν = 3287, 2961, 2925, 2115,
˜
2
3
1126, 1113, 1093, 798 cm–1. C12H12O3 (204.08): calcd. C 70.57, H
5.92; found C 70.78, H 6.05.
Compound 24: NaH (66.0 mg, 1.40 mmol) and 1-bromobut-2-yne
(0.13 mL, 1.40 mmol) were added to a solution of diol 22 (60.0 mg,
0.5 mmol) in DMF (3.0 mL) at 0 °C. Purification by column
chromatography (SiO2, hexane/AcOEt, 7:3) gave 97.0 mg (89%) of
1
pure 24 as a colourless oil. H NMR (C6D6, 300 MHz): δ = 6.36
(t, J = 0.90 Hz, 2 H, 2-H, 3-H), 4.88 (m, 2 H, 5-H, 6-H), 4.13 (dd,
J = 2.80, 1.60 Hz, 2 H, 1-H, 4-H), 4.02 (dq, J = 15.50, 2.30 Hz, 4
H, 2ϫCH3CϵCCH2O), 1.43 (t,
J
=
2.30 Hz,
6
H,
2ϫCH3CϵCCH2O) ppm. 13C NMR (C6D6, 75 MHz): δ = 134.90
(C-2, C-3), 82.32 (2ϫCH3CϵCCH2O), 79.98 (C-5, C-6),
76.38
(2ϫCH3CϵCCH2O),
75.42
(C-1,
C-4),
58.19
(2ϫCH3CϵCCH2O),
3.22
(2ϫCH3CϵCCH2O) ppm.
IR
(CHCl ): ν = 2921, 2854, 2239, 1716, 1167, 1138, 1023 cm–1.
˜
74.76 (HCϵC-CO ), 73.03 (C-2), 33.33 (C-3) ppm. IR (CHCl ): ν
˜
3
2
3
= 3258, 2922, 2851, 2115, 1713, 1233, 1025 cm–1. C9H8O3 (164.16):
C14H16O3 (232.11): calcd. C 72.39, H 6.94; found C 72.16, H 6.75.
calcd. C 65.85, H 4.91; found C 65.94, H 5.13.
Esterification Reaction of 22. Synthesis of Compound 25: But-2-
Compound 19: Et3N (0.28 mL, 2.0 mmol), but-2-ynoic acid
ynoic acid (157.0 mg, 1.9 mmol), DMPA (38.0 mg, 0.3 mmol) and
(84.0 mg, 2.0 mmol), DMPA (16.0 mg, 0.13 mmol) and DCC DCC (385.0 mg, 1.90 mmol) were added to a solution of com-
(414.0 mg, 2.0 mmol) were added to a solution of compound 15
(150.0 mg, 1.30 mmol) in CH2Cl2 (7.0 mL, 5 mL/mmol) under ar-
gon at 0 °C. The reaction mixture was stirred under argon at room
pound 22 (80.0 mg, 0.62 mmol) in CH2Cl2 (3.1 mL, 5 mL/mmol)
under argon at 0 °C. The reaction mixture was stirred at room
temp. overnight. After this time 1  HCl (10 mL) was added and
828
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 822–832

Polycyclic Derivatives with a Dioxabicyclononane System
then the mixture was extracted with CH2Cl2 (3ϫ10 mL). The
crude reaction was washed with NaHCO3 (saturated solution;
15 mL), NaCl (saturated solution; 15 mL) and the organic layer
dried with MgSO4. After filtration, the solvent was removed in
vacuo, the reaction crude was purified by column chromatography
(SiO2, hexane/AcOEt, 8:2) to give 117.0 mg (72%) of pure 25 as
(1.0 mmol) in CH2Cl2 (25 mL/mmol) under argon. This mixture
was stirred at reflux and when the reaction was complete (between
2–6 h) the solvent was removed in vacuo and the reaction crude
was purified as indicated in each case.
Compound 35: From 16 (60.0 mg, 0.36 mmol) and 34 (0.039 mL,
0.36 mmol) in CH2Cl2 (9.0 mL) and 27 (30.0 mg, 0.036 mmol) in
CH2Cl2 (1.8 mL). After 2 h the reaction crude was purified by col-
umn chromatography (SiO2, hexane/AcOEt, 3:1) to give 54.0 mg
(58%) of 35 as a mixture (E/Z = 1:1). 1H NMR (CDCl3, 300 MHz):
δ = 6.02 (d, J = 4.3 Hz, 1 H, 7-H), 5.95 (m, 2 H, CH=CH), 4.98
(s, 1 H, C=CH2), 4.90 (s, 1 H, C=CH2), 4.75–4.40 (m, 5 H,
CH2OAc, 2-H, 3a-H, 7a-H), 4.15 (d, J = 15.2 Hz, 1 H, 5-H), 4.02
(d, J = 15.2 Hz, 1 H, 5Ј-H), 2.55 (m, 2 H, 3-H, 3Ј-H), 2.01 (s, 3 H,
CH3CO2), 1.90 (s, 3 H, C-CH3) ppm. 13C NMR (CDCl3, 50 MHz):
δ = 172.2 (CO2CH3), 140.7 (C-6), 135.2, 126.4, 118.3 (C-7), 112.7
(C=CH2), 78.7 (C-7a), 76.2 (C-2), 74.3 (C-3a), 65.2 (CH2-O), 60.2
(C-5), 40.3 (C-3), 21.0 (CCH3), 20.5 (CH3CO2) ppm. IR (CHCl3):
1
white solid (m.p. 142.7–144.6 °C). H NMR (CDCl3, 300 MHz): δ
= 6.55 (t, J = 1.00 Hz, 2 H, 5-H, 6-H), 5.22 (dd, J = 2.90, 1.50 Hz,
2 H, 2-H, 3-H), 5.12 (m, 2 H, 1-H, 4-H), 1.99 (s, 6 H, CH3-
CϵCCO2) ppm. 13C NMR (CDCl3, 75 MHz):
δ = 153.03
(2ϫCH3CϵC-CO2), 135.41 (C-5, C-6), 87.66 (2ϫCH3CϵC-CO2),
79.05 (C-1, C-4), 72.04 (2ϫCH3CϵC-CO2), 69.79 (C-2, C-3), 4.41
(2ϫCH CϵC-CO ) ppm. IR (CHCl ): ν = 2928, 2855, 2239, 1714,
˜
3
2
3
1262, 1241, 736 cm–1. C14H12O5 (260.07): calcd. C 64.61, H 4.65;
found C 64.40, H 4.51.
General Procedure for the Metathesis Reactions of Compounds 16
and 18: Catalyst 27 (0.05 mmol) in CH2Cl2 (55 mL/mmol catalyst)
was added to a solution of compounds 16 and 18 (1.0 mmol) in
CH2Cl2 (22 mL/mmol) under argon. This mixture was stirred at
room temp. When the reaction was complete, the solvent was re-
moved in vacuo and the reaction crude was purified as indicated
in each case.
ν = 1720, 1650, 1215 cm–1. C H O (264.14): calcd. C 68.16, H
˜
15 20
4
7.63; found C 68.32, H 7.95.
Compound 36: From 20a (50.0 mg, 0.21 mmol), 34 (0.023 mL,
0.21 mmol) in CH2Cl2 (5.2 mL) and 27 (17.0 mg, 0.021 mmol) in
CH2Cl2 (1.1 mL). After 6 h the reaction crude was purified by col-
umn chromatography (SiO2, hexane/AcOEt, 4:1) to give 42.0 mg
(60%) of 36 as a mixture (E/Z = 1:1). 1H NMR (CDCl3, 300 MHz):
δ = 7.25–7.60 (m, 5 H, Ar), 6.15 (d, J = 5.1 Hz, 1 H, 7-H), 5.75
(m, 2 H, CH=CH), 4.90 (s, 1 H, C=CH2), 4.80 (s, 1 H, C=CH2),
4.75–4.60 (m, 4 H, CH2OAc, 2-H, 7a-H), 4.40 (d, J = 16.2 Hz, 1
H, 5Ј-H), 3.90 (d, J = 16.2 Hz, 1 H, 5-H), 2.40–2.30 (m, 2 H, 3-H,
3Ј-H), 2.05 (s, 3 H, CH3CO), 1.95 (s, 3 H, CCH3) ppm. 13C NMR
(CDCl3, 50 MHz): δ = 172.2 (OCOCH3), 141.2, 140.7 (C-6), 135.2,
128.6, 127.1, 126.4, 126.1, 120.3 (C-7), 114.7 (C=CH2), 82.3 (C-
3a), 79.7 (C-7a), 77.2 (C-2), 66.2 (CH2-O), 62.2 (C-5), 41.4 (C-3),
Compound 28: From 16 (35.0 mg, 0.23 mmol) in CH2Cl2 (5.1 mL)
and 27 (9.6 mg, 12ϫ10–3 mmol) in CH2Cl2 (1.7 mL). After 1 h,
the reaction crude was purified by column chromatography (SiO2,
hexane/AcOEt, 8:2) to give 37.0 mg (88%) 28 as a colourless oil.
1H NMR (CDCl3, 300 MHz): δ = 6.33 (dd, J = 18.20, 11.00 Hz, 1
H, C-6-CH=CH2), 5.99 (ddd, J = 17.15, 10.30, 7.40 Hz, 1 H, C-2-
CH=CH2), 5.98 (m, 1 H, 7-H), 5.25 (ddd, J = 17.10, 1.47, 1.40 Hz,1
H, C-2-CH=CH2trans), 5.16–5.11 (m, 3 H, C-2-CH=CH2cis, C-6-
CH=CH2), 4.47 (d, J = 15.50 Hz, 1 H, 5-H), 4.34 (qm, J = 7.30 Hz,
1 H, 2-H), 4.17–4.05 (m, 2 H, 5Ј-H, 3a-H), 3.97 (m, 1 H, 7a-H),
2.53 (ddd, J = 14.10, 8.00, 6.70 Hz, 1 H, 3-H), 1.85 (ddd, J = 14.10,
7.30, 1.80 Hz, 1 H, 3Ј-H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
140.02 (C-6), 139.03 (C-2-CH=CH2), 135.82 (C-6-CH=CH2),
122.53 (C-7), 117.00 (C-2-CH=CH2), 114.66 (C-6-CH=CH2), 80.40
(C-2), 76.00 (C-3a), 74.44 (C-7a), 64.55 (C-5), 40.01 (C-3) ppm. IR
21.3 (CCH ), 20.6 (CH CO ) ppm. IR (CHCl ): ν = 1710, 1640,
˜
3
3
2
3
1225 cm–1. C21H24O4 (340.17): calcd. C 74.09, H 7.11; found C
74.30, H 7.24.
Compound 37: From 20b (40.0 mg, 0.33 mmol), 34 (0.036 mL,
0.33 mmol) in CH2Cl2 (8.2 mL) and 27 (27.0 mg. 0.033 mmol) in
CH2Cl2 (1.7 mL). After 3 h the reaction crude was purified by col-
umn chromatography (SiO2, hexane/AcOEt, 3:1) to give 32.0 mg
(55%) of 37 as a mixture (E/Z = 1:1). 1H NMR (CDCl3, 300 MHz):
δ = 5.95 (d, J = 4.9 Hz, 1 H, 7-H), 5.65 (m, 2 H, CH=CH), 5.00
(s, 1 H, C=CH2), 4.90 (s, 1 H, C=CH2), 4.75–4.60 (m, 4 H,
CH2OAc, 2-H, 7a-H), 4.40 (d, J = 16.8 Hz, 1 H, 5-H), 4.10 (d, J
= 16.8 Hz, 1 H, 5Ј-H), 2.20 (m, 2 H, 3-H, 3Ј-H), 2.05 (s, 3 H,
CH3CO), 1.95 (s, 3 H, CCH3), 1.35 (q, J = 7.0 Hz, 2 H, CH3CH2),
0.95 (t, J = 7.0 Hz, 3 H, CH3CH2) ppm. 13C NMR (CDCl3,
50 MHz): δ = 172.8 (CO2CH3), 140.7 (C-6), 135.2, 126.4, 117.3 (C-
7), 110.6 (C=CH2), 79.8 (C-3a), 77.6 (C-7a), 73.2 (C-2), 69.2 (CH2-
O), 60.4 (C-5), 39.8 (C-3), 25.2, 21.0 (CCH3), 20.5 (CH3CO2), 9.1
(CHCl ): ν = 3084, 2881, 2836, 1190, 1155, 1054 cm–1. C H O
˜
3
11 14
2
(178.23): calcd. C 74.13, H 7.92; found C 73.91, H 8.06.
Compound 29: From 18 (29.0 mg, 0.18 mmol) in CH2Cl2 (4.0 mL)
and 27 (7.5 mg, 9ϫ10–3 mmol) in CH2Cl2 (1.0 mL). After 3 h, the
reaction crude was purified by column chromatography (SiO2, hex-
ane/AcOEt, 7:3) to give 26.0 mg (79%) of 29 as a colourless oil.
1H NMR (CDCl3, 300 MHz): δ = 6.07 (d, J = 4.50 Hz, 1 H, 7-H),
5.98 (ddd, J = 17.00, 10.30, 7.40 Hz, 1 H, C-2-CH=CH2), 5.25
(ddd, J = 17.20, 1.50, 1.00 Hz, 1 H, CH=CH2trans), 5.12 (ddd, J =
10.20, 1.50, 0.80 Hz, 1 H, CH=CH2cis), 4.99 (m, 1 H, C=CH2), 4.90
(m, 1 H, C=CH2), 4.50 (d, J = 15.30 Hz, 1 H, 5-H), 4.33 (q, J =
7.40 Hz, 1 H, 2-H), 4.13 (dt, J = 15.30, 1.90 Hz, 1 H, 5Ј-H), 4.04
(ddd, J = 6.60, 3.50, 1.80 Hz, 1 H, 3a-H), 3.96 (m, 1 H, 7a-H), 2.52
(ddd, J = 14.00, 7.90, 6.60 Hz, 1 H, 3-H), 1.92 (dd, J = 1.20,
0.50 Hz, 3 H, CH3-C=), 1.83 (ddd, J = 14.00, 7.20, 1.80 Hz, 1 H,
3Ј-H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 140.08 (CH3-C=),
140.03 (C-6), 139.01 (CH=CH2), 118.85 (C-7), 117.06 (CH=CH2),
113.03 (C=CH2), 80.39 (C-2), 76.61 (C-3a), 74.53 (C-7a), 65.58 (C-
(CH CH ) ppm. IR (CHCl ): ν = 1715, 1650, 1220 cm–1. C H O
˜
3
2
3
17 24
4
(292.17): calcd. C 69.84, H 8.27; found C 69.93, H 8.34.
General Procedure for the Metathesis Reactions of Compounds 23
and 24: Catalyst 27 (0.1 mmol) in CH2Cl2 (55 mL/mmol of catalyst)
was added to a solution of compounds 23 and 24 (1.0 mmol) in
CH2Cl2 (22 mL/mmol) under argon. This mixture was stirred at
room temp. and when the reaction was complete, the solvent was
removed in vacuo and the reaction crude was purified as indicated
in each case.
5), 40.04 (C-3), 20.54 (CH -C=) ppm. IR (CHCl ): ν = 3430, 3081,
˜
3
3
2969, 2927, 1170, 1116, 1058, 990 cm–1. C12H16O2 (192.12): calcd.
C 74.97, H 8.39; found C 75.19, H 8.58.
General Procedure for the Metathesis Reactions of Compounds 16,
20a and 20b in the Presence of Allyl Acetate 34: Catalyst 27
(0.1 mmol) in CH2Cl2 (50 mL/mmol of cat.) was added to a solu-
tion of compounds 16, 20a and 20b (1.0 mmol) and allyl acetate 34
Compound 38: From 23 (40.0 mg, 0.20 mmol) in CH2Cl2 (4.3 mL)
and 27 (16.0 mg, 0.02 mmol) in CH2Cl2 (1.1 mL). After 3 h the
reaction crude was purified by column chromatography (SiO2, hex-
ane/AcOEt, 8:2) to give 39.0 mg, (85%) of 38 as a colourless oil.
Eur. J. Org. Chem. 2009, 822–832
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
829

A. Aljarilla, M. C. Murcia, A. G. Csákÿ, J. Plumet
1H NMR (CDCl3, 300 MHz): δ = 6.32 (dd, J = 17.90, 11.10 Hz, 2 138.50 (C-5-CH=CH2), 132.72 (C-2-CH=CH2), 119.59 (C-2-
FULL PAPER
H, 2ϫCH=CH2), 5.98 (dm, J = 4.40 Hz, 2 H, 4-H, 6-H), 5.16 (br.
d, J = 17.90 Hz, 2 H, 2ϫCH=CH2cis), 5.14 (br. d, J = 11.00 Hz, 2
H, 2ϫCH=CH2trans), 4.65 (br. d, J = 15.40 Hz, 2 H, 2-H, 8-H),
CH=CH2), 117.23 (C-5-CH=CH2), 86.66 (CH3CϵCCO2), 82.80
(C-2), 79.21 (C-5), 77.27 (C-3), 72.62 (CH3CϵCCO2), 39.21 (C-4),
4.31 (CH CϵCCO ) ppm. IR (CHCl ): ν = 3082, 2987, 2919, 2848,
˜
3
2
3
4.31 (dd, J = 2.80, 1.30 Hz, 2 H, 9a-H, 9b-H), 4.15 (dt, J = 15.40, 2240, 1708, 1254, 1073 cm–1. C12H14O3 (206.09): calcd. C 69.88, H
2.00 Hz, 2 H, 2Ј-H, 8Ј-H), 4.02 (m, 2 H, 4a-H, 5a-H) ppm. 13C
NMR (CDCl3, 75 MHz): 140.15 (C-3, C-7), 135.31
6.84; found C 70.06, H 7.02.
δ
=
Compound 46: From 17 (25.0 mg, 0.15 mmol) in CH2Cl2 (3.3 mL)
and 31 (4.8 mg, 0.008 mmol) in CH2Cl2 (0.5 mL) at room temp.
After 2 h the reaction crude was purified by column chromatog-
raphy (SiO2, hexane/AcOEt, 7:3) to give 13.0 mg (44%) of 46 as a
colourless oil. 1H NMR (CDCl3, 300 MHz): δ = 5.96 (ddd, J =
17.30, 10.20, 7.00 Hz, 1 H, C-5-CH=CH2), 5.89 (ddd, J = 17.20,
10.40, 6.70 Hz, 1 H, C-2-CH=CH2), 5.47–5.38 (m, 2 H, 3-H, C-2-
CH=CH2), 5.24 (dd, J = 10.20, 1.30 Hz, 1 H, C-2-CH=CH2cis),
5.23 (dd, J = 17.20, 1.10 Hz, 1 H, C-5-CH=CH2trans), 5.17 (dt, J =
10.40, 1.20 Hz, 1 H, C-5-CH=CH2cis), 4.43–4.33 (m, 2 H, 2-H, 5-
H), 2.90 (s, 1 H, CO2CϵCH), 2.59 (ddd, J = 14.20, 7.80, 6.75 Hz,
1 H, 4-H), 1.90 (ddd, J = 14.20, 7.10, 3.20 Hz, 1 H, 4Ј-H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 152.44 (HCϵCCO2), 138.38 (C-
5-CH=CH2), 132.48 (C-2-CH=CH2), 119.76 (C-2-CH=CH2),
117.25 (C-5-CH=CH2), 82.78 (C-2), 79.18 (C-5), 77.90 (C-3), 77.60
(2ϫCH=CH2), 121.30 (C-4, C-6), 114.75 (2ϫCH=CH2), 76.24 (C-
9a, C-9b), 73.16 (C-4a, C-5a), 64.38 (C-2, C-8) ppm. IR (CHCl3):
ν = 2924, 2853, 1067, 1013, 893 cm–1. C H O (232.11): calcd. C
˜
14 16
3
72.39, H 6.94; found C 72.22, H 6.72.
Compound 39: From 24 (35.0 mg, 0.15 mmol) in CH2Cl2 (3.3 mL)
and 27 (12.0 mg, 0.015 mmol) in CH2Cl2 (0.8 mL). After 3 h the
reaction crude was purified by column chromatography (SiO2, hex-
ane/AcOEt, 8:2) to give 36.5 mg (93%) of 39 as a colourless oil.
1H NMR (CDCl3, 300 MHz): δ = 6.09 (br. d, J = 4.10 Hz, 2 H, 4-
H, 6-H), 5.02 (, 2 H, 2ϫCH3-C=CH2), 4.94 (br. s, 2 H, 2ϫCH3-
C=CH2), 4.69 (br. d, J = 15.10 Hz, 2 H, 2-H, 8-H), 4.30 (dd, J =
2.80, 1.30 Hz, 2 H, 9a-H, 9b-H), 4.19 (dt, J = 15.10, 2.00 Hz, 2 H,
2Ј-H, 8Ј-H), 4.05 (m, 2 H, 4a-H, 5a-H), 1.92 (s, 6 H, 2ϫCH3-
C=CH2) ppm. 13C NMR (CDCl3, 75 MHz): δ = 141.65 (2ϫCH3-
C=CH2), 140.22 (C-3, C-7), 117.98 (C-4, C-6), 113.37 (2ϫCH3-
C=CH2), 76.21 (C-9a, C-9b), 73.62 (C-4a, C-5a), 65.68 (C-2, C-8),
(HCϵCCO ), 75.57 (HCϵCCO ), 39.16 (C-4) ppm. IR (CHCl ): ν
˜
2
2
3
= 3528, 2922, 2851, 1713, 1233, 1025 cm–1. C11H12O3 (192.08):
20.48 (2ϫCH -C=CH ) ppm. IR (CHCl ): ν = 2924, 2853, 1722,
˜
calcd. C 68.74, H 6.29; found C 68.99, H 6.42.
3
2
3
1121, 1055, 1016, 889 cm–1. C16H20O3 (260.33): calcd. C 73.82, H
Metathesis Reaction of Compound 25: Catalyst 31 (8.7 mg,
0.0015 mmol) in CH2Cl2 (0.8 mL, 55 mL/mmol of catalyst) was
added to a solution of 25 (30.0 mg, 0.14 mmol) in CH2Cl2 (3.0 mL,
22 mL/mmol) under argon. This mixture was stirred at room temp.
overnight. After this time, the solvent was removed in vacuo and
the reaction crude was purified by column chromatography (SiO2,
CH2Cl2/AcOEt, 7:3) to give 15 mg (37%) of 48 as a colourless oil.
1H NMR (CDCl3, 300 MHz): δ = 5.92 (ddd, J = 17.30, 10.30,
7.30 Hz, 2 H, 2ϫCH=CH2), 5.51 (dd, J = 4.10, 1.60 Hz, 2 H, 3-
H, 4-H), 5.38 (dt, J = 17.30, 1.00 Hz, 2 H, 2ϫCH=CH2trans), 5.31
(dt, J = 10.30, 1.00 Hz, 2 H, 2ϫCH=CH2cis), 4.57 (ddm, J = 7.30,
7.74; found C 74.06, H 7.50.
General Procedure for the Metathesis Reactions of Compounds 17
and 19: Catalyst 31 (0.05 mmol) in CH2Cl2 (55 mL/mmol of cat.)
was added to a solution of compounds 17 and 19 (1.0 mmol) in
CH2Cl2 (22 mL/mmol) under argon. This mixture was stirred at
different temperatures. When the reaction was complete, the solvent
was removed in vacuo and the reaction crude was purified as indi-
cated in each case.
Compounds 44 and 45: From 19 (20.0 mg, 0.14 mmol) in CH2Cl2
(2.5 mL) and 31 (4.0 mg, 0.006 mmol) in CH2Cl2 (0.3 mL). After
4 h (CH2Cl2, sealed tube, oil bath 50–60 °C) the reaction crude was
purified by column chromatography (SiO2, hexane/AcOEt, 8:2) to
give 10.0 mg (43%) of 44 and 13.0 mg (56%) of 45 both as colour-
less oils.
Compound 44: 1H NMR (CDCl3, 300 MHz): δ = 6.75 (d, J =
5.60 Hz, 1 H, 7-H), 5.92 (ddd, J = 17.20, 10.15, 7.15 Hz, 1 H,
CH=CH2), 5.46 (m, 1 H, CH2=C), 5.28 (dt, J = 17.20, 1.20 Hz, 1
H, CH=CH2trans), 5.21 (q, J = 1.55 Hz, 1 H, CH2=C), 5.17 (dt, J
= 10.15, 1.20 Hz, 1 H, CH=CH2cis), 5.00 (ddd, J = 6.20, 4.20,
2.30 Hz, 1 H, 3a-H), 4.48 (q, J = 7.15 Hz, 1 H, 2-H), 4.29 (dd, J
= 5.60, 4.20 Hz, 1 H, 7a-H), 4.48 (q, J = 7.15 Hz, 1 H, 2-H), 2.62
(ddd, J = 14.20, 8.30, 6.20 Hz, 1 H, 3-H), 2.20 (ddd, J = 14.20,
6.20, 2.30 Hz, 1 H, 3Ј-H), 2.00 (dd, J = 1.30, 0.8 Hz, 3 H,
CH3C=) ppm. 13C NMR (CDCl3, 75 MHz): δ = 161.13 (C-5),
139.37 (C-6), 137.70 (CH=CH2), 136.40 (CH2=C), 133.73 (C-7),
118.99 (CH2=C), 117.39 (CH=CH2), 79.98 (C-3a), 79.81 (C-2),
4.10 Hz, 2 H, 2-H, 5-H), 2.01 (s, 6 H, 2ϫCH3CϵCCO2) ppm. 13
C
NMR (CDCl3, 75 MHz): δ = 152.61 (2ϫCH3CϵCCO2), 132.66
(2ϫCH=CH2), 120.24 (2ϫCH=CH2), 87.44 (2ϫCH3CϵCCO2),
79.83 (C-2, C-5), 74.26 (C-3, C-4), 71.83 (2ϫCH3CϵCCO2), 4.20
(2ϫCH CϵCCO ) ppm. IR (CHCl ): ν = 2920, 2852, 1718, 1262,
˜
3
2
3
1244, 1056 cm–1. C16H16O5 (288.1): calcd. C 66.66, H 5.59; found
C 66.89, H 5.31.
General Procedure for the Diels–Alder Cycloaddition of Compounds
28, 29 and 44: N-Phenylmaleimide (1.0 mmol) was added to a solu-
tion of compounds 28, 29 and 44 (1.0 mmol) in CH2Cl2 (10 mL/
mmol) under argon. This mixture was stirred at room temp. for 4–
7 d. When the reaction was complete, the solvent was removed in
vacuo and the reaction crude was purified as indicated in each case.
Compound 50: From 28 (20.0 mg, 0.11 mmol) in CH2Cl2 (1.0 mL)
and N-phenylmaleimide (19.0 mg). After 7 d the reaction crude was
purified by column chromatography (SiO2, hexane/AcOEt, 7:3) to
give 34.0 mg (86%) of 50 as a colourless oil. 1H NMR (CDCl3,
300 MHz): δ = 7.42–7.34 (m, 3 H, Ar-H), 7.22–7.16 (m, 2 H, Ar-
H), 5.97 (ddd, J = 17.10, 10.30, 7.20 Hz, 1 H, CH=CH2), 5.73 (m,
1 H, 6-H), 5.32 (dt, J = 17.10, 1.30 Hz, 1 H, CH=CH2trans), 5.18
71.08 (C-7a), 39.89 (C-3), 22.00 (CH C=) ppm. IR (CHCl ): ν =
˜
3
3
2922, 2857, 17204, 1246, 1070, 1057 cm–1. C12H14O3 (206.09):
calcd. C 69.88, H 6.84; found C 69.63, H 6.96.
Compound 45: 1H NMR (CDCl3, 300 MHz): δ = 5.95 (ddd, J =
17.30, 10.20, 7.20 Hz, 1 H, C-5-CH=CH2), 5.90 (ddd, J = 17.10, (ddd, J = 10.30, 1.30, 0.80 Hz, 1 H, CH=CH2cis), 4.50 (dd, J =
10.40, 6.60 Hz, 1 H, C-2-CH=CH2), 5.46–5.36 (m, 2 H, C-2- 4.40, 1.60 Hz, 1 H, 10c-H), 4.40 (dd, J = 4.40, 3.00 Hz, 1 H, 3a-
CH=CH2, 3-H), 5.33–5.25 (m, 2 H, 2ϫCH=CH2), 5.17 (dt, J =
H), 4.32 (dm, J = 14.00 Hz, 1 H, 5-H), 4.21 (q, J = 7.20 Hz, 1 H,
10.20, 1.20 Hz, 1 H, C-5-CH=CH2), 4.41–4.32 (m, 2 H, 2-H, 5- 2-H), 3.88 (dqd, J = 14.00, 2.50, 1.80 Hz, 1 H, 5Ј-H), 3.49 (dd, J
H), 2.57 (ddd, J = 14.00, 7.70, 6.60 Hz, 1 H, 4-H), 1.99 (s, 3 H,
CH3CϵCCO2), 1.88 (ddd, J = 14.00, 7.20, 3.40 Hz, 1 H, 4Ј-
H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 153.51 (CH3CϵCCO2),
= 8.80, 5.90 Hz, 1 H, 10a-H), 3.34 (ddd, J = 8.80, 7.20, 1.40 Hz, 1
H, 7a-H), 2.85 (ddd, J = 15.25, 7.20, 1.40 Hz, 1 H, 7-H), 2.80 (m,
1 H, 10b-H), 2.57 (dd, J = 14.00, 7.20 Hz, 1 H, 3-H), 2.27 (m, 1
830
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 822–832

Polycyclic Derivatives with a Dioxabicyclononane System
H, 7Ј-H), 1.82 (ddd, J = 14.00, 8.40, 3.00 Hz, 1 H, 3Ј-H) ppm. 13C H), 3.53 (dd, J = 8.70, 5.90 Hz, 2 H, 1c-H, 15a-H), 3.35 (dd, J =
NMR (CDCl3, 75 MHz): δ = 178.91 (C-10), 178.09 (C-8), 138.34 8.70, 6.80 Hz, 2 H, 4a-H, 12a-H), 2.86 (dd, J = 15.30, 6.80 Hz, 2
(CH=CH2), 136.88 (C-5a), 132.18 (C-Ar), 129.55 (2ϫCH-Ar), H, 5-H, 12-H), 2.79 (m, 2 H, 1b-H, 15b-H), 2.30 (m, 2 H, 5Ј-H,
129.10 (CH-Ar), 126.82 (2ϫCH-Ar), 119.76 (C-6), 117.24 12Ј-H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 178.57 (C-4, C-13),
(CH=CH2), 78.44 (C-2), 78.18 (C-3a), 77.00 (C-10c), 66.27 (C-5), 177.68 (C-2, C-15), 136.10 (C-6a, C-10a), 131.82 (2ϫC-Ar), 129.31
44.23 (C-10a), 40.94 (C-7a), 40.23 (C-3), 37.22 (C-10b), 25.09 (C-
(4ϫCH-Ar), 128.90 (2ϫCH-Ar), 126.53 (4ϫCH-Ar), 119.89 (C-
6, C-11), 78.15 (C-8a, C-8b), 74.05 (C-1a, C-15c), 67.81 (C-7, C-
10), 43.29 (C-1c, C-15a), 40.21 (C-4a, C-12a), 37.26 (C-1c, C-11b),
7) ppm. IR (CHCl ): ν = 2924, 2854, 1707, 1385 cm–1. C H NO
˜
3
21 21
4
(351.40): calcd. C 70.78, H 6.02; found C 70.53, H 5.80.
24.29 (C-5, C-12) ppm. IR (CHCl ): ν = 3057, 2920, 2851, 1705,
˜
3
Compound 51: From 29 (17.0 mg, 0.09 mmol) in CH2Cl2 (0.9 mL)
and N-phenylmaleimide (15.0 mg). After 5 d the reaction crude was
purified by column chromatography (SiO2, hexane/AcOEt, 7:3) to
give 26.0 mg (81%) of 51 as a colourless oil. 1H NMR (CDCl3,
300 MHz): δ = 7.49–7.34 (m, 3 H, Ar-H), 7.18–7.13 (m, 2 H, Ar-
H), 5.93 (ddd, J = 17.20, 10.20, 7.20 Hz, 1 H, CH=CH2), 5.30 (dm,
J = 17.20 Hz, 1 H, CH=CH2trans), 5.17 (dm, J = 10.20 Hz, 1 H,
CH=CH2cis), 4.49 (br. d, J = 14.20 Hz, 1 H, 5-H), 4.47 (dd, J =
4.40, 1.80 Hz, 1 H, 10c-H), 4.31 (m, 1 H, 3a-H), 4.22 (q, J =
7.20 Hz, 1 H, 2-H), 3.92 (dm, J = 14.20 Hz, 1 H, 5Ј-H), 3.44 (dd,
J = 8.80, 5.60 Hz, 1 H, 10a-H), 3.31 (ddd, J = 8.80, 7.20, 1.50 Hz,
1 H, 7a-H), 2.78 (m, 1 H, 10b-H), 2.68 (dd, J = 14.70, 1.50 Hz, 1
H, 7-H), 2.56 (dt, J = 14.00, 7.20 Hz, 1 H, 3-H), 2.38 (m, 1 H, 7Ј-
H), 1.83 (ddd, J = 14.00, 7.20, 2.70 Hz, 1 H, 3Ј-H), 1.71 (m, 3 H,
CH3) ppm. 13C NMR (CDCl3, 75 MHz): δ = 178.85 (C-10), 178.35
(C-8), 138.51 (CH=CH2), 132.19 (C-Ar), 129.62 (2ϫCH-Ar),
129.13 (CH-Ar), 128.21 (C-6), 127.21 (C-5a), 126.80 (2ϫCH-Ar),
117.22 (CH=CH2), 78.45 (C-2), 77.61 (C-3a), 77.45 (C-10c), 63.45
(C-5), 44.77 (C-10a), 40.86 (C-7a), 40.22 (C-3), 37.63 (C-10b), 31.70
1328, 1153 cm–1. C34H30N2O7 (578.21): calcd. C 70.58, H 5.23;
found C 70.73, H 5.40.
Compound 54: From 39 (16.0 mg, 0.06 mmol) in CH2Cl2 (0.6 mL)
and N-phenylmaleimide (21.0 mg). Purification by column
chromatography (SiO2, hexane/AcOEt, 7:3) gave 32.0 mg (85%) of
1
54 as a colourless oil. H NMR (CDCl3, 300 MHz): δ = 7.50–7.35
(m, 6 H, Ar-H), 7.19–7.14 (m, 4 H, Ar-H), 4.67 (m, 4 H, 1a-H, 7-
H, 10-H, 15c-H), 4.43 (dd, J = 3.50, 1.20 Hz, 2 H, 8a-H, 8b-H),
3.91 (br. d, J = 14.00 Hz, 2 H, 7Ј-H, 10Ј-H), 3.48 (dd, J = 8.70,
5.60 Hz, 2 H, 1c-H, 15a-H), 3.32 (ddd, J = 8.70, 7.00, 1.50 Hz, 2
H, 4a-H, 12a-H), 2.76 (m, 2 H, 1b-H, 15b-H), 2.68 (dd, J = 14.80,
1.50 Hz, 2 H, 5-H, 12-H), 2.40 (dd, J = 14.80, 7.00 Hz, 2 H, 5Ј-H,
12Ј-H), 1.72 (s, 6 H, 2ϫCH3) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 178.57 (C-4, C-13), 177.89 (C-2, C-15), 131.84 (2ϫC-Ar), 129.37
(4ϫCH-Ar), 128.91 (2ϫCH-Ar), 128.21 (C-6, C-11), 126.80 (C-
6a, C-10a), 126.50 (4ϫCH-Ar), 126.50 (C-8a, C-8b), 74.23 (C-1a,
C-15c), 64.74 (C-7, C-10), 43.60 (C-1c, C-15a), 40.21 (C-4a, C-12a),
37.86 (C-1b, C-11b), 31.46 (C-5, C-12), 18.85 (2ϫ-CH3) ppm. IR
(CHCl ): ν = 2923, 2853, 1705, 1384, 1090 cm–1. C H N O
˜
(C-7), 18.84 (CH ) ppm. IR (CHCl ): ν = 2920, 2851, 1707, 1384,
˜
3
36 34
2
7
3
3
1190 cm–1. C22H23NO4 (365.42): calcd. C 72.31, H 6.34; found C
(606.24): calcd. C 71.27, H 5.65; found C 70.09, H 5.79.
72.56, H 6.60.
Supporting Information (see also the footnote on the first page of
this article). 1H and 13C NMR spectra for all compounds described
in this paper and results of the NOESY experiments for com-
pounds 50 and 54. The results of the COSY (45), HMQC and
HMBC NMR experiments on these compounds are available upon
request from the senior author of this article.
Compound 52: From 42 (20.0 mg, 0.1 mmol) in CH2Cl2 (1.0 mL)
and N-phenylmaleimide (15.0 mg). After 4 d the reaction crude was
purified by column chromatography (SiO2, hexane/AcOEt, 7:3) to
give 23.0 mg (68%) of 52 as a colourless oil. 1H NMR (CDCl3,
300 MHz): δ = 7.51–7.38 (m, 3 H, Ar-H), 7.14–7.10 (m, 2 H, Ar-
H), 5.93 (ddd, J = 17.00, 10.10, 7.80 Hz, 1 H, CH=CH2), 5.23 (dm,
J = 17.00 Hz, 1 H, CH=CH2trans), 5.13 (dm, J = 10.10 Hz, 1 H,
CH=CH2cis), 5.03 (dd, J = 4.60, 1.90 Hz, 1 H, 3a-H), 4.56 (d, J =
1.90 Hz, 1 H, 10c-H), 4.50 (m, 1 H, 2-H), 3.53 (m, 2 H, 7a-H, 10a-
H), 3.06 (m, 1 H, 10b-H), 3.01 (dd, J = 15.00, 1.90 Hz, 1 H, 7-H),
2.56 (m, 2 H, 7Ј-H, 3-H), 2.45 (dd, J = 2.30, 0.70 Hz, 3 H, CH3),
2.19 (dd, J = 14.30, 4.00 Hz, 1 H, 3Ј-H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 177.49 (C-10), 177.05 (C-8), 162.75 (C-5), 157.78 (C-
Acknowledgments
The Ministerio de Educación y Ciencia (MEC) (Spain, Projects 96-
0641 and CTQ-2006-15279–03–01) is gratefully thanked for finan-
cial support. A. A. and M. C. M. thank the MEC for grants.
6), 138.90 (CH=CH2), 131.59 (C-Ar), 129.74 (2ϫCH-Ar), 129.51 [1] For a general treatise, see: a) R. H. Grubbs (Ed.), Handbook of
Metathesis, three-volume set, Wiley-VCH, Weinheim, 2003.
See, in particular, vol. 2, “Applications in Organic Synthesis”.
For other selected, comprehensive and recent accounts, see: b)
R. H. Grubbs, T. M. Trnka, “Ruthenium-Catalyzed Olefin Me-
tathesis” in Ruthenium in Organic Synthesis (Ed.: S. I. Murah-
ashi), Wiley-VCH, Weinheim, 2006, chapter 6; c) M. Mori,
“Recent Progress in Metathesis Reactions” in New Frontiers in
Asymmetric Catalysis (Eds.: M. Koinichi, M. Lautens), Wiley-
VCH, Weinheim, 2007, chapter 6, pp. 153–206; d) J. C. Mol,
P. W. N. M. van Leeuwen, “Metathesis of Alkenes” in Hand-
book of Heterogeneous Catalysis (Eds.: G. Ertl, H. Knötzinger,
F. Schüth, J. Weitkamp), 2nd ed., Wiley-VCH, Weinheim, 2008,
vol. 7, pp. 3240–3256.
(CH-Ar), 126.69 (2ϫCH-Ar), 117.12 (C-5a), 117.15 (CH=CH2),
79.15 (C-3a), 78.80 (C-2), 76.91 (C-10c), 44.08 (C-7a), 40.76 (C-3),
39.46 (C-10a), 37.84 (C-10b), 35.41 (C-7), 24.00 (CH3) ppm. IR
(CHCl ): ν = 2924, 2854, 1707, 1386, 1190 cm–1. C H NO
˜
3
22 21
5
(365.42): calcd. C 69.64, H 5.58; found C 69.87, H 5.79.
General Procedure for the Diels–Alder Cycloaddition of Compounds
38 and 39: N-Phenylmaleimide (2.0 mmol of) was added to a solu-
tion of compounds 38 and 39 (1.0 mmol) in CH2Cl2 (10 mL/mmol)
under argon. After 4 d the reaction was completed, the solvent was
removed at vacuo and the reaction crude was purified as indicated
in each case.
[2] For two selected reviews, see: a) A. H. Hoveyda, A. R. Zhugra-
lin, Nature 2007, 450, 243–251; b) S. Kotha, K. Lahiri, Synlett
2007, 2767–2784.
[3] For recent reviews, see: a) S. T. Diver, J. Mol. Catal. A 2006,
254, 29–42; b) E. C. Hansen, D. Lee, Acc. Chem. Res. 2006, 39,
509–519; c) H. Villar, M. Frings, C. Bolm, Chem. Soc. Rev.
2007, 36, 55–66; d) M. Mori, Adv. Synth. Catal. 2007, 349,
121–135.
Compound 53: From 38 (24.0 mg, 0.10 mmol) in CH2Cl2 (1.0 mL)
and N-phenylmaleimide (36.0 mg). Purification by column
chromatography (SiO2, hexane/AcOEt, 1:1) gave 54.0 mg (90%) of
1
53 as a colourless oil. H NMR (CDCl3, 300 MHz): δ = 7.50–7.34
(m, 6 H, Ar-H), 7.2–7.16 (m, 4 H, Ar-H), 5.76 (br. s, 2 H, 6-H, 11-
H), 4.68 (dd, J = 3.40, 1.20 Hz, 2 H, 1a-H, 15c-H), 4.45 (m, 4 H,
7-H, 8a-H, 8b-H, 10-H), 3.95 (dm, J = 13.70 Hz, 2 H, 7Ј-H, 10Ј-
Eur. J. Org. Chem. 2009, 822–832
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
831

A. Aljarilla, M. C. Murcia, A. G. Csákÿ, J. Plumet
FULL PAPER
[4]
proaches to these compounds and derivatives, see: c) M. Sa-
saki, N. Akiyama, K. Tsubone, M. Shoji, M. Oikawa, R. Sakai,
Tetrahedron Lett. 2007, 48, 5697–5700; d) K. Takahashi, T.
Matsumura, J. Ishihara, S. Hatakeyama, Chem. Commun. 2007,
4158–4160; e) M. Sasaki, K. Tsubone, K. Aoki, N. Akiyama,
M. Shoji, M. Oikawa, R. Sakai, K. Shimamoto, J. Org. Chem.
2008, 73, 264–273, and references cited within these papers.
[18] For reviews, see: a) M. A. Brimble, Tetrahedron 2000, 56, 1937–
1992; b) J. Sperry, P. Bachu, M. A. Brimble, Nat. Prod. Rep.
2008, 25, 376–400, and references cited therein; see also: c)
M. A. Brimble, Pure Appl. Chem. 2000, 72, 1635–1639; d) S.
Claessens, G. Verniest, J. Jacobs, E. Van Hende, P. Habonim-
ana, T. N. Van, L. Van Puyuelde, N. De Kimpe, Synlett 2007,
829–850.
[19] For reviews, see: a) H. B. Mereyala, M. Joe, Curr. Med. Chem.:
Anti-Cancer Agents 2001, 1, 293–300; b) G. Zhao, B. Wu, X. Y.
Wu, Y. Z. Zhang, Mini-Rev. Org. Chem. 2005, 2, 333–353; c)
A. de Fátima, L. V. Modolo, L. S. Conegero, R. A. Pilli, C. V.
Ferrera, L. K. Kohn, J. E. de Carvalho, Curr. Med. Chem.
2006, 13, 3371–3384; d) M. Mondon, J. P. Gesson, Curr. Org.
Synth. 2006, 3, 41–75; see also: e) S. H. Inayat-Hussein, A. B.
Osman, L. B. Din, N. Taniguchi, Toxicol. Lett. 2002, 131, 153–
159.
[20] a) M. S. M. Timmer, M. Verdoes, L. A. J. M. Sliedregt, B. A.
van der Marel, J. H. van Boom, H. S. Overkleeft, J. Org. Chem.
2003, 68, 9406–9411; b) A. Aljarilla, M. C. Murcia, J. Plumet,
Synlett 2006, 831–832.
[21] O. Arjona, A. G. Csákÿ, M. C. Murcia, J. Plumet, Tetrahedron
Lett. 2000, 41, 9777–9779.
[22] a) For a review, see: P. Vogel, J. Cossy, J. Plumet, O. Arjona,
Tetrahedron 1999, 55, 13521–13642; for another method for the
synthesis of 14 in an optically pure form, see: b) A. Forster, T.
Kovac, H. Mosimann, P. Vogel, Tetrahedron: Asymmetry 1999,
10, 567–571.
a) For the first report, see: A. Kinoshita, N. Sakakibara, M.
Mori, J. Am. Chem. Soc. 1997, 119, 12388–12389; For the first
review, see: b) M. Mori, Alkene Metathesis in Organic Synthe-
sis, Topics in Organometallic Chemistry, Springer, Berlin, 1998,
vol. 1, pp. 133–154.
a) S. Kotha, N. Sreenivasachary, E. Brahmachary, Tetrahedron
Lett. 1998, 39, 2805–2808; b) S. Kotha, N. Sreenivasachary, E.
Brahmachary, Eur. J. Org. Chem. 2001, 787–792; c) S. Kotha,
S. Halder, E. Brahmachary, Tetrahedron 2002, 58, 9203–9208;
d) S. Kotha, K. Mandal, S. Banerjee, S. M. Robin, Eur. J. Org.
Chem. 2007, 1244–1255; e) S. Kotha, P. Khedkar, Synthesis
2008, 2925–2928.
a) R. Duboc, Ch. Henaut, M. Savignac, J. P. Genet, H. Bhat-
nager, Tetrahedron Lett. 2001, 42, 2461–2464; b) N. Desroy, F.
Robert-Peillard, J. Toueg, R. Duboc, Ch. Henaut, M. N. Rager,
M. Savignac, J. P. Genet, Eur. J. Org. Chem. 2004, 4840–4849;
c) N. Desroy, F. Robert-Peillard, J. Toueg, Ch. Henaut, R. Du-
boc, M. N. Rager, M. Savignac, J. P. Genet, Synthesis 2004,
2665–2672.
a) K. P. Kaliappan, V. Ravikumar, Org. Biol. Chem. 2005, 3,
848–851; b) K. P. Kaliappan, A. V. Subrahmanyan, Org. Lett.
2007, 9, 1121–1124.
a) S. C. Schurer, S. Blechert, Tetrahedron Lett. 1999, 40, 1877–
1880; b) S. Bentz, S. Laschat, Synthesis 2000, 1766–1773; c) M.
Moreno-Mañas, R. Pleixats, A. Santamaria, Synlett 2001,
1784–1786; d) H. Guo, R. Madhusaw, F. W. Shen, R. S. Liu,
Tetrahedron 2002, 58, 5627–5637; e) S. Imhof, S. Blechert, Syn-
lett 2003, 609–614; f) H. Y. Lee, H. Y. Kim, H. Tae, B. G. Kim,
J. Lee, Org. Lett. 2003, 5, 3439–3442; g) Y. K. Yang, J. Tae,
Synlett 2003, 2017–2020; h) M. Rosillo, G. Domínguez, L. Cas-
arrubios, U. Amador, J. Pérez-Castells, J. Org. Chem. 2004, 69,
2084–2093; i) S. Mix, S. Blechert, Org. Lett. 2005, 7, 2015–
2018; j) K. C. Majumdar, H. Rahaman, S. Muhuri, B. Roy,
Synlett 2006, 466–468; k) S. K. Chattopadhyay, T. Biswas, K.
Neogi, Chem. Lett. 2006, 35, 376–377; l) F. D. Boyer, I. Hanna,
Org. Lett. 2007, 9, 715–718; m) L. Evanno, A. Deville, B. Bodo,
B. Nay, Tetrahedron Lett. 2007, 48, 4331–4333; n) J. C. Lovely,
Y. Chen, E. V. Ekamayake, Heterocycles 2007, 74, 873–894; o)
R. Ben-Othman, M. Othman, S. Coste, B. Decroix, Tetrahe-
dron 2008, 64, 559–567; p) S. Aritmitsu, B. Fernández, C.
del Pozo, S. Fustero, G. B. Hammond, J. Org. Chem. 2008, 73,
2656–2661.
[5]
[6]
[7]
[8]
[23] P. Vogel, D. Fattori, F. Gasparini, C. le Drian, Synlett 1990,
173–185.
[24] O. Arjona, R. Fernández, A. Mallo, S. Pérez, J. Plumet, J. Org.
Chem. 1989, 54, 4158–4164.
[25] The structures of the compounds synthesized in this paper were
1
secured by IR and H and 13C NMR spectroscopy and com-
bustion analysis. In some cases HMQC, HMBC, COSY 45 and
MS experiments were also used; see Supporting Information.
[26] For illustrative accounts of alkyne metathesis, see: a) A.
Fürstner, P. W. Davies, Chem. Commun. 2005, 2307–2320; b)
A. Mortreux, O. Coutellier, J. Mol. Catalyst 2006, 254, 96–104;
for an interesting note on the mechanism of alkyne metathesis,
see: c) U. H. F. Bunz, Science 2005, 308, 216–217.
[27] See, for instance: O. Coutellier, A. Mortreux, Adv. Synth. Catal.
2007, 349, 2259–2263, and references cited therein.
[28] a) J. A. Smulik, S. T. Diver, Org. Lett. 2000, 2, 2271–2274; b)
J. A. Smulik, S. T. Diver, J. Org. Chem. 2000, 65, 1788–1792.
[29] M. Mori, N. Sakakibara, A. Kinoshita, J. Org. Chem. 1998,
63, 6082–6083.
[9]
[10]
C. S. Poulsen, R. Madsen, J. Org. Chem. 2002, 67, 4441–4449.
Y. K. Yang, J. H. Choi, J. Tae, J. Org. Chem. 2005, 70, 6995–
6998.
[11] G. Zheng, T. J. Dougherty, R. K. Pandey, R. K. Pandey, Chem.
Commun. 1999, 2469–2470.
[12] For a review, see: M. North, Adv. Strain. Interesting Molecules
2000, 8, 145–185.
[13] For a review, see: R. Madan, A. Srivastava, R. C. Anand, J. K.
Varma, Prog. Polym. Sci. 1998, 23, 621–663.
[14] a) D. Banti, M. North, Tetrahedron Lett. 2002, 43, 1561–1564;
b) D. Banti, M. North, Adv. Synthesis Catal. 2002, 344, 694– [30] A. Aljarilla, J. Plumet, Synthesis 2008, 3516–3524.
704; see also: c) E. Groaz, D. Banti, M. North, Eur. J. Org. [31] O. Arjona, A. G. Csákÿ, M. C. Murcia, J. Plumet, J. Org.
Chem. 2007, 3727–3745.
Chem. 1999, 64, 9739–9741. For a discussion on the compati-
bility of catalyst 27 with conjugated electron-deficient alkenes,
see pp. 1903–1904 of ref.[15c]. For a ROM–RCM reaction of an
oxanorbornenic α,β-unsaturated ketone, see: C. L. Chandler,
A. J. Phillips, Org. Lett. 2005, 7, 3493–3495.
[15] For a review of metathesis reactions in oxa- and azanorbornene
derivatives, see; a) O. Arjona, A. G. Csákÿ, J. Plumet, Eur. J.
Org. Chem. 2003, 611–622; see also: b) O. Arjona, A. G. Csákÿ,
J. Plumet, Synthesis 2000, 857–861; c) S. J. Connon, S. Blechert,
Angew. Chem. Int. Ed. 2003, 42, 1900–1923; d) R. Medel, J.
Plumet, Targets Heterocycl. Systems 2004, 8, 162–186.
[16] A. Basso, L. Banfi, R. Riva, R. Guanti, Tetrahedron 2006, 62,
8830–8837.
[32] See ref.[20b]. Commercially available catalyst 43 shows efficienc-
ies similar to catalyst 31 but with different substrate selectivity.
Both catalysts promote ROM–CM reactions even in unstrained
cycloalkenes. See, for instance: S. Randl, S. J. Connon, S. Ble-
chert, Chem. Commun. 2001, 1796–1797.
[17] For reviews, see: a) M. Oikawa, M. Sasaki, Tohoku J. Agricul-
tural Res. 2006, 57, 59–65; b) R. Sakai, G. T. Swanson, M.
Sasaki, K. Shimamoto, H. Kamiya, Central Nervous System
Agent Med. Chem. 2006, 6, 83–108; for recent synthetic ap-
[33] See p. 1904 of ref.[15c], and references cited therein.
Received: September 25, 2008
Published Online: January 8, 2009
832
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 822–832