Combination of RCM and the Pauson-Khand reaction: One-step synthesis of tricyclic structures

Article abstract of DOI:10.1002/ejoc.200800332

The combination of ring-closing metathesis (RCM) followed by an intramolecular Pauson-Khand reaction gives direct entry to tricyclic compounds. The RCM was carried out on a hexacarbonylcobalt-complexed alkyne, this complex acting as a protecting group against enyne metathesis. The procedure was studied for dienynes containing heteroatoms and allows the building of [6,5,5] and [7,5,5] tricyclic systems. The feasibility of the process depends strongly on the nature of the substrate. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800332

FULL PAPER
DOI: 10.1002/ejoc.200800332
Combination of RCM and the Pauson–Khand Reaction: One-Step Synthesis of
Tricyclic Structures
Marta Rosillo,[a] Eduardo Arnáiz,[a] Delbrin Abdi,[a] Jaime Blanco-Urgoiti,[a]
Gema Domínguez,[a] and Javier Pérez-Castells*[a]
Keywords: Pauson–Khand reaction / Metathesis / Cyclization / One-pot reaction / Tricyclic compounds
The combination of ring-closing metathesis (RCM) followed
by an intramolecular Pauson–Khand reaction gives direct en-
try to tricyclic compounds. The RCM was carried out on a
hexacarbonylcobalt-complexed alkyne, this complex acting
allows the building of [6,5,5] and [7,5,5] tricyclic systems. The
feasibility of the process depends strongly on the nature of
the substrate.
as a protecting group against enyne metathesis. The pro- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
cedure was studied for dienynes containing heteroatoms and
Germany, 2008)
place before completion of the RCM. We have shown in a
preliminary communication of this work our first results of
the RCM/PKR of acyclic dienes bearing a complexed triple
bond.[8] We present herein our complete study of the combi-
nation of these two powerful reactions.
Introduction
Metathesis reactions catalyzed by ruthenium carbenes
have become a mature tool in synthetic chemistry. The use
of ring-closing metathesis (RCM) in natural product syn-
theses is common and current challenges include the combi-
nation of these reactions with other processes to enhance
their synthetic power.[1] Among the transition-metal-cata-
lyzed or -mediated reactions capable of producing polycy-
clic scaffolds that can be further functionalized, Pauson–
Khand reactions (PKRs) are outstanding.[2] The construc-
tion of tricyclic structures by PKRs for the total synthesis
of natural products such as dendrobine,[3] asteriscanolide,[4]
and epoxydictimene[5] has been reported by several groups.
Five- to eight-membered cycles as well as macrocycles have
readily been obtained by the RCM reaction. These cycloal-
kenes could take part in PKRs. If an alkynyl moiety is suit-
ably situated, RCM followed by an intramolecular PKR
would give a tricyclic cyclopentenone. As reported by many
groups, competition between RCM and enyne metathesis
generally favors the latter reaction, so the combination of
RCM and a PKR would require the protection of the triple
bond. The formation of a hexacarbonyldicobalt complex
prior to the RCM reaction would solve the problem, giving
the cobalt a dual role in the transformation (Scheme 1,
path a). Green[6] and Young and co-workers[7] have recently
shown the feasibility of carrying out RCM in structures
containing hexacarbonyldicobalt–alkyne complexes. As the
PKR usually needs promoters or severe reaction conditions,
this reaction (Scheme 1, path b) hopefully would not take
Scheme 1. General scheme of the RCM/PKR process.
Results and Discussion
Our first aim was the synthesis of substrates containing
a propargyl ether moiety, which normally gives good results
in PKRs. Thus, starting from the corresponding alkenols
or from 7-bromohept-1-ene, we synthesized compounds 3
following the strategy depicted in Scheme 2. Compounds
3a,b were obtained in 51 and 95%, respectively, overall
yields after three steps, whereas compound 3c required four
steps and was obtained in 19% overall yield.
[a] Departamento de Química, Facultad de Farmacia, Universidad
San Pablo – CEU,
Urb. Montepríncipe, 28668 Boadilla del Monte, Madrid, Spain
Fax: +34-913510496
E-mail: jpercas@ceu.es
Eur. J. Org. Chem. 2008, 3917–3927
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3917

J. Pérez-Castells et al.
FULL PAPER
Scheme 2. Synthesis of oxygen-containing dienynes.
Compound 3a was treated with 5% Grubbs’ catalyst,
[(Cy3P)2Cl2Ru=CHPh] ([Ru]-I), to explore the competition
among the possible metathesis processes. We obtained a
complex mixture that could not be separated and that con-
tained at least three metathesis products. Thus we com-
plexed compound 3a to octacarbonyldicobalt and submit-
ted the resulting hexacarbonyldicobalt–alkyne complex 4a
to the same conditions. The reaction did not take place un-
less the cobalt complex had previously been purified in
which case clean conversion to 5 was observed; the product
was then obtained in 94% yield after purification
(Scheme 3). We then submitted compound 5 to PK reaction
conditions using our procedure based on the use of molecu-
lar sieves and trimethylamine N-oxide (TMANO) as co-
promoters of the reaction.[9] We obtained the desired com-
pound 6 as a single diastereomer in 45% yield.
Scheme 3. One-pot RCM/PKR with dienynes 3.
We then carried out the reaction of complex 4a with diastereoselectivity in the Pauson–Khand process. Com-
Grubbs’ catalyst [Ru]-I and when TLC showed complete parison of the three reaction conditions used for the PKR
disappearance of the starting material we added a promoter showed that NMO (conditions C) gave the best yields of 7
for the PKR. Several promoters were examined: A combi- and minimized the formation of 8. Finally, none of the reac-
nation of molecular sieves and TMANO in toluene (condi- tion conditions tested gave any conversion with cobalt com-
tions A),[9] TMANO in DCM (conditions B), and NMO in plex 4c. The one-pot process was sluggish and gave mix-
DCM (conditions C). The best conditions (conditions C) tures in which no RCM products could be detected
gave the desired compound 6 as a single diastereomer in (Scheme 3).
81% yield. The relative stereochemistry of 6 was assigned
The latter result is caused by the problematic formation
on the basis of NOE experiments; the cis configuration was of an eight-membered ring by RCM. This metathesis would
determined, as depicted in Scheme 3.[10] Compound 3b was need harsh conditions that would allow the PKR to occur
treated with [Co2(CO)8] and the resulting pure complex 4b before the formation of the RCM product. Next we de-
(83%) was treated as above. In this case the RCM was not signed a substrate with less conformational mobility to see
complete after 18 hours. NMR analysis of an aliquot of the if this would favor the formation of medium-sized rings un-
reaction mixture showed 75% conversion. Addition of more der mild conditions. Thus, we synthesized dienyne 13 start-
ruthenium catalyst did not improve the conversion. We at- ing from 3-(2-oxocyclohexyl)propanenitrile (10), which was
tempted the reaction with the second-generation catalyst first protected as the ethylene acetal and subsequently re-
[(Cy3P)(NHC)Cl2Ru=CHPh] ([Ru]-II), but this complex did duced with DIBAL-H to give the corresponding aldehyde
not give any conversion after 20 hours, even when heating (Scheme 4). This intermediate was treated with vinylmagne-
the reaction at 40 °C. Thus, we proceeded with the PKR sium bromide to give 11 in 36% yield after the three steps.
and obtained a mixture of diastereomers 7 that could not The sodium alkoxide derived from 11 was treated with pro-
be separated, along with compound 8. In this case the for- pargyl bromide to give, after hydrolysis of the acetal, 12.
mation of a seven-membered ring does not allow complete At this point, 12 was transformed into 13 by reaction with
3918
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3917–3927

One-Step Synthesis of Tricyclic Structures
vinylmagnesium bromide. The final dienyne was obtained (3:2) mixture of diastereomers,[11] which were separated and
in good overall yields as a mixture of two diastereomers, assigned by NOE experiments (Scheme 6).[12] The major
which were inseparable by traditional chromatography. As isomer was in this case the cis,trans compound 19bα. Again,
our aim was the study of the feasibility of the one-pot the formation of the seven-membered ring led to a mixture
RCM/PKR process, we did not develop a selective synthesis of diastereomers. The three methods used gave similar re-
of 13 and used the mixture in the following steps.
sults in terms of yield and diastereoselectivity. On the other
hand, compound 18a was unreactive under all the condi-
tions tested, leading to partial recovery of the starting mate-
rial. One possible reason for this lack of reactivity in the
RCM step is the steric hindrance of the bulky Boc group in
the starting product.
Scheme 4. Synthesis of substrate 13.
Compound 13 was transformed into the corresponding
cobalt complex 14, which was submitted to different RCM
reaction conditions. Unfortunately no conversion took
place at room temp. using either [Ru]-I or [Ru]-II catalysts
and DCM or toluene as solvents. Complex 14 was stirred
in toluene, gradually elevating the temperature in the pres-
ence of 5% [Ru]-I; no reaction was observed until 55 °C.
After disappearance of the starting material, we isolated
compound 16 in 44% yield as the only reaction product.
Traces of the desired polycycle 15 were detected in the crude
mixture but could not be isolated. Compound 16 is the re-
sult of PKR of the complex 14 (Scheme 5).
Scheme 6. Synthesis and one-pot RCM/PKR of dienynes 18.
Finally we planned the synthesis of skeletons with no
heteroatoms. The starting dienynes were obtained from
pentan-5-olide and hexan-6-olide. The first starting mate-
rial was reduced to the corresponding lactol which, upon
Wittig reaction and oxidation, gave the ketone 20a. On the
other hand, hydrolysis, oxidation, and Wittig reaction of
hexan-6-olide gave ester 21 in 78% overall yield. Saponifica-
tion of 21 followed by reaction with MeLi yielded the par-
ent ketone 20b. These ketones were converted into the di-
methylhydrazones 22a,b following the procedure of Kitch-
ing and co-workers,[13] and the corresponding enolates were
treated with trimethylsilylpropargyl bromide to give, after
hydrolysis, 23a,b in good yields. Finally, the reaction with
vinylmagnesium bromide and subsequent desilylation gave
24a,b. The overall yields for the synthesis of these dienynes
were 25 and 23%, respectively (Scheme 7).
Scheme 5. Behavior of substrate 13a under RCM/PKR conditions.
The next step consisted of the synthesis of a nitrogen-
When we carried out the one-pot RCM/PKR process
containing substrate. Thus, from hex-5-enal and hept-6-enal with complex 25a under the same set of experimental condi-
we carried out the synthesis of propargylamines 17a,b by tions as described above we obtained only 15% yield of the
reaction of the corresponding propargylimine with a vinyl desired product 26a as a single diastereomer with 20% of
Grignard reagent. Compounds 17a,b, obtained in moderate another compound whose structure, in accord with its
yields, were protected as Boc derivatives and complexed NMR spectroscopic data, was assigned to 27. This latter
with cobalt to give 18a,b. The one-pot reaction of substrate product implies that the Pauson–Khand reaction occurred
18b led to the desired tricyclic products 19bα and 19bβ as a with the ethylene formed in the metathesis process. To avoid
Eur. J. Org. Chem. 2008, 3917–3927
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3919

J. Pérez-Castells et al.
FULL PAPER
Scheme 7. Synthesis and one-pot RCM/PKR of dienynes 24.
the formation of 27 we carried out another experiment in from the PKR of 25b. This mixture was obtained in around
which argon was bubbled through the reaction mixture af- 35% yield.
ter completion of the metathesis. In this case 27 was isolated
Our final aim was the synthesis of a polycyclic structure
in 14% yield and 26a in 20% yield. The formation of a six- described as an intermediate in the synthesis of the steroidic
membered ring in the RCM allows total diastereoselectivity alkaloid Conessine. This natural product, which has signifi-
in the Pauson–Khand process, as in the synthesis of 6. On cant biological activity against dysentery,[14] has been syn-
the other hand, the reaction of complex 25b required a tem- thesized by Meyers[15] and other groups.[16] In particular,
perature of 40 °C. In this case, an inseparable (3:2) mixture Meyers and co-workers described a nonracemic synthesis
of products 26b and 28 was obtained, the latter coming of Conessine in which polycyclic enone 33 was obtained as
Scheme 8. Intramolecular PKR of allenynes.
3920
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3917–3927

One-Step Synthesis of Tricyclic Structures
28.4, 33.7, 43.5, 114.8, 138.5, 200.5 ppm. IR (film): ν = 3080, 2940,
˜
an intermediate, although with benzyl as a protecting
group. We envisioned that this tetracyclic framework could
1730, 1640 cm–1.
be created by RCM/PKR starting from dienyne 31. Thus, Oct-7-enal (1c): A dried two-necked flask equipped with a con-
compound 29[17] was oxidized to the corresponding alde-
hyde 30, which was transformed into amine 31 by reductive
amination. Then the amine group was protected and the
denser and a magnetic stirrer under vacuum was charged with
NaCN (0.67 g, 13.8 mmol). This flask was heated at 110 °C for
20 min. Upon cooling to 90 °C, DMSO (4 mL) and 7-bromohept-
1-ene (2.00 g, 11.3 mmol) were added. The mixture was stirred at
triple bond was complexed to cobalt. The subsequent RCM
90 °C overnight (around 15 h). Then, water (3 mL) was added and
gave the desired dihydropyrrole 32 in moderate yield. The
the crude was extracted with diethyl ether (3ϫ5 mL) and dried
reaction conditions for the PKR used with previous sub-
strates were unsuccessful with 32. The problem with this
substrate is the substitution at the double bond. This im-
with sodium sulfate. Oct-7-enenitrile was isolated (1.31 g, 94%) as
a colorless oil. DIBAL-H (6.76 mL (6.7 mmol) was added dropwise
to a solution of oct-7-enenitrile (0.67 g, 5.4 mmol) in anhydrous
plies the formation of a quaternary carbon in the PKR,
ether (25 mL) at –78 °C. The resulting mixture was stirred at –78 °C
which is normally problematic. In previous studies we have for 2 h. The reaction was quenched with saturated NH4Cl (10 mL)
and stirred for 15 min, after which 5% H2SO4 (5 mL) was added
and the mixture was stirred for 10 min more. The reaction was
extracted with diethyl ether (3ϫ20 mL), dried, filtered, and con-
centrated. Product 1c was isolated (0.44 g, 43%) as a colorless oil.
1H NMR (300 MHz, CDCl3): δ = 1.29–1.46 (m, 4 H), 1.59–1.68
(m, 2 H), 2.01–2.08 (m, 2 H), 2.43 (td, J1 = 7.1, J2 = 1.6 Hz, 2 H),
4.91–5.03 (m, 2 H), 5.74–5.83 (m, 1 H), 9.76 (s, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 21.8, 28.5, 28.5, 33.4, 43.7, 114.4,
succeeded in making these kinds of substrates reactive by
adding an additional rhodium catalyst to the reaction.[17]
Thus, when 32 was refluxed in toluene in the presence of
molecular sieves and with 5% [Rh(PPh3)ClCO], we ob-
tained the desired product 33 in 30% yield along with an-
other product which could not be completely purified.
These products appeared in the crude mixture as a 3:2 mix-
ture. We have assigned provisionally the latter product to
structure 34 on the basis of its 1H NMR spectroscopic data.
This product is a result of the isomerization of the double
bond formed in the RCM and insertion of the complexed
triple bond into a C–H bond of the olefinic fragment, a
well-known side-reaction in PK chemistry (Scheme 8).
138.6, 202.8 ppm. IR (film): ν = 2940, 2240, 1720, 1640 cm–1.
˜
General Procedure for the Reaction of Grignard Reagents with Car-
bonyl Compounds: The corresponding aldehyde (15.0 mmol) in an-
hydrous THF (5 mL) was added dropwise to a solution of the Grig-
nard reagent at 0 °C. The crude was stirred at room temperature
until completion of the reaction (TLC). Then the reaction was
poured into an ice/water bath and extracted with EtOAc
(3ϫ20 mL). The organic layer was washed with brine (20 mL),
dried with MgSO4, filtered, and concentrated. Purification was ac-
complished by column chromatography.
Conclusions
Octa-1,7-dien-3-ol (2a): Following the general procedure for the re-
action of Grignard reagents with carbonyl compounds, from hex-
5-enal (1.50 g, 15.3 mmol), 1.91 g (99%) of 2a (hexane/AcOEt
10%) were obtained as a colorless oil. 1H NMR (300 MHz,
CDCl3): δ = 1.44–1.56 (m, 4 H), 2.08–2.11 (m, 2 H), 4.12 (br. s, 1
H), 4.95–5.26 (m, 4 H), 5.80–5.88 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 24.5, 33.5, 36.3, 72.8, 114.3, 114.5, 138.5,
In summary we have developed a new access to tricyclic
structures by means of a combined RCM/Pauson–Khand
process. The methodology is currently being extended to
new precursors of systems with different ring sizes.
141.2 ppm. IR (film): ν = 3380, 3080, 2940, 1640 cm–1. C H O
˜
8
14
Experimental Section
(126.20): calcd. C 76.14, H 11.18; found C 76.95, H 11.42.
General Procedure for the Oxidation of Alcohols: A solution of the
corresponding alcohol (10.0 mmol) in DCM (4 mL) was added to
a suspension of PCC (15.0 mmol) in DCM (15 mL) at 0 °C. The
crude was stirred at room temperature until completion of the reac-
tion (TLC). The reaction was diluted by addition of Et2O (50 mL)
and filtered through a small pad of silica gel (with ether rinsing).
The solvent was removed under vacuum at room temperature. The
product was used without further purification.
Nona-1,8-dien-3-ol (2b): Following the general procedure for the
reaction of Grignard reagents with carbonyl compounds, from
hept-6-enal (2.00 g, 17.8 mmol), 2.50 g (100%) of 2b (hexane/Ac-
OEt 10%) were obtained as a colorless oil. 1H NMR (300 MHz,
CDCl3): δ = 1.26–1.60 (m, 6 H), 2.03–2.08 (m, 2 H), 4.09–4.12 (m,
1 H), 4.93–5.26 (m, 4 H), 5.77–5.93 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 24.7, 28.7, 33.6, 36.7, 73.1, 114.3, 114.5,
138.8, 141.2 ppm. IR (film): ν = 3360, 3080, 2920, 1640 cm–1.
˜
C9H16O (140.12): calcd. C 77.09, H 11.50; found C 76.91, H 11.62.
Hex-5-enal (1a): Following the general procedure for the oxidation
of alcohols, from hex-5-en-1-ol (5.00 g, 58.1 mmol), 4.14 g (85%)
of 1a were obtained as a colorless oil. 1H NMR (300 MHz, CDCl3):
δ = 1.72–1.77 (m, 2 H), 2.09–2.12 (m, 2 H), 2.46 (t, J = 7.7 Hz, 2
H), 4.98–5.07 (m, 2 H), 5.71–5.81 (m, 1 H), 9.79 (s, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 21.0, 32.8, 43.0, 115.4, 137.4,
Deca-1,9-dien-3-ol (2c): Following the general procedure for the re-
action of Grignard reagents with carbonyl compounds, from 1c
(0.44 g, 3.2 mmol), 0.38 g (71%) of 2c (hexane/AcOEt 10%) were
obtained as a colorless oil. 1H NMR (300 MHz, CDCl3): δ = 1.32–
1.46 (m, 6 H), 1.49–1.58 (m, 2 H), 2.01–2.08 (m, 2 H), 4.09–4.11
(m, 1 H), 4.91–5.25 (m, 4 H), 5.74–5.92 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 25.1, 28.7, 28.9, 33.6, 36.9, 73.1, 114.2,
202.5 ppm. IR (film): ν = 3080, 1760, 1640 cm–1.
˜
Hept-6-enal (1b): Following the general procedure for the oxidation
of alcohols, from hept-6-en-1-ol (0.94 g, 9.4 mmol), 0.92 g (100%)
of 1b were obtained as a colorless oil. 1H NMR (300 MHz, CDCl3):
δ = 1.39–1.49 (m, 2 H), 1.60–1.68 (m, 2 H), 2.05–2.12 (m, 2 H),
114.4, 139.0, 141.3 ppm. IR (film): ν = 3300, 3060, 2920, 2840,
˜
1640 cm–1. C10H18O (154.14): calcd. C 77.87, H 11.76; found C
78.02, H 11.89.
2.45 (td, J1 = 7.4, J2 = 1.6 Hz, 2 H), 4.95–5.05 (m, 2 H), 5.73–5.86 General Procedure for the Propargylation Reaction: A solution of
(m, 1 H), 9.77 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.6,
the corresponding alcohol (1 mmol) in anhydrous THF (3 mL) was
Eur. J. Org. Chem. 2008, 3917–3927
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3921

J. Pérez-Castells et al.
FULL PAPER
1
added to a suspension of NaH (60% dispersion in mineral oil,
3 mmol, washed with hexane) in anhydrous THF (1 mL) at 0 °C.
The resulting mixture was stirred at room temperature for 30 min.
Then propargyl bromide was added dropwise and the reaction was
left to reach room temp. overnight. The mixture was cooled down
to 0 °C and was quenched with water dropwise, after which it was
extracted with AcOEt (3ϫ20 mL), dried, filtered, and concen-
trated. The residue was purified by column chromatography.
red oil. H NMR (300 MHz, CDCl3): δ = 1.22–1.64 (m, 6 H), 2.03
(br. s, 2 H), 3.84–3.86 (m, 1 H), 4.47 (d, J = 13.7 Hz, 1 H), 4.67
(d, J = 13.2 Hz, 1 H), 4.92–5.02 (m, 2 H), 5.20–5.25 (m, 2 H), 5.68–
5.77 (m, 2 H), 6.02 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 24.6, 28.8, 33.7, 35.1, 68.0, 71.4, 81.3, 92.3, 114.2, 117.4, 138.8,
138.9, 199.8 ppm. IR (film): ν = 2100, 2060, 2020 cm–1.
˜
Complex 4c: Hexacarbonyldicobalt–3-(Prop-2-ynyloxy)deca-1,9-
diene: Following the general procedure, from 3c (0.18 g, 0.9 mmol),
0.34 g (83%) of 4c (hexane/AcOEt 1%) were obtained as a dark-
red oil. 1H NMR (300 MHz, CDCl3): δ = 1.27–1.42 (m, 6 H), 1.52–
1.60 (m, 2 H), 2.03–2.05 (m, 2 H), 3.81–3.88 (m, 1 H), 4.47 (d, J
3-(Prop-2-ynyloxy)octa-1,7-diene (3a): Following the general pro-
cedure for the propargylation reaction, from 2a (1.00 g, 7.9 mmol),
0.78 g (60%) of 3a (hexane) were obtained as a colorless oil. 1H
NMR (300 MHz, CDCl3): δ = 1.40–1.69 (m, 6 H), 2.40 (t, J = = 13.2 Hz, 1 H), 4.66 (d, J = 13.7 Hz, 1 H), 4.92–5.02 (m, 2 H),
2.2 Hz, 1 H), 3.84–3.91 (m, 1 H), 4.02 (dd, J1 = 15.7, J2 = 2.5 Hz,
1 H), 4.19 (dd, J1 = 15.7, J2 = 2.5 Hz, 1 H), 4.93–5.04 (m, 2 H),
5.22–5.27 (m, 2 H), 5.58–5.70 (m, 1 H), 5.74–5.87 (m, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 24.5, 33.5, 34.5, 55.0, 73.7, 79.9,
5.19–5.25 (m, 2 H), 5.65–5.82 (m, 2 H), 6.02 (s, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 24.9, 28.8, 29.0, 33.7, 35.2, 68.0, 71.4,
81.3, 92.3, 114.2, 117.4, 138.8, 139.1, 199.9 ppm. IR (film): ν =
˜
2100, 2060, 2020 cm–1.
80.1, 114.5, 118.1, 137.8, 138.6 ppm. IR (film): ν = 3300, 3180,
˜
Complex 5: Hexacarbonyldicobalt–3-(Prop-2-yn-1-yloxy)cyclohex-
ene: [Ru]-I (0.82 g, 0.1 mmol) was added to a solution of 4a (0.48 g,
1.1 mmol) in anhydrous toluene (100 mL) under argon. The re-
sulting mixture was stirred at room temperature until completion
of the reaction (TLC) The crude mixture was filtered through di-
atomaceous earth and the solvent evaporated under vacuum. The
residue was purified by column chromatography (hexane/AcOEt
2%) to obtain 0.42 g (94%) of 5 as a dark-red oil. 1H NMR
(300 MHz, CDCl3): δ = 1.69–1.89 (m, 4 H), 1.98–2.05 (m, 2 H),
4.09 (br. s, 1 H), 4.66–4.75 (m, 2 H), 5.79–5.91 (m, 2 H), 6.06 (s, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.0, 25.2, 28.3, 68.0,
2940, 2120, 1640 cm–1. C11H16O (164.24): calcd. C 80.44, H 9.82;
found C 80.69, H 10.03.
3-(Prop-2-ynyloxy)nona-1,8-diene (3b): Following the general pro-
cedure for the propargylation reaction, from 2b (1.00 g, 7.1 mmol),
1.23 g (95%) of 3b (hexane/AcOEt 5%) were obtained as a colorless
oil. 1H NMR (300 MHz, CDCl3): δ = 1.36–1.43 (m, 6 H), 2.03–
2.07 (m, 2 H), 2.39 (t, J = 2.5 Hz, 1 H), 3.83–3.91 (m, 1 H), 4.02
(dd, J1 = 15.7, J2 = 2.5 Hz, 1 H), 4.19 (dd, J1 = 15.7, J2 = 2.5 Hz,
1 H), 4.92–5.03 (m, 2 H), 5.21–5.26 (m, 2 H), 5.57–5.69 (m, 1 H),
5.74–5.88 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.7,
28.7, 33.6, 35.0, 55.1, 73.7, 80.1, 80.2, 114.3, 118.1, 137.9,
71.8, 72.7, 92.4, 127.2, 131.3, 199.6 ppm. IR (film): ν = 2100, 2060,
˜
138.9 ppm. IR (film): ν = 2120, 1740, 1640 cm–1. C H O (178.14):
˜
2020 cm–1.
12 18
calcd. C 80.85, H 10.18; found C 80.99, H 10.34.
Procedure for the RCM/Pauson–Khand Reaction: [Ru]-I
(0.05 mmol) was added to a solution of the hexacarbonyldicobalt–
alkyne complex (1 mmol) in anhydrous DCM (or toluene in
method A) (50 mL) under argon, was added. The reaction was
stirred at room temp. and when TLC showed the disappearance of
the starting material, the promoters for the Pauson–Khand reac-
tion were added.
3-(Prop-2-ynyloxy)deca-1,9-diene (3c): Following the general pro-
cedure for the propargylation reaction, from 2c (1.60 g,
10.4 mmol), 0.76 g (66%) of 3c (hexane/AcOEt 5%) were obtained
1
as a colorless oil. H NMR (300 MHz, CDCl3): δ = 1.27–1.41 (m,
8 H), 2.01–2.06 (m, 2 H), 2.40 (t, J = 2.5 Hz, 1 H), 3.83–3.89 (m,
1 H), 4.02 (dd, J1 = 15.7, J2 = 2.5 Hz, 1 H), 4.19 (dd, J1 = 15.7, J2
= 2.5 Hz, 1 H), 4.92–5.04 (m, 2 H), 5.21–5.27 (m, 2 H), 5.58–5.69
(m, 1 H), 5.75–5.88 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 25.1, 28.8, 28.9, 33.7, 35.1, 55.1, 73.7, 80.2, 80.2, 114.2, 118.1,
Method A: After cooling the reaction to –20 °C, eight times the
mass of the enyne of powdered molecular sieves and a suspension
of TMANO (9 mmol) in anhydrous toluene (2 mL) were added.
137.9, 139.1 ppm. IR (film): ν = 2120, 1740, 1640 cm–1. C H O
˜
13 20
Method B: A suspension of TMANO (6 mmol) in anhydrous DCM
(192.15): calcd. C 81.20, H 10.48; found C 81.01, H 10.73.
(2 mL) was added to the reaction at room temp.
General Procedure for the Complexation of Enynes with [Co2-
(CO)8]: [Co2(CO)8] (1.1 mmol) was added to a solution of the cor-
responding alkyne (1.0 mmol) in anhydrous ether (7 mL). The re-
sulting mixture was stirred until total complexation of the alkyne
(TLC). The crude was filtered through diatomaceous earth and the
solvent evaporated under vacuum. The residue was purified by col-
umn chromatography.
Method C: A suspension of NMO (6 mmol) in anhydrous DCM
(2 mL) was added to the reaction at room temp.
(4aS*,7aR*,7bR*)-4a,5,6,7,7a,7b-Hexahydroindeno[7,7a,1-bc]furan-
4(2H)one (6): Treatment of 4a (0.54 g, 1.2 mmol) as described in
method C for the RCM/Pauson–Khand reaction afforded 0.16 g
(81%) of 6 as a colorless oil (hexane/AcOEt 35%) as a single dia-
1
Complex 4a: Hexacarbonyldicobalt–3-(Prop-2-ynyloxy)octa-1,7- stereomer. H NMR (300 MHz, CDCl3): δ = 0.99–1.26 (m, 3 H),
diene: Following the general procedure, from 3ª (0.50 g,
3.05 mmol), 1.13 g (82%) of 4a (hexane/AcOEt 5%) were obtained
as a dark-red oil. H NMR (300 MHz, CDCl3): δ = 1.46–1.53 (m,
1.57–1.61 (m, 1 H), 1.83–1.91 (m, 1 H), 1.96–2.05 (m, 1 H), 2.83–
2.91 (m, 1 H), 3.35 (t, J = 7.2 Hz, 1 H), 4.34–4.42 (m, 1 H), 4.57–
4.70 (m, 2 H), 5.97 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 21.0, 25.3, 28.6, 46.7, 47.5, 64.6, 75.2, 121.8, 182.0, 213.2 ppm.
IR (film): ν˜ = 1710, 1650 cm–1. NOE (7a-HǞ7b-H 5%, 7b-
1
2 H), 1.58–1.69 (m, 2 H), 2.03–2.10 (m, 2 H), 3.83–3.90 (m, 1 H),
4.47 (dd, J1 = 13.2, J2 = 1.1 Hz, 1 H), 4.67 (dd, J1 = 13.2, J2
=
1.1 Hz, 1 H), 4.93–5.03 (m, 2 H), 5.20–5.25 (m, 2 H), 5.66–5.84 (m, HǞ7a-H 5%, 7b-HǞ4a-H 5%, 4a-HǞ7b-H 5%). C10H12O2
2 H), 6.02 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.4,
(164.08): calcd. C 73.15, H 7.37; found C 73.01, H 7.25.
33.6, 34.7, 68.0, 71.4, 81.2, 92.3, 114.5, 117.4, 138.7, 138.7,
(4aS*,8aR*,8bR*)- and (4aS*,8aS*,8bR*)-5,6,7,8,8a,8b-Hexahy-
dro-2H-azuleno[8,8a,1-bc]furan-4(4aH)-one (7) and 3-(Hex-5-enyl)-
3a,4-dihydro-1H-cyclopenta[c]furan-5(3H)-one (8): Treatment of 4b
(0.46 g, 1.0 mmol) as described in method B for the RCM/Pauson–
Khand reaction afforded (hexane/AcOEt 10%) 0.14 g (70%) of 7
199.8 ppm. IR (film): ν = 2100, 2060, 2020 cm–1.
˜
Complex 4b: Hexacarbonyldicobalt–3-(Prop-2-ynyloxy)nona-1,8-
diene: Following the general procedure, from 3b (0.50 g, 2.8 mmol),
1.08 g (83%) of 4b (hexane/AcOEt 1%) were obtained as a dark-
3922
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3917–3927

One-Step Synthesis of Tricyclic Structures
as a mixture of diastereomers that were not separable by traditional tered, and concentrated in vacuo to yield 0.52 g (95%) of 12 as a
1
chromatography (as colorless oil) and 0.05 g (19%) of pure 8 as a
colorless oil.
yellow oil (hexane/AcOEt 5%). H NMR (300 MHz, CDCl3): δ =
1.13–1.85 (m, 9 H), 1.96–2.08 (m, 2 H), 2.18–2.31 (m, 2 H), 2.35
(t, J = 2.2 Hz, 1 H), 3.76–3.84 (m, 1 H), 3.92 (dd, J1 = 14.3, J2 =
1.7 Hz, 1 H), 4.11 (dd, J1 = 15.4, J2 = 2.2 Hz, 1 H), 5.15–5.21 (m,
2 H), 5.50–5.63 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
24.7, 24.8, 24.8, 25.2, 25.5, 27.8, 27.9, 32.3, 32.7, 33.7, 33.9, 41.8,
41.9, 50.2, 50.5, 54.9, 55.0, 73.7, 73.7, 79.9, 80.1, 118.0, 118.1,
7: 1H NMR (300 MHz, CDCl3): δ = 1.00–1.40 (m, 6 H), 1.56–1.77
(m, 4 H), 1.92–2.23 (m, 6 H), 2.55–2.64 (m, 1 H), 2.72 (q, J =
6.0 Hz, 1 H), 3.06 (br. t, J = 8.8 Hz, 1 H), 3.37 (td, J1 = 11.2, J2 =
1.6 Hz, 1 H), 3.59 (br. t, J = 6.6 Hz, 1 H), 4.30–4.37 (m, 1 H),
4.51–4.64 (m, 3 H), 4.73 (d, J = 15.4 Hz, 1 H), 6.02 (s, 1 H), 6.17
(s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.1, 26.4, 27.0,
27.1, 32.9, 37.5, 46.2, 48.4, 53.0, 56.2, 63.5, 63.8, 66.2, 77.7, 79.9,
137.4, 137.5, 193.6, 193.7 ppm. IR (film): ν = 2100, 1700,
˜
1640 cm–1.
81.2, 124.6, 124.9, 183.0, 183.4, 210.4, 211.5 ppm. IR (film): ν = 2-[3-(Prop-2-ynyloxy)pent-4-enyl]-1-vinylcyclohexanol (13): Follow-
˜
1710, 1640 cm–1.
ing the general procedure for the reaction of Grignard reagents
with carbonyl compounds, from 12 (0.50 g, 2.27 mmol), 0.43 g
(77%) of 13 were obtained as a yellow oil (hexane/AcOEt 5%). 1H
NMR (300 MHz, CDCl3): δ = 0.96–1.78 (m, 13 H), 2.39 (t, J =
2.2 Hz, 1 H), 3.76–7.84 (m, 1 H), 4.01 (dd, J1 = 16.0, J2 = 1.8 Hz,
1 H), 4.17 (dd, J1 = 16.0, J2 = 2.8 Hz, 1 H), 5.08 (dd, J1 = 12.1, J2
= 1.1 Hz, 1 H), 5.20–5.27 (m, 3 H), 5.53–5.67 (m, 1 H), 5.78–5.89
(m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3, 25.2, 25.3,
25.7, 25.8, 26.5, 26.6, 33.1, 33.2, 38.9, 38.9, 43.9, 44.0, 55.0, 73.7,
74.6, 80.0, 80.1, 80.2, 80.5, 111.5, 111.6, 137.6, 137.8, 146.1,
8: 1H NMR (300 MHz, CDCl3): δ = 1.25–1.49 (m, 4 H), 1.66–1.83
(m, 2 H), 2.06–2.16 (m, 3 H), 2.61 (dd, J1 = 17.6, J2 = 6.0 Hz, 1
H), 2.86–2.88 (m, 1 H), 3.39–3.47 (m, 1 H), 4.55 (d, J = 15.9 Hz,
1 H), 4.73 (d, J = 15.9 Hz, 1 H), 4.93–5.04 (m, 2 H), 5.73–5.87 (m,
1 H), 6.03 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.9,
28.6, 33.4, 34.0, 39.0, 50.6, 65.7, 83.1, 114.4, 124.0, 138.4, 185.0,
208.7 ppm. IR (film): ν = 1710, 1640 cm–1. C H O (206.13):
˜
13 18
2
calcd. C 75.69, H 8.80; found C 75.84, H 8.89.
146.2 ppm. IR (film): ν = 3490, 2110, 1680 cm–1.
5-(1,4-Dioxaspiro[4.5]decan-6-yl)pent-1-en-3-ol (11):
A
flask
˜
equipped with a Dean–Stark apparatus was charged with 10
(2.00 g, 19.9 mmol), ethane-1,2-diol (0.90 g, 21.85 mmol), and p-
toluenesulfonic acid (0.30 g, 1.58 mmol) in benzene (225 mL). The
solution was refluxed for 18 h. The crude was concentrated under
vacuum, poured into water (100 mL) and extracted with Et2O
(3ϫ50 mL). The organic layer was washed with a solution of 5%
NaHCO3 (100mL), dried with MgSO4, filtered, and concentrated.
The residue was purified by column chromatography (hexane/Ac-
OEt, 4:1) obtaining 3.00 g (77%) of 3-(1,4-dioxaspiro[4.5]decan-6-
yl)propanenitrile. DIBAL-H (65.7 mL, 65.66 mmol) was added
dropwise to a solution of this product (6.50 g, 32.83 mmol) in anhy-
drous DCM (20 mL) at –78 °C. The mixture was stirred for 2 h at
this temperature. The reaction was quenched at –78 °C with AcOEt
(8.3 mL) and a saturated solution of sodium potassium tartrate
(150 mL). The resulting mixture was stirred overnight. The crude
was extracted with AcOEt (3ϫ75 mL). The residue was purified
by column chromatography (hexane/AcOEt, 9:1) to obtain 4.24 g
(66%) of 3-(1,4-dioxaspiro[4.5]decan-6-yl)propanal. The aldehyde
(1.10 g, 5.61 mmol) obtained before in anhydrous THF (35 mL)
was added dropwise to a flask charged with a solution of vinylmag-
nesium bromide (7.3 mL, 7.30 mmol) at –78 °C. The solution was
stirred for 15 min at the same temperature and then warmed to
0 °C and stirred for 4 h. The reaction was quenched with saturated
NH4Cl (10 mL), and extracted with AcOEt (3ϫ5 mL). The residue
was purified by column chromatography (hexane/AcOEt 10%) to
obtain 0.89 g (71%) of 11 as a yellow oil. 1H NMR (300 MHz,
Complex 14: Hexacarbonyldicobalt–2-[3-(Prop-2-ynyloxy)pent-4-
enyl]-1-vinylcyclohexanol: Following the general procedure, from 13
(0.05 g, 0.20 mmol), 0.10 g (95%) of 14 (hexane/AcOEt 2%) were
obtained as a dark-red oil. 1H NMR (300 MHz, CDCl3): δ = 0.94–
1.02 (m, 1 H), 1.15–1.35 (m, 3 H), 1.38–1.74 (m, 9 H), 3.79 (br. s,
1 H), 4.45 (d, J = 13.2 Hz, 1 H), 4.64 (d, J = 13.2 Hz, 1 H), 5.07
(d, J = 11.0 Hz, 1 H), 5.18–5.27 (m, 3 H), 5.62–5.74 (m, 1 H), 5.82
(dd, J1 = 17.6, J2 = 11.0 Hz, 1 H), 6.01 (s, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.4, 25.2, 25.8, 26.6, 33.7, 38.9, 44.3, 68.0,
71.4, 74.7, 81.5, 111.6, 117.4, 138.7, 146.2, 296.6 ppm. IR (film): ν
˜
= 2930, 2860, 2250, 2090, 2050, 2020 cm–1.
3-[2-(2-Hydroxy-2-vinylcyclohexyl)ethyl]-3a,4-dihydro-1H-cyclo-
penta[c]furan-5(3H)-one (16): [Ru]-I (0.04 g, 0.058 mmol) was added
to a solution of 14 (0.30 g, 0.58 mmol) in anhydrous toluene
(80 mL). The resulting mixture was stirred at room temperature
After 72 h TLC showed the presence of starting material. The reac-
tion was warmed to 55 °C overnight. The crude was filtered
through diatomaceous earth and the solvent evaporated under vac-
uum. The residue was purified by column chromatography (hexane/
AcOEt 2%) obtaining 0.07 g (44%) of 16 as a colorless oil. 1H
NMR (300 MHz, CDCl3): δ = 1.05–1.95 (m, 13 H), 2.11 (dt, J1 =
17.6, J2 = 2.76 Hz, 1 H), 2.54–2.64 (m, 1 H), 2.84 (br. s, 1 H), 3.33–
3.41 (m, 1 H), 4.52 (d, J = 16.0 Hz, 1 H), 4.71 (d, J = 16.5 Hz, 1
H), 5.08 (dt, J1 = 11.0, J2 = 1.6 Hz, 1 H), 5.24 (dd, J1 = 15.9, J2
= 1.6 Hz, 1 H), 5.82 (dd, J1 = 17.0, J2 = 6.6 Hz, 1 H), 6.02 (br. s,
CDCl3): δ = 1.03–1.83 (m, 13 H), 3.91–3.99 (m, 4 H), 4.09 (br. s, 1 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3, 21.3, 25.6, 25.6,
H), 5.10 (d, J = 10.4 Hz, 1 H), 5.23 (dd, J1 = 17.6, J2 = 1.6 Hz, 1
H), 5.82–5.94 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.8,
23.9, 24.0, 24.4, 29.2, 29.3, 34.5, 34.6, 35.1, 35.1, 44.3, 44.5, 64.1,
64.7, 64.7, 73.2, 73.8, 110.8, 114.4, 114.6, 141.2, 141.3 ppm. IR
25.7, 26.5, 26.6, 32.3, 32.5, 39.0, 39.3, 39.3, 43.9, 44.1, 50.8, 50.9,
65.9, 74.5, 83.6, 83.6, 111.8, 111.9, 124.2, 124.2, 145.9, 146.0, 185.1,
209.1 ppm. IR (film): ν = 3490, 1710, 1680, 1640 cm–1.
˜
N-(Prop-2-ynyl)octa-1,7-dien-3-amine
(17a):
Propargylamine
(film): ν = 3430, 1640 cm–1.
˜
(45.0 mmol) was added to a solution of 1a (4.00 g, 40.8 mmol) in
anhydrous ether (150 mL) and powdered molecular sieves (four
times the mass of the aldehyde, 16.00 g). The reaction was then
stirred at room temp. overnight (around 12 h). The resulting mix-
ture at 0 °C was added dropwise to a 1.0  solution of vinylmagne-
sium bromide (80.0 mmol). The crude was stirred at room temp.
until completion of the reaction (TLC) and then quenched with
saturated NH4Cl (200 mL) and extracted with diethyl ether
(3ϫ200 mL). The organic layer was dried with MgSO4, filtered,
and concentrated. The crude product was purified by column
2-[3-(Prop-2-ynyloxy)pent-4-enyl]cyclohexanone (12): Following the
general procedure for the propargylation reaction, from alcohol 11
(2.00 g, 8.85 mmol), 2.06 g (88%) of 5-(1,4-dioxaspiro[4.5]decan-6-
yl)pent-1-en-3-ol were obtained as a yellow oil. Concentrated HCl
(3.0 mL) was added to a solution of this enyne (0.68 g, 2.49 mmol)
in EtOH (6 mL). The resulting mixture was stirred for 15 min at
room temp. and quenched with water (10 mL) dropwise. The crude
was then extracted with AcOEt (3ϫ5 mL). The organic layer was
washed with saturated NaHCO3 (15 mL), dried with MgSO4, fil-
Eur. J. Org. Chem. 2008, 3917–3927
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3923

J. Pérez-Castells et al.
FULL PAPER
chromatography, obtaining 3.39 g (51%) of 17a (hexane/AcOEt
10%) as a yellow oil. H NMR (300 MHz, CDCl3): δ = 1.37–1.49 27.9, 28.4, 33.4, 47.2, 49.5, 56.6, 62.2, 80.2, 124.7, 156.0, 176.3,
5.94 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.2, 27.5,
1
(m, 4 H), 2.03–2.10 (m, 2 H), 2.20 (t, J = 2.5 Hz, 1 H), 3.19–3.23
(m, 1 H), 3.31 (dd, J1 = 17.0, J2 = 2.2 Hz, 1 H), 3.46 (dd, J1
210.2 ppm. IR (film): ν = 1700, 1650 cm–1. NOE (8b-HǞ8a-H
˜
=
8%, 8b-HǞ4a-H 12%, 4a-HǞ8b-H 12%). C16H23NO3 (277.17):
17.0, J2 = 2.7 Hz, 1 H), 3.66 (t, J = 6.6 Hz, 1 H), 4.93–5.04 (m, 2 calcd. C 69.29, H 8.36, N 5.05; found C 69.37, H 8.67, N 4.99.
H), 5.13–5.20 (m, 2 H), 5.46–5.58 (m, 1 H), 5.73–5.87 (m, 1
19bβ: Obtained as a mixture of two rotamers. 1H NMR (300 MHz,
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 25.0, 33.6, 34.7, 35.4,
CDCl3): δ = 0.97–1.47 (m, 4 H), 1.47 (s, 9 H), 1.60–1.75 (m, 2 H),
60.1, 71.0, 82.3, 114.6, 117.1, 138.5, 139.9 ppm. IR (film): ν = 3300,
˜
1.76–1.93 (m, 1 H), 2.10–2.30 (m, 1 H), 2.65–2.75 (m, 1 H), 3.49
(q, J = 8.2 Hz, 1 H), 4.09–4.33 (m, 3 H), 6.14, 6.18 (s, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 25.8, 26.3, 27.9, 28.0, 28.4, 28.4,
45.2, 45.7, 47.1, 51.9, 52.5, 59.7, 60.4, 80.0, 126.1, 126.3, 153.3,
3180, 2940, 1640 cm–1. C11H17N (163.14): calcd. C 80.93, H 10.50,
N 8.58; found C 80.70, H 10.35, N 8.71.
N-(Prop-2-ynyl)nona-1,8-dien-3-amine (17b): Following the same
procedure as for the synthesis of 17a, from 1b (0.92 g, 8.2 mmol),
0.61 g (42%) of 17b (hexane/AcOEt 20%) were obtained as a yel-
low oil. 1H NMR (300 MHz, CDCl3): δ = 1.31–1.48 (m, 6 H), 2.01–
153.7, 179.6, 180.1, 211.3, 211.2 ppm. IR (film): ν = 1700,
˜
1650 cm–1. NOE (8b-HǞ4a-H 12%, 4a-HǞ8b-H 6%).
C16H23NO3 (277.17): calcd. C 69.29, H 8.36, N 5.05; found C
2.07 (m, 2 H), 2.20 (t, J = 2.5 Hz, 1 H), 3.21 (q, J = 7.7 Hz, 1 H), 69.53, H 8.49, N 4.97.
3.31 (dd, J1 = 17.0, J2 = 2.7 Hz, 1 H), 3.46 (dd, J1 = 17.0, J2
=
General Procedure for the Wittig Reaction: KHMDS (1.3 mmol,
0.5 ) was added dropwise to a solution of the corresponding phos-
phonium salt (1.5 mmol) in anhydrous THF (8 mL). The resulting
solution was stirred at room temperature for 30 min and sub-
sequently added to a THF solution (4 mL) of the aldehyde
(1.0 mmol). The reaction was stirred at room temp. until comple-
tion (TLC). The resulting suspension was poured into a (1:1) Et2O/
H2O mixture, the aqueous phase was extracted with AcOEt
(3ϫ20 mL), and the combined organic layers were dried with
Na2SO4 and concentrated. The crude product was purified by flash
column chromatography with hexane/AcOEt mixtures as eluent.
2.8 Hz, 1 H), 3.65 (t, J = 6.6 Hz, 1 H), 4.93–5.03 (m, 2 H), 5.14–
5.20 (m, 2 H), 5.47–5.58 (m, 1 H), 5.74–5.88 (m, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 25.1, 28.7, 33.5, 35.1, 35.3, 60.1, 71.0,
82.1, 114.2, 117.0, 138.6, 139.9 ppm. IR (film): ν = 3300, 3080,
˜
2940, 1640 cm–1. C12H19N (177.15): calcd. C 81.30, H 10.80, N
7.90; found C 81.41, H 11.00, N 8.03.
General Procedure for the Protection of Amines as tert-Butoxycar-
bonyl Derivatives: (Boc)2O (10.0 mmol) was added to a solution of
the corresponding amine (5.0 mmol) in methanol (15 mL) was and
the reaction was stirred at room temp. overnight. The product was
purified by distillation.
Hept-6-en-2-one (20a):
A
solution of DIBAL-H (53 mL,
52.6 mmol) in anhydrous THF (60 mL) was added to a solution of
5-hexanolide (5.00 g, 43.8 mmol) in anhydrous THF (150 mL) at
–78 °C. The resulting mixture was stirred at the same temperature
for 4 h. Then the reaction was quenched with saturated sodium
tartrate (50 mL) and slowly warmed to room temperature. The mix-
ture was transferred to a separating funnel and extracted with Ac-
OEt (50 mL). The organic layer was washed with water (2ϫ20 mL)
and dried with MgSO4. Removal of the solvent in vacuo gave 5.00 g
(100%) of 6-methyltetrahydro-2H-pyran-2-ol (mixture of isomers)
as a colorless oil. Treatment of this product (4.00 g, 34.5 mmol) as
described in the general procedure for the Wittig reaction afforded
2.38 g (60%) of pure hept-6-en-2-ol as a colorless oil after flash
chromatography (hexane/AcOEt 10%). Finally, this oil (3.41 g,
29.9 mmol) was treated as described in the general procedure for
the oxidation of alcohols, obtaining 2.65 g (100%) of 20a (hexane/
Complex 18a: Hexacarbonyldicobalt–[N-(tert-Butoxycarbonyl)-N-
(prop-2-ynyl)octa-1,7-dien-3-amine]: Following the general pro-
cedure for the protection of amines as tert-butoxycarbonyl deriva-
tives, from 17a (0.60 g, 3.7 mmol), 0.66 g (68%) of tert-butyl octa-
1,7-dien-3-yl(prop-2-yn-1-yl)carbamate were obtained as a white
oil. Treatment of this carbamate (0.40 g, 1.5 mmol) as described in
the general procedure for the synthesis of hexacarbonyldicobalt–
alkyne complexes afforded pure 18a (0.92 g, 88%) as a dark-red oil
after flash chromatography (hexane/AcOEt 10%). 1H NMR
(300 MHz, CDCl3): δ = 1.41–1.54 (m, 11 H), 1.69–1.73 (m, 2 H),
2.08–2.15 (m, 2 H), 4.27–4.31 (m, 1 H), 4.45–4.56 (m, 2 H), 4.97–
5.22 (m, 4 H), 5.77–5.94 (m, 2 H), 6.00 (s, 1 H) ppm.
Complex 18b: Hexacarbonyldicobalt–[N-(tert-Butoxycarbonyl)-N-
(prop-2-ynyl)nona-1,8-dien-3-amine]: Following the general pro-
cedure for the protection of amines as tert-butoxycarbonyl deriva-
tives, from 17b (0.30 g, 1.7 mmol), 0.41 g (88%) of tert-butyl nona-
1,8-dien-3-yl(prop-2-ynyl)carbamate were obtained as a white oil.
Treatment of this carbamate (0.34 g, 1.2 mmol) as described in the
general procedure for the synthesis of hexacarbonyldicobalt–alkyne
complexes afforded pure 18b (0.52 g, 76%) as a dark-red oil after
flash chromatography (hexane/AcOEt 5%). 1H NMR (300 MHz,
CDCl3): δ = 1.29–1.38 (m, 4 H), 1.48 (s, 9 H), 1.69–1.72 (m, 2 H),
2.06–2.09 (m, 2 H), 4.29 (br. s, 1 H), 4.44–4.56 (m, 2 H), 4.95–5.22
(m, 4 H), 5.77–5.88 (m, 2 H), 6.00 (s, 1 H) ppm.
1
AcOEt 10%) as a colorless oil. H NMR (300 MHz, CDCl3): δ =
1.63–1.72 (m, 2 H), 2.03–2.10 (m, 2 H), 2.14 (s, 3 H), 2.44 (t, J =
7.4 Hz, 2 H), 4.96–5.05 (m, 2 H), 5.70–5.84 (m, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 22.7, 29.9, 33.0, 42.8, 115.1, 137.9,
208.8 ppm. IR (film): ν = 1720, 1640 cm–1. C H O (112.09): calcd.
˜
7
12
C 74.95, H 10.78; found C 75.07, H 10.85.
2-(Hept-6-en-2-ylidene)-1,1-dimethylhydrazine (22a): Compound
20a (2.64 g, 23.6 mmol) and a catalytic amount of AcOH were
added to a solution of N,N-dimethylhydrazine (70.7 mmol) in abso-
lute EtOH (150 mL). The mixture was refluxed for 4 h. The solvent
was eliminated, and the crude was extracted with AcOEt
(2ϫ20 mL). The organic layer was washed with saturated
NaHCO3 (2ϫ20 mL), and dried with MgSO4. Removal of the sol-
vent in vacuo gave 3.18 g (88%) of 22a as a colorless oil after vac-
tert-Butyl (4aS*,8aS*,8bR*)-4-Oxo-1,2,4,4a,5,6,7,8,8a,8b-deca-
hydroazuleno[8,8a,1-bc]pyrrole-1-carboxylate (19bα) and tert-Butyl
(4aS*,8aR*,8bR*)-4-Oxo-1,2,4,4a,5,6,7,8,8a,8b-decahydroazulene-
[8,8a,1-bc]pyrrole-1-carboxylate (19bβ): Treatment of 18b (0.35 g,
0.6 mmol) as described in method B for the RCM/Pauson–Khand
reaction afforded 19bα (0.07 g, 38%) and pure 19bβ (0.06 g, 33%)
both as brown oils (hexane/AcOEt 20%).
1
uum distillation. H NMR (300 MHz, CDCl3): δ = 1.56–1.68 (m,
4 H), 1.92 (s, 3 H, minor), 1.94 (s, 3 H, major), 2.04–2.14 (m, 4 H),
2.18–2.23 (m, 4 H), 2.40 (s, 3 H, minor), 2.43 (s, 3 H, major), 4.95–
19bα: H NMR (300 MHz, CDCl3): δ = 1.10–1.40 (m, 4 H), 1.40 5.07 (m, 4 H), 5.74–5.88 (m, 2 H) ppm. 13C NMR (75 MHz,
1
(s, 9 H), 1.68–2.00 (m, 3 H), 2.50–2.60 (m, 1 H), 2.90–2.95 (m, 1 CDCl3): δ = 16.5, 22.6, 25.7, 26.3, 31.0, 33.3, 33.8, 38.5, 47.0, 47.5,
H), 3.03–3.10 (m, 1 H), 3.17–3.22 (m, 1 H), 4.22–4.34 (m, 2 H), 114.9, 115.2, 138.0, 138.2, 167.6, 169.3 ppm. IR (film): ν = 1720,
˜
3924
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3917–3927

One-Step Synthesis of Tricyclic Structures
1640 cm–1. C9H18N2 (154.15): calcd. C 70.08, H 11.76, N 18.16;
found C 70.21, H 11.88, N 18.26.
H), 2.21–2.32 (m, 1 H), 2.52–2.65 (m, 1 H), 2.71–2.80 (m, 1 H),
2.84–2.95 (m, 1 H), 3.05–3.06 (m, 1 H), 5.77 (s, 1 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 19.3, 25.5, 25.8, 35.2, 41.3, 44.9, 55.5,
1-(Trimethylsilyl)dec-9-en-1-yn-5-one (23a): nBuLi (19.4 mmol) was
added dropwise to a solution of iPr2NH (2.0 g, 19.4 mmol) in anhy-
drous THF (50 mL) at –40 °C and the reaction was stirred at
–40 °C for 3 h. The solution was cooled down to –78 °C and 22a
(1.50 g, 9.7 mmol) in anhydrous THF (10 mL) was added. The re-
action was stirred for another 3 h at the same temperature. Finally,
(3-bromoprop-1-ynyl)trimethylsilane (2.2 g, 11.6 mmol) in anhy-
drous THF (6 mL) was added to the reaction and the resulting
mixture was allowed to stir at room temp. overnight. Then it was
poured into a (1:1) water/ether mixture and transferred to a sepa-
rating funnel. Upon extraction, the organic layer was washed with
water (2ϫ40 mL) and brine (2ϫ40 mL). The organic layer was
concentrated under vacuum to half of the initial volume. MeOH
(20 mL), silica gel (2.0 g), and HCl (0.6 mL) were added to the
resulting solution, which was stirred for 4 h, extracted with diethyl
ether (2ϫ40 mL) and the combined organic layers were washed
with brine (40 mL) and dried with MgSO4. The solvent was evapo-
rated under vacuum and the crude purified by flash chromatog-
raphy (hexane/AcOEt 5%) obtaining 1.90 g (88%) of 23a as a col-
orless oil. 1H NMR (300 MHz, CDCl3): δ = 0.14 (s, 9 H), 1.65–
1.75 (m, 2 H), 2.03–2.10 (m, 2 H), 2.42–2.51 (m, 4 H), 2.63–2.67
(m, 2 H), 4.97–5.05 (m, 2 H), 5.70–5.84 (m, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 0.0, 14.4, 22.6, 33.0, 41.5, 41.9, 84.9, 105.7,
76.0, 123.3, 185.8, 210.8 ppm. IR (film): ν = 3450, 1690, 1630 cm–1.
˜
C11H14O2 (178.10): calcd. C 74.13, H 7.92; found C 74.01, H 7.78.
27: 1H NMR (300 MHz, CDCl3): δ = 1.67–1.75 (m, 6 H), 1.94–
2.09 (m, 2 H), 2.25–2.30 (m, 2 H), 2.39–2.42 (m, 2 H), 2.56–2.58
(m, 2 H), 5.64 (d, J = 9.9 Hz, 1 H), 5.80–5.86 (m, 1 H), 7.33 (br.
s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.9, 19.1, 25.1,
26.4, 34.6, 35.2, 39.9, 69.4, 130.2, 132.1, 146.4, 157.4, 210.2 ppm.
IR (film): ν = 3440, 3020, 1690, 1630 cm–1. C H O (206.13):
˜
13 18
2
calcd. C 75.69, H 8.80; found C 75.80, H 8.89.
Methyl Hept-6-enoate (21): A solution of 6-hexanolide (3.00 g,
26.3 mmol) in dry MeOH (20 mL) was bubbled with dry HCl gas
for 15 min. The reaction was refluxed overnight and upon cooling
to room temp. the solvent was evaporated under vacuum half and
a saturated NaHCO3 solution was added until basic pH. The mix-
ture was extracted with EtOAc (3ϫ20 mL). The organic layers
were washed with brine (20mL), dried with MgSO4, filtered, and
concentrated in vacuo to yield 3.86 g (100%) of methyl 6-hydroxy-
hexanoate. Following the general procedure for the oxidation of
alcohols, from methyl 6-hydroxyhexanoate (15.00 g, 102.7 mmol),
13.6 g (92%) of methyl 6-oxohexanoate were obtained as a colorless
oil. Treatment of the aldehyde (4.37 g, 29.9 mmol) as described in
the general procedure for the Wittig reaction afforded 21 (3.6 g,
85%) as a colorless oil (hexane/AcOEt 10%). 1H NMR (300 MHz,
CDCl3): δ = 1.40–1.48 (m, 2 H), 1.61–1.70 (m, 2 H), 2.07 (q, J =
7.1 Hz, 2 H), 2.32 (t, J = 7.7 Hz, 2 H), 3.68 (s, 3 H), 4.94–5.05 (m,
2 H), 5.76–5.85 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
115.2, 137.8, 208.6 ppm. IR (film): ν = 2180, 1720, 1640 cm–1.
˜
C13H22OSi (222.14): calcd. C 70.21, H 9.97; found C 70.38, H 9.81.
5-Vinyldec-9-en-1-yn-5-ol (24a): Following the general procedure
for the reaction of Grignard reagents with carbonyl compounds,
from 23a (1.80 g, 8.1 mmol), 1.45 g (72%) of 1-trimethylsilyl-5-vin-
yldec-9-en-1-yn-5-ol were obtained as a colorless oil. This product
(1.45 g, 5.8 mmol) was dissolved in anhydrous THF (30 mL) at
0 °C followed by dropwise addition of TBAF (12.9 mL, 11.8 mmol,
1.1 ). The reaction mixture was stirred for 2 h at this temperature.
The residue was taken up in a mixture of ether/hexane (1:1, 60 mL).
The organic layer was washed with water (40 mL), dried with
MgSO4, and concentrated. The crude was purified by flash
chromatography (hexane/AcOEt 15%) obtaining 0.78 g (76%) of
24.3, 28.2, 33.3, 33.8, 51.3, 114.6, 138.3, 174.0 ppm. IR (film): ν =
˜
1740, 1640 cm–1. C8H14O2 (142.10): calcd. C 67.57, H 9.92; found
C 67.49, H 10.07.
Oct-7-en-2-one (20b):
A solution of 1  NaOH (144.2 mL,
144.2 mmol) was added to a solution of 21 (2.05 g, 14.4 mmol) in
EtOH (70 mL). The reaction was refluxed for 4 h, cooled to room
temp., concentrated under vacuum, and concentrated HCl added
to acid pH. The resulting crude was extracted with DCM
(3ϫ20 mL) and the organic layers were washed with brine (20mL),
dried with MgSO4, filtered, and concentrated in vacuo to yield
1.73 g (94%) of hept-6-enoic acid as a colorless oil. CH3Li (17 mL,
27 mmol) in anhydrous THF (25 mL) was added dropwise to a
solution of this acid (1.57 g, 12.2 mmol) in anhydrous THF
(25 mL) at –78 °C. The final mixture was stirred for 10 min at the
same temperature and then allowed to stir for 3 h at room temp.
The crude was poured into 1  HCl (90 mL) at 0 °C and then ex-
tracted with diethyl ether (3ϫ20 mL). The organic layer was
washed with saturated NaHCO3 (2ϫ20 mL) and brine (20 mL),
dried with MgSO4, filtered, and concentrated in vacuo to yield
1.45 g (94%) of 20b as a colorless oil. 1H NMR (300 MHz, CDCl3):
δ = 1.34–1.44 (m, 2 H), 1.55–1.62 (m, 2 H), 2.07 (q, J = 7.1 Hz, 2
H), 2.15 (s, 3 H), 2.44 (t, J = 7.4 Hz, 2 H), 4.94–5.09 (m, 2 H),
5.73–5.89 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.2,
1
24a as a colorless oil. H NMR (300 MHz, CDCl3): δ = 1.37–1.58
(m, 4 H), 1.68–1.90 (m, 2 H), 1.98 (t, J = 2.7 Hz, 1 H), 2.02–2.08
(m, 2 H), 2.21–2.28 (m, 2 H), 4.94–5.04 (m, 2 H), 5.17 (dd, J1
=
10.7, J2 = 1.4 Hz, 1 H), 5.25 (dd, J1 = 17.3, J2 = 1.4 Hz, 1 H),
5.72–5.86 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.9,
22.5, 33.8, 38.8, 40.5, 68.6, 75.1, 84.7, 113.3, 114.6, 138.4,
142.5 ppm. IR (film): ν = 2120, 1640 cm–1. C H O (178.19):
˜
12 18
calcd. C 80.85, H 10.18; found C 80.73, H 10.25.
Complex 25a: Hexacarbonyldicobalt–5-Vinyldec-9-en-1-yn-5-ol:
Treatment of 24a (0.50 g, 2.8 mmol) as described in the general
procedure to obtain enyne complexes with [Co2(CO)8] afforded
1.22 g (93%) of pure 25a as a dark-red oil after flash chromatog-
raphy (hexane/AcOEt 10%). 1H NMR (300 MHz, CDCl3): δ =
1.43–1.46 (m, 2 H), 1.58–1.61 (m, 2 H), 1.79–1.89 (m, 2 H), 2.06–
2.09 (m, 2 H), 2.84–2.89 (m, 2 H), 4.95–5.05 (m, 2 H), 5.18–5.29
(m, 2 H), 5.81–5.86 (m, 2 H), 6.01 (s, 1 H) ppm.
28.3, 29.8, 33.5, 43.5, 114.6, 138.4, 209.1 ppm. IR (film): ν = 1720,
˜
1640 cm–1.
4a-Hydroxy-3,4,4a,5,6,7,7a,7b-octahydro-1H-cyclopenta[cd]inden-1-
one (26a) and 2-[2-(1-Hydroxycyclohex-2-enyl)ethyl]cyclopent-2-en-
one (27): Treatment of 25a (1.22 g, 2.6 mmol) as described in
method C (but in toluene) for the RCM/Pauson–Khand reaction
afforded pure 26a (0.09 g, 20%) and 0.08 g (14%) of 27, both as
colorless oils after flash chromatography (hexane/AcOEt 10%).
1
1,1-Dimethyl-2-(oct-7-en-2-ylidene)hydrazine (22b): Compound 20b
(2.00 g, 17.9 mmol) was treated as for the synthesis of 22a, yielding
1.70 g (63%) of 22b (mixture of isomers) as a colorless oil after
vacuum distillation. 1H NMR (300 MHz, CDCl3): δ = 1.36–1.57
(m, 8 H), 1.91 (s, 3 H, minor), 1.94 (s, 3 H, major), 2.03–2.10 (m,
4 H), 2.17–2.22 (m, 4 H), 2.40 (s, 3 H, minor), 2.43 (s, 3 H, major),
26a: H NMR (300 MHz, CDCl3): δ = 1.06–1.19 (m, 1 H), 1.26– 4.93–5.03 (m, 4 H), 5.73–5.86 (m, 2 H) ppm. 13C NMR (75 MHz,
1.36 (m, 1 H), 1.43–1.71 (m, 3 H), 1.79 (s, 1 H), 2.02–2.10 (m, 2
CDCl3): δ = 16.3, 22.5, 25.7, 26.3, 28.3, 28.7, 31.1, 33.3, 33.4, 38.7,
Eur. J. Org. Chem. 2008, 3917–3927
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3925

J. Pérez-Castells et al.
46.9, 47.4, 114.4, 114.5, 138.4, 138.5, 167.7, 169.4 ppm. IR (film): perature overnight and then was filtered through diatomaceous
FULL PAPER
ν = 1760, 1640 cm–1. C H N (168.16): calcd. C 71.37, H 11.98,
N 16.65; found C 71.50, H 12.13, N 16.83.
earth and the solvent evaporated under vacuum to obtain 0.34 g
(98%) of 30 as a yellow oil. The product was used without further
purification. 1H NMR (300 MHz, CDCl3): δ = 2.53–2.57 (m, 2 H),
2.84–2.90 (m, 2 H), 3.15 (s, 1 H), 3.74 (s, 3 H), 5.95 (s, 1 H), 6.15
(s, 1 H), 6.63–6.66 (m, 2 H), 7.35 (dd, J1 = 9.3, J2 = 2.2 Hz, 1 H),
9.50 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 28.3, 32.4,
54.9, 79.5, 82.0, 111.4, 113.5, 114.2, 133.9, 134.6, 145.2, 148.7,
˜
10 20
2
1-(Trimethylsilyl)undec-10-en-1-yn-5-one (23b): Treatment of 22b
(0.95 g, 5.6 mmol) as described for the synthesis of 23a afforded
pure 23b (0.84 g, 63%) as a colorless oil after flash chromatography
1
(hexane/AcOEt 5%). H NMR (300 MHz, CDCl3): δ = 0.14 (s, 9
H), 1.34–1.44 (m, 2 H), 1.56–1.66 (m, 2 H), 2.03–2.10 (m, 2 H),
2.42–2.51 (m, 4 H), 2.63–2.68 (m, 2 H), 4.94–5.04 (m, 2 H), 5.73–
5.86 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = –0.1, 14.3,
23.0, 28.2, 33.3, 41.3, 42.5, 84.8, 105.6, 114.6, 138.2, 208.5 ppm. IR
159.6, 194.3 ppm. IR (film): ν = 2100, 1690, 1610 cm–1.
˜
N-Allyl-4-(2-ethynyl-5-methoxyphenyl)-2-methylenebutan-1-amine
(31): Molecular sieves (1.4 g) and allylamine (0.13 mL, 1.8 mmol)
were added to a solution of 30 (0.34 g, 1.6 mmol) in anhydrous
ether (20 mL) under argon. The resulting mixture was stirred at
room temp. overnight. The reaction was filtered and concentrated
in vacuo. The residue was redissolved in absolute EtOH (10 mL)
and NaBH4 (0.12 g, 3.20 mmol) was added. The mixture was
stirred for 4 h at room temp. The crude was concentrated under
vacuum, Et2O (15 mL) was added, and the mixture was washed
with brine (20mL), dried with MgSO4, filtered, and concentrated.
The reaction afforded 0.28 g (70%) of 31 as a yellow oil without
further purification. 1H NMR (300 MHz, CDCl3): δ = 2.33–2.38
(m, 2 H), 2.86–2.92 (m, 2 H), 3.15 (s, 1 H), 3.21–3.23 (m, 4 H),
3.78 (s, 3 H), 4.89 (s, 1 H), 4.94 (s, 1 H), 5.07 (d, J = 10.4 Hz, 1
H), 5.15 (dd, J1 = 17.0, J2 = 1.6 Hz, 1 H), 5.83–5.96 (m, 1 H),
6.65–6.73 (m, 2 H), 7.38 (d, J = 8.8 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 29.4, 33.1, 34.8, 51.4, 53.3, 54.9, 79.2, 82.1,
110.2, 111.1, 113.4, 114.1, 115.6, 134.0, 136.6, 146.2, 146.8,
(film): ν = 2180, 1720, 1640 cm–1. C H OSi (236.16): calcd. C
˜
14 24
71.12, H 10.23; found C 71.33, H 10.40.
5-Vinylundec-10-en-1-yn-5-ol (24b): Following the general pro-
cedure for the reaction of a Grignard reagent with carbonyl com-
pounds, from 23b (0.84 g, 3.6 mmol), 0.92 g (100%) of 1-(trimethyl-
silyl)-5-vinylundec-10-en-1-yn-5-ol were obtained as a colorless oil.
This product (1.00 g, 3.8 mmol) was dissolved in anhydrous THF
(20 mL) at 0 °C followed by dropwise addition of TBAF (8.9 mL,
8.1 mmol, 1.1 ). The reaction mixture was stirred for 2 h at this
temperature. The residue was then taken up in a mixture of ether/
hexane (1:1, 50 mL). The organic layer was washed with water,
dried with MgSO4, and concentrated. The crude was purified by
flash chromatography (hexane/AcOEt 10%) to obtain 0.62 g (85%)
1
of 24b as a colorless oil. H NMR (300 MHz, CDCl3): δ = 1.26–
1.44 (m, 4 H), 1.49–1.61 (m, 2 H), 1.68–1.90 (m, 2 H), 1.98 (t, J =
2.8 Hz, 1 H), 2.02–2.09 (m, 2 H), 2.21–2.29 (m, 2 H), 4.93–5.03 (m,
2 H), 5.17 (d, J = 10.4 Hz, 1 H), 5.25 (d, J = 17.6 Hz, 1 H), 5.73–
5.87 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.7, 22.6,
29.0, 33.4, 38.7, 40.8, 68.4, 75.0, 84.6, 113.1, 114.2, 138.5,
159.6 ppm. IR (film): ν = 3290, 2100, 1610 cm–1.
˜
Complex 32: Hexacarbonyldicobalt–1-(tert-Butoxycarbonyl)-3-[2-(2-
ethynyl-5-methoxyphenyl)ethyl]-2,5-dihydro-1H-pyrrole: (Boc)2O
(0.49 g, 2.2 mmol) was added to a solution of 31 (0.28 g, 1.1 mmol)
in dioxane (6 mL) and the reaction was allowed to stir at room
temp. for 4 h. The residue was concentrated and taken up in a mix-
ture of diethyl ether/water (1:1, 20 mL). The organic layer was
washed with brine, dried with MgSO4, and concentrated. The crude
was purified by flash chromatography (hexane/AcOEt, 20:1), ob-
taining 0.25 g (64 %) of tert-butyl allyl[4-(2-ethynyl-5-meth-
oxyphenyl)-2-methylenebutyl]carbamate as a yellow oil. Treatment
of this product (0.15 g, 0.43 mmol) as described in the general pro-
cedure for the synthesis of hexacarbonyldicobalt–alkyne complexes
afforded the corresponding pure hexacarbonyldicobalt complex as
a dark-red oil. [Ru]-I (0.03 g, 0.04 mmol) was added to a solution
of this complex (0.43 mmol) in anhydrous benzene (30 mL) under
argon. The reaction mixture was stirred for 17 h at room temp.,
filtered through diatomaceous earth, and the solvent evaporated
under vacuum. The residue was purified by column chromatog-
raphy (hexane/AcOEt 10%) to obtain 0.13 g (50%) of 32 as a dark-
142.4 ppm. IR (film): ν = 3460, 3300, 2940, 2120, 1640 cm–1.
˜
C13H20O (192.15): calcd. C 81.20, H 10.48; found C 81.04, H 10.56.
Complex 25b: Hexacarbonyldicobalt–5-Vinylundec-10-en-1-yn-5-ol:
Treatment of 24b (0.46 g, 2.2 mmol) as described in the general
procedure for the synthesis of hexacarbonyldicobalt–alkyne com-
plexes afforded pure 25b (1.02 g, 88%) as a dark-red oil after flash
chromatography (hexane/AcOEt 10%). 1H NMR (300 MHz,
CDCl3): δ = 1.27–1.43 (m, 4 H), 1.49–1.59 (m, 2 H), 1.71–1.89 (m,
2 H), 2.02–2.10 (m, 2 H), 2.84–2.92 (m, 2 H), 4.95–5.05 (m, 2 H),
5.17–5.30 (m, 2 H), 5.75–5.89 (m, 2 H), 6.02 (s, 1 H) ppm.
4a-Hydroxy-4,4a,5,6,7,8,8a,8b-octahydrocyclopenta[cd]azulen-
1(3H)-one (26b) and 6-(Hex-5-en-1-yl)-6-hydroxy-4,5,6,6a-tetra-
hydropentalen-2(1H)-one (28): [Ru]-I (0.17 g, 0.1 mmol) was added
to a solution of 25b (1.02 g, 2.1 mmol) in anhydrous toluene
(150 mL) under argon. The reaction was stirred at room temp. Af-
ter 48 h the TLC showed the presence of the starting material. The
reaction was warmed to 40 °C, and a suspension of NMO
(12 mmol) in anhydrous toluene (4 mL) was added to the reaction
mixture, which was then stirred overnight. The crude was filtered
through diatomaceous earth and the solvent evaporated under vac-
uum. The residue was purified by column chromatography (hexane/
AcOEt 35%), obtaining 0.18 g of a mixture of 26b and 28 (3:2)
which were inseparable by chromatography. 1H NMR (300 MHz,
CDCl3): δ = 1.24–1.31 (m, 2 H), 1.41–1.46 (m, 2 H), 1.53–1.75 (m,
6 H), 1.86–1.94 (m, 1 H), 2.02–2.25 (m, 8 H), 2.36–2.38 (m, 2 H),
2.50–2.58 (m, 1 H), 2.70–2.74 (m, 4 H), 2.88–2.90 (m, 2 H), 2.96
(d, J = 7.4 Hz, 1 H, major), 4.95–5.04 (m, 2 H, minor), 5.74–5.87
(m, 1 H, minor), 5.94 (br. s, 1 H, major), 5.99 (br. s, 1 H,
minor) ppm.
1
red oil. H NMR (300 MHz, CDCl3): δ = 1.47 (s, 9 H), 2.32–2.39
(m, 2 H), 2.85–2.92 (m, 2 H), 3.80 (s, 3 H), 4.04–4.14 (m, 4 H),
5.48 (d, J = 17.0 Hz, 1 H), 6.31 (s, 1 H), 6.66 (d, J = 2.2 Hz, 1 H),
6.81 (d, J = 8.8 Hz, 1 H), 7.57 (dd, J1 = 8.8, J2 = 2.2 Hz, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 28.5, 29.8, 32.2, 53.2, 54.7, 55.1,
75.0, 79.3, 87.0, 112.7, 114.2, 119.1, 126.9, 136.1, 138.9, 141.0,
154.2, 159.5, 199.6 ppm. IR (film): ν = 2090, 2040, 2020, 1700,
˜
1660, 1600 cm–1.
tert-Butyl 2-Methoxy-6-oxo-6a,7,8,9,10,11-hexahydro-6H-benzo-
[4,5]indeno[1,7a-c]pyrrole-8-carboxylate (33) and tert-Butyl 7-Meth-
oxy-10-methylene-1,2,3,4,5,10-hexahydrobenzo[5,6]cyclohepta-
[1,2-b]pyrrole-1-carboxylate (34): Molecular sieves (0.11 g) and
[Rh(PPh3)2ClCO] (3.2 mg, 0.005 mmol) were added to a solution
of 32 (0.06 g, 0.09 mmol) in anhydrous toluene (1.8 mL). The reac-
tion was refluxed at room temperature under argon for 24 h. The
4-(2-Ethynyl-5-methoxyphenyl)-2-methylenebutanal (30): MnO2
(1.39 g, 16.0 mmol) was added to a solution of 29 (0.35 g,
1.6 mmol) in MeCN (15 mL). The crude was stirred at room tem-
3926
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3917–3927

One-Step Synthesis of Tricyclic Structures
[3]
[4]
[5]
J. Cassayre, S. Z. Zard, J. Am. Chem. Soc. 1999, 121, 6072–
6073.
M. E. Krafft, Y. Y. Cheung, K. A. Abboud, J. Org. Chem. 2001,
66, 7443–7448.
T. F. Jamison, S. Shambayati, W. E. Crowe, S. L. Schreiber, J.
Am. Chem. Soc. 1997, 119, 4353–4363.
crude was filtered through diatomaceous earth and the solvent
evaporated under vacuum. The residue was purified by column
chromatography (hexane/AcOEt 5%), obtaining 0.02 g (30%) of 33
as a colorless oil and 0.01 g (20%) of 34 as a yellow oil.
1
33: H NMR (300 MHz, CDCl3): δ = 1.41 (s, 9 H), 1.99–2.09 (m,
1 H), 2.23 (dd, J1 = 12.6, J2 = 3.3 Hz, 1 H), 2.62 (d, J = 6.6 Hz, 1
H), 2.92–3.13 (m, 2 H), 3.31 (d, J = 11.5 Hz, 1 H), 3.41–3.47 (m,
1 H), 3.47–3.86 (m, 1 H), 3.86 (s, 3 H), 4.03 (d, J = 11.5 Hz, 1 H),
6.24 (s, 1 H), 6.74 (s, 1 H), 6.84 (d, J = 8.8 Hz, 1 H), 7.58 (d, J =
8.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.9, 28.3,
32.2, 47.3, 53.1, 53.2, 55.4, 57.2, 79.9, 113.6, 113.7, 120.8, 121.9,
[6]
[7]
J. R. Green, Synlett 2001, 353–356.
a) D. G. Young, J. A. Burlison, U. Peters, J. Org. Chem. 2003,
68, 3494–3497; b) J. A. Burlison, J. M. Gray, D. G. J. Young,
Tetrahedron Lett. 2001, 42, 5363–5365.
M. Rosillo, L. Casarrubios, G. Domínguez, J. Pérez-Castells,
Org. Biomol. Chem. 2003, 1, 1450–1451.
[8]
[9]
L. Pérez-Serrano, J. Blanco-Urgoiti, L. Casarrubios, G.
Domínguez, J. Pérez-Castells, J. Org. Chem. 2000, 65, 3513–
3519, and references therein.
When irradiating 7b-H a NOE increment of 5% was observed
both in the signal of 7a-H and 4a-H.
Calculated by integration of the signals corresponding to the
olefinic proton in the 1H NMR spectrum of the crude mixture.
Compound 19bα: No NOE increments in 8a-H were observed
when irradiating 8b-H or 4a-H. Compound 19bβ: when irradi-
ating 8b-H a NOE increment of 8% was observed in the signal
of 8a-H and a 12% increment was observed in the signal of
4a-H. The signals were assigned on the basis of a COSYGR
experiment.
129.8, 140.5, 154.5, 162.1, 170.0, 208.4 ppm. IR (film): ν = 1690,
˜
1630 cm–1. C21H25NO4 (355.43): calcd. C 70.96, H 7.09, N 3.94;
found C 70.82, H 7.31, N 4.05.
[10]
[11]
[12]
1
34: H NMR (300 MHz, CDCl3): δ = 1.41 (s, 9 H), 1.60–1.69 (m,
2 H), 1.79–1.82 (m, 2 H), 2.73–2.94 (m, 2 H), 3.38–3.64 (m, 2 H),
3.73 (s, 3 H), 4.93 (s, 1 H), 5.41 (br. s, 1 H), 6.64 (s, 1 H), 6.75 (d,
J = 8.8 Hz, 1 H), 7.57 (d, J = 8.8 Hz, 1 H) ppm.
Acknowledgments
This work was supported by the Spanish Ministerio de Educación
y Ciencia (MEC) (grant no. CTQ2006/00601). M. R. C. acknowl-
edges the Dirección General de Educación Superior e Investigación
Científica (DGESIC), Spanish Ministerio de Ciencia y Tecnología
(MCYT) for a predoctoral fellowship. A. P. and A. G.-G. acknow-
ledge the fellowships awarded by the Fundación Universitaria San
Pablo-CEU.
[13]
[14]
Y. Q. Tu , A . H übener, H. Zhang, C. J. Moore, M. T. Fletcher, P.
Hayes, K. Dettner, W. Francke, C. S. P. McErlean, W. Kitching,
Synthesis 2000, 1956–1978.
a) O. Jeger, V. Prelog in The Alkaloids: Chemistry and Phy-
siology (Ed.: R. H. F Manske), Academic Press, New York,
1960, vol. VII, p. 319; b) K. K. Bhutani, M. Ali, S. R. Sharma,
R. M. Vaid, D. K. Gupta, Phytochemistry 1988, 27, 925–928;
c) K. K. Bhutani, R. M. Vaid, M. Ali, R. Kapoor, S. R.
Soodan, D. Kumar, Phytochemistry 1990, 29, 969–997.
M. E. Kopach, A. H. Fray, A. I. Meyers, J. Am. Chem. Soc.
1996, 118, 9876–9883.
a) G. Stork, S. D. Darling, I. T. Harrison, P. S. Wharton, J. Am.
Chem. Soc. 1962, 84, 2018–2020; b) W. Nagata, T. Terasawa,
T. Aoki, Tetrahedron Lett. 1963, 4, 869–871; c) J. A. Marshall,
W. S. Johnson, J. Am. Chem. Soc. 1962, 84, 1485–1486; d) B.
Jiang, M. Xu, Angew. Chem. Int. Ed. 2004, 43, 2543–2546.
The synthesis of 29 and the study of the PKR conditions of
substituted alkenes will be published soon: E. Arnáiz, J.
Blanco-Urgoiti, D. Abdi, G. Domínguez, J. Pérez-Castells, J.
Organomet. Chem. DOI:10.1016/j.jorganchem.2008.04.023.
Received: March 31, 2008
[1] For reviews on olefin metathesis, see: a) T. Katz, Angew. Chem.
Int. Ed. 2005, 44, 3010–3019; b) R. R. Schrock, J. Mol. Catal.
A 2004, 213, 21–30; c) A. H. Hoveyda, R. R. Schrock, Compr.
Asymmetric Catal. 2004, 1, 207–233; d) R. H. Grubbs, Tetrahe-
dron 2004, 60, 7117–7140; e) R. H.Grubbs, T. M. Trnka in Ru-
thenium in Organic Synthesis (Ed.: S.-I. Murahashi), Wiley-
VCH, Weinheim, 2004, chapter 6.
[2] For recent reviews on the Pauson–Khand reaction, see: a) J.
Blanco-Urgoiti, L. Anorbe, L. Perez-Serrano, G. Dominguez,
J. Perez-Castells, Chem. Soc. Rev. 2004, 33, 32–42; b) T. Sugih-
ara, M. Yamaguchi, M. Nishizawa, Chem. Eur. J. 2001, 7,
1589–1595; c) K. M. Brummond, J. L. Kent, Tetrahedron 2000,
56, 3263–3283; d) S. E. Gibson, N. Mainolfi, Angew. Chem. Int.
Ed. 2005, 44, 3022–3037.
[15]
[16]
[17]
Published Online: June 3, 2008
Eur. J. Org. Chem. 2008, 3917–3927
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3927