An efficient catalytic protocol for the Pauson-Khand reaction

Article abstract of DOI:10.1016/j.tet.2007.10.089

New experimental conditions have been developed for an efficient catalytic Pauson-Khand reaction. These are based on the use of a mixture of molecular sieves and tert-butanol as inducers of the process. This mixture, with the appearance of a paste, is abl

Full text of DOI:10.1016/j.tet.2007.10.089

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 67e74
www.elsevier.com/locate/tet
An efficient catalytic protocol for the PausoneKhand reaction
y
*
´
Jaime Blanco-Urgoiti , Delbrin Abdi, Gema Domınguez, Javier Perez-Castells
´
Departamento de Qu´ımica, Facultad de Farmacia, Universidad San Pablo-CEU, Urb. Montepr´ıncipe, Boadilla del Monte, 28668 Madrid, Spain
Received 5 October 2007; received in revised form 18 October 2007; accepted 25 October 2007
Available online 19 November 2007
Abstract
New experimental conditions have been developed for an efficient catalytic PausoneKhand reaction. These are based on the use of a mixture
of molecular sieves and tert-butanol as inducers of the process. This mixture, with the appearance of a paste, is able to adsorb CO, thus improv-
ing the conversion and making it possible to effect the reactions in the absence of a CO atmosphere. The protocol is applied to known and un-
known substrates and compared to previously described conditions, showing good results with intra- and intermolecular examples.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: PausoneKhand; Catalysis; Cyclization
1. Introduction
generally with high CO pressures. Cobalt on mesoporous
silica,11 charcoal,12 Raney cobalt,13 colloidal14 cobalt particles
or heterogeneous bimetallic catalyst15 have also been used to
catalyze the reaction with high yields although using severe con-
ditions. Still, most of these studies lack generality and are made
only with a few substrates gem-disubstituted or bearing hetero-
atoms that act as soft ligands.
The establishment of an efficient catalytic protocol for the
PausoneKhand1 reaction has received great attention in the
past years.2 The only possibility of fulfilling the principles
of green chemistry in this reaction would be the use of effi-
cient and reusable metal catalysts. The first reports3 used
severe reaction conditions with high CO pressures, or chemi-
cal additives like phosphites to induce the reaction.4 The situ-
ation changed after the contributions of Livinghouse5 and
Krafft.6 These groups made extensive studies with reactions
carried out at 1 atm of CO. Thus, Livinghouse determined
the best temperature for a catalytic PausoneKhand reaction,
which was situated in the narrow gap of 65e75 ꢀC. Krafft
reported good results with commercial non-purified Co2(CO)8,
and indicated a generally favorable effect of the addition of
cyclohexylamine in the reaction. Both groups used alternatively
as catalyst a preformed and purified cobalthexacarbonyle
Other metals give an interesting alternative for the catalysis
of this reaction. Ruthenium,16 iridium17 or molybdenum18
have been used, although the most promising complexes are
actually those of rhodium.19 The main problems to be solved
in catalytic PKR are the finding of an efficient procedure that
avoids or minimizes the use of CO and that is applicable to
a wide variety of substrates including intermolecular reactions.
In the past years, new reaction protocols and promoters
have increased the use of the reaction to new substrates.20 In
particular we have shown that molecular sieves can act as
new efficient promoters for PausoneKhand reactions.21 This
zeolites improve the conversion of known and new substrates
and have allowed new applications of this reaction in benzenic
enynes22 and enynoindoles.23 The aim of the present work is
to develop a new protocol for a catalytic version of the Pau-
soneKhand reaction based on the use of molecular sieves.24
As zeolites are able to adsorb small molecules such as CO,
we believe this will help in the recovery of active cobalt
alkyne complex.7 Other cobalt sources like Co2(CO)7PPh3,8
Co4(CO)12,9 or alkylidene-Co3(CO)9
10
have been used
* Corresponding author.
E-mail address: jpercas@ceu.es (J. Perez-Castells).
´
y
´
Present address: Centro de investigacion Lilly, S. A., Avda. de la industria,
30, 28108 Alcobendas, Madrid, Spain.
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.089

68
J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
species thus improving the catalytic cycle, and allowing
milder conditions.
1 atm of CO (entry 4). In view of the result of entry 3, we
˚
prepared a suspension of powdered 4 A molecular sieves in
Performing a catalytic PKR implies the use of a CO atmo-
sphere. This discourages many potential users of this powerful
synthetic process. A couple of groups have developed a new
way to produce CO in situ by using aldehydes as a source of
this gas via a decarbonylation process induced by the same rho-
dium complex that catalyses the PKR.25 We believed that it was
worth trying to tune up a procedure in which the use of CO gas
could be minimized, being experimentally easy and efficient.
tert-butanol. This mixture was submitted to three cycles of
vacuum/CO, and then it was kept in the fridge producing
a pale brown paste. The use of tert-butanol was intended to
slow the diffusion of the CO, being this solvent easily elimi-
nated after the reaction in vacuo, and able to solidify in the
fridge so that it could be kept for long time without losing effi-
ciency. The mixture of molecular sieves and tert-butanol treated
with CO (1 g per mmol of substrate) was added to a flask with
substrate 1a and 10% of Co2(CO)8 dissolved in toluene, and af-
ter 16 h the PKR had finished and the product was obtained in
60% yield. The activity of this paste along time was checked,
repeating the reaction after 2 days and 2 weeks, using the
same batch of paste. Yields were kept in these experiments in
the same range (entry 5, note d). Next, the procedure was
used with substrates 1bed. The use of the paste gives similar
results (entries 6, 11, 13, and 15) than with standard conditions
under CO atmosphere (entries 8, 12, 14, and 16). With non-
terminal alkyne 1b, a reaction at higher temperature was tested
showing an important decrease in yield (entry 7). In addition,
this substrate was submitted to a rhodium catalyzed reaction
and gave similar results with the standard conditions (entry
10) and with the use of the paste (entry 9).
2. Results and discussion
We investigated a catalytic PausoneKhand reaction in the
absence of a CO atmosphere, to see if molecular sieves could fa-
vor the recovery of active species giving rise to catalytic cycles.
The beneficial effect of the zeolites in the PKR may be due to
surface interaction with the enyne that would stabilize the pre-
transition state, as suggested for the DSAC conditions (Dry State
Adsorption Conditions), described in early times by Smit and
Caple.26 Adsorption of CO by the sieves and regeneration of
active cobalt species is probably responsible for their favorable
effect. With the aim to develop a new catalytic protocol, we sub-
mitted compound 1a to three reactions in air atmosphere with
10% cobalt octacarbonyl (entries 1e3, Table 1): blank reaction,
addition of molecular sieves, and addition of molecular sieves
heated to 200 ꢀC and cooled under carbon monoxide.
Next we extended this methodology to other substrates. In
particular we selected aromatic enynes 3. Compound 3a was
used as a model and the stoichiometric PKRs that we de-
scribed previously27 are indicated in Table 2 for comparative
reasons. These conditions are: combination of trimethylamine
N-oxide (TMANO) with molecular sieves in toluene at room
The results showed an important increase in conversion
with sieves, reaching 65% with the pre-treated zeolite. This re-
sult was comparable with standard catalytic conditions under
Table 1
Tuning up of catalytic PKR conditions with substrates 1
R'
EtO2C
EtO2C
EtO2C
Catalyst
R'
R
O
toluene
EtO2C
R
1a-d
2a-d
Entry
Catalyst/loading
Additive
CO
R
R0
Product
Temp (ꢀC)
Time (h)
Method
Yield (%)
1
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
[Rh(CO)2Cl]2/2.5%
[Rh(CO)2Cl]2/2.5%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
Co2(CO)8/10%
No
No
No
No
H
H
H
H
H
H
H
H
H
H
H
2a
2a
65
65
18
18
18
24
16
24
24
24
36
31
48
20
48
24
40
24
A
B
C
D
E
E
E
D
F
15
30
65
58
60d
62
15
60
68
70
62
65
71
73
67
63
2
M.S.a
Pre-CO M.S.b
No
H
3
H
2a
2a
65
65
4
1 atm
No
No
H
5
Pastec
Pastec
Pastec
No
Pastec
No
Pastec
No
H
2a
2b
65
65
6
Me
Me
Me
Me
Me
H
7
No
1 atm
No
2b
2b
100
65
8
9
2b
2b
100
100
65
10
11
12
13
14
15
16
a
1 atm
No
G
E
D
E
D
E
D
Z-OMe
cis-2c
cis-2c
trans-2c
trans-2c
trans-2d
trans-2d
1 atm
No
H
Z-OMe
E-OMe
E-OMe
E-OMe
E-OMe
65
65
Paste
No
Pastec
No
H
1 atm
No
1 atm
H
65
65
Me
Me
65
˚
M.S.: powdered 4 A molecular sieves.
˚
Pre-CO M.S.: powdered 4 A molecular sieves heated at 200 C and cooled under CO in a separate flask.
b
c
d
ꢀ
˚
Paste: mixture of powdered 4 A molecular sieves/tert-butanol treated with CO (see Section 4) 1 g/mmol of substrate.
This reaction was repeated 2 days and 2 weeks after preparation of the paste with the following yields: 58% and 61%, respectively.

J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
69
Table 3
PKR of different substrates comparing our protocol with paste (conditions E)
with standard conditions D and stoichiometric conditions I
temperature (method H, entry 1) and only with molecular
sieves as promoters in refluxing toluene (method I, entry
2).21 The catalytic reactions were performed using methods
D and E (with cobalt, entries 3 and 4, Table 1). The results
are summarized in Table 2.
Entry Starting material
Product
Yield (%)
Method Method Method
D
E
I
The first two entries, corresponding to the stoichiometric
versions show that different reaction products were obtained
depending on the reaction conditions. Thus, the hydroxy-tetra-
line 4a was obtained at room temperature, while in refluxing
toluene, dehydration and isomerization lead to naphthalene 6
with good yields. Compound 4a was obtained as a single ste-
reoisomer, which resulted to be trans-fused as shown by the
NOE experiments. Entries 3 and 4 show that there are no sig-
nificant differences when using our procedure and a standard
catalytic method. Compound 3b gave under catalytic condi-
tions D and E similar yields of an only stereoisomer of 4b
(entries 5 and 6), in contrast with what we had observed in pre-
vious stoichiometric reactions where a mixture of diastereo-
isomers was obtained.27 For compound 3c elevation of the
reaction temperature gave better results (entries 7e9). This
compound was also reacted using rhodium catalysis, giving
similar results with both methods (entries 10 and 11), although
worse than with cobalt catalysis. The reaction with rhodium
proceeded only at 100 ꢀC, not observing any conversion at
lower temperatures. In these aromatic compounds our proce-
dure gives, in general, comparable although slightly lower
yields than with standard conditions.
O
1
2
3
48
52
55
60
61
O
O
BOC
N
45
50
40
50
BOC
N
O
EtO2C
EtO2C
EtO2C
EtO2C
O
Ph
O
4
5
6
51
41
78
49
55
68
54
60
75
Ph
O
O
Ph
Ph
+
O
+
O
H
CO2Et
+
C3H7
C3H7
25a
40a
EtOOC
7
8
10
62
O
Finally we selected a bunch of substrates, including some
intermolecular examples, and compared the results of our
O
60
60
O
Table 2
PKR of compounds 3 in different conditions
O
a
This reaction was carried out in sealed tube.
R'
catalyst/ toluene
paste or CO
protocol (conditions E) with standard catalytic conditions D
and stoichiometric conditions I (Table 3). The results show
that our procedure works well with different structures and
gives similar results than other catalytic protocols under CO
atmosphere. In some examples (entries 2, 3, 5, and 7) stoichio-
metric reactions give significant better yields than both cata-
lytic protocols. The intermolecular PKR is still limited in
scope to certain strained alkenes and some allenes. We tested
the reaction of norbornene with 1-hexyne and phenylacetylene
(entries 5 and 6) with moderate to good results. In addition, the
catalytic reaction of ethyl 2,3-butadienoate with 3-hexyne
gave the desired cyclopentenone in low yield although not
far from the result with stoichiometric conditions (entry 7).
This latter reaction was performed in sealed tube to avoid
evaporation of the starting materials.
R
3a-c
O
H
O
R'
R'
+
+
R
4a-c
R
5a-c
6
Entry
Subs.
Method
R
R0
Temp (ꢀC)
Yield (%)
4
5
6
1
3a
3a
3a
3a
3b
3b
3c
3c
3c
3c
3c
H
I
OH
OH
H
rt
77
d
40
55
40
57
24
65
75
38
40
d
d
d
d
d
d
38a
d
d
d
8
d
75
<5
<5
d
d
d
d
d
d
d
2
H
110
65
3
D
E
D
E
D
D
E
F
OH
OH
H
4
H
65
65
5
OTBS
OTBS
OTBS
OTBS
OTBS
OTBS
OTBS
H
6
H
65
65
7
Me
Me
Me
Me
Me
3. Conclusion
8
110
110
100
100
9
10
11
a
A new easy procedure for catalytic PKR is shown. The pro-
tocol diminishes the use of CO gas in the lab and gives similar
results as other procedures described in the literature. The
G
Obtained as a 1:1 mixture of Z/E isomers.

70
J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
preparation of the paste still needs the usual safety conditions
to operate with CO gas, but this mixture can be used in a dif-
ferent lab with only standard working conditions and the pro-
cedure allows carrying out a set of reactions at the same time.
Although not reusable, one batch of this paste can be used for
several reactions along, at least, 2 weeks. Different substrates
including intermolecular examples can be used and the condi-
tions work both with cobalt catalysis and rhodium complexes.
The possible applications of the paste described herein to other
reactions are underway.
added. The mixture was stirred 2 h at ꢂ78 ꢀC, and the reaction
was quenched with saturated NH4Cl. The mixture was ex-
tracted with EtOAc, washed with water (2ꢁ100 mL) and brine
(2ꢁ100 mL). The organic layer was dried over anhydrous
MgSO4, filtered and concentrated under vacuo. Purification
by flash chromatography with hexaneeEtOAc 10:1 as eluent
gave a product (1.64 g, 70% yield) as colorless oil. This prod-
uct (0.31 g, 1.3 mmol) was dissolved in anhydrous THF
(50 mL) at 0 ꢀC, and 19.6 mL (19.6 mmol) of 1 N TBAF
was added. The mixture was stirred at this temperature for
2.5 h and quenched with water, hexane, and diethylether.
The organic layer was washed with water (2ꢁ100 mL) and
brine (2ꢁ100 mL), dried over anhydrous MgSO4 and concen-
trated under vacuo. Purification by flash chromatography with
hexaneeEtOAc 10:1 as eluent gave 3a (0.18 g, 83% yield) as
4. Experimental
4.1. General methods
General methods have been published before.28 The synthe-
sis of 1a29 and 1b29 have been done according to literature
procedures. Starting materials and products shown in Table 3
are also known (except that of entry 7).
colorless oil. H NMR (CDCl3) d 2.37e2.47 (m, 1H), 2.56e
1
2.65 (m, 1H), 2.90 (br s, 1H), 3.33 (s, 1H), 5.10e5.21
(m, 3H), 5.78e5.91 (m, 1H), 7.20 (td, 1H, J1¼7.1 Hz,
J2¼1.1 Hz), 7.34 (td, 1H, J1¼7.7 Hz, J2¼1.1 Hz), 7.45 (dd,
1H, J1¼7.7 Hz, J2¼1.1 Hz), 7.50 (d, 1H, J¼7.7 Hz). 13C
NMR (CDCl3) d 42.5, 70.8, 81.3, 82.2, 117.9, 119.1, 125.2,
126.8, 129.0, 132.6, 134.4, 146.3. IR (film) n 3400, 3295,
2940, 2100 cmꢂ1. Anal. Calcd for C12H12O: C, 83.69; H,
7.02. Found: C, 83.40; H, 7.26.
4.2. Starting materials
4.2.1. (Z,E )-Diethyl 2-(3-methoxyallyl)-2-(prop-2-ynyl)-
malonate, 1c
To a suspension of 7.43 g (21.7 mmol) of methoxymethyl-
triphenylphosphonium chloride in THF (30 mL), 36.40 mL
(18.2 mmol) of KHMDS 0.5 M was added. The mixture was
stirred 30 min and was cannulated to a solution of 2.08 g
(8.7 mmol) of diethyl 2-(2,2-diethoxyethyl)-2-(2-propynyl)-
malonate in THF (30 mL). The mixture was stirred at room
temperature for 30 min and then was poured to a mixture of
diethyletherewater 1:1. The organic layer was extracted,
washed with water (2ꢁ60 mL) and brine (2ꢁ60 mL), dried
over anhydrous MgSO4 and concentrated in vacuo. Purifica-
tion by flash chromatography with hexaneeEtOAc 20:1 as el-
uent. The product was obtained (1.07 g E-1c, 0.65 g Z-1c,
82% yield) as colorless oils. Z-isomer: 1H NMR (CDCl3)
d 1.25 (t, 6H, J¼7.1 Hz), 1.99 (t, 1H, J¼2.7 Hz), 2.78 (d,
2H, J¼2.7 Hz), 2.83 (dd, 2H, J1¼7.7 Hz, J2¼1.1 Hz), 3.56
(d, 3H, J¼2.2 Hz), 4.16e4.24 (m, 5H), 6.00 (dd, 1H,
J1¼4.9 Hz, J2¼1.1 Hz). 13C NMR (CDCl3) d 13.9, 22.5,
26.7, 56.7, 59.4, 61.4, 70.8, 79.1, 98.9, 149.3, 169.9. Anal.
Calcd for C14H20O5: C, 62.67; H, 7.51. Found: C, 62.51; H,
4.2.3. tert-Butyl(1-(2-ethynylphenyl)but-3-enyloxy)dimethyl
silane, 3b
To a solution of 1.51 g (8.7 mmol) of 3a in DMF (50 mL) at
room temperature, 1.38 g (21.8 mmol) of imidazole and 2.60 g
(17.4 mmol) of tert-butyldimethylsilyl chloride were added.
The mixture was stirred 2 h and the mixture was extracted
with diethylether. The organic layer was washed with water
(4ꢁ50 mL) and brine (4ꢁ50 mL), dried over anhydrous
MgSO4, filtered and concentrated under vacuo. Purification
by flash chromatography with hexaneeEtOAc 5:1 as eluent
gave 3b (2.17 g, 87% yield) as colorless oil. 1H NMR
(CDCl3) d ꢂ0.13 (s, 3H), 0.03 (s, 3H), 0.88 (s, 9H), 2.34e
2.51 (m, 2H), 3.29 (s, 1H), 4.98 (s, 1H), 5.02 (d, 1H,
J¼4.4 Hz), 5.21 (dd, 1H, J1¼7.1 Hz, J2¼4.4 Hz), 5.78e5.92
(m, 1H), 7.17 (td, 1H, J1¼7.7 Hz, J2¼1.1 Hz), 7.34 (td, 1H,
J1¼7.7 Hz, J2¼1.1 Hz), 7.42 (dd, 1H, J1¼7.7 Hz,
J2¼1.1 Hz), 7.53 (d, 1H, J¼7.7 Hz). 13C NMR (CDCl3)
d ꢂ5.0, ꢂ4.8, 18.2, 25.8, 44.2, 72.2, 81.5, 81.8, 116.8,
118.8, 126.1, 126.5, 128.9, 132.3, 135.2, 147.7. IR (film) n
3300, 3060, 3950, 3920, 3850, 2100 cmꢂ1. Anal. Calcd for
C18H26OSi: C, 75.46; H, 9.15. Found: C, 75.72; H, 8.99.
1
7.66. E-isomer: H NMR (CDCl3) d 1.25 (t, 3H, J¼7.1 Hz),
1.26 (t, 3H, J¼7.1 Hz), 2.02 (t, 1H, J¼2.7 Hz), 2.68 (d, 2H,
J¼7.7 Hz), 2.79 (d, 2H, J¼2.7 Hz), 3.50 (d, 3H, J¼1.6 Hz),
4.21 (q, 2H, J¼7.1 Hz), 4.22 (q, 2H, J¼7.1 Hz), 4.49 (dtd,
1H, J1¼12.6 Hz, J2¼7.7 Hz, J3¼1.6 Hz), 6.40 (d, 1H,
J¼12.6 Hz). 13C NMR (CDCl3) d 13.9, 22.1, 30.3, 55.6,
57.0, 61.3, 71.2, 78.8, 94.8, 150.2, 169.6. IR (film) n 3280,
2980, 2940, 2840, 2120, 1740, 1660 cmꢂ1. Anal. Calcd for
C14H20O5: C, 62.67; H, 7.51. Found: C, 62.39; H, 7.46.
4.2.4. tert-Butyldimethyl(1-(2-(prop-1-ynyl)phenyl)-
but-3-enyl oxy)silane, 3c
To a solution of 0.10 g (0.42 mmol) of 3b in anhydrous
THF (4 mL) at ꢂ78 ꢀC, 0.3 mL (0.46 mmol) of 1.6 M BuLi
was added. The mixture was stirred 10 min at ꢂ78 ꢀC, and
0.03 mL (0.46 mmmol) of iodomethane was added. The mix-
ture was stirred 22 h at room temperature, and the reaction was
quenched with saturated NH4Cl. The mixture was extracted
with diethylether (3ꢁ2.5 mL) and washed with brine
(2.5 mL). The organic layer was dried over anhydrous
4.2.2. 1-(2-Ethynylphenyl)but-3-en-1-ol, 3a
To a solution of 2.00 g (9.8 mmol) of 2-trimethylsilylethy-
nylbenzaldehyde in anhydrous THF (50 mL) at ꢂ78 ꢀC,
11.8 mL (11.8 mmol) of 1 N allylmagnesium bromide was

J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
71
MgSO4, filtered and concentrated under vacuo. Purification by
flash chromatography with hexane as eluent gave a product
(0.096 g, 80% yield) as colorless oil. 1H NMR (CDCl3)
d ꢂ0.13 (s, 3H), 0.03 (s, 3H), 0.89 (s, 9H), 2.09 (s, 3H),
2.33e2.51 (m, 2H), 4.99e5.05 (m, 2H) 5.17 (dd, 1H,
J1¼7.7 Hz, J2¼4.4 Hz), 5.80e5.95 (m, 1H), 7.14 (t, 1H,
J¼7.2 Hz), 7.24e7.34 (m, 2H), 7.50 (d, 1H, J¼8.2 Hz). 13C
NMR (CDCl3) d ꢂ5.0, ꢂ4.7, 4.4, 18.2, 25.8, 44.1, 72.4,
77.5, 90.4, 116.6, 120.7, 125.8, 126.4, 127.6, 131.5, 135.7.
IR (film) n 3060, 2950, 2920, 2850, 1640 cmꢂ1. Anal. Calcd
for C19H28OSi: C, 75.94; H, 9.39. Found: C, 75.69; H, 9.16.
heated in a sealed tube. After filtration and solvent elimination
the crude was purified and/or separated by flash chromatogra-
phy (hexaneeEtOAc mixtures).
4.3.6. Method F
Enyne of 1.00 mmol was dissolved in toluene (12 mL). To
this solution, 0.1 mmol of [Rh(CO)2Cl]2 and 1 g of paste (vide
infra) was added and the resulting mixture stirred at 110 ꢀC.
After filtration and solvent elimination the crude was purified
and/or separated by flash chromatography (hexaneeEtOAc
mixtures).
4.3. General procedures for the PausoneKhand reaction
4.3.7. Method G
To a solution of 1.00 mmol of the enyne in toluene
(12 mL), 0.1 mmol of [Rh(CO)2Cl]2 was added and the result-
ing mixture was submitted to three Ar-vacuo cycles and three
vacuo-CO cycles. The reaction was carried out at 110 ꢀC, un-
der a 1 atm of CO. After filtration and solvent elimination the
crude was purified and/or separated by flash chromatography
(hexaneeEtOAc mixtures).
4.3.1. Method A
To a solution of 1.00 mmol of the enyne in toluene
(12 mL), 0.1 mmol of Co2(CO)8 was added and the mixture
was stirred at 65 ꢀC. After filtration and solvent elimination
the crude was purified and/or separated by flash chromatogra-
phy (hexaneeEtOAc mixtures).
4.3.2. Method B
Enyne of 1.00 mmol was dissolved in toluene (12 mL), in
a flask containing two times the mass of the enyne of pow-
4.3.8. Method H
Enyne of 1.00 mmol was dissolved in dry toluene (40 mL)
at room temperature under argon, in a flask containing eight
˚
dered 4 A molecular sieves. To this solution, 0.1 mmol of
˚
times the mass of the enyne of powdered 4 A molecular sieves.
Co2(CO)8 was added and the resulting mixture was submitted
to three Ar-vacuo cycles and three vacuo-CO cycles. The reac-
tion was carried out at 65 ꢀC, under a 1 atm of CO. After
filtration and solvent elimination the crude was purified and/
or separated by flash chromatography (hexaneeEtOAc
mixtures).
To this solution, 1.20 mmol of Co2(CO)8 was added and the
resulting mixture was stirred for 2 h until total complexation
of the enyne (TLC). The reaction was then cooled to
ꢂ10 ꢀC with an ice/salt bath, and a suspension of Me3NO
(9.00 mmol) in toluene at 0 ꢀC was added drop wise. Stirring
was continued at room temperature until completion. The mix-
ture was filtrated, the solvent was evaporated under vacuum
and the crude was purified and/or separated by flash chroma-
tography (hexaneeEtOAc mixtures).
4.3.3. Method C
Enyne of 1.00 mmol was dissolved in toluene (12 mL), in
a flask containing two times the mass of the enyne of pow-
˚
dered 4 A molecular sieves. To this solution, 0.1 mmol of
4.3.9. Method I
Enyne of 1.00 mmol was dissolved in dry toluene (40 mL)
at room temperature under argon, in a flask containing eight
Co2(CO)8 was added and the mixture was stirred at 65 ꢀC.
After filtration and solvent elimination the crude was purified
and/or separated by flash chromatography (hexaneeEtOAc
mixtures).
˚
times the mass of the enyne of powdered 4 A molecular sieves.
To this solution, 1.20 mmol of Co2(CO)8 was added and the
resulting mixture was stirred for 2 h until total complexation
of the enyne (TLC). The reaction was refluxed until comple-
tion. After filtration and solvent elimination the crude was
purified and/or separated by flash chromatography (hexanee
EtOAc mixtures).
4.3.4. Method D
To a solution of 1.00 mmol of the enyne in toluene (12 mL)
or 1.5 mmol of alkyne, 1.00 mmol of alkene or allene,
0.10 mmol of Co2(CO)8 was added and the resulting mixture
was submitted to three Ar-vacuo cycles and three vacuo-CO
cycles. The reaction was carried out at 65 or 100 ꢀC, under
a 1 atm of CO. After filtration and solvent elimination the
crude was purified and/or separated by flash chromatography
(hexaneeEtOAc mixtures).
4.3.10. Preparation of the PASTE
In a 250 mL flask, 20 g of powdered 4 A molecular sieves
˚
was placed and 25 mL of tert-butanol was added. The flask
was stoppered and submitted to three vacuo-CO cycles. The
resulting mixture was stirred for 30 min under CO atmosphere.
The flask was then kept in the fridge until used.
4.3.5. Method E
Enyne of 1.00 mmol or alkyne of 1.5 mmol and alkene or
allene of 1.00 mmol was dissolved in toluene (12 mL). To
this solution, 0.1 mmol of Co2(CO)8 and 1 g of paste (vide in-
fra), was added and the mixture was stirred at 65 or 100 ꢀC. In
the case of the reaction of entry 7 (Table 3), the reaction was
4.3.11. Preparation of diethyl 5-oxo-3,3a,4,5-
tetrahydropentalene-2,2(1H )-dicarboxylate, 2a29
From 1 mmol of 1a, yield of 2a is as follows. Method A:
15%, method B: 30%, method C: 65%, method D: 58%,

72
J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
1
method E: 60%. Yellow oil (hexaneeEtOAc 9:1). H NMR
(CDCl3) d 1.27 (t, 3H, J¼7.1 Hz), 1.29 (t, 3H, J¼7.1 Hz),
1.75 (t, 1H, J¼12.6 Hz), 2.14 (dd, 1H, J1¼18.1 Hz,
J2¼3.3 Hz), 2.63 (dd, 1H, J1¼18.1 Hz, J2¼6.6 Hz), 2.80 (dd,
1H, J1¼12.6 Hz, J2¼7.7 Hz), 3.10e3.15 (m, 1H), 3.26 (d,
1H, J¼18.6 Hz), 3.36 (d, 1H, J¼18.6), 4.21 (q, 2H,
J¼7.1 Hz), 4.26 (q, 2H, J¼7.1 Hz), 5.94 (s, 1H). IR (film)
n 2985, 2910, 1725 cmꢂ1. Anal. Calcd for C14H18O5: C,
63.15; H, 6.81. Found: C, 63.04; H, 6.96.
(0%), H3b/H3ab (6%). Anal. Calcd for C15H20O6: C, 60.80;
H, 6.80. Found: C, 60.67; H, 6.71.
4.3.15. Preparation of (3aS*,4R*)-diethyl 4-methoxy-6-
methyl-5-oxo-3,3a,4,5-tetrahydropentalene-2,2(1H )-
dicarboxylate, trans-2d
From 1 mmol of E-1d, yield of trans-2d is as follows.
Method E: at 65 ꢀC, 67%, method D: 63%. Colorless oil (hex-
aneeEtOAc 7:1). 1H NMR (CDCl3) d 1.24 (t, 3H, J¼7.14 Hz),
1.26 (t, 3H, J¼7.14 Hz), 1.71 (s, 3H), 1.88 (dd, 1H,
J1¼12.1 Hz, J2¼11.0 Hz), 2.82e2.94 (m, 2H), 3.11 (d, 1H,
J¼19.2 Hz), 3.22 (d, 1H, J¼19.2 Hz), 3.52 (s, 3H), 3.65 (d,
1H, J¼2.8 Hz), 4.15e4.26 (m, 4H). 13C NMR (CDCl3)
d 205.7, 172.5, 171.2, 170.8, 131.8, 88.0, 62.2, 62.1, 60.8,
58.3, 49.1, 38.3, 34.1, 14.0, 8.8. IR (film) n 2980, 2925,
1725, 1670 cmꢂ1. NOE: H3ab/H3b (7%), H4a/H3a (4%),
H4a/OCH3 (2%). Anal. Calcd for C16H22O6: C, 91.92; H,
7.15. Found: C, 91.84; H, 7.06.
4.3.12. Preparation of diethyl 6-methyl-5-oxo-3,3a,4,5-
tetrahydropentalene-2,2(1H )-dicarboxylate, 2b
From 1 mmol of 1b, yield of 2b is as follows. Method E: at
65 ꢀC, 62%; at 100 ꢀC, 15%, method D: 60%, method F: 68%,
1
method G: 70%. Yellow oil (hexaneeEtOAc 7:1). H NMR
(CDCl3) d 1.23 (t, 3H, J¼7.14 Hz), 1.24 (t, 3H, J¼7.14 Hz),
1.61 (t, 1H, J¼12.7 Hz), 1.68 (s, 3H), 2.05 (dd, 1H,
J1¼18.1 Hz, J2¼3.0 Hz), 2.61 (dd, 1H, J1¼18.2 Hz,
J2¼6.6 Hz), 2.74 (dd, 1H, J1¼12.7 Hz, J2¼7.1 Hz), 2.93 (br
s, 1H), 3.13 (d, 1H, J¼18.6 Hz), 3.21 (d, 1H, J¼19.2 Hz),
4.14e4.25 (m, 4H). 13C NMR (CDCl3) d 8.6, 14.0, 14.1,
34.0, 39.1, 41.4, 42.7, 60.9, 61.9, 62.1, 133.0, 171.0, 171.6,
4.3.16. PKR of compound 3a
From 1 mmol of 3a, yield of 4a and 6 are as follows.
Method D: 40% of 4a and 6 detected in crude, method E:
55% of 4a and 6 detected in crude, method H: 77% of 4a,
method I: 75% of 6.
117.9, 209.5. IR (film) n 2980, 2920, 1725, 1665 cmꢂ1
.
Anal. Calcd for C15H20O5: C, 64.27; H, 7.19. Found: C,
64.45; H, 7.22.
4.3.16.1. (3aS*,5R*)-5-Hydroxy-3,3a,4,5-tetrahydro-2H-cyclo-
penta[a]naphthalen-2-one, 4a. Yellow oil (hexaneeEtOAc
1:1). 1H NMR (CDCl3) d 1.79 (td, 1H, J1¼13.7 Hz,
J2¼3.3 Hz), 2.16 (dd, 1H, J1¼18.1 Hz, J2¼3.3 Hz), 2.38e
2.44 (m, 1H), 2.73 (dd, 1H, J1¼18.1 Hz, J2¼6.6 Hz), 3.17
(br s, 1H), 3.52e3.58 (m, 1H), 4.92e4.93 (m, 1H), 6.36 (d,
1H, J¼2.2 Hz), 7.36e7.40 (m, 1H), 7.44e7.46 (m, 2H),
7.64 (d, 1H, J¼7.7 Hz). 13C NMR (CDCl3) d 208.5, 174.9,
139.1, 131.6, 130.5, 129.1, 128.5, 126.6, 124.0, 66.9, 41.9,
4.3.13. Preparation of (3aS*,4S*)-diethyl 4-methoxy-5-oxo-
3,3a,4,5-tetrahydropentalene-2,2(1H )-dicarboxylate, cis-2c
From 1 mmol of Z-1c, yield of cis-2b is as follows. Method
E: at 65 ꢀC, 62%, method D: 65%. Colorless oil (hexanee
EtOAc 7:1). 1H NMR (CDCl3) d 1.21 (t, 3H, J¼7.1 Hz),
1.24 (t, 3H, J¼7.1 Hz), 1.88 (dd, 1H, J1¼13.2 Hz,
J2¼12.6 Hz), 2.52 (dd, 1H, J1¼12.6 Hz, J2¼7.7 Hz), 3.10e
3.23 (m, 1H), 3.20 (d, 1H, J¼19.2 Hz), 3.29 (dd, 1H,
J1¼18.2 Hz, J2¼1.1 Hz), 3.46 (d, 3H, J¼1.1 Hz), 3.72 (dd,
1H, J1¼6.1 Hz, J2¼1.6 Hz), 4.13e4.23 (m, 4H), 5.84 (s,
1H). 13C NMR (CDCl3) d 13.9, 32.0, 35.4, 48.8, 58.4, 60.1,
61.9, 62.0, 80.1, 122.7, 170.5, 171.6, 184.8, 206.7. IR (film)
n 2980, 2940, 1730, 1640 cmꢂ1. NOE: H3ab/H4b (11%),
H3b/H3ab (8%). Anal. Calcd for C15H20O6: C, 60.80; H,
6.80. Found: C, 60.63; H, 6.65.
37.1, 33.7. IR (film) n 3390, 2910, 1690, 1665, 1595 cmꢂ1
.
NOE: H3b/H3ab (5%), H5a/H4a (4%). Anal. Calcd for
C13H12O2: C, 77.98; H, 6.04. Found: C, 77.79; H, 5.89.
4.3.16.2. 1H-Cyclopenta[a]naphthalen-2(3H )-one, 6. Yellow
solid (mp 113e116 ꢀC) 1H NMR (CDCl3) d 3.73 (s, 2H),
3.84 (s, 2H), 7.42 (d, 1H, J¼7.7 Hz), 7.46e7.57 (m, 2H),
7.68 (d, 1H, J¼7.7 Hz), 7.79 (d, 1H, J¼7.7 Hz), 7.88 (d, 1H,
J¼7.7 Hz). 13C NMR (CDCl3) d 42.3, 44.8, 122.6, 124.0,
125.6, 126.6, 127.7, 128.7, 129.7, 132.5, 133.7, 134.8,
4.3.14. Preparation of (3aS*,4R*)-diethyl 4-methoxy-5-oxo-
3,3a,4,5-tetrahydropentalene-2,2(1H )-dicarboxylate,
trans-2c
209.6. IR (KBr) n 3060, 3940, 2250, 2050, 1750 cmꢂ1
.
Anal. Calcd for C13H10O: C, 85.69; H, 5.53. Found: C,
85.45; H, 5.37.
From 1 mmol of E-1c, yield of trans-2c is as follows.
Method E: at 65 ꢀC, 71%, method D: 73%. Colorless oil (hex-
aneeEtOAc 7:1). 1H NMR (CDCl3) d 1.15 (t, 3H, J¼7.1 Hz),
1.17 (t, 3H, J¼7.1 Hz), 1.88 (dd, 1H, J1¼12.6 Hz,
J2¼12.1 Hz), 2.77 (dd, 1H, J1¼12.6 Hz, J2¼8.2 Hz), 2.92e
2.98 (m, 1H), 3.10 (d, 1H, J¼19.2 Hz), 3.24 (d, 1H,
J¼19.2 Hz), 3.43 (s, 3H), 3.63 (d, 1H, J¼3.3 Hz), 4.10 (q,
2H, J¼7.1 Hz), 4.14 (d, 2H, J¼7.1 Hz), 5.86 (d, 1H,
J¼1.6 Hz). 13C NMR (CDCl3) d 13.7, 35.2, 37.6, 50.4, 58.2,
60.4, 61.9, 62.0, 88.3, 123.6, 170.3, 170.8, 179.9, 205.4. IR
(film) n 2980, 2940, 1730, 1640 cmꢂ1. NOE: H4a/H3ab
4.3.17. PKR of compound 3b
From 1 mmol of 3b, yield of 4b is as follows. Method D:
40%, method E. 57%.
4.3.17.1. (3aS*,5R*)-5-(tert-Butyldimethylsilyloxy)-3,3a,4,5-
tetrahydro-2H-cyclopenta[a]naphthalen-2-one, 4b. Yellow oil
(hexaneeEtOAc 19:1). 1H NMR (CDCl3) d 0.12 (s, 3H), 0.19
(s, 3H), 0.87 (s, 9H), 1.80 (td, 1H, J1¼13.2 Hz, J2¼
2.7 Hz), 2.20 (dd, 1H, J1¼18.7 Hz, J2¼3.8 Hz), 2.29 (dt, 1H,

J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
73
J1¼13.2 Hz, J2¼3.3 Hz), 2.79 (dd, 1H, J1¼18.7 Hz,
J2¼6.0 Hz), 3.62e3.67 (m, 1H), 4.92 (t, 1H, J¼2.7 Hz),
6.41 (d, 1H, J¼2.2 Hz), 7.32 (d, 1H, J¼7.7 Hz), 7.34e7.45
(m, 2H), 7.68 (dd, 1H, J1¼7.7 Hz, J2¼1.1 Hz). 13C NMR
(CDCl3) d ꢂ4.4, ꢂ4.3, 17.9, 25.7, 33.9, 38.4, 42.2, 68.1,
124.2, 126.8, 128.3, 129.3, 130.4, 131.3, 139.6, 174.9,
Colorless oil (hexaneeEtOAc 20:1). 1H NMR (CDCl3)
d 1.07 (t, 3H, J¼7.3 Hz), 1.17 (t, 3H, J¼7.9 Hz), 1.33 (t,
3H, J¼7.3 Hz), 2.36 (q, 2H, J¼7.3 Hz), 2.56 (q, 2H,
J¼7.9 Hz), 3.38 (d, 2H), 4.23 (q, 2H, J¼7.3 Hz), 5.98 (s,
1H). 13C NMR (CDCl3) d 13.0, 13.4, 14.2, 17.0, 19.1, 39.3,
60.3, 111.0, 149.8, 152.3, 165.6, 166.2, 202.8. IR (film) n
208.1. IR (film) n 2950, 2920, 2880, 2850, 1690, 1595 cmꢂ1
.
2980, 2940, 1710, 1640, 1600 cmꢂ1. NOE: H2/HCH Et
2
NOE: H3ab/H5a (0%). Anal. Calcd for C19H26O2Si: C,
72.56; H, 8.33. Found: C, 72.84; H, 8.40.
(6%), H2/HCH Et (3%). Anal. Calcd for C13H18O3: C,
70.24; H, 8.16. Found: C, 70.51; H, 7.95.
3
4.3.18. PKR of compound 3c
Acknowledgements
From 1 mmol of 3c, yield of 4c and 5c are as follows.
Method D: at 65 ꢀC 24% of 4c and 38% of 5c; at 110 ꢀC
65% of 4c, method E: 75% of 4c, method F: 38% of 4c,
method G: 40% of 4c and 8% of 5c.
The authors are grateful to the DGCYT (MEC Spain,
CTQ2006-00601/BQU) for financial support. Pre-doctoral fel-
lowship from the Lilly, S. A. is gratefully acknowledged by
J. B.-U.
4.3.18.1. (3aS*,5R*)-5-(tert-Butyldimethylsilyloxy)-1-methyl-
3,3a,4,5-tetrahydro-2H-cyclopenta[a]naphthalen-2-one, 4c.
References and notes
1
White solid (mp 126e129 ꢀC). H NMR (CDCl3) d 0.12 (s,
3H), 0.17 (s, 3H), 0.85 (s, 9H), 1.73 (td, 1H, J1¼12.6 Hz,
J2¼3.5 Hz), 2.05 (s, 3H), 2.10 (dd, 1H, J1¼18.7 Hz,
J2¼3.3 Hz), 2.27 (dt, 1H, J1¼13.2 Hz, J2¼2.2 Hz), 2.76 (dd,
1H, J1¼18.7 Hz, J2¼6.6 Hz), 3.41e3.49 (m, 1H), 4.89 (t,
1H, J¼2.8 Hz), 7.32e7.41 (m, 3H), 7.71e7.75 (m, 1H). 13C
NMR (CDCl3) d ꢂ4.3, ꢂ4.2, 10.0, 18.0, 25.7, 32.5, 39.3,
40.4, 68.3, 127.8, 128.2, 130.0, 130.6, 131.2, 133.3, 140.1,
165.8, 208.8. IR (KBr) n 2950, 2920, 2880, 2845, 1790,
1. Recent reviews on the PausoneKhand reaction: (a) Blanco-Urgoiti, J.;
Anorbe, L.; Perez-Serrano, L.; Dominguez, G.; Perez-Castells, J. Chem.
Soc. Rev. 2004, 33, 32; (b) Rivero, M. R.; Adrio, J.; Carretero, J. C.
Eur. J. Org. Chem. 2002, 2881; (c) Sugihara, T.; Yamaguchi, M.;
Nishizawa, M. Chem.dEur. J. 2001, 7, 1589; (d) Brummond, K. M.;
Kent, J. L. Tetrahedron 2000, 56, 3263.
2. Reviews on catalytic PKR: (a) Shibata, T. Adv. Synth. Catal. 2006, 348,
2328; (b) Gibson, S. E.; Stevenazzi, A. Angew. Chem., Int. Ed. 2003,
42, 1800.
1600 cmꢂ1
C20H28O2Si: C, 73.12; H, 8.59. Found: C, 73.23; H, 8.68.
.
NOE: H3ab/H5a (0%). Anal. Calcd for
´
3. Rautenstrauch, V.; Megard, P.; Conesa, J.; Kuster, W. Angew. Chem., Int.
¨
Ed. Engl. 1990, 29, 1413.
4. (a) Jeong, N.; Hwang, S. H.; Lee, Y.; Chung, Y. K. J. Am. Chem. Soc.
1994, 116, 3159; (b) Sugihara, T.; Yamaguchi, M. Synlett 1998, 1384.
5. (a) Belanger, D. B.; O’Mahony, D. J.; Livinghouse, T. Tetrahedron Lett.
1998, 39, 7637; (b) Belanger, D. B.; Livinghouse, T. Tetrahedron Lett.
1998, 39, 7641.
4.3.18.2.
tert-Butyl-(4-ethyliden-3-methylen-1,2,3,4-tetrahy-
dronaphthalen-1-yloxy)dimethylsilane, 5c. E-isomer: yellow
1
oil. H NMR (CDCl3) d 0.12 (s, 3H), 0.14 (s, 3H), 0.94 (s,
~
6. (a) Krafft, M. E.; Bonaga, V. R. L.; Hirosawa, C. Tetrahedron Lett. 1999,
40, 9171; (b) Krafft, M. E.; Hirosawa, C.; Bonaga, V. R. L. Tetrahedron
9H), 1.97 (d, 3H, J¼7.1 Hz), 2.51 (dd, 1H, J1¼13.2 Hz,
J2¼9.9 Hz), 2.74 (dd, 1H, J1¼13.2 Hz, J2¼5.5 Hz), 4.79 (dd,
1H, J1¼9.9 Hz, J2¼5.5 Hz), 5.04 (s, 1H), 5.24 (s, 1H), 6.19
(q, 1H, J¼7.1 Hz), 7.20 (dd, 2H, J1¼6.1 Hz, J2¼3.3 Hz),
7.39 (dd, 1H, J1¼5.5 Hz, J2¼3.3 Hz), 7.46 (dd, 1H,
J1¼5.5 Hz, J2¼3.8 Hz). 13C NMR (CDCl3) d ꢂ4.7, ꢂ4.3,
16.0, 18.2, 25.9, 43.1, 70.5, 114.2, 122.0, 122.9, 126.1,
126.7, 127.4, 136.0, 136.1, 139.3, 140.1. IR (film) n 2950,
2920, 2850 cmꢂ1. NOE: HCHethyliden/H5 (23%). Anal. Calcd
for C19H28OSi: C, 75.94; H, 9.39. Found: C, 75.74; H, 9.11. Z-
~
~
Lett. 1999, 40, 9177; (c) Krafft, M. E.; Bonaga, V. R. L.; Hirosawa, C.
J. Org. Chem. 2001, 66, 3004.
7. Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 2002, 67, 3398.
8. Gibson, S. E.; Johnstone, C.; Stevenazzi, A. Tetrahedron 2002, 58, 4937.
9. (a) Kim, J. W.; Chung, Y. K. Synthesis 1998, 142; (b) Krafft, M. E.;
~
Bonaga, V. R. Angew. Chem., Int. Ed. 2000, 39, 3676.
10. Sugihara, T.; Yamaguchi, M. J. Am. Chem. Soc. 1998, 120, 10782.
11. Kim, S. W.; Son, S. U.; Lee, S. I.; Hyeon, T.; Chung, Y. K. J. Am. Chem.
Soc. 2000, 122, 1550.
12. (a) Son, S. U.; Park, K. H.; Chung, Y. K. Org. Lett. 2002, 4, 3983; (b) Son,
S. U.; Lee, S. I.; Chung, Y. K. Angew. Chem., Int. Ed. 2000, 39, 4158; (c)
Son, S. U.; Park, K. H.; Seo, H.; Chung, Y. K.; Lee, S. G. Chem. Commun.
2001, 2440.
1
isomer: yellow oil. H NMR (CDCl3) d 0.09 (s, 3H), 0.12 (s,
3H), 0.94 (s, 9H), 1.91 (d, 3H, J¼7.7 Hz), 2.35e2.45 (m,
1H), 2.78 (dd, 1H, J1¼15.4 Hz, J2¼5.0 Hz), 4.67 (dd, 1H,
J1¼10.5 Hz, J2¼5.0 Hz), 4.75 (s, 1H), 5.28 (s, 1H) 6.16 (q,
1 h, J¼7.1 Hz), 7.25e7.26 (m, 3H), 7.47e7.50 (m, 1H). 13C
NMR (CDCl3) d ꢂ4.6, 15.4, 18.3, 25.9, 40.4, 68.7, 106.7,
121.5, 123.4, 125.8, 126.1, 126.4, 126.7, 127.7, 129.5,
131.5. IR (film) n 2950, 2920, 2850 cmꢂ1. Anal. Calcd for
C19H28OSi: C, 75.94; H, 9.39. Found: C, 75.68; H, 9.18.
13. Muller, J. L.; Rickers, A.; Leitner, W. Adv. Synth. Catal. 2007, 349, 287.
14. (a) Son, S. U.; Lee, S. I.; Chung, Y. K.; Kim, S. W.; Hyeon, T. Org. Lett.
2002, 4, 277; (b) Kim, S. W.; Son, S. U.; Lee, S. S.; Hyeon, T.; Chung,
Y. K. Chem. Commun. 2001, 2212.
15. Heterogeneous bimetallic catalysts Co/M (M¼Rh, Ru); see: (a) Park,
K. H.; Chung, Y. K. Adv. Synth. Catal. 2005, 347, 854; (b) Park, K. H.;
Son, S. U.; Chung, Y. K. Chem. Commun. 2003, 1898.
16. (a) Jeong, N.; Kim, D. H.; Choi, J. H. Chem. Commun. 2004, 1134; (b)
Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem.
1997, 62, 3762; (c) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T.
J. Am. Chem. Soc. 1997, 119, 6187.
4.3.19. Preparation of ethyl (2E )-(2,3-diethyl-4-
oxocyclopent-2-en-1-ylidene)ethanoate
The yield of the compound is as follows. Method D: 10%,
method E: at 110 ꢀC in sealed tube, 25%, method I: 40%.
17. Shibata, T.; Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852.
18. Rios, R.; Pericas, M. A.; Moyano, A.; Maestro, M. A.; Mahia, J. Org. Lett.
2002, 4, 1205.

74
J. Blanco-Urgoiti et al. / Tetrahedron 64 (2008) 67e74
´ ´ ´
23. (a) Perez-Serrano, L.; Domınguez, G.; Perez-Castells, J. J. Org. Chem.
19. (a) Fan, B. M.; Xie, J. H.; Li, S.; Tu, Y. Q.; Zhou, Q. L. Adv.Synth. Catal.
2005, 347, 759; (b) Shibata, T.; Toshida, N.; Takagi, K. Org. Lett. 2002, 4,
1619; (c) Shibata, T.; Toshida, N.; Takagi, K. J. Org. Chem. 2002, 67,
7446; (d) Morimoto, T.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K. J. Am.
Chem. Soc. 2002, 124, 3806; (e) Jeong, N.; Sung, B. K.; Choi, Y. K.
J. Am. Chem. Soc. 2000, 122, 6771.
´
2004, 69, 5413; (b) Perez-Serrano, L.; Casarrubios, L.; Domınguez, G.;
´
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Perez-Castells, J. Chem. Commun. 2001, 2602.
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