Intramolecular dimerizations of cyclopentadienones

Article abstract of DOI:10.1055/s-2007-983789

The generation of bis-cyclopentadienones joined by a tether results in the stereoselective, intramolecular dimerization of these reactive intermediates. This cycloaddition leads to structures of high molecular complexity from relatively simple starting ma

Full text of DOI:10.1055/s-2007-983789

2370
PAPER
Intramolecular Dimerizations of Cyclopentadienones
Intramolecular
Dimeri
i
c
of Cyclope
h
ntadienonesael Harmata,* Kanok-on Rayanil
Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, USA
Fax +1(573)8822754; E-mail: harmataM@missouri.edu
Received 6 April 2007
This paper is dedicated to Professor Paul A. Wender on the occasion of his 60th birthday.
Abstract: The generation of bis-cyclopentadienones joined by a
tether results in the stereoselective, intramolecular dimerization of
these reactive intermediates. This cycloaddition leads to structures
of high molecular complexity from relatively simple starting mate-
rials.
H
CO
H
O
Key words: cycloadditions, cyclopentadienones, intramolecular,
dimerizations, antiaromaticity
O
H
In considering possible synthetic routes to mangicols 1–3
(Figure 1), compounds with cytotoxic and anti-inflamma-
tory activities,1 we wondered whether the carbocyclic
skeleton could be assembled by an intramolecular cyclo-
pentadienone dimerization as illustrated in Scheme 1.
Such a process might involve the reaction of two ‘stable’
cyclopentadienones that could be induced to react in-
tramolecularly, the reaction of a ‘stable’ cyclopentadi-
enone with one that would dimerize rapidly under normal
circumstances, or the intramolecular reaction of two reac-
tive cyclopentadienones. To the best of our knowledge,
there are no examples of intramolecular cyclopentadi-
enone dimerizations in the literature. Initially, we chose to
examine the most difficult of the scenarios presented
above, the intramolecular cycloaddition of two reactive
cyclopentadienones.
O
Scheme 1 Retrosynthesis of the carbocyclic core of the mangicols
synthesis of cubane and related caged hydrocarbons,3 cy-
clopentadienone dimerization represents a profound in-
crease in molecular complexity as the monomer proceeds
to a dimer. We speculated that it would be possible to gen-
erate two reactive species that were joined by a tether and
have them react intramolecularly rather than intermolecu-
larly. Among other things, we reasoned that it would be
important to generate these reactive species contempora-
neously, lest two molecules with one reactive fragment
collide and begin the process of oligomerization. This pa-
per reports the success of what we view as principle stud-
ies that presage and justify further synthetic efforts.
In 2001, we reported the generation of cyclopentadi-
enones via dehydrobromination of 2-bromocyclopent-2-
enones giving various cyclopentadienone dimers. Treat-
ment of 2-bromo-substituted compound 4 with triethyl-
amine in refluxing 2,2,2-trifluoroethanol (TFE) gave the
cyclopentadienone dimer 5 in 90% yield (Scheme 2).4
This work was extended to develop the first examples of
an electrocyclic reaction involving an antiaromatic spe-
cies (Scheme 3)5 and a new method for generating a reac-
tive cyclopentadienone that served as an excellent
dienophile in the Diels–Alder reaction (Scheme 4).6
OH
OH
H
HO
R2
H
OH
R1
1, R1 = H, R2 = OH; mangicol A
2, R1 = OH, R2 = H; mangicol B
3, R1 = R2 = H; mangicol C
Figure 1
We began our study by preparing molecules that had two
bromocyclopentenone units, to be used as bis-cyclopenta-
Cyclopentadienones are antiaromatic species. As such,
they are generally quite reactive and undergo dimerization
very rapidly, unless stabilized through substitution with
bulky or electron-donating substituents. Such ‘stable’ cy-
clopentadienones have been used productively both as
dienes and dienophiles, and offer great potential in syn-
thesis.2 Though not generally recognized, except in the
O
O
Et3N, TFE
Br
reflux, 90%
4
5
O
SYNTHESIS 2007, No. 15, pp 2370–2378
x
x.
x
x
.
2
0
0
7
Advanced online publication: 12.07.2007
Scheme 2 Formation of the cyclopentadienone dimer
DOI: 10.1055/s-2007-983789; Art ID: C02407SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Intramolecular Dimerizations of Cyclopentadienones
2371
O
O
O
Br
Br
H
Et3N (3 equiv)
TFE, 70 °C, 2 d
61%
O
Br
Me
Me
TFEO
14
O
bases
TFE or MeCN
reflux
MeO
MeO
6
7
or
O
Scheme 3 Cyclopentadienone electrocyclization
O
16
Br
O
Br
15
+
Br
O
O
MeO
CO2Me
O
C
8
9
x
O
17
Et3N (3 equiv)
toluene, reflux
1.5 h, 80%
Scheme 6 Attempted cyclization of 14 and 15
CO2Me
MeO
10
We were forced to find a better bis-cyclopentadienone
precursor and decided to pursue the sequence shown in
Scheme 7. We synthesized bis-cyclopentenone com-
pound 19 using the Pauson–Khand reaction of hepta-1,6-
diyne (18) and norbornadiene according to the procedure
reported by Krafft.7 Introduction of a nucleophile into 19
using lithium dimethylcuprate gave 20 in 75% yield.8 A
Lewis acid induced retro-Diels–Alder reaction of 20 using
methylaluminum dichloride and an excess of maleic an-
hydride as a cyclopentadiene trap afforded 21 in 77%
yield.9 Bromination of 21 with 4.2 equivalents of N-bro-
mosuccinimide (NBS) in the presence of 10 mol% 2,2¢-
azobis(isobutyronitrile) (AIBN) in refluxing carbon tetra-
chloride presumably introduced four bromine atoms at
both a- and g-positions. We used excess reagent to add
mass to the material. However, this process was not clean,
as indicated in the 1H and 13C NMR spectra of the crude
product. Because of the complexity of the mixture con-
taining 22, the crude product was directly subjected to the
next step without any purification. An ethereal solution of
crude 22 was slowly added to an ethereal solution of 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) at room tempera-
ture and the mixture stirred for five hours. Happily, the
polycyclic cycloadduct 24 was isolated in 30% yield.10
The structure of 24 was based on 1H and 13C NMR spec-
troscopy and the precedent that dimerizations of cyclo-
pentadienones typically take place in an endo fashion.11
Scheme 4 Diels–Alder reaction via the generation of a reactive cy-
clopentadienone
dienone precursors. The preparation of these compounds
was straightforward and will not be further discussed
here. To evaluate our proposed intramolecular dimeriza-
tion, compound 11 was treated with three equivalents of
triethylamine in refluxing TFE (Scheme 5). However, no
evidence of cycloadduct 13 was observed. The reaction
led to the formation of a complex mixture.
Et3N (3 equiv)
(0.05 M) TFE
Br
Br
reflux, 2 h
O
O
O
O
11
12
O
O
C
x
Excited by the result, we wanted to see if an analogue of
22, namely 25 (Figure 2), would undergo cycloaddition at
room temperature upon treatment with base; the hope be-
ing that if that base was strong enough, rapid formation of
cyclopentadienones and intramolecular cycloaddition
would ensue.
13
Scheme 5 Attempted cyclization of 11
Our attempts to generate bis-cyclopentadienone interme-
diate 16 from precursors 14 or 15 by using different types
of base [Et3N, DBU, 2,2,6,6-tetramethylpiperidine
(TMP), 2,6-lutidine] in refluxing TFE or acetonitrile also
did not provide the corresponding cycloadduct 17
(Scheme 6). As before, polymerization and decomposi-
tion appeared to occur.
Compound 25 was treated with five equivalents of DBU
in a mixture of diethyl ether and dichloromethane under
reflux. Another experiment was also performed using tri-
ethylamine as base in refluxing TFE. Both experiments
Synthesis 2007, No. 15, 2370–2378 © Thieme Stuttgart · New York

2372
M. Harmata, K. Rayanil
PAPER
O
O
Me2CuLi
1. Co2(CO)8, THF, 12 h
Et2O, –78 °C to r.t., 77%
(10 equiv)
2.
18
19
toluene, 98 °C, 16 h, 68%
O
O
O
O
MeAlCl2
AIBN (10 mol%), NBS (4.2 equiv)
CCl4, reflux, 3 h
maleic anhydride
DCE, 55 °C, 10 h, 77%
Me
Me
Me
Me
20
21
Br
O
O
O
O
O
DBU (5 equiv)
Et2O (0.005 M), r.t.
30% (2 steps)
Br
Br
Br
Me
O
Br
Br
C
Me
Me
22
Br
Br
Me
23
Me
Me
24
Scheme 7 The first example of an intramolecular cyclopentadienone dimerization
O
brominating agent or the conditions used. Though we
could not isolate any clean side products, it is likely that
radicals formed during the bromination process could re-
act inter- or intramolecularly to form byproducts. Poly-
bromination and non-regioselective bromination could
also be a problem. However, even with lower amounts of
brominating agent, as used in the formation of 24f, the
crude product was still not clean.
O
Br
Br
Me
Me
25
Figure 2
All of the cycloadducts isolated were single compounds
led to complex mixtures with no evidence of cycloadduct
formation.
1
and structural assignments were made using H and 13C
NMR spectroscopy; endo selectivity was assumed,11 but
supported by the X-ray crystal structure of another cy-
cloadduct (see below).
We then decided to turn our attention to investigating
more examples of the cycloaddition process that gave cy-
cloadduct 24 (Scheme 7), in spite of the low yield ob-
served. We began with the synthesis of norbornene
derivatives 20 from 1,4-addition to compounds 19 and 26
using organocopper reagents (Table 1). The Michael ad-
ducts 20 were obtained in moderate to good yields.
From the results shown in Table 1, we wondered if a dif-
ferent substrate might afford a bis-cyclopentadienone so
that cyclization yields could be evaluated for products de-
rived from clean, characterized precursors. To explore
this, we synthesized bis-cyclopentenones 28 and 29 from
the Pauson–Khand reaction using vinyl benzoate as an
ethene equivalent in the presence of hydrated N-methyl-
morpholine N-oxide as shown in Scheme 8.12 The reac-
tions afforded adducts 28 and 29 in 60 and 62% yield,
respectively. Allylic bromination of these compounds re-
sulted in the formation of complex mixtures of dibromo-
substituted enones, as determined by NMR spectroscopic
examination of the crude products. As before, we none-
theless proceeded to take the unstable crude products
through the dimerization step by treatment with DBU in
diethyl ether solution. Cycloadducts 30 and 31 were iso-
lated in 19 and 18% yield, respectively. The X-ray crystal
structure of 30 confirmed the endo nature of the cycload-
duct, as illustrated in Figure 3.13
We then subjected the norbornene derivatives 20 to the
Lewis acid induced retro-Diels–Alder reaction described
above. The corresponding bis-cyclopentenones 21 were
obtained in reasonable yields.
Finally, investigations on the bromination and intramolec-
ular dimerization of the different bis-cyclopentenone sub-
strates were conducted. The cyclizations were performed
at room temperature, given that higher temperatures did
not improve the results and lower temperatures might
slow the formation of the cyclopentadienones, a circum-
stance we did not desire.10 All of the dimers were pro-
duced in moderate yields, at around 45% per step
(bromination and cyclization, Table 1). We believe the
main cause of such moderate yields is that the bromina-
tion reaction was never clean, regardless of the amount of
Synthesis 2007, No. 15, 2370–2378 © Thieme Stuttgart · New York

PAPER
Intramolecular Dimerizations of Cyclopentadienones
2373
Table 1 Intramolecular Cyclopentadienone Dimerizations
O
O
O
O
organocopper reagent
Et2O, –78 °C to r.t.
n
n
R
X
R
19: n = 1
26: n = 2
20
R
O
O
O
( )n
MeAlCl2
1. AIBN, NBS
2. DBU, Et2O
n
O
C
maleic anhydride
R
DCE, 55 °C, 10 h
R
R
21
X
24
Entry
n
1
1
1
1
1
1
2
2
2
Ra
Product
20
Yield (%)
Productc
Yield (%)
X
Producte,f
Yield (%)
1
2
3
4
5
6
7
8
9
Me
77
53
55
66
82
83
64
67
68
21
77
56
72
93
63
62
59
64
61
Br
Br
Br
Br
Br
Br
Hd
Br
Br
24
30
21
23
26
19
21
29
23
21
Etb
20a
20b
20c
21a
21b
21c
21d
21e
21f
21g
21h
24a
24b
24c
24d
24e
24f
24g
24h
n-Prb
n-Bu
n-Hex
Ph
20d
20e
Me
20f
n-Bu
n-Hex
20g
20h
a All organocopper reagents were prepared at –20 °C from the corresponding organolithium (10 equiv) and CuI (5 equiv).
b Ethyl- and propyllithium reagents were freshly prepared from EtI and PrI with t-BuLi at –78 °C.
c All reactions were conducted at 55 °C in the presence of MeAlCl2 (5 equiv) and maleic anhydride (10 equiv) in 0.1 M DCE.
d In this case, 2.1 equiv of NBS were used in the bromination step.
e Bromination reactions were performed in the presence of 10 mol% AIBN and NBS (4.2 equiv) in 0.1 M CCl4 under reflux conditions.
f All cyclization reactions were conducted at r.t. with DBU (5 equiv) in 0.005 M Et2O.
O
O
n
1. Co2(CO)8, THF, 12 h
2. NMO⋅H2O (20 equiv)
CH2Cl2, vinyl benzoate
r.t., overnight
n
28: n = 1; 60%
29: n = 2; 62%
18: n = 1
27: n = 2
O
1. AIBN (10 mol%)
NBS (2.1 equiv)
CCl4, reflux, 1 h
2. DBU (5 equiv)
Et2O, r.t., 5 h
n
O
C
30: n = 1; 19%
31: n = 2; 18%
Figure 3 Crystal structure of 30
Scheme 8 Cyclization of simple bis-cyclopentadienone precursors
In summary, we have demonstrated for the first time that
cycloaddition between cyclopentadienones can occur to
diastereoselectively generate cycloadducts that are the re-
sult of intramolecular dimerization. At this stage, the
yields are too low, but we believe that clean cyclopentadi-
enone precursors will give the products in much higher
yields. Thus, our future work will involve the synthesis of
new cyclopentadienone precursors and studying the in-
tramolecular dimerizations of cyclopentadienones that
have a lower reactivity profile, as will be necessary for a
synthetic approach to the mangicols. Results will be re-
ported in due course.
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2374
M. Harmata, K. Rayanil
PAPER
All reactions were carried out under an atmosphere of N2 in oven-
dried glassware and with a magnetic stir bar. THF was distilled from
Na/benzophenone. Chromatographic separations were carried out
using Silicycle ultrapure silica gel (230–400 mesh). Analytical TLC
was performed on EM Reagent 0.25-nm silica gel 60-F plates. Vi-
sualization of the developed chromatogram was performed by phos-
phomolybdic acid stain solution followed by heating. Infrared
spectra were recorded on a Perkin Elmer 1600 series FT-IR spec-
trometer. NMR spectra were recorded on a Bruker ARX-250 (250
MHz), DRX-300 (300 MHz), and DRX-500 (500 MHz) spectrom-
eter using TMS as an internal standard. High-resolution mass spec-
trometry was carried out on a Waters Quattro II instrument using
electrospray ionization (ESI).
Compound 19 (0.125 g, 0.376 mmol) was added and the resulting
mixture was slowly warmed to r.t. After the solution was stirred at
r.t. for 5 h, it was poured into chilled H2O (30 mL). The aqueous
mixture was filtered over a pad of Celite and the ethereal layer was
separated. The aqueous solution was further extracted with Et2O (3
×10 mL). The combined organic layers were dried (MgSO4), fil-
tered, and concentrated. The crude product was purified by flash
chromatography (10% EtOAc–hexane) to provide a yellow oil.
Yield: 0.106 g (77%).
IR (neat): 3056, 2962, 2868, 1723, 1458, 1372, 1266, 1050 cm–1.
1H NMR (250 MHz, CDCl3): d = 6.16 (dd, J = 3.0, 5.4 Hz, 2 H),
6.11 (dd, J = 3.0, 5.4 Hz, 2 H), 3.09 (d, J = 1.0 Hz, 2 H), 2.72 (s, 2
H), 2.28 (d, J = 9.0 Hz, 2 H), 2.18–2.10 (m, 2 H), 1.81 (t, J = 8.0 Hz,
2 H), 1.63–1.49 (m, 2 H), 1.46–1.23 (m, 8 H), 1.21 (d, J = 6.4 Hz, 6
H), 1.03 (d, J = 9.4 Hz, 2 H).
2,2¢-Propane-1,3-diylbis(3a,4,7,7a-tetrahydro-4,7-methano-1H-
inden-1-one) (19); Typical Procedure
13C NMR (62.5 MHz, CDCl3): d = 218.3, 138.2, 137.4, 60.5, 54.2,
48.7, 46.6, 44.9, 44.8, 44.4, 40.2, 40.0, 27.8, 27.7, 24.6, 24.4, 21.1,
21.0.
HRMS: m/z [M + Na]+ calcd for C25H32O2: 387.2294; found:
387.2298.
A 200-mL, round-bottomed flask was charged with hepta-1,6-diyne
(18; 0.32 g, 1.628 mmol) and Co2(CO)8 (2.62 g, 4.640 mmol) in
THF (34 mL) under an Ar atmosphere. The red-brown solution was
stirred at r.t. until complex formation was completed, as judged by
TLC. The excess solvent was removed under reduce pressure and
the dicobalt–diyne complex was purified by filtration through a
short plug of silica gel.
Conjugate Addition (Method B): 2,2¢-Propane-1,3-diylbis(3-
ethyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-inden-1-one)
(20a); Typical Procedure
To a solution of EtI (2.346 g, 15.04 mmol) in Et2O (20 mL) at –78
°C was added dropwise a 0.89 M soln of t-BuLi in pentane (34 mL,
30.10 mmol) over 10 min. The resulting solution was stirred at –78
°C for 1 h and at r.t. for another 1 h.
A 30-mL sealed tube was charged with the hepta-1,6-diynedicobalt
complex (0.540 g, 0.8132 mmol), norbornadiene (0.749 g, 8.133
mmol), and toluene (8.1 mL). The mixture was heated at 98 °C for
16 h. After the mixture was cooled to r.t., it was filtered through a
pad of Celite. The solvent was removed and the crude product was
purified by flash column chromatography (silica gel, hexane–
EtOAc, 4:1) to afford a colorless semisolid. Yield: 0.184 g (68%).
Anhyd CuI (1.432 g, 7.52 mmol) and Et2O (10 mL) were placed in
a 200-mL round-bottomed flask fitted with a septum and a stir bar
under an Ar atmosphere. The resulting suspension was stirred at
–20 °C for 10 min before adding the EtLi soln prepared above. The
mixture was stirred for 30 min at –20 °C and then was cooled to
–78 °C. The mixture was added dropwise to a solution of 19 (0.500
g, 1.504 mmol) in THF (5 mL) and the resulting mixture was al-
lowed to warm to r.t. After 6 h, the reaction was quenched with ice
water and was extracted with Et2O (3 × 20 mL). The combined or-
ganic layers were washed with brine, dried (MgSO4), and concen-
trated. Purification of the yellow residue by column
chromatography (10% EtOAc–hexane) provided a colorless oil.
Yield: 0.310 g (53%).
IR (film): 3052, 2970, 2938, 2868, 1695, 1626, 1569, 1324, 1213,
1139, 1008 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.20 (br, 2 H), 6.28 (dd, J = 3.2,
5.3 Hz, 2 H), 6.20 (dd, J = 3.2, 5.3 Hz, 2 H), 2.90 (s, 2 H), 2.71 (s,
2 H), 2.67 (s, 2 H), 2.27 (d, J = 7.0 Hz, 2 H), 2.19 (t, J = 7.0 Hz, 4
H), 1.72–1.62 (m, 2 H), 1.37 (d, J = 9.2 Hz, 2 H), 1.19 (d, J = 9.3
Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): d = 209.9, 159.3, 150.0, 138.4,
137.0, 52.5, 47.7, 43.6, 42.9, 41.2, 25.6, 24.8.
HRMS: m/z [M + Na]+ calcd for C23H24O2: 355.1668; found:
355.1669.
IR (neat): 2958, 2925, 1728, 1454, 1324, 1217 cm–1.
2,2¢-Butane-1,4-diylbis(3a,4,7,7a-tetrahydro-4,7-methano-1H-
1H NMR (250 MHz, CDCl3): d = 6.19 (dd, J = 3.0, 5.6 Hz, 2 H),
6.13 (dd, J = 3.0, 5.6 Hz, 2 H), 3.11 (s, 2 H), 2.71 (s, 2 H), 2.28 (d,
J = 9.0 Hz, 2 H), 2.25–2.15 (m, 2 H), 1.92–1.86 (m, 2 H), 1.83–1.73
(m, 2 H), 1.63–1.51 (m, 2 H), 1.47–1.18 (m, 10 H), 1.05 (t, J = 7.2
Hz, 8 H).
13C NMR (62.5 MHz, CDCl3): d = 218.9, 138.3, 137.6, 58.8, 54.4,
48.2, 46.6, 46.4, 44.7, 29.0, 28.3, 25.0, 11.8.
inden-1-one) (26)
IR (film): 3056, 2972, 2938, 1696, 1617, 1458, 1319, 1209, 1061
cm–1.
1H NMR (250 MHz, CDCl3): d = 7.16 (d, J = 1.2 Hz, 2 H), 6.28 (dd,
J = 3.0, 6.6 Hz, 2 H), 6.20 (dd, J = 3.0, 6.6 Hz, 2 H), 2.90 (s, 2 H),
2.71–2.70 (m, 2 H), 2.66 (s, 2 H), 2.29–2.26 (m, 2 H), 2.18 (t, J =
6.0 Hz, 4 H), 1.52–1.46 (m, 4 H), 1.38–1.35 (m, 2 H), 1.19 (d, J =
9.2 Hz, 2 H).
HRMS: m/z [M]+ calcd for C27H36O2: 392.2710; found: 392.2667.
13C NMR (62.5 MHz, CDCl3): d = 209.7, 158.9, 150.4, 138.3,
2,2¢-Propane-1,3-diylbis(3-propyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20b)
137.0, 52.5, 47.6, 43.6, 42.9, 41.1, 27.5, 24.7.
HRMS: m/z [M + Na]+ calcd for C24H26O2: 369.1825; found:
369.1823.
IR (neat): 3064, 2958, 1728, 1454, 1356, 1209 cm–1.
1H NMR (250 MHz, CDCl3): d = 6.18 (dd, J = 3.0, 5.5 Hz, 2 H),
6.12 (dd, J = 3.0, 5.5 Hz, 2 H), 3.11 (s, 2 H), 2.70 (s, 2 H), 2.29 (d,
J = 9.2 Hz, 2 H), 2.20 (br, 2 H), 1.91–1.86 (m, 2 H), 1.66–1.50 (m,
6 H), 1.44–1.26 (m, 12 H), 1.07–0.92 (m, 8 H).
Conjugate Addition (Method A): 2,2¢-Propane-1,3-diylbis(3-
methyl-2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-inden-1-one)
(20); Typical Procedure
13C NMR (62.5 MHz, CDCl3): d = 218.9, 138.3, 138.0, 137.6,
137.4, 59.2, 59.1, 54.4, 54.3, 48.2, 47.1, 46.9, 44.8, 44.8, 44.7, 44.6,
44.5, 39.1, 28.3, 28.2, 24.9, 24.6, 20.7, 14.5.
HRMS: m/z [M + Na]+ calcd for C29H40O2: 443.2921; found:
443.2921.
A 25-mL round-bottomed flask was charged with CuI (0.358 g, 1.89
mmol) and Et2O (5.6 mL). The suspension was cooled to –20 °C for
10 min and then a 1.08 M soln of MeLi in THF–cumene (3.48 mL,
3.76 mmol) was added dropwise. The mixture was stirred at –20 °C
for 30 min and then it was cooled to –78 °C for another 10 min.
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Intramolecular Dimerizations of Cyclopentadienones
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2,2¢-Propane-1,3-diylbis(3-butyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20c)
HRMS: m/z [M + Na]+ calcd for C32H46O2: 485.3390; found:
485.3391.
IR (neat): 3060, 2962, 2917, 2868, 1732, 1458, 1319, 1217 cm–1.
2,2¢-Butane-1,4-diylbis(3-hexyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20h)
1H NMR (250 MHz, CDCl3): d = 6.19 (dd, J = 3.0, 5.5 Hz, 2 H),
6.12 (dd, J = 3.0, 5.5 Hz, 2 H), 3.11 (s, 2 H), 2.70 (s, 2 H), 2.29 (d,
J = 9.0 Hz, 2 H), 2.22–2.11 (m, 2 H), 1.91–1.86 (m, 2 H), 1.69–1.64
(m, 2 H), 1.63–1.50 (m, 4 H), 1.47–1.22 (m, 16 H), 1.04 (d, J = 9.0
Hz, 2 H), 0.95 (t, J = 7.0 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 218.7, 138.3, 138.2, 137.3, 59.2,
59.1, 54.4, 54.3, 48.1, 47.0, 44.9, 44.7, 44.6, 36.4, 36.2, 29.6, 28.2,
28.1, 28.0, 24.8, 24.6, 23.0, 22.9, 14.0.
IR (neat): 2957, 2925, 2855, 1732, 1460, 1217 cm–1.
1H NMR (250 MHz, CDCl3): d = 6.20 (dd, J = 3.0, 5.6 Hz, 2 H),
6.13 (dd, J = 3.0, 5.6 Hz, 2 H), 3.11 (s, 2 H), 2.70 (s, 2 H), 2.29 (d,
J = 8.9 Hz, 2 H), 2.23–2.12 (m, 2 H), 1.91–1.85 (m, 2 H), 1.71–1.61
(m, 2 H), 1.42–1.19 (m, 30 H), 1.06 (d, J = 9.1 Hz, 2 H), 0.90 (t, J =
6.6 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 218.8, 138.3, 137.4, 59.3, 54.4,
48.2, 47.0, 44.8, 44.7, 44.6, 36.7, 31.8, 29.7, 27.6, 27.5, 27.4, 27.3,
22.6, 14.1.
HRMS: m/z [M]+ calcd for C31H44O2: 448.3336; found: 448.3320.
2,2¢-Propane-1,3-diylbis(3-hexyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20d)
HRMS: m/z [M + Na]+ calcd for C36H54O2: 541.4016; found:
541.4027.
IR (neat): 2925, 2855, 1732, 1459, 1325 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.20–6.11 (m, 4 H), 3.11 (s, 2 H),
2.70 (s, 2 H), 2.29 (d, J = 9.0 Hz, 2 H), 2.19–2.18 (m, 2 H), 1.91–
1.86 (m, 2 H), 1.63–1.49 (m, 4 H), 1.46–1.20 (m, 26 H), 1.05 (d, J =
9.0 Hz, 2 H), 0.91 (t, J = 6.5 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 218.8, 138.3, 137.3, 59.2, 59.1,
54.4, 48.1, 47.0, 45.0, 44.7, 36.7, 31.9, 29.7, 28.3, 28.2, 27.4, 22.7,
14.1.
Retro-Diels–Alder Reaction: 5,5¢-Propane-1,3-diylbis(4-meth-
ylcyclopent-2-en-1-one) (21); Typical Procedure
A 50-mL two-necked flask equipped with a reflux condenser was
charged with compound 20 (0.374 g, 1.024 mmol), maleic anhy-
dride (1.004 g, 10.24 mmol), and 0.1 M DCE (10.24 mL) under an
Ar atmosphere. A 1 M soln of MeAlCl2 in hexane (4.30 mL, 4.30
mmol) was added at r.t. and the resulting mixture was heated in an
oil bath at 55 °C for 10 h. The mixture was cooled to r.t. and the sol-
vent was removed in vacuo. The residue was dissolved in EtOAc
(20 mL) and washed with sat. aq NaHCO3. The aqueous layer was
extracted with EtOAc (3×10 mL). The combined organic layers
were dried (MgSO4) and concentrated. The crude product was puri-
fied by flash column chromatography (30% EtOAc–hexane) to af-
ford a colorless oil. Yield: 0.225 g (77%).
HRMS: m/z [M + Na]+ calcd for C35H52O2: 527.3860; found:
527.3868.
2,2¢-Propane-1,3-diylbis(3-phenyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20e)
IR (neat): 3060, 2958, 1728, 1601, 1491, 1454, 1323, 1209 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.30 (m, 4 H), 7.28–7.19 (m,
6 H), 6.12 (dd, J = 3.0, 5.4 Hz, 2 H), 6.06 (dd, J = 3.0, 5.4 Hz, 2 H),
3.16 (s, 2 H), 2.75 (s, 2 H), 2.44 (d, J = 9.0 Hz, 2 H), 2.38–2.34 (m,
1 H), 2.31–2.28 (m, 1 H), 2.26–2.18 (m, 2 H), 1.54–1.37 (m, 4 H),
1.30–1.23 (m, 2 H), 1.20–1.13 (m, 2 H), 1.07 (t, J = 8.9 Hz, 2 H),
0.98–0.86 (m, 2 H).
IR (neat): 2970, 2933, 1760, 1728, 1585, 1450 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.56 (dd, J = 2.4, 5.6 Hz, 2 H),
6.10 (d, J = 2.0 Hz, 1 H), 6.08 (d, J = 2.0 Hz, 1 H), 2.71–2.61 (m, 2
H), 1.90–1.84 (m, 2 H), 1.81–1.74 (m, 2 H), 1.59–1.43 (m, 4 H),
1.26–1.21 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 217.1, 144.7, 144.6, 138.2, 137.5,
128.7, 127.5, 127.4, 126.6, 60.2, 54.1, 54.0, 52.2, 52.1, 49.9, 49.7,
46.7, 46.5, 44.7, 44.6, 27.7, 27.3, 23.7, 23.6.
13C NMR (62.5 MHz, CDCl3): d = 212.0, 211.9, 168.5, 168.3,
132.5, 132.4, 55.3, 53.2, 42.8, 42.7, 30.6, 30.4, 24.9, 24.7, 19.6.
HRMS: m/z [M + Na]+ calcd for C15H20O2: 255.1355; found:
255.1361.
HRMS: m/z [M]+ calcd for C35H36O2: 488.2709; found: 488.2726.
2,2¢-Butane-1,4-diylbis(3-methyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20f)
5,5¢-Propane-1,3-diylbis(4-ethylcyclopent-2-en-1-one) (21a)
IR (neat): 2962, 2925, 2851, 1777, 1691, 1589, 1458, 1176 cm–1.
IR (neat): 3030, 2956, 1732, 1460, 1325, 1213 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.62–7.59 (m, 2 H), 6.11 (d, J =
1.9 Hz, 1 H), 6.09 (d, J = 1.9 Hz, 1 H), 2.57–2.51 (m, 2 H), 1.97–
1.94 (m, 2 H), 1.72–1.67 (m, 2 H), 1.63–1.53 (m, 4 H), 1.52–1.44
(m, 4 H), 0.99 (dt, J = 1.9, 7.6 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 212.0, 211.9, 166.8, 132.8,
132.7, 50.7, 50.6, 49.3, 49.1, 31.2, 31.0, 27.1, 24.5, 24.2, 11.5.
1H NMR (250 MHz, CDCl3): d = 6.17 (dd, J = 3.0, 5.5 Hz, 2 H),
6.12 (dd, J = 3.0, 5.5 Hz, 2 H), 3.10 (s, 2 H), 2.73 (s, 2 H), 2.29 (d,
J = 9.0 Hz, 2 H), 2.17–2.11 (m, 2 H), 1.82 (t, J = 8.1 Hz, 2 H), 1.61–
1.54 (m, 2 H), 1.46–1.32 (m, 10 H), 1.22 (d, J = 6.4 Hz, 6 H), 1.05
(d, J = 9.1 Hz, 2 H).
13C NMR (62.5 MHz, CDCl3): d = 218.3, 218.2, 138.2, 137.4, 60.6,
54.2, 48.7, 46.6, 44.8, 44.4, 40.0, 39.9, 27.3, 27.2, 27.1, 27.0, 21.0.
HRMS: m/z [M + Na]+ calcd for C17H24O2: 283.1669; found:
283.1662.
HRMS: m/z [M + Na]+ calcd for C26H34O2: 401.2457; found:
401.2452.
5,5¢-Propane-1,3-diylbis(4-propylcyclopent-2-en-1-one) (21b)
IR (neat): 2954, 2864, 1703, 1589, 1462, 1364 cm–1.
2,2¢-Butane-1,4-diylbis(3-butyl-2,3,3a,4,7,7a-hexahydro-4,7-
methano-1H-inden-1-one) (20g)
1H NMR (250 MHz, CDCl3): d = 7.62–7.58 (m, 2 H), 6.10–6.07 (m,
2 H), 2.62–2.56 (m, 2 H), 1.97–1.93 (m, 2 H), 1.74–1.66 (m, 2 H),
1.58–1.33 (m, 12 H), 1.00–0.88 (m, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 212.1, 167.2, 132.7, 132.6, 51.4,
51.3, 47.8, 47.7, 36.7, 31.3, 31.2, 24.5, 24.2, 20.7, 14.2.
IR (neat): 2957, 2925, 2855, 1732, 1460, 1319, 1217 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.20–6.18 (m, 2 H), 6.14–6.11 (m,
2 H), 3.11 (s, 2 H), 2.70 (s, 2 H), 2.29 (d, J = 8.8 Hz, 2 H), 2.18 (br
s, 2 H), 1.89–1.86 (m, 2 H), 1.67–1.66 (m, 2 H), 1.55–1.20 (m, 22
H), 1.05 (d, J = 8.8 Hz, 2 H), 0.94 (t, J = 6.8 Hz, 6 H).
HRMS: m/z [M + Na]+ calcd for C19H28O2: 311.1982; found:
311.1975.
13C NMR (75 MHz, CDCl3): d = 218.9, 138.3, 137.4, 59.3, 54.4,
48.2, 47.0, 44.7, 44.6, 36.4, 29.7, 27.6, 27.5, 27.4, 27.3, 23.0, 14.1.
Synthesis 2007, No. 15, 2370–2378 © Thieme Stuttgart · New York

2376
M. Harmata, K. Rayanil
PAPER
5,5¢-Propane-1,3-diylbis(4-butylcyclopent-2-en-1-one) (21c)
13C NMR (62.5 MHz, CDCl3): d = 212.0, 167.0, 132.6, 51.4, 51.3,
47.8, 47.7, 34.4, 31.9, 30.9, 30.8, 29.2, 27.3, 27.1, 27.0, 22.4, 13.9.
IR (neat): 2953, 2929, 1704, 1589, 1485 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.62–7.57 (m, 2 H), 6.10–6.08 (m,
2 H), 2.63–2.52 (m, 2 H), 2.00–1.92 (m, 2 H), 1.70–1.66 (m, 2 H),
1.52–1.25 (m, 16 H), 0.92 (t, J = 6.1 Hz, 6 H).
Anal. Calcd for C26H42O2: C, 80.77; H, 10.95. Found: C, 80.59; H,
10.73.
Pauson–Khand Reaction Using a Vinyl Ester as an Ethene
Equivalent: 2,2¢-Propane-1,3-diylbis(cyclopent-2-en-1-one)
(28); Typical Procedure
13C NMR (62.5 MHz, CDCl3): d = 212.0, 167.2, 132.7, 132.6, 51.3,
51.2, 47.9, 47.8, 34.1, 31.2, 31.1, 29.5, 24.4, 24.2, 22.7, 13.8.
HRMS: m/z [M]+ calcd for C21H32O2: 316.2397; found: 316.2418.
To a stirred solution of hepta-1,6-diynedicobalt complex (1.00 g,
1.506 mmol) formed from 18 (see above) in CH2Cl2 (8 mL) was
added vinyl benzoate (8.0 mL) at r.t. The mixture was slowly added
to a solution of NMO·H2O (5.34 g, 30.12 mmol) in CH2Cl2 (15 mL)
over 3 h and stirring was continued overnight at r.t. The mixture was
filtered through a short pad of Celite and the solvent was removed
in vacuo. The crude product was purified by flash column chroma-
tography (30% EtOAc–hexane) to give a colorless semisolid. Yield:
0.183 g (60%).
5,5¢-Propane-1,3-diylbis(4-hexylcyclopent-2-en-1-one) (21d)
IR (neat): 2954, 2926, 2856, 1707, 1585, 1458, 1348, 1172 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.61–7.59 (m, 2 H), 6.10–6.08 (m,
2 H), 2.63–2.56 (m, 2 H), 1.97–1.93 (m, 2 H), 1.73–1.67 (m, 2 H),
1.53–1.48 (m, 6 H), 1.39–1.29 (m, 18), 0.89 (t, J = 7.1 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 212.1, 212.0, 167.2, 132.7,
132.6, 51.3, 51.2, 48.0, 47.9, 34.5, 31.6, 31.3, 31.2, 29.4, 27.3, 24.5,
24.3, 22.5, 14.0.
IR (film): 2933, 2884, 1691, 1617, 1442, 1331, 1262, 1200 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.35–7.34 (m, 2 H), 2.58–2.56 (m,
4 H), 2.40–2.38 (m, 4 H), 2.21–2.17 (m, 4 H), 1.73–1.66 (m, 2 H).
HRMS: m/z [M + Na]+ calcd for C25H40O2: 395.2921; found:
395.2917.
13C NMR (125 MHz, CDCl3): d = 209.9, 157.8, 145.7, 34.5, 26.4,
5,5¢-Propane-1,3-diylbis(4-phenylcyclopent-2-en-1-one) (21e)
IR (neat): 3027, 2933, 2856, 1773, 1703, 1589, 1491, 1450, 1331,
1176, 1082 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.55–7.53 (m, 2 H), 7.32–7.30 (m,
4 H), 7.27–7.23 (m, 2 H), 7.13–7.08 (m, 4 H), 6.26 (dd, J = 2.1, 5.6
Hz, 2 H), 3.71–3.67 (m, 2 H), 2.62–2.21 (m, 2 H), 1.80–1.76 (m, 2
H), 1.60–1.43 (m, 4 H).
25.5, 24.4.
HRMS: m/z [M + Na]+ calcd for C13H16O2: 227.1048; found:
227.1043.
2,2¢-Butane-1,4-diylbis(cyclopent-2-en-1-one) (29)
IR (film): 2924, 2848, 1691, 1617, 1646, 1626, 1462, 1356, 1258,
1127 cm–1.
13C NMR (125 MHz, CDCl3): d = 212.6, 165.3, 165.2, 141.3, 133.1,
133.0, 129.0, 127.3 (2 C), 127.2, 54.9, 54.7, 53.7 (2 C), 30.7, 30.6,
24.5, 24.3.
1H NMR (500 MHz, CDCl3): d = 7.36–7.30 (m, 2 H), 2.59–2.53 (m,
4 H), 2.42–2.38 (m, 4 H), 2.23–2.15 (m, 4 H), 1.53–1.47 (m, 4 H).
13C NMR (125 MHz, CDCl3): d = 210.1, 157.8, 146.0, 34.4, 27.4,
26.3, 24.4.
HRMS: m/z [M]+ calcd for C25H24O2: 356.1771; found: 356.1739.
Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 77.69; H,
8.45.
5,5¢-Butane-1,4-diylbis(4-methylcyclopent-2-en-1-one) (21f)
IR (neat): 2925, 2856, 1700, 1593, 1454, 1344 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.52 (dd, J = 2.4, 10.7 Hz, 2 H),
6.10 (d, J = 1.9 Hz, 1 H), 6.07 (d, J = 1.9 Hz, 1 H), 2.67–2.62 (m, 2
H), 1.85–1.76 (m, 4 H), 1.43–1.42 (m, 6 H), 1.23 (d, J = 7.2 Hz, 6
H).
13C NMR (62.5 MHz, CDCl3): d = 212.0, 168.2, 132.4 (2 C), 53.4,
53.3, 42.7, 42.6, 30.4, 30.3, 27.4, 27.3, 19.6, 19.5.
Intramolecular Dimerization of Bis-cyclopentenone 21; Typical
Procedure
A 10-mL round-bottomed flask equipped with a reflux condenser
was charged with 21 (0.0622 g, 0.268 mmol), AIBN (4.4 mg,
0.0268 mmol), NBS (0.1906 g, 1.071 mmol), and CCl4 (2.7 mL).
The mixture was refluxed in an oil bath for 1 h. The mixture was
then cooled, diluted with CCl4, and filtered through a pad of Celite.
The solution was washed with 10% aq Na2S2O3, H2O, and brine.
The organic layer was dried (MgSO4), filtered, and concentrated.
The crude product was used in the next step without any purifica-
tion.
HRMS: m/z [M + H]+ calcd for C16H22O2: 247.1698; found:
247.1704.
5,5¢-Butane-1,4-diylbis(4-butylcyclopent-2-en-1-one) (21g)
IR (neat): 2928, 2858, 1708, 1589, 1462, 1348 cm–1.
To a stirred solution of DBU (0.2025 g, 1.33 mmol) in Et2O (34 mL)
at r.t. was slowly added the crude product solution in Et2O (20 mL).
The mixture was stirred for 5 h at r.t. and it was quenched with sat.
aq NH4Cl. The ethereal layer was separated and the aqueous layer
was further extracted with Et2O (3 × 10 mL). The combined ethereal
solution was dried (MgSO4), filtered, and concentrated. The crude
product was purified by flash column chromatography (10%
EtOAc–hexane) to provide the dimer product 24. Yield: 0.0301 g
(30%).
1H NMR (250 MHz, CDCl3): d = 7.52 (dd, J = 2.4, 5.4 Hz, 2 H),
6.10 (d, J = 1.3 Hz, 1 H), 6.08 (d, J = 1.3 Hz, 1 H), 2.60–2.54 (m, 2
H), 1.94–1.91 (m, 2 H), 1.71–1.67 (m, 2 H), 1.52–1.35 (m, 18 H),
0.92 (t, J = 7.0 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 212.0, 167.0, 132.6, 51.4, 51.3,
47.8, 47.7, 34.1, 30.9, 30.8, 29.4, 27.1, 27.0, 22.6, 13.8.
Anal. Calcd for C22H34O2: C, 79.95; H, 10.37. Found: C, 79.79; H,
10.27.
IR (film): 2959, 2872, 1798, 1720, 1687, 1668, 1589, 1430, 1263
cm–1.
1H NMR (250 MHz, CDCl3): d = 7.43 (s, 1 H), 5.92 (q, J = 1.6 Hz,
1 H), 2.53–2.36 (m, 1 H), 2.25–2.15 (m, 1 H), 2.10–1.99 (m, 2 H),
1.88–1.78 (m, 1 H), 1.73 (d, J = 3.2 Hz, 3 H), 1.54–1.45 (m, 1 H),
1.27 (s, 3 H).
5,5¢-Butane-1,4-diylbis(4-hexylcyclopent-2-en-1-one] (21h)
IR (neat): 2926, 2856, 1706, 1589, 1461, 1348 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.52 (dd, J = 2.5, 5.6 Hz, 2 H),
6.10 (d, J = 1.4 Hz, 1 H), 6.08 (d, J = 1.4 Hz, 1 H), 2.60–2.54 (m, 2
H), 1.95–1.90 (m, 2 H), 1.71–1.66 (m, 2 H), 1.49–1.29 (m, 26 H),
0.92 (t, J = 7.0 Hz, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 200.4, 193.7, 160.7, 142.5,
130.4, 127.9, 69.7, 68.7, 63.1, 53.6, 28.9, 25.8, 19.4, 18.5, 15.4.
Synthesis 2007, No. 15, 2370–2378 © Thieme Stuttgart · New York

PAPER
Intramolecular Dimerizations of Cyclopentadienones
2377
HRMS: m/z [M]+ calcd for C15H14Br2O2: 385.9335; found:
385.9365.
1.5 Hz, 3 H), 1.63–1.59 (m, 1 H), 1.42 (t, J = 1.5 Hz, 1 H), 1.25 (dd,
J = 3.5, 13.5 Hz, 1 H), 1.21 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 207.9, 195.1, 163.1, 143.6, 138.5,
24a
129.0, 56.2, 55.3, 51.5, 45.8, 27.5, 21.8, 21.2, 20.1, 18.9, 15.3.
IR (film): 2964, 1796, 1716, 1588, 1460, 1282 cm–1.
HRMS: m/z [M + Na]+ calcd for C16H18O2: 265.1204; found:
265.1205.
1H NMR (300 MHz, CDCl3): d = 7.37 (s, 1 H), 5.91–5.90 (m, 1 H),
2.50–2.38 (m, 1 H), 2.31–2.13 (m, 2 H), 2.11–1.94 (m, 6 H), 1.43–
1.33 (m, 1 H), 0.96 (t, J = 7.4 Hz, 3 H), 0.88–0.79 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 200.8, 193.6, 160.7, 147.2, 130.5,
126.4, 70.6, 69.1, 62.0, 58.7, 29.1, 25.4, 24.1, 22.1, 18.7, 10.7, 10.0.
24g
IR (neat): 2957, 2931, 2870, 1790, 1714, 1590 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.35 (s, 1 H), 5.88 (t, J = 2.0 Hz,
1 H), 2.12–1.92 (m, 8 H), 1.43–1.25 (m, 10 H), 0.92–0.87 (m, 8 H).
HRMS: m/z [M + Na]+ calcd for C17H18Br2O2: 434.5966; found:
434.5965.
13C NMR (125 MHz, CDCl3): d = 200.1, 194.2, 160.3, 147.5, 130.3,
128.3, 69.6, 58.2, 57.4, 51.7, 31.8, 29.3, 27.8, 27.6, 27.3, 23.5, 22.2,
21.5, 21.3, 20.4, 13.9, 13.8.
HRMS: m/z [M + H]+ calcd for C22H28Br2O2: 483.0534; found:
483.0518.
24b
IR (neat): 2954, 2864, 1798, 1712, 1585, 1458 cm–1.
1H NMR (250 MHz, CDCl3): d = 7.38 (s, 1 H), 5.88 (t, J = 1.9 Hz,
1 H), 2.47–2.30 (m, 1 H), 2.21–2.05 (m, 2 H), 2.02–1.90 (m, 5 H),
1.47–1.22 (m, 3 H), 1.17–1.10 (m, 2 H), 0.94–0.85 (m, 7 H).
13C NMR (62.5 MHz, CDCl3): d = 200.8, 193.6, 160.7, 147.2,
130.5, 126.4, 70.6, 69.1, 62.0, 58.7, 29.1, 25.4, 24.1, 22.1, 18.7,
10.7, 10.0.
30
IR (film): 2958, 2925, 2855, 1773, 1683, 1580, 1348, 1176 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32 (dd, J = 2.7, 5.7 Hz, 1 H),
6.35–6.29 (m, 2 H), 6.15 (dd, J = 3.5, 6.9 Hz, 1 H), 3.31 (t, J = 4 Hz,
1 H), 3.21 (br s, 1 H), 2.41–2.31 (m, 1 H), 2.21–2.16 (m, 1 H), 2.05–
1.95 (m, 4 H).
HRMS: m/z [M + Na]+ calcd for C19H22Br2O2: 462.9879; found:
462.9872.
13C NMR (62.5 MHz, CDCl3): d = 209.6, 201.3, 159.9, 140.0,
24c
133.8, 127.8, 69.9, 68.1, 51.6, 48.7, 29.9, 25.6, 20.5.
IR (neat): 2962, 2925, 1802, 1716, 1585, 1462 cm–1.
HRMS: m/z [M]+ calcd for C13H12O2: 200.0832; found: 200.0837.
1H NMR (300 MHz, CDCl3): d = 7.37 (s, 1 H), 5.89 (t, J = 1.8 Hz,
1 H), 2.49–2.35 (m, 1 H), 2.20–2.09 (m, 2 H), 2.07–1.93 (m, 5 H),
1.35–1.25 (m, 8 H), 1.09–1.02 (m, 2 H), 0.89 (t, J = 7.4 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 200.8, 193.7, 160.2, 146.0, 130.3,
127.0, 70.6, 69.2, 62.2, 58.1, 31.0, 29.2, 28.7, 27.8, 25.3, 23.2, 22.2,
19.0, 13.8.
31
IR (film): 2959, 2929, 1729, 1462, 1274, 1123 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.26 (dd, J = 2.7, 5.7 Hz, 1 H),
6.28 (dd, J = 1.2, 6.0 Hz, 1 H), 6.13 (dd, J = 3.9, 6.6 Hz, 1 H), 6.01
(dd, J = 1.5, 6.6 Hz, 1 H), 3.19–3.16 (m, 1 H), 2.99–2.96 (m, 1 H),
2.12–2.01 (m, 3 H), 1.99–1.94 (m, 1 H), 1.79–1.72 (m, 1 H), 1.65–
1.15 (m, 2 H), 1.33 (td, J = 3.6, 13.8 Hz, 1 H).
HRMS: m/z [M]+ calcd for C21H26Br2O2: 470.0274; found:
470.0274.
13C NMR (75 MHz, CDCl3): d = 209.1, 201.8, 159.2, 140.0, 136.6,
24d
128.9, 56.6, 51.5, 50.3, 48.2, 29.8, 22.5, 22.2, 20.5.
IR (neat): 2955, 2929, 2858, 1796, 1718, 1585 cm–1.
HRMS: m/z [M + H]+ calcd for C14H14O2: 215.1072; found:
215.1066.
1H NMR (250 MHz, CDCl3): d = 7.37 (s, 1 H), 5.88 (t, J = 1.8 Hz,
1 H), 2.15–1.97 (m, 6 H), 1.25–1.24 (m, 20 H), 0.91–0.84 (m, 6 H).
13C NMR (62.5 MHz, CDCl3): d = 200.8, 193.7, 160.2, 146.1,
130.3, 126.9, 70.6, 69.2, 62.2, 58.1, 31.4, 31.3, 29.8, 29.2, 28.9,
28.8, 26.6, 25.7, 25.3, 23.2, 22.5, 22.4, 19.0, 14.0, 13.9.
Acknowledgment
This work was supported by the National Science Foundation to
which we are grateful.
HRMS: m/z [M + Na]+ calcd for C25H34Br2O2: 547.0818; found:
547.0851.
References
24e
IR (neat): 3064, 2958, 1797, 1716, 1589, 1491 cm–1.
(1) (a) Pichlmair, S.; de Lera Ruiz, M.; Vilotijevic, I.; Paquette,
L. A. Tetrahedron 2006, 62, 5791. (b) Pichlmair, S.; de
Lera Ruiz, M.; Basu, K. I.; Paquette, L. A. Tetrahedron
2006, 62, 5178. (c) Araki, K.; Saito, K.; Arimoto, H.;
Uemura, D. Angew. Chem. Int. Ed. 2004, 43, 81.
1H NMR (250 MHz, CDCl3): d = 7.83 (s, 1 H), 7.40–7.30 (m, 7 H),
7.25–7.17 (m, 3 H), 6.48 (s, 1 H), 2.41–2.25 (m, 3 H), 1.94–1.89 (m,
1 H), 1.59–1.50 (m, 1 H), 1.11–1.00 (m, 1 H).
13C NMR (62.5 MHz, CDCl3): d = 201.1, 193.2, 158.8, 145.3,
136.7, 132.6, 131.4, 130.6, 129.1, 128.9, 128.7, 128.6, 128.4, 128.3,
128.1, 128.0, 127.7, 71.9, 66.1, 65.6, 63.2, 31.0, 25.7, 21.3.
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2000, 65, 4843.
(2) (a) Sato, S.; Isobe, H.; Tanaka, T.; Ushijima, T.; Nakamura,
E. Tetrahedron 2005, 61, 11449. (b) Isobe, H.; Sato, S.;
Tanaka, T.; Tokuyama, H.; Nakamura, E. Org. Lett. 2004, 6,
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HRMS: m/z [M]+ calcd for C25H18Br2O2: 509.9648; found:
509.9616.
24f
IR (film): 2917, 1789, 1683, 1430 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.20 (d, J = 6.0 Hz, 1 H), 6.34 (d,
J = 6.0 Hz, 1 H), 5.86 (d, J = 1.5 Hz, 1 H), 3.11–3.10 (m, 1 H), 2.08–
1.99 (m, 3 H), 1.82–1.80 (m, 1 H), 1.74–1.71 (m, 1 H), 1.66 (d, J =
(3) Eaton, P. E. Angew. Chem., Int. Ed. Engl. 1992, 31, 1421.
Synthesis 2007, No. 15, 2370–2378 © Thieme Stuttgart · New York

2378
M. Harmata, K. Rayanil
PAPER
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(13) Crystallographic data (excluding structure factors) for the
structure in this paper have been deposited with the
Cambridge Crystallographic Data Centre (CCDC) as
supplementary publication number CCDC 638954(30).
Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road Cambridge CB2 1EZ,
UK, fax: +44(1223)336033, e-mail:
(6) Harmata, M.; Gomes, M. G. Eur. J. Org. Chem. 2006, 2273.
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(10) A rigorous temperature study will be performed when we
have a clean cyclopentadienone precursor in hand.
deposit@ccdc.cam.ac.uk.
Synthesis 2007, No. 15, 2370–2378 © Thieme Stuttgart · New York