Facile synthesis of 4-functionalized cyclopentenones

Article abstract of DOI:10.1080/00397910701354392

1-8-Diazabicyclo[5.4.0]undec-7-ene(DBU)-catalyzed Michael addition of nitroalkanes to dicyclopentadienone (1) followed by flash vacuum pyrolysis (FVP) provided a high-yielding synthesis of extremely pure 4-nitroalkyl cyclopentenones (3). The optimized Nef reaction of the nitro adducts (2) provided 4-ketoalkyl cyclopentenones (5) in the similar way. Copyright Taylor & Francis Group, LLC.

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Facile Synthesis of 4‐Functionalized
Cyclopentenones
Sujit Kumar Ghorai a , Nirmal Kumar Hazra a & Dipakranjan Mal a
a Department of Chemistry, Indian Institute of Technology, Kharagpur, India
Published online: 22 Jun 2007.
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of 4‐Functionalized Cyclopentenones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:12, 1949-1956
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Synthetic Communicationsw, 37: 1949–1956, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701354392
Facile Synthesis of 4-Functionalized
Cyclopentenones
Sujit Kumar Ghorai, Nirmal Kumar Hazra, and
Dipakranjan Mal
Department of Chemistry, Indian Institute of Technology,
Kharagpur, India
Abstract: 1-8-Diazabicyclo[5.4.0]undec-7-ene(DBU)-catalyzed Michael addition of
nitroalkanes to dicyclopentadienone (1) followed by flash vacuum pyrolysis (FVP)
provided a high-yielding synthesis of extremely pure 4-nitroalkyl cyclopentenones
(3). The optimized Nef reaction of the nitro adducts (2) provided 4-ketoalkyl cyclopen-
tenones (5) in the similar way.
Keywords: flash vacuum pyrolysis (FVP), Michael addition, Nef reaction, nitroalkanes
Because of their multifunctional properties, substituted cyclopentenones are
versatile intermediates for the synthesis of several bioactive natural products
containing five-membered rings.[1] 4-Substituted cyclopentenones, especially
4-nitroalykl cyclopentenones, could be considered the more important inter-
mediates because a nitroalkyl group provides a new reaction center in
addition to their existing five reactive carbon centers. Although the Pauson–
Khand[2] reaction has been extensively used for the synthesis of cyclopente-
nones using alkenes, alkynes, and high-pressure carbon monoxide, newer pre-
parative methods are still being developed.[3] In recent years, Klunder and
coworkers have shown the utility of flash vacuum pyrolysis (FVP) for the
synthesis of substituted cyclopentenones.[4] As a part of our current study[5]
directed toward synthesis of stealthins and kinamycin antibiotics, in which
Received in India October 26, 2006
Address correspondence to Dipakranjan Mal, Department of Chemistry, Indian
Institute of Technology, Kharagpur 721302, India. E-mail: dmal@chem.iitkgp.ernet.in
1949

1950
S. K. Ghorai, N. K. Hazra, and D. Mal
cyclopentenone moieties are embedded, we successfully synthesized 4-nitro-
methyl cyclopentenones in excellent yield using FVP as a key step.
Therefore, we decided to generalize the method. Herein, we report a new
and general synthesis of 4-nitroalkyl cyclopentenones (3) as well as a general
synthesis of 4-(1-oxoalkyl)cyclopentenones (4).
RESULTS AND DISCUSSION
Dicyclopentadineone 1 was prepared on a large scale (ꢀ50 g) in two steps
from commercially available dicyclopentadiene according to the literature
method.[6] Treatment of the enone 1 with 15-fold excess of nitromethane in
the presence of DBU provided 2a in high yield (Scheme 1). All other bases
i
t
t
(e.g., NaOH, KOH, NaOEt, Et3N, Pr2NH, BuOK, and BuOLi) examined
in the place of DBU resulted in either very poor yields of the products or
no products. When the nitro adduct 2a was subjected to FVP at 4008C and
0.01 Torr., the expected cyclopentenone 3a was obtained in excellent yield
1
(.90%). Two signals of olefinic protons in the H NMR spectrum and two
strong peaks in the IR spectrum at 1711 cm21 and 1548 cm21 corresponding
to carbonyl and nitro groups left no doubt about the structure of the compound
3a. Compounds 2b, 2c, and 2d were similarly prepared by treatment of enone
1 with an excess of the respective nitroalkanes (6). Compounds 2b and 2c, and
their corresponding thermolyzed products 3b and 3c were obtained as insepar-
able mixtures of two respective diastereomers. 13C NMR spectra of all the
compounds showed two sets of signals corresponding to each carbon. When
the compound 2d was subjected to FVP at 4508C and 0.01 Torr., the corre-
sponding thermolyzed product 3d was obtained in 70% yield along with 3e
(15%), which was deposited in the different regions of the collection tube.
The unusual formation of the second compound 3e could be explained by
the loss of HNO2 followed by retro Diels–Alder reaction of 2d. Although
organonitro compounds tend to detonate at high temperatures, compounds
3a–3d showed no sign of instability to heat.
Scheme 1.

4-Functionalized Cyclopentenones
1951
The Nef reaction[7] (i.e., the reaction for the conversion of a nitroalkyl
to carbonyl functionality) is a well-studied reaction. However, the outcome
of the reaction with respect to yield of a keto product is highly dependent
on the nature of reagents and reaction conditions. A reliable prescription is
still lacking in the literature. After scrutiny of several reagents, buffered
[8]
TiCl3 was found to be the most suitable for the present study, and it
was successfully utilized for the conversion of nitro compounds 2a, 2b,
and 2c to the respective keto compounds (Scheme 2). Both the
compounds 4b and 4c could be purified by silica-gel column chromato-
graphy. Compound 4a could not be fully purified. It was sufficiently pure
for spectral characterization. The appearance of a signal at d10.1 ppm in
1
the H NMR spectrum of compound 4a was indicative of its formation,
but it was too unstable for further characterization. Flash vacuum
pyrolysis of 4b and 4c at 3508C and 0.01 Torr. provided the expected
cyclopentenones 5b and 5c in good yields.
In conclusion, we have described an easy preparation of 4-functionalized
cyclopentenones from easily accessible starting materials. Although the route
is easily conceivable on the basis of well-established retro Diels–Alder
reactions, the finding on the use of DBU for the successful Michael
additions is critically important.
EXPERIMENTAL
General
1H NMR spectra were recorded at 200 MHz (Brucker) solution for 2H
chloroform with tetramethylsilane as the internal standard. IR spectra were
obtained on a Perkin-Elmer instrument, model 883, using KBr pellets (for
solids) or neat (for liquids). Melting points were determined in open
capillary tubes and are uncorrected. All solvents used for the reactions
were purified before use.
Scheme 2.

1952
S. K. Ghorai, N. K. Hazra, and D. Mal
2,3,3a,4,7,7a-Hexahydro-4,7-methano-3-nitromethyl-1H-indene-1-
one (2a)
To a stirred solution of 3a,4,7,7a-tetrahydro-4,7-methano-1H-inden-1-one 1
(2.5 g, 10.25 mmol) and nitromethane (15 eq.), DBU (3 drops) was added at
08C and allowed to stir at room temperature overnight. The reaction
mixture was diluted with diethyl ether (150 mL) and washed with 5% HCl,
water, and brine. The organic layer was then dried (Na2SO4) and concentrated
to provide a crude product. The crude was purified by chromatography to
1
furnish 2a as an oil (1.31 g, 67%). H NMR (200 MHz): d 6.21 (brs, 2H,
CH55CH), 4.48–4.26 (m, 2H, CH2NO2), 3.24–3.22 (m, 1H, ring-H), 3.1
(brs, 1H, ring-H), 3.05–2.9 (m, 1H, ring-H), 2.8–2.7 (m, 1H, ring-H), 2.6–
2.48 (m, 1H, CH-CH2NO2), 2.4–1.97 (m, 2H, CH2-O), 1.61 (Ad, 1H,
J ¼ 8.6 Hz, CH2-bridge), 1.4 (ABq, 1H, J ¼ 8.6 Hz, CH2-bridge); 13C
NMR (50 MHz): d 216.3, 136.9, 134.6, 79.8, 54.7, 52.2, 46.9, 46.4, 46,
44.6, 35.2; IR (cm21): 1733, 1549, 1381, 1190, 735; MS(m/z): 207 (Mþ).
4-(1-Nitromethyl)cyclopent-1-enone (3a)
This compound was prepared as a colorless oil in 95% yield by FVP of 2a, at
4508C, 0.01 mm. 1H NMR (200 MHz): d7.59–7.55 (m, 1H, CH55), 6.34–6.30
(m, 1H, CH55), 4.51–4.43 (m, 2H, CH2-NO2), 3.75–3.70 (m, 1H, ring-H),
2.67 (ABq, 1H, J ¼ 18.8, 2.6 Hz, CH2CO), 2.18 (ABq, 1H, J ¼ 18.8, 2.6
Hz, CH2CO); 13C NMR (50 MHz): d 206.31, 161.18, 136.46, 77.39, 39.24,
38.07; IR (cm21): 1711, 1548, 1381, 1179.
2,3,3a,4,7,7a-Hexahydro-4,7-methano-3-(1-nitroethyl)-1H-indene-
1-one (2b)
This compound was prepared as a colorless oil in 84% yield from 1 and nitro-
methane following the procedure adopted for the preparation of compound 2a.
1H NMR (200 MHz): (mixture of diastereomers) d 6.19–6.17 (m, 2H,
CH55CH), 4.54-4.43 (m, 1H, CH-NO2), 3.20 (brs, 1H, ring-H), 3.03–2.94
(m, 2H, ring-H), 2.80–2.68 (m, 1H, ring-H), 2.32–2.09 (m, 3H, CH2-CO),
1.67-1.41 (m, 5H, bridge-CH2, CH3); 13C NMR (50 MHz): d (216.75,
216.55), (136.97, 136.72), (134.91, 134.60), (87.43, 86.88), (55.14, 54.96),
(52.24, 52.22), (47.11, 47.03), (46.01, 45.90), (45.37, 44.55), (44.46, 44.10),
(41.54, 41.37), (17.45, 16.81); IR (cm21): 1730, 1541, 1132, 730.
4-(1-Nitroethyl)-cyclopent-2-enone (3b)
This compound was prepared as a colorless oil in 95% yield by FVP of 2b. 1H
NMR (200 MHz): (mixture of diastereomers) d 7.59–7.45 (m, 1H, CH55),

4-Functionalized Cyclopentenones
1953
6.30–6.25 (m, 1H, CH55), 4.65–4.56 (m, 1H, CH-NO2), 3.58–3.49 (m, 1H,
ring-H), 2.53 (dd, J ¼ 19.0, 6.8 Hz, 1H, CH2), 2.23–2.10 (m, 1H, CH2),
1.58–1.52 (m, 3H, CH3); 13C NMR (50 MHz): (206.25, 206.12), (161.09,
160.74), (136.81, 136.36), (84.58, 84.43), (44.98, 44.78), (37.21, 36.56),
(16.45, 16.29); IR (cm21): 2989, 1716, 1546, 1398, 1185.
2,3,3a,4,7,7a-Hexahydro-4,7-methano-3-(1-nitropropyl)-1H-indene-
1-one (2c)
This compound was prepared as a colorless oil in 84% yield from 1 and 2-
nitropropane following the procedure adopted for the preparation of
1
compound 2a. H NMR (200 MHz): (mixture of diastereomers) d 6.21–
6.16 (m, 2H, CH55), 4.37–4.26 (m, 1H, CH-NO2), 3.18 (brs, 1H, ring-H),
3.03–2.91 (m, 2H, ring-H), 2.82–2.73 (m, 2H, ring-H), 2.27–2.11 (m, 2H,
CH2CO), 2.06–1.82 (m, 2H, CH2-CH3), 1.71–1.40 (m, 2H, CH2), 1.04–
0.92 (m, 3H, CH3); 13C NMR (50 MHz): d (216.50, 216.28), (137.16,
136.97), (135.11, 134.63), (94.81, 94.35), (55.12, 54.94), 52.34, (47.12,
47.03), (45.85, 45.73), 45.44, (44.98, 44.59), (40.74, 40.62), (25.48, 25.02),
(10.35, 10.20); MS (m/z): 236 (Mþ þ 1).
4-(1-Nitropropyl)-cyclopent-2-enone (3c)
This compound was prepared as an odorless oil in 94% yield by FVP of 2c. 1H
NMR (200 MHz): d 7.62–7.43 (m, 1H, CH55), 6.35–6.29 (m, 1H, CH55),
4.49–4.28 (m, 1H, CH-NO2), 3.60–3.42 (m, 1H, ring-CH), 2.49–1.76
(m, 4H, CH2CO, CH2CH3), 1.03 (t, 3H, J ¼ 7.3 Hz, CH3); IR (cm21):
1716, 1545, 1163, 1063, 795.
2,3,3a,4,7,7a-Hexahydro-4,7-methano-3-(2-nitropropyl)1H-indene-
1-one (2d)
This compound was prepared as white solid in 88% yield from 1, following the
procedure adopted for the preparation of compound 2a. Mp: 808C; 1H NMR (200
MHz): d 6.26–6.20 (m, 2H, CH55CH), 3.21–3.19 (m, 1H, ring-H), 3.01–2.91
(m, 2H, ring-H), 2.74–2.65 (m, 1H, ring-H), 2.49–2.38 (m, 1H, ring-H), 2.19-
2.10 (m, 2H, CH2, CH2CO), 1.56 (s, 6H, CH3), 1.48–1.41 (m, 2H, bridge-CH2);
13C NMR (50 MHz): d 217.77, 136.76, 134.69, 90.96, 55.24, 52.16, 47.67, 46.51,
45.83, 44.18, 43.43, 24.33, 22.89; IR (cm21) 1729, 1524, 1344, 1137, 734.
4-(2-Nitropropyl)-cyclopent-2-enone (3d)
This compound was prepared as a white solid in 70% yield by FVP of 2d. Mp:
1
798C; H NMR (200 MHz): 7.52–7.47 (m, 1H, CH55), 6.34–6.30 (m, 1H,

1954
S. K. Ghorai, N. K. Hazra, and D. Mal
CH55), 3.72–3.63 (m, 1H, ring-H), 2.53 (ABq, 1H, J ¼ 19, 6.8 Hz, CH2CO),
2.14 (ABq, 1H, J ¼ 19, 2.8 Hz, CH2CO), 1.60 (s, 3H, CH3), 1.49 (s, 3H, CH3);
13C NMR (50 MHz): d 206.38, 161.08, 136.69, 89.14, 49.52, 36.86, 23.60,
23.26; IR (cm21): 1707, 1528, 1348, 1191, 845, 734.
4-(2-Propylidine)-cycolpent-2-enone (3e)
This compound was formed as a white solid in 15% yield during the synthesis
of compound 3d. Mp: 818C. 1H NMR (200 MHz): d 8.98 (d, 1H, J ¼ 5.6 Hz,
CH55), 6.16 (d, 1H, J ¼ 5.6 Hz, CH55), 2.88 (s, 2H, CH2CO), 1.60 (s, 3H,
CH3), 1.49 (s, 3H, CH3); IR (cm21): 1710, 1192, 773.
2,3,3a,4,7,7a-Hexahydro-4,7-methano-3(1-oxoethyl)-1H-indene-1-
one (4b)
A solution of nitro compound 2b (0.5 g, 2.26 mmol) in methanol (35 mL) was
treated sequentially with sodium methoxide (6.84 mmol) and a solution of
titanium trichloride (15% w/v, 13.2 mL) in ammonium acetate (6 g in
13.2 mL of water). The mixture was stirred under nitrogen for 30 min
and with external cooling (ice water). Diethyl ether (50 mL) and brine
(35 mL) was added, and the layers were separated. The aqueous layer was
extracted with diethyl ether (2 ꢀ 35 mL). The combined organic layer was
washed with aqueous sodium bicarbonate (3 ꢀ 60 mL), water (60 mL), and
brine (40 mL) and then dried (Na2SO4) and concentrated to provide a crude
product, which was purified by column (silica-gel) chromatography to give
1
pure product as an oil (0.35 g, 83% yield). H NMR (200 MHz): d 6.20
(brs, 2 H, CH55CH), 3.21 (brs, 1H, ring-H), 3.13 (brs, 1H, ring-H), 3.04–
2.95 (m, 2H, ring-H), 2.70–2.65 (m, 1H, CH2CO), 2.58–2.54 (m, 1H, CH2-
CO), 2.23 (s, 3H, CH3), 2.12–2.08 (m, 1H, CH2-CO), 1.64 (ABd, 1H,
J ¼ 8.4 Hz, CH2), 1.49 (ABd, 1H, J ¼ 8.4, CH2); 13C NMR (50 MHz): d
216.95, 207.16, 137.31, 134.00, 54.11, 52.25, 49.56, 46.98, 46.00, 44.36,
42.34, 28.42; IR (cm21) 2973, 1729, 1354, 1175.
4-(1-Oxoethyl)-cyclopent-2-enone (5b)
This compound was prepared as a colorless oil in 78% yield by FVP of 4b. 1H
NMR (200 MHz): d 7.67–7.65 (dd, J ¼ 12, 3 Hz, 1H, CH55), 6.24–6.22 (dd,
J ¼ 12, 2, 1H, CH55), 3.93–3.86 (m, 1H, ring-H), 2.43–2.40 (m, 2H, ring-H),
2.35–2.26 (m, 3H, CH3); 13C NMR (50 MHz): d 207.43, 294.19, 160.00,
135.24, 54.77, 35.89, 28.44; IR (cm21): 1722, 722.

4-Functionalized Cyclopentenones
1955
2,3,3a,4,7,7a-Hexahydro-4,7-methano-3-(1-oxopropyl)-1 H-inden-1-
one (4c)
This compound was prepared as a colorless oil in 81% yield from 3c,
1
following the procedure adopted for the preparation of compound 4b. H
NMR (200 MHz): d 6.29–6.25 (m, 2H, CH55CH), 3.23 (brs, 1H, ring-H),
3.13 (brs, 1H, ring-H), 3.01-2.98 (m, 2H, ring-H), 2.62–2.48 (m, 3H, ring-
H, CH2CO), 2.39–2.34 (m, 2H, ring-CH2CO), 1.64 (ABd, 1H, J ¼ 7.9 Hz,
ring-CH2), 1.51–1.47 (ABd, 1H, J ¼ 7.9 Hz, ring-CH2), 1.10 (t, 3H,
J ¼ 7.1 Hz, CH3); 13C NMR (50 MHz): d 218.06, 211.06, 137.27, 134.17,
54.25, 52.30, 48.52, 47.03, 46.05, 44.83, 42.78, 34.78, 27.84; IR (cm21):
2976, 1727, 1454, 1118, 1123, 735.
4-(1-Oxopropyl)-cyclopent-2-enone (5c)
This compound was prepared as colorless oil in 74% yield by FVP of 4c. 1H
NMR (200 MHz): d 7.68–7.64 (m, 1H, CH55), 6.25–6.21 (m, 1H, CH55),
3.98–3.91 (m, 1H, ring-H), 3.14 (dd, 1H, J ¼ 8.8, 2.5 Hz, ring-CH2CO),
2.67–2.48 (m, 3 H, CH2CO, ring-CH2-CO), 1.08 (t, 3H, J ¼ 7.3 Hz, CH3);
13C NMR (50 MHz): 207.50, 207.09, 160.22, 135.10, 53.71, 36.11, 34.72,
7.56; IR (cm21): 2980, 2934, 1716, 1690, 1189, 779.
ACKNOWLEDGMENT
Financial assistance for this work from the Department of Science and Tech-
nology (DST) and the Council of Scientific and Industrial Research (CSIR),
New Delhi, is gratefully acknowledged.
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