An expedient protocol for cyclopentenone annulation

Article abstract of DOI:10.1055/s-2004-831208

A convenient and general protocol for the cyclopentenone annulation process is described.

Full text of DOI:10.1055/s-2004-831208

FEATURE ARTICLE
2919
An Expedient Protocol for Cyclopentenone Annulation
An
E
xpedient Protocol
u
f
or Cyclope
k
ntenone
A
nn
u
ulation nd G. Kulkarni,* Saryu I. Davawala, Aniruddha K. Doke, Dhananjay S. Pendharkar
Department of Chemistry, University of Pune, Ganeshkhind, Pune – 411 007, India
Fax +91(20)25691728; E-mail: mgkulkarni@chem.unipune.ernet.in
Received 20 January 2004; revised 13 April 2004
This publication is dedicated to Prof. Hsing-Jang Liu on the occasion of his 60th birthday.
rene,19 we have developed a convenient and efficient pro-
tocol for the construction of 4-substituted and 4,4-
disubstituted-2-cyclopentenones. This consists of four
steps: Wittig olefination to an allyl vinyl ether;20 Claisen
rearrangement;21–23 Wacker oxidation;24 and finally, in-
tramolecular aldol condensation.
Abstract: A convenient and general protocol for the cyclopenten-
one annulation process is described.
Key words: cyclopentenone annulation, Wittig olefination, Claisen
rearrangement, Wacker oxidation, polyquinanes
Wittig olefination of aldehydes and ketones with
allyloxymethylenetriphenylphosphonium chloride under
reported reaction conditions20 afforded the corresponding
allyl vinyl ethers, in most cases, as an inseparable mixture
of E and Z isomers25 (Table 1). Heating these allyl vinyl
ethers in refluxing xylene effected the Claisen rearrange-
ment and gave substituted 4-pentenals in near quantitative
yields. Under standard Wacker oxidation conditions,
these 4-pentenals were converted smoothly to the corre-
sponding ketoaldehydes in good yields. The aldehyde
group remained unaffected under the Wacker conditions.
The cyclopentenone annulation process has considerable
synthetic value, as one or more cyclopentane rings are part
of several natural products1–8 like the polyquinanes. The
importance of this is evident by the numerous cyclopen-
tenone annulation methodologies currently available.9–20
In spite of this, construction of a sterically crowded cyclo-
pentane ring is still a challenging task and inspires the de-
velopment of novel approaches toward this end. In the
context of our interests in the synthesis of cyclopentanoid
natural products, namely ( )-a-cuparenone19 and ( )-lau-
Table 1
R1
R2
a
b
c
Ph
CH3
CH3
CH3
83%
81%
81%
96%
93%
97%
83%
84%
83%
89%
90%
86%
[4-(Me)C6H4]
[3,4-di-(OMe)-
C6H3]CH2CH2
d
e
f
[4-(OMe)C6H4]CH2CH2
CH3CH2CH2
CH3
85%
94%
89%
88%
84%
95%
76%
71%
73%
72%
76%
88%
83%
81%
82%
87%26
CH3CH2CH2
CH3(CH2)3
CH3
78%31
77%31
74%31
86%
CH3CH2CH2
g
h
CH3CH2
[3,4-di-(OMe)C6H3]
H
Reagents and Conditions:
i) CH2CHCH2OCH2Ph3P+Cl-, THF, t-BuO-K+/t-BuOH, 0 °C. ii) Xylene, reflux, 4–5 h. iii) PdCl2/CuCl2 (10 mol% each), O2, H2O–DME (1:9),
r.t., 2–3 h. iv) 5% aq. methanolic KOH, r.t., 2 h.
SYNTHESIS 2004, No. 17, pp 2919–2926
x
x.
x
x
.
2
0
0
4
Advanced online publication: 02.09.2004
DOI: 10.1055/s-2004-831208; Art ID: Z01204SS
© Georg Thieme Verlag Stuttgart · New York

2920
M. G. Kulkarni et al.
FEATURE ARTICLE
Varian Mercury 300 instrument. Elemental analyses were obtained
on a HOSLI semi-automatic C, H analyzer.
Intramolecular aldol condensation of the ketoaldehydes
with 5% methanolic KOH afforded 2-cyclopentenones in
excellent yields. The whole sequence is short enough to be
executed in a single long working day.
General Procedures32
To a suspension of aldehyde or ketone 1a–h (5 mmol) and
allyloxymethylenetriphenylphosphonium chloride (1.2 equiv) in
dry THF at 0 °C was dropwise added a solution of KOt-Bu (1.2
equiv) in dry t-BuOH. After one hour, the normal aqueous extrac-
tive work up gave crude allyl vinyl ethers. Passing these crude prod-
ucts through a short silica gel column afforded the allyl vinyl ethers
2a–h in 74–86% yield and in sufficiently pure form for the next re-
action.
All solvents were distilled and dried before use. ‘Acme’ silica gel
(100–200 mesh) was used for column chromatography, and a hex-
ane–EtOAc solvent system was used for elution. The mp and bp val-
ues are uncorrected and were obtained using a paraffin oil bath. The
FT-IR spectra were recorded on a Perkin-Elmer 1600 series instru-
1
ment. H and 13C NMR spectra were recorded on JEOL FX 90Q/
Biographical Sketches
Mukund G. Kulkarni was sity of Alberta in 1985. He include total synthesis of
born in India in 1953. He re- returned to India and was a natural products, newer syn-
ceived his B.Sc. in 1973 and lecturer at the University of thetic methods, asymmetric
M.Sc. in 1975 from the Uni- Pune from January 1989 to synthesis, chemistry of car-
versity of Pune, and his doc- December 1996 and is cur- bohydrates and radical cy-
toral degree in organic rently a reader at the same clisation
chemistry from the Univer- place. His research interests synthesis.
methods
in
Saryu I. Davawala was ance of Dr. M. G. Kulkarni. appointed as a lecturer in the
born in India in 1969. She She worked as a postdoctor- Department of Chemistry,
received her B.Sc. in 1990 al fellow in Dr. Reddy’s University of Pune from
and M.Sc. in 1992 from the Research Foundation, Hy- September 2001 to August
University of Pune and derabad from May to Au- 2002 and from November
completed her Ph. D. from gust, 2000. She worked as 2002 to July 2003. She is
the Department of Chemis- an Executive R&D in currently a Young Scientist,
try, University of Pune, in SPARC, Baroda from Janu- DST, in the same depart-
May 1999 under the guid- ary to April, 2001. She was ment.
Aniruddha K. Doke was as a research associate in his doctoral degree under
born in India in 1976. He re- Colgate-Palmolive (India) the guidance of Dr. M. G.
ceived his B.Sc. in 1996 and Ltd, Mumbai, India from Kulkarni.
M.Sc. in 1998 from the Uni- June to December of 1998.
versity of Pune. He served He is currently pursuing
Dhananjay S. Pendharkar Department of Chemistry, joined Wockhardt, India,
was born in India in 1969. University of Pune, in 1998 Aurangabad and is currently
He completed his B.Sc. in under the guidance of Dr. working in Aurigene Dis-
1990 from Shivaji Universi- M. G. Kulkarni. He pursued covery Tech. Ltd., Banga-
ty, Kolhapur, and his M.Sc. postdoctoral research at the lore.
in 1992 from the University University of Kentucky
of Pune and Ph.D. from the from 1998 to 2000. He then
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York

FEATURE ARTICLE
An Expedient Protocol for Cyclopentenone Annulation
2921
A solution of the allyl vinyl ethers 2a–h was heated in refluxing xy-
lene for 4–5 h. Removal of xylene under reduced pressure gave 4-
pentenals 3a–h in 84–97% yield and in fairly pure form.
The crude ketoaldehydes 4a–4h were dissolved in 5% aq. methan-
olic KOH and stirred at r.t. until the reaction was complete. Remov-
al of methanol under reduced pressure and purification of the
product on a silica gel column gave 2-cyclopentenones 5a–g,j in
81–90% yield.
The 4-pentenals 3a–h, PdCl2 (10 mol%), and CuCl2 (10 mol%)
were dissolved in aqueous DME (1:9) and stirred under an oxygen
atmosphere for 2–3 h. When the reaction was observed to be com-
plete, normal aqueous extractive work-up gave the ketoaldehydes
4a–h in 71–84% yield.
Table 2
Compound
Bp/Mp
[°C] (Torr) (neat/nujol)
IR [cm–1]
1H NMR (CDCl3) d J (Hz)
13C NMR (CDCl3) d
Microanalysis
calcd/found
C
H
2a
–
1645.0, 1513.4, 1.84, 1.96 (2 × s, 3 H, E,Z
16.6, 21.4 (-C=C-CH3), 74.6
(-O-CH2CH), 109.4 (Ar-
C=CH-), 117.9 (-CH=CH2),
127.7 (Carompara), 128.1
82.72
82.92
8.10
8.28
viscous liquid
1434.1, 1378.7, -C=C-CH3), 4.30 (m, 2 H,
814.6.
-O-CH2CH=), 5.32 (m, 2 H,
-C=CH2), 5.91 (m, 1 H,
-C=CH-), 6.20, 6.48 (2 × s, 1 H, (Carommeta), 129.4 (Caromortho),
E,Z O-CH=C), 7.31 (s, 5 H, Ar- 133.8 (CH2-C=CH2), 135.8
H)
(Carom1), 138.7 (O-CH=C)
2b
–
1654.1, 1512.8, 2.04, 2.12 (2 × s, 3 H, E,Z C=C- 16.5, 21.3 (-C=C-CH3), 21.4
82.93
8.57
8.62
viscous liquid
1434.1, 1378.6, CH3), 2.44 (s, 3 H, Ar-CH3),
812.8. 4.64 (m, 2 H, -OCH2-), 5.62 (m, 109.5 (Ar-C=CH), 118.1
2 H, C=CH2), 6.24 (m, 1 H, (-CH=CH2-), 128.3 (Caromme-
(Ar-CH3), 74.7 (-O-CH2CH=), 83.11
-C=CH-), 6.48, 6.84 (2 × s, 1 H, ta), 129.6 (Caromortho), 133.7
E,Z -O-CH=C), 7.66 (m, 4 H,
Ar-H)
(-CH2-C=CH2), 135.9 (Carom1),
137.3 (Carompara), 138.8 (-O-
CH=C-)
2c
–
1682.0, 1603.0, 1.57, 1.68 (2 × s, 3 H, E,Z C=C- 16.8, 21.2 (=C-CH3), 32.8 (Ar- 73.25
1522.0, 1461.0, CH3), 2.15, 2.39 (t, 2 H, C=C- CH2-CH2-), 33.8 (Ar-CH2-), 73.40
8.45
8.61
viscous liquid
820.0
CH2-, J = 7.7 Hz), 2.64 (m, 2 H, 55.8, 55.9 (2 × -O-CH3), 74.8
Ar-CH2-), 3.84 (s, 3 H, -OCH3), (-O-CH2-CH=), 108.9
3.86 (s, 3 H, -OCH3), 4.12–4.17 (CH3C=C-O-), 113.1
(m, 2 H, -OCH2), 5.16–5.27 (m, (Carom5meta), 114.5
2 H, -C=CH2-), 5.81–5.89 (m, 1 (Carom2ortho), 118.1
H, CH2=CH-), 6.70, 6.79 (2 × s, (-CH=CH2), 121.5
1 H, E,Z -CH=C), 6.75–6.87
(Carom6ortho), 131.6 (Carom1),
133.3 (-CH2-C=CH2), 137.9
(-O-CH=C), 144.1
(m, 3 H, Ar-H)
(Carom4para), 147.8
(Carom3meta)
2d
–
1675.0, 1621.0, 1.55, 1.68 (2 × s, 3 H, E,Z
1520.0, 1445.0, -C=C-CH3), 2.14, 2.38 (2 × t, 2 CH2-CH2-), 33.5 (Ar-CH2-),
835.0. H, J = 8.0 Hz, -C=C-CH2-), 55.8 (-O-CH3), 74.5 (-O-CH2-
2.65 (m, 2 H, Ar-CH2-), 3.78 (s, CH=), 109.5 (CH3C=C-O-),
3 H, -OCH3), 4.12–4.18 (m, 2 114.1 (Carommeta), 117.9
16.4, 21.0 (=C-CH3), 32.6 (Ar- 77.55
8.68
8.49
viscous liquid
77.66
H, -OCH2), 5.19–5.28 (m, 2 H, (-CH=CH2), 128.2(Caromortho),
-CH=CH2-), 5.78–5.92 (m, 1 H, 131.9 (Carom1), 133.1 (CH2-
-CH=CH2), 6.81, 6.83 (2 × s, 1 C=CH2), 138.2 (-O-CH=C),
H, E,Z -O-CH=C), 7.07–7.15
148.7 (Carompara)
(m, 4 H, Ar-H)
2e
liquid
167–169
(760)
2933.2, 1651.3, 0.95 (m, 6 H, 2 × -CH3), 1.29
1464.7, 1168.2 (m, 4 H, 2 × -CH2-CH3), 1.87
(m, 4 H, 2 × -CH2-CH2-CH3),
13.7 (CH3CH2-), 22.4
(CH3CH2-), 30.5, 34.1
(CH3CH2CH2-), 74.2 (-OCH2-),
114.2 (-C=CH-O-), 118.3
78.51
78.42
11.98
11.79
4.59 (m, 2 H, -O-CH2-), 5.26
(m, 2 H, -CH=CH2), 5.96 (m, 1 (-CH2CH=CH2), 132.8
H, -CH2-CH=CH2), 6.4 (s, 1 H, (-CH2CH=CH2), 139.7 (-O-
-O-CH=C-) CH=C-)
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York

2922
M. G. Kulkarni et al.
FEATURE ARTICLE
Table 2 (continued)
Compound
Bp/Mp
[°C] (Torr) (neat/nujol)
IR [cm–1]
1H NMR (CDCl3) d J (Hz)
13C NMR (CDCl3) d
Microanalysis
calcd/found
H
C
2f
liquid
181–182
(760)
2920.5, 1653.2, 0.94–1.0 (m, 6 H, 2 × -CH3),
1462.5, 1157.9 1.25–1.40 (m, 6 H, -CH2CH3,
-CH2CH2CH2CH3), 1.86–1.93
13.9 (CH3CH2-), 17.8
(CH3CH2-), 20.7, 22.5 (2 ×
-CH2CH3), 29.2, 29.8 (2 ×
79.06
78.92
12.16
12.27
(m, 4 H, 2 × -CH2-C-), 4.58 (m, -CH2CH2CH3), 31.8
2 H, -O-CH2-), 5.21–5.40 (m, 2 (-CH2C=CH), 73.8 (-O-CH2-),
H, -CH=CH2), 5.96 (m, 1 H, 112.2 (-C=CH-O-), 117.2
-CH2CH=CH2), 6.41, 6.48 (2 × (-CH2CH=CH2), 133.1
s, 1 H, E,Z -O-CH=C-)
(-CH2CH=CH2), 138.6 (-O-
CH=C-)
2g
liquid
142–144
(760)
2925.8, 1658.7, 0.92 (m, 3 H, -CH2CH3), 1.41
1454.2, 1164.9 (s, 3 H, -C-CH3), 1.93 (m, 2 H, (E,Z CH3-C-), 28.4 (CH3CH2-),
14.1 (CH3CH2-), 17.7, 21.6
76.14 75.92
11.18
11.31
-CH2CH3), 4.51 (m, 2 H, -O-
CH2-), 5.21–5.36 (m, 2 H,
-CH=CH2), 5.94 (m, 1 H,
73.9 (-O-CH2-), 108.9 (-C=CH-
O-), 118.1 (-CH2CH=CH2),
134.1 (-CH2CH=CH2), 138.3
-CH2CH=CH2), 6.42, 6.48 (2 × (-O-CH=C-)
s, 1 H, E,Z -O-CH=C-)
2h
–
1681.2, 1653.6, 4.20 (s, 6 H, 2 × -OCH3), 4.66
55.8, 56.1 (2 × O-CH3), 73.9
70.90
71.01
7.32
7.54
viscous liquid
1601.7, 1515.6, (m, 2 H, -O-CH2C=), 5.68 (m, 2 (-O-CH2-), 99.5 (Ar-C=C-),
859.0
H, -CH=CH2-), 6.42 (m, 1 H,
-CH2CH=CH2), 6.60 (d, 1 H,
110.7 (Carom2ortho), 113.3
(Carom5meta), 117.2
J = 8.0 Hz, -O-CH=CH-), 7.44 (-CH=CH2), 119.6
(m, 3 H, Ar-H), 7.82 (d, 1 H,
(Carom6ortho), 128.7 (Carom1),
J = 10.2 Hz, OCH=CH-)
134.7 (-C=CH2), 143.2 (-O-
CH=C), 146.1 (Carom4para),
148.3 (Carom3meta)
3a
liquid
82 (3)
2729.1, 1720.9, 1.32 (s, 3 H, -C-CH3), 2.58 (d, 2 21.4 (C-CH3), 39.5
1651.3, 1446.5, H, J = 7.7 Hz, -C=CHCH2-), (-CH2CH=CH2), 55.9 (Ar-C-
922.0 5.24 (m, 2 H, -C=CH2), 5.44 CHO), 118.6 (-CH=CH2),
(m, 1 H, -C=CH-), 7.28 (s, 5 H, 124.7 (Caromortho), 126.3
82.72 82.63
8.10
7.96
Ar-H), 9.60 (s, 1 H, -CHO)
(Carompara), 128.7 (Carommeta),
135.3 (-CH=CH2), 137.6
(Carom1), 201.1 (-CHO)
3b
liquid
91 (1.6)
2721.0, 1724.0, 1.51 (s, 3 H, -C-CH3), 2.53 (s, 3 20.9 (Ar-CH3), 21.3 (-C-CH3), 82.93
8.57
8.79
1645.0, 920.0
H, Ar-CH3), 2.78 (d, 2 H,
39.6 (-CH2-CH=CH2), 55.8
83.09
J = 7.5 Hz, =CHCH2-), 5.22
(Ar-C-CHO), 118.7
(m, 2 H, -CH=CH2), 5.64 (m, 1 (-CH=CH2), 124.6(Caromortho),
H, -CH=CH2), 7.44 (s, 4 H, Ar- 129.7 (Carommeta), 135.2
H), 9.93 (s, 1 H, -CHO)
(-CH=CH2), 135.6 (Carompara),
136.2 (Carom1), 201.2 (-CHO)
3c
liquid
128 (1)
2690.0, 1710.0, 1.10 (s, 3 H, -C-CH3), 1.81 (m, 20.8 (-C-CH3), 30.2 (Ar-CH2-), 73.25
1631.0, 1580.0, 2 H, -C-CH2-C), 2.29 (m, 2 H, 34.8 (Ar-CH2-CH2), 38.1 73.45
1507.0, 919.0 -C=C-CH2-), 2.45 (m, 2 H, Ar- (-CH2-CH=), 51.2 (-C-CHO),
CH2-), 3.82 (s, 3 H, -OCH3), 55.7, 55.8 (2 × -OCH3), 113.2
8.45
8.59
3.85 (s, 3 H, -OCH3), 5.01–5.16 (Carom5meta), 114.4
(m, 2 H, -C=CH2), 5.71 (m, 1 H, (Carom2ortho), 118.3
-CH=CH2-), 6.60–6.80 (m, 3 H, (-CH=CH2), 120.9
Ar-H), 9.48 (s, 1 H, -CHO)
(Carom6ortho), 133.6 (Carom1),
138.6 (-CH=CH2), 144.9
(Carom4para), 147.7
(Carom3meta), 202.5 (-CHO)
3d
liquid
148 (2)
2705.8, 1724.8, 1.11 (s, 3 H, -C-CH3), 1.76 (m, 20.7 (-C-CH3), 30.3 (Ar-CH2-), 77.55
1639.3, 1583.5, 2 H, -C-CH2-C-), 2.30 (t, 2 H, 35.1 (Ar-CH2CH2), 38.2 77.46
8.68
8.84
1512.8, 912.6
J = 8.1 Hz, -C=CHCH2-), 2.61 (-CH2CH=), 51.3 (-C-CHO),
(m, 2 H, Ar-CH2-), 3.78 (s, 3 H, 55.8 (-O-CH3), 114.1
-OCH3), 5.13 (m, 2 H,
-C=CH2), 5.84 (m, 1 H,
-CH=CH2-), 6.82 (d, 2 H,
(Carommeta), 118.4 (-CH=CH2),
128.4 (Caromortho), 132.1
(Carom1), 138.3 (-CH=CH2),
J = 8.2 Hz, Ar-H), 7.10 (m, 2 H, 149.7 (Carompara), 202.6
Ar-H), 9.50 (s, 1 H, -CHO) (-CHO)
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York

FEATURE ARTICLE
An Expedient Protocol for Cyclopentenone Annulation
2923
Table 2 (continued)
Compound
Bp/Mp
[°C] (Torr) (neat/nujol)
IR [cm–1]
1H NMR (CDCl3) d J (Hz)
13C NMR (CDCl3) d
Microanalysis
calcd/found
C
H
3e
liquid
187-188
(760)
2730.3, 1718.5, 0.9–1.02 (m, 6 H, 2 × CH3),
1533.4, 1428.2 1.3–1.42 (m, 4 H, 2 × CH3-
CH2-), 1.46–1.55 (m, 4 H,
13.8 (-CH3), 18.7 (-CH2CH3),
33.8 (-CH2CH2CH3), 37.4
(-CH2CH=), 49.1 (-C-CHO),
117.4 (-CH=CH2), 138.2
78.51 78.37
11.98
12.07
CH3CH2CH2-), 2.33 (m, 2 H,
-CH2CH=CH2), 5.02–5.16 (m, (-CH=CH2), 202.5 (-CHO)
2 H, -CH=CH2), 5.72 (m, 1 H,
-CH=CH2), 9.53 (s, 1 H, -CHO)
3f
liquid
202–203
(760)
2726.1, 1720.2, 0.9–1.03 (m, 6 H, 2 × CH3),
1548.7, 1433.3 1.17–1.43 (m, 6 H, -CH2CH3,
-CH2CH2CH2CH3), 1.49–1.58
13.6, 14.1 (-CH3), 18.9
(-CH2CH3), 23.2, 26.4
(-CH2CH2CH3), 33.2, 33.7
79.06 79.21
12.12
12.01
(m, 4 H, 2 × -CH2-C-), 2.31 (m, (-CH2-C-), 37.6
2 H, -CH2CH=CH2), 5.03–5.14 (-CH2CH=CH2), 48.7 (-C-
(m, 2 H, -CH=CH2), 5.73 (m, 1 CHO), 117.9 (-CH=CH2),
H, -CH=CH2), 9.57 (s, 1 H,
138.7 (-CH=CH2), 202.3
-CHO)
(-CHO)
3g
liquid
179–181
(760)
2722.2, 1719.7, 0.90–0.97 (t, 3 H, J = 7.0 Hz,
1543.6, 1427.1 -CH2CH3), 1.22 (s, 3 H, -C-
11.3 (CH3CH2-), 17.4 (CH3C-), 76.14 76.31
22.2 (CH3CH2-), 37.3
11.18
11.05
CH3), 1.54 (q, 2 H, J = 7.0 Hz, (-CH2CH=CH2), 48.4 (-C-
-CH2CH3), 2.27 (m, 2 H,
CHO), 116.8 (-CH=CH2),
-CH2CH=CH2), 5.05–5.20 (m, 137.3 (-CH=CH2), 202.1
2 H, -CH=CH2), 5.74 (m, 1 H, (-CHO)
-CH=CH2), 9.48 (s, 1 H, -CHO)
3h
liquid
157 (2)
2719.3, 1722.0, 2.79 (m, 2 H, -CH2CH=C), 3.68 32.8 (-CH2CH=), 55.7 (Ar-C-
70.89
7.32
7.49
1681.2, 1590.5, (m, 1 H, -CH-CHO), 4.02 (s, 6 CHO), 55.9, 56.1 (2 × -OCH3), 70.71
1517.5, 918.0.
H, 2 × -OCH3), 5.3 (m, 2 H,
-C=CH2), 6.00 (m, 1 H,
112.3 (Carom2ortho), 113.7
(Carom5meta), 119.6
CH2=CH-), 6.96–7.88 (m, 3 H, (-CH=CH2), 121.3
Ar-H), 10.24 (d, 1 H, J = 2.40 (Carom6ortho), 130.5 (Carom1),
Hz, -CHO)
136.7 (-C=CH2), 147.1
(Carom4para), 147.8
(Carom3meta), 201.7 (-CHO)
4a
liquid
121 (2.5)
123 (2.5)
136 (0.6)
2689.2, 1718.8, 1.56 (s, 3 H, -C-CH3), 2.04 (s, 3 21.8 (-C-CH3), 27.9 (CH3-
1711.3. H, -COCH3), 3.10 (s, 2 H, C=O), 48.9 (-CH2-C=O), 53.3
-COCH2-), 7.35 (s, 5 H, Ar-H), (Ar-C-CHO), 125.8
9.66 (s, 1 H, -CHO) (Caromortho), 126.9 (Carompara),
75.76
75.94
7.42
7.38
128.6 (Carommeta), 137.1
(Carom1), 201.3 (-CHO), 206.7
(CH3-C=O)
4b
liquid
2681.0, 1722.0, 1.62 (s, 3 H, -C-CH3), 2.11 (s, 3 21.0 (Ar-CH3), 21.7 (-C-CH3), 76.44
7.90
8.01
1707.0
H, -COCH3), 2.39 (s, 3 H, Ar-
CH3), 3.16 (s, 2 H, -CH2-CO),
27.8 (CH3-C=O), 49.1 (-CH2-
C=O), 53.5 (Ar-C-CHO), 125.6
76.31
7.42 (s, 4 H, Ar-H), 9.88 (s, 1 H, (Caromortho), 125.9 (Carommeta),
-CHO)
133.5 (Carom1), 135.4
(Carompara), 201.1 (-CHO),
206.6 (CH3-C=O)
4c
liquid
2695.0, 1716.0, 1.19 (s, 3 H, -C-CH3), 1.83 (m, 20.4 (C-CH3), 26.1 (CH3-C=O), 69.04
1707.0. 2 H, -C-CH2-), 2.12 (s, 3 H, 30.2 (Ar-CH2-), 34.4 (Ar- 69.15
-COCH3), 2.45 (t, 2 H, J = 8.6 CH2CH2), 46.2 (-CH2-C=O),
7.97
7.99
Hz, Ar-CH2-), 2.69 (d, 1 H,
J = 17.8 Hz, -CO-CH2-), 2.84
(d, 1 H, J = 17.8 Hz, -CO-
CH2-), 3.82 (s, 3 H, -OCH3),
47.1 (-C-CHO), 55.8, 55.9
(2 × -OCH3), 113.5
(Carom5meta), 114.3
(Carom2ortho), 120.8
3.84 (s, 3 H, -OCH3), 6.55–6.85 (Carom6ortho), 133.8 (Carom1),
(m, 3 H, Ar-H), 9.58 (s, 1 H,
-CHO)
145.4 (Carom4para), 147.8
(Carom3meta), 204.5 (-CHO),
206.4 (CH3-C=O)
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York

2924
M. G. Kulkarni et al.
FEATURE ARTICLE
Table 2 (continued)
Compound
Bp/Mp
[°C] (Torr) (neat/nujol)
IR [cm–1]
1H NMR (CDCl3) d J (Hz)
13C NMR (CDCl3) d
Microanalysis
calcd/found
H
C
4d
solid
41–42
2712.1, 1718.1, 1.22 (s, 3 H, -C-CH3), 1.72–
20.5 (-C-CH3), 26.3 (CH3-
72.55
72.76
8.12
8.20
1705.6.
1.85 (m, 2 H, -C-CH2-C-), 2.12 C=O), 30.1 (Ar-CH2-), 34.3
(s, 3 H, -COCH3), 2.46 (t, 2 H, (Ar-CH2CH2), 46.3 (-CH2-
J = 8.5 Hz, Ar-CH2-), 2.67 (d, 1 C=O), 47.2 (-C-CHO), 55.7
H, J = 17.7 Hz, -CO-CH2-),
2.84 (d, 1 H, J = 17.7 Hz, -CO- 128.5 (Caromortho), 132.3
CH2-), 3.77 (s, 3 H, -OCH3), (Carom1), 149.8 (Carompara),
(-OCH3), 114.3 (Carommeta),
6.81 (d, J = 8.2 Hz, 2 H, Ar-H), 204.6 (-CHO) 206.7 (CH3-
7.05 (d, J = 8.0 Hz, 2 H, Ar-H), C=O)
9.58 (s, 1 H, -CHO)
4e
–
2705.6, 1718.1, 0.91–1.02 (m, 6 H, 2 × CH3),
13.8 (-CH2CH3), 17.6
(-CH2CH3), 26.2 (CH3-C=O),
33.1 (-CH2CH2CH3), 44.8
71.70 71.95
10.94
10.77
viscous liquid
1706.2
1.3–1.43 (m, 4 H, 2 × CH3-
CH2-), 1.5–1.6 (m, 4 H,
2 × CH3CH2CH2), 2.11 (s, 3 H, (O=C-CH2), 47.6 (-C-CHO),
CH3-C=O), 2.69 (d, 1 H,
J = 17.1 Hz, O=C-CH2), 2.81
(d, 1 H, J = 17.1 Hz, O=C-
CH2), 9.57 (s, 1 H, -CHO)
202.3 (-CHO), 205.1 (CH3-
C=O)
4f
–
2698.3, 1719.4, 0.9–1.05 (m, 6 H, 2 × CH3),
13.9, 14.3 (CH3CH2-), 17.7
(CH3CH2CH2-C-), 23.1
72.68 72.83
11.18
11.33
viscous liquid
1704.9
1.28–1.44 (m, 6 H,
CH3CH2CH2-C,
CH3CH2CH2CH2-), 1.52–1.63
(CH3CH2CH2CH2-), 26.2
(CH3CH2CH2CH2), 26.4 (CH3-
(m, 4 H, 2 × -CH2-C-), 2.13 (s, C=O), 32.2 (CH3CH2CH2CH2-
3 H, CH3-C=O), 2.67 (d, 1 H,
J = 17.3 Hz, O=C-CH2), 2.79
(d, 1 H, J = 17.3 Hz, O=C-
CH2), 9.61 (s, 1 H, -CHO)
C), 33.4 (CH3CH2CH2-C), 44.9
(O=C-CH2), 47.8 (-C-CHO),
202.1 (-CHO), 205.4 (CH3-
C=O)
4g
–
2701.2, 1717.3, 0.90–0.97 (t, 3 H, J = 7.1 Hz,
1705.8 -CH2CH3), 1.21 (s, 3 H, -C-
10.2 (CH3-CH2-), 16.1 (CH3-
C-), 25.6 (CH3CH2-), 45.2
67.57 67.39
9.92
9.84
viscous liquid
CH3), 1.54 (q, 2 H, J = 7.1 Hz, (O=C-CH2), 47.3 (-C-CHO),
-CH2CH3), 2.11 (s, 3 H, CH3- 202.4 (-CHO), 205.7 (CH3-
C=O), 2.71 (d, 1 H, J = 17 Hz, C=O)
O=C-CH2), 2.83 (d, 1 H, J = 17
Hz, O=C-CH2), 9.48 (s, 1 H,
-CHO)
4h
solid
58–60
2685.0, 1721.0, 2.17 (s, 3 H, -CO-CH3), 2.62 (d, 27.6 (CH3-C=O), 43.6 (CH2-
1698.0. 1 H, J = 11.3 Hz, -CH2-CO-), C=O), 52.7 (Ar-C-CHO), 55.9, 65.98
66.08
6.83
6.87
3.31 (m, 1 H, -CH-CHO), 3.84 56.2 (2 × -OCH3), 113.1
(s, 6 H, 2 × -OCH3), 4.15 (br s, (Carom5meta), 114.2
1 H, -CH2-CO-), 6.64 (s, 1 H,
(Carom2ortho), 121.7
Ar-H), 6.69 (d, J = 8.1 Hz, 1 H, (Carom6ortho), 130.7 (Carom1),
Ar-H), 6.82 (d, J = 6.0 Hz, 1 H, 147.3 (Carom4para), 148.1
Ar-H), 9.63 (s, 1 H, -CHO)
(Carom3meta), 203.8 (-CHO),
206.5 (CH3-C=O)
5a
liquid
110 (1.2)
86 (0.4)
1715.2, 1587.7, 1.60 (s, 3 H, -C-CH3), 2.58 (s, 2 22.3 (CH3-C), 48.2 (Ar-C), 54.3 83.69
7.02
7.14
1512.9, 1454.2 H, -COCH2-), 6.24 (d, 1 H,
J = 5.6 Hz, -COCH=C-), 7.32
(s, 5 H, Ar-H), 7.74 (d, 1 H,
(CH2-C=O), 124.9(Caromortho), 83.58
125.7 (Carompara), 127.9
(Carommeta), 128.2 (-C=C-
J = 5.6 Hz, CH=CH-CO-)
C=O), 146.5 (Carom1), 147.6
(-C=C-C=O), 200.1 (-C=O)
5b
liquid
1709.0, 1655.0, 1.76 (s, 3 H, -C-CH3), 2.51 (s, 3 21.8 (Ar-CH3), 22.4 (CH3-C-), 83.83
1580.0, 1500.0 H, Ar-CH3), 2.69, 2.72 (2 × s, 2 48.3 (Ar-C-), 56.9 (-CH2-C=O), 83.99
7.58
7.61
H, -COCH2-), 6.48 (d, 1 H,
J = 5.9 Hz, -CO-CH=CH-),
7.52 (s, 4 H, Ar-H), 8.00 (d, 1
H, J = 5.9 Hz, -CO-CH=CH-)
126.6 (Caromortho), 128.7
(Carommeta), 129.5 (-C=C-
C=O), 135.1 (Carompara), 144.5
(Carom1), 147.8 (-C=C-C=O),
200.2 (-C=O)
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York

FEATURE ARTICLE
An Expedient Protocol for Cyclopentenone Annulation
2925
Table 2 (continued)
Compound
Bp/Mp
[°C] (Torr) (neat/nujol)
IR [cm–1]
1H NMR (CDCl3) d J (Hz)
13C NMR (CDCl3) d
Microanalysis
calcd/found
C
H
5c
liquid
158 (1.5)
1692.0, 1590.0, 1.24 (s, 3 H, -C-CH3), 1.75 (m, 24.3 (CH3-C-), 31.4 (Ar-
1511.0, 1445.0 2 H, -C-CH2-), 2.13 (d, 1 H, CH2-),39.3 (Ar-CH2-CH2-),
J = 18.6 Hz, -COCH2-), 2.31 (d, 48.8 (CH3-C-),55.6 (-CH2-
1 H, J = 18.6 Hz, -COCH2-), C=O), 55.9, 56.1 (2 × -OCH3),
2.44 (m, 2 H, Ar-CH2-), 3.79 (s, 113.2(Carom5meta), 114.2
73.82
73.70
7.74
7.71
3 H, -OCH3), 3.82 (s, 3 H,
(Carom2ortho), 120.7
-OCH3), 6.01 (d, 1 H, J = 5.5
(Carom6ortho), 129.3 (-C=C-
Hz, -CO-CH=CH-), 6.61–6.82 C=O), 133.6 (Carom1), 145.6
(m, 3 H, Ar-H), 7.42 (d, 1 H,
(Carom4para), 147.9
J = 5.5 Hz, -CO-CH=CH-)
(Carom3meta), 149.9 (-C=C-
C=O), 200.4 (-C=O)
5d
solid
83–84
1705.0, 1610.0, 1.25 (s, 3 H, -C-CH3), 1.81 (m, 24.1 (CH3-C-), 31.5 (Ar-
1581.0, 1508.0 2 H, -C-CH2-C), 2.17 (d, 1 H,
J = 18.6 Hz, -COCH2-), 2.38 (d, 48.8 (CH3-C-), 55.5 (-CH2-
1 H, J = 18.6 Hz, -COCH2-), C=O), 56.1 (-O-CH3), 114.0
2.51 (m, 2 H, Ar-CH2-), 3.85 (s, (Carommeta), 128.7 (Caromortho),
78.29
7.88
8.04
CH2CH2-), 39.6 (Ar-CH2CH2), 78.10
3 H, -OCH3), 6.06 (d, 1 H,
J = 5.5 Hz, -CO-CH=CH-),
129.1 (-C=C-C=O), 132.5
(Carom1), 149.2 (Carompara),
6.81 (d, 2 H, J = 8.4 Hz, Ar-H), 149.9 (-C=C-C=O), 200.6
7.05 (d, 2 H, J = 8.4 Hz, Ar-H), (-C=O)
7.44 (d, 1 H, J = 5.5 Hz, -CO-
CH=CH-)
5e
–
–
1704.2, 1588.3, 0.89–1.03 (m, 6 H, 2 × CH3),
1471.2 1.2–1.46 (m, 8 H, 2 × -CH2-
14.1 (CH3CH2-), 18.7
(CH3CH2-), 34.5 (CH3CH2
79.46 79.61
79.94 79.76
10.91
10.74
viscous liquid
CH2-), 2.57 (s, 2 H, O=C-CH2), CH2-), 45.3 (-C-CH=C), 55.2
6.04 (d, 1 H, J = 5.9 Hz, CO- (O=C-CH2), 128.9 (O=C-CH=
CH=CH), 7.02 (d, 1 H, J = 5.9 CH-), 146.4 (O=C-CH=CH-),
Hz, CO-CH=CH)
202.2 (O=C-)
5f
1701.1, 1598.4, 0.92–1.05 (m, 6 H, 2 × CH3),
14.1, 14.5 (CH3CH2-), 18.5
(CH3CH2CH2C), 22.8
11.18
11.29
viscous liquid
1482.9
1.21–1.48 (m, 10 H, 5 ×
-CH2-), 2.23 (d, 1 H, J = 17.3
Hz, O=C-CH2), 2.39 (d, 1 H,
J = 17.3 Hz, O=C-CH2), 6.08
(d, 1 H, J = 6.1 Hz, CO-
(CH3CH2CH2CH2C), 28.2
(CH3CH2CH2CH2C), 34.7
(CH3CH2CH2C), 35.2 (CH3CH2
CH2 CH2C), 45.2 (-CH=CH-
CH=CH), 7.04 (d, 1 H, J = 6.1 C-), 55.6 (O=C-CH2), 128.2
Hz, CO-CH=CH)
(O=C-CH=CH-), 147.4 (O=C-
CH=CH-), 202.6 (O=C-)
5g
–
1699.3, 1586.3, 0.92–1.0 (m, 3 H, CH3-CH2-),
1478.1
11.2 (CH3CH2-), 22.7 (CH3C-), 77.38 77.51
1.27 (s, 3 H, CH3C-), 1.3–1.36 32.8 (CH3CH2-), 43.1
12.88
12.69
viscous liquid
(m, 2 H, CH3CH2-), 2.25 (d, 1
H, J = 17.1 Hz, O=C-CH2),
(-CH=CH-C-), 56.3 (O=C-
CH2), 124.9 (O=C-CH=CH-),
2.37 (d, 1 H, J = 17.1 Hz, O=C- 147.6 (O=C-CH=CH-), 201.1
CH2), 6.03 (d, 1 H, J = 6.2 Hz, (O=C-)
CO-CH=CH), 7.05 (d, 1 H,
J = 6.2 Hz, CO-CH=CH)
5j(26)
solid
148–149
1680.0, 1595.0, 2.53 (m, 2 H, -CO-CH2CH2),
1500.0, 1446.0 2.99 (m, 2 H, -CO-CH2-), 3.90 (-CH2-C=O), 55.7, 55.9
30.2 (-CO-CH2CH2-), 36.8
71.54
71.38
6.47
6.61
(s, 6 H, 2 × -OCH3), 6.43 (s, 1
H, -CO-CH=C-), 6.88 (d,
(-OCH3), 114.7 (Carom5meta),
115.6 (Carom2ortho), 117.8
J = 7.6 Hz, 1 H, Ar-H), 7.11 (s, (Carom6ortho), 131.1 (-C=C-
1 H, Ar-H), 7.24 (d, J = 7.6 Hz, C=O), 131.4 (Carom1), 147.1
1 H, Ar-H)
(Carom4para), 147.4
(Carom3meta), 154.9 (-C=C-
C=O), 201.1 (-C=O)
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York

2926
M. G. Kulkarni et al.
FEATURE ARTICLE
(20) (a) Kulkarni, M. G.; Pendharkar, D. S. Tetrahedron Lett.
1997, 53, 3167. (b) Kulkarni, M. G.; Pendharkar, D. S. J.
Chem. Soc., Perkin Trans. 1 1997, 3127.
Acknowledgment
DSP and AKD would like to thank CSIR, New Delhi for the fel-
lowship.
(21) Kulkarni, M. G.; Pendharkar, D. S.; Rasne, R. M.
Tetrahedron Lett. 1997, 38, 1459.
(22) (a) Claisen, L. Chem. Ber. 1912, 45, 3157. (b) Claisen, L.
Chem. Ber. 1936, 69, 77.
References
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(26) Under aldol condensation conditions product 5h underwent
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process27–30 via 5i (Scheme 1).
4991.
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(12) Curran, D. P. Synthesis 1988, 489.
(13) Schore, N. E. Chem. Rev. 1988, 88, 1081.
(14) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1;
Angew. Chem. 1986, 9, 1.
(15) Ellison, R. A. Synthesis 1973, 397.
(16) Trost, B. M. Chem. Soc. Rev. 1982, 141.
(17) Paquette, L. A. Aldrichimica Acta 1984, 17, 43.
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Rev. 1996, 96, 365.
Scheme 1
(27) Atwater, N. W. J. Am. Chem. Soc. 1960, 82, 2847.
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1966, 31, 2171.
(30) Herrmann, J. L.; Kieczykowski, G. R.; Schlessinger, R. H.
Tetrahedron Lett. 1973, 26, 2433.
(31) Calculated on the basis of recovered substrate.
(32) All the new compounds gave satisfactory analytical and
spectroscopic data (Table 2).
(19) Mehta, G.; Karra, S. R. Tetrahedron Lett. 1991, 32, 3215.
Synthesis 2004, No. 17, 2919–2926 © Thieme Stuttgart · New York