Annulation of 2-Oxoalkylidenetriphenylphosphoranes with enediones: A one-step synthesis of substituted cyclopentenones

Article abstract of DOI:10.1055/s-2002-25761

2-Oxoalkylidenetriphenylphosphoranes undergo [3+2] annulation with enediones to give cyclopentenones as major products along with cyclohexenones.

Full text of DOI:10.1055/s-2002-25761

PAPER
739
Annulation of 2-Oxoalkylidenetriphenylphosphoranes with Enediones:
A One-Step Synthesis of Substituted Cyclopentenones
S
ynthesis of Subst
i
itute
d
C
r
yclopen
o
tenones yoshi Kitano, Satoshi Minami, Toshio Morita, Kazutsugu Matsumoto,1 Minoru Hatanaka*
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910, Japan
Fax +81(776)278747; E-mail: hatanaka@acbio.acbio.fukui-u.ac.jp
Received 15 January 2002; revised 13 March 2002
phenylphosphoranes with non electron-withdrawing sub-
stituents, such as alkyl and alkoxy, at the 3-position,
which would provide a direct access to a variety of cyclo-
pentenones.
Abstract: 2-Oxoalkylidenetriphenylphosphoranes undergo [3+2]
annulation with enediones to give cyclopentenones as major prod-
ucts along with cyclohexenones.
Key words: ylides, enediones, annulation, carbocycles, regioselec-
tivity
2-Oxopropylidenetriphenylphosphorane (1a) was first ex-
amined as a simple model. When the phosphorane 1a was
treated at –78 °C with s-BuLi in THF followed by (E)-1,4-
diphenylbut-2-ene-1,4-dione (2), Michael addition pro-
ceeded smoothly within 30 minutes. Warming the reac-
tion mixture at 30 °C for 48 hours after neutralization with
acetic acid effected the intramolecular Wittig reaction to
afford the cyclopentenone 3a and cyclohexenone 4a in 79
and 10% yields, respectively (Scheme 1). Annulation of
3-alkyl and 3-methoxy substituted phosphoranes 1b–d
with 2 was then examined in a similar way. Reaction of 2-
oxobutylidenetriphenylphosphorane (1b) with 2 gave the
cyclopentenone 3b and cyclohexenone 4b in 43 and 27%
yields, respectively. trans-Relationship of the substituents
in both products was confirmed by NMR experiments and
any cis-congeners were not detected. The 1H NMR spec-
tra of 3b showed NOE (12%) between 5-Me and 4-H,
whilst NOE (less than 1%) between 5-CH3 and 4-CH2.
Assignment of the 5,6-trans orientation in 4b was based
on the observed H-H coupling constant (J5,6 = 11.6 Hz).
Quite similar results were obtained with 2-oxopentyliden-
etriphenylphosphorane (1c) which produced 3c (43%)
and 4c (21%). Annulation of 3-methoxy-2-oxopropyl-
idenetriphenylphosphorane (1d) also gave trans-5-meth-
oxycyclopentenone (3d) in 21% yield along with trans-6-
Annulation to form 5-membered carbocycles is still an at-
tractive subject of organic chemists, because there are
many biologically active compounds bearing a 5-mem-
bered unit, such as prostaglandins, methylenomycin, and
cyclopentanoid antibiotics.2 We have demonstrated a use-
ful method for this purpose using phosphoranes, such as
allylidenetriphenylphosphoranes and 2-oxopropylidenet-
riphenylphosphoranes, which serve as versatile 1,3-biden-
tate reagents in the [3+2] pentaannulation leading to
successful formation of a variety of cyclopentanoids.3 For
instance, 3-alkoxycarbonyl-2-oxopropylidenetriphenyl-
phosphorane undergoes annulation with glyoxals and 1,2-
diacylethylenes to afford 4-hydroxy- and 4-acylmethyl
substituted cyclopentenones in good yields.3c,d Especially,
in the latter case cyclopentenones were produced exclu-
sively without attendant formation of other possible cy-
clohexenones.4 The annulation proceeded smoothly in the
presence or absence of base via carbanion formation at the
3-position of 3-alkoxycarbonyl-2-oxopropylidenetriphe-
nylphosphorane, because the phosphorane has an active
methylene at this position. In order to extend the scope of
the reaction, we studied use of 2-oxopropylidenetri-
O
O
COPh
R
Ph3P
COPh
COPh
Ph
R
1) s-BuLi
THF, -78 °C
O
3
PhCO
COPh
Ph3P
+
R
2) AcOH
30 °C, 48 h
O
1
2
O
COPh
R
Ph3P
COPh
Ph
COPh
R
4
Scheme 1
Synthesis 2002, No. 6, 29 04 2002. Article Identifier:
1437-210X,E;2002,0,06,0739,0744,ftx,en;F00402SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

740
H. Kitano et al.
PAPER
methoxycyclohexenone (4d) (17% yield). Apparently, an
increase of cyclohexenone formation was observed with
alkyl and methoxy substituted phosphoranes 1b–d in
comparison to the annulation of phosphorane 1a (Table 1,
entry 1). This may be ascribed to the formation of a syn-
anti isomeric mixture at the Michael addition stage in
which the anti-isomer subsequently cyclizes to give 3 and
the syn-isomer leads to 4.
1) s-BuLi,
THF, -78 °C
O
O
R
+
Me
Ph3P
2) AcOH, 30 °C
O
5
1a
O
O
+
COR
Me
COR
Table 1 Annulation of Phosphoranes 1 with trans-1,4-Diphenylbut-
2-ene-1,4-dione (2)
Me
6
7
Entry
1
R
Yield of 3
Yield of 4
Scheme 2
(%)a
(%)a
1
2
3
4
a
b
c
H
79
43
43
21
10
27
21
17
Table 2 Annulation of Phosphorane 1a with Unsymmetrical Enedi-
ones 5
Me
Et
Entry
5
R
Yield of 6 Yield of 7
(%)a
(%)a
d
MeO
a The yields are based on 2.
1
2
3
4
5
a
b
c
Ph
59
4
6
5
4
–
4-MeOC6H4
4-FC6H4
2,4-Me2C6H3
SEt
63
Annulation of phosphorane 1a with various unsymmetri-
cal enediones 5 was next investigated and the results are
depicted in Table 2. Thus, (E)-1-phenylpent-2-ene-1,4-di-
one (5a) reacted with 1a under the same conditions as de-
scribed above to give cyclopentenone 6a in 59% yield
along with cyclohexenone 7a (4% yield) (Scheme 2).
Each product was single and the corresponding regioiso-
mer was not detected. It is evident that 6a is formed via the
initial Michael addition at the 3-position of 5a followed
by the intramolecular Wittig reaction with the 4-keto
group, whilst 7a arises from the Michael addition at the 2-
position and subsequent Wittig reaction with the 4-keto
group. Attempted efforts to improve the yield with addi-
tives including TMEDA and CuCN 2LiCl were unsuc-
cessful and resulted in lowering the yield. Several
substituents were then introduced on the phenyl group in
order to test attendant changes of the product distribution
(Table 2, entries 2–4). However, the accompanied forma-
tion of cyclohexenones was observed at an analogous rate
in all cases although somewhat improvement of the yield
was achieved with 5b (entry 2). Nevertheless, cyclopen-
tenones were mainly produced and could be purified
readily by column chromatography. With (E)-hex-3-ene-
2,5-dione, poor yields of cyclization products were ob-
tained and a large amount of the enedione was recovered,
probably implying that proton transfer occurred in prefer-
ence to Michael addition. However, thioester 5e was
found to give cyclopentenone 6e as a sole cyclization
product in a moderate yield.
57
d
e
44
33
a The yields are based on the starting enediones 5.
asymmetric induction was therefore studied using phos-
phorane 1a. Thus, methyl (S)-(–)-2,2-dimethyl-1,3-diox-
olane-4-carboxylate was converted into enedione 8 by
treatment with dimethyl methylphosphonate in the pres-
ence of BuLi followed by phenylglyoxal.5 When 1a was
allowed to react with chiral enedione 8, cyclopentenone 9
was obtained as the main product in a moderate yield, but
with high diastereoselection (87% de). Recrystallization
of the diastereomeric mixture afforded 9 as a single dia-
stereomer (Scheme 3). The stereochemistry of 9 was esti-
mated from the previous results.3c In the initial Michael
addition, the carbanion of 1a may attack preferentially
from the less hindered bottom face of the s-cis-oriented
double bond to the carbonyl group.
In summary, this paper describes the annulation using
readily available 2-oxoalkylidenetriphenylphosphoranes,
which react with enediones in the presence of s-BuLi to
give 3,4-di- and 3,4,5-trisubstituted cyclopentenones as
major products. Further studies on the applications of the
reaction to synthesis of enantiomerically enriched cyclo-
pentanoids are now in progress.
We have described in a previous publication a highly di-
astereoselective annulation of 3-allyloxycarbonyl-2-oxo-
propylidenetriphenylphosphorane with a chiral triacyl
substrate to form an optically active cyclopentenone in
91% de.3c However, the phosphorane showed a low level
of both the diasteroselectivity (less than 50% de) and the
regioselectivity with chiral enediones such as 8. This
All mps were measured on a Yanagimoto hot stage apparatus and
are uncorrected. IR spectra were recorded on a Hitachi 270-30 spec-
trometer. 1H NMR spectra were measured at 500 MHz in CDCl3 on
a JEOL Lambda 500 spectrometer, using SiMe4 as the internal stan-
dard. J-Values are given in Hz. 13C NMR spectra were recorded at
125 MHz on the spectrometer and solvent peak (CDCl3:
77.0)
C
was used for the internal standard. Mass spectra were recorded on a
Synthesis 2002, No. 6, 739–744 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Substituted Cyclopentenones
741
EIMS: m/z (%) = 276 (M+, 67), 171 (100), 105 (82), 77 (38).
O
1) LiCH2PO(OMe)2
-78 °C
CO2Me
Ph
Anal. Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.83; H,
5.83.
O
O
O
O
O
2) PhCOCHO
4a
LiCl, i-Pr2NEt
8
Colorless solid; mp 107–108 °C (hexane–EtOAc).
IR (Nujol): 1686, 1664, 1348, 1252, 754, 708, 686 cm–1.
O
1) 1a, s-BuLi,
1H NMR (500 MHz, CDCl3): = 2.73 (m, 2 H), 3.01 (dd, 1 H,
J = 18.0, 4.6 Hz), 3.15 (ddd, 1 H, J = 18.0, 10.4, 2.1 Hz), 4.22 (m, 1
H), 6.51 (d, 1 H, J = 2.1 Hz), 7.42 (m, 3 H), 7.51 (br t, 2 H, J = 7.3
Hz), 7.55 (m, 2 H), 7.62 (br t, 1 H, J = 7.3 Hz), 7.98 (br d, 2 H,
J = 7.3 Hz).
13C NMR (125 MHz, CDCl3): = 199.82, 197.60, 157.71, 138.19,
135.12, 133.73, 130.34, 129.03, 128.90, 128.47, 126.18, 125.03,
42.54, 39.71, 30.71.
THF, -78 °C
COPh
2) AcOH, 30 °C,
48 h
O
O
37%
9
87% de
O
O
H
EIMS: m/z (%) = 171 (M+ – COPh, 63), 105 (100), 77 (44).
O
Ar
Anal. Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.31; H,
6.04.
O
(4S*,5S*)-5-Methyl-4-(2-oxo-2-phenylethyl)-3-phenylcyclo-
pent-2-en-1-one (3b) and (5R*,6S*)-6-Methyl-3-phenyl-5-benz-
oylcyclohex-2-en-1-one (4b)
Scheme 3
Synthesized according to TP-1 by the reaction of 1b with 2. The
crude product was purified by flash chromatography (hexane–
EtOAc, 8:1) to give 3b in 43% yield as a colorless oil and 4b in 27%
yield as a colorless solid.
Shimadzu GCMS-QP5000 spectrometer or a JEOL JMS-700T
spectrometer. HPLC data was obtained on a JASCO TRI ROTAR-
VI instrument. All reactions were carried out under Ar in dried
glassware. Flash chromatography was performed on Wakogel C-
300. Extracts were dried over MgSO4 and evaporated under reduced
pressure. THF was distilled from sodium benzophenone ketyl under
Ar prior to use. (E)-1-phenylpent-2-ene-1,4-dione (5a) and S-ethyl
(E)-4-oxopent-2-enethioate (5e) were prepared according to litera-
ture procedures.6,7 The phosphoranes 1b–d were prepared accord-
ing to the literature procedures.8,9 All other commercially available
reagents were used as received.
3b
IR (neat): 3098, 3005, 1686, 1594, 1448, 1356, 1328, 1186, 768,
754, 690 cm–1.
1H NMR (500 MHz, CDCl3): = 1.42 (d, 3 H, J = 7.3 Hz), 2.20 (br
q, 1 H, J = 7.3 Hz), 3.02 (dd, 1 H, J = 18.0, 11.0 Hz), 3.35 (dd, 1 H,
J = 18.0, 2.4 Hz), 3.75 (d, 1 H, J = 11.0 Hz), 6.47 (br s, 1 H), 7.44
(br t, 2 H, J = 7.9 Hz), 7.47 (m, 3 H), 7.56 (br t, 1 H, J = 7.9 Hz),
7.60 (m, 2 H), 7.89 (br d, 2 H, J = 7.9 Hz).
13C NMR (125 MHz, CDCl3): = 210.99, 197.98, 175.74, 136.47,
133.46, 133.23, 131.04, 129.18, 128.70, 127.99, 127.56, 127.19,
49.44, 44.56, 43.67, 17.72.
EIMS: m/z (%) = 290 (M+, 15), 185 (51), 170 (23), 105 (100), 77
(72).
Annulation of Phosphoranes 1 with Enediones 2; 4-(2-Oxo-2-
phenylethyl)-3-phenylcyclopent-2-en-1-one (3a) and 3-Phenyl-
5-benzoylcyclohex-2-en-1-one (4a); Typical Procedure (TP-1)
To a solution of 1a (159 mg, 0.5 mmol) in THF (8 mL) was added
a 1.0 M solution of s-BuLi in hexane (0.5 mL) at –78 °C. The reac-
tion mixture was stirred for 30 min at that temperature. To the mix-
ture was added dropwise a solution of 2 (58 mg, 0.33 mmol) in THF
(1 mL). After stirring for 1 h at –78 °C, the mixture was treated with
AcOH (29 L, 0.5 mmol) and sat. aq NaHCO3 (1 mL) and the stir-
ring was then continued for 48 h at r.t. The mixture was poured into
brine and extracted with EtOAc. The extract was dried and evapo-
rated. The residue was purified by flash chromatography (hexane–
EtOAc, 8:1) to give 3a (72 mg, 79%) and 4a (9 mg, 10%).
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.70; H,
6.22.
4b
Mp 75–76 °C (hexane–EtOAc).
IR (Nujol): 1664, 1612, 1594, 1360, 1266, 1234, 1200, 758, 708,
692 cm–1.
1H NMR (500 MHz, CDCl3): = 1.16 (d, 3 H, J = 6.7 Hz), 2.99 (m,
2 H), 3.06 (ddd, 1 H, J = 18.0, 10.7, 2.4 Hz), 4.04 (dt, 1 H, J = 11.0,
4.8 Hz), 6.50 (d, 1 H, J = 2.4 Hz), 7.40 (m, 3 H), 7.51 (m, 2 H), 7.52
(br t, 2 H, J = 7.9 Hz), 7.62 (br t, 1 H, J = 7.9 Hz), 8.02 (br d, 2 H,
J = 7.9 Hz).
13C NMR (125 MHz, CDCl3): = 200.80, 200.40, 155.64, 137.97,
136.33, 133.79, 130.17, 128.99, 128.84, 128.44, 126.03, 124.54,
48.26, 42.58, 31.77, 13.34.
3a
Colorless solid; mp 109–110 °C (hexane–EtOAc).
IR (Nujol): 1684, 1596, 1360, 1180, 762, 752, 692 cm–1.
1H NMR (500 MHz, CDCl3): = 2.14 (dd, 1 H, J = 18.9, 1.5 Hz),
3.01 (dd, 1 H, J = 18.0, 6.6 Hz), 3.02 (dd, 1 H, J = 18.9, 11.2 Hz),
3.36 (dd, 1 H, J = 18.0, 2.4 Hz), 4.17 (m, 1 H), 6.52 (d, 1 H, J = 1.2
Hz), 7.43 (br t, 2 H, J = 8.2 Hz), 7.48 (m, 3 H), 7.56 (br t, 1 H,
J = 8.2 Hz), 7.59 (m, 2 H), 7.88 (br d, 2 H, J = 8.2 Hz).
13C NMR (125 MHz, CDCl3): = 207.67, 197.82, 177.12, 136.42,
133.53, 133.17, 131.08, 129.27, 129.24, 128.72, 128.02, 127.18,
43.79, 43.50, 36.06.
EIMS: m/z (%) = 185 (M+ – COPh, 91), 157 (15), 105 (100), 77
(71).
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.95; H,
6.28.
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H. Kitano et al.
PAPER
(4S*,5S*)-5-Ethyl-4-(2-oxo-2-phenylethyl)-3-phenylcyclopent-
2-enone (3c) and (5R*,6S*)-6-Ethyl-3-phenyl-5-benzoylcyclo-
hex-2-enone (4c)
Synthesized according to TP-1 by reaction of 1c with 2. The crude
product was purified by flash chromatography (hexane–EtOAc,
8:1) to give 3c in 43% yield as a colorless oil and 4c in 21% yield
as a colorless solid.
EIMS: m/z (%) = 306 (M+, 12), 201 (10), 186 (27), 105 (100), 77
(64).
Anal. Calcd for C20H18O3: H, 5.92; C, 78.41. Found: H, 5.73; C,
78.70.
4d
Mp 99–100 °C (hexane–EtOAc).
IR (Nujol): 1676, 1654, 762, 708 cm–1.
3c
1H NMR (500 MHz, CDCl3): = 3.02 (dd, 1 H, J = 17.7, 3.7 Hz),
3.16 (ddt, 1 H, J = 18.0, 5.2, 2.7 Hz), 3.58 (s, 3 H), 4.31 (m, 2 H),
6.47 (d, 1 H, J = 2.4 Hz), 7.33 (m, 3 H), 7.49 (br t, 2 H, J = 8.1 Hz),
7.50 (m, 2 H), 7.61 (br t, 1 H, J = 8.1 Hz), 8.03 (br d, 2 H, J = 8.1
Hz).
13C NMR (125 MHz, CDCl3): = 199.86, 198.25, 156.11, 137.46,
136.46, 133.71, 130.42, 128.88, 128.80, 128.71, 126.11, 123.81,
81.99, 60.78, 47.97, 31.71.
IR (neat): 2960, 2928, 1684, 1598, 1574, 1352, 1330, 1218, 766,
752, 692 cm–1.
1H NMR (500 MHz, CDCl3): = 0.99 (t, 3 H, J = 7.3 Hz), 1.42 (dq,
2 H, J = 7.3, 1.8 Hz), 2.20 (dt, 1 H, J = 5.8, 1.2 Hz), 3.06 (dd, 1 H,
J = 17.7, 10.4 Hz), 3.30 (dd, 1 H, J = 17.7, 2.4 Hz), 3.86 (dt, 1 H,
J = 10.4, 1.2 Hz), 6.47 (br d, 1 H, J = 0.9 Hz), 7.43 (br t, 2 H, J = 8.2
Hz), 7.46 (m, 3 H), 7.55 (br t, 1 H, J = 8.2 Hz), 7.62 (m, 2 H), 7.88
(br d, 2 H, J = 8.2 Hz).
13C NMR (125 MHz, CDCl3): = 210.51, 197.97, 176.14, 136.50,
133.38, 133.05, 131.02, 129.13, 128.63, 128.15, 127.96, 127.11,
55.45, 43.67, 41.91, 25.39, 10.58.
EIMS: m/z (%) = 201 (M+ – COPh, 9), 105 (55), 77 (51).
Anal. Calcd for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.49; H,
5.71.
EIMS: m/z (%) = 304 (M+, 11), 199 (39), 184 (65), 105 (100), 77
(93).
Enediones; (E)-1-(4-Methoxyphenyl)pent-2-ene-1,4-dione (5b);
Typical Procedure (TP-2)
Anal. Calcd for C21H20O2: C, 82.86; H, 6.62. Found: C, 82.92; H,
6.80.
A solution of 1a (159 mg, 0.5 mmol) and 4-methoxyphenylglyoxal
(91 mg, 0.5 mmol) in THF (10 mL) was stirred at r.t. for 3 h. The
solvent was evaporated and the residue was purified by column
chromatography (hexane–EtOAc, 20:1) to give 5b (77 mg, 76%) as
pale yellow crystals; mp 65–66 °C.
4c
Mp 97–98 °C (hexane–EtOAc).
IR (Nujol): 1664, 1610, 1596, 1576, 1306, 1258, 1212, 760, 690
cm–1.
IR (Nujol): 1676, 1654, 1302, 1280, 1210, 1180, 836 cm–1.
1H NMR (500 MHz, CDCl3): = 2.43 (s, 3 H), 3.90 (s, 3 H), 6.98
(br d, 2 H, J = 8.9 Hz), 7.08 (br d, 1 H, J = 15.6 Hz), 7.71 (br d, 1
H, J = 15.6 Hz), 7.99 (br d, 2 H, J = 8.9 Hz).
13C NMR (125 MHz, CDCl3): = 197.96, 188.35, 164.22, 137.69,
134.08, 131.26, 129.76, 114.11, 55.56, 29.05.
1H NMR (500 MHz, CDCl3): = 0.94 (t, 3 H, J = 7.6 Hz), 1.68 (dq,
1 H, J = 7.6, 0.9 Hz), 1.84 (dq, 1 H, J = 4.8, 1.8 Hz), 2.93 (dq, 1 H,
J = 4.8, 1.2 Hz), 3.03 (d, 2 H, J = 7.3 Hz), 4.21 (m, 1 H), 6.45 (t, 1
H, J = 1.5 Hz), 7.33 (m, 3 H), 7.50 (m, 2 H), 7.51 (br t, 2 H, J = 8.2
Hz), 7.62 (br t, 1 H, J = 8.2 Hz), 8.00 (br d, 2 H, J = 8.2 Hz).
13C NMR (125 MHz, CDCl3): = 200.66, 199.92, 155.03, 137.95,
135.84, 133.67, 130.09, 128.99, 128.80, 128.39, 126.03, 124.96,
48.22, 45.05, 30.76, 21.24, 11.29.
EIMS: m/z (%) = 199 (M+ – COPh, 92), 171 (35), 105 (100), 77
(62).
EIMS: m/z (%) = 204 (M+, 23), 189 (11), 173 (4), 161 (12), 135
(100), 107 (12), 92 (14), 77 (26).
Anal. Calcd for C12H12O3: C, 70.57; H, 5.92. Found: C, 70.37; H,
5.88.
(E)-(4-Fluorophenyl)-4-methylbut-2-ene-1,4-dione (5c)
Synthesized according to TP-2 by reaction of 1a with 4-fluorophe-
nylglyoxal. The crude product was purified by flash chromatogra-
phy (hexane–EtOAc, 20:1) to give 5c in 94% yield as a yellow
solid; mp 64–65 °C (hexane–EtOAc)
Anal. Calcd for C21H20O2: C, 82.86; H, 6.62. Found: C, 82.60; H,
6.54.
(4R*,5S*)-5-Methoxy-4-(2-oxo-2-phenylethyl)-3-phenylcyclo-
pent-2-enone (3d) and (5R*,6S*)-6-Methoxy-3-phenyl-5-benz-
oylcyclohex-2-enone (4d)
IR (Nujol): 1678, 1654, 1596, 1570, 1326, 1210, 838 cm–1.
Synthesized according to TP-1 by reaction of 1d with 2. The crude
product was purified by flash chromatography (hexane-EtOAc, 8:1)
to give 3d in 21% yield as a colorless solid and 4d in 17% yield as
a colorless solid.
1H NMR (500 MHz, CDCl3): = 2.44 (s, 3 H), 7.10 (br d, 1 H,
J = 15.9 Hz), 7.20 (dd, 2 H, J = 8.6, 8.5 Hz), 7.68 (br d, 1 H,
J = 15.9 Hz), 8.03 (dd, 2 H, J = 8.6, 8.5 Hz).
13C NMR (125 MHz, CDCl3): = 197.68, 188.61, 167.24, 165.20,
138.47, 133.49, 131.62, 116.25, 29.17.
3d
Mp 109–110 °C (hexane–EtOAc).
IR (Nujol): 1700, 1596, 768, 692 cm–1.
EIMS: m/z (%) = 192 (M+, 8), 177 (26), 164 (7), 149 (18), 123
(100).
1H NMR (500 MHz, CDCl3): = 3.15 (dd, 1 H, J = 17.7, 9.5 Hz),
3.37 (dd, 1 H, J = 17.7, 3.1 Hz), 3.63 (s, 3 H), 3.66 (d, 1 H, J = 1.5
Hz), 3.98 (dq, 1 H, J = 9.5, 1.5 Hz), 6.47 (br d, 1 H, J = 1.2 Hz), 7.44
(br t, 2 H, J = 7.9 Hz), 7.46 (m, 3 H), 7.56 (br t, 1 H, J = 7.9 Hz),
7.58 (m, 2 H), 7.88 (br d, 2 H, J = 7.9 Hz).
13C NMR (125 MHz, CDCl3): = 209.56, 204.96, 175.21, 133.55,
132.98, 131.37, 129.20, 128.73, 127.99, 127.37, 126.81, 100.05,
85.20, 58.53, 42.99, 40.77.
Anal. Calcd for C11H9O2F: C, 68.74; H, 4.72. Found: C, 68.66; H,
5.01.
(E)-4-Methyl-1-(2,4-dimethylphenyl)but-2-ene-1,4-dione (5d)
Synthesized according to TP-2 by reaction of 1a with 2,4-dimeth-
ylphenylglyoxal. The crude product was purified by flash chroma-
tography (hexane–EtOAc, 20:1) to give 5d in 94% yield as a yellow
oil.
IR (neat): 3236, 2924, 1662, 1610, 1260, 816 cm–1.
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Synthesis of Substituted Cyclopentenones
743
1H NMR (500 MHz, CDCl3): = 2.38 (s, 3 H), 2.40 (s, 3 H), 2.48
(s, 3 H), 6.84 (br d, 1 H, J = 15.9 Hz), 7.09 (d, 1 H, J = 7.9 Hz), 7.11
(s, 1 H), 7.41 (br d, 1 H, J = 15.9 Hz), 7.51 (d, 1 H, J = 7.9 Hz).
Anal. Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.38; H,
6.53.
7b
13C NMR (125 MHz, CDCl3): = 198.19, 193.91, 142.76, 139.02,
138.31, 137.57, 134.00, 132.84, 129.76, 126.33, 28.56, 21.44,
20.97.
IR (neat): 3052, 2982, 1710, 1666, 1598, 758, 690 cm–1.
1H NMR (500 MHz, CDCl3): = 2.01 (s, 3 H), 2.44 (dd, 1 H,
J = 18.3, 4.1 Hz), 2.59 (m, 2 H), 2.73 (dd, 1 H, J = 18.3, 10.4 Hz),
3.89 (s, 3 H), 4.03 (m, 1 H), 5.96 (s, 1 H), 6.96 (d, 2 H, J = 8.9 Hz),
7.94 (d, 2 H, J = 8.9 Hz).
13C NMR (125 MHz, CDCl3): = 198.26, 197.64, 163.94, 160.56,
130.76, 128.10, 126.34, 114.12, 55.56, 41.98, 39.63, 33.49, 24.39.
EIMS: m/z (%) = 202 (M+, 5), 159 (100), 133 (46), 105 (34).
Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.39; H,
6.88.
(RS)-3-Methyl-4-(2-oxo-2-phenylethyl)cyclopent-2-enone (6a)
Synthesized according to TP-1 by reaction of 1a with 5a. The crude
product was purified by flash chromatography (hexane–EtOAc,
5:1) to give 6a in 59% yield as a colorless solid and 3-methyl-5-ben-
zoylcyclohex-2-enone (7a) in 4% yield as a colorless oil.
(RS)-4-[2-(4-Fluorophenyl)-2-oxoethyl]-3-methylcyclopent-2-
enone (6c)
Synthesized according to TP-1 by reaction of 1a with 5c. The crude
product was purified by flash chromatography (hexane–EtOAc,
5:1) to give 6c in 57% yield as a colorless solid and 3-methyl-5-(4-
fluorobenzoyl)cyclohex-2-enone (7c) in 5% yield as a colorless oil.
6a
Mp 91–92 °C (hexane–EtOAc).
IR (Nujol): 1678, 1614, 1596, 1364, 1182, 756, 690 cm–1.
6c
1H NMR (500 MHz, CDCl3): = 2.06 (dd, 1 H, J = 18.9, 2.1 Hz),
2.15 (s, 3 H), 2.82 (dd, 1 H, J = 18.9, 6.4 Hz), 2.99 (dd, 1 H,
J = 17.1, 9.8 Hz), 3.40 (dd, 1 H, J = 17.1, 4.0 Hz), 3.44 (m, 1 H),
5.97 (s, 1 H), 7.50 (br t, 2 H, J = 7.3 Hz), 7.61 (br t, 1 H, J = 7.3 Hz),
7.94 (br d, 2 H, J = 7.3 Hz).
13C NMR (125 MHz, CDCl3): = 208.17, 197.79, 179.77, 136.55,
133.54, 131.74, 128.80, 128.02, 43.10, 41.84, 39.91, 17.49.
Mp 92–93 °C (hexane–EtOAc).
IR (Nujol): 1676, 1616, 1594, 1234, 828 cm–1.
1H NMR (500 MHz, CDCl3): = 2.04 (dd, 1 H, J = 18.9, 2.1 Hz),
2.14 (s, 3 H), 2.82 (dd, 1 H, J = 18.9, 6.7 Hz), 2.93 (dd, 1 H,
J = 17.4, 10.1 Hz), 3.37 (dd, 1 H, J = 17.4, 4.0 Hz), 3.44 (m, 1 H),
6.00 (t, 1 H, J = 1.2 Hz), 7.16 (br d, 2 H, J = 8.3 Hz), 7.98 (br d, 2
H, J = 8.3 Hz).
13C NMR (125 MHz, CDCl3): = 208.01, 196.11, 179.50, 166.98,
164.95, 131.80, 130.71, 115.83, 43.05, 41.73, 39.83, 17.45.
EIMS: m/z (%) = 214 (M+, 15), 109 (88), 105 (100), 77 (72).
Anal. Calcd for C14H14O2: C, 78.48; H, 6.59. Found: C, 78.23; H,
6.89.
EIMS: m/z (%) = 232 (M+, 69), 123 (81), 109 (100), 95 (83).
Anal. Calcd for C14H13O2F: C, 72.40; H, 5.64. Found: C, 72.73; H,
5.57.
7a
IR (neat): 3052, 2982, 1710, 1668, 1578, 1356, 1250, 760, 696 cm–1.
1H NMR (500 MHz, CDCl3): = 2.01 (s, 3 H), 2.48 (dd, 1 H,
J = 18.0, 4.3 Hz), 2.61 (m, 2 H), 2.72 (dd, 1 H, J = 18.0, 10.1 Hz),
4.09 (m, 1 H), 5.97 (s, 1 H), 7.50 (br t, 2 H, J = 7.3 Hz), 7.61 (br t,
1 H, J = 7.3 Hz), 7.95 (br d, 2 H, J = 7.3 Hz).
13C NMR (125 MHz, CDCl3): = 207.71, 197.32, 157.68, 138.14,
135.15, 128.93, 128.88, 125.07, 47.84, 38.76, 33.28, 24.35.
7c
IR (neat): 2956, 2920, 1726, 1680, 1596, 1260, 818, 736 cm–1.
1H NMR (500 MHz, CDCl3): = 2.01 (s, 3 H), 2.45 (dd, 1 H,
J = 18.6, 4.9 Hz), 2.60 (m, 2 H), 2.72 (dd, 1 H, J = 18.6, 11.3 Hz),
4.05 (m, 1 H), 5.97 (s, 1 H), 7.17 (d, 2 H, J = 8.6 Hz), 7.98 (d, 2 H,
J = 8.6 Hz).
13C NMR (125 MHz, CDCl3): = 199.56, 197.12, 167.77, 160.27,
132.09, 130.89, 126.41, 116.06, 42.26, 38.75, 33.26, 22.99.
HRMS(FAB): m/z calcd for C14H15O2 [MH+]: 215.1072, found
215.1040.
HRMS (FAB): m/z calcd for C14H14O2F [MH+]: 233.0978, found
233.0977.
(RS)-4-[2-(4-Methoxyphenyl)-2-oxoethyl]-3-methylcyclopent-
2-enone (6b)
Synthesized according to TP-1 by reaction of 1a with 5b. The crude
product was purified by flash chromatography (hexane–EtOAc,
5:1) to give 6b in 63% yield as a colorless solid and 3-methyl-5-(4-
methoxybenzoyl)cyclohex-2-enone (7b) in 6% yield as a colorless
oil.
(RS)-4-[2-(2,4-Dimethylphenyl)-2-oxoethyl]-3-methylcyclo-
pent-2-enone (6d)
Synthesized according to TP-1 by reaction of 1a with 5d. The crude
product was purified by flash chromatography (hexane–EtOAc,
5:1) to give 6d in 44% yield as a colorless solid and 3-methyl-5-
(2,4-dimethylbenzoyl)cyclohex-2-enone (7d) in 4% yield as a col-
orless oil.
6b
Mp 125–127 °C (hexane–EtOAc).
IR (Nujol): 1696, 1672, 1616, 1600, 1310, 1264, 1174, 840 cm–1.
6d
1H NMR (500 MHz, CDCl3): = 2.05 (dd, 1 H, J = 18.9, 2.1 Hz),
2.13 (s, 3 H), 2.80 (dd, 1 H, J = 18.9, 6.7 Hz), 2.92 (dd, 1 H,
J = 17.1, 10.1 Hz), 3.32 (dd, 1 H, J = 17.1, 4.0 Hz), 3.44 (m, 1 H),
3.88 (s, 3 H), 5.99 (t, 1 H, J = 1.2 Hz), 6.95 (br d, 2 H, J = 8.9 Hz),
7.94 (br d, 2 H, J = 8.9 Hz).
13C NMR (125 MHz, CDCl3): = 208.30, 196.26, 180.03, 163.82,
131.65, 130.34, 129.66, 113.92, 55.54, 43.11, 41.43, 40.07, 17.50.
Mp 74–75 °C (hexane–EtOAc).
IR (Nujol): 1676, 1612, 818, 712 cm–1.
1H NMR (500 MHz, CDCl3): = 2.04 (dd, 1 H, J = 18.9, 2.1 Hz),
2.13 (s, 3 H), 2.39 (s, 3 H), 2.50 (s, 3 H), 2.79 (dd, 1 H, J = 18.9, 6.4
Hz), 2.89 (dd, 1 H, J = 17.1, 9.8 Hz), 3.31 (dd, 1 H, J = 17.1, 4.0
Hz), 3.40 (m, 1 H), 5.97 (t, 1 H, J = 1.2 Hz), 7.07 (br d, 1 H, J = 8.2
Hz), 7.09 (br s, 1 H), 7.57 (br d, 1 H, J = 8.2 Hz).
EIMS: m/z (%) = 244 (M+, 76), 150 (32), 135 (100), 109 (45).
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744
H. Kitano et al.
PAPER
13C NMR (125 MHz, CDCl3): = 208.22, 200.84, 180.03, 142.56,
138.97, 134.29, 133.16, 131.63, 129.03, 126.45, 44.28, 42.99,
40.28, 21.64, 21.39, 17.48.
Anal. Calcd for C15H16O4: C, 69.22; H, 6.20. Found: C, 68.97; H,
6.50.
(4S)-3-[(4R)-2,2-Dimethyl-1,3-dioxolane-4-yl]-4-(2-oxo-2-phen-
ylethyl)cyclopent-2-enone (9)
EIMS: m/z (%) = 242 (M+, 89), 227 (23), 133 (100), 109 (78).
Anal. Calcd for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.62; H,
7.68.
Synthesized according to TP-1 by reaction of 1a with 8. The crude
product was purified by flash chromatography (hexane–EtOAc,
5:1) to give 9 in 37% yield as a colorless solid, which was estimated
1
7d
to have 87% de on the basis of the vinyl proton signals in the H
IR (neat): 2976, 2908, 1726, 1690, 1378, 816, 724 cm–1.
NMR spectra. Recrystallization of the solid afforded 9 in a single di-
astereomeric form. The ee of the the cyclopentenone was deter-
mined to be 96% (HPLC conditions: Daisel Chiralcel OD-H,
45 250 mm, = 254 nm, hexane–propan-2-ol, 8:2, tmajor = 37.1
1H NMR (500 MHz, CDCl3): = 1.99 (s, 3 H), 2.36 (s, 3 H), 2.42
(s, 3 H), 2.43 (dd, 1 H, J = 18.0, 4.9 Hz), 2.55 (m, 2 H), 2.62 (dd, 1
H, J = 18.0, 10.1 Hz), 3.91 (m, 1 H), 5.94 (s, 1 H), 7.07 (br d, 1 H,
J = 7.9 Hz), 7.09 (br s, 1 H), 7.48 (br d, 1 H, J = 7.9 Hz).
13C NMR (125 MHz, CDCl3): = 203.28, 197.59, 160.35, 142.21,
138.87, 133.58, 133.05, 128.20, 126.46, 122.35, 44.69, 39.05,
33.13, 24.33, 21.36, 21.14.
21
min, tminor = 34.2 min); mp 103–104 °C (hexane–EtOAc); [ ]D
–3.6 (c = 0.36, CDCl3).
IR (Nujol): 1676, 1616, 1374, 760, 702 cm–1.
1H NMR (500 MHz, CDCl3): = 1.40 (s, 3 H), 1.45 (s, 3 H), 2.14
(dd, 1 H, J = 18.9, 2.1 Hz), 2.88 (dd, 1 H, J = 19.2, 6.7 Hz), 3.08
(dd, 1 H, J = 17.7, 8.2 Hz), 3.46 (dd, 1 H, J = 17.7, 5.2 Hz), 3.55 (m,
1 H), 3.84 (dd, 1 H, J = 8.2, 6.4 Hz), 4.36 (dd, 1 H, J = 8.2, 7.0 Hz),
4.84 (dd, 1 H, J = 7.0, 6.4 Hz), 6.27 (t, 1 H, J = 1.5 Hz), 7.49 (br t,
2 H, J = 8.2 Hz), 7.60 (br t, 1 H, J = 8.2 Hz), 7.94 (br d, 2 H, J = 8.2
Hz).
13C NMR (125 MHz, CDCl3): = 207.06, 197.53, 179.85, 136.26,
133.71, 129.84, 128.81, 127.98, 110.41, 74.17, 68.45, 43.24, 42.49,
36.28, 26.18, 25.33.
HRMS(FAB): m/z calcd for C16H19O2 [MH+]: 243.1385, found
243.1387.
(RS)-4-(2-Ethylthio-2-oxoethyl)-3-methylcyclopent-2-enone
(6e)
Synthesized according to TP-1 by reaction of 1a with 5e. The crude
product was purified by flash chromatography (hexane–EtOAc,
5:1) to give 6e in 33% yield as a colorless oil.
IR (neat): 2968, 2924, 1680, 1618, 1438, 1410, 1184, 1044, 1024,
986 cm–1.
EIMS: m/z (%) = 285 (M+ -Me, 14), 270 (19), 226 (15), 105 (100).
1H NMR (500 MHz, CDCl3): = 1.26 (t, 3 H, J = 7.3 Hz), 2.21 (dd,
1 H, J = 18.9, 2.1 Hz), 2.11 (s, 3 H), 2.52 (dd, 1 H, J = 15.6, 9.8 Hz),
2.65 (dd, 1 H, J = 18.9, 6.7 Hz), 2.91 (q, 2 H, J = 7.3 Hz), 2.96 (dd,
1 H, J = 15.6, 4.6 Hz), 3.27 (m, 1 H), 5.97 (t, 1 H, J = 1.2 Hz).
Anal. Calcd for C18H20O4: C, 71.98; H, 6.71. Found: C, 71.93; H,
6.46.
Acknowledgement
13C NMR (125 MHz, CDCl3): = 207.56, 197.32, 178.83, 131.85,
46.59, 41.71, 41.05, 23.62, 17.32, 14.67.
EIMS: m/z (%) = 198 (M+, 23), 137 (30), 109 (100), 95 (38).
We thank Professors K. Isa and Y. Tokunaga of Fukui University
for their kind discussions on mass spectroscopic analysis.
Anal. Calcd for C10H14O2S: C, 60.58; H, 7.12. Found: C, 60.36; H,
7.39.
References
(1) New address: K. Matsumoto, Department of Chemistry,
College of Science and Engineering, Meisei University,
Hodokubo, Hino, Tokyo 191-8506, Japan.
(2) (a) Collins, P. W.; Djuric, S. W. Chem. Rev. 1993, 93, 1533.
(b) Rigby, J. H. In Comprehensive Organic Synthesis, Vol.
5; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991,
626.
(3) (a) Himeda, Y.; Tanaka, Y.; Ueda, I.; Hatanaka, M. J. Chem.
Soc., Perkin Trans. 1 1998, 138. (b) Himeda, Y.; Yamataka,
Y.; Ueda, I.; Hatanaka, M. J. Org. Chem. 1997, 62, 6529.
(c) Hatanaka, M.; Ishida, A.; Tanaka, Y.; Ueda, I.
Tetrahedron Lett. 1996, 37, 401. (d) Hatanaka, M.; Tanaka,
Y.; Ueda, I. Tetrahedron Lett. 1995, 36, 3719.
(e) Hatanaka, M.; Himeda, Y.; Imashiro, R.; Tanaka, Y.;
Ueda, I. J. Org. Chem. 1994, 59, 111.
(4) For cyclohexenone synthesis with , -unsaturated
aldehydes, see: Pietrusiewicz, K. M.; Monkiewicz, J.;
Bodalski, R. J. Org. Chem. 1983, 48, 788.
(5) Yamanoi, T.; Akiyama, T.; Ishida, E.; Abe, H.; Amemiya,
M.; Inazu, T. Chem. Lett. 1989, 335.
(6) Shevchuk, M. I.; Volynskaya, E. M.; Dombrovskii, A. V. Zh.
Obshch. Khim. 1970, 40, 48; Chem. Abstr. 1970, 72, 100817.
(7) Wladislaw, B.; Marzorati, L.; Gruber, J. Synth. Commun.
1990, 20, 2937.
(E)-1-[(4S)-2,2-Dimethyl-1,3-dioxolane-4-yl]-4-phenylbut-2-
ene-1,4-dione (8)
Methyl (S)-(–)-2,2-dimethyl-1,3-dioxolane-4-carboxylate was con-
verted into dimethyl 2-[(S)-2,2-dimethyl-1,3-dioxolane-4-yl]-2-ox-
oethylphosphonate in 87% yield by treatment with dimethyl
methylphosphonate in the presence of BuLi according to the proce-
dure reported by Yamanoi et al. To a stirred suspension of LiCl (27
mg, 0.63 mmol) in anhyd MeCN (6 mL) was added a solution of this
phosphonate (159 mg, 0.63 mmol) in MeCN (1 mL) followed by the
addition of i-Pr2NEt (68 mg, 0.53 mmol) at r.t. The mixture was
cooled to –30 °C and treated with a solution of phenylglyoxal (80
mg, 0.53 mmol) in MeCN (1 mL). After stirring for 10 min at r.t.,
the mixture poured into brine and extracted with EtOAc. The extract
was dried and evaporated. The residue was purified by flash chro-
matography (hexane–EtOAc, 20:1) to give 8 (133 mg, 81%) as a
yellow solid; mp 45–47 °C (hexane–EtOAc); [ ]D25 –41.3 (c = 1.17,
CDCl3)
IR (Nujol): 1698, 1662, 1330, 1294, 1264, 1060, 690 cm–1.
1H NMR (500 MHz, CDCl3): = 1.44 (s, 3 H), 1.49 (s, 3 H), 4.15
(dd, 1 H, J = 8.9, 5.2 Hz), 4.26 (dd, 1 H, J = 8.9, 7.6 Hz), 4.68 (dd,
1 H, J = 7.6, 5.2 Hz), 7.52 (dd, 1 H, J = 8.2, 7.3 Hz), 7.53 (br d, 1
H, J = 15.6 Hz), 7.63 (tt, 1 H, J = 7.3, 1.2 Hz), 7.90 (br d, 1 H,
J = 15.6 Hz), 8.01 (dd, 2 H, J = 8.2, 1.2 Hz).
13C NMR (125 MHz, CDCl3): = 198.93, 189.81, 136.69, 135.26,
133.91, 133.46, 128.89, 128.85, 111.44, 79.99, 66.38, 26.03, 25.11.
EIMS: m/z (%) = 245 (M+ – Me, 8), 159 (87), 105 (36), 101 (100),
(8) Schuda, P. T.; Ebner, C. B.; Potlock, S. J. Synthesis 1987,
1055.
(9) Bell, T. W.; Sondheimer, F. J. Org. Chem. 1981, 46, 217.
77 (51).
Synthesis 2002, No. 6, 739–744 ISSN 0039-7881 © Thieme Stuttgart · New York