Palladium-catalyzed cyclopentenone formation by carbonylative cycloaddition of allylic tosylates and alkynes

Article abstract of DOI:10.1055/s-2006-942538

Carbonylative cycloaddition of allyl tosylates and alkynes proceeded in the presence of palladium catalysts to afford a range of cyclopentenones. In the presence of methanol, five-component coupling reactions gave methyl cyclopentenyl acetates, whereas in the absence of methanol, (cyclopentenoylmethylidene)furanones were formed from six components. Allyl tosylate was found to be essential for these reactions, as allyl acetate and allyl bromide proved to be ineffective. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942538

PAPER
3003
Palladium-Catalyzed Cyclopentenone Formation by Carbonylative
Cycloaddition of Allylic Tosylates and Alkynes
P
alladium-Catalyz
a
e
d
Cyclope
o
ntenone Form
f
ation umi Tsukada,* Shuichi Sugawara, Tomohiro Okuzawa, Yoshio Inoue
Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan
Fax +81(22)7955876; E-mail: tsukada@aporg.che.tohoku.ac.jp
Received 18 April 2006; revised 31 May 2006
into p-allylnickel is also an essential step in Chiusolis car-
bonylative cycloaddition,3,4 we anticipated that our strate-
gy of using allyl tosylates as the allylic component7,8
might be applicable to the palladium-catalyzed intermo-
Abstract: Carbonylative cycloaddition of allyl tosylates and
alkynes proceeded in the presence of palladium catalysts to afford a
range of cyclopentenones. In the presence of methanol, five-compo-
nent coupling reactions gave methyl cyclopentenyl acetates,
whereas in the absence of methanol, (cyclopentenoylmeth- lecular carbonylative cycloaddition for unactivated
ylidene)furanones were formed from six components. Allyl tosylate
alkynes. We report here the results of an investigation that
was found to be essential for these reactions, as allyl acetate and al-
lyl bromide proved to be ineffective.
focused on the synthesis of several cyclopentenones by
the reaction of allylic tosylates, alkynes and carbon mon-
oxide.
Key words: carbonylations, cycloadditions, palladium, alkynes,
homogeneous catalysis
Treatment of allyl tosylate with 2-butyne and methanol in
the presence of 5 mol% of Pd2(dba)3·CHCl3 and 10 mol%
of phosphine ligands in 1,2-dichloroethane (DCE) at
The development of methodologies for the synthesis of
80 °C for 6 hours under 5 atmospheres of carbon monox-
cyclopentenones from readily available substrates is one
ide, afforded the cyclopentenone 1a (Table 1), which is a
of the most active and challenging fields in organic syn-
key intermediate in the production of methylenomycin
thesis due to their occurrence in a large number of natural
B.4a The cyclopentenone was obtained as a sole product,
products. Transition-metal-catalyzed cycloaddition of
with neither benzenes 27 nor 3 observed in the cycloaddi-
alkynes, alkenes and carbon monoxide (known as the Pau-
tion. Other typical allylic reagents, such as allyl acetate
son–Khand reaction1) has been recognized as one of the
and allyl bromide, did not undergo any cycloaddition.
most important methods for the construction of the cyclo-
When using triaryl- or trialkylphosphine as a ligand, the
pentenone skeleton2 and has been extensively utilized for
yield of 1a was low (entries 1–3). The use of P(OPh)3 in-
the synthesis of a variety of natural compounds.2b,2c,2e,2f,2h
creased the yield to 46% (entry 4). Other P(OR)3 ligands
A closely related reaction, the nickel carbonyl mediated
were less reactive than P(OPh)3 (entries 6 and 7). The use
carbonylative cycloaddition of allylic halides and alkynes
of either sub-stoichiometric or excess P(OPh)3 per palla-
via a h3-allyl intermediate, was first reported by Chiusoli
dium, led to a decrease in yield. The cyclopentenone 1a
et al. in the 1960s.3 This method has been the subject of
was obtained in 55% yield (entry 5) after optimizing the
continuous study by Moretó et al., and has been widely
reaction temperature and the amount of methanol. The use
applied in organic synthesis.4 However, most of the reac-
of larger amounts of methanol decreased the yield of 1a,
tions require more than stoichiometric amounts of the haz-
whereas changes of carbon monoxide pressure scarcely
ardous nickel complex. Apart from the so-called ‘metallo-
affected the yield between 1 and 10 atmospheres, al-
ene-type’ cyclization/carbonylation sequence, catalyzed
though higher pressure (40 atmospheres) decreased the
by nickel or palladium complexes,6 there have been few
yield.
examples of catalytic versions of the cycloaddition reac-
tion.5 Chatani et al. reported palladium-catalyzed in-
danone formation from carbon monoxide, allyl acetate
and benzyne, a highly reactive alkyne.5a Recently, Moretó
et al. made the above, nickel-mediated cyclocarbonyla-
tion, catalytic by adding iron powder.5b
Table 2 summarizes the results obtained from the reac-
tions of allyl tosylate with several alkynes. The reactions
of symmetrical alkynes, 3-hexyne and 4-octyne, gave the
corresponding cyclopentenones 1b and 1c in 36% and
20% yield, respectively (entries 1 and 2). In the reactions
of phenyl-substituted alkynes, 2-phenylcyclopentenones
1d and 1e were selectively obtained, although the yield
was low (entries 3 and 4). The reaction of methyl 2-bu-
tynoate also proceeded regioselectively to afford 1f alone
(entry 5). Since, in most reactions, the alkynes were re-
covered with no other products observed, the low yield
may be attributed to the low reactivity of the alkynes and/
or the low stability of the allyl tosylate. Reactions with ex-
cess alkyne or excess allyl tosylate, however, did not im-
prove the yields.
Previously, we reported that palladium-catalyzed benzan-
nulation from alkynes and allyl tosylate led to penta- or
tri-substituted benzenes.7 In this cycloaddition, the use of
allyl tosylate as an allylic compound was essential, and
the key step was the insertion of an alkyne into a p-al-
lylpalladium intermediate. As the insertion of an alkyne
SYNTHESIS 2006, No. 18, pp 3003–3008
x
x.
x
x
.
2
0
0
6
Advanced online publication: 02.08.2006
DOI: 10.1055/s-2006-942538; Art ID: F06106SS
© Georg Thieme Verlag Stuttgart · New York

3004
N. Tsukada et al.
PAPER
Table 2 Pd-Catalyzed Carbonylative Cycloaddition of Allyl Tosyl-
Table 1 Pd-Catalyzed Carbonylative Cycloaddition of Allyl Tosyl-
ate to Alkynesa
ate to 2-Butynea
OTs
+
+
+
CO MeOH
Entry Alkyne
Product
Yieldb
(%)
Pd2(dba)3·CHCl3
ligand
1
2
3
36
Et
Et
Et
CO2Me
1a
ClCH2CH2Cl
CO2Me
O
Et
O
Entry
Ligand
Yieldb (%)
1b
n-Pr
20
1
2
3
4
5c
6
7
PCy3
7
22
21
46
55
18
32
n-Pr
Pr-n
PPh3
CO2Me
n-Pr
P(o-Tol)3
P(OPh)3
P(OPh)3
P(O-o-Tol)3
P(OMe)3
O
1c
14c,d
Et
Ph
Et
CO2Me
CO2Me
Ph
O
1d
4
5
11c,d
Ph
a All reactions were carried out in the presence of Pd2(dba)3·CHCl3
(0.025 mmol) and a ligand (0.05 mmol) with allyl tosylate (0.5
mmol), 2-butyne (0.6 mmol) and MeOH (2.0 mmol) in DCE (3 mL)
at 80 °C for 6 h under 5 atm CO.
Ph
O
1e
MeO2C
b GC yields.
25c
CO2Me
c Reaction using 3.0 mmol of MeOH at 100 °C.
CO2Me
O
1f
a All reactions were carried out in the presence of Pd2(dba)3·CHCl3
(0.025 mmol) and P(OPh)3 (0.05 mmol) with allyl tosylate (0.5
mmol), alkyne (0.6 mmol) and MeOH (3.0 mmol) in DCE (3 mL) at
100 °C for 6 h under 5 atm CO.
b GC yields.
2
3
c Isolated yields.
Figure 1
d Contaminated with a small amount of an isomer.
The reactions of 2-butyne and a range of substituted allyl
tosylates were also investigated. The results are summa-
rized in Table 3. Methallyl tosylate and 2-phenyl-2-
propenyl tosylate also underwent carbonylative cyclo-
addition to give the corresponding cyclopentenones 1g
and 1h (entries 1 and 2). The reaction of crotyl tosylate
gave a mixture of isomers 1i and 4 (entry 3). In the reac-
tion of 2-hexenyl tosylate (entry 4), b-hydride elimination
occurred instead of the second insertion of carbon monox-
ide, giving cyclopentenones 5 and 6 in 43% combined
yield. Since these products include no methoxy group, the
reaction did not require the addition of methanol. The
yield was improved to 59% using PPh3 as a ligand, and
63% after optimization of other reaction conditions
(Equation 1).
OTs
+
+
CO
2 equiv
1 atm
5 mol% Pd2(dba)3·CHCl3
10 mol% PPh3
5 + 6
ClCH2CH2Cl, 100 °C, 12 h
63% yield
(5:6 = 53:47)
Equation 1
per palladium gave 7a in 70% and 67% yield, respectively
(entries 2 and 3).9 In contrast, a dramatic decrease in yield
occurred without PPh3 (entry 1) or with two equivalents
PPh3 (entry 4). Since triphenylphosphite was less effec-
tive in this reaction, it seems that PPh3 is better than
P(OPh)3 for the reaction without methanol. Higher tem-
perature and higher pressure of carbon monoxide de-
creased the yield. Dialkylethynes, such as 2-butyne and 4-
octyne, also underwent carbonylative cycloaddition to af-
ford the corresponding cyclopentenones 7b and 7c (en-
Unexpectedly, the reaction of unsubstituted allyl tosylate,
in the absence of methanol, did not give methylenecyclo-
pentenones corresponding to the cyclopentenone 5. In-
stead, the cyclopentenone 7a, which consists of six
components, was obtained from allyl tosylate and 3-hex-
yne. The amount of PPh3 had a significant effect on the
yield of 7a. The reaction using 0.5 and 1 equivalents PPh3
Synthesis 2006, No. 18, 3003–3008 © Thieme Stuttgart · New York

PAPER
Palladium-Catalyzed Cyclopentenone Formation
3005
Table 3 Pd-Catalyzed Carbonylative Cycloaddition of 2-Butyne to
Table 4 Pd-Catalyzed Carbonylative Cycloaddition of Allyl Tosyl-
Allyl Tosylatesa
ate and Alkynes in the Absence of Methanola
OTs
+
+
CO
Yieldb (%)
31
R
R
Entry Allyl tosylate
Product
R
O
1
O
5 mol% Pd2(dba)3·CHCl3
PPh3
OTs
R
R
CO2Me
ClCH2CH2Cl, 80 °C
O
R
O
7a (R = Et)
1g
7b (R = Me)
2
3
42
7c (R = n-Pr)
Ph
Ph
OTs
Yieldb (%)
CO2Me
CO2Me
Entry
R
Amount of Product
PPh3 (mol%)
O
1h
1
Et
0
5
7a
7a
7a
7a
7b
7c
12
70
67
6
34c
1i:4 = 61:39
OTs
2
Et
3
Et
10
20
5
O
4
Et
1i
5
Me
n-Pr
48c
28c
6d
5
CO2Me
O
a All reactions were carried out in the presence of Pd2(dba)3·CHCl3
0.025 mmol) and PPh3 with allyl tosylate (0.5 mmol) and an alkyne
(2.0 mmol) in DCE (3 mL) at 80 °C for 1 h under 1 atm CO.
b GC yields.
4
4
43c
5:6 = 64:36
OTs
c Isolated yields.
d Reaction time: 12 h.
O
5
for the reaction. The subsequent insertion of carbon mon-
oxide into the vinylpalladium 10, followed by the in-
tramolecular insertion of a double bond, gives the
cyclopentenone intermediate 12.6f In the presence of
methanol, the insertion of carbon monoxide into 12 is fol-
lowed by termination by methanol to afford the cyclopen-
tenone 1. In the reaction of crotyl tosylate, b-hydride
elimination also takes place on the intermediate 12. Rein-
sertion of the double bond of 14 and insertion of carbon
monoxide to 15 give the cyclopentenone 4. In the reaction
of 2-hexenyl tosylate, insertion of carbon monoxide into
12 does not take place. Elimination of palladium with a b-
hydride affords the cyclopentenone 5 and 1-butenylcyclo-
pentene 6. The latter could be formed by isomerization of
the double bond of the 1-butenylcyclopentenone. When
the reaction is carried out in the absence of methanol, the
insertion of carbon monoxide into 12 is followed by suc-
cessive insertion of an alkyne and carbon monoxide, giv-
ing the acylpalladium 17. Cyclization of the enol tautomer
of 18 affords the cyclopentenone 7.
O
6
a All reactions were carried out in the presence of Pd2(dba)3·CHCl3
(0.025 mmol) and P(OPh)3 (0.05 mmol) with substituted allyl tosylate
(0.5 mmol), 2-butyne (0.6 mmol) and MeOH (2.0 mmol) in DCE (3
mL) at 100 °C for 6 h under 5 atm CO.
b Isolated yields.
c Yields for a mixture of isomers.
tries 5 and 6), although the reaction of 4-octyne required
prolonged reaction time. Diphenylacetylene and dimethyl
acetylenedicarboxylate did not react under these condi-
tions.
A plausible mechanism for the present palladium-cata-
lyzed carbonylative cycloaddition is illustrated in
Scheme 1. The insertion of an alkyne into the p-allylpal-
ladium 8, gives vinylpalladium 10. This insertion reaction
could be a key step in the cycloaddition. When typical al-
lylic reagents, such as allyl acetate and allyl bromide, are
employed instead of allyl tosylate, the acetate and bro-
mide ligands on 8 coordinate firmly to palladium and
hinder the coordination of an alkyne. Similarly, higher
carbon monoxide pressure or excess phosphine ligands in-
hibit the coordination of an alkyne. Weak coordination of
the tosylate ligand and the amount of phosphine ligands
(one equivalent per palladium or less) are thus important
In summary, we have found the Chiusoli carbonylative
cycloaddition proceeded catalytically by using allyl tosyl-
ate instead of allyl halide and palladium complexes as
catalyst. Although the yields were moderate, multiple car-
bon–carbon bond formation was achieved in a single op-
eration.10 In the presence of methanol, five-component
coupling reactions gave methyl cyclopentenyl acetates.
The reaction without methanol afforded (cyclopentenoyl-
methylidene)furanones from six components.
Synthesis 2006, No. 18, 3003–3008 © Thieme Stuttgart · New York

3006
N. Tsukada et al.
PAPER
R
R
R
R'
R'
OTs
R
R'
R'
CO
Pd(0)
[Pd]
R
R'
[Pd]
11
[Pd]
8
9
10
R'
R'
[Pd]
O
1
MeOH
O
R'
R'
CO
(R = H, Me)
[Pd]
12
R'
[Pd]
13
R'
R
R
O
O
R
R
(R = Me)
(R' = H)
O
(R = n-Pr)
R'
R'
5,6
[Pd]
[Pd]
H
R'
R'
R'
7
R'
O
O
16
14
CO
[Pd]
O
[Pd]
HO
R'
R'
R'
R'
O
O
CO
MeOH
4
R'
R'
R'
R'
[Pd]
R'
R'
O
O
O
17
18
15
Scheme 1
2,3-Diethyl-5-(methoxycarbonyl)methyl-2-cyclopentenone
(1b)4c
Spectroscopic measurements were carried out with the following
instruments: Bruker DPX-400 and DRX-500 (1H NMR and 13C
NMR), JEOL FT/IR-350 (FT-IR). Alkynes were purchased from
Aldrich or TCI and used without purification. Allyl tosylates were
prepared by reaction of the corresponding allylic alcohol with ex-
cess TsCl and KOH. DCE was distilled from CaH2 under a nitrogen
atmosphere.
IR (neat): 2968, 2940, 1739, 1696, 1641, 1437, 1360, 1311, 1217,
1172 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.69 (s, 3 H, OMe), 2.86 (dd,
J = 4.1, 16.4 Hz, 1 H, CHHCO2Me), 2.82 (m, 1 H, C=CCHH) 2.69
(m, 1 H, CHCOC=C), 2.44 (q, J = 7.7 Hz, 2 H, 2-CH2CH3), 2.34
(dd, J = 9.7, 16.4 Hz, 1 H, CHHCO2Me), 2.24 (m, 1 H,
CHCOC=C), 2.20 (q, J = 7.5 Hz, 2 H, 3-CH2CH3), 1.13 (t, J = 7.7
Hz, 3 H, 2-CH2CH3), 0.98 (t, J = 7.5 Hz, 3 H, 3-CH2CH3).
General Procedure
To a solution of Pd2(dba)3·CHCl3 (26 mg, 0.025 mmol) and P(OPh)3
(13.1 mL, 0.05 mmol) in DCE (3 mL) was added an allylic tosylate
(0.5 mmol), an alkyne (0.6 mmol) and MeOH (2.0 mmol) under ni-
trogen atmosphere in a stainless autoclave. After the autoclave was
pressurized with CO and heated at 100 °C for 6 h, the mixture was
cooled and filtered through a short silica gel column using Et2O as
eluent. Solvent and excess alkyne were removed under reduced
pressure, and cyclopentenones were purified by silica gel column
chromatography. The structure and stereochemistry of products
were determined by NMR spectra and NOE experiments.
13C NMR (100 MHz, CDCl3): d = 209.34, 173.24, 172.83, 140.37,
51.75, 41.33, 35.76, 35.39, 23.97, 16.38, 13.29, 12.06.
5-(Methoxycarbonyl)methyl-2,3-propyl-2-cyclopentenone (1c)
IR (neat): 2959, 2871, 1739, 1698, 1638, 1437, 1364, 1214, 1170
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.68 (s, 3 H, OMe), 2.86 (dd,
J = 4.1, 16.5 Hz, 1 H, CHHCO2Me), 2.81 (dd, J = 6.8, 18.2 Hz, 1 H,
CHCOC=C) 2.69 (ddd, J = 4.1, 6.8, 9.6 Hz, 1 H, CHCOC=C), 2.40
(t, J = 7.5 Hz, 2 H, 2-CH2CH2CH3), 2.35 (dd, J = 9.6, 16.5 Hz, 1 H,
CHHCO2Me), 2.23 (d, J = 18.2 Hz, 1 H, C=CCHH), 2.16 (t, J = 7.7
Hz, 2 H, 3-CH2CH2CH3), 1.56 (m, 2 H, 2-CH2CH2CH3), 1.40 (m,
2 H, 2-CH2CH2CH3), 0.96 (t, J = 7.4 Hz, 3 H, 2-CH2CH2CH3), 0.89
(t, J = 7.4 Hz, 3 H, 2-CH2CH2CH3).
5-(Methoxycarbonyl)methyl-2,3-dimethyl-2-cyclopentenone
(1a)4a
IR (neat): 2949, 2920, 1739, 1700, 1650, 1437, 1388, 1330, 1219,
1173 cm–1
1H NMR (400 MHz, CDCl3): d = 3.68 (s, 3 H, OMe), 2.85 (m, 1 H,
CHHCO2Me), 2.80 (m, 1 H, C=CCHH), 2.71 (m, 1 H, CHCOC=C),
2.35 (dd, J = 7.8, 13.2 Hz, 1 H, CHHCO2Me), 2.25 (d, J = 17.8 Hz,
1 H, C=CCHH), 2.04 (s, 3 H, 2-Me), 1.70 (s, 3 H, 3-Me).
13C NMR (100 MHz, CDCl3): d = 209.79, 173.24, 169.01, 135.88,
52.23, 41.79, 39.19, 35.77, 17.57, 8.54.
13C NMR (125 MHz, CDCl3): d = 209.48, 172.78, 172.41, 139.55,
51.74, 41.24, 36.10, 35.37, 32.96, 25.18, 21.80, 20.77, 14.14, 14.08.
Anal. Calcd for C14H22O3: C, 70.56; H, 9.30. Found: C, 70.58; H,
9.24.
3-Ethyl-5-(methoxycarbonyl)methyl-2-phenyl-2-cyclopenten-
one (1d)
IR (neat): 2926, 1737, 1697, 1355, 1175, 909, 733, 700 cm–1.
Synthesis 2006, No. 18, 3003–3008 © Thieme Stuttgart · New York

PAPER
Palladium-Catalyzed Cyclopentenone Formation
3007
1H NMR (400 MHz, CDCl3): d = 7.40 (m, 2 H, Ar), 7.32 (m, 1 H,
Ar), 7.26 (m, 2 H, Ar), 3.71 (s, 3 H, OMe), 3.01 (dd, J = 7.0, 18.5
Hz, 1 H, C=CCHH), 2.96 (dd, 1 H, J = 4.0, 16.4 Hz, CHHCO2Me),
2.89 (m, 1 H, CHCOC=C), 2.57 (q, J = 7.6 Hz, 2 H, CH2CH3), 2.48
(dd, J = 9.4, 16.4 Hz, 1 H, CHHCO2Me), 2.43 (dd, J = 2.8, 18.5 Hz,
1 H, C=CCHH), 1.17 (t, J = 7.6 Hz, 3 H, CH2CH3).
13C NMR (125 MHz, CDCl3): d = 207.45, 175.27, 172.64, 138.87,
131.76, 129.05, 128.25, 127.68, 51.79, 41.65, 35.77, 35.36, 24.70,
12.14.
IR (neat): 2921, 1736, 1699, 1648, 1437, 1388, 1330, 1201, 1057
cm–1.
1H NMR (500 MHz, CDCl3): d = 3.71 (s, 3 H, OMe), 3.03 (m, 1 H,
CHMe), 2.83 (m, 1 H, CHCOC=C), 2.58 (m, 1 H, C=CCH), 2.34
(m, 1 H, C=CCH), 2.05 (s, 3 H, 2-Me), 1.69 (s, 3 H, 3-Me), 0.97 (d,
J = 7.0 Hz, 3 H, MeCCO2Me).
13C NMR (125 MHz, CDCl3): d = 209.03, 175.80, 169.27, 136.31,
51.81, 46.58, 38.99, 34.48, 17.08, 11.56, 7.94.
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 67.00; H,
8.29.
HRMS (ESI): m/z [M + Na]+ calcd for C16H18NaO3: 281.1154;
found: 281.1147.
Isomer B
5-(Methoxycarbonyl)methyl-2-phenyl-2-cyclopentenone (1e)11
IR (neat): 2920, 1735, 1700, 1654, 1437, 1388, 1330, 1204, 1172,
1060 cm–1.
IR (neat): 2952, 1731, 1493, 1436, 1215, 884, 764, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.80 (t, J = 2.9 Hz, 1 H, C=CH),
7.71 (m, 2 H, m-Ar), 7.39–7.32 (m, 3 H, o- and m-Ar), 3.70 (s, 3 H,
OMe), 3.03 (ddd, J = 2.9, 6.8, 19.4 Hz, 1 H, C=CCHH), 2.97–2.87
(m, 2 H, CHHCO2Me and CHCOC=C), 2.54 (m, 1 H,
CHHCO2Me), 2.47 (dt, J = 19.4, 2.9 Hz, 1 H, C=CCHH).
13C NMR (125 MHz, CDCl3): d = 207.27, 172.41, 157.08, 142.49,
131.45, 128.58, 128.44, 128.41, 126.96, 51.81, 47.58, 42.76, 35.04,
33.27.
1H NMR (500 MHz, CDCl3): d = 3.61 (s, 3 H, OMe), 3.03 (m, 1 H,
CHMe), 2.62 (m, 1 H, CHCOC=C), 2.52 (m, 1 H, C=CCH), 2.32
(m, 1 H, C=CCH), 2.03 (s, 3 H, 2-Me), 1.70 (s, 3 H, 3-Me), 1.28 (d,
J = 7.3 Hz, 3 H, MeCCO2Me).
13C NMR (125 MHz, CDCl3): d = 208.98, 174.80, 167.73, 135.84,
51.59, 47.57, 39.62, 35.82, 17.03, 15.02, 7.97.
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 67.16; H,
8.66.
3-Methoxycarbonyl-5-(methoxycarbonyl)methyl-2-methyl-2-
cyclopentenone (1f)4c
5-[2-(Methoxycarbonyl)ethyl]-2,3-dimethyl-2-cyclopentenone
(4)
IR (neat) 2953, 2912, 1717, 1438, 1229, 911, 732 cm–1.
IR (neat): 2921, 1737, 1698, 1653, 1437, 1387, 1174, 1053, 756
1H NMR (400 MHz, CDCl3): d = 3.86 (s, 3 H, OMe), 3.69 (s, 3 H,
OMe), 3.08 (ddq, J = 7.0, 18.5, 2.2 Hz, 1 H, C=CCHH), 2.85 (dd,
J = 4.1, 16.7 Hz, 1 H, CHHCO2Me), 2.76 (m, 1 H, CHCOC=C),
2.56 (dd, J = 8.3, 16.7 Hz, 1 H, CHHCO2Me), 2.50 (m, 1 H,
C=CCHH), 2.08 (t, J = 2.2 Hz, 3 H, C=CMe).
13C NMR (100 MHz, CDCl3): d = 209.72, 172.03, 165.67, 152.62,
146.78, 52.12, 51.92, 41.04, 34.57, 33.44, 10.02.
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.67 (s, 3 H, OMe), 2.69 (m, 1 H,
C=CCHH), 2.44 (m, 2 H, CH2CO2Me), 2.36 (m, 1 H, CHCOC=C),
2.15 (m, 1 H, C=CCHH), 2.07 (m, 1 H, CHHCH2CO2Me), 2.03 (s,
3 H, 2-Me), 1.70 (m, 1 H, CHHCH2CO2Me), 1.68 (m, 3 H, 3-Me).
13C NMR (100 MHz, CDCl3): d = 210.60, 173.67, 168.14, 135.56,
51.57, 43.96, 38.42, 31.77, 26.78, 17.04, 7.93.
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 66.92; H,
8.39.
5-(Methoxycarbonyl)methyl-2,3,5-trimethyl-2-cyclopentenone
(1g)
IR (neat): 2953, 2924, 2252, 1737, 1699, 1655, 1437, 1204, 1018,
(E)-5-Butylidene-2,3-dimethyl-2-cyclopentenone (5)12
914, 732 cm–1.
IR (neat) 2960, 2930, 1697, 1670, 1640, 1389, 1330, 1094 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.62 (s, 3 H, OMe), 2.72 (m, 1 H,
C=CCHH), 2.52 (s, 2 H, CH2CO2Me), 2.32 (m, 1 H, C=CCHH),
2.03 (m, 3 H, 2-Me), 1.72 (m, 3 H, 3-Me), 1.12 (s, 3 H, COCMe).
13C NMR (100 MHz, CDCl3): d = 211.74, 171.91, 167.19, 133.47,
51.43, 45.81, 44.15, 41.00, 24.25, 16.98, 8.11.
1H NMR (400 MHz, CDCl3): d = 6.54 (t, 1 H, J = 7.6 Hz, C=CH),
3.01 (s, 2 H, C=CCH2C=C), 2.18 (q, J = 7.3 Hz. 2 H, CH3CH2CH2),
2.07 (s, 3 H, 2-Me), 1.77 (s, 3 H, 3-Me), 1.51 (sext, J = 7.3 Hz, 2 H,
CH3CH2CH2), 0.94 (t, J = 7.3 Hz, 3 H, CH3CH2CH2).
13C NMR (100 MHz, CDCl3): d = 196.46, 162.28, 138.21, 134.82,
133.14, 35.17, 31.50, 21.84, 16.62, 13.88, 8.22.
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 67.14; H,
8.59.
5-(2-Butenyl)-2,3-dimethyl-2-cyclopentenone (6)
5-(Methoxycarbonyl)methyl-2,3-dimethyl-5-phenyl-2-cyclo-
pentenone (1h)
1H NMR (400 MHz, CDCl3): d = 5.56–5.43 (m, 1 H, C=CH), 5.39–
5.27 (m, 1 H, C=CH), 2.67–2.35 (m, 3 H, two allyl protons and one
methyne proton), 2.23–2.10 (m, 1 H, one allyl proton), 2.03 (s, 3 H,
2-Me), 2.03–1.94 (m, 1 H, one allyl proton), 1.69 (m, 3 H, 3-Me),
1.67–1.60 (m, 3 H, C=CMe).
IR (neat): 2968, 2921, 1740, 1702, 1653, 1437, 1330, 1172, 698
cm–1.
1H NMR (500 MHz, CDCl3): d = 7.29–7.27 (m, 4 H, Ph), 7.21 (m,
1 H, Ph), 3.59 (s, 3 H, OMe), 3.09 (d, J = 16.4 Hz, 1 H, C=CHH),
3.05 (m, 2 H, CH2CO2Me), 2.93 (d, J = 16.4 Hz, 1 H, C=CCHH),
2.09 (m, 3 H, 2-Me), 1.76 (m, 3 H, 3-Me).
13C NMR (125 MHz, CDCl3): d = 208.46, 171.61, 167.74, 141.80,
134.63, 128.64, 126.89, 126.05, 52.10, 51.65, 46.73, 41.48, 17.04,
8.38.
13C NMR (125 MHz, CDCl3): d = 211.30, 168.82, 135.65, 135.50,
128.15, 127.13, 127.03, 125.86, 44.75, 37.82, 34.54, 28.50, 17.95,
17.14, 12.94, 7.99.
Anal. Calcd for C11H16O: C, 80.44; H, 9.82. Found: C. 80.46; H.
9.55.
HRMS (ESI): m/z [M + Na]+ calcd for C16H18NaO3: 281.1154;
found: 281.1148.
(Z)-3,4-Diethyl-5-[(3,4-diethyl-2-oxo-3-cyclopentenyl)meth-
ylidene]-2-(5H)-furanone (7a)
IR (neat): 2973, 2921, 2874, 1764, 1699, 1637, 1459, 1029, 912,
732 cm–1.
5-[1-(Methoxycarbonyl)ethyl]-2,3-dimethyl-2-cyclopentenone
(1i)
Isomer A
Synthesis 2006, No. 18, 3003–3008 © Thieme Stuttgart · New York

3008
N. Tsukada et al.
PAPER
G., Eds.; Elsevier: New York, 1995, 703. (e) Geis, O.;
Schmalz, H. G. Angew. Chem. Int. Ed. 1998, 37, 911.
(f) Jeong, N. In Transition Metals in Organic Synthesis, Vol.
1; Beller, M.; Bolm, C., Eds.; Wiley-VCH: Weinhem, 1998,
560. (g) Chung, Y. K. Coord. Chem. Rev. 1999, 188, 297.
(h) Brummond, K. M.; Kent, J. L. Tetrahedron 2000, 56,
3263.
1H NMR (400 MHz, CDCl3): d = 5.28 (d, J = 8.0 Hz, 1 H, C=CH),
3.59 (m, 1 H, CHCOC=C), 3.03 (dd, J = 7.3, 18.3 Hz, 1 H,
C=CCHH), 2.51–2.43 (m, 5 H, C=CCHH and 2 × CH2CH3), 2.35
(q, J = 7.6 Hz, 2 H, CH2CH3), 2.22 (q, J = 7.6 Hz, 2 H, CH2CH3),
1.19–1.12 (m, 9 H, 3 × Me), 1.01 (t, J = 7.6 Hz, 3 H, Me).
13C NMR (100 MHz, CDCl3): d = 207.74, 173.57, 170.25, 152.05,
150.89, 140.11, 129.50, 107.28, 43.62, 36.66, 24.05, 17.90, 17.10,
16.50, 14.38, 13.30, 13.05, 12.04.
(3) (a) Cassar, L.; Chiusoli, G. P. Tetrahedron Lett. 1965, 3295.
(b) Chiusoli, G. P.; Cassar, L. Angew. Chem. Int. Ed. Engl.
1967, 6, 124. (c) Chiusoli, G. P. Acc. Chem. Res. 1973, 6,
422. (d) Cassar, L.; Chiusoli, G. P.; Guerrieri, F. Synthesis
1973, 509.
Anal. Calcd for C18H24O3: C, 74.97; H, 8.39. Found: C, 74.41; H,
7.89.
(Z)-3,4-Dimethyl-5-[(3,4-dimethyl-2-oxo-3-cyclopenten-
yl)methylidene]-2-(5H)-furanone (7b)
Mp 160.8–161.2 °C.
(4) (a) Camps, F.; Coll, J.; Moretó, J. M.; Torras, J. Tetrahedron
Lett. 1985, 26, 6397. (b) Camps, F.; Coll, J.; Moretó, J. M.;
Torras, J. Tetrahedron Lett. 1987, 28, 4745. (c) Camps, F.;
Coll, J.; Moretó, J. M.; Torras, J. J. Org. Chem. 1989, 54,
1969. (d) Camps, F.; Moretó, J. M.; Pagès, L. Tetrahedron
1992, 48, 3147. (e) Camps, F.; Llebaria, A.; Moretó, J. M.;
Pagès, L. Tetrahedron Lett. 1992, 33, 109. (f) Pagès, L.;
Llebaria, A.; Camps, F.; Molins, E.; Miravitlles, C.; Moretó,
J. M. J. Am. Chem. Soc. 1992, 114, 10449. (g) Llebaria, A.;
Camps, F.; Moretó, J. M. Tetrahedron Lett. 1993, 49, 1283.
(h) Villar, J. M.; Delgado, A.; Llebaria, A.; Moretó, J. M.
Tetrahedron 1996, 52, 10525. (i) García-Gómez, G.;
Moretó, J. M. J. Am. Chem. Soc. 1999, 121, 878. (j) Carbó,
J. J.; Bo, C.; Poblet, J. M.; Moretó, J. M. Organometallics
2000, 19, 3516.
IR (KBr): 2922, 1753, 1693, 1675, 1642, 1383, 1075, 1011, 854,
756 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.22 (d, J = 7.8 Hz, 1 H, C=CH),
3.61 (dt, J = 3.0, 7.8 Hz, 1 H, CHCOC=C), 2.99 (m, 1 H,
C=CCHH), 2.48 (m, 1 H, C=CCHH), 2.07 (s, 3 H, Me on furanone),
2.03 (s, 3 H, Me on cyclopentenone), 1.91 (s, 3 H, Me on furanone),
1.74 (s, 3 H, Me on cyclopentenone).
13C NMR (100 MHz, CDCl3): d = 207.76, 170.57, 168.91, 151.98,
146.88, 135.20, 124.75, 107.00, 43.41, 39.41, 17.12, 9.91, 8.66,
8.19.
Anal. Calcd for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.48; H,
6.92.
(5) (a) Chatani, N.; Kamitani, A.; Oshita, M.; Fukumoto, Y.;
Murai, S. J. Am. Chem. Soc. 2001, 123, 12686. (b) Nadal,
M. L.; Bosch, J.; Vila, J. M.; Klein, G.; Ricart, S.; Moretó,
M. J. Am. Chem. Soc. 2005, 127, 10476.
(Z)-3,4-Dipropyl-5-[(3,4-dipropyl-2-oxo-3-cyclopentenyl)meth-
ylidene]-2-(5H)-furanone (7c)
(6) (a) Oppolzer, W.; Keller, T. H.; Bedoya-Zurita, M.; Stone,
C. Tetrahedron Lett. 1989, 30, 5883. (b) Oppolzer, W.
Angew. Chem., Int. Ed. Engl. 1989, 28, 38. (c) Oppolzer,
W. Pure Appl. Chem. 1990, 62, 1941. (d) Oppolzer, W.;
Xu, J.-Z.; Stone, C. Helv. Chim. Acta 1991, 74, 465.
(e) Oppolzer, W.; Robyr, C. Tetrahedron 1994, 50, 415.
(f) Negishi, E.; Wu, G.; Tour, J. M. Tetrahedron Lett. 1988,
29, 6745. (g) Ihle, N. C.; Heathcock, C. H. J. Org. Chem.
1993, 58, 560.
IR (neat): 2962, 2933, 2872, 2252, 1762, 1698, 1636, 1464, 910,
733 cm–1.
1H NMR (500 MHz, CDCl3): d = 5.26 (d, J = 7.9 Hz, 1 H, C=CH),
3.60 (dt, J = 2.9, 7.9 Hz, 1 H, CHCOC=C), 3.02 (dd, J = 7.9, 18.4
Hz, 1 H, C=CCHH), 2.49–2.36 (m, 5 H, C=CCHH and 2 ×
CH2CH2CH3), 2.33–2.26 (m, 2 H, CH2CH2CH3), 2.24–2.13 (m,
2 H, CH2CH2CH3), 1.64–1.53 (m, 6 H, 3 × CH2CH2CH3), 1.51–1.39
(m, 2 H, CH2CH2CH3), 1.03–0.84 (m, 12 H, 4 × Me).
13C NMR (125 MHz, CDCl3): d = 207.66, 172.54, 170.09, 151.09,
150.85, 139.07, 128.37, 107.29, 43.41, 36.83, 28.28, 26.41, 25.64,
25.09, 21.83, 21.58, 21.39, 20.58, 13.99, 13.98, 13.90, 13.84.
(7) (a) Tsukada, N.; Sugawara, S.; Inoue, Y. Org. Lett. 2000, 2,
655. (b) Tsukada, N.; Sugawara, S.; Nakaoka, K.; Inoue, Y.
J. Org. Chem. 2003, 68, 5961.
(8) (a) Tsukada, N.; Sato, T.; Inoue, Y. Chem. Commun. 2001,
237. (b) Tsukada, N.; Sato, T.; Inoue, Y. Chem. Commun.
2003, 2404. (c) Tsukada, N.; Yagura, Y.; Sato, T.; Inoue, Y.
Synlett 2003, 1431.
Anal. Calcd for C22H32O3: C, 76.70; H, 9.36. Found: C, 76.96; H,
9.60.
(9) The 2:1 ratio of palladium and PPh3 was also applied to the
reactions in entries 5 and 6 because the yield of 7a was
higher when using palladium and PPh3 in 2:1 ratio than in
1:1 ratio, although the 2:1 ratio is unusual.
(10) (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl.
1993, 32, 131. (b) Bunce, R. A. Tetrahedron 1995, 51,
13103. (c) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(d) Ikeda, S.-I. Acc. Chem. Res. 2000, 33, 511.
References
(1) (a) Khand, J. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.;
Foreman, M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977.
(b) Pauson, P. L. Tetrahedron 1985, 41, 5855. (c) Pauson,
P. L. In Organometallics in Organic Synthesis, Aspects of a
Modern Interdisciplinary Field; de Meijere, A.; tom Dieck,
H., Eds.; Springer-Verlag: Berlin, 1988, 233.
(2) For recent reviews, see: (a) Schore, N. E. Chem. Rev. 1988,
88, 1081. (b) Schore, N. E. Org. React. 1991, 40, 1.
(11) (a) Llebaria, A.; Camps, F.; Moretó, J. M. Tetrahedron 1993,
49, 1283. (b) Camps, F.; Coll, J.; Llebaria, A.; Moretó, J. M.
Tetrahedron Lett. 1988, 29, 5811.
(c) Schore, N. E. In Comprehensive Organic Synthesis, Vol.
5; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991,
1037. (d) Schore, N. E. In Comprehensive Organometallic
Chemistry II, Vol. 12; Abel, E. W.; Stone, F. A.; Wilkinson,
(12) Murakami, M.; Itami, K.; Ito, Y. Organometallics 1999, 18,
1326.
Synthesis 2006, No. 18, 3003–3008 © Thieme Stuttgart · New York