Yb(OTf)3-promoted ZnCl2-catalyzed conia-ene reaction of linear β-alkynic β-dicarbonyls

Article abstract of DOI:10.1055/s-0030-1258213

An atom-economical and solvent-free ytterbium(III) triflate promoted, zinc(II) chloride catalyzed Conia-ene method has been developed for the construction of five- to six-membered-ring carbocycles. In the presence of zinc(II) chloride and ytterbium(III) triflate, a variety of linear β-alkynic β-keto esters and -alkynic -diketones were cyclized under neat conditions in moderate to good yields. It is noteworthy that the selectivity toward five- or six-membered-ring carbocycles depends on substituents at the terminal alkynes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258213

PAPER
3663
Yb(OTf)3-Promoted ZnCl2-Catalyzed Conia-Ene Reaction of Linear
b-Alkynic b-Dicarbonyls
Yu Liu, Ren-Jie Song, Jin-Heng Li*
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), Hunan Normal University,
Changsha 410081, P. R. of China
Fax +86(731)88872101; E-mail: jhli@hunnu.edu.cn
Received 25 June 2010; revised 20 July 2010
great advantages of these methods, certain drawbacks and
Abstract: An atom-economical and solvent-free ytterbium(III) tri-
limitations still exist: 1) the reported catalytic systems are
highly expensive, 2) the used solvents are harmful in view
of the environment, and 3) most are focused on a-alkynic
flate promoted, zinc(II) chloride catalyzed Conia-ene method has
been developed for the construction of five- to six-membered-ring
carbocycles. In the presence of zinc(II) chloride and ytterbium(III)
triflate, a variety of linear b-alkynic b-keto esters and b-alkynic b- b-keto esters, and only two papers have been reported on
linear b-alkynic b-keto ester substrates.4e,7a In 2006,
diketones were cyclized under neat conditions in moderate to good
yields. It is noteworthy that the selectivity toward five- or six-
Sawamura and co-workers reported a linear b-alkynic b-
membered-ring carbocycles depends on substituents at the terminal
keto ester substrate for the Conia-ene reaction using
alkynes.
[Au(N(SO2CF3)2(triethynyphosphine)] catalysis.4e Subse-
Key words: zinc(II) chloride, ytterbium(III) triflate, Conia-ene re-
action, linear b-alkynic b-dicarbonyl, carbocycle
quently, we have developed an effective Cu/Ag-catalyzed
protocol for the Conia-ene reactions of linear b-alkynic b-
keto esters (Equations 1 and 2 in Scheme 1).7a In the pres-
ence of (CuOTf)2·C6H6 and silver(I) (AgSbF6 or AgOAc),
a variety of linear b-alkynic b-keto esters selectively un-
derwent the Conia-ene intramolecular reaction to afford
the corresponding exo- or endo-products in moderate to
good yields. For the reaction of b-(substituted alkynic) b-
keto esters, however, the yields are unsatisfactory. Re-
cently, we reported a general and inexpensive Zn-cata-
lyzed Conia-ene route, which allows a wide range of a-
alkynic dicarbonyl compounds to proceed the Conia-ene
reaction with inexpensive zinc(II) chloride under neat
The development of new Lewis acid catalyzed Conia-ene
route is of long-standing interest to organic chemists, be-
cause this process can construct new chemical bonds in an
efficient and atom-economical manner.1–7 In recent years,
several efficient catalytic systems, including Au/Ag,4
Ni(acac)2/Yb(OTf)3,5 In(NTf2)3,6 and (CuOTf)2·C6H6/
Ag,7 have been reported for the intramolecular Conia-ene
reaction of numerous alkynic b-keto esters.4–7 Despite the
O
O
O
R1
O
O
O
O
R1
R1
R1
R2
R2
(CuOTf)2⋅C6H6
R2
R2
R4
(CuOTf)2⋅C6H6
R4
R4
R3
+
(1)
(2)
(3)
[Ag], DCE
R
[Ag], DCE
R3 = H
R3
3 = aryl
R3
R3
O
O
O
O
O
O
(CuOTf)2⋅C6H6
+
OMe
OMe
AgSbF6, DCE
95 °C, 24 h
OMe
R2
O
R2
O
ZnCl2
R1
O
R1
O
O
neat, 100 °C, Ar
n = 2, 3
n
n
O
O
O
O
R1
R1
O
R1
ZnCl2
Yb(OTf)3
ZnCl2
Yb(OTf)3
R2
R2
R2
R4
R4
(4)
R4
R3
R3 = H
n = 1, 2
R
3 = aryl, Me
n = 1
R3
n
n
n
R3
Scheme 1 Conia-ene reactions of alkynic dicarbonyl compounds
SYNTHESIS 2010, No. 21, pp 3663–3669
x
x.
x
x
.
2
0
1
0
Advanced online publication: 13.08.2010
DOI: 10.1055/s-0030-1258213; Art ID: F10810SS
© Georg Thieme Verlag Stuttgart · New York

3664
Y. Liu et al.
PAPER
Table 1 The Conia-Ene Reaction of Ethyl 3-Oxohept-6-ynoate (1a)
Table 2 Ytterbium(III) Triflate Promoted, Zinc(II) Chloride Cata-
lyzed Conia-Ene Reactions of Terminal Alkynes 1a
in the Presence of Zinca
O
O
Yield (%)b
O
Entry Terminal alkyne 1
Product 2
O
[Zn]
OEt
O
O
O
OEt
O
additive
OMe
1
2
3
4
73
OMe
1a
2a
Entry [Zn]
Additive (equiv)
–
Temp (°C) Yield (%)b
2b
1b
1c
1d
1e
O
O
1
2
3
4
5c
6
7
8
9
ZnCl2
100
55
56
61
77
80
52
38
45
36
32
72
O
O
O
O
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnI2
Yb(OTf)3 (0.2)
Yb(OTf)3 (0.5)
Yb(OTf)3 (1)
Yb(OTf)3 (1)
Mg(ClO4)2 (1)
CuCl2 (1)
100
100
100
100
100
100
100
100
40
66
53
85
O
2c
2d
2e
O
O
O
OMe
OMe
Yb(OTf)3 (1)
Yb(OTf)3 (1)
Yb(OTf)3 (1)
Yb(OTf)3 (1)
O
O
O
O
Zn(OTf)2
ZnCl2
ZnCl2
OEt
OEt
10
11
120
O
O
O
a Reaction conditions: 1a (0.3 mmol), [Zn] (10 mol%), and additive in
argon atmosphere under neat conditions for 24 h.
b Isoalted yield.
O
OMe
5
6
7
64
75
68
OMe
c DCE (4 mL) was added.
2f
1f
conditions (Equation 3, Scheme 1).8 Thus, we decided to
employ the reported zinc(II) chloride conditions for the
Conia-ene reaction of linear b-alkynic b-keto esters and b-
alkynic b-diketones. After a series of trials, we found that
zinc(II) chloride combined with ytterbium(III) triflate dis-
played high efficiency for this purpose. Herein, we report
an effective route to construct five- to six-membered-ring
carbocycles by ytterbium(III) triflate promoted, zinc(II)
chloride catalyzed Conia-ene reaction of linear b-alkynic
b-dicarbonyls under neat conditions (Equation 4,
Scheme 1).
O
O
O
O
O
O
O
OEt
OEt
2g
1g
O
2h
1h
1i
O
O
O
O
The reaction of ethyl 3-oxohept-6-ynoate (1a), a linear b-
alkynic b-keto ester, was chosen as a model reaction to
optimize the reaction conditions, and the results are sum-
marized in Table 1. Initially, the reaction of substrate 1a
with zinc(II) chloride was carried out under the reported
conditions, and the target exo-product 2a was isolated in
55% yield (Table 1, entry 1). In the previously reported
Ph
8
81
Ph
2i
a Reaction conditions: 1 (0.3 mmol), ZnCl2 (10 mol%), and Yb(OTf)3
(1.0 equiv) at 100 °C in argon atmosphere under neat conditions for
results, ytterbium(III) triflate was found to favor the gen- 24 h.
b Isolated yield.
eration of the enol form leading to the improvement of the
corresponding reactions.5 As expected, the yield was en-
hanced in the presence of ytterbium(III) triflate (entries 2–
4). While 0.2 equivalent of ytterbium(III) triflate in-
creased the yield slightly (entry 2), 1 equivalent enhanced
the yield to 77% (entry 4). Two other additives,
Mg(ClO4)2 and copper(II) chloride, were subsequently
evaluated, and they were less effective (entries 6 and 7).
The solvent, dichloroethane, has no effect on the reaction
(entry 7). Both zinc(II) iodide and zinc(II) triflate dis-
played less efficiency than zinc(II) chloride in the pres-
ence of ytterbium(III) triflate (entries 8 and 9). Among the
effect of the reaction temperatures examined, 100 °C
turned out to be the most suitable for the reaction (entry 4
Synthesis 2010, No. 21, 3663–3669 © Thieme Stuttgart · New York

PAPER
Conia-Ene Cyclization of Linear b-Alkynic b-Dicarbonyls
3665
Table 3 Ytterbium(III) Triflate Promoted, Zinc(II) Chloride Cata-
lyzed Conia-Ene Reactions of Internal Alkynes 1a (continued)
vs entries 10 and 11). It was noted that the yield was low-
ered to 32% when the reaction was carried out at 40 °C
(entry 10), and to 72% at 120 °C (entry 11).
Entry Internal alkyne 1
Product 2
Yield (%)b
With the optimal conditions in hand, the scope for the
Conia-ene reaction was explored (Tables 2 and 3). As
shown in Table 2, a variety of terminal alkynes were sur-
veyed in the presence of zinc(II) chloride and ytterbi-
um(III) triflate.
O
O
O
O
O
O
Ph
Ph
Ph
Ph
5
58
The results demonstrated that various b-alkynic b-keto es-
ters 1b–g and b-diketones 1h–i were successfully reacted
with zinc(II) chloride and ytterbium(III) triflate under
neat conditions, affording the corresponding exo-products
alone in moderate to good yields. We found that the me-
thyl and isopropyl ester, 1b and 1c, could successfully un-
dergo the reaction, although the yields were decreased to
some extent (Table 2 entries 1 and 2). Moderate to good
yields were still achieved from g-substituted substrates
1d–f (entries 3–5). Gratifyingly, a six-membered-ring
product 2g was obtained from ethyl 3-oxooct-7-ynoate
(1g) in 75% yield (entry 6). Diketones 1h and 1i could
also be converted into the desired products in 68 and 71%
yield, respectively (entries 7 and 8).
MeO
O
MeO
O
3n
1n
O
Ph
6
70
OMe
OMe
3o
1o
O
O
O
Ph
7
8
9
52
80
62
Table 3 Ytterbium(III) Triflate Promoted, Zinc(II) Chloride Cata-
lyzed Conia-Ene Reactions of Internal Alkynes 1a
O
O
Yield (%)b
3p
3q
Entry Internal alkyne 1
Product 2
1p
1q
O
O
O
O
O
O
O
O
O
O
O
Ph
Ph
Ph
Ph
1
2
60
Ph
O
1j
3j
O
O
O
O
O
O
OMe
OMe
Ph
Ph
59
54
36
O
O
3k
3r
1k
1r
O
O
a Reaction conditions: 1 (0.3 mmol), ZnCl2 (10 mol%), and Yb(OTf)3
(1.0 equiv) at 100 °C in argon atmosphere under neat conditions for
O
Ph
Ph
24 h.
b Isolated yield.
3
4
The cyclization of internal alkynes 1j–q were subsequent-
ly investigated under the optimal conditions, and the se-
lectivity was shifted toward the endo-products 3
(Table 3). Compared with the reported Cu/Ag catalytic
system, the present Zn/Yb system is more efficient. In the
presence of zinc(II) chloride and ytterbium(III) triflate,
diketones 1j–p, bearing either electron-rich or electron-
deficient aryl groups at the terminal alkyne, underwent the
reaction smoothly to afford the corresponding endo-prod-
ucts 3j–p in moderate to good yields (Table 3, entries 1–
7). However, both the steric hindrance and the electron-
deficient aryl groups disfavored the reaction. We found
3l
1l
O
O
O
Ph
Ph
3m
1m
Synthesis 2010, No. 21, 3663–3669 © Thieme Stuttgart · New York

3666
Y. Liu et al.
PAPER
O
O
R1
Zn
O
O
R2 = H
R1
O
O
O
R1
H
M
O
H
R1
2
B
M
Zn
O
O
O
R1
R2
R2
O
1
A
R1
Zn
M = Zn and Yb
R2 = Me, aryl
R2
R2
3
C
Scheme 2 A possible mechanism
that the active order of methyl-substituted substrates 1k– In summary, we have developed a zinc(II) chloride and yt-
m is para-1k > meta-1l > ortho-1m in terms of yields (en- terbium(III) triflate catalytic system for the Conia-ene in-
tries 2–4). While substrate 1o bearing an electron-donat- tramolecular reaction of linear b-alkynic b-dicarbonyls
ing aryl group afforded the desired product 3o in 70% under neat conditions. In the presence of zinc(II) chloride
yield (entry 6), electron-deficient diketone 1p lowered the and ytterbium(III) triflate, the present Conia-ene route al-
yield to 52% (entry 7). To our delight, another diketone 1q lows the selective construction of five- to six-membered-
with a methyl group at the terminal alkyne was also cy- ring carbocycles from various linear b-alkynic b-keto es-
clized in good yield (entry 8). Keto ester 1r, the reportedly ters and b-alkynic b-diketones. It is noteworthy that this
less active substrate,7a was also compatible with the opti- protocol is atom-economical and environmentally benign
mal conditions to afford the desired endo-product in 62% (solvent-free).
yield (entry 9).
A possible mechanism as outlined in Scheme 2 was pro-
posed on the basis of the present results and the reported
mechanisms.1–8 Generally, two mechanisms are described
for the Conia-ene reaction: 1) nucleophilic attack on an
M-alkyne complex by the enol form of the keto ester, and
2) an M-enolate formation by directly complex with the b-
keto ester, followed by a cis-carbon metalation of the
All melting points are uncorrected. IR spectra were recorded using
KBr optics. NMR spectroscopy was performed on a Bruker-500
spectrometer operating at 500 MHz (1H NMR) and 125 MHz (13C
NMR). TMS was used an internal standard and CDCl3 was used as
the solvent. Mass spectrometric analysis was performed on GC-MS
analysis (Shimadzu GCMS-QP2010 plus).
Conia-Ene Reaction; General Procedure
alkyne.1–8 The present results suggest that the intermedi- To a Schlenk tube was added dicarbonyl 1 (0.3 mmol), ZnCl2 (10
mol%), and Yb(OTf)3 (1.0 equiv). Then the mixture was stirred in
argon atmosphere under neat conditions at 100 °C for the indicated
ate A may be generated by the complexation of zinc with
alkyne, and another metal (Zn or/and Yb) with dicarbonyl,
time until complete consumption of the starting material as moni-
which is similar to the mechanism proposed by Toste.2a,7
tored by TLC. After completion of the reaction, the mixture was
poured into EtOAc (10 mL) and the EtOAc layer was washed with
Subsequently, the intramolecular attack of the M-enolate
on the Zn-alkyne complex takes place to form the inter-
mediates B (terminal alkynes) and C (internal alkynes),
followed by protonation/isomerization sequence to give
the corresponding exo- or endo-products. The present re-
sults show that the selectivity toward exo- or endo-prod-
ucts depends on the properties of alkynes: Zn often adds
to the less sterically hindered position of the alkyne during
the intramolecular attack (intermediate B); however, the
formation of less strained ring is preferable when there are
similar substituents at the ends of the CºC bond (interme-
diate C). We deduce that ytterbium(III) triflate can im-
prove the reaction by complexing with dicarbony groups
leading to the formation of enol form.
brine (3 × 5 mL). The aqueous washings were extracted with EtOAc
(3 × 5 mL), the combined organic layers were dried (Na2SO4), and
evaporated under vacuum. The residue was purified by flash col-
umn chromatography on silica gel (hexane–EtOAc) to afford the
pure product.
Ethyl 2-Methyl-5-oxocyclopent-2-enecarboxylate (2a)7a
Colorless oil.
IR (film): 1749, 1717 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.34–4.30 (m, 2 H), 2.66 (t, J = 5.0
Hz, 2 H), 2.49 (t, J = 5.0 Hz, 2 H), 2.39 (s, 3 H), 1.35 (t, J = 7.5 Hz,
3 H).
13C NMR (125 MHz, CDCl3): d = 203.5, 184.2, 163.3, 132.8, 60.8,
35.0, 32.6, 19.3, 14.2.
A radical cyclization mechanisn for the endo-cyclization
has been proposed.9 Thus, two controlled experiments us-
ing the substrate 1j were carried out in the presence of two
radical inhibitors, 1,1-diphenylethylene or TEMPO. We
found that these radical inhibitors could not affect this re-
action, suggesting that the free radical mechanism can be
ruled out.
LRMS (EI, 70 eV): m/z (%) = 168 (M+, 13), 123 (83), 96 (100).
Methyl 2-Methyl-5-oxocyclopent-1-enecarboxylate (2b)7a
Colorless oil.
IR (film): 1741, 1720 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.85 (s, 3 H), 2.68 (t, J = 5.0 Hz,
2 H), 2.50 (t, J = 5.0 Hz, 2 H), 2.41 (s, 3 H).
Synthesis 2010, No. 21, 3663–3669 © Thieme Stuttgart · New York

PAPER
Conia-Ene Cyclization of Linear b-Alkynic b-Dicarbonyls
3667
13C NMR (125 MHz, CDCl3): d = 203.5, 185.6, 163.7, 132.3, 51.8,
IR (film): 1716, 1699 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.68 (t, J = 5.0 Hz, 2 H), 2.49–2.47
(m, 5 H), 2.41 (s, 3 H).
35.0, 32.8, 19.4.
LRMS (EI, 70 eV): m/z (%) = 154 (M+, 40), 123 (100).
13C NMR (125 MHz, CDCl3): d = 205.6, 197.4, 186.1, 138.7, 34.9,
Isopropyl 2-Methyl-5-oxocyclopent-1-enecarboxylate (2c)
Colorless oil.
IR (film): 1740, 1718 cm–1.
33.0, 30.8, 19.7.
LRMS (EI, 70 eV): m/z (%) = 138 (M+, 84), 123 (100).
1H NMR (500 MHz, CDCl3): d = 5.22–5.17 (m, 1 H), 2.65 (t, J = 5.0
Hz, 2H), 2.49–2.47 (m, 2 H), 2.36 (s, 3 H), 1.34 (s, 3 H), 1.33 (s, 3
H).
13C NMR (125 MHz, CDCl3): d = 203.5, 182.8, 162.8, 133.2, 68.4,
34.9, 32.5, 21.8, 19.1.
2-Benzoyl-3-methylcyclopent-2-enone (2i)11
Colorless oil.
IR (film): 1699, 1653 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.81 (d, J = 8.5 Hz, 2 H), 7.59 (t,
J = 7.5 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 2 H), 2.76 (t, J = 5.0 Hz, 2 H),
2.60 (t, J = 5.0 Hz, 2 H), 2.16 (s, 3 H).
LRMS (EI, 70 eV): m/z (%) = 182 (M+, 4), 123 (100).
HRMS (EI): m/z calcd for C10H14O3 (M+): 182.0942; found:
182.0940.
13C NMR (125 MHz, CDCl3): d = 205.0, 193.3, 179.4, 141.3, 136.6,
133.8, 129.4, 128.5, 35.2, 32.6, 18.6.
LRMS (EI, 70 eV): m/z (%) = 200 (M+, 68), 199 (100).
Methyl 2,4-Dimethyl-5-oxocyclopent-1-enecarboxylate (2d)7a
Colorless oil.
IR (film): 1740, 1718 cm–1.
2-Benzoyl-3-phenylcyclohex-2-enone (3j)
White solid; mp 110.3–111.4 °C.
1H NMR (500 MHz, CDCl3): d = 3.85 (s, 3 H), 2.93, 2.89 (dd,
J = 7.0, 7.0 Hz, 1 H), 2.50–2.47 (m, 1 H), 2.40 (s, 3 H), 2.30, 2.26
(dd, J = 2.5, 2.5 Hz, 1 H), 1.21 (d, J = 7.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 205.9, 183.8, 163.7, 130.9, 51.7,
41.6, 40.3, 19.2, 16.2.
IR (KBr): 1681, 1644 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.73 (d, J = 7.0 Hz, 2 H), 7.45–
7.41 (m, 1 H), 7.30 (t, J = 7.5 Hz, 2 H), 7.26–7.24 (m, 2 H), 7.21–
7.19 (m, 3 H), 2.87 (t, J = 6.0 Hz, 2 H), 2.64 (t, J = 6.0 Hz, 2 H),
2.31–2.26 (m, 2 H).
LRMS (EI, 70 eV): m/z (%) = 168 (M+, 66), 137 (100).
13C NMR (125 MHz, CDCl3): d = 197.2, 196.6, 159.3, 138.5, 137.4,
136.7, 133.2, 129.3, 128.9, 128.4, 128.3, 127.0, 37.4, 31.7, 22.4.
Ethyl 4-Ethyl-2-methyl-5-oxocyclopent-1-enecarboxylate (2e)
Colorless oil.
IR (film): 1741, 1721 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.33–4.29 (m, 2 H), 2.84, 2.81 (dd,
J = 6.5, 6.5 Hz, 1 H), 2.38–2.33 (m, 5 H), 1.89–1.82 (m, 1 H), 1.45–
1.39 (m, 1 H), 1.35 (t, J = 7.5 Hz, 3 H), 0.96 (t, J = 7.5 Hz, 3 H).
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 88), 105 (96), 77 (100).
HRMS (EI): m/z calcd for C19H16O2 (M+): 276.1150; found:
276.1153.
2-Benzoyl-3-p-tolylcyclohex-2-enone (3k)
White solid; mp 85.3–86.3 °C.
13C NMR (125 MHz, CDCl3): d = 205.4, 183.0, 163.4, 132.1, 60.7,
IR (KBr): 1681, 1653 cm–1.
47.2, 39.1, 24.3, 19.2, 14.2, 11.3.
1H NMR (500 MHz, CDCl3): d = 7.74 (d, J = 7.5 Hz, 2 H), 7.45 (t,
J = 7.5 Hz, 1 H),7.33 (t, J = 8.0 Hz, 2 H), 7.15 (d, J = 8.5 Hz, 2 H),
7.01 (d, J = 8.0 Hz, 2 H), 2.87 (t, J = 6.5 Hz, 2 H), 2.63 (t, J = 7.0
Hz, 2 H), 2.30–2.25 (m, 2 H), 2.23 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 197.3, 196.9, 159.4, 139.6, 137.1,
136.8, 135.6, 133.2, 129.1, 129.0, 128.4, 127.1, 37.5, 31.9, 22.5,
21.2.
LRMS (EI, 70 eV): m/z (%) = 196 (M+, 4), 168 (44), 122 (100).
HRMS (EI): m/z calcd for C11H16O3 (M+): 196.1099; found:
196.1096.
Methyl 2,4,4-Trimethyl-5-oxocyclopent-1-enecarboxylate (2f)10
Colorless oil.
IR (film): 1747, 1721 cm–1.
LRMS (EI, 70 eV): m/z (%) = 290 (M+, 73), 275 (93), 105 (100).
1H NMR (500 MHz, CDCl3): d = 3.85 (s, 3 H), 2.55 (s, 2 H), 2.40
(s, 3 H), 1.13 (s, 6 H).
HRMS (EI): m/z calcd for C20H18O2 (M+): 290.1307; found:
290.1306.
13C NMR (125 MHz, CDCl3): d = 207.8, 182.6, 163.8, 129.4, 51.6,
2-Benzoyl-3-m-tolylcyclohex-2-enone (3l)
Colorless oil.
IR (film): 1682, 1649 cm–1.
49.5, 43.8, 24.8, 19.1.
LRMS (EI, 70 eV): m/z (%) = 182 (M+, 69), 167 (100).
Ethyl 2-Methyl-6-oxocyclohex-1-enecarboxylate (2g)6a
White solid; mp 35.2–36.7 °C.
IR (KBr): 1713, 1692 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.33–4.29 (m, 2 H), 2.44–2.38 (m,
4 H), 2.04–2.00 (m, 5 H), 1.33 (t, J = 7.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 195.0, 166.8, 160.0, 133.2, 61.2,
36.8, 31.5, 22.0, 21.6, 14.1.
LRMS (EI, 70 eV): m/z (%) = 182 (M+, 24), 136 (76), 99 (100).
1H NMR (500 MHz, CDCl3): d = 7.73 (d, J = 8.0 Hz, 2 H), 7.46–
7.42 (m, 1 H), 7.32 (t, J = 7.5 Hz, 2 H), 7.09–7.00 (m, 4 H), 2.87 (t,
J = 6.0 Hz, 2 H), 2.64 (t, J = 6.0 Hz, 2 H), 2.30–2.25 (m, 2 H), 2.20
(s, 3 H).
13C NMR (125 MHz, CDCl3): d = 197.2, 196.7, 159.6, 138.5, 138.1,
137.4, 136.9, 133.1, 130.0, 128.9, 128.3, 128.3, 127.7, 124.2, 37.5,
31.8, 22.5, 21.2.
LRMS (EI, 70 eV): m/z (%) = 290 (M+, 46), 119 (100).
HRMS (EI): m/z calcd for C20H18O2 (M+): 290.1307; found:
290.1303.
2-Acetyl-3-methylcyclopent-2-enone (2h)7a
Colorless oil.
Synthesis 2010, No. 21, 3663–3669 © Thieme Stuttgart · New York

3668
Y. Liu et al.
PAPER
2-Benzoyl-3-o-tolylcyclohex-2-enone (3m)
Colorless oil.
IR (film): 1681, 1652 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.66 (t, J = 8.5 Hz, 2 H), 7.46–
7.43 (m, 1 H), 7.32 (t, J = 8.0 Hz, 2 H), 7.09–7.03 (m, 2 H), 6.96 (t,
J = 7.5 Hz, 1 H), 6.91 (d, J = 7.5 Hz, 1 H), 2.70–2.67 (m, 4 H),
2.32–2.27 (m, 2 H), 2.25 (s, 3 H).
1H NMR (500 MHz, CDCl3): d = 7.84 (t, J = 8.0 Hz, 2 H), 7.56 (t,
J = 7.5 Hz, 1 H), 7.45 (t, J = 8.0 Hz, 2 H), 2.52–2.48 (m, 4 H),
2.15–2.10 (m, 2 H), 1.87 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 197.1, 196.8, 159.8, 137.6, 136.7,
133.6, 129.0, 128.7, 37.2, 31.9, 22.0, 21.8.
LRMS (EI, 70 eV): m/z (%) = 214 (M+, 40), 213 (100).
Methyl 2-(4-Acetylphenyl)-6-oxocyclohex-1-enecarboxylate
13C NMR (125 MHz, CDCl3): d = 197.1, 195.6, 161.5, 138.7, 137.9,
137.0, 133.7, 133.1, 130.3, 128.7, 128.4, 126.6, 125.5, 37.7, 31.9,
22.7, 19.6.
LRMS (EI, 70 eV): m/z (%) = 290 (M+, 34), 175 (25), 119 (100).
HRMS (EI): m/z calcd for C20H18O2 (M+): 290.1306; found:
(3r)7a
Colorless oil.
IR (film): 1745, 1721, 1716 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.97 (d, J = 8.5 Hz, 2 H), 7.44 (d,
J = 8.0 Hz, 2 H), 3.60 (s, 3 H), 2.76 (t, J = 6.0 Hz, 2 H), 2.63 (s, 3
H), 2.58 (t, J = 7.2 Hz, 2 H), 2.22–2.17 (m, 2 H).
290.1303.
2-Benzoyl-3-(2-methoxyphenyl)cyclohex-2-enone (3n)
Colorless oil.
13C NMR (125 MHz, CDCl3): d = 197.2, 194.9, 166.7, 158.2, 143.3,
137.6, 129.8, 128.6, 128.8, 52.2, 36.9, 31.1, 26.6, 22.1.
IR (film): 1676, 1654 cm–1.
LRMS (EI, 70 eV): m/z (%) = 272 (M+, 100).
1H NMR (500 MHz, CDCl3): d = 7.73 (d, J = 8.0 Hz, 2 H), 7.43–
7.40 (m, 1 H), 7.28 (t, J = 7.5 Hz, 2 H), 7.16–7.12 (m, 1 H), 7.04–
7.02 (m, 1 H), 6.78 (t, J = 7.5 Hz, 1 H), 6.68 (d, J = 8.5 Hz, 1 H),
3.66 (s, 3 H), 2.80 (t, J = 6.0 Hz, 2 H), 2.65 (t, J = 6.0 Hz, 2 H),
2.29–2.23 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 197.2, 195.8, 159.8, 155.1, 138.1,
136.8, 132.9, 130.2, 128.8, 128.7, 128.0, 127.5, 120.4, 110.5, 55.0,
37.9, 31.3, 22.6.
Acknowledgment
The authors thank the Scientific Research Fund of Hunan Provincial
Education Department (No. 08A037) and National Natural Science
Foundation of China (No. 20872112) for financial support.
References
LRMS (EI, 70 eV): m/z (%) = 306 (M+, 6), 275 (100).
HRMS (EI): m/z calcd for C20H18O3 (M+): 306.1256; found:
(1) Caine, D. In Comprehensive Organic Synthesis, Vol. 3;
Trost, B. M.; Fleming, I., Eds.; Pergamon Press: New York,
1991, 1–63.
306.1251.
(2) Pd: (a) Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc. 2005,
127, 17168. (b) Lomberget, T.; Bouyssi, D.; Balme, G.
Synthesis 2005, 311. (c) Fournet, G.; Balme, G.;
2-Benzoyl-3-(4-methoxyphenyl)cyclohex-2-enone (3o)
Colorless oil.
IR (film): 1679, 1654 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.75 (d, J = 8.5 Hz, 2 H), 7.45–
7.42 (m, 1 H), 7.32 (t, J = 8.0 Hz, 2 H), 7.24–7.21 (m, 2 H), 6.73–
6.71 (m, 2 H), 3.70 (s, 3 H), 2.87 (t, J = 6.5 Hz, 2 H), 2.62 (t, J = 6.5
Hz, 2 H), 2.29–2.23 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 197.1, 197.0, 160.3, 158.8, 136.6,
136.4, 133.1, 128.8, 128.8, 128.3, 113.7, 55.0, 37.3, 31.5, 22.3.
Van Hemelryck, B.; Gore, J. Tetrahedron Lett. 1990, 31,
5147. (d) Fournet, G.; Balme, G.; Gore, J. Tetrahedron
1991, 47, 6293. (e) Balme, G.; Bouyssi, D.; Faure, R.; Gore,
J.; Van Hemelryck, B. Tetrahedron 1992, 48, 3891.
(f) Monteiro, N.; Gore, J.; Balme, G. Tetrahedron 1992, 48,
10103. Mo: (g) McDonald, F. E.; Olson, T. C. Tetrahedron
Lett. 1997, 38, 7691. Cu: (h) Bouyssi, D.; Monteiro, N.;
Balme, G. Tetrahedron Lett. 1999, 40, 1297. (i) Perez-
Hernandez, N.; Febles, M.; Perez, C.; Perez, R.; Rodriguez,
M. L.; Foces-Foces, C.; Martin, J. D. J. Org. Chem. 2006,
71, 1139. Ti: (j) Kitagawa, O.; Suzuki, T.; Inoue, T.;
Watanabe, Y.; Taguchi, T. J. Org. Chem. 1998, 63, 9470.
Hg: (k) Boaventura, M. A.; Conia, J. M. Synthesis 1983,
801.
LRMS (EI, 70 eV): m/z (%) = 306 (M+, 100), 250 (46), 105 (68).
HRMS (EI): m/z calcd for C20H18O3 (M+): 306.1256; found:
306.1258.
3-(4-Acetylphenyl)-2-benzoylcyclohex-2-enone (3p)
White solid; mp 130.6–131.8 °C.
IR (KBr): 1683, 1653, 1647 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.80 (d, J = 8.5 Hz, 2 H), 7.73 (d,
J = 7.0 Hz, 2 H), 7.47 (t, J = 7.0 Hz, 1 H), 7.36–7.27 (m, 4 H), 2.87
(t, J = 5.0 Hz, 2 H), 2.67 (t, J = 6.0 Hz, 2 H), 2.51 (s, 3 H), 2.33–
2.31 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 197.3, 196.9, 196.2, 157.8, 143.1,
138.3, 137.2, 136.6, 133.6, 129.0, 128.6, 128.4, 127.3, 37.4, 31.6,
26.6, 22.5.
(3) For papers on Lewis acid mediated reactions, see, for Ti or
Zn (an example): (a) Kitagawa, O.; Suzuki, T.; Inoue, T.;
Watanabe, Y.; Taguchi, T. J. Org. Chem. 1998, 63, 9470.
Sn: (b) Kitagawa, O.; Fujiwara, H.; Suzuki, T.; Taguchi, T.;
Shiro, M. J. Org. Chem. 2000, 65, 6819.
(4) Au: (a) Yang, S.; Ferrali, A.; Sladojevich, F.; Campbell, L.;
Dixon, D. J. J. Am. Chem. Soc. 2009, 131, 9140.
(b) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am.
Chem. Soc. 2004, 126, 4526. (c) Staben, S. T.; Kennedy-
Smith, J. J.; Toste, F. D. Angew. Chem. Int. Ed. 2004, 43,
5350. (d) Mezailles, N.; Ricard, L.; Gagosz, F. Org. Lett.
2005, 7, 4133. (e) Ochida, A.; Ito, H.; Sawamura, M. J. Am.
Chem. Soc. 2006, 128, 16486. (f) Pan, J.-H.; Yang, M.; Gao,
Q.; Zhu, N.-Y.; Yang, D. Synthesis 2007, 2539. (g) Ito, H.;
Makida, Y.; Ochida, A.; Ohmiya, H.; Sawamura, M. Org.
Lett. 2008, 10, 5051. (h) Kuninobu, Y.; Kawata, A.; Takai,
K. Org. Lett. 2005, 7, 4823.
LRMS (EI, 70 eV): m/z (%) = 319 (M+, 73), 318 (100), 105 (95).
HRMS (EI): m/z calcd for C21H18O3 (M+): 318.1256; found:
318.1253.
2-Benzoyl-3-methylcyclohex-2-enone (3q)12
White solid; mp 71.0–72.3 °C.
IR (KBr): 1650, 1659, 1641 cm–1.
Synthesis 2010, No. 21, 3663–3669 © Thieme Stuttgart · New York

PAPER
(5) Ni: Gao, Q.; Zheng, B.-F.; Li, J.-H.; Yang, D. Org. Lett.
Conia-Ene Cyclization of Linear b-Alkynic b-Dicarbonyls
3669
(8) Deng, C.-L.; Song, R.-J.; Liu, Y.-L.; Li, J.-H. Adv. Synth.
Catal. 2009, 351, 3096.
2005, 7, 2185.
(6) In: (a) Tsuji, H.; Yamagata, K.-i.; Itoh, Y.; Endo, K.;
Nakamura, M.; Nakamura, E. Angew. Chem. Int. Ed. 2007,
46, 8060. (b) Itoh, Y.; Tsuji, H.; Yamagata, K.-i.; Endo, K.;
Tanaka, I.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc.
2008, 130, 17161. (c) Takahashi, K.; Midori, M.; Kawano,
K.; Ishihara, J.; Hatakeyama, S. Angew. Chem. Int. Ed. 2008,
47, 6244.
(9) Snider, B. B.; Merritt, J. E.; Dombroski, M. A.; Buckman, B.
O. J. Org. Chem. 1991, 56, 5544.
(10) Crimmins, M. T.; Mascarella, S. W.; DeLoach, J. A. J. Org.
Chem. 1984, 49, 3033.
(11) D’Ascoli, R.; D’Auria, M.; Iavarone, C.; Piancatelli, G.;
Scettri, A. J. Org. Chem. 1980, 45, 4502.
(12) Pei, T.; Wang, X.; Widenhoefer, R. A. J. Am. Chem. Soc.
(7) Cu/Ag: (a) Deng, C.-L.; Song, R.-J.; Guo, S.-M.; Wang, Z.-
Q.; Li, J.-H. Org. Lett. 2007, 9, 5111. (b) Deng, C.-L.; Zou,
T.; Wang, Z.-Q.; Song, R.-J.; Li, J.-H. J. Org. Chem. 2009,
74, 412. (c) Yang, T.; Ferrali, A.; Sladojevich, F.; Campbell,
L.; Dixon, D. J. J. Am. Chem. Soc. 2009, 131, 9140.
2003, 125, 648.
Synthesis 2010, No. 21, 3663–3669 © Thieme Stuttgart · New York