Cationic vanadium(IV) complexes as efficient catalysts for nazarov cyclizations

Article abstract of DOI:10.1002/ejoc.200700156

Vanadium(IV) species generated in situ from V(salen)Cl₂ complexes (1) by reaction with 2 equiv. of AgSbF₆ are effective catalysts for Nazarov cyclizations. Thus, dialkenyl ketones bearing α-ester groups are efficiently converted to c

Full text of DOI:10.1002/ejoc.200700156

FULL PAPER
DOI: 10.1002/ejoc.200700156
Cationic Vanadium(IV) Complexes as Efficient Catalysts for Nazarov
Cyclizations
Irene Walz,[a] Andreas Bertogg,[a] and Antonio Togni*[a]
Keywords: Electrocyclic reactions / Homogeneous catalysis / Vanadium / Schiff bases
Vanadium(IV) species generated in situ from V(salen)Cl2
complexes (1) by reaction with 2 equiv. of AgSbF6 are effec-
tive catalysts for Nazarov cyclizations. Thus, dialkenyl
ketones bearing α-ester groups are efficiently converted to
corresponding cyclopentenones in good yields at room tem-
perature, in the presence of 2 mol-% catalyst. Under such
conditions full conversion takes place within minutes for sub-
strates bearing an electron-donating group at position 1 of
the 1,4-dien-3-one system.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
often formed by chloride abstraction from a suited corre-
sponding precursor, are required for both good conversion
and enantioselectivity in the Nazarov cyclization.[5] With
this in mind, we prepared the new achiral dichloridovanadi-
um(IV) complex 1a as well as the analogous chiral deriva-
tive 1b shown in Figure 2.
Introduction
Five-membered carbocycles are useful building blocks in
synthetic chemistry. One of the most versatile approaches
to their synthesis is the Nazarov cyclization,[1] a pericyclic
reaction involving a conratotory 4π process of a pentadienyl
cation (Figure 1). This reaction has witnessed increasing
interest in the past decade.
Figure 1. Nazarov cyclization pathway.
In general, to promote the reaction high temperature
and/or strong Lewis acids are required, one or more mo-
lar equiv. of which are necessary. Searching for milder alter-
natives, such as reactions at ambient temperature and Lewis
acids that can be used in catalytic amounts,[2] several re-
earch groups have recently reported new developments in
Nazarov chemistry, including a few enantioselective vari-
ants of the reaction using either catalytic or stoichiometric
amounts of metal complexes bearing chiral ligands.[3] How-
ever, this approach still remains quite rare. The stepwise
nature of the Nazarov cyclization has been discussed in
early mechanistic works.[4]
Figure 2. Vanadium salen complexes 1a and 1b.
The chemistry of vanadium(IV) is dominated by the
stable VO2+ entity and a large amount of data on vanadyl
complexes containing tetradentate salen ligands are avail-
able.[6] The synthetic applications of oxovanadium deriva-
tives are basically limited to oxidation reactions[7] and only
few examples of other C–C or C–O bond-forming reactions
catalyzed by oxovanadium(IV) complexes are known.[8]
Surprisingly, even though a large number of dichlorido-
vanadium complexes have been described, as obtained by
known deoxygenation reactions of oxovanadium species,[9]
it appears that VIVCl2 complexes have not been used as cat-
alysts or catalyst precursors before.
Results and Discussion
Previous studies have shown that coordinatively unsatu-
rated cationic complexes bearing C2 symmetric ligands,
[a] Department of Chemistry and Applied Biosciences, Swiss Fed-
eral Institute of Technology, ETH Zürich,
Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland
2650
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2650–2658

Efficient Catalysts for Nazarov Cyclizations
FULL PAPER
[14]
Our rationale for using dichlorido(salen)vanadium com- resulting alcohol was oxidized with MnO2
or DMP
plexes for Nazarov cyclization is based on the following (Dess–Martin periodane).[15] Subsequent Knoevenagel con-
reasons. i. Treatment of the dichloridovanadium complex densation of the β-keto ester 3 with the appropriate alde-
with a chloride abstracting agent should form an extremely hyde gave the desired dialkenyl ketones[16] with overall
reactive dicationic species, which can serve as a Lewis-acidic yields of 29–71% (Table 1).
catalyst. ii. Many metal salen complexes displaying the cis-
In order to introduce bulkier ester or amide groups at
β configuration are known.[10] This configuration, which the C2 position of the dialkenyl ketone system, the ethyl
should also be accessible for the [V(salen)]2+ fragment, pro- ester 4a was saponified to give the corresponding acid,
vides two coordination sites in mutual cis position, suited which was then treated with the appropriate alcohol or
for the coordination of the two carbonylic oxygen atoms of amine to afford the desired products in overall yields of 34–
a Nazarov substrate in a bidentate manner.[11]
62% (Table 2).
It has been previously reported that the electronic prop-
erties of the Nazarov substrate has a strong influence on
both cyclization rates and efficiency of the reaction.[2a,12]
With this in mind, we have prepared and tested three dif-
ferent types of substrates (Figure 3) representing different
polarization states of the basic dialkenyl ketone structure.
All substrates were obtained by standard synthetic pro-
cedures and have been partly reported before.
Table 2. Modification of substrate 4a.[a]
Compound
R
% Yield[b]
4j
OBn
59
34
55
62
4k
4l
OMES[c]
ONp[d]
NBn2
4m
[a] Reagents and conditions: i. KOH, EtOH, H2O, 55 °C. ii. ROH,
DMAP, DCC, CH2Cl2, 0 °C; ii. (amide synthesis): Bn2NH, DMAP,
DCC, DMF, room temp. [b] Isolated overall yields of 4j–m. [c]
MES = 2,4,6-trimethylphenyl. [d] Np = 1-naphthyl.
Initial experiments with the vanadium system 1a, after
in-situ activation with two equiv. of AgSbF6, were carried
out with Nazarov substrates of type 5. However, compound
Figure 3. The types of dialkenyl ketones tested in this study.
Thus, substrates 4 were obtained by the addition of the 5a did not give any cyclized product even not after eleven
enolate of ethyl acetate to either an aldehyde or an acyl days at room temperature in CH2Cl2 with 2 mol-% of the
chloride. In the case of the addition to the aldehyde,[13] the vanadium complex. For comparison, the more polarized
Table 1. Synthesis of dialkenyl ketones.[a]
Compound
R1
R2
% Yield[b]
4a
4b
4c
4d
4e
4f
4g
4h
4i
Me
Me
Me
Me
Me
Ph
Ph
H
2,4,6-trimethoxyphenyl
4-methoxyphenyl
2,4,6-trimethoxyphenyl
phenyl
71
64
59
71
57
58
64
29
25
4-nitrophenyl
2,4,6-trimethoxyphenyl
4-methoxyphenyl
4-methoxyphenyl
2,4,6-trimethoxyphenyl
H
[a] 3a–g were prepared starting from 2a–b. Reagents and conditions i. (A): (1) LDA, THF, EtOAc, –78 °C. (2) MnO2, CH2Cl2; or DMP,
CH2Cl2. 3c was prepared from 2c. Reagents and conditions ii. (B): (1) (COCl2)2, DMF, CH2Cl2, 0 °C; (2) LDA, THF, EtOAc, –78 °C.
iii. (a) TiCl4, CCl4, THF, R2CHO, pyridine, 0 °C; (b) R2CHO, AcOH, piperidine, benzene, 100 °C. [b] Isolated overall yields of 4a–i.
Eur. J. Org. Chem. 2007, 2650–2658
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2651

I. Walz, A. Bertogg, A. Togni
FULL PAPER
substrate 5b cyclized within three days under the same con- Table 3. Influence of different solvents on the cyclization of 4a.
ditions. Even though the corresponding product was ob-
tained in very good yield, the reaction is still very slow.
Moreover, substrate 6 was cyclized within twenty minutes
affording the product in good yield, however, as a mixture
of regioisomers.[17]
We therefore focused on substrates of type 4, which
turned out to be the most reactive with respect to our vana-
dium catalyst. Initial experiments addressed the nature of
the activating reagent and were carried out by using sub-
Entry
Solvent
Time [min]
% Yield
strate 4a in dichloromethane at room temperature. These
experiments showed that only AgSbF6 was able to generate
a catalytically active species, whereas the other common
chloride abstracting agents [Et3O]PF6, TlPF6, AgPF6, and
AgBF4 did not. This may be due to two main reasons: i.
Ag+ is usually a more efficient chloride scavenger than tri-
ethyloxonium and Tl+.[18] ii. The possible coordinating
properties of the anion play a crucial role. Only the least
1
2
3
4
CH2Cl2
toluene
THF
2
5
10
3 d
94
85
41[a]
20
CH3CN
[a] Mixture of regioisomers.
Table 4. Nazarov cyclization under optimized conditions.
–
coordinating SbF6 is compatible with the postulated inter-
action of the substrate with the VIV metal center.[19] There-
fore, we assume that a dicationic vanadium complex is the
active catalytic species. The formation of a white precipitate
(AgCl) and a color change of the solution from dark blue
to dark purple followed the addition of AgSbF6 to the
dichloridovanadium complex 1a. No noticeable effect of the Com-
AgCl precipitate present in the reaction mixture could be
R1
R2
R3
Time
% Yield
pound
7a
7b
7c
7d
7e
7f
7g
7j
7k
7l
Me
Me
Me
Me
Me
Ph
Et
Et
Et
Et
Et
Et
Et
Bn
MES[d]
Np[e]
TMP[a]
MES
2 min
5 min
10 min
3 h
94
63[b]
37
87
80
98
97
65
99
80
discerned. Removal of AgCl by filtration did not change
neither the reaction time nor the yield. We also took the
precaution of verifying that any soluble silver salt alone
would be able to catalyze the reaction and found that
1 equiv. of AgSbF6 led to only ca. 17% conversion of 4a in
2 d. This means that the Ag-catalyzed reaction constitutes
only a very weak and therefore negligible background.
Using the dialkenyl ketone 4a we also tested different
solvents and found that in CH2Cl2 the reaction is fastest,
affording the best yield at room temperature (Table 3). In-
deed, when working with 2 mol-% of the catalyst precursor
1a the reaction reaches complete conversion within ca.
2 min, as shown by TLC monitoring. Coordinating solvents
drastically reduce the reaction rate.
PMP[c]
Ph
4-NO2Ph
TMP
PMP
TMP
TMP
TMP
6 h
10 min
10 min
5 min
15 min
1.5 h
Ph
Me
Me
Me
[a] TMP = 2,4,6-trimethoxyphenyl. [b] Cyclization of 4b gave an
exocyclic double bond isomer, see Scheme 1. [c] PMP = 4-meth-
oxyphenyl. [d] MES = 2,4,6-trimethylphenyl. [e] Np = 1-naphthyl.
Under these optimized conditions a number of dialkenyl
ketones of type 4 was subjected to the V-catalyzed cycliza-
tion and the results are reported in Table 4.
From these data it is apparent that the electronic proper-
ties of the substituent at C1 of the 3-oxopentadiene system
considerably influences the reactivity of compounds 4 in
this V-catalyzed cyclization. Thus, dialkenyl ketone 4a,
bearing the electron-rich trimethoxyphenyl group, cyclize
within two minutes, whereas the cyclization of the simple
Scheme 1. Cyclization of 4b.
phenyl derivative 4d takes three hours. Moreover, the reac- clic double bond isomers. Cyclization of dialkenyl ketones
tion of dialkenyl ketone 4e, having a 4-nitrophenyl group at 4j–l, bearing relatively bulky ester groups, results in slightly
C1, requires about six hours for full conversion.
lower reaction rates, whereas dialkenyl ketone 4m, having
Nearly all dialkenyl ketones 4 give the expected cyclopen- an amide instead of an ester group, do not show any ap-
tenone derivatives as products with an endocyclic double preciable conversion after two days at room temperature.
bond. Surprisingly, however, 4b affords the cyclic enol 7b in
which the olefinic double bond is exocyclic (Scheme 1).
Dialkenyl ketones 4h–i and 8 (Figure 4) were also sub-
jected to optimized reaction conditions. Substrate 8 was
Furthermore, substrates 4c react within minutes, but give synthesized similarly to ketones 4 via Knoevenagel conden-
an only modest yield of a mixture of endocyclic and exocy- sation of β-keto ester 3a with 4,6-dimethoxysalicylaldehyde,
2652
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2650–2658

Efficient Catalysts for Nazarov Cyclizations
FULL PAPER
followed by lactonization with concomitant loss of etha- the first unsuccessful attempts towards an asymmetric vari-
nol.[20] In the cases of 4h–i no cyclization could be ob- ant of the reaction using a catalyst derived from complex
served, even not after two days at room temperature. We 1b, we will further explore chiral enantiopure catalysts.
tentatively ascribe this lack of reactivity to the preferred s-
cis conformation of the C3–C4 bond in these two substrates
Experimental Section
favored by the absence of substituents at C4. The failure of
the cyclization in the case of 8 can be rationalized in terms
of rigidity of the lactone, detrimental in view of the required
conrotatory movement.
General: All catalysis experiments were conducted under an atmo-
sphere of argon or nitrogen using standard Schlenk techniques or
in a glove box. All vanadium-promoted Nazarov cylizations were
carried out at ambient temperature in the glove box, due to the air
sensitivity of the involved dicationic species. All solvents were
stored over activated molecular sieves (4 Å) unless otherwise indi-
cated. In the case of freshly distilled solvents, the following drying
agents were used: Na/benzophenone for THF and Et2O; Na for
toluene; CaH2 for CH2Cl2. Chromatography was carried out with
Merck silica gel 60. The NMR spectra were recorded at 25 °C on
Bruker Avance 250 (250.1 MHz, 1H; 62.9 MHz, 13C), 300
(300.1 MHz, 1H; 75.5 MHz, 13C) spectrometers. 1H and 13C chemi-
cal shifts (δ) were referenced internally by the residual solvent sig-
nal. High-resolution MALDI mass spectra were measured by the
analytical service of the Organic Chemistry Laboratory of the ETH
Zürich on an IonSpec ultima FT MALDI mass spectrometer. Ele-
mental analyses were obtained on a Leco CHN-900 analyzer. All
commercially available chemicals were used without further
purification. {N,NЈ-Bis[3,5-bis(tert-butyl)salicylidene]ethylene-1,2-
diamino}vanadium(IV) oxide[21] and {(1R,2R)-N,NЈ-bis[3,5-bis-
Figure 4. Conformations of divinyl ketones.
Because of their propensity to act as bidentate ligands
(two-points binding), we reckon that dialkenyl ketones 4
can be suitable substrates for a catalytic asymmetric pro-
cess. However, our attempts to develop an asymmetric ver-
sion of the Nazarov cyclization using the chiral vanadium
salen precursor 1b were unsuccessful. In fact, when the re- (tert-butyl)salicylidene]cyclohexane-1,2-diamino}vanadium(IV) ox-
ide[22] were prepared according to the literature procedures.
action of 4a was carried out using a catalyst generated in
situ from complex 1b, in different solvents, with different
catalyst loadings, and at various temperatures, the product
was invariably isolated in racemic form (Table 5).
{N,NЈ-Bis[3,5-bis(tert-butyl)salicylidene]ethylene-1,2-diamino}-
vanadium(IV) Dichloride (1a):[23] {N,NЈ-Bis[3,5-bis(tert-butyl)sal-
icylidene]ethylene-1,2-diamino}vanadium(IV) oxide (2 g,
3.59 mmol. 1 equiv.) was dissolved in dry toluene (50 mL) under
argon atmosphere and SOCl2 (0.33 mL, 4.56 mmol, 1.3 equiv.) was
added to the reaction mixture. The green reaction solution turned
immediately to dark blue and a precipitate was formed. The reac-
tion mixture was refluxed for 30 min. After cooling to ambient tem-
perature, the solvent was removed to dryness; the black residue was
washed with cold toluene. The crude complex was recrystallized by
dissolution in a small volume of EtOH (1 mL) followed by the ad-
dition of n-hexane (3 mL) and subsequent slow evaporation. The
black solid was washed with cold n-hexane (2ϫ3 mL) to afford
Table 5. Attempted asymmetric Nazarov cyclization of 4a.[a]
(2.2 g, 100%) the title compound. IR (KBr): ν = 2956.6, 1605.1,
˜
Entry
Solvent
1b [mol-%]
T [°C]
% Yield
1541.4, 1435.5, 1363.6, 1269.9, 1248.1, 917.1, 873.6, 843.7, 758.4,
597.1, 582.7 cm–1. C32H46Cl2N2O2V (612.57): calcd. C 62.74, H
7.57, N 4.57, O 5.22, Cl 11.57; found C 62.46, H 7.54, N 4.59, Cl
1 1 . 2 9 . M S ( H R M A L D I ) : m / z 5 7 6 . 2 6 8 7 ( c a l c d . f o r
C32H46ClN2O2V); found 575.2682 [M+ – Cl].
1
2
3
4
5
CH2Cl2
CH2Cl2
toluene
THF
2
100
2
2
2
20
–78
20
20
20
93
92
80
38
25
CH3CN
{(1R,2R)-N,NЈ-Bis[3,5-bis(tert-butyl)salicylidene]cyclohexane-1,2-
diamino}vanadium(IV) Dichloride (1b): This compound was synthe-
sized analogously to 1a; reaction time 30 min, yield 86%, black
[a] All cyclizations afforded racemic cyclopentenone 7a.
solid. IR (KBr): ν = 2953.2, 1605.4, 1642.2, 1542.2, 1464.2, 1364.1,
˜
1271.1, 1243.6, 919.8, 868.9, 850.8, 760.1, 568.0 cm– 1
.
Conclusions
C36H52Cl2N2O2V (666.67): calcd. C 64.86, H 7.86, N 4.20, O 4.80,
Cl 10.64; found C 64.83, H 7.83, N 4.12, O 5.02, Cl 10.51. MS
(HR MALDI): m/z 630.3157 (calcd. for C36H52ClN2O2V), found
630.3164 [M+ – Cl].
In conclusion, we have developed the first vanadium(IV)-
catalyzed Nazarov cyclization. Good to excellent yields can
be obtained for substrates displaying 1,2,4,5-tetrasubstitu-
tion pattern of the dialkenyl ketone system. The short reac-
tion times of just a few minutes when working at room
temp. with 2 mol-% of the vanadium complex and therefore
average TOF’s of up to 25 min–1 are unprecedented for
Knoevenagel condensations were carried out by Method A, a repre-
sentative procedure of which is given below.
Method A.[24] Ethyl 4-Methyl-3-oxo-5-phenyl-2-(2,4,6-trimeth-
oxybenzylidene)pent-4-enoate (4a): To a stirred solution of ethyl 4-
transition-metal-catalyzed Nazarov cyclizations. Despite methyl-3-oxo-5-phenylpent-4-enoate (2 g, 8.61 mmol, 1 equiv.) in
Eur. J. Org. Chem. 2007, 2650–2658
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2653

I. Walz, A. Bertogg, A. Togni
FULL PAPER
benzene (50 mL) AcOH (0.25 mL, 4.3 mmol, 0.5 equiv.), piperidine
(0.08 mL, 0.86 mmol, 0.1 equiv.) and 2,4,6-trimethoxybenzal-
dehyde (1.69 g, 8.61 mmol, 1 equiv.) were added. The yellow solu-
tion was refluxed in a Dean–Stark apparatus at 100 °C. After 4 h,
the reaction was complete, the orange solution was cooled down
to ambient temperature and diluted with water and diethyl ether
(each 50 mL). The organic layer was separated and the aqueous
layer was extracted with diethyl ether (50 mL). The combined or-
ganic layers were washed with 1  HCl (2 ϫ 50 mL), NaHCO3
(2ϫ50 mL), dried with MgSO4 and the solvent removed under re-
duced pressure. The residue was purified by column chromatog-
raphy eluting with cyclohexane/ethyl acetate (7:3), Rf = 0.35 to give
the title compound as a yellow solid (3.4 g, 96%) and as an E/Z
found C 79.76, H 7.31. MS (HR MALDI): m/z 363.1960 (calcd.
for C24H27O3), found 363.1955 [MH+].
Ethyl Benzylidene-4-methyl-3-oxo-5-phenyl-4-pentenoate (4d) and
Ethyl 4-Methyl-2-(4-nitrobenzylidene)-3-oxo-5-phenyl-4-enoate (4e)
were synthesized according to the procedure given in ref.[3b]
Ethyl 3-Oxo-4,5-diphenyl-2-(2,4,6-trimethoxybenzylidene)pent-4-en-
oate (4f): This compound was prepared according to method A,
yield 90%, E/Z (1:9); cyclohexane/TBME (3:2); yellow foam; Rf =
1
3
0.25. H NMR (300.1 MHz, CDCl3): δ = 1.30 (t, JH,H = 7.2 Hz,
3 H, OCH2CH3), 3.76 (s, 6 H, 2 x OCH3), 3.86 (s, 3 H, OCH3),
3
4.21 (q, JH,H = 7.2 Hz, 2 H, OCH2CH3), 6.13 (s, 2 H, CHAr),
7.01–7.05 (m, 2 H, CHAr), 7.17–7.21 (m, 5 H, CHAr), 7.35–7.38
(m, 3 H, CHAr), 7.61 (s, 1 H, CH), 7.99 (s, 1 H, CH) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 14.29, 55.06, 55.40, 61.00, 90.34,
105.52, 127.56, 128.16, 128.25, 128.74, 130.20, 130.46, 135.24,
135.61, 135.99, 139.83, 140.57, 159.63, 163.38, 166.68, 194.36 ppm.
C29H28O6 (472.53): calcd. C 73.71, H 5.97; found C 73.54, H 6.03.
MS (HR MALDI): m/z 473.1964 (calcd. for C29H29O6), found
473.1959 [MH+].
1
3
mixture (1:9). H NMR (300.1 MHz, CDCl3): δ = 1.17 (t, JH,H
=
3
7.2 Hz, 3 H, OCH2CH3, minor isomer), 1.25 (t, JH,H = 7.2 Hz, 3
4
H, OCH2CH3, major isomer), 2.16 (d, JH,H = 1.2 Hz, 3 H, CH3,
4
major isomer), 2.28 (d, JH,H = 1.2 Hz, 3 H, CH3, minor isomer),
3.68 (s, 6 H, 2 OCH3, major isomer), 3.76 (s, 3 H, OCH3, major
3
isomer), 3.82 (s, 3 H, OCH3, minor isomer), 4.16 (q, JH,H
=
3
7.2 Hz, 2 H, OCH2CH3, minor isomer), 4.24 (q, JH,H = 7.2 Hz, 2
H, OCH2CH3, major isomer), 6.02 (s, 2 H, CHAr, major isomer),
6.10 (s, 2 H, CHAr, minor isomer), 7.25–7.40 (m, 5 H, CHAr), 7.45
(s, 1 H, CH, minor isomer), 8.06 (s, 1 H, CH, major isomer) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 13.02, 14.08, 14.25, 14.32,
55.05, 55.35, 55.40, 55.44, 60.39, 60.89, 90.31, 90.34, 105.38,
105.75, 128.22, 128.30, 128.35, 128.38, 129.34, 129.51, 129.64,
133.38, 135.43, 135.58, 135.96, 136.33, 136.80, 137.67, 139.16,
139.71, 159.53, 159.54, 163.27, 163.39, 166.86, 167.41, 196.20,
196.73 ppm. C24H26O6 (410.47): calcd. C 70.23, H 6.38; found C
70.20, H 6.48. MS (HR MALDI): m/z 433.1627 (calcd. for
C24H26O6Na), found 433.1622 [MNa+].
Ethyl 2-(4-Methoxybenzylidene)-3-oxo-4,5-diphenylpent-4-enoate
(4g): This compound was prepared according to method A, yield
98%) E/Z (1:9); cyclohexane/TBME (3:2), yellow viscous oil, Rf =
0.28 cyclohexane/ethyl acetate (8:2). 1H NMR (300.1 MHz,
CDCl3): δ = 1.34 (t, 3JH,H = 7.2 Hz, 3 H, CH2CH3, minor isomer),
3
1.35 (t, JH,H = 7.2 Hz, 3 H, CH2CH3, major isomer), 3.79 (s, 3 H,
OCH3, minor isomer), 3.85 (s, 3 H, OCH3, major isomer) 4.30 (q,
3
3JH,H = 7.2 Hz, 2 H, CH2CH3, major isomer), 4.38 (q, JH,H
=
7.2 Hz, 2 H, CH2CH3, minor isomer), 6.82–7.59 (m, 10 H, CHAr,
both isomers), 7.69 (s, 1 H, CH), 7.83 (s, 1 H, CH) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 14.01, 14.29, 55.37, 55.41, 61.37, 61.62,
114.17, 114.37, 125.31, 125.92, 126.38, 128.13, 128.31, 128.61,
128.88, 128.92, 129.11, 129.43, 129.67, 129.70, 129.88, 130.35,
130.67, 130.98, 132.06, 132.22, 132.46, 134.44, 135.23, 135.45,
137.77, 137.88, 139.48, 140.66, 141.71, 142.84, 144.37, 161.45,
162.12, 165.37, 167.50, 196.88, 197.03 ppm. C27H24O4 (412.48):
calcd. C 78.62, H 5.86; found C 78.35, H 5.91. MS (HR MALDI):
m/z 413.1453 (calcd. for C27H25O4), found 413.1747 [MH+].
Ethyl 2-(4-Methoxybenzylidene)-4-methyl-3-oxo-5-phenylpent-4-en-
oate (4b): This compound was prepared according to method A,
yield 86%, cyclohexane/ethyl acetate (8:2), yellow oil, Rf = 0.37. 1H
3
NMR (300.1 MHz, CDCl3): δ = 1.29 (t, JH,H = 7.2 Hz, 3 H,
3
CH2CH3), 2.24 (s, 3 H, CH3), 3.82 (s, 3 H, OCH3), 4.28 (q, JH,H
4
= 7.2 Hz, 2 H, CH2CH3), 6.85 (d, JH,H = 8.4 Hz, 2 H, CHAr),
7.34–7.42 (m, 7 H, CHAr), 7.51 (s, 1 H, CH), 7.85 (s, 1 H, CH)
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 12.65, 14.23, 55.29, 61.28,
114.33, 125.81, 128.46, 128.98, 129.03, 129.94, 132.05, 135.59,
137.12, 141.79, 142.69, 161.30, 165.49, 198.55 ppm. C22H22O4
(350.41): calcd. C 75.41, H 6.33; found C 75.67, H 6.39. MS (HR
MALDI): m/z 373.1416 (calcd. for C22H22O4Na), found 373.1410
[MNa+].
Ethyl 2-(4-Methoxybenzylidene)-3-oxo-5-phenylpent-4-enoate (4h):
This compound was prepared according to ref.[3b], yield 96%, cy-
clohexane/ethyl acetate (9.5:0.5), yellow oil, Rf = 0.21. 1H NMR
3
(300.1 MHz, CDCl3): δ = 1.28 (t, JH,H = 7.2 Hz, 3 H, CH2CH3,
3
major isomer), 1.34 (t, JH,H = 7.2 Hz, 3 H, CH2CH3, minor iso-
mer), 3.75 (s, 3 H, OCH3, major isomer), 3.83 (s, 3 H, OCH3, minor
3
isomer), 4.28 (q, JH,H = 7.2 Hz, 2 H, CH2CH3, major isomer),
Ethyl 4-Methyl-3-oxo-5-phenyl-2-(2,4,6-trimethylbenzylidene)pent-
4-enoate (4c): This compound was prepared according to method
A, yield 80%, E/Z (4:6), cyclohexane/ethyl acetate (9.5:0.5), yellow
3
4.41 (q, JH,H = 7.2 Hz, 2 H, CH2CH3, major isomer), 6.81–6.93
(m, 2 H, CHAr, both isomers), 7.19–7.81 (m, 9 H, CHAr, CH,
both isomers), 7.86 (s, 1 H, CH, major isomer) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 14.04, 14.22, 55.29, 55.39, 61.37, 61.66,
114.34, 11437, 121.59, 125.51, 125.70, 127.20, 128.49, 128.56,
128.95, 129.02, 130.60, 130.90, 131.94, 132.26, 132.50, 134.26,
134.76, 141.33, 142.08, 144.44, 146.08, 161.46, 161.82, 165.29,
168.42, 186.25, 190.73, 196.18 ppm. C21H20O4 (336.39): calcd. C
74.98, H 5.99; found C 74.88, H 6.15. MS (HR MALDI): m/z
337.1440 (calcd. for C21H22O4), found 337.1434 [MH+].
1
3
oil, Rf = 0.26. H NMR (250.1 MHz, CDCl3): δ = 1.05 (t, JH,H
=
7.2 Hz, 3 H, CH2CH3, minor isomer), 1.36 (t, 3JH,H = 7.0 Hz, 3 H,
CH2CH3, major isomer), 1.89 (d, 4JH,H = 3.0 Hz, 3 H, CH3, major
isomer), 2.23 (s, major isomer, 6 H, CH3Ar), 2.25 (s, major isomer,
4
3 H, CH3Ar), 2.28 (d, JH,H = 3.0 Hz, 3 H, CH3, minor isomer),
2.31 (s, 6 H, CH3Ar, minor isomer), 2.33 (s, 3 H, CH3Ar, minor
3
isomer), 4.10 (q, JH,H = 7.2 Hz, 2 H, CH2CH3, minor isomer),
3
4.36 (q, JH,H = 7.0 Hz, 2 H, CH2CH3, minor isomer), 6.81 (s, 1
H, CHAr, major isomer), 6.92 (s, 1 H, CHAr, minor isomer), 7.28–
7.57 (m, 6 H, CHAr, CH, both isomers), 8.07 (s, 1 H, CH) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 12.62, 13.74, 13.77, 14.23,
20.37, 20.42, 20.98, 21.08, 60.92, 61.49, 128.10, 128.32, 128.46,
(1Z,4E)-4-Methyl-3-oxo-5-phenyl-2-(2,4,6-trimethoxybenzylidene)-
pent-4-enoic Acid (S1): To a stirred solution of KOH (3.38 g,
55.3 mmol, 10 equiv.) in EtOH/water (150:75 mL) ethyl (1Z,4E)-4-
methyl-3-oxo-5-phenyl-2-(2,4,6-trimethoxybenzylidene)pent-4-eno-
128.63, 128.72, 128.93, 129.57, 129.84, 130.37, 131.35, 134.83, ate (2.27 g, 5.53 mmol, 1 equiv.) was added and the mixture was
135.37, 135.38, 135.53, 135.56, 136.19, 137.34, 137.48, 137.51, heated quickly to 55 °C. After 9 h at this temperature, it was cooled
137.74, 137.80, 141.22, 141.37, 143.90, 143.95, 164.82, 165.00, to ambient temperature, and CH2Cl2 (100 mL) was added. The re-
195.53, 196.27 ppm. C24H26O3 (362.47): calcd. C 79.53, H 7.23;
action mixture was then quenched with 0.5  HCl (180 mL). The
2654
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2650–2658

Efficient Catalysts for Nazarov Cyclizations
two layers were separated; the aqueous layer was extracted with 125.6, 125.8, 126.0, 126.0, 126.2, 126.3, 126.3, 126.4, 126.8, 126.8,
FULL PAPER
CH2Cl2 (2ϫ100 mL). The combined organic layers were dried with
MgSO4, filtered and the solvent was removed under reduced pres-
sure to give 2.11 g (quant.) of orange foam. The carboxylic acid
was subjected to esterification without further purification. 1H
NMR (250.1 MHz, CDCl3): δ = 2.01 (d, 4JH,H = 1.0 Hz, 3 H, CH3),
3.74 (s, 6 H, 2 OCH3), 3.78 (s, 3 H, OCH3), 5.99 (s, 2 H, CHAr),
7.05–7.12 (m, 2 H, CHAr), 7.23–7.33 (m, 4 H, CHAr, CH), 8.37
126.9, 127.1, 127.2, 127.3, 127.5, 127.6, 127.6, 127.6, 127.7, 127.7,
127.8, 128.2, 128.2, 128.4, 128.5, 128.5, 128.8, 129.2, 129.7, 129.8,
129.9, 131.0, 131.7, 132.6, 134.6, 134.6, 134.6, 135.9, 135.9, 136.2,
136.5, 136.9, 136.9, 137.2, 137.4, 137.5, 137.6, 137.8, 138.2, 138.8,
140.4, 140.5, 146.8, 146.9, 146.9, 156.9, 159.6, 159.7, 160.0, 160.2,
163.6, 163.7, 164.0, 164.2, 164.6, 164.7, 165.0, 165.8, 194.7, 196.1,
196.9, 199.2 ppm. C32H28O6 (508.57): calcd. C 75.58, H 5.55; found
(s, 1 H, CH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 13.01, 55.41, C 75.55, H 5.73. MS (HR MALDI): m/z 531.1784 (calcd. for
55.44, 90.31, 105.89, 125.89, 128.27, 128.41, 129.46, 135.92, 135.94,
140.44, 141.57, 159.51, 163.91, 168.98, 199.02 ppm.
C32H28O6Na), found 531.1778 [MNa+].
(2Z,4E)-N,N-Dibenzyl-4-methyl-3-oxo-5-phenyl-2-(2,4,6-trimeth-
oxybenzylidene)pent-4-enamide (4m): To a stirred solution of
(1Z,4E)-4-methyl-3-oxo-5-phenyl-2-(2,4,6-trimethoxybenzylidene)-
pent-4-enoic acid (139 mg, 365 µmol, 1 equiv.) in DMF (15 mL)
dibenzylamine (71 µL, 365 µmol, 1 equiv.), HOBT (49 mg,
365 µmol, 1 equiv.) and DCC (82 mg, 397 µmol, 1.09 equiv.) were
added in this order. After 19 h the solvent was evaporated to dry-
ness. The residue was taken up in CH2Cl2, and the organic layer
was washed with H2O, dried with MgSO4, filtered and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography eluting with cyclohexane/MTBE (1:1), to
The esterifications of (1Z,4E)-4-methyl-3-oxo-5-phenyl-2-(2,4,6-tri-
methoxybenzylidene)pent-4-enoic acid were carried out by method
B as given below.
Benzyl 4-Methyl-3-oxo-5-phenyl-2-(2,4,6-trimethoxybenzylidene)-
pent-4-enoate (Method B) (4j): To a stirred solution of benzylic
alcohol (262 µL, 2.53 mmol, 1.5 equiv.), (1Z,4E)-4-methyl-3-oxo-5-
phenyl-2-(2,4,6-trimethoxybenzylidene)pent-4-enoic acid
(646.27 mg, 1.69 mmol, 1 equiv.) DMAP (31 mg, 253 µmol,
0.15 equiv.) and dichloromethane (15 mL) at 0 °C DCC (383 mg,
1.86 mmol, 1.1 equiv.) was added, giving a yellow reaction solution.
After 10 min at this temperature, a white precipitate was formed
and the reaction mixture was warmed to ambient temperature. Af-
ter 10 h, the reaction mixture was filtered, dried with MgSO4, fil-
tered and the solvent was removed under reduced pressure. The
residue was purified by column chromatography eluting with cyclo-
hexane/ethyl acetate (8:2), Rf = 0.3 to give 641 mg (80%) of an
yellow foam. 1H NMR (300.1 MHz, CDCl3): δ = 2.13 (s, 3 H,
CH3), 3.72 (s, 6 H, 2 OCH3), 3.82 (s, 3 H, OCH3), 5.26 (s, 2 H,
OCH2), 6.04 (s, 2 H, CHAr), 7.23–7.41 (m, 11 H, CHAr, CH), 8.14
(s, 1 H, CH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 13.09, 55.07,
55.39, 66.52, 90.28, 105.39, 127.82, 127.94, 128.18, 128.31, 128.37,
1
180 mg (88%) of an white foam. H NMR (300.1 MHz, CDCl3): δ
4
= 1.96 (d, JH,H = 1.2 Hz, 3 H, CH3), 3.69 (s, 6 H, OCH3), 3.75 (s,
3 H, OCH3), 4.62 (br., 2 H, C(O)NCH2), 4.73 (br., 2 H, C(O)-
NCH2), 6.01 (s, 2 H, CHAr), 7.09–7.13 (m, 2 H, CHAr), 7.22–7.39
(m, 14 H, CHAr, CH), 7.41–7.44 (m, 1 H, CHAr) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 12.97, 55.31, 55.34, 90.18, 106.35, 127.17,
127.42, 127.87, 127.99, 128.05, 128.47, 128.60, 129.42, 135.12,
135.87, 136.42, 136.92, 141.65, 158.41, 162.08, 170.66, 196.75 ppm.
C
36H35NO5 (561.68): calcd. C 76.98, H 6.28, N 2.49; found C
76.74, H 6.40, N 2.59. MS (HR MALDI): m/z 562.2593 (calcd. for
C36H36NO5), found 562.2588 [MH+].
128.86, 129.63, 136.02, 136.24, 136.35, 136.90, 139.90, 159.70, Ethyl 2-Benzoyl-3-(4-methoxyphenyl)acrylate (5a): This compound
163.46, 166.72, 196.16 ppm. C29H28O6 (472.53): calcd. 73.71, H was prepared according to method A, yield quant.), reaction time
5.97; found C 73.46, H 6.16. MS (HR MALDI): m/z 473.1964 12 h, hexane/ethyl acetate (8:2), yellow oil, Rf = 0.26. 1H NMR
3
(calcd. for C29H29O6), found 473.1959 [MH+].
(300.1 MHz, CDCl3): δ = 1.18 (t, JH,H = 7.2 Hz, 3 H, CH2CH3),
3
3.77 (s, 3 H, OCH3), 4.22 (q, JH,H = 7.2 Hz, 2 H, CH2CH3), 6.77
(d, JH,H = 8.7 Hz, 2 H, CHAr), 7.32–7.60 (m, 5 H, CHAr), 7.92
Mesityl 4-Methyl-3-oxo-5-phenyl-2-(2,4,6-trimethoxybenzylidene)-
pent-4-enoate (4k): This compound was prepared according to
method B, yield 46%, cyclohexane/ethyl acetate (8:2), yellow foam,
Rf = 0.2. 1H NMR (300.1 MHz, CDCl3): δ = 2.1 (s, 6 H, CH3),
2.18 (s, 3 H, CH3), 2.30 (s, 3 H, CH3), 3.76 (s, 6 H, 2 OCH3), 3.78
(s, 3 H, OCH3), 6.12 (s, 2 H, CHAr), 6.90 (s, 2 H, CHAr), 7.32–
3
(s, 1 H, CH), 7.98 (d, 3JH,H = 7.2 Hz, 2 H, CHAr) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 14.04, 55.28, 61.31, 114.28, 125.49, 128.65,
128.80, 129.15, 132.25, 133.77, 136.37, 142.307, 161.36, 165.30,
196.18 ppm. CAS number 25364-67-4.
7.42 (m, 5 H, CHAr), 7.55 (s, 1 H, CH), 8.26 (s, 1 H, CH) ppm. Ethyl 2-(Benzo[d][1,3]dioxol-5-ylcarbonyl)-3-(4-methoxyphenyl)-
13C NMR (62.9 MHz, CDCl3): δ = 13.08, 16.51, 20.79, 55.11,
acrylate (5b): This compound was prepared according to method
55.43, 90.32, 105.35, 127.59, 128.32, 128.42, 129.06, 129.62, 130.01,
135.08, 136.29, 136.32, 137.23, 140.24, 146.15, 160.03, 163.79, oil, Rf = 0.19. H NMR (250.1 MHz, CDCl3): δ = 1.23 (t, JH,H
165.11, 196.25 ppm. C31H32O6 (500.58): calcd. C 74.38, H 6.44;
B, yield 94%, reaction time 12 h, hexane/ethyl acetate (9:1), yellow
1
3
=
=
3
7.0 Hz, 3 H, CH2CH3), 3.79 (s, 3 H, OCH3), 4.25 (q, JH,H
found C 74.53, H 6.56. MS (HR MALDI): m/z 501.2277 (calcd. 7.0 Hz, 2 H, CH2CH3), 6.07 (s, 2 H, OCCH2CO), 6.77–6.82 (m, 3
for C31H33O6), found 501.2272 [MH+].
H, CHAr), 7.32–7.36 (m, 2 H, CHAr), 7.51–7.56 (m, 2 H, CHAr),
7.88 (s, 1 H, CH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.12,
55.27, 61.31, 101.99, 108.18, 108.24, 114.28, 125.52, 126.34, 128.67,
131.32, 132.22, 141.85, 148.46, 152.54, 161.31, 165.33, 194.16 ppm.
C20H18O6 (354.35): calcd. C 67.79, H 5.12; found C 67.73, H 5.22.
MS (HR MALDI): m/z 355.1182 (calcd. for C20H19O6), found
355.1176 [MH+].
Naphthalen-1-yl 4-Methyl-3-oxo-5-phenyl-2-(2,4,6-trimethoxyben-
zylidene)pent-4-enoate (4l): This compound was prepared according
to method B, yield 74%, cyclohexane/ethyl acetate (8:2), yellow
foam, Rf = 0.28. 1H NMR (300.1 MHz, CDCl3): δ = 2.23 (d, 3JH,H
4
= 1.2 Hz, 3 H, CH3), 2.26 (d, JH,H = 0.9 Hz, 3 H, CH3), 2.31 (d,
4JH,H = 1.2 Hz, 3 H, CH3), 3.58 (s, 6 H, OCH3), 3.77 (s, 3 H,
OCH3), 3.78 (s, 6 H, OCH3), 3.80 (s, 3 H, OCH3), 3.83 (s, 3 H, Ethyl 2-(Cyclopent-1-enylcarbonyl)-3-(2,4,6-trimethoxyphenyl)acry-
OCH3), 3.85 (s, 6 H, OCH3), 3.88 (s, 3 H, OCH3), 6.04 (s, 2 H, late (6): This compound was prepared according to method A,
CHAr), 6.07 (s, 2 H, CHAr), 6.15 (s, 2 H, CHAr), 7.13–8.41 (m, yield 40%, cyclohexane/ethyl acetate (7:3); yellow solid; Rf = 0.28.
14 H, CHAr, CH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 13.2, 1H NMR (250.1 MHz, CDCl3) (one isomer given): δ = 1.28 (t,
14.4, 21.3, 22.7, 22.9, 25.0, 25.6, 33.9, 49.0, 55.1, 55.2, 55.4, 55.5,
55.6, 55.7, 90.2, 90.4, 90.6, 90.7, 105.4, 105.5, 105.7, 105.8, 117.2,
118.0, 118.1, 121.8, 122.1, 122.3, 125.2, 123.2, 125.3, 125.3, 125.4,
3JH,H = 7.0 Hz, 3 H, CH2CH3), 1.85–2.0 (m, 2 H, CH2), (m, 2 H,
CH2), (m, 2 H, CH2), 3.72 (s, 6 H, OCH3), 3.83 (s, 3 H, OCH3),
4.26 (q, JH,H = 7.2 Hz, 2 H, CH2), 6.02 (s, 2 H, CHAr), 6.45 (m,
3
Eur. J. Org. Chem. 2007, 2650–2658
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2655

I. Walz, A. Bertogg, A. Togni
FULL PAPER
1 H, CH), 7.95 (s, 1 H, CH) ppm. 13C NMR (62.9 MHz, CDCl3):
δ = 14.25, 23.22, 30.54, 33.75, 55.03, 55.37, 60.89, 90.15, 105.55,
129.75, 134.37, 144.19, 145.22, 159.49, 163.21, 166.84, 191.66 ppm.
C20H24O6 (360.41): calcd. C 66.65, H 6.71; found C 66.72, H 6.83.
MS (HR MALDI): m/z 383.1471 (calcd. for C20H24O6Na), found
383.1482 [MNa+].
149.38, 167.26, 169.81 ppm. C24H26O3 (362.47): calcd. C 79.53, H
7.23; found C 79.39, H 7.32. MS (HR MALDI): m/z 363.4694
(calcd. for C24H27O3), found 363.4682 [MH+].
Ethyl 5-(4-Methoxyphenyl)-3-methyl-2-oxo-4-phenylcyclopent-3-
ene-1-carboxylate (7c): This compound was synthesized by using
method C, reaction time 10 min, yield 37%) keto and enol forms
mixture (9:1), cyclohexane/ethyl acetate (9:1), colorless oil, Rf =
(E)-5,7-Dimethoxy-3-(2-methyl-3-phenylacryloyl)-2H-chromen-2-
one (8): This compound was prepared according to method A, yield
95%, recrystallized from CH2Cl2/n-hexane, yellow solid, cyclohex-
1
3
0.4. H NMR (300.1 MHz, CDCl3): δ = 1.34 (t, JH,H = 7.2 Hz, 3
4
3
H, CH2CH3), 2.03 (d, JH,H = 1.8 Hz, 3 H, CH3), 3.45 (d, JH,H
=
1
2.7 Hz, 1 H, C(O)CHC(O)), 3.73 (s, 3 H, OCH3), 4.24–4.32 (m, 2
ane/ethyl acetate (8:2), Rf = 0.28. H NMR (250.1 MHz, CDCl3):
3
3
4
H, CH2CH3), 4.86 (t, JH,H = 1.8 Hz, 1 H, CH), 6.75 (d, JH,H
=
δ = 2.23 (d, JH,H = 1.2 Hz, 3 H, CH3), 3.89 (s, 3 H, OCH3), 3.90
3
(s, 3 H, OCH3), 6.31 (d, 4JH,H = 2.2 Hz, 1 H, CHAr), 6.46 (d, 4JH,H
= 2.0 Hz, 1 H, CHAr), 7.26 (s, 1 H, CH), 7.33–7.46 (m, 5 H,
CHAr), 8.28 (s, 1 H, CH) ppm. 13C NMR (62.9 MHz, CDCl3): δ
= 13.65, 56.01, 56.10, 92.77, 95.16, 103.64, 121.63, 128.45, 128.80,
129.95, 135.67, 137.12, 140.32, 142.20, 157.57, 158.0, 159.06,
165.30, 194.82 ppm. C21H18O5 (350.36): calcd. C 71.99, H 5.18;
found C 71.72, H 5.26. MS (HR MALDI): m/z 373.1052 (calcd.
for C21H18O5Na), found 373.1046 [MNa+].
8.7 Hz, 2 H, CHAr), 7.00 (d, JH,H = 8.7 Hz, 2 H, CHAr), 7.30–
7.36 (m, 5 H, CHAr) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
10.21, 14.23, 50.34, 55.15, 61.79, 61.88, 113.68, 114.30, 127.59,
127.90, 128.31, 128.38, 128.65, 129.32, 132.72, 134.64, 135.72,
158.57, 168.69, 169.19, 201.72 ppm. C22H22O4 (350.41): calcd. C
75.41, H 6.33; found C 74.86, H 6.20. MS (HR MALDI): m/z
351.1596 (calcd. for C22H23O4), found 351.1591 [MH+].
Ethyl 2-Methyl-2-oxo-4,5-diphenylcyclopent-3-ene-1-carboxylate
(7d): This compound was synthesized by using method C, yield
87%, cyclohexane/ethyl acetate (9:1), yellowish oil, Rf = 0.24. 1H
General Procedure for the Nazarov Cyclization Catalyzed by VIV-
(salen) Complex (Method C): The vanadium salen complex 1a
(0.6 mg, 1 µmol, 0.02 equiv.) was treated with a solution of AgSbF6
(0.7 mg, 2 µmol, 0.04 equiv.) in dry CH2Cl2 (2 mL) turning the blue
solution to purple. A white precipitate of AgCl was formed imme-
diately. After 10 min, the substrate (0.05 mmol, 1 equiv.) was
treated with this suspension, whereby the reaction mixture changed
from purple to brown and then black, which indicates complete
conversion. The reaction was quenched with water (1 mL), the lay-
ers were separated and the aqueous phase was extracted with
CH2Cl2 (2ϫ1 mL), the combined organic layers were dried with
MgSO4, filtered, the solvent was evaporated in vacuo and the re-
sulting residue was purified by flash column chromatography to
give the cyclized product.
3
NMR (300.1 MHz, CDCl3): δ = 1.34 (t, JH,H = 7.2 Hz, 3 H,
4
3
CH2CH3), 2.05 (d, JH,H = 1.8 Hz, 3 H, CH3), 3.49 (d, JH,H
=
2.7 Hz, 1 H, C(O)CHC(O)), 4.25–4.32 (m, 2 H, CH2CH3), 4.91 (d,
3JH,H = 2.1 Hz, 1 H, CH), 7.08–7.40 (m, 10 H, CHAr) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 10.28, 14.25, 51.01, 61.73, 61.84,
127.16, 127.67, 128.33, 128.43, 128.93, 129.42, 134.53, 135.93,
140.77, 168.62, 169.00, 201.61 ppm. CAS number 650605-56-4.
Ethyl 3-Methyl-5-(4-nitrophenyl)-2-oxo-4-phenylcyclopent-3-ene-1-
carboxylate (7e): This compound was synthesized by using method
C, reaction time 6 h, yield 80%, cyclohexane/ethyl acetate (8:2),
1
beige solid, Rf = 0.24. H NMR (300.1 MHz, CDCl3): δ = 1.33 (t,
3JH,H = 7.2 Hz, 3 H, CH2CH3), 2.06 (d, 4JH,H = 2.1 Hz, 3 H, CH3),
3
3.43 (d, JH,H = 3.3 Hz, 1 H, C(O)CHC(O)), 4.24–4.34 (m, 2 H,
Ethyl 3-Methyl-2-oxo-4-phenyl-5-(2,4,6-trimethoxyphenyl)-
cyclopent-3-ene-1-carboxylate (7a): This compound was synthesized
by using method C, reaction time 2 min, yield 94%, cyclohexane/
ethyl acetate (7:3); yellowish solid; Rf = 0.33. 1 H NMR
3
3
CH2CH3), 5.07 (t, JH,H = 2.7 Hz, 1 H, CH), 7.27 (d, JH,H
=
=
3
8.7 Hz, 2 H, CHAr), 7.30–7.38 (m, 5 H, CHAr), 8.07 (d, JH,H
8.7 Hz, 2 H, CHAr) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
10.31, 14.21, 50.36, 61.09, 62.18, 124.24, 128.17, 128.63, 128.75,
129.90, 133.78, 136.73, 147.08, 148.36, 167.26, 167.97, 200.27 ppm.
CAS number 650605-47-3.
3
(300.1 MHz, CDCl3): δ = 1.31 (t, JH,H = 7.2 Hz, 3 H, CH2CH3),
4
1.96 (d, JH,H = 2.2 Hz, 3 H, CH3), 3.55 (s, 1 H, OCH3), 3.69 (d,
3JH,H = 3.3 Hz, 1 H, C(O)CHC(O)), 3.72 (s, 1 H, OCH3), 3.84 (s,
1 H, OCH3), 4.18–4.32 (m, 2 H, CH2CH3), 5.42 (t, 3JH,H = 2.5 Hz,
Ethyl 2-Oxo-3,4-diphenyl-5-(2,4,6-trimethoxyphenyl)cyclopent-3-
ene-1-carboxylate (7f): This compound was synthesized by using
method C, reaction time 10 min, yield 98%, cyclohexane/ethyl ace-
tate (7:3), yellowish solid, Rf = 0.23. 1H NMR (250.1 MHz,
4
4
1 H, CH), 5.89 (d, JH,H = 2.0 Hz, 1 H, CHAr), 6.06 (d, JH,H
=
2.0 Hz, 1 H, CHAr), 7.25–7.35 (m, 5 H, CHAr) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 10.03, 14.25, 40.50, 55.14, 55.17, 56.13,
58.31, 61.18, 90.62, 90.87, 108.14, 127.90, 127.91, 128.85, 133.17,
135.11, 158.77, 159.41, 160.34, 170.13, 171.50, 202.86 ppm.
C24H26O6 (410.47): calcd. C 70.23, H 6.38; found C 70.42, H 6.49.
MS (HR MALDI): m/z 411.1808 (calcd. for C24H27O6), found
411.1802 [MH+].
3
CDCl3): δ = 1.30 (t, JH,H = 7.2 Hz, 3 H, CH2CH3), 3.61 (s, 3 H,
3
OCH3), 3.74 (s, 3 H, OCH3), 3.79 (d, JH,H = 3.2 Hz, 1 H, CH),
3
3.90 (s, 3 H, OCH3), 4.13–4.31 (m, 2 H, CH2CH3), 5.53 (d, JH,H
= 3.2 Hz, 1 H, C(O)CHC(O)), 5.94 (d, 4JH,H = 2.0 Hz, 1 H, CHAr),
4
6.12 (d, JH,H = 2.0 Hz, 1 H, CHAr), 7.09–7.33 (m, 1 H, CHAr)
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.27, 40.45, 55.17, 55.23,
56.20, 59.17, 61.31, 90.70, 90.87, 107.98, 127.58, 127.72, 128.20,
128.52, 129.07, 129.72, 132.21, 134.61, 136.62, 158.78, 159.37,
160.49, 169.77, 173.05, 200.57 ppm. C29H28O6 (472.53): calcd. C
73.71, H 5.97; found C 73.56, H 6.07. MS (HR MALDI): m/z
473.1964 (calcd. for C29H29O6), found 473.1963 [MH+].
Ethyl 2-Hydroxy-5-mesityl-3-methylene-4-phenylcyclopent-1-ene-1-
carboxylate (7b): This compound was synthesized by using method
C, reaction time 10 min, yield 63 %, cyclohexane/diethyl ether
1
(9.8:0.2); yellowish oil; Rf = 0.2. H NMR (300.1 MHz, CDCl3): δ
3
= 0.99 (t, JH,H = 6.9 Hz, 3 H, CH2CH3), 1.92 (s, 3 H, CH3Ar),
2.24 (s, 3 H, CH3Ar), 2.26 (s, 3 H, CH3Ar), 3.92 (d, 3JH,H = 3.3 Hz,
3
1 H, CH), 4.01–4.10 (m, 2 H, CH2CH3), 4.49 (d, JH,H = 3.9 Hz, Ethyl 2-Oxo-3,4-diphenyl-5-(4-methoxyphenyl)cyclopent-3-ene-1-
4
4
1 H, CH), 5.10 (d, JH,H = 2.1 Hz, 1 H, CHAr), 5.82 (d, JH,H
=
carboxylate (7g): This compound was synthesized by using method
3.0 Hz, 1 H, CHAr), 6.75 (s, 1 H, CHAr), 6.80 (s, 1 H, CHAr),
7.13–7.15 (m, 2 H, CHAr), 7.25–7.33 (m, 3 H, CHAr), 10.23 (s, 1
C, reaction time 10 min, yield 97%, cyclohexane/ethyl acetate (8:2),
1
yellowish oil, Rf = 0.25. H NMR (300.1 MHz, CDCl3): δ = 1.34
3
3
H, OH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 13.84, 20.39, (t, JH,H = 6.9 Hz, 3 H, CH2CH3), 3.64 (d, JH,H = 3.0 Hz, 1 H,
20.85, 21.25, 49.84, 52.85, 60.18, 109.16, 112.01, 126.72, 127.96, CH), 3.74 (s, 3 H, OCH3), 4.21–4.38 (m, 2 H, CH2CH3), 4.99 (d,
3
128.74, 128.87, 131.10, 135.34, 135.85, 136.22, 137.07, 144.77, 3JH,H = 2.7 Hz, 1 H, C(O)CHC(O)), 6.79 (d, JH,H = 8.7 Hz, 2 H,
2656
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2650–2658

Efficient Catalysts for Nazarov Cyclizations
FULL PAPER
3
3
CHAr), 7.10 (d, JH,H = 8.7 Hz, 2 H, CHAr), 7.12–7.37 (m, 10 H, CH2CH3), 4.79 (d, JH,H = 4.0 Hz, 1 H, CH), 6.06 (s, 2 H,
CHAr) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.24, 50.35, OCCH2CO), 6.59 (s, 1 H, CHAr), 6.85 (d, JH,H = 8.7 Hz, 2 H,
3
3
55.17, 61.87, 62.71, 114.46, 128.20, 128.23, 128.37, 128.78, 128.97, CHAr), 7.05 (d, JH,H = 8.7 Hz, 2 H, CHAr), 7.12 (s, 1 H, CHAr)
129.57, 129.90, 131.31, 132.44, 134.21, 138.57, 158.70, 168.44, ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.21, 47.71, 55.30, 61.72,
170.28, 199.61 ppm. C27H24O4 (412.48): calcd. C 78.62, H 5.86;
64.06, 102.29, 102.53, 105.72, 114.43, 128.85, 129.64, 133.78,
found C 78.27, H 5.93. MS (HR MALDI): m/z 413.1753 (calcd. 148.97, 154.61, 155.08, 158.98, 168.63, 196.57 ppm. C20H18O6
for C27H25O4), found 413.1747 [MH+].
(354.35): calcd. C 67.79, H 5.12; found C 67.44, H 4.89. MS (HR
MALDI): m/z 361.1651 (calcd. for C20H25O6), found 361.1646
[MH+].
Benzyl 3-Methyl-2-oxo-4-phenyl-5-(2,4,6-trimethoxyphenyl)cy-
clopent-3-ene-1-carboxylate (7j): This compound was synthesized
by using method C, reaction time 5 min, yield 65%, cyclohexane/
ethyl acetate (8:2), beige solid, Rf = 0.19. 1H NMR (300.1 MHz,
Ethyl 1-Oxo-3-(2,4,6-trimethoxyphenyl)-1,2,3,4,5,6-hexahy-
dropentalene-2-carboxylate (S3): This compound was synthesized
by using method C, reaction time 2 h, yield 61%, cyclohexane/ethyl
acetate (7:3), yellowish solid, Rf = 0.39. 1H NMR (250.1 MHz,
4
CDCl3): δ = 1.97 (d, JH,H = 2.4 Hz, 3 H, CH3), 3.54 (s, 3 H,
OCH3), 3.72 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 3.79 (d, 3J =
3.3 Hz, 1 H, CH), 5.19 (d, 2JH,H = 12.6 Hz, 1 H, C(O)CH2Ph), 5.30
3
CDCl3): δ = 1.29 (t, JH,H = 7.2 Hz, 3 H, CH2CH3), 2.26–2.37 (m,
2
(d, JH,H = 12.6 Hz, 1 H, C(O)CH2Ph), 5.42–5.47 (m, 1 H, C(O)-
4 H, CH2), 2.43–2.45 (m, 2 H, CH2), 3.73 (s, 6 H, OCH3), 3.82 (s,
4
4
3
CHC(O)), 5.87 (d, JH,H = 2.1 Hz, 1 H, CHAr), 6.03 (d, JH,H
=
3 H, OCH3), 3.84 (d, JH,H = 3.0 Hz, 1 H, C(O)CHC(O)), 4.14–
1.8 Hz, 1 H, CHAr), 7.25–7.46 (m, 10 H, CHAr) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 10.05, 40.49, 55.15, 56.07, 58.24, 66.82,
90.61, 90.83, 108.03, 127.90, 127.91, 127.93, 127.99, 128.00, 128.44,
128.86, 133.22, 135.08, 136.01, 158.74, 159.39, 160.35, 170.00,
202.59 ppm. MS (HR MALDI): m/z 473.1964 (calcd. for
C29H29O6), found 473.1959 [MH+]; no elemental analysis is avail-
able because the compound is unstable.
4.30 (m, 2 H, CH2CH3), 4.89 (br., 1 H, CH), 6.11 (s, 2 H, CHAr)
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 14.26, 24.81, 27.85, 30.61,
37.84, 55.34, 55.71, 61.10, 64.85, 90.76, 106.69, 145.09, 159.32,
160.56, 170.13, 191.14, 191.14, 196.57 ppm. C20H24O6 (360.41):
calcd. C 66.65, H 6.71; found C 66.43, H 6.59. MS (HR MALDI):
m/z 361.1651 (calcd. for C20H25O6), found 361.1646 [MH+].
Mesityl 3-Methyl-2-oxo-4-phenyl-5-(2,4,6-trimethoxyphenyl)cy-
clopent-3-enecarboxylate (7k): This compound was synthesized by
using method C, reaction time 15 min, yield 99 %, cyclohexane/
ethyl acetate (8:2), beige solid, Rf = 0.2. 1H NMR (300.1 MHz,
CDCl3): δ = 2.03 (d, 4JH,H = 2.1 Hz, 3 H, CH3), 2.19 (s, 3 H, CH3),
2.19 (s, 3 H, CH3), 2.28 (s, 3 H, CH3), 3.60 (s, 3 H, OCH3), 3.74
Acknowledgments
Support from the Swiss National Science Foundation is gratefully
acknowledged.
3
(s, 3 H, OCH3), 3.84 (s, 3 H, OCH3), 3.98 (d, JH,H = 3.3 Hz, 1 H,
4
CH), 5.57–5.64 (m, 1 H, C(O)CHC(O)), 5.93 (d, JH,H = 2.1 Hz, 1
[1] a) K. L. Habermas, S. E. Denmark, T. K. Jones, Org. React.
1994, 45, 1–159; b) M. A. Tius, Eur. J. Org. Chem. 2005, 2193–
2206.
4
H, CHAr), 6.08 (d, JH,H = 2.0 Hz, 1 H, CHAr), 6.89 (s, 2 H,
CHAr), 7.26–7.43 (m, 5 H, CHAr) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 10.09, 16.19, 20.77, 40.99, 55.15, 55.24, 55.76, 58.24,
90.33, 90.79, 107.79, 127.92, 127.99, 128.97, 129.14, 129.99, 133.45,
135.04, 135.27, 145.96, 158.57, 159.52, 160.48, 168.40, 171.86,
202.61 ppm. C31H32O6 (500.59): calcd. C 74.38, H 6.44; found C
74.53, H 6.56. MS (HR MALDI): m/z 501.2277 (calcd. for
C31H33O6), found 501.2272 [MH+].
[2] a) W. He, X. Sun, A. J. Frontier, J. Am. Chem. Soc. 2003, 125,
14278–14279; b) C. Bee, E. Leclerc, M. Tius, Org. Lett. 2003,
5, 4927–4930; c) G. Liang, S. N. Grandl, D. Trauner, Org. Lett.
2003, 5, 4931–4934; d) M. Janka, W. He, A. J. Frontier, R. Ei-
senberg, J. Am. Chem. Soc. 2004, 126, 6864–6865.
[3] a) G. Liang, D. Trauner, J. Am. Chem. Soc. 2004, 126, 9544–
9545; b) V. K. Aggarwal, A. J. Belfield, Org. Lett. 2003, 5,
5075–5078.
[4] a) C. W. Shopee, R. E. Lack, J. Chem. Soc. C 1969, 1346–1349;
b) C. W. Shopee, B. J. Cooke, J. Chem. Soc., Perkin Trans. 1
1972, 2271–2276; c) C. W. Shoppee, B. J. Cooke, J. Chem. Soc.,
Perkin Trans. 1 1973, 1026–1032; d) R. D. Woodward, Chem.
Soc. Special Publication No. 21 1967, 237–239.
[5] H. Pellissier, Tetrahedron 2005, 61, 6479–6517.
[6] T. R. J. Achard, L. A. Clutterbuck, M. North, Synlett 2005, 12,
1828–1847.
[7] C. Bolm, Coord. Chem. Rev. 2003, 237, 245–256.
[8] a) A. Togni, Organometallics 1990, 9, 3113–3121; b) C.-T.
Chen, S.-W. Hon, S.-S. Weng, Synlett 1999, 6, 816–818; c) Y. N.
Belokon, M. North, T. Parsons, Org. Lett. 2000, 2, 1617–1619.
[9] M. Pasquali, A. Torres-Filho, C. Floriani, J. Chem. Soc., Chem.
Commun. 1975, 534–535.
[10] T. Katsuki, Chem. Soc. Rev. 2004, 33, 437–444.
[11] V. Vergopoulos, S. Jantzen, D. Rodewald, D. Rehder, J. Chem.
Soc., Chem. Commun. 1995, 377–378.
[12] M. Janka, W. He, A. J. Frontier, C. Flaschenriem, R. Eisenberg,
Tetrahedron 2005, 61, 6193–7606.
[13] R. Zibuck, J. M. Streiber, J. Org. Chem. 1989, 54, 4717–4719.
[14] A. Aoyama, N. Sodona, M. Yamauchi, K. Toriyama, A. Ando,
T. Shioiri, Synlett 1998, 35–36.
[15] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155–4156.
[16] Divinyl ketones are drawn as the Z-isomer, although most of
them were isolated as E/Z mixtures.
Naphthalen-1-yl 3-Methyl-2-oxo-4-phenyl-5-(2,4,6-trimethoxy-
phenyl)cyclopent-3-ene-1-carboxylate (7l): This compound was syn-
thesized by using method C, reaction time 5 h, yield 76%, cyclohex-
ane/ethyl acetate (8:2), beige solid, Rf = 0.37. 1 H NMR
(300.1 MHz, CDCl3): δ = 2.07 (s, 3 H, CH3), 3.62 (s, 3 H, OCH3),
3.76 (s, 3 H, OCH3), 3.91 (s, 3 H, OCH3), 4.14 (s, 1 H, CH), 5.69–
5.74 (m, 1 H, C(O)CHC(O)), 5.95 (d, 4JH,H = 1.5 Hz, 1 H, CHAr),
3
6.14 (s, 1 H, CHAr), 7.22–7.58 (m, 10 H, CHAr), 7.77 (d, JH,H
=
3
7.5 Hz, 1 H, CHNp), 7.88 (d, JH,H = 6.9 Hz, 1 H, CHNp), 8.16
(d, JH,H = 7.2 Hz, 1 H, CHNp) ppm. 13C NMR (75.5 MHz,
3
CDCl3): δ = 10.15, 40.87, 55.21, 55.27, 56.16, 58.54, 90.62, 90.94,
107.79, 118.14, 121.87, 125.31, 126.09, 126.40, 126.52, 126.97,
127.77, 127.96, 127.99, 129.03, 133.31, 134.65, 134.97, 146.90,
158.82, 159.49, 160.58, 168.85, 172.03, 202.41 ppm. C32H28O6
(508.56): calcd. C 75.57, H 5.55; found C 75.34, H 5.55. MS (HR
MALDI): m/z 509.1964 (calcd. for C32H29O6), found 509.1959
[MH+].
Ethyl 5-(4-Methoxyphenyl)-7-oxo-6,7-dihydro-5H-indeno[5,6-
d][1,3]dioxole-6-carboxylate (S2): This compound was synthesized
by using method C, reaction time 72 h, yield 99%, cyclohexane/
ethyl acetate (7:3), beige solid, Rf = 0.5. 1H NMR (250.1 MHz,
3
3
CDCl3): δ = 1.29 (t, JH,H = 7.2 Hz, 3 H, CH2CH3), 3.60 (d, JH,H
= 4.2 Hz, 1 H, CH), 3.79 (s, 3 H, OCH3), 4.19–4.29 (m, 2 H,
Eur. J. Org. Chem. 2007, 2650–2658
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2657

I. Walz, A. Bertogg, A. Togni
FULL PAPER
[17] Three double bond isomers were isolated, but only one of them
was characterized. See experimental section.
[22] Y. N. Belokon, P. Carta, A. V. Gutnov, V. Maleev, M. A. Mos-
kalenko, L. V. Yashkina, N. S. Ikonnikov, N. V. Voskoboev,
V. N. Khrustalev, M. North, Helv. Chim. Acta 2002, 85, 3301–
3312.
[23] a) M. Pasquali, F. Marchetti, C. Floriani, Inorg. Chim. Acta
1979, 18, 2401–2404; b) H. Schmidt, D. Reheder, Inorg. Chim.
Acta 1998, 267, 229–238.
[18] CRS Handbook of Chemistry and Physics 1984–1985 (Ed.:
R. C. Weast), CRS Press, Boca Raton, Florida, 65th ed.
[19] D. A. Evans, J. A. Murry, P. Matt, R. D. Norcross, S. J. Miller,
Angew. Chem. Int. Ed. Engl. 1995, 34, 798–800.
[20] J. A. M.
Van den Goorbergh,
M.
Van der Steeg,
A.
Van Der Gen, Synthesis 1984, 859–860.
[24] R. Anonioletti, P. Bovicelli, S. Malancona, Tetrahedron 2002,
58, 589–596.
[21] I. A. Fallis, D. M. Murphy, D. J. Willock, R. J. Tucker, R. D.
Farley, R. Jenkins, R. R. Strevens, J. Am. Chem. Soc. 2004,
126, 15660–15661.
Received: February 20, 2007
Published Online: April 23, 2007
2658
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2650–2658