Thermal and catalytic isomerization of exomethylenecycloheptadienes. Experimental and theoretical studies

Article abstract of DOI:10.1016/j.tet.2009.10.065

The intermolecular [3+2+2] cycloaddition reaction of ethyl cyclopropylideneacetate with alkynes proceeded in the presence of a Ni(0)/PPh₃ catalyst, and cycloheptadiene derivatives were obtained. However, in the reaction of 1-cyclopropylidene-2-

Full text of DOI:10.1016/j.tet.2009.10.065

Tetrahedron 65 (2009) 10631–10636
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Tetrahedron
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Thermal and catalytic isomerization of exomethylenecycloheptadienes.
Experimental and theoretical studies
,
Yukiko Fukusaki a, Jun Miyazaki a y, Isao Azumaya b, Kosuke Katagiri b, Shinsuke Komagawa a,
,
Ryu Yamasaki a, Shinichi Saito a
*
a Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku, Tokyo 162-8601, Japan
b Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Kagawa 769-2193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 July 2009
Received in revised form 17 October 2009
Accepted 19 October 2009
Available online 22 October 2009
The intermolecular [3þ2þ2] cycloaddition reaction of ethyl cyclopropylideneacetate with alkynes
proceeded in the presence of a Ni(0)/PPh3 catalyst, and cycloheptadiene derivatives were obtained.
However, in the reaction of 1-cyclopropylidene-2-propanone with phenylacetylene, a cycloheptatriene
derivative was isolated. It was anticipated that the isomerization of the initially formed cycloheptadiene
derivative led to the formation of the cycloheptatriene derivative. In this paper, we report the isomer-
ization of cycloheptadiene derivatives under thermal, acidic and basic conditions. The stability of the
products was also studied by theoretical calculations. The effects of substituents and the mechanism of
the isomerization were discussed.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
CO2Et
CO2Et
The isomerization of cycloheptadienes and cycloheptatrienes
proceeds via various pathways and the mechanism has been studied
in depth. For example, the 1,5-sigmatropic shift of cycloheptatriene
derivatives has been extensively studied.1 This rearrangement is
cat. Ni(cod)2-PPh3
(a)
R2
R1
R1
+
2
R2
R2
Ph
R1
closely related to the frontier orbital interaction between the
s*
COMe
orbital of the migrating group and the pHOMO of a conjugated diene
system. The conformation of the starting material can affect the
rates and the product distributions of the process. In addition, the
interconversion of norbornadiene, norcaradiene, cycloheptadiene,
and toluene has been reported.2 There have been several studies
related to the isomerization of cycloheptadiene derivatives to
cycloheptatrienones under basic or acidic conditions.3 In most ex-
amples, the tautomerization of imine-enamine or cyclo-
heptadienone–cycloheptatrienol was discussed.3a,b
COMe
+
cat. Ni(cod)2-PPh3
(b)
Ph
2
Ph
COMe
Ph
We have previously reported that
a new intermolecular
Ph
[3þ2þ2] cycloaddition reaction of ethyl cyclopropylideneacetate
with alkynes proceeded in the presence of a Ni(0)/PPh3 catalyst,
and cycloheptadiene derivatives were obtained (Scheme 1a).4
However, in the reaction of 1-cyclopropylidene-2-propanone with
Scheme 1.
It was anticipated that the isomerization of the initially formed
cycloheptadiene derivative led to the formation of the cyclo-
heptatriene derivative. Since conjugated enoates are generally more
stable than non-conjugated enoates, we were interested in the
formation of a cycloheptatriene, instead of the expected cyclo-
heptadiene derivative, in this reaction. Herein, we describe the
isomerization of cycloheptadiene derivatives, which were generated
by the [3þ2þ2] cycloaddition reactions of electron-deficient
phenylacetylene,
a cycloheptatriene derivative was isolated
(Scheme 1b).4a,4c
* Corresponding author. Tel.: þ81 3 5228 8715; fax: þ81 3 5261 4631.
E-mail address: ssaito@rs.kagu.tus.ac.jp (S. Saito).
y
Present address: Department of Liberal Arts and Basic Sciences, College of In-
dustrial Technology, Nihon University, Shinei 2-11-1, Narashino, Chiba 275-8576,
Japan.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.065

10632
Y. Fukusaki et al. / Tetrahedron 65 (2009) 10631–10636
methylenecyclopropanes and alkynes. The mechanism of the
reactions as well as the substituent effects was discussed. We also
studied the stability of the isomers by density functional theory (DFT)
calculations and compared the experimental and theoretical results.
The slow isomerization of 1 proceeded at 100 ꢀC in DMF, and
a mixture of 1 and isomers (2–4) were obtained (Scheme 2a).
Compound 2 was identified as the major product.5 On the other
hand, the treatment of 1 with 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) for a long period (260 h) at room temperature affor-
ded the isomer 3, which was obtained as a minor product under
thermal conditions (Scheme 2b).6 The structure of 3 was similar
to the product isolated by the nickel-catalyzed reaction of 1-
cyclopropylidene-2-propanone with alkynes (Scheme 1b).4a,4c To
examine the possibility of the formation of other isomers, we
also carried out the isomerization reaction under acidic condi-
tions. Thus, the reaction of cycloheptadiene 1 at room temper-
ature for 50 h in the presence of trifluoroacetic acid (TFA)
afforded two isomers (3 and 4) in addition to the starting ma-
terial. When the reaction time was extended to 190 h, the
amount of 4 decreased and compound 3 was isolated as the
major product (Scheme 2c). The result indicated that compound
3 was formed by the isomerization of the initially formed isomer
4. We next studied the acid-catalyzed interconversion between 3
and 4 to examine the existence of the equilibrium between the
isomers. Treatment of the isomer 3 with TFA at room tempera-
ture for 190 h afforded a mixture of 3 and 4 (3:4¼100:24,
Scheme 2d). Similarly, the isomer 4 was treated under acidic
conditions for 386 h to afford a mixture of 3 and 4 (3:4¼100:50,
Scheme 2e).7,8
2. Results and discussion
2.1. Synthesis and isomerization of cycloheptadienes
We selected two cycloheptadienes and studied the isomeriza-
tion reactions under thermal, acidic, and basic conditions. We
initiated our study by carrying out the isomerization of 1, which has
two electron-donating groups (t-Bu groups). The results are
summarized in Scheme 2.
CO2Et
DMF
100 °C
t-Bu
64 h
83%
t-Bu
1
(a)
CO2Et
CO2Et
CO2Et
+
+
1
+
t-Bu
t-Bu
t-Bu
Subsequently, we investigated the isomerization of cyclo-
heptadiene 5 (Scheme 3). Thermal reaction (100 ꢀC) of 5 in DMF
gave the isomers 6 and 7 (Scheme 3a).9 When the thermal reaction
was carried out in dioxane, the isomer 6 was isolated in high yield
(Scheme 3b). It is noteworthy that a single isomer was isolated in
this reaction. On the other hand, the exposure of 5 to DBU afforded
6, together with another isomer 7 (Scheme 3c). To examine the
existence of the equilibrium between the isomers, compounds 6
and 7 were isolated and exposed to the same reaction conditions.
Both compounds were converted to a mixture of 6 and 7, and the
ratios of the isomers were similar (Scheme 3d–e). When lithium
diisopropylamide (LDA) was used as a base, the decomposition of 5
was observed. Meanwhile, compound 5 was not reactive under
acidic conditions: the reaction of 5 did not proceed in the presence
of TFA at room temperature, and the starting material was re-
covered (Scheme 3f).
t-Bu
t-Bu
t-Bu
2
4
3
61
:
35
:
4
:
trace
(NMR)
CO2Et
CO2Et
DBU 0.1 eq
1
(b)
+
t-Bu
t-Bu
rt
260 h
92%
t-Bu
t-Bu
3
1
20
:
100
(NMR)
CO2Et
CO2Et
CO2Et
TFA,
excess
2.2. DFT calculations
+
(c)
1
+
t-Bu
t-Bu
t-Bu
dioxane
rt
quant
Density functional theory calculations were performed in order
to estimate the relative energies of the cycloheptatriene de-
rivatives. The Gaussian0310 software program with B3LYP/6-
311þG* basis set was employed to estimate the energy of the
cycloheptadiene 1 and the cycloheptatriene isomers 2–4. The en-
ergy of a structurally similar compound 8 and a supposed in-
termediate 9 (vide infra) was also calculated.11 We performed the
geometry optimization and thermochemistry analysis at 298.15 K.
The initial structure used for the geometry optimization of 1 was
referred to the crystal structure of a cycloheptadiene (A).4a,4c The
structural information of cycloheptatriene (B) was utilized for the
optimization of 2–4, and 8 (Fig. 1).12 The structures with the global
minimum energy were determined by DFT calculations. The opti-
mized structures of the compounds and the relative energies are
shown in Figure 2.
t-Bu
t-Bu
t-Bu
1
3
4
11
0
:
:
100
100
:
:
67 (50 h)
25 (190 h)
(NMR)
CO2Et
TFA excess
dioxane, rt
190 h
quant
3
+
:
4
(d)
(e)
t-Bu
100
24
t-Bu
(NMR)
3
CO2Et
In the optimized structure of 1, the
heptadiene and the exomethylene groups were coplanar, so that
compound 1 has a long -conjugated system. At the same time,
p-bonds of cyclo-
TFA excess
dioxane, rt
386 h
66%
3
+
:
4
p
t-Bu
100
50
compound 1 would be destabilized by the steric interaction be-
tween the bulky ethoxycarbonyl group and the methylene group
located at the cycloheptadiene ring. The small dihedral angle
between the C–H bonds of the –CH2CH2– group might also
t-Bu
(NMR)
4
Scheme 2.

Y. Fukusaki et al. / Tetrahedron 65 (2009) 10631–10636
10633
CO2Et
COOEt
A
DMF
EtO2C
EtO2C
CO2Et
CO2Et
100 °C
64 h
OMe
5
(a)
CO2Et
CO2Et
MeO
+
CO2Et
CO2Et
EtO2C
EtO2C
CO2Et
EtO2C
EtO2C
B
COMe
CO2Et
F
F
7
6
F
F
40%
41%
F
F
F
F
CO2Et
CO2Et
dioxane
reflux
F
F
(100 °C )
Figure 1. The structures and ORTEP views of compounds A–B.
CO2Et
CO2Et
(b)
CO2Et
CO2Et
EtO2C
EtO2C
EtO2C
50 h
91%
EtO2C
(CHT)>8 (Fig. 2). Especially, large substituents bound to C2 or C5
atom might induce the deformation of the structure (compare 2
vs 3 or 4). A notable exception is 8, of which the ring is more
planar to reduce the unfavorable interaction between the bulky
t-Bu groups at C1 and C6 positions.
The observed isomer distribution by the isomerization
reactions generally reflects the relative energies of the isomers by
DFT calculation. Thus, compound 2 was isolated as the major
product under thermal conditions (Scheme 2a) and the formation
of 3 (and 4) was observed in the acid- or base-catalyzed isomer-
ization of 1 (Scheme 2b–e). As expected, a very unstable isomer
(8) was not detected throughout our study. At the same time, the
most stable isomer (2) was not always isolated as the major
product because of the high activation energy required for the
conversion (vide infra).
6
5
CO2Et
DBU 0.1 eq
rt
5
+
6
+
7
(c)
EtO2C
CO2Et
CO2Et
56
0
:
:
100
80
:
:
61 (0.5 h)
100 (23 h)
EtO2C
5
CO2Et
DBU 0.1 eq
(d)
CO2Et
CO2Et
6
+
:
7
EtO2C
EtO2C
EtO2C
rt
23 h
61%
75
100
EtO2C
6
2.3. Mechanistic consideration
CO2Et
The proposed mechanism of the isomerization14,15 of cyclo-
heptadienes under thermal condition is shown in Scheme 4. The [1,
5] sigmatropic rearrangement1 of 1 would proceed at 100 ꢀC, and
compound 9 would be generated as an intermediate. The rapid keto-
enol tautomerization of 9 would proceed because of the high acidity
of the methylene protons, and cycloheptatriene 2 would be isolated
as the final product.16 The instability of 9 was also indicated by the
DBU 0.1 eq
6
+
:
7
(e)
CO2Et
CO2Et
rt
23 h
64%
70
100
EtO2C
7
CO2Et
TFA excess
dioxane, rt
172 h
no reaction
(72% recovery)
(f)
CO2Et
CO2Et
O
O
EtO2C
O
O
[1,5] sigmatropic
rearrangement
5
Scheme 3.
R
R'
R
R'
R
R'
R
R'
reduce the stability of 1. On the other hand, these unfavorable
interactions are not present in the cycloheptatrienes (2–4,and 8).
The higher stability of 2–4 compared to 1 could be reasonably
explained by considering these interactions. The optimized
structure of the isomers 2–4 and 8 adopted boat conformation,
which is generally considered as the most stable conformation
for the cycloheptatrienes.13 Based on the relative energies of the
compounds, the calculated order of the isomer stability was
2>3>4>8. We assume that the substituents might cause the
deformation of the structure and make the most stable boat
conformation strained (and less stable). Thus, the order of the
1 (R = tBu, R' = H)
5 (R, R' = CO2Et)
9 (R = tBu, R' = H)
10 (R, R' = CO2Et)
H
O
CO2Et
O
keto-
keto-
enol
enol
R
R'
R
R'
R
R
R'
R'
2 (R = tBu, R' = H)
6 (R, R' = CO2Et)
nonplanarity angle (
of the cycloheptatriene ring, was 4>3>2>cycloheptatriene
a
),13d which is a benchmark for the planarity
Scheme 4.

10634
Y. Fukusaki et al. / Tetrahedron 65 (2009) 10631–10636
Figure 2. The optimized structures, relative energies, and
a values (in parentheses) of compounds 1–4, 8–9 and CHT.
result of the DFT calculation (Fig. 2). A similar mechanism could be
postulated for the thermal isomerization of the pentaester 5.17 The
isomerization of the initially formed isomer (6) might proceed to
give 7 when the reaction was carried out in DMF.
isomerization proceeded to give 7 as the major product. The
formation of 6 as a kinetic product might be explained by postu-
lating that the protonation of the anion 12 proceeded selectively.
Thus, the protonation of C4, which is located between the
ethoxycarbonylmethylene group and the ethoxycarbonyl group, is
a kinetically favorable process, while the protonation of C2 is slow
because of the presence of three bulky ethoxycarbonyl groups close
to C2.
The proposed mechanism of the isomerization of 1 under acidic
condition is shown in Scheme 6. The cycloheptadiene 1 would be
protonated to give a cation (13),18 which is converted to a mixture
of 3 and 4. When the reaction proceeded via path (a), the kinetically
favored isomer 4 would be generated. On the other hand, the
thermodynamic product 3 would be isolated when the reaction
proceeded via path (b). Since the acid-catalyzed interconversion
between 3 and 4 under acidic conditions was observed, the isomer
3 would become the major product when a mixture of 3 and 4 was
treated with an acid (TFA) for a long period. The recovery of the
starting material (5) under acidic conditions could be explained in
terms of the low basicity of 5.
The proposed mechanism of the isomerization of cyclo-
heptadienes under basic condition is shown in Scheme 5. The
cycloheptadiene 1 would be deprotonated by base (DBU) to give the
enolate and then protonated to afford the isomer 3 (Scheme 5a).
The trisubstituted exoolefin structure of 1 is strained because of the
1,3-allylic strain among the substituents. On the other hand,
the cycloheptatriene 3 would adopt boat conformation and the
ethoxycarbonylmethyl group of 3 would rotate freely to remove
the strain. Consequently, compound 3 would be more stable com-
pared to 1. Since the acidity of 3 is much lower than the acidity of 1,
the deprotonation of 3 would not proceed and the most stable
isomer (2) would not be formed under the reaction conditions. It is
possible to explain the formation of a cycloheptatriene in the
reaction of 1-cyclopropylidene-2-propanone (Scheme 1b) based on
the observed results. Thus, the initially formed cycloheptadiene
would isomerize rapidly under the reaction conditions because
a base (PPh3) is present in the reaction mixture. The presence of the
acetyl group instead of the ethoxycarbonyl group would enhance
the acidity of the cycloheptadiene and accelerate the isomerization
reaction.
Though compound 2 was assumed to be the most stable isomer
based on the theoretical study, the formation of 2 was not observed
under the acidic conditions. The result could be explained in terms
of the high energy barrier for the conversion of 3 (or 4) to 2
(Scheme 7). Thus, the acid-catalyzed isomerization of 3–4 (or 4–3)
would proceed via cation 14,19 while the generation of the cation 15
is essential for the formation of 2. Since the cation 15 is less stable
The initial step of the reaction of the cycloheptadiene 5 proceeds
via similar deprotonation-protonation, and the intermediate 11
would be generated (Scheme 5b). The acidity of 11 is much higher
compared to that of 3, and the deprotonation of 11 would proceed
smoothly in the presence of DBU. The protonation of the anion 12
affords a mixture of 6 and 7. The results shown in Scheme 3 indicate
that the formation of 6 proceeded faster, and the base-catalyzed
compared to 14, which has a longer
p-conjugated system, the
formation of 2 would be suppressed. The structures and relative
energies of 14 and 15 were calculated, and we confirmed that the
cation 15 is 32.83 kJ/mol less stable than 14.

Y. Fukusaki et al. / Tetrahedron 65 (2009) 10631–10636
10635
CO2Et
B
O
O
O
O
H
H
-H
4
t-Bu
H
H
H
CO2Et
H
t-Bu
t-Bu
14
(more stable)
CO2Et
t-Bu
-H
t-Bu
t-Bu
(a)
t-Bu
1
t-Bu
CO2Et
3
2
t-Bu
t-Bu
15
t-Bu
(less stable)
t-Bu
3
Scheme 7.
O
O
B
3. Conclusion
O
O
H
H
EtO2C
In conclusion, we studied the isomerization of cycloheptadiene
derivatives, which was prepared by the intermolecular [3þ2þ2]
cycloaddition reaction of ethyl cyclopropylideneacetate with
alkynes, under thermal, basic and acidic conditions. The relative
stability of the products was calculated and the results were com-
pared with the observed isomer distributions. The mechanism of
the isomerization was discussed in detail. The study will contribute
to the understanding of the structure and stability, and reactivity of
cycloheptatriene derivatives.
CO2Et
CO2Et
CO2Et
EtO2C
EtO2C
EtO2C
CO2Et
5
CO2Et
CO2Et
4
B
H
1
CO2Et
CO2Et
EtO2C
EtO2C
CO2Et
EtO2C
2
EtO2C
CO2Et
12
4. Experimental
11
(b)
H
H
4.1. Typical experimental procedures
CO2Et
CO2Et
4.1.1. Isomerization of 1 under thermal conditions. A solution of 1
(59 mg, 0.2 mmol) in dry DMF (2 mL) was heated at 100 ꢀC for 64 h.
The reaction mixture was purified by a silica gel column chroma-
tography (hexane/AcOEt 40:1) to give a mixture of products
(48.9 mg, 83%). The ratio was estimated by 1H NMR analysis.
B
CO2Et
CO2Et
CO2Et
CO2Et
EtO2C
EtO2C
EtO2C
EtO2C
6
7
4.1.2. Isomerization of 1 under basic conditions. A mixture of 1
(290 mg, 1 mmol) and DBU (15.0 ml, 0.1 mmol) was stirred at room
Scheme 5.
temperature under Ar. The progress of the reaction was monitored
by TLC. The mixture was purified by silica gel column chromatog-
raphy (hexane/AcOEt 100:1) to give 3.
H
O
O
O
O
4.1.3. Isomerization of 1 under acidic conditions. To a solution of
cycloheptadiene 1 (29 mg, 0.1 mmol) in dioxane (10 mL) was added
TFA (5 mL, 64.9 mmol) under Ar and the mixture was stirred at
room temperature. The progress of the reaction was monitored by
TLC. The residue was purified by silica gel column chromatography
(hexane/AcOEt 60:1) to give 3 and 4.
H
t-Bu
t-Bu
t-Bu
t-Bu
1
H
O
HO
O
O
CO2Et
H
(b)
4.1.3.1. Compound 2. Colorless oil; 1H NMR (300 MHz, CDCl3)
6.30 (d, J¼5.8 Hz, 1H), 6.11 (s, 1H), 5.93 (d, J¼5.8 Hz, 1H), 4.17 (q,
J¼7.2 Hz, 2H), 3.22 (s, 2H), 2.38 (s, 2H), 1.27 (t, J¼7.2 Hz, 3H), 1.15 (s,
9H), 1.13 (s, 9H); 13C NMR (125 MHz, CDCl3) 171.7, 152.3, 146.3,
128.6, 125.4, 121.2, 118.0, 60.7, 42.2, 36.3, 36.2, 32.1, 30.6, 29.4, 14.2;
IR (neat) 2964, 1738, 1626, 1463, 1362, 1249, 1155, 1034 cmꢁ1. HRMS
(ESI) Calcd for [C19H30O2þNa]þ: 313.2138. Found: 313.2136.
H
H
(a)
t-Bu
t-Bu
t-Bu
(a)
t-Bu
path a
t-Bu
(a)
t-Bu
4
13
H
H
O
path b
CO2Et
O
H
4.1.3.2. Compound 3. Pale yellow oil; 1H NMR (400 MHz, CDCl3)
6.34 (s, 1H), 5.99 (s, 1H), 5.23 (t, J¼6.9 Hz, 1H), 4.10 (q, J¼7.2 Hz, 2H),
3.08(s, 2H), 2.19 (d, J¼6.6 Hz, 2H),1.21 (t, J¼7.2 Hz, 3H),1.14 (s, 9H) 1.11
(s, 9H); 13C NMR (150 MHz, CDCl3) 172.2, 152.8, 147.9, 130.6, 122.7,
121.3,116.6, 60.4, 41.4, 36.4, 35.9, 30.7, 29.8, 28.8,14.2; IR (neat) 2964,
2905, 2870,1736,1626,1551,1476,1463,1389,1362,1328,1297, 1250,
t-Bu
t-Bu
t-Bu
t-Bu
3
Scheme 6.

10636
Y. Fukusaki et al. / Tetrahedron 65 (2009) 10631–10636
1153,1096,1034,933,864,794,731, 648, 440, 412 cmꢁ1. Anal. Calcdfor
C19H30O2: C, 78.6; H, 10.4. Found: C, 78.3; H, 10.6.
precluded the detailed analysis of the reaction. When the thermal reaction was
carried out in toluene, the reaction was very sluggish. The total yield of the
isomers was 31% and the starting material still remained when the reaction
was carried out at 100 ꢀC for 231 h. The decomposition of 1 was observed when
the reaction of 1 was carried out in dioxane at 100 ꢀC.
6. Exposure of 1 to a solution of DBU in dioxane for a long period at room tem-
perature also afforded 3. The structure of 3 was confirmed by an NOESY
experiment as shown below.
4.1.3.3. Compound 4. Pale yellow oil; 1H NMR (300 MHz, CDCl3)
6.62 (s, 1H), 6.00 (d, J¼1.2 Hz, 1H), 5.23 (t, J¼6.9 Hz, 1H), 4.12 (q,
J¼7.2 Hz, 2H), 3.21 (d, J¼0.9 Hz, 2H), 2.19 (d, J¼6.9 Hz, 2H), 1.24 (t,
J¼7.2 Hz, 3H), 1.15 (s, 9H), 1.05 (s, 9H); 13C NMR (150 MHz, CDCl3)
171.6,150.9,146.5,130.5,123.7,123.2,115.0, 60.6, 43.6, 36.3, 34.9, 31.5,
30.6, 30.3, 14.2; IR (neat) 3452, 3048, 2965, 2869, 2360, 1739, 1637,
NOE
CO2Et
1464,1389,1364,1330,1248,1154,1036, 866, 822, 669, 468, 406 cmꢁ1
.
H
H
Anal. Calcd for C19H30O2: C, 78.6; H, 10.4. Found: C, 78.3; H, 10.7.
H
t-Bu
NOE
H
4.1.3.4. Compound 6. Pale yellow oil; 1H NMR (300 MHz, CDCl3)
7.72 (d, J¼6.3 Hz, 1H), 6.43 (d, J¼6.3 Hz, 1H), 4.70 (s, 1H), 3.87–4.33
(m, 10H), 3.48 (d, J¼15.3 Hz, 1H), 3.35 (d, J¼15.9 Hz, 1H), 1.03–1.32
(m, 15H); 13C NMR (150 MHz, CDCl3) 171.7, 150.8, 146.5, 130.5, 123.7,
123.2, 114.9, 60.6, 43.6, 36.3, 34.8, 31.4, 30.7, 30.65 30.60, 30.3, 29.8,
14.2; IR (neat) 3629, 3433, 2983, 2940, 2905, 1732, 1627, 1556, 1466,
1446, 1391, 1368, 1253, 1178, 1095, 1055, 1027, 958, 918, 863, 841,
772, 729, 471 cmꢁ1. Anal. Calcd for C23H30O10: C, 59.2; H, 6.48.
Found: C, 59.0; H, 6.48.
3
t-Bu
7. We also monitored the isomerization of 1 in dioxane-d8-TFA by 1H NMR and
confirmed that compounds 3 and 4 were formed and isomerized in the reaction
mixture.
8. Though we carried out the isomerization of several substrates to examine the
effect of the substituents, the isolation and analysis of the products turned out
to be extremely difficult.
9. The structures of 6 and 7 were confirmed by an NOESY experiment and an
HMBC experiment as shown below.
4.1.3.5. Compound 7. Pale yellow oil; 1H NMR (300 MHz, CDCl3)
7.42 (d, J¼6.0 Hz, 1H), 6.81 (d, J¼6.3 Hz, 1H), 5.59 (s, 1H), 3.91–4.36
(m, 10H), 3.36 (d, J¼16.2 Hz, 1H), 3.29 (d, J¼16.2 Hz, 1H), 1.11–1.31
(m, 15H); 13C NMR (150 MHz, CDCl3) 169.5, 168.6, 167.1, 164.7, 164.3,
139.3, 136.0, 134.4, 133.2, 128.0, 124.9, 62.1, 61.9, 61.6, 61.3, 61.1, 41.5,
40.7, 14.2, 14.1, 14.0, 14.0, 13.8; IR (neat) 3648, 2983, 2939, 2906,
1738, 1616, 1541, 1467, 1446, 1391, 1368, 1331, 1258, 1176, 1097, 1082,
HMBC
NOE
CO2Et
CO2Et
H
H
HMBC
CO2Et
CO2Et
H
H
C
EtO2C
EtO2C
NOE
C
CO2Et
CO2Et
H
EtO2C
EtO2C
H
6
7
1053, 1028, 937, 862, 803, 766, 441 cmꢁ1. Anal. Calcd for C23H30O10
C, 59.2; H, 6.48. Found: C, 59.1; H, 6.47.
:
10. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, J. T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Lyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian03,
Revision B.03; Gaussian: Pittsburgh, PA, 2003.
11. The theoretical calculation of 5 and the isomers was not carried out since the
compounds were expected to adopt various conformations and the analysis
would be very difficult.
12. Compound B was synthesized by the [3þ2þ2] cocyclization and an X-ray
crystallographic analysis was carried out. The details are described in Supple-
mentary data.
13. (a) Saebø, S.; Boggs, J. E. J. Mol. Struct.: THEOCHEM 1982, 87, 365–373; (b)
Schulman, J. M.; Disch, R. L.; Sabio, M. L. J. Am. Chem. Soc. 1982, 104, 3785–3788;
(c) Kao, J. J. Am. Chem. Soc. 1987, 109, 3817–3829; (d) Donovan, W. H.; White, W.
E. J. Org. Chem. 1996, 61, 969–977.
Acknowledgements
S.K. thanks JSPS for providing Research Fellowships for Young
Scientists.
Supplementary data
Experimental procedures and characterization data (pdf), and
the details of the X-ray structural determination of B (CIF) are
available. Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2009.10.065.
References and notes
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18. Calculation indicated that the stability of 13 was comparable to that of 15 (vide
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19. Attempted observation of the cation 14 in TFA was unsuccessful, probably due
to the low basicity of 3. Alternatively, the formation of another cationic species,
which was tentatively assigned as a tropylium ion, was observed. As for the
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5. When the thermal reaction of 1 was carried out at higher temperature (130 ꢀC)
or for a longer period (150 h), the amount of 1 decreased and compound 2 was
formed as the major product. However, the formation of unidentified products