Lewis acid promoted reactions of ethenetricarboxylates with allenes: Synthesis of indenes and γ-lactones via conjugate addition/cyclization reaction

Article abstract of DOI:10.1021/jo1009855

(Figure presented) Indenes are important core structures in organic chemistry. Few simple arylallenes have been used to construct indene skeletons by Friedel-Crafts reaction. Lewis acid catalyzed reaction of ethenetricarboxylates 1 and arylallenes has been examined in this study. The reaction of arylallenes and ethenetricarboxylate triesters with SnCl₄ gave indene derivatives efficiently, via a conjugate addition/Friedel-Crafts cyclization reaction. On the other hand, the reactions of 1,1-diethyl 2-hydrogen ethenetricarboxylate and arylallenes or alkylallenes with SnCl₄ at -78 °C or room temperature and subsequent treatment with Et₃N gave γ-lactones. The reactions of triethyl ethenetricarboxylate and 1,1-dialkylallenes with SnCl₄ at room temperature also gave γ-lactones.

Full text of DOI:10.1021/jo1009855

pubs.acs.org/joc
Lewis Acid Promoted Reactions of Ethenetricarboxylates
with Allenes: Synthesis of Indenes and γ-Lactones via Conjugate
Addition/Cyclization Reaction
Shoko Yamazaki,*,† Yuko Yamamoto,† Yugo Fukushima,† Masachika Takebayashi,†
Tetsuma Ukai,† and Yuji Mikata‡
†Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, Japan, and
‡KYOUSEI Science Center, Nara Women’s University, Nara 630-8506, Japan
yamazaks@nara-edu.ac.jp
Received May 19, 2010
Indenes are important core structures in organic chemistry. Few simple arylallenes have been used to
construct indene skeletons by Friedel-Crafts reaction. Lewis acid catalyzed reaction of ethenetri-
carboxylates 1 and arylallenes has been examined in this study. The reaction of arylallenes and
ethenetricarboxylate triesters with SnCl4 gave indene derivatives efficiently, via a conjugate addition/
Friedel-Crafts cyclization reaction. On the other hand, the reactions of 1,1-diethyl 2-hydrogen
ethenetricarboxylate and arylallenes or alkylallenes with SnCl4 at -78 °C or room temperature and
subsequent treatment with Et3N gave γ-lactones. The reactions of triethyl ethenetricarboxylate and
1,1-dialkylallenes with SnCl4 at room temperature also gave γ-lactones.
Introduction
used as ligands in metallocene-based olefin polymerization
catalysts.3 There have been a number of reports on the
development of synthetic methods to construct indene ring
systems.4 Among the methods developed, Lewis acid cata-
lyzed intramolecular and intermolecular Friedel-Crafts re-
actions of arynes leading to indene derivatives have been
effectively utilized.5 Allene derivatives play an important
Indenes are important core structures in organic chemis-
try. They serve as building blocks for bioactive pharmaceu-
tical compounds1 and functional materials.2 They are also
ꢀ
(1) (a) Guillon, J.; Dallemagne, P.; Leger, J.-M.; Sopkova, J.; Bovy, P. R.;
Jarry, C.; Rault, S. Bioorg. Med. Chem. 2002, 10, 1043. (b) Kolanos, R.;
Siripurapu, U.; Pullagurla, M.; Riaz, M.; Setola, V.; Roth, B. L.; Dukat, M.;
Glennon, R. A. Bioorg. Med. Chem. Lett. 2005, 15, 1987. (c) Watanabe, N.;
Nakagava, H.; Ikeno, A.; Minato, H.; Kohayakawa, C.; Tsuji, J. Bioorg.
Med. Chem. Lett. 2003, 13, 4317. (d) Karaguni, I.-M.; Glusenkamp, K.-H.;
Langerak, A.; Geisen, C.; Ullrich, V.; Winde, G.; Moroy, T.; Muller, O.
Bioorg. Med. Chem. Lett. 2002, 12, 709.
(2) (a) Barber, J.; Rakitin, O. A.; Ros, M. B.; Torroba, T. Angew. Chem.,
Int. Ed. 1998, 37, 296. (b) Yang, J.; Lakshmikantham, M. V.; Cava, M. P.;
Lorcy, D.; Bethelot, J. R. J. Org. Chem. 2000, 65, 6739.
(5) (a) Olah, G. A.; Krishnamurit, R.; Prakash, G. K. S. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds; Pergamon Press: Oxford,
1991; Vol. 3, p 293. (b) Heaney, H. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds; Pergamon Press: Oxford, 1991; Vol. 2, p 753.
(c) Johnson, W. S. Org. React. 1944, 2, 114. For recent examples, see: (d)
Womack, G. B.; Angeles, J. G.; Fanelli, V. E.; Heyer, C. A. J. Org. Chem.
2007, 72, 7046. (e) Rendy, R.; Zhang, Y.; McElrea, A.; Gomez, A.; Klumpp,
D. A. J. Org. Chem. 2004, 69, 2340. (f ) Ho, T.-L.; Lee, K.-Y.; Chen, C.-K.
J. Org. Chem. 1997, 62, 3365. (g) Zhou, X.; Zhang, H.; Xie, X.; Li, Y. J. Org.
Chem. 2008, 73, 3958. (h) Basavaiah, D.; Reddy, K. R. Org. Lett. 2007, 9, 57.
(i) Fillion, E.; Fishlock, D. Tetrahedron 2009, 65, 6682. ( j) Zhang, X.; Teo,
W. T.; Chan, P. W. H. Org. Lett. 2009, 11, 4990. (k) Wang, S.; Zhu, Y.; Wang,
Y.; Lu, P. Org. Lett. 2009, 11, 2615. (l) Reeves, J. T.; Fandrick, D. R.; Tan, Z.;
Song, J. J.; Yee, N. K.; Senanayake, C. H. Tetrahedron Lett. 2009, 50, 3077.
(m) Shi, M.; Xu, B.; Huang, J.-W. Org. Lett. 2004, 6, 1175.
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(3) Alt, H. G.; Koppl, A. Chem. Rev. 2000, 100, 1205.
(4) For recent examples, see: (a) Khan, Z. A.; Wirth, T. Org. Lett. 2009,
11, 229. (b) Saito, A.; Umakoshi, M.; Yagyu, N.; Hanzawa, Y. Org. Lett.
2008, 10, 1783. (c) Kuninobu, Y.; Nishina, Y.; Takai, K. Org. Lett. 2006, 8,
2891. (d) Peng, L.; Zhang, X.; Zhang, S.; Wang, J. J. Org. Chem. 2007, 72,
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5216 J. Org. Chem. 2010, 75, 5216–5222
Published on Web 07/16/2010
DOI: 10.1021/jo1009855
r
2010 American Chemical Society

Yamazaki et al.
JOCArticle
SCHEME 1
TABLE 1. Reaction of 1b-e and Arylallenes 2a-c,ea
entry 1 2 Lewis Acid (equiv) tempb Z1 Z2 yield (%)c
3
X
1
2
3
4
5
6
7
8
9
1b 2a
1b 2a
1b 2a
1b 2a
1c 2a
1c 2a
1d 2a
1e 2a
1b 2b
SnCl4 (0.2)
SnCl4 (1.0)
AlCl3 (0.2)
ZnI2 (0.2)
SnCl4 (0.2)
SnCl4 (1.0)
SnCl4 (1.0)
SnCl4 (1.0)
SnCl4 (1.0)
SnCl4 (0.2)
SnCl4 (0.2)
SnCl4 (1.0)
SnCl4 (0.2)
SnCl4 (0.2)
ZnI2 (0.2)
AlCl3 (0.2)
rt
rt
3a CO2Et
3a CO2Et
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
99
86
69
71
81
71
93
64
81
92
79
99
86
0d
80 °C 3a CO2Et
80 °C 3a CO2Et
rt
rt
rt
rt
rt
80 °C 3e CO2Et Cl
rt
rt
3b CO2Me H
3b CO2Me H
3c CO2 Pr H
i
3d CN
3e CO2Et Cl
H
10 1b 2b
11 1b 2c
12 1b 2c
13 1b 2c
14 1b 2e
15 1b 2e
16 1b 2e
3f CO2Et Me Me
3f CO2Et Me Me
80 °C 3f CO2Et Me Me
rt
rt
rt
3g CO2Et OMe H
3g CO2Et OMe H
3g CO2Et OMe H
30e
44e
aReactions were carried out with 0.5-1.0 mmol of 1, 1 equiv of 2, and
b
Lewis acid in 1-2 mL of solvent for 17-19 h. CH2Cl2 was used as a
c
d
solvent at rt, and ClCH2CH2Cl was used at 80 °C. Isolated yield. A
complex mixture. eSmall amounts of impurity could not be removed. A
trace amount of the possible indene regioisomer could be formed as a
minor product; however, it was not confirmed because of the difficulty in
removal of other impurities.
Results and Discussion
A Lewis acid catalyzed reaction of ethenetricarboxylates
and arylallenes has been examined. The arylallenes were
prepared from 1,1-dibromocyclopropanes.6a,11 Since SnCl4
has been shown to be an effective catalyst for reactions
of ethenetricarboxylates 1 with alkenes and allenes
(Scheme 1),9,10 the SnCl4-catalyzed reaction was initially
examined. The reaction of 1,1-diarylallenes 2a,b,c and ethe-
netricarboxylate triesters 1b-d and the analogue 1e with
SnCl4 at room temperature overnight gave indene deriva-
tives 3a-f in 64-99% yield, via conjugate addition/Friedel-
Crafts cyclization reaction (eq 1, Table 1, entries 1-13). The
indene structure of the product 3b was determined by X-ray
analysis (Figure S1 in Supporting Information).
The catalytic use (0.2 equiv) of other Lewis acids such as
AlCl3 and ZnI2 was also effective for the indene formation
for the reaction of 1b and 2a. The reaction temperature was
raised to 80 °C in 1,2-dichloroethane when the reaction did
not go to completion at room temperature (entries 3, 4, 10).
The reaction of 1b and 2a with 0.2 equiv of ZnBr 2 at room
temperature or 80 °C also produced indene 3a; however the
reaction did not go to completion, and the product 3a could
not be isolated from the starting material 1b by column
chromatography. Use of 0.2 equiv of FeCl3, TiCl4, InBr3,
role in organic synthesis because of their structural features.6
However, few simple arylallenes have been used to construct
indene skeletons by Friedel-Crafts reaction.7,8 Herein, we
report a new indene formation via Lewis acid promoted
conjugate addition/Friedel-Crafts reactions of arylallenes.
We have recently studied various Lewis acid promoted
reactions of ethenetricarboxylate derivatives 1 and reported
that they function as highly electrophilic Michael acceptors.
For example, the reaction of 1,1-diethyl 2-hydrogen ethene-
tricarboxylate (1a) and various alkenes in the presence of a
Lewis acid gave cycloadduct γ-lactones (route a in Scheme 1).9
We have also reported that the reaction of ethenetricarbox-
ylate triester with chloroallenes, which are generated in situ
by the reaction of γ-trifluoromethyl-R-aryl propargyl alco-
hols and SnCl4, gave cyclobutane derivatives (route b).10
Simple arylallenes are expected to add to ethenetricarbo-
xylates in the presence of Lewis acid and undergo further bond
formation reaction on benzene ring via the common zwitter-
ionic intermediate A (route c). In this study, Lewis acid
catalyzed reactions of ethenetricarboxylates and arylallenes
and also alkylallenes for comparison have been examined.
Zn(OTf )2, Sc(OTf )3, and BF4 Et2O at room temperature or
3
80 °C gave starting materials or complex mixtures. The
appropriate selection of Lewis acids among numerous Lewis
acids is still a difficult task.12,5a The alkene 1 needs to be
activated with Lewis acid for 1,1-diphenylallene 2a, which
has relatively low nucleophilicity and is unstable.6 SnCl4 may
have suitable Lewis acidity for this reaction.
(6) (a) The Chemistry of Allenes; Landor, S. R., Ed; Academic: London,
1982; Vol. 1. (b) Modern Allene Chemistry; Krause, N., Hashmi, A. S. K.,
Eds; Wiley-VCH: Weinheim, 2004; Vols. 1 and 2. (c) Ma, S. Palladium-
Catalyzed Two- or Three-Component Cyclization of Functionalized Allenes in
Palladium in Organic Synthesis; Tsuji, J., Ed; Springer: Berlin, 2005; pp
183-210. (d) Ma, S. Acc. Chem. Res. 2009, 42, 1679. (e) Zimmer, R.; Dinesh,
C. U; Nandanan, E.; Khan, F. A. Chem. Rev. 2000, 100, 3067. (f ) Ma, S.
Chem. Rev. 2005, 105, 2829. (g) Ma, S. Acc. Chem. Res. 2003, 36, 701. (h)
Sydnes, L. K. Chem. Rev. 2003, 103, 1133. (i) Hassan, H. H. A. M. Curr. Org.
Synth. 2007, 4, 413.
The reaction of 2a and 1,1-diethyl 2-ethyl, methyl, and
isopropyl ethenetricarboxylates 1b-d gave indene derivatives
smoothly,; however, 1,1-diethyl 2-tert-butyl ethenetricarboxylate
(7) (a) Lu, J.-M.; Shi, M. Org. Lett. 2006, 8, 5317. (b) Xu, G.-C.; Liu,
L.-P.; Lu, J.-M.; Shi, M. J. Am. Chem. Soc. 2005, 127, 14552.
ꢀ
(8) For synthesis of tetralines, see: Tarselli, M. A.; Gagne, M. R. J. Org.
Chem. 2008, 73, 2439.
(9) Yamazaki, S.; Ohmitsu, K.; Ohi, K.; Otsubo, T.; Moriyama, K. Org.
(11) Baird, M. S.; Nizovtsev, A. V.; Bolesov, I. G. Tetrahedron 2002, 58,
1581.
Lett. 2005, 7, 759.
(10) Yamazaki, S.; Yamamoto, Y.; Mikata, Y. Tetrahedron 2009, 65,
1988.
(12) (a) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817. (b) Lewis Acids in
Organic Synthesis; Yamamoto, H., Ed; Wiley-VCH: Weinheim, 2000; Vols. 1
and 2.
J. Org. Chem. Vol. 75, No. 15, 2010 5217

Yamazaki et al.
JOCArticle
TABLE 2. Reaction of 1b-e and 1-Aryl-1-methylallenes 2f-h
SCHEME 2
entry
1
2
SnCl4 (equiv)
3
R
Z
yield (%)
1
2
3
4
1b
1c
1b
1b
2f
2f
2g
2h
1.0
1.0
1.0
0.2
3h
3i
3j
3k
Et
Me
Et
H
H
Cl
Me
53
48
52
65a
Et
aUse of 1 equiv of SnCl4 gave 3k in lower yield (ca. 19%) as a mixture
with diethyl malonate.
t
(1f, X = CO2 Bu) gave a mixture containing a dimethyl-
γ-lactone derivative by the Lewis acid catalyzed formal isomeri-
zation reaction of 1f.9
room temperature gave indene derivative 3l in 17% yield
along with a complex mixture (Scheme 2). Interestingly, the
reactions of 1a and 2a at -78 °C and subsequent treatment
with Et3N gave γ-lactone 5a in 55% yield.
The reaction of 1b and 1,1-di(4-methoxyphenyl)allene (2d,
Z1 = Z2 = OMe) with SnCl4 or ZnI2 (0.2 equiv) at room
temperature gave a complex mixture along with an unreacted
starting material 1b. The reaction of unsymmetrically sub-
stituted 1,1-diarylallene 2e with SnCl4 (0.2 equiv) also gave a
complex mixture. The reaction with ZnI2 or AlCl3 (0.2 equiv)
gave an indene derivative 3g as a major product but in lower
yield (30-44% yield) (Table 1, entries 15 and 16).
A Lewis acid catalyzed cycloaddition reaction of 1,1-
diethyl 2-hydrogen ethenetricarboxylate (1a) and various
aryl and alkyl allenes has also been examined (eq 3, Table 3).
The reactions of 1a and 1-aryl-1-methylallenes 2f,g and phe-
nylallene 2i in the presence of SnCl4 (1 equiv) at -78 °C and
subsequent treatment with Et3N gave R,β-unsaturated-γ-lac-
tones 5f,g as the only isolable products. The reaction of 1-aryl-
1-methylallenes 2f,g at room temperature decreased the yields
of the lactone 5f,g, but the formation of the corresponding
indene derivatives was not observed (entries 1-4). The reac-
tions of 1a and alkyl allenes 2j,k,l in the presence of SnCl4 at
-78 °C or room temperature and treatment with Et3N gave
R,β-unsaturated-γ-lactones 5j,k,l in 17-49% yield.
The reactions of 1,1-diethyl 2-hydrogen ethenetricarbo-
xylate (1a) and allenes 2 in the presence of SnCl4 gave
exomethylene γ-lactones 4 and/or the conjugated isomers,
R,β-unsaturated-γ-lactones 5 after usual workup. The exo-
methylene γ-lactones 4 are unstable to distillation or column
chromatography and difficult to be purified. Treatment of
γ-lactones 4 or the mixture of 4 and 5 with Et3N gave
γ-lactones 5. For dialkyl substituted allenes, 2j,k,l and
phenylallene 2i, the product yields increased slightly at room
temperature (entries 5-11).
The reaction of 1-aryl-1-methylallenes 2f,g,h and ethenetri-
carboxylate triesters 1b,c with SnCl4 gave indene derivatives
3h-k with somewhat lower yields than the corresponding 1,1-
diarylallenes (48-65% yield, eq 2, Table 2). This may be due to
the lower stability of the intermediate A (Scheme 1) for R1 =
Me, compared to R1 = aryl. For 1-aryl-1-methylallenes, use of
1 equiv of SnCl4 gave better yields than the catalytic use of
SnCl4 or other Lewis acids except for entry 4.
The reaction of phenylallene 2i (PhCHdCdCH2) and 1b
in the presence of SnCl4 gave a complex mixture. The reaction
of diethyl benzylidenemalonate (PhCHdC(CO2Et)2) with
allene 2a in the presence of SnCl4 was also examined. The
reaction gave the starting material, diethyl benzylidenemalo-
nate, and a complex mixture, and the possible indene product
could not be isolated. Thus, the high reactivity of ethenetri-
carboxylate triesters 1 compared to benzylidenemalonate was
shown by this efficient indene formation.
Next, the SnCl4-catalyzed reaction of triethyl ethenetricar-
boxylate (1b) and alkylallenes 2j,k,l was examined. The reac-
tion of 1,1-dialkylallenes at room temperature also gave
γ-lactones with better yields than the reaction of 1a and 2a-c, in
49-82% yield (eq 4).13 One ethyl group is lost in the reaction.14
The reactions of 1,1-diethyl 2-hydrogen ethenetricarbo-
xylate (1a) and allene 2a in the presence of SnCl4 (1 equiv) at
(13) Use of 0.2 equiv of SnCl4 led to incomplete reaction.
(14) Snider, B. B.; Roush, D. M. J. Org. Chem. 1979, 44, 4229.
5218 J. Org. Chem. Vol. 75, No. 15, 2010

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JOCArticle
TABLE 3. Reaction of 1a and Aryl and Alkylallenes 2a
SCHEME 3
entry
2
R1
R2
temp/time
5
yield (%)
1
2
3
4
5
6
7
8
2f
2f
2g
2g
2i
2i
2j
2j
Me
Me
Me
Me
H
Ph
Ph
4-Cl-C6H4
4-Cl-C6H4
Ph
Ph
Me
Me
-78 °C/3 h
rt/17 h
-78 °C/3 h
rt/17 h
-78 °C/3 h
rt/17 h
-78 °C/3 h
rt/17 h
5f
5f
5g
5g
5i
5i
5j
5j
49
25
45
38
43
63
H
Me
Me
Me
Me
39 (49b)
46
14
17
31c
9
10
11
2k
2k
2l
(CH2)4CH3
(CH2)4CH3
-(CH2)5-
-78 °C/3 h
rt/17 h
rt/17 h
5k
5k
5l
aReactions were carried out with 0.5 mmol of 2, 1 equiv (0.5 mmol) of
1a, and 1 equiv (0.5 mmol) of SnCl4 in CH2Cl2 (2 mL) unless otherwise
stated. b2 equiv of 1a was used. cAt -78 °C, a trace amount of 5l formed.
In the reaction of 1b and 2j, other Lewis acids, AlCl3, FeCl3,
TiCl4, and ZnBr2, gave a small amount of 5j, which could not
be isolated, along with the starting material 1b and complex
mixtures. Efficiency of SnCl4 may arise from its suitable Lewis
acidity for the reaction of 1b and 2j, similar to the reaction of 1b
and 2a. Stronger Lewis acids such as AlCl3 and FeCl3, may lead
to decomposition of starting materials or products. Further
study on the choice of Lewis acids is under investigation.
SCHEME 4
The probable mechanism for indene formation is shown in
Scheme 3. Initially, SnCl4 may coordinate to 1 in the diester
moiety as shown. The coordination increases the electrophi-
licity of Cβ of 1. Conjugate addition of allene at C2 to SnCl4-
coordinated 1 gives a stabilized allylic and benzylic cation
intermediate A.15 Friedel-Crafts cyclization from the inter-
mediate A leads to the indene skeleton. The transformation
might also be considered as 4π-electrocycization of a dienyl
cation.16 Further study on the effect of Lewis acids to
conjugate addition and cyclization is under investigation.
Formation of γ-lactones from 1a and 1b may also proceed
through the common allylic cation intermediate A (Scheme 4).
Formation of intermediate B may be reversible. The reaction
of 1a and arylarenes at lower temperature leads to γ-lactones 4
and 5. At higher temperature the equilibrium moves to the
stable C-C bond formation through a Friedel-Crafts reac-
tion in the case of arylallenes. Using these simple aryl and
alkylallenes, cyclobutanes have not been formed under the
reaction conditions.
synthesize functionalized indene derivatives. Investigation of
the detailed reaction mechanism, further study on the use of
the other electrophiles in indene fomation, and transforma-
tion of the products to potentially useful compounds are
under investigation.
Experimental Section
Typical Experimental Procedure (eq 1, Table 1, entry 1). To a
solution of 1 (122 mg, 0.5 mmol) in CH2Cl2 (1 mL) were added
allene (2a) (96 mg, 0.5 mmol) and SnCl4 (26 mg, 12 μL, 0.1
mmol). The mixture was stirred at room temperature for 17 h.
The reaction mixture was quenched by water and then saturated
aqueous NaHCO3. The mixture was extracted with dichloro-
methane, and the organic phase was dried (Na2SO4) and evaporated
in vacuo. The residue was purified by column chromatography over
silica gel with hexane-ether as eluent to give 3a (218 mg, 99%).
In summary, a new reaction of ethenetricarboxylates and
arylallenes in the presence of SnCl4 to give indene derivatives
3 was found. The tandem conjugate addition/Friedel-Crafts
cyclization of arylallenes may become a useful method to
1
3a. Rf = 0.4 (hexane-ether = 2:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 0.913 (t, J = 7.1 Hz, 3H), 1.21 (t,
J = 7.1 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H), 3.42 (d, J = 23.0 Hz,
1H), 3.67 (d, J = 23.0 Hz, 1H), 3.79 (dq, J = 10.6, 7.1 Hz, 1H),
4.01 (dq, J = 10.8, 7.1 Hz, 1H), 4.09-4.24 (m, 5H), 4.50 (d, J =
11.7 Hz, 1H), 7.18-7.26 (m, 3H), 7.38-7.51 (m, 6H). Selected
NOEs are between δ 4.50 (CH) and δ 4.09-4.24 (CH(CO2Et)2),
7.38-7.51 (Ph) and between δ 3.67 (indene C(1)HH) and δ
(15) 1,1-Diphenylallene 2a has larger HOMO at C2 (HOMO coefficients:
C2, þ0.44; C1, þ0.36; C3, -0.07). These calculations were performed at the
RHF/STO-3G//B3LYP/6-31G* level.
(16) (a) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital
Symmetry; Verlag Chemie: Weinheim, 1970. (b) Habermas, K. L.; Denmark,
S. E.; Jones, T. K. Org. React. 1994, 45, 1. (c) Pellissier, H. Tetrahedron 2005,
61, 6479. (d) Frontier, A. J.; Collison, C. Tetrahedron 2005, 61, 7577. (e)
Suzuki, T.; Ohwada, T.; Shudo, K. J. Am. Chem. Soc. 1997, 119, 6774.
J. Org. Chem. Vol. 75, No. 15, 2010 5219

Yamazaki et al.
JOCArticle
4.09-4.24 (CH(CO2Et)2); 13C NMR (100.6 MHz, CDCl3) δ
(ppm) 13.7 (q), 14.0 (q), 14.1 (q), 37.9 (t), 44.8 (d), 54.1 (d), 61.59
(t), 61.62 (t), 61.9 (t), 120.7 (d), 123.8 (d), 125.4 (d), 126.4 (d),
127.9 (d), 128.7 (d), 129.2 (d), 134.0 (s), 135.2 (s), 142.7 (s), 144.5
(s), 145.2 (s), 167.2 (s), 167.8 (s), 171.6 (s). Selected HMBC
correlations are between δ 4.50 (CH) and δ 135.2 (indene C(2)),
144.5 (indene C(3)), 37.9 (indene C(1)H2), between δ 4.09-4.24
(CH(CO2Et)2) and δ 135.2 (indene C(2)), and between δ 3.42,
3.67 (indene C(1)H2) and δ 135.2 (indene C(2)), 144.5 (indene
C(3)); IR (neat) 2982, 1733, 1462, 1444, 1369, 1300, 1230, 1159,
1029 cm-1; MS (EI) m/z 436 (Mþ, 19), 390 (48), 380 (46), 337
(100%); HRMS Mþ 436.1885 (calcd for C26H28O6 436.1886).
3b. Rf = 0.3 (hexane-ether = 2:1); colorless crystals, mp
102-104 °C (hexane-EtOAc); 1H NMR (400 MHz, CDCl3) δ
(ppm) 0.906 (t, J = 7.1 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H), 3.41 (d,
J = 23.0 Hz, 1H), 3.67 (d, J = 23.0 Hz, 1H), 3.72 (s, 3H), 3.79
(dq, J = 10.7, 7.1 Hz, 1H), 4.01 (dq, J = 10.7, 7.1 Hz, 1H),
4.11-4.24 (m, 2H), 4.19 (d, J = 11.7 Hz, 1H) 4.53 (d, J = 11.7
Hz, 1H), 7.18-7.26 (m, 3H), 7.38-7.43 (m, 1H), 7.44-7.51 (m,
5H). Selected NOEs are between δ 4.53 (CH) and δ 4.19
(CH(CO2Et)2), 7.44-7.51 (Ph) and between δ 3.67 (indene
C(1)HH) and δ 4.19 (CH(CO2Et)2); 13C NMR (100.6 MHz,
CDCl3) δ (ppm) 13.6 (q), 14.0 (q), 38.0 (t), 44.6 (d), 52.7 (q), 54.1
(d), 61.6 (t), 61.9 (t), 120.7 (d), 123.8 (d), 125.5 (d), 126.4 (d),
127.9 (d), 128.7 (d), 129.1 (d), 133.9 (s), 135.0 (s), 142.7 (s), 144.5
(s), 145.1 (s), 167.1 (s), 167.8 (s), 172.2 (s). Selected HMBC
correlations are between δ 4.53 (CH) and δ 135.0 (indene C(2)),
144.5 (indene C(3)), 38.0 (indene C(1)H2), between δ 4.19
(CH(CO2Et)2) and δ 135.0 (indene C(2)), and between δ 3.41,
3.67 (indene C(1)H2) and δ 135.0 (indene C(2)), 144.5 (indene
C(3)); IR (KBr) 2992, 1750, 1734, 1371, 1311, 1286, 1266, 1146
cm-1; MS (EI) m/z 422 (Mþ, 34), 390 (92), 298 (55), 288 (51), 203
(100%); HRMS Mþ 422.1730 (calcd for C25H26O6 422.1729).
Anal. Calcd for C25H26O6: C, 71.07; H, 6.20. Found: C, 71.02;
H, 6.21.
δ (ppm) 13.8 (q), 14.0 (q), 30.6 (d), 38.2 (t), 54.2 (d), 62.4 (t), 62.7
(t), 118.2 (s), 121.1 (d), 124.0 (d), 126.2 (d), 126.8 (d), 128.5 (d),
128.8 (d), 129.2 (d), 131.5 (s), 133.1 (s), 142.2 (s), 144.4 (s), 145.7
(s), 165.3 (s), 165.9 (s). Selected HMBC correlations are between
δ 4.63 (CH) and δ 131.5 (indene C(2)), 145.7 (indene C(3)), 38.2
(indene C(1)H2), between δ 3.91 (CH(CO2Et)2) and δ 131.5
(indene C(2)), and between δ 3.64, 3.72 (indene C(1)H2) and δ
131.5 (indene C(2)), 145.7 (indene C(3)); IR (neat) 2983, 2244,
1758-1732, 1491, 1463, 1444, 1391, 1370, 1300, 1258, 1192,
1096, 1030 cm-1; MS (EI) m/z 389 (Mþ, 100), 343 (13), 315 (24),
286 (29), 270 (43%); HRMS Mþ 389.1624 (calcd for C24H23NO4
389.1627).
3e. Rf = 0.6 (hexane-ether = 2:1); colorless crystals, mp
1
88-89 °C; H NMR (400 MHz, CDCl3) δ (ppm) 0.953 (t, J =
7.1 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H), 3.41
(d, J = 23.2 Hz, 1H), 3.64 (d, J = 23.2 Hz, 1H), 3.84 (dq, J = 10.8,
7.1 Hz, 1H), 4.03 (dq, J = 10.8, 7.1 Hz, 1H), 4.10-4.25 (m, 4H),
4.16 (d, J = 11.7 Hz, 1H), 4.40 (d, J = 11.7 Hz, 1H), 7.05 (dd, J =
8.1, 0.4 Hz, 1H), 7.23 (dd, J = 8.1, 1.9 Hz, 1H), 7.39 (bd, J = 8.1
Hz, 2H), 7.44 (dd, J = 1.9, 0.4 Hz, 1H), 7.48 (d-like, J = 8.1 Hz,
2H). Selected NOEs are between δ 4.40 (CH) and δ 4.16
(CH(CO2Et)2), 7.39 (Ar) and between δ 3.64 (indene C(1)HH)
and δ4.16 (CH(CO2Et)2);13C NMR (100.6 MHz, CDCl3) δ(ppm)
13.8 (q), 14.0 (q), 14.1 (q), 37.9 (t), 44.9 (d), 53.8 (d), 61.7 (t), 61.8
(t), 62.0 (t), 121.2 (d), 124.3 (d), 126.8 (d), 129.2 (d), 130.5 (d), 131.8
(s), 132.0 (s), 134.1 (s), 136.2 (s), 142.8 (s), 143.3 (s), 144.2 (s), 167.1
(s), 167.6 (s), 171.1 (s). Selected HMBC correlations are between δ
4.40 (CH) and δ 136.2 (indene C(2)), 142.8 (indene C(3)), 37.9
(indene C(1)H2), between δ 4.16 (CH(CO2Et)2) and δ 136.2
(indene C(2)), and between δ 3.41, 3.64 (indene C(1)H2) and δ
136.2 (indene C(2)), 142.8 (indene C(3)); IR (KBr) 2984, 1737,
1728, 1307, 1252, 1229, 1162, 1039 cm-1; MS (EI) m/z 506 (Mþ,
6.3), 504 (Mþ, 8.8), 460 (15), 458 (22), 430 (23), 384 (26), 356 (35),
271 (81), 249 (100%); HRMS Mþ 504.1113, 506.1095 (calcd for
C26H26Cl2O6 504.1106, 506.1077). Anal. Calcd for C26H26Cl2O6:
C, 61.79; H, 5.19. Found: C, 61.91; H, 5.21.
3c. Rf = 0.5 (hexane-ether = 2:1); colorless crystals, mp
82-83 °C (hexane); 1H NMR (400 MHz, CDCl3) δ (ppm) 0.912
(t, J = 7.1 Hz, 3H), 1.18 (d, J = 6.2 Hz, 3H), 1.22 (t, J = 7.1 Hz,
3H), 1.28 (d, J = 6.2 Hz, 3H), 3.43 (d, J = 22.9 Hz, 1H), 3.67 (d,
J = 22.9 Hz, 1H), 3.79 (dq, J = 10.8, 7.1 Hz, 1H), 4.01 (dq, J =
10.8, 7.1 Hz, 1H), 4.09-4.23 (m, 2H), 4.18 (d, J = 11.7 Hz, 1H)
4.46 (d, J = 11.7 Hz, 1H), 5.00 (septet, J = 6.2 Hz, 1H), 7.18-7.26
(m, 3H), 7.38-7.42 (m, 1H), 7.46-7.51 (m, 5H). Selected NOEs
are between δ4.46 (CH) andδ4.18 (CH(CO2Et)2), 7.46-7.51 (Ph)
and between δ 3.67 (indene C(1)HH) and δ 4.18 (CH(CO2Et)2);
13C NMR (100.6 MHz, CDCl3) δ (ppm) 13.7 (q), 14.0 (q), 21.6 (q),
21.7 (q), 37.8 (t), 45.1 (d), 54.1 (d), 61.6 (t), 61.8 (t), 69.1 (d), 120.6
(d), 123.8 (d), 125.3 (d), 126.4 (d), 127.8 (d), 128.7 (d), 129.2 (d),
134.0 (s), 135.4 (s), 142.7 (s), 144.5 (s), 145.2 (s), 167.2 (s), 167.8 (s),
170.9 (s). Selected HMBC correlations are between δ 4.46 (CH)
and δ 135.4 (indene C(2)), 144.5 (indene C(3)), 37.8 (indene
C(1)H2), between δ 4.18 (CH(CO2Et)2) and δ 135.4 (indene C(2)),
and between δ 3.43, 3.67 (indene C(1)H2) and δ 135.4 (indene
C(2)), 144.5 (indene C(3)); IR (KBr) 2986, 1736, 1726, 1461, 1369,
1311, 1230, 1104, 1038 cm-1; MS (EI) m/z 450 (Mþ, 67), 390 (99),
362 (86), 288 (88), 244 (75), 216 (100%); HRMS Mþ 450.2046
(calcd for C27H30O6 450.2042). Anal. Calcd for C27H30O6: C,
71.98; H, 6.71. Found: C, 71.87; H, 6.68.
3f. Rf = 0.6 (hexane-ether = 2:1); colorless crystals, mp
87-88 °C (hexane); 1H NMR (400 MHz, CDCl3) δ (ppm) 0.918
(t, J = 7.1 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H), 1.24 (t, J = 7.1 Hz,
3H), 2.39 (s, 3H), 2.42 (s, 3H), 3.36 (d, J = 22.9 Hz, 1H), 3.61 (d,
J = 22.9 Hz, 1H), 3.79 (dq, J = 10.8, 7.1 Hz, 1H), 4.00 (dq, J =
10.8, 7.1 Hz, 1H), 4.08-4.23 (m, 4H), 4.17 (d, J = 11.7 Hz, 1H),
4.48 (d, J = 11.7 Hz, 1H), 7.05 (dd, J = 7.7, 0.6 Hz, 1H), 7.08 (d,
J = 7.7 Hz, 1H), 7.28 (d, J = 7.7 Hz, 2H), 7.28-7.29 (m, 1H),
7.36 (d, J = 7.7 Hz, 2H). Selected NOEs are between δ 4.48 (CH)
and δ 4.17 (CH(CO2Et)2), 7.36 (Ar) and between δ 3.61 (indene
C(1)HH) and δ 4.17 (CH(CO2Et)2); 13C NMR (100.6 MHz,
CDCl3) δ (ppm) 13.7 (q), 14.0 (q), 14.1 (q), 21.4 (q), 21.5 (q), 37.6
(t), 44.8 (d), 54.0 (d), 61.5 (t), 61.6 (t), 61.8 (t), 120.3 (d), 124.7
(d), 127.1 (d), 129.0 (d), 129.4 (d), 131.2 (s), 133.8 (s), 135.2 (s),
137.4 (s), 142.7 (s), 143.0 (s), 144.3 (s), 167.2 (s), 167.9 (s), 171.7
(s). Selected HMBC correlations are between δ 4.48 (CH) and δ
133.8 (indene C(2)), 144.3 (indene C(3)), 37.6 (indene C(1)H2),
between δ 4.17 (CH(CO2Et)2) and δ 133.8 (indene C(2)), and
between δ 3.36, 3.61 (indene C(1)H2) and δ 133.8 (indene C(2)),
144.3 (indene C(3)); IR (KBr) 2981, 1758, 1736, 1646, 1508,
1464, 1370, 1263, 1160, 1022 cm-1; MS (EI) m/z 464 (Mþ, 22),
418 (21), 326 (42), 231 (100%); HRMS Mþ 464.2197 (calcd for
C28H32O6 464.2199). Anal. Calcd for C28H32O6: C, 72.39; H,
6.94. Found: C, 72.66; H, 7.07.
3d. Rf = 0.3 (hexane-ether = 2:1); pale yellow oil; 1H NMR
(400 MHz, CDCl3) δ (ppm) 1.02 (t, J = 7.1 Hz, 3H), 1.28 (d, J =
7.1 Hz, 3H), 3.64 (d, J = 22.7 Hz, 1H), 3.72 (d, J = 22.7 Hz, 1H),
3.91 (d, J = 10.6 Hz, 1H), 3.96 (dq, J = 10.8, 7.1 Hz, 1H), 4.08
(dq, J = 10.8, 7.1 Hz, 1H), 4.21-4.33 (m, 2H), 4.63 (d, J = 10.6
Hz, 1H), 7.18-7.23 (m, 1H), 7.25-7.31 (m, 2H), 7.37-7.40 (m,
2H), 7.43-7.48 (m, 1H), 7.51-7.55 (m, 3H). Selected NOEs are
between δ 4.63 (CH) and δ 3.91 (CH(CO2Et)2), 7.37-7.40 (Ph)
and between δ 3.64, 3.72 (indene C(1)H2) and δ 3.91
(CH(CO2Et)2), 7.51-7.55 (Ar); 13C NMR (100.6 MHz, CDCl3)
3g (including a small amount of impurity). Rf = 0.4
1
(hexane-ether = 2:1); pale yellow oil; H NMR (400 MHz,
CDCl3) δ (ppm) 0.913 (t, J = 7.1 Hz, 3H), 1.21 (t, J = 7.1 Hz,
3H), 1.25 (t, J = 7.1 Hz, 3H), 3.38 (d, J = 22.7 Hz, 1H), 3.63 (d,
J = 22.7 Hz, 1H), 3.79 (dq, J = 10.6, 7.1 Hz, 1H), 3.82 (s, 3H),
4.01 (dq, J = 10.6, 7.1 Hz, 1H), 4.10-4.24 (m, 4H), 4.17 (d, J =
11.7 Hz, 1H), 4.46 (d, J = 11.7 Hz, 1H), 6.79 (dd, J = 8.4, 2.4
Hz, 1H), 7.06 (d, J = 2.0 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H),
5220 J. Org. Chem. Vol. 75, No. 15, 2010

Yamazaki et al.
JOCArticle
7.37-7.42 (m, 1H), 7.47-7.50 (m, 4H). Selected NOEs are
between δ 4.46 (CH) and δ 4.17 (CH(CO2Et)2), 7.47-7.50
(Ar) and between δ 3.63 (indene C(1)HH) and δ 4.17
(CH(CO2Et)2); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 13.7
(q), 14.0 (q), 14.1 (q), 37.9 (t), 44.8 (d), 54.0 (d), 55.6 (q), 61.5 (t),
61.6 (t), 61.8 (t), 110.2 (d), 112.1 (d), 121.0 (d), 127.8 (d), 128.7
(d), 129.1 (d), 132.7 (s), 134.2 (s), 138.3 (s), 144.0 (s), 144.5 (s),
158.4 (s), 167.2 (s), 167.8 (s), 171.7 (s). Selected HMBC correla-
tions are between δ 4.46 (CH) and δ 132.7 (indene C(2)),
144.0 (indene C(3)), 37.9 (indene C(1)H2), between δ 4.17
(CH(CO2Et)2) and δ 132.7 (indene C(2)), and between δ 3.38,
3.63(indeneC(1)H2) andδ132.7 (indene C(2)), 144.0(indeneC(3));
IR (neat) 2982, 1732, 1609, 1480, 1466, 1445, 1369, 1287, 1269, 1248,
1176, 1032 cm-1; MS (EI) m/z 466 (Mþ, 76), 420 (66), 318 (76), 233
(100%); HRMS Mþ 466.1990 (calcd for C27H30O7 466.1992).
(s), 138.2 (s), 144.2 (s), 144.4 (s), 167.4 (s), 167.9 (s), 171.4 (s).
Selected HMBC correlations are between δ 4.47 (CH) and δ 133.9
(indeneC(2)), 138.2 (indeneC(3)), 37.6(indeneC(1)H2), betweenδ
4.16 (CH(CO2Et)2) and δ 133.9 (indene C(2)), and between δ 3.21,
3.43 (indene C(1)H2) and δ 133.9 (indene C(2)), 138.2 (indene
C(3)); IR (neat) 2982, 1733, 1467, 1391, 1369, 1300, 1227, 1160,
1096, 1029 cm-1; MS (EI) m/z 410 (Mþ, 23), 408 (Mþ, 60), 364
(22), 362 (59), 334 (74), 153 (100%); HRMS Mþ 408.1334,
410.1319 (calcd for C21H25ClO6 408.1340, 410.1310).
3k. Rf = 0.4 (hexane-ether = 2:1); pale yellow oil; 1H NMR
(400 MHz, CDCl3) δ (ppm) 0.983 (t, J = 7.1 Hz, 3H), 1.20 (t, J =
7.1 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), 2.13 (t, J = 2.2 Hz, 3H), 2.38
(s, 3H), 3.17 (dq, J = 22.6, 1.8 Hz, 1H), 3.40 (d, J = 22.6, 2.0 Hz,
1H), 3.91-4.29 (m, 6H), 4.18 (d, J = 11.8 Hz, 1H), 4.47 (d, J =
11.8 Hz, 1H), 7.09 (d-like, J = 7.7 Hz, 1H), 7.17 (d, J = 7.7 Hz,
1H), 7.22 (bs, 1H). Selected NOEs are between δ 4.47 (CH) and δ
4.18 (CH(CO2Et)2), 2.13 (CH3), between δ 3.40 (indene C(1)HH)
and δ 4.18 (CH(CO2Et)2), and between δ 2.13 (CH3) and δ 7.17
(indene H(4)); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 10.6 (q),
13.8 (q), 14.05 (q), 14.13 (q), 21.5 (q), 37.5 (t), 44.8 (d), 53.7 (d),
61.4 (t), 61.6 (t), 61.9 (t), 118.8 (d), 124.4 (d), 126.9 (d), 132.3 (s),
134.8 (s), 138.6 (s), 142.9 (s), 143.4 (s), 167.5 (s), 168.0 (s), 171.7 (s).
Selected HMBC correlations are between δ 4.47 (CH) and δ 132.3
(indene C(2)), 138.6 (indene C(3)), 37.5 (indene C(1)H2), between
δ 4.18 (CH(CO2Et)2) and δ 132.3 (indene C(2)), and between δ
3.17, 3.40 (indene C(1)H2) and δ 132.3 (indene C(2)), 138.6 (indene
C(3)); IR (neat) 2982, 1752, 1734, 1369, 1299, 1159, 1030 cm-1;MS
(EI) m/z 388 (Mþ, 93), 342 (100), 314 (92), 268 (88%); HRMS Mþ
388.1886 (calcd for C22H28O6 388.1886). Anal. Calcd for
C22H28O6: C, 68.02; H, 7.27. Found: C, 67.73; H, 7.00.
3l. Rf = 0.3 (hexane-ether =1:2); colorless crystals, mp
156-159 °C; 1H NMR (400 MHz, CDCl3) δ (ppm) 0.917 (t,
J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H), 3.48 (d, J = 22.9 Hz,
1H), 3.66 (d, J = 22.9 Hz, 1H), 3.80 (dq, J = 10.8, 7.1 Hz, 1H),
4.03 (dq, J = 10.8, 7.1 Hz, 1H), 4.09-4.24 (m, 2H), 4.14 (d, J =
11.6 Hz, 1H) 4.54 (d, J = 11.6 Hz, 1H), 7.18-7.24 (m, 3H),
7.39-7.50 (m, 6H). Selected NOEs are between δ 4.54 (CH) and δ
4.14 (CH(CO2Et)2), 7.39-7.50 (Ph) and between δ 3.66 (indene
C(1)HH) and δ 4.14 (CH(CO2Et)2); 13C NMR (100.6 MHz,
CDCl3) δ (ppm) 13.7 (q), 14.0 (q), 37.9 (t), 44.5 (d), 53.9 (d),
61.8 (t), 62.1 (t), 120.8 (d), 123.9 (d), 125.6 (d), 126.5 (d), 128.0 (d),
128.8 (d), 129.2 (d), 133.8 (s), 134.2 (s), 142.7 (s), 145.0 (s), 145.3 (s),
166.9 (s), 167.6 (s), 176.5 (s). Selected HMBC correlations are
between δ 4.54 (CH) and δ 134.2 (indene C(2)), 145.3 (indene
C(3)), 37.9 (indene C(1)H2), between δ 4.14 (CH(CO2Et)2) and δ
134.2 (indene C(2)), and between δ 3.48, 3.66 (indene C(1)H2) and
δ 134.2 (indene C(2)), 145.3 (indene C(3)); IR (KBr) 3050-2590,
2981, 1746, 1705, 1463, 1296, 1267, 1189, 1149, 1031 cm-1;MS(EI)
m/z 408 (Mþ, 6.8), 390 (21), 364 (32), 298 (37), 244 (59), 215 (75),
204 (100%); HRMS Mþ 408.1574 (calcd for C24H24O6 408.1573).
Typical Procedure for Preparation of γ-Lactones. To a solu-
tion of 1,1-diethyl 2-hydrogen ethenetricarboxylate (1a) (108
mg, 0.5 mmol) (prepared from 1,1-diethyl 2-tert-butyl ethene-
tricarboxylate (1f ) upon treatment with CF3CO2H)9 in dichlo-
romethane (1 mL) was added 3-methyl-1,2-butadiene (2j) (34 mg,
50 μL, 0.5 mmol), followed by SnCl4 (130 mg, 60 μL, 0.5 mmol) at
-78 °C. The mixture was stirred for 3 h. The reaction mixture was
quenched by water. The mixture was extracted with dichloro-
methane, and the organic phase was washed with saturated
aqueous NaHCO3, dried (Na2SO4), and evaporated in vacuo to
give crude γ-lactone 4 (R1 = R2 = Me).
1
3h. Rf = 0.4 (hexane-ether = 2:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 0.972 (t, J = 7.1 Hz, 3H), 1.21 (t,
J = 7.1 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H), 2.16 (t, J = 2.0 Hz,
3H), 3.22 (dq, J = 22.2, 2.0 Hz, 1H), 3.44 (d, J = 22.2, 2.0 Hz,
1H), 3.91-4.30 (m, 6H), 4.19 (d, J = 11.8 Hz, 1H), 4.50 (d, J =
11.8 Hz, 1H), 7.16-7.22 (m, 1H), 7.26-7.31 (m, 2H), 7.40 (d,
J = 7.3 Hz, 1H). Selected NOEs are between δ 4.50 (CH) and δ
4.19 (CH(CO2Et)2), 2.16 (CH3), between δ 3.44 (indene C(1)HH)
and δ 4.19 (CH(CO2Et)2), and between δ 2.16 (CH3) and δ
7.26-7.31 (indene H(4)); 13C NMR (100.6 MHz, CDCl3) δ
(ppm) 10.6 (q), 13.8 (q), 14.05 (q), 14.12 (q), 37.7 (t), 44.8 (d),
53.8 (d), 61.4 (t), 61.6 (t), 61.9 (t), 119.2 (d), 123.5 (d), 125.1 (d),
126.3 (d), 133.4 (s), 138.8 (s), 142.6 (s), 145.9 (s), 167.4 (s), 168.0 (s),
171.6 (s). Selected HMBC correlations are between δ 4.50 (CH)
and δ 133.4 (indene C(2)), 138.8 (indene C(3)), 37.7 (indene
C(1)H2), between δ 4.19 (CH(CO2Et)2) and δ 133.4 (indene C(2)),
and between δ 3.22, 3.44 (indene C(1)H2) and δ 133.4 (indene
C(2)), 138.8 (indene C(3)); IR (neat) 2982, 1733, 1467, 1369, 1300,
1158, 1030 cm-1; MS (EI) m/z 374 (Mþ, 56), 328 (83), 300 (100%);
HRMS Mþ 374.1726 (calcd for C21H26O6 374.1729). Anal. Calcd
for C21H26O6: C, 67.36; H, 7.00. Found: C, 67.18; H, 6.97.
1
3i. Rf = 0.4 (hexane-ether = 2:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 0.973 (t, J = 7.1 Hz, 3H), 1.28 (t,
J = 7.1 Hz, 3H), 2.15 (t, J = 2.2 Hz, 3H), 3.22 (dq, J = 22.5, 2.2
Hz, 1H), 3.44 (d, J = 22.5, 2.2 Hz, 1H), 3.67 (s, 3H), 3.91-4.05
(m, 2H), 4.17-4.30 (m, 2H), 4.19 (d, J = 11.8 Hz, 1H), 4.52 (d,
J = 11.8 Hz, 1H), 7.16-7.22 (m, 1H), 7.26-7.31 (m, 2H), 7.39
(d-like, J = 7.3 Hz, 1H). Selected NOEs are between δ 4.52 (CH)
and δ 4.19 (CH(CO2Et)2), 2.15 (CH3), between δ 3.44 (indene
C(1)HH) and δ 4.19 (CH(CO2Et)2), and between δ 2.15 (CH3)
and δ 7.26-7.31 (indene H(4)); 13C NMR (100.6 MHz, CDCl3)
δ (ppm) 10.6 (q), 13.8 (q), 14.1 (q), 37.7 (t), 44.6 (d), 52.5 (q), 53.8
(d), 61.6 (t), 62.0 (t), 119.2 (d), 123.5 (d), 125.2 (d), 126.3 (d),
133.2 (s), 138.9 (s), 142.6 (s), 145.8 (s), 167.4 (s), 168.0 (s), 172.2
(s). Selected HMBC correlations are between δ 4.52 (CH) and δ
133.2 (indene C(2)), 138.9 (indene C(3)), 37.7 (indene C(1)H2),
between δ 4.19 (CH(CO2Et)2) and δ 133.2 (indene C(2)), and
between δ 3.22, 3.44 (indene C(1)H2) and δ 133.2 (indene C(2)),
138.9 (indene C(3)); IR (neat) 2982, 1758-1733, 1468, 1436, 1369,
1299, 1161, 1032 cm-1; MS (EI) m/z 360 (Mþ, 45), 328 (92), 300
(100%); HRMS Mþ 360.1573 (calcd for C20H24O6 360.1573).
3j. Rf = 0.5 (hexane-ether = 1:1); colorless oil; 1H NMR (400
MHz, CDCl3) δ (ppm) 0.976 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1
Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H), 2.13 (t, J= 2.2 Hz, 3H), 3.21 (dq,
J= 22.7, 1.6 Hz, 1H), 3.43 (d, J= 22.7, 1.6 Hz, 1H), 3.91-4.30 (m,
6H), 4.16 (d, J = 11.7 Hz, 1H), 4.47 (d, J = 11.7 Hz, 1H), 7.19 (dd,
J = 8.0, 0.5 Hz, 1H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H), 7.36 (dd, J =
2.0, 0.5 Hz, 1H). Selected NOEs are between δ4.47 (CH) andδ4.16
(CH(CO2Et)2), 2.13 (CH3), between δ 3.43 (indene C(1)HH) and δ
4.16 (CH(CO2Et)2), and between δ 2.13 (CH3) and δ 7.19 (indene
H(4)); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 10.6 (q), 13.8 (q),
14.05 (q), 14.13 (q), 37.6 (t), 44.8 (d), 53.7 (d), 61.5 (t), 61.6 (t), 62.0
(t), 120.0 (d), 123.9 (d), 126.5 (d), 128.3 (s), 129.6 (s), 131.1 (s), 133.9
4 (R1 = R2 = Me). Colorless oil; 1H NMR (400 MHz, CDCl3)
δ (ppm) 1.29 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.52 (s,
3H), 1.56 (s, 3H), 3.97 (ddd, J = 3.8, 3.3, 2.8 Hz, 1H), 4.01 (d, J =
3.8 Hz, 1H), 4.18-4.32 (m, 4H), 5.09 (dd, J = 2.8, 1.3 Hz, 1H),
5.12 (dd, J = 3.3, 1.3 Hz, 1H). Selected NOEs are between δ 5.12
(dCHH) and δ 1.52, 1.56 ((CH3)2), between δ 5.09 (dCHH) and δ
3.97 (CH), 4.01 (CH(CO2Et)2), between δ 3.97 (CH) and δ 1.52
J. Org. Chem. Vol. 75, No. 15, 2010 5221

Yamazaki et al.
JOCArticle
(CH3), and between δ 4.01 (CH(CO2Et)2) and δ 1.56 (CH3); 13
C
171.9 (OCdO); IR (neat) 2984, 1753, 1678, 1494, 1306, 1250,
1155, 1097, 1034, 1013 cm-1; MS (EI) m/z 382 (Mþ, 10), 380
(Mþ, 27), 339 (49), 337 (100), 291 (65), 263 (86), 139 (91%);
HRMS Mþ 380.1025, 382.1004 (calcd for C19H21ClO6 380.1027,
328.0997). Anal. Calcd for C19H21ClO6: C, 59.92; H, 5.56.
Found: C, 59.63; H, 5.55.
NMR (100.6 MHz, CDCl3) δ (ppm) 13.95 (q), 14.00 (q), 26.9 (q),
29.4 (q), 43.4 (d), 51.9 (d), 62.0 (t), 62.2 (t), 86.4 (s), 107.3 (t), 149.7
(s), 167.0 (s), 167.2 (s), 173.5 (s). Selected HMBC correlations are
between δ 5.09, 5.12 (dCH2), 1.52, 1.56 ((CH3)2) and δ 149.7
(CdCH2), between δ 5.09, 5.12 (dCH2), 1.52, 1.56 ((CH3)2) and δ
86.4 (OC(CH3)2), and between δ 5.09, 5.12 (dCH2) and δ 43.4
(CH); IR (neat) 2980, 1771, 1750, 1466, 1371, 1283, 1247, 1178,
1
5i. Rf = 0.3 (hexane-ether = 1:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 1.28 (t, J = 7.1 Hz, 3H), 1.31 (t, J =
7.1 Hz, 3H), 1.91 (s, 3H), 4.21-4.33 (m, 4H), 4.71 (s, 1H), 5.70 (s,
1H), 7.23-7.25 (m, 2H), 7.38-7.41 (m, 3H). Selected NOEs are
1119, 1033 cm-1
.
To a solution of the crude 4 (R1 = R2 = Me) in dichlo-
romethane (1 mL) was added triethylamine (51 mg, 69 μL, 0.5
mmol) at room temperature. The mixture was stirred for 1 h.
The reaction mixture was concentrated in vacuo. The residue
was purified by column chromatography over silica gel eluting
with hexane-ether (1:1) to give to give 5j (110 mg, 39%).
between δ 5.70 (OCHPh) and δ 1.91 (CH3), 7.23-7.25 (Ph); 13
C
NMR (100.6 MHz, CDCl3) δ (ppm) 13.4 (q), 14.1 (q), 47.9 (d),
62.3 (t), 62.4 (t), 85.8 (d), 120.4 (s), 127.4 (d), 129.2 (d), 129.7 (d),
134.2 (s), 165.1 (s), 166.58 (s), 166.64 (s), 172.8 (s). Selected
HMBC correlations are between δ 5.70 (OCHPh) and δ 172.8
(CO-O), 165.1 (CdCCH3), 134.2 (Ph) and between δ 1.91 (CH3)
and δ 165.1 (CdCCH3), 85.8 (OCHPh), 120.4 (CdCCH3);
IR (neat) 2984, 1752, 1679, 1456, 1369, 1307, 1261, 1156, 1030
cm-1; MS (EI) m/z 332 (Mþ, 85), 258 (50), 213 (67), 169 (99),
105 (100%); HRMS Mþ 332.1261 (calcd for C18H20O6
332.1260).
1
5j. Rf = 0.4 (hexane-ether = 1:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 1.28 (t, J = 7.1 Hz, 6H), 1.47 (s, 6H),
2.05 (s, 3H), 4.23 (q, J = 7.1 Hz, 2H), 4.24 (q, J = 7.1 Hz, 2H),
4.61 (s, 1H). Selected NOEs are between δ 1.47 ((CH3)2) and δ
2.05 (CH3); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 12.2 (q),
14.1 (q), 24.5 (q), 47.7 (d), 62.2 (t), 86.6 (s), 119.0 (s), 166.8 (s),
170.1 (s), 171.6 (s). Selected HMBC correlations are between δ
1.47 ((CH3)2) and δ 170.1 (CdCCH3), 86.6 (OC(CH3)2) and
between δ 2.05 (CH3) and δ 170.1 (CdCCH3), 86.6 (OC(CH3)2),
119.0 (CdCCH3); IR (neat) 2982, 1755, 1681, 1465, 1368, 1293,
1264, 1156, 1032 cm-1; MS (EI) m/z 284 (Mþ, 100), 269 (29%);
HRMS Mþ 284.1263 (calcd for C14H20O6 284.1260).
1
5k. Rf = 0.4 (hexane-ether = 1:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 0.859 (t, J = 7.0 Hz, 3H), 0.98-1.08
(m, 1H), 1.19-1.32 (m, 5H), 1.275 (t, J = 7.1 Hz, 3H), 1.277 (t,
J = 7.1 Hz, 3H), 1.44 (s, 3H), 1.61-1.68 (m, 1H), 1.83-1.90 (m,
1H), 2.00 (s, 3H), 4.20-4.26 (m, 4H), 4.62 (s, 1H). Selected
NOEs are between δ 1.44 (CH3) and δ 2.00 (CH3); 13C NMR
(100.6 MHz, CDCl3) δ (ppm) 12.4 (q), 14.02 (q), 14.08 (q), 14.11
(q), 22.46 (t), 22.48 (t), 23.8 (q), 31.7 (t), 37.0 (t), 47.8 (d), 62.2 (t),
88.9 (s), 120.0 (s), 166.80 (s), 166.82 (s), 169.1 (s), 172.0 (s).
Selected HMBC correlations are between δ 1.44 (CH3) and δ
169.1 (CdCCH3), 88.9 (OCCH3) and between δ 2.00 (CH3) and
δ 169.1 (CdCCH3), 88.9 (OCCH3), 120.0 (CdCCH3); IR (neat)
2938, 2865, 1752, 1464, 1369, 1305, 1256, 1154, 1036 cm-1; MS
(EI) m/z 341 ((Mþ1)þ, 35), 340 (Mþ, 3.4), 297 (100%); HRMS
Mþ 340.1890 (calcd for C18H28O6 340.1886).
1
5a. Rf = 0.2 (CH2Cl2); colorless oil; H NMR (400 MHz,
CDCl3) δ (ppm) 1.26 (t, J = 7.1 Hz, 6H), 2.06 (s, 3H), 4.24 (q,
J = 7.1 Hz, 4H), 4.74 (s, 1H), 7.29-7.32 (m, 4H), 7.36-7.40 (m,
6H). Selected NOEs are between δ 2.06 (CH3) and δ 4.74
(CH(CO2Et)2), 7.29-7.32 (Ph); 13C NMR (100.6 MHz, CDCl3)
δ (ppm) 14.1 (q), 14.4 (q), 48.0 (d), 62.3 (t), 93.6 (s), 121.0 (s),
128.0 (d), 128.6 (d), 129.0 (d), 138.2 (s), 166.6 (s), 168.1 (s), 171.9
(s). Selected HMBC correlations are between δ 2.06 (CH3) and δ
168.1 (CdCCH3), 93.6 (OCPh2), 121.0 (CdCCH3) and between
δ 4.74 (CH(CO2Et)2) and δ 168.1 (CdCCH3), 121.0 (CdCCH3),
166.6 (CO2Et), 171.9 (OCdO); IR (neat) 2983, 1755, 1677, 1447,
1305, 1177, 1157, 1034 cm-1; MS (EI) m/z 408 (Mþ, 24), 303
(82), 229 (63), 202 (58), 105 (100%); HRMS Mþ 408.1574 (calcd
for C24H24O6 408.1573).
1
5l. Rf = 0.6 (hexane-ether = 1:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 1.20-1.28 (m, 1H), 1.28 (t, J = 7.1
Hz, 6H), 1.52 (bd, J = 10.3 Hz, 2H), 1.66-1.84 (m, 7H), 2.03 (s,
3H), 4.226 (q, J = 7.1 Hz, 2H), 4.227 (q, J = 7.1 Hz, 2H), 4.61 (s,
1H). Selected NOEs are between δ 2.03 (CH3) and δ 4.61
(CH(CO2Et)2); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 12.4
(q), 14.0 (q), 21.9 (t), 24.6 (t), 33.2 (t), 47.7 (d), 62.1 (t), 88.3 (s),
119.1 (s), 166.8 (s), 170.3 (s), 171.9 (s). Selected HMBC
correlations are between δ 2.03 (CH3) and δ 170.3 (CdCCH3),
88.3 (OC(CH2)5-), 119.1 (CdCCH3) and between δ 4.61
(CH(CO2Et)2) and δ 170.3 (CdCCH3), 119.1 (CdCCH3),
166.8 (CO2Et), 171.9 (OCdO); IR (neat) 2983, 2939, 2864,
1
5f. Rf = 0.4 (hexane-ether = 1:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 1.25 (t, J = 7.1 Hz, 3H), 1.30 (t, J =
7.1 Hz, 3H), 1.88 (s, 3H), 1.89 (s, 3H), 4.228 (q, J = 7.1 Hz, 2H),
4.233-4.29 (m, 2H), 4.68 (s, 1H), 7.31-7.40 (m, 5H). Selected
NOEs are between δ 1.88 (CH3), 1.89 (CH3) and δ 7.31-7.40
(Ph); 13C NMR (100.6 MHz, CDCl3) δ (ppm) 12.5 (q), 14.05 (q),
14.06 (q), 22.3 (q), 47.8 (d), 62.3 (t), 88.8 (s), 119.3 (s), 125.7 (d),
128.85 (d), 128.85 (d), 137.5 (s), 166.6 (s), 166.7 (s), 169.6 (s),
172.2 (s). Selected HMBC correlations are between δ 1.88
(CH3), 1.89 (CH3) and δ 169.6 (CdCCH3), 88.8 (OCMePh)
and between δ 4.68 (CH(CO2Et)2) and δ 169.6 (CdCCH3),
119.3 (CdCCH3), 166.6 (CO2Et), 166.7 (CO2Et), 172.2
(OCdO); IR (neat) 2984, 1754, 1678, 1447, 1369, 1306, 1250,
1155, 1029 cm-1; MS (EI) m/z 346 (Mþ, 22), 303 (100), 229
(69%); HRMS Mþ 346.1422 (calcd for C19H22O6 346.1416).
1750, 1676, 1449, 1368, 1307, 1265, 1227, 1155, 1033 cm-1
;
MS (EI) m/z 324 (Mþ, 100), 279 (51), 232 (78), 223 (71), 133
(69%); HRMS Mþ 324.1574 (calcd for C17H24O6 324.1573).
Anal. Calcd for C17H24O6: C, 62.95; H, 7.46. Found: C, 62.49;
H, 7.38.
Acknowledgment. This work was supported by the Min-
istry of Education, Culture, Sports, Science, and Technology
of the Japanese Government. We thank Mr. Y. Matsui and
Mr. H. Yoshida (Nara University of Education) for experi-
mental help. We thank Nara Institute of Science and Tech-
nology (NAIST) and Prof. K. Kakiuchi (NAIST) for mass
spectra. We also thank to Prof. S. Umetani (Kyoto
University) for elemental analyses.
1
5g. Rf = 0.4 (hexane-ether = 1:1); colorless oil; H NMR
(400 MHz, CDCl3) δ (ppm) 1.26 (t, J = 7.1 Hz, 3H), 1.31 (t, J =
7.1 Hz, 3H), 1.87 (s, 3H), 1.88 (s, 3H), 4.24 (q, J = 7.1 Hz, 2H),
4.23-4.29 (m, 2H), 4.67 (s, 1H), 7.26 (d-like, J = 8.8 Hz, 2H),
7.35 (d-like, J = 8.8 Hz, 2H). Selected NOEs are between δ 1.87
(CH3), 1.88 (CH3) and δ 7.26 (Ar); 13C NMR (100.6 MHz,
CDCl3) δ (ppm) 12.4 (q), 14.0 (q), 22.2 (q), 47.7 (d), 62.3 (t), 88.1
(s), 119.6 (s), 127.2 (d), 129.0 (d), 134.9 (s), 136.1 (s), 166.49 (s),
166.54 (s), 169.2 (s), 171.9 (s). Selected HMBC correlations are
between δ 1.87 (CH3), 1.88 (CH3) and δ 169.2 (CdCCH3),
88.1 (OCMeAr) and between δ 4.67 (CH(CO2Et)2) and δ 169.2
(CdCCH3), 119.6 (CdCCH3), 166.49 (CO2Et), 166.54 (CO2Et),
Supporting Information Available: Additional experimental
procedures, spectral data, and crystallographic data including
CIF file. This material is available free of charge via the Internet
at http://pubs.acs.org.
5222 J. Org. Chem. Vol. 75, No. 15, 2010