Iridium-catalyzed [2+2+2] cycloaddition of α,ω-diynes with alkynyl ketones and alkynyl esters

Article abstract of DOI:10.1016/j.tet.2014.09.038

We found that the combination of [Ir(cod)Cl]₂ and rac-BINAP served as an efficient catalyst for the [2+2+2] cycloaddition of 2,7-nonadiyne derivatives and related compounds with alkynyl ketones and alkynyl esters. The corresponding products wer

Full text of DOI:10.1016/j.tet.2014.09.038

Tetrahedron 70 (2014) 8681e8689
Contents lists available at ScienceDirect
Tetrahedron
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Iridium-catalyzed [2þ2þ2] cycloaddition of
a,
u-diynes with alkynyl
ketones and alkynyl esters
*
Toru Hashimoto, Arisa Okabe, Takeshi Mizuno, Mao Izawa, Ryo Takeuchi
Department of Chemistry and Biological Science, Aoyama Gakuin University, 5-10-1 Fuchinobe, Chuo, Sagamihara, Kanagawa 252-5258, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2014
Received in revised form 12 September 2014
Accepted 12 September 2014
Available online 19 September 2014
We found that the combination of [Ir(cod)Cl]2 and rac-BINAP served as an efficient catalyst for the
[2þ2þ2] cycloaddition of 2,7-nonadiyne derivatives and related compounds with alkynyl ketones and
alkynyl esters. The corresponding products were obtained in high yields under mild reaction conditions.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Iridium
Cycloaddition
Alkyne
Alkynyl ketone
Alkynyl ester
1. Introduction
can be used in this reaction. However, we did not previously ex-
amine monoynes in which a functional group is directly connected
Aromatic compounds play important roles in chemistry as well
as material science. They are valuable building blocks for the syn-
thesis of pharmaceuticals, agrochemicals, and functional materials.
Traditionally, the synthesis of aromatic compounds has been based
on the electrophilic substitution of a benzene ring under acidic
conditions, which gives waste as a by-product.1 Multisubstituted
benzene requires a tedious multi-step synthesis. It would be useful if
organic chemists could synthesize the precise structure of such
compounds in a minimum number of steps and in an atom-
economical manner. Transition metal catalysis is a good solution
to this problem. The transition metal-catalyzed [2þ2þ2] cycload-
dition of alkynes is an efficient and atom-economical reaction for the
synthesis of multisubstituted benzenes, since multiple bonds can be
formed in a single operation under neutral conditions.2 A wide va-
riety of transition metal complexes such as those of Ni,3 Co,4 Rh,5
Ru,6 Pd,7 and Fe8 have been reported as catalysts for the construc-
tion of an aromatic ring by alkyne cycloaddition. Despite this prog-
ress, there is still a need to further improve the catalyst efficiency
and regio- and stereoselectivity. Newcatalysts are needed to address
these issues. In 2001, we first reported that an iridium complex was
to an alkyne carbon. The [2þ2þ2] cycloaddition of such monoynes is
especially important, since this reaction would be an atom-
economical and direct route to benzene substituted with a func-
tional group. Further extension of the scope of this reaction would
increase the value of an iridium catalyst in alkyne cycloaddition
chemistry.10 In this article, we report the [2þ2þ2] cycloaddition of
a,u-diynes with alkynyl ketones and alkynyl esters. We performed
a systematic study of the reaction and were able to extend the scope
of the iridium-catalyzed cycloaddition of alkynes. The reaction de-
scribed here is an atom-economical alternative to FriedeleCrafts
acylation and related reactions that give waste as a by-product.
2. Results and discussion
2.1. Optimization of the reaction conditions
Diyne 1a reacted with alkynyl ketone 2a to give 3aa. The phos-
phine ligand had a profound effect on the reaction. Screening of
phosphine ligands was performed in the reaction of diyne 1a with
2.0 equiv of alkynyl ketone 2a in the presence of 1 mol % [Ir(cod)Cl]2
under refluxing benzene at a ratio of P/Ir¼2. The results are sum-
marized in Table 1. [Ir(cod)Cl]2 without any ligand gave 3aa in 36%
yield (entry 1). PPh3 was not an effective ligand (entry 2), and the
yield of 3aa was only 10%. The reaction using DPPE gave 3aa in 49%
yield (entry 3) with a dimer of 1a (0.18 mmol) and a trimer of 1a
(0.04 mmol). The reaction with 2a competed with the dimerization
and trimerization of 1a. In our previous study, DPPE was the most
an efficient catalyst for the [2þ2þ2] cycloaddition of
a,u-diynes
with monoynes to give benzenes.9 However, the scope of function-
alized monoynes that were suitable for use in this reaction is still
relatively unexplored. Propargylic alcohols and propargylic amines
* Corresponding author. Tel.: þ81 42 759 6231; fax: þ81 42 759 6493; e-mail
address: takeuchi@chem.aoyama.ac.jp (R. Takeuchi).
http://dx.doi.org/10.1016/j.tet.2014.09.038
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

8682
T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
Table 1
Reaction of diyne 1a with alkynyl ketone 2aa
Entry
Ligand
Conditions
Yield of 3aab (%)
1
None
PPh3
DPPE
DPPP
DPPB
DPPF
BIPHEP
rac-BINAP
F-DPPE
Xantphos
rac-BINAP
rac-BINAP
rac-BINAP
rac-BINAP
rac-BINAP
Benzene, reflux, 24 h
Benzene, reflux, 24 h
Benzene, reflux, 3 h
Benzene, reflux, 24 h
Benzene, reflux, 24 h
Benzene, reflux, 24 h
Benzene, reflux, 24 h
Benzene, reflux, 12 h
Benzene, reflux, 24 h
Benzene, reflux, 24 h
Benzene, 50 ꢀC, 19 h
EtOH, reflux, 19 h
36
10
49
30
20
13
87
94
33
0
56
68
72
75
75
2c
3
4
5
6
7
8
9
10
11
12
13
14
15d
THF, reflux, 18 h
DCE, reflux, 18 h
Benzene, reflux, 1 h
a
Reaction conditions: 1a (1 mmol), 2a (2 mmol) in the presence of catalyst in solvent (5 mL).
Isolated yield.
PPh3 (4 mol %).
b
c
d
Compounds 1a (0.5 mmol), 2a (0.6 mmol) in the presence of catalyst in solvent (2.5 mL).
effective ligand for the reaction of 1a with a simple terminal alkyne
decreased the yield of 3aa from 94% to 56% (entry 11). Benzene gave
better results than EtOH, THF, and DCE (entries 12e14).
The molar ratio of 2a to 1a was important for obtaining 3aa in
high yield. A decrease in the molar ratio of 2a/1a from 2 to 1.2
decreased the yield of 3aa from 94% to 75% (entry 15). Thus, a ratio
of 2.0 equiv of 2a to 1a is needed to obtain 3aa in high yield.
and an internal alkyne such as 1-hexyne or 3-hexyne. The moderate
yield of 3aa could be explained by the fact that [Ir(cod)Cl]2/DPPE
effectively promoted the dimerization and trimerization of 1a. As
the number of methylene units between the two phosphorous
atoms in diphosphine increased from 2 to 4, the yield of 3aa de-
creased from 49% to 20% (entry 5). Biaryldiphosphine was more
effective for the reaction than DPPE, DPPP, DPPB, and DPPF. The
reaction using BIPHEP gave 3aa in 87% yield (entry 7). rac-BINAP
was the best ligand (entry 8), and 3aa was obtained in 94% yield.
Xantphos and F-DPPE were less effective (entries 9 and 10). Thus,
the reaction conditions were optimized using rac-BINAP as a ligand.
A reduction in the reaction temperature from 80 ꢀC to 50 ꢀC
2.2. Scope of alkynyl ketones 2 and alkynyl esters 4
We examined the reaction of 1a with various alkynyl ketones 2
under the optimized reaction conditions described above. A wide
range of alkynyl ketones could be used in the reaction, and the
results are summarized in Table 2. The effect of the substituent on
Table 2
Scope of alkynyl ketone 2a
Entry
Alkynyl ketone 2
Time (h)
Product 3
Yield of 3b (%)
1
2
2b: R1¼n-Hex, R2¼Et
24
8
24
24
1
17
17
18
17
19
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
91
92
70
89
56
76
82
53
75
91
2c: R1¼n-Oct, R2¼Et
3c
4d
5
2d: R1¼Ph, R2¼Et
2e: R1¼1-cyclohexenyl, R2¼Et
2f: R1¼n-Bu, R2¼Ph
6
7
8
9
2g: R1¼n-Bu, R2¼CH]CHCH3
2h: R1¼n-Oct, R2¼Me
2i: R1¼n-Bu, R2¼2-thienyl
2j: R1¼n-Bu, R2¼isopropyl
2k: R1¼n-Bu, R2¼n-Pent
3aj
3ak
10
a
Reaction conditions: 1a (1 mmol), 2 (2 mmol), [Ir(cod)Cl]2 (0.01 mmol), rac-BINAP (0.02 mmol) in benzene (5 mL).
b
c
Isolated yield.
Toluene (5 mL).
BIPHEP (0.02 mmol).
d

T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
8683
alkyne was examined by using ethyl ketone. A longer alkyl group
such as an n-hexyl group or n-octyl group gave good results. Diyne
1a smoothly reacted with 2b and 2c to give 3ab and 3ac in re-
spective yields of 91% and 92% (entries 1 and 2). Phenyl-substituted
ketone 2d gave the product in a lower yield than with longer alkyl-
substituted ketones 2b and 2c. The reaction with 2d gave 3ad in
70% yield (entry 3). Alkenyl-substituted ketone 2e gave the product
3ae in a yield that was comparable to those with longer alkyl-
substituted ketones 2b and 2c. The reaction with 2e gave 3ae in
89% yield (entry 4). The substituent on ketone also affected the
reaction. The reactions of 1a with phenyl ketone 2f and alkenyl
ketone 2g gave lower yields than those with ethyl ketone (2aec)
(entries 5 and 6). The reaction of 1a with methyl ketone 2h gave
3ah in 82% yield (entry 7). The reaction with methyl ketone 2h gave
a slightly decreased yield compared to that with ethyl ketone 2c.
The reaction with 2-thienyl ketone 2i gave a yield comparable to
that with phenyl ketone 2f (entry 8). A thiophene ring could tol-
erate the reaction conditions. Due to the steric hindrance of the
isopropyl group, the reaction with isopropyl ketone 2j gave the
product in a lower yield than that with ethyl ketone 2a (entry 9). n-
Pentyl ketone 2k gave a result similar to that with ethyl ketone 2b.
The reaction with 2k gave 3ak in 91% yield (entry 10).
We next examined the reaction of diyne 1a with alkynyl esters 4
under the optimized conditions described above. The results are
summarized in Table 3. The reaction of 1a with 4a gave a complex
mixture. This decrease in the yield of 5aa was due to the fact that
the cyclotrimerization of 4a competed with the reaction of 1a with
4a. A longer alkyl chain on alkyne inhibited the cyclotrimerization
of 4. As a result, the yield of 5 increased. The reactions with 4a and
4b gave 5aa and 5ab in respective yields of 83% and 88% (entries 2
and 3). When the substituent on alkyne was a phenyl or alkenyl
group, the yields of the products were slightly lower than those
obtained with alkyl-substituted substrates 4a and 4b (entries 4 and
5). We previously reported [2þ2þ2] cycloaddition with dimethyl
acetylenedicarboxylate (DMAD).10b Alkyne in which both alkyne
carbons are substituted by carbonyl group such as DMAD is highly
reactive toward self-cyclotrimerization. Two molecules of DMAD
reacted with one molecule of another alkyne to give 2:1 coupling
product. The reaction of diynes such as 1a with DMAD did not give
1:1 coupling product such as 5.
components, since these substrates gave good results as described
above. Phenyl-substituted diyne 1b underwent cycloaddition with
2a and 4b to give 6a and 6b in respective yields of 89% and 85%
(entries 1 and 2). Although a phenyl group is more hindered than
a methyl group, the reactivity of phenyl-substituted diyne 1b was
comparable to that of methyl-substituted diyne 1a. A teraryl
structure in which a central aromatic ring was substituted with
a carbonyl group could be easily constructed by this reaction in an
atom-economical manner. Heteroaromatic substituents could be
used instead of a phenyl substituent. The reactions of thiophene-
substituted diyne 1c and pyridine-substituted diyne 1d with
alkynyl ketone 2a gave good results (entries 3 and 5). The reaction
of 1d with alkynyl ester 4b gave lower yields than that with 2a
(entry 6). A ter(hetero)aryl structure is usually constructed by
a sequential cross-coupling reaction. An advantage of this reaction
over cross-coupling is that the ring can be constructed and con-
nected in a single operation. Ethyl-substituted diyne 1e reacted
with 2a and 4b to give 6g and 6h in respective yields of 82% and 81%
(entry 7 and 8). Both aromatic-substituted diyne and alkyl-
substituted diyne could be used as substrates. In contrast, termi-
nally unsubstituted diyne 1f gave a disappointing result. The re-
action of 1f with 2a and 4b did not give the corresponding product.
Instead, the self-dimerization and -trimerization of 1f occurred
preferentially over the reaction with 2a and 4b. To suppress the
self-dimerization and -trimerization of a diyne, slow addition of the
diyne by a syringe-pump is generally used. Therefore, we per-
formed the slow addition of a mixture of diyne 1f and 2a or 4b to
a catalytic solution under refluxing benzene. Products 6i and 6j
were obtained in low yields (entries 9 and 10). We tried the re-
action of 1f with 4a. The corresponding product was not obtained.
We next examined the effect of the diyne backbone on the reaction
of methyl-substituted diyne. Similar to the reaction of malonate-
derived diyne 1a, acetylacetone-derived diyne 1g reacted with 2a
and 4b to give 6k and 6l in respective yields of 81% and 77% (entries
11 and 12). Diyne 1h bearing a methone moiety gave a result
comparable to those with malonate-derived diyne 1a and
acetylacetone-derived diyne 1f (entries 13 and 14).
Hydroxymethyl-substituted diyne 1i gave the product in a lower
yield than diynes 1a, 1g, and 1h (entries 15 and 16). These results
showed that the substituent at the 5-position in 2,7-nonadiyne
strongly affects cyclization. It is clear that the ThorpeeIngold ef-
fect11 plays an important role in this reaction. Nitrogen-tethered
diyne 1j could be used as a substrate, and reacted with 2a and 4b
to give 6q and 6r in respective yields of 53% and 64% (entry 17 and
18). The reaction of 1j is a convenient route to functionalized 2,3-
dihydro-1H-isoindole, which is an important structure in phar-
maceuticals and agrochemicals.12 On the other hand, the reaction of
2.3. Scope of diynes 1
Various diynes were subjected to cycloaddition with alkynyl
ketones and alkynyl esters in the presence of a catalytic amount of
[Ir(cod)Cl]2 and rac-BINAP. The results are summarized in Table 4.
Alkynyl ketone 2a and alkynyl ester 4b were used as monoyne
Table 3
Scope of alkynyl esters 4a
Entry
Alkynyl ester 4
Time (h)
Product 5
Yield of 5b (%)
1
2
3
4
5
4a: R¼Me
24
2
2
16
7
5aa
5ab
5ac
5ad
5ae
Complex mixture
4b: R¼n-Pent
4c: R¼n-Oct
83
88
76
68
4d: R¼Ph
4e: R¼1-cyclohexenyl
a
Reaction conditions: 1a (1 mmol), 4 (2 mmol), [Ir(cod)Cl]2 (0.01 mmol), rac-BINAP (0.02 mmol) in benzene (5 mL).
b
Isolated yield.

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T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
Table 4
Scope of diyne 1a
Entry
Diyne
Monoyne
Conditions
Product 6
Yield of 6b (%)
1
2
2a
4b
Toluene, reflux, 24 h
Toluene, reflux, 24 h
6a
6b
89
85
1b
3d
4d
2a
4b
Toluene, reflux, 2 h
Toluene, reflux, 16 h
6c
88
88
1c
6d
5d
2a
Toluene, reflux, 24 h
6e
88
6d
1d
1e
1f
4b
2a
4b
2a
4b
2a
4b
Toluene, reflux, 17 h
Benzene, reflux, 24 h
Benzene, reflux, 5 h
Benzene, reflux, 6 h
Benzene, reflux, 23 h
Benzene, reflux, 24 h
Benzene, reflux, 18 h
6f
6g
6h
6i
58
82
81
22
25
81
77
7
8c
9e
10c,d,e
11c
12
6j
6k
6l
1g
13d
2a
Toluene, reflux, 21 h
6m
73
14d
15c,d
16
1h
1i
4b
2a
4b
2a
4b
Toluene, reflux, 24 h
Toluene, reflux, 24 h
Toluene, reflux, 24 h
Benzene, reflux, 1 h
Benzene, reflux, 2 h
6n
6o
6p
6q
6r
69
32
26
53
64
17c,d
18c,d
1j
a
Reaction conditions: 1a (1 mmol), 2a or 4b (2 mmol), [Ir(cod)Cl]2 (0.02 mmol), rac-BINAP (0.04 mmol) in solvent (5 mL).
Isolated yield.
[Ir(cod)Cl]2 (0.01 mmol), rac-BINAP (0.02 mmol).
Compound 2a or 4b (3 mmol).
Slow addition of 2a or 4b (2 mmol) for 1 h.
b
c
d
e

T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
8685
bis (2-butyn-1-yl) ether and 2,8-decadiyne with 2a did not give the
2.7. The reaction in the presence of (R)-BINAP
corresponding product.
We examined the reaction of 11 with 2a in the presence of
2 mol % of [Ir(cod)Cl]2 and 4 mol % of (R)-BINAP. Product 12 was
obtained in 87% yield with 7% ee (Scheme 3).
2.4. Reaction with alkynyl aldehyde
Alkynyl ketones and alkynyl esters are good coupling partners
for diyne 1. The reaction is an atom-economical route to aryl ke-
tones and aryl esters. If an alkynyl aldehyde can be used for the
reaction, the product is an aromatic aldehyde. Considering that
aldehyde functionality can be easily transformed to various other
functional groups, the cycloaddition of a diyne with an alkynyl al-
dehyde should be an atom-economical route to synthetically im-
portant aromatic aldehydes instead of the conventional
VilsmeiereHaack synthesis,13 which gives waste as a by-product.
We examined the reaction of diyne 1 with alkynyl aldehyde 7.
The result was shown in Scheme 1. Despite the use of more forcing
reaction conditions than in the reaction of diyne 1 with alkynyl
ketone 2 or alkynyl ester 4, the reaction of diyne 1 with aldehyde 7
resulted in the formation of product 8 in a lower yield. This result
led to the disappointing conclusion that alkynyl aldehyde 7 is not as
good of a coupling partner as alkynyl ketone 2 or alkynyl ester 4.
Ph
O
n-Bu
Et
MeO2C
2a
11
2 mol% [Ir(cod)Cl]2
4 mol% (R)-BINAP
n-Bu
O
Ph
*
MeO2C
benzene, reflux, 1 h
Et
12
Yield 87%
Scheme 3. The reaction of 11 with 2a in the presence of (R)-BINAP.
3. Conclusion
In summary, we could extend the scope of iridium-catalyzed
[2þ2þ2] cycloaddition to give benzene derivatives by choosing
a suitable phosphine. We have shown that a monoyne in which
a carbonyl group is directly substituted to an alkyne carbon is
a good coupling partner for a,u-diyne. This success gives an atom-
economical route to functionalized benzene derivatives. This re-
action is an alternative to the conventional FriedeleCrafts reaction.
The experimental procedure is very simple and convenient. The
procedure simply requires mixing of [Ir(cod)Cl]2 and an appropri-
ate diphosphine ligand in solvent before the addition of substrates.
The results described here should lead to new opportunities for the
application of iridium complex catalysis in cycloaddition chemistry.
Scheme 1. The reaction of 1a with 7.
4. Experimental section
4.1. General
2.5. Reaction with alkynyl amide and alkynyl carboxylic acid
1H and 13C NMR spectra were measured on a JEOL JNM-ECP
500A, JEOL ECS-400, and JEOL Excalibur 270 spectrometers using
TMS as an internal standard. Samples were dissolved in CDCl3. GC
We examined the reaction of diyne 1a with alkynyl amide 9 and
alkynyl carboxylic acid 10. Both reactions did not give the corre-
sponding product.
analyses were performed on
a
Shimadzu GC-14B using
3.2 mmꢁ2 m glass columns packed with 5% OV-17 on 60/80 mesh
Chromosorb WAW-DMCS. The products were purified by column
chromatography on 63e210 mesh silica gel (Kanto Kagaku; Silica
Gel 60N). High-resolution mass spectra were obtained with a JEOL
Mstation JMS-700. All reagents and solvents were dried and puri-
fied before use by the usual procedures. [Ir(cod)Cl]2 was prepared
as described previously.16 Diynes 1a,10d 1e,17 1f,10d 1g,18 1j,18 and
1117 were prepared as described in the literature. Diyne 1h was
prepared by reaction of the sodium salt of dimedone with 1-bromo-
2-butyne.19 Aldehyde 7 was prepared as described in the litera-
ture.20 Amide 9 was prepared by the reaction of acid 10 with N,N-
diethylamine.21 Esters 4aed and acid 10 were purchased.
2.6. Mechanistic considerations
Metallacyclopentadiene is
[2þ2þ2] cycloaddition of
a
common intermediate in the
alkynes.14
Various metal-
lacyclopentadienes have been isolated and their reactivities have
been studied. It is reasonable to consider that iridacyclopenta-
diene15 could act as an intermediate for the reaction. Oxidative
cyclization of diyne gives iridacyclopentadiene. The reaction of
4.2. Reaction of diyne 1a with alkynyl ketone 2
iridacyclopentadiene with monoyne gives
(Scheme 2).
a final product
Representative procedure for the [2þ2þ2] cycloaddition of diyne
1a with alkynyl ketone 2.
A flask was charged with [Ir(cod)Cl]2 (7.0 mg, 0.01 mmol) and
rac-BINAP (12.2 mg, 0.02 mmol). The flask was evacuated and filled
with argon. To the flask were added benzene (5 mL) and 4-nonyn-
3-one (2a) (279 mg, 2.0 mmol). Diyne 1a (234 mg, 1.0 mmol) was
added to the reaction mixture. The mixture was stirred under reflux
for 12 h. The progress of the reaction was monitored by GLC. After
Scheme 2. Plausible reaction mechanism.

8686
T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
the reaction was complete, the solvent was evaporated in vacuo.
Column chromatography of the residue gave 3aa (n-hexane/
AcOEt¼8:2, 348 mg, 0.93 mmol, 94% yield).
(s, 2H), 3.78 (s, 6H), 7.42e7.45 (m, 2H), 7.55e7.58 (m, 1H), 7.79e7.81
(m, 2H); 13C NMR (CDCl3, 125 MHz)
13.6, 15.2, 16.2, 22.9, 30.5,
d
32.6, 39.9, 40.6, 52.9, 59.3, 126.8, 128.6, 129.5, 129.6, 133.4, 136.5,
136.6, 137.8, 138.9, 139.7, 172.3, 200.8; HRMS (EI) m/z [M]þ calcd for
4.2.1. Dimethyl
5-butyl-4,7-dimethyl-6-propionyl-1H-indene-2,2-
C26H30O5 422.2093; found 422.2087.
(3H)-dicarboxylate (3aa). Yellow oil; Rf¼0.46 (hexane/AcOEt¼7:3);
IR (neat) 2954, 2933, 2873, 1732, 1704, 1593, 1431, 1274, 1249, 1199,
1164, 1081, 1063, 950, 924, 859, 805, 731; 1H NMR (CDCl3,
4.2.7. (E)-Dimethyl 5-(but-2-enoyl)-6-butyl-4,7-dimethyl-1H-in-
dene-2,2-(3H)-dicarboxylate (3ag). White solid; Rf¼0.46 (hexane/
AcOEt¼7:3); IR (neat) 3008, 2951, 2867, 1752, 1718, 1652, 1435,
1378, 1314, 1251, 1195, 1082, 1066, 977, 963, 873, 753, 577; mp
500 MHz)
d
0.91 (t, J¼6.5 Hz, 3H), 1.19 (t, J¼7.0 Hz, 3H), 1.31e1.44
(m, 4H), 2.05 (s, 3H), 2.17 (s, 3H), 2.34e2.37 (m, 2H), 2.69 (q,
J¼7.0 Hz, 2H), 3.52 (s, 2H), 3.56 (s, 2H), 3.76 (s, 6H); 13C NMR
68.1e69.5 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
0.88 (t, J¼7.0 Hz, 3H),
(CDCl3, 125 MHz)
d
7.6, 13.7, 15.1, 15.9, 23.1, 30.6, 33.0, 38.6, 39.7,
1.29e1.37 (m, 4H), 1.90 (dd, J¼1.5, 7.0 Hz, 3H), 2.01 (s, 3H), 2.18 (s,
3H), 2.29e2.45 (m, 2H), 3.53 (s, 2H), 3.57 (s, 2H), 3.77 (s, 6H), 6.33
(dd, J¼1.5, 16 Hz, 1H), 6.49 (dq, J¼7.0, 16 Hz, 1H); 13C NMR (CDCl3,
40.3, 53.0, 59.2, 125.0, 129.6, 134.8, 136.6, 139.3, 141.9, 172.2, 211.7;
HRMS (EI) m/z [M]þ calcd for C22H30O5 374.2093; found 374.2079.
125 MHz)
d 13.7, 15.2, 16.1, 18.4, 23.1, 30.5, 32.8, 39.8, 40.4, 53.0,
4.2.2. Dimethyl
(3H)-dicarboxylate
5-hexyl-4,7-dimethyl-6-propionyl-1H-indene-2,2-
59.1, 126.5, 129.4, 134.5, 136.2, 136.3, 139.1, 139.3, 148.0, 172.3,
201.7; HRMS (EI) m/z [M]þ calcd for C23H30O5 386.2093; found
386.2101.
(3ab). Yellow solid; Rf¼0.50 (hexane/
AcOEt¼7:3); IR (neat) 2955, 2932, 2871, 1745, 1724, 1701, 1593, 1428,
1309,1255,1195,1173,1058, 957, 944, 856; mp 56.8e58.2 ꢀC; 1H NMR
(CDCl3, 500 MHz)
d
0.88 (t, J¼7.0 Hz, 3H), 1.19 (t, J¼7.5 Hz, 3H),
4.2.8. Dimethyl 5-acetyl-4,7-dimethyl-6-octyl-1H-indene-2,2-(3H)-
dicarboxylate (3ah). Pale yellow solid; Rf¼0.53 (hexane/
AcOEt¼17:3); IR (neat) 2952, 2924, 2851, 1729, 1696, 1594, 1431,
1281, 1261, 1244, 1162, 1080, 1063, 956, 866, 722, 630, 573; mp
1.26e1.44 (m, 8H), 2.05(s, 3H), 2.17 (s, 3H), 2.33e2.36(m, 2H), 2.69(q,
J¼7.0 Hz, 2H), 3.52 (s, 2H), 3.56 (s, 2H), 3.76 (s, 6H); 13C NMR (CDCl3,
125 MHz)
d 7.5, 14.0, 15.1, 15.9, 22.5, 29.8, 30.8, 30.9, 31.4, 38.5, 39.7,
40.3, 53.0, 59.1, 124.9, 129.6, 134.9, 136.5, 139.3, 141.8, 172.2, 211.7;
75.8e76.4 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
0.88 (t, J¼7.0 Hz, 3H),
HRMS (EI) m/z [M]þ calcd for C24H34O5 402.2406; found 402.2402.
1.27e1.35 (m, 10H), 1.39e1.45 (m, 2H), 2.09 (s, 3H), 2.17 (s, 3H),
2.38e2.41 (m, 2H), 2.46 (s, 3H), 3.52 (s, 2H), 3.56 (s, 2H), 3.76 (s,
4.2.3. Dimethyl
4,7-dimethyl-5-octyl-6-propionyl-1H-indene-2,2-
6H); 13C NMR (CDCl3, 125 MHz)
d 14.1, 15.2, 15.9, 22.6, 29.2, 29.3,
(3H)-dicarboxylate (3ac). Yellow oil; Rf¼0.40 (hexane/AcOEt¼4:1);
30.1, 30.9, 31.0, 31.8, 33.0, 39.8, 40.4, 53.0, 59.2, 124.7, 129.7, 134.7,
IR (neat) 2952, 2930, 2871, 1730, 1693, 1592, 1432, 1276, 1245, 1197,
136.6, 139.4, 141.9, 172.2, 209.1; HRMS (FAB) m/z [M]þ calcd for
1164, 1079, 1061, 950, 928; 1H NMR (CDCl3, 270 MHz)
d
0.88 (t,
C25H36O5 416.2563; found 416.2560.
J¼7.0 Hz, 3H), 1.17e1.44 (m, 15H), 2.05 (s, 3H), 2.17 (s, 3H),
2.32e2.37 (m, 2H), 2.69 (q, J¼7.3 Hz, 2H), 3.52 (s, 2H), 3.56 (s, 2H),
4.2.9. Dimethyl 5-butyl-4,7-dimethyl-6-(thiophene-2-carbonyl)-1H-
indene-2,2-(3H)-dicarboxylate (3ai). White solid; Rf¼0.41 (hexane/
AcOEt¼7:3); IR (neat) 2953, 2860, 1734, 1638, 1434, 1405, 1248,
1200, 1159, 1080, 1063, 1050, 846, 743, 671, 576; mp
3.76 (s, 6H); 13C NMR (CDCl3, 67.8 MHz)
d 7.5, 14.0, 15.1, 15.9, 22.6,
29.1, 29.2, 30.1, 30.8, 30.9, 31.8, 38.5, 39.7, 40.3, 53.0, 59.1, 124.9,
129.6, 134.9, 136.5, 139.3, 141.8, 172.2, 211.7; HRMS (EI) m/z [M]þ
calcd for C26H38O5 430.2719; found 430.2732.
100.4e102.1 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
0.80 (t, J¼7.2 Hz, 3H),
1.21e1.31 (m, 3H), 1.41e1.49 (m, 1H), 2.04 (s, 3H), 2.20 (s, 3H),
2.28e2.35 (m, 1H), 2.47e2.54 (m, 1H), 3.55 (d, J¼4.4 Hz, 2H), 3.61
(d, J¼5.6 Hz, 2H), 3.77 (s, 3H), 3.79 (s, 3H), 7.06e7.08 (m, 1H),
7.30e7.31 (m, 1H), 7.70e7.71 (m, 1H); 13C NMR (CDCl3, 100 MHz)
4.2.4. Dimethyl 4,7-dimethyl-5-phenyl-6-propionyl-1H-indene-2,2-
(3H)-dicarboxylate (3ad). Pale yellow solid; Rf¼0.43 (hexane/
AcOEt¼7:3); IR (neat) 2979, 2950, 1729, 1707, 1600, 1432, 1275,
1253,1200,1168,1081,1065, 941, 859, 771, 704; mp 148.2e150.0 ꢀC;
d
13.7, 15.2, 16.3, 23.0, 30.6, 32.8, 39.8, 40.5, 53.0, 53.1, 59.2, 126.8,
1H NMR (CDCl3, 500 MHz)
d
0.70 (t, J¼7.5 Hz, 3H), 2.00 (3H), 2.09 (q,
128.2, 129.6, 134.9, 135.0, 136.4, 136.6, 138.7, 139.9, 145.5, 172.1,
172.4, 193.1; HRMS (EI) m/z [M]þ calcd for C24H28O5S 428.1657;
found 428.1662.
J¼7.5 Hz, 2H), 2.12 (s, 3H), 3.61 (s, 4H), 3.79 (s, 6H), 7.14e7.16 (m,
2H), 7.29e7.32 (m, 1H), 7.34e7.38 (m, 2H); 13C NMR (CDCl3,
125 MHz)
d 7.5, 16.0, 16.5, 38.0, 40.0, 40.3, 53.1, 59.1, 125.8, 127.2,
128.1, 129.2, 130.2, 136.6, 138.3, 138.8, 139.4, 142.1, 172.2, 210.8;
4.2.10. Dimethyl 5-butyl-6-isobutyryl-4,7-dimethyl -1H-indene-2,2-
HRMS (EI) m/z [M]þ calcd for C24H26O5 394.1780; found 394.1772.
(3H)-dicarboxylate
(3aj). White
solid;
Rf¼0.51
(hexane/
AcOEt¼7:3); IR (neat) 2957, 2894, 2873, 1733, 1687, 1588, 1445,
4.2.5. Dimethyl
5-(cyclohex-1-en-1-yl)-4,7-dimethyl-6-propionyl-
1433, 1385, 1271, 1250, 1167, 1081, 953, 929, 850, 714, 692; mp
1H-indene-2,2-(3H)-dicarboxylate (3ae). White solid; Rf¼0.39
(hexane/AcOEt¼4:1); IR (neat) 2932, 2856, 1731, 1696, 1585, 1435,
1277,1251,1200,1162,1122, 1078,1061, 956, 942, 920, 859, 805, 727,
98.9e100.1 ꢀC; 1H NMR (CDCl3, 270 MHz)
d
0.91 (t, J¼6.8 Hz, 3H),
1.17 (d, J¼7.0 Hz, 6H), 1.31e1.45 (m, 4H), 2.06 (s, 3H), 2.18 (s, 3H),
2.28e2.45 (m, 2H), 2.91 (septet, J¼7.0 Hz, 1H), 3.53 (s, 2H), 3.57 (s,
661, 576; mp 101.2e102.6 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
1.12 (t,
2H), 3.76 (s, 6H); 13C NMR (CDCl3, 67.8 MHz)
d 13.7, 15.2, 16.5, 18.1,
J¼7.0 Hz, 3H), 1.56e1.73 (m, 4H), 2.03e2.19 (m, 10H), 2.54e2.68 (m,
23.1, 31.1, 32.9, 39.8, 40.3, 42.7, 52.9, 59.1, 125.8, 129.6, 135.5, 136.6,
139.4, 140.9, 172.2, 214.7; HRMS (EI) m/z [M]þ calcd for C23H32O5
388.2250; found 388.2233.
2H), 3.54 (s, 4H), 3.77 (s, 6H), 5.48 (s, 1H); 13C NMR (CDCl3,
125 MHz) d 7.7, 15.8, 16.0, 21.9, 22.8, 25.5, 30.3, 38.2, 39.8, 40.2, 53.0,
59.2, 125.4, 128.8, 129.0, 136.6, 137.4, 138.7, 139.1, 141.4, 172.2,
210.6; HRMS (EI) m/z [M]þ calcd for C24H30O5 398.2093; found
398.2097.
4.2.11. Dimethyl
5-butyl-6-hexanoyl-4,7-dimethyl-1H-indene-2,2-
(3H)-dicarboxylate (3ak). Yellow oil; Rf¼0.40 (hexane/AcOEt¼4:1);
IR (neat) 2955, 2931, 2871, 1736, 1700, 1581, 1435, 1404, 1381, 1274,
1248, 1199, 1164, 1081, 1062, 958, 863, 730; 1H NMR (CDCl3,
4.2.6. Dimethyl
(3H)-dicarboxylate
5-benzoyl-6-butyl-4,7-dimethyl-1H-indene-2,2-
(3af). White solid; (hexane/
Rf¼0.39
500 MHz) d 0.90e0.92 (m, 6H), 1.34e1.43 (m, 8H), 1.69e1.76 (m,
AcOEt¼4:1); IR (neat) 2953, 2934, 2874, 2856, 1732, 1662, 1594,
2H), 2.06 (s, 3H), 2.17 (s, 3H), 2.32e2.42 (m, 2H), 2.67 (t, J¼8.0 Hz,
1579, 1431, 1276, 1235, 1205, 1164, 1057, 916, 881, 716, 688, 672; mp
2H), 3.52 (s, 2H), 3.56 (s, 2H), 3.76 (s, 6H); 13C NMR (CDCl3,
79.4e81.2 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
0.76 (t, J¼7.5 Hz, 3H),
125 MHz)
d 13.7,13.9,15.1,15.9, 22.5, 22.9, 23.1, 30.5, 31.3, 33.0, 39.8,
1.12e1.45 (m, 4H), 1.96 (s, 3H), 2.14e2.51 (m, 5H), 3.56 (s, 2H), 3.62
40.4, 45.4, 53.0, 59.2, 125.0, 129.6, 134.8, 136.6, 139.3, 142.0, 172.2,

T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
8687
211.1; HRMS (EI) m/z [M]þ calcd for C25H36O5 416.2563; found
416.2560.
(neat) 2955, 2872, 1734, 1697, 1602, 1578, 1434, 1270, 1243,
1200, 1162, 1072, 954, 931, 752, 703; 1H NMR (CDCl3, 500 MHz)
d
0.62 (t, J¼7.0 Hz, 3H), 0.74 (t, J¼7.0 Hz, 3H), 0.99e1.06 (m,
4.3. Reaction of diyne 1a with alkynyl ester 4
2H), 1.24e1.30 (m, 2H), 2.18 (q, J¼7.0 Hz, 2H), 2.28e2.31 (m,
2H), 3.29 (s, 2H), 3.47 (s, 2H), 3.67 (s, 6H), 7.24e7.30 (m, 4H),
Representative procedure for the [2þ2þ2] cycloaddition of diyne
1a with alkynyl ester 4.
7.33e7.46 (m, 6H); 13C NMR (CDCl3, 125 MHz)
d 7.6, 13.4, 22.8,
30.2, 33.8, 38.5, 40.3, 40.8, 52.9, 59.6, 127.1, 127.6, 128.40,
128.44, 129.0, 129.5, 133.4, 135.8, 135.9, 138.25, 138.29, 139.2,
139.8, 141.8, 171.9, 210.4; HRMS (EI) m/z [M]þ calcd for
A flask was charged with [Ir(cod)Cl]2 (7.0 mg, 0.01 mmol) and
rac-BINAP (12.2 mg, 0.02 mmol). The flask was evacuated and filled
with argon. To the flask were added benzene (5 mL) and methyl 2-
undecynoate (4c) (444 mg, 2.3 mmol). Diyne 1a (234 mg, 1.0 mmol)
was added to the reaction mixture. The mixture was stirred under
reflux for 2 h. The progress of the reaction was monitored by GLC.
After the reaction was complete, the solvent was evaporated in
vacuo. Column chromatography of the residue gave 5ac (n-hexane/
AcOEt¼85:15, 378 mg, 0.87 mmol, 88% yield).
C
32H34O5 498.2406; found 498.2410.
4.4.2. Trimethyl 6-pentyl-4,7-diphenyl-1H-indene-2,2,5(3H)-tri-
carboxylate (6b). Yellow solid; Rf¼0.38 (hexane/AcOEt¼4:1); IR
(neat) 2952, 2925, 2871, 1736, 1723, 1603, 1573, 1498, 1431, 1270,
1246, 1200, 1154, 1128, 1071, 963, 874, 757, 702, 623, 603, 561; mp
116.3e119.0 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
0.72 (t, J¼7.2 Hz, 3H),
1.01e1.12 (m, 4H), 1.30e1.38 (m, 2H), 2.40e2.45 (m, 2H), 3.29 (s,
2H), 3.46 (s, 2H), 3.47 (s, 3H), 3.67 (s, 6H), 7.23e7.26 (m, 2H),
4.3.1. Trimethyl
4,7-dimethyl-6-pentyl-1H-indene-2,2,5(3H)-tri-
carboxylate (5ab). White solid; Rf¼0.44 (hexane/AcOEt¼4:1); IR
(neat) 2953, 2927, 2872, 1597, 1747, 1721, 1432, 1309, 1253, 1195,
1167, 1058, 958, 859, 816, 789, 732, 672, 629; mp 76.3e77.8 ꢀC; 1H
7.32e7.46 (m, 8H); 13C NMR (CDCl3,125 MHz)
d 13.7, 21.9, 30.8, 30.9,
31.9, 40.3, 40.8, 51.6, 52.9, 59.7, 127.2, 127.4, 128.2, 128.4, 128.6,
128.9, 133.3, 135.2, 135.9, 137.3, 137.9, 138.7, 139.0, 140.6, 170.4,
171.8; HRMS (EI) m/z [M]þ calcd for C32H34O6 514.2355; found
514.2344.
NMR (CDCl3, 500 MHz)
d
0.90 (t, J¼7.5 Hz, 3H), 1.32e1.35 (m, 4H),
1.45e1.49 (m, 2H), 2.14 (s, 3H), 2.18 (s, 3H), 2.46e2.49 (m, 2H), 3.53
(s, 2H), 3.56 (s, 2H), 3.76 (s, 6H), 3.89 (s, 3H); 13C NMR (CDCl3,
125 MHz)
d
14.0, 15.3, 16.3, 22.3, 30.2, 31.1, 32.3, 39.8, 40.4, 51.8,
4.4.3. Dimethyl 5-butyl-6-propionyl-4,7-di(thiophen-2-yl)-1H-indene-
2,2(3H)-dicarboxylate (6c). Brown oil; Rf¼0.43 (hexane/AcOEt¼7:3);
IR (neat) 2955, 2872, 1734, 1698, 1580, 1434, 1273, 1245, 1199, 1163,
53.0, 59.2, 127.1, 129.4, 133.6, 136.4, 136.7, 140.2, 171.3, 172.1; HRMS
(EI) m/z [M]þ calcd for C22H30O6 390.2042; found 390.2032.
1070, 1051, 848, 835, 729, 699; 1H NMR (CDCl3, 500 MHz)
d 0.72 (t,
4.3.2. Trimethyl 4,7-dimethyl-6-octyl-1H-indene-2,2,5(3H)-tricarbox-
ylate (5ac). Yellow oil; Rf¼0.50 (hexane/AcOEt¼7:3); IR (neat) 2952,
2925, 2854, 1731, 1593, 1434, 1280, 1247, 1196, 1162, 1063, 955, 913,
J¼7.0 Hz, 3H), 0.87 (t, J¼7.0 Hz, 3H), 1.09e1.17 (m, 2H), 1.36e1.42 (m,
2H), 2.29 (q, J¼7.5 Hz, 2H), 2.36e2.39 (m, 2H), 3.43 (s, 2H), 3.64 (s,
2H), 3.70 (s, 6H), 6.93e6.94 (m, 2H), 7.05e7.07 (m, 1H), 7.10e7.12 (m,
863, 834, 733, 650, 576; 1H NMR (CDCl3, 500 MHz)
d
0.88 (t, J¼7.0 Hz,
1H), 7.39e7.41 (m, 2H); 13C NMR (CDCl3, 125 MHz)
d 7.8, 13.5, 22.9,
3H), 1.28e1.36 (m, 10H), 1.44e1.50 (m, 2H), 2.13 (s, 3H), 2.18 (s, 3H),
2.46e2.49 (m, 2H), 3.53 (s, 2H), 3.56 (s, 2H), 3.75 (s, 6H), 3.88 (s, 3H);
30.7, 34.4, 38.0, 40.8, 41.0, 53.0, 59.4, 125.8, 126.7, 127.0, 127.1, 127.3,
129.2,131.4,137.0,138.1,138.8,141.9,142.5,171.7, 209.7; HRMS (EI) m/
z [M]þ calcd for C28H30O5S2 510.1535; found 510.1534.
13C NMR (CDCl3,125 MHz)
d 14.1,15.3,16.3, 22.6, 29.2, 29.3, 30.1, 30.5,
31.2, 31.8, 39.8, 40.4, 51.8, 53.0, 59.2, 127.1, 129.4, 133.6, 136.4, 136.7,
140.2, 171.2, 172.1; HRMS (EI) m/z [M]þ calcd for C25H36O6 432.2512;
found 432.2501.
4.4.4. Trimethyl 6-pentyl-4,7-di(thiophen-2-yl)-1H-indene-2,2,5(3H)-
tricarboxylate (6d). Brown solid; Rf¼0.42 (hexane/AcOEt¼7:3); IR
(neat) 2952, 2927, 2873,1736,1720,1578,1431,1269,1248,1197,1154,
1071, 1047, 960, 850, 828, 796, 704, 626, 580; mp 122.5e124.8 ꢀC; 1H
4.3.3. Trimethyl 4,7-dimethyl-6-phenyl-1H-indene-2,2,5(3H)-tri-
carboxylate (5ad). White solid; Rf¼0.38 (hexane/AcOEt¼17:3); IR
(neat) 2997, 2946, 1730, 1600, 1431, 1280, 1251, 1200, 1167, 1082,
1066, 1056, 1022, 955, 861, 769, 747, 701, 672, 632, 603, 569; mp
NMR (CDCl3, 500 MHz)
d
0.78 (t, J¼7.0 Hz, 3H), 1.12e1.18 (m, 4H),
1.43e1.49 (m, 2H), 2.50e2.53 (m, 2H), 3.44 (s, 2H), 3.60 (s, 3H), 3.62
(s, 2H), 3.68 (s, 6H), 6.93e6.94 (m, 1H), 7.03e7.06 (m, 2H), 7.10e7.11
(m, 1H), 7.36e7.37 (m, 1H), 7.39e7.40 (m, 1H); 13C NMR (CDCl3,
147.2e149.4 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
1.98 (s, 3H), 2.22 (s,
3H), 3.41 (s, 3H), 3.60 (s, 2H), 3.62 (s, 2H), 3.79 (s, 6H), 7.16e7.17
(m, 2H), 7.29e7.37 (m, 3H); 13C NMR (CDCl3, 125 MHz)
16.3, 16.7,
125 MHz) d 13.7, 21.8, 31.1, 31.3, 31.9, 40.6, 40.9, 51.7, 52.8, 59.3, 77.2,
d
125.8, 126.2, 126.8, 127.0, 127.3, 128.6, 130.9, 134.4, 137.2, 138.3, 138.4,
139.2, 142.5, 169.7, 171.4; HRMS (EI) m/z [M]þ calcd for C28H30O6S2
526.1484; found 526.1485.
39.9, 40.4, 51.5, 53.1, 59.3, 127.0, 127.3, 127.9, 129.3, 129.4, 133.8,
138.0, 138.5, 139.4, 140.2, 170.3, 172.1; HRMS (EI) m/z [M]þ calcd
for C23H24O6 396.1573; found 396.1570.
4.4.5. Dimethyl 5-butyl-6-propionyl-4,7-di(pyridin-2-yl)-1H-indene-
2,2(3H)-dicarboxylate (6e). White solid; Rf¼0.21 (hexane/
AcOEt¼1:3); IR (neat) 2956, 2938, 2865, 1739, 1726, 1695, 1585,
1566, 1478, 1429, 1275, 1254, 1200, 1161, 1068, 1048, 954, 785, 749,
4.3.4. Trimethyl
6-(cyclohex-1-en-1-yl)-4,7-dimethyl-1H-indene-
2,2,5(3H)-tricarboxylate (5ae). White solid; Rf¼0.45 (hexane/
AcOEt¼7:3); IR (neat) 2996, 2935, 2855, 1731, 1589,1429,1278, 1250,
1196,1164,1079,1055,1019,953,922,861, 799,769, 737, 690,663, 634,
616, 604; mp 127.8e130.0 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 0.62 (t,
604, 574; mp 122.1e123.8 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
1.55e1.61
J¼7.5 Hz, 3H), 0.85 (t, J¼7.0 Hz, 3H), 0.99e1.07 (m, 2H), 1.22e1.31
(m, 2H), 2.28 (q, J¼7.5 Hz, 2H), 2.37e2.40 (m, 2H), 3.36 (s, 2H), 3.61
(s, 2H), 3.67 (s, 6H), 7.24e7.32 (m, 2H), 7.35e7.36 (m, 1H), 7.38e7.39
(m, 1H), 7.73e7.75 (m, 1H), 7.78e7.82 (m, 1H), 8.67e8.68 (m, 1H),
(m, 1H), 1.65e1.73 (m, 3H), 2.09e2.18 (m, 10H), 3.54 (s, 2H), 3.55 (s,
2H), 3.76 (s, 6H), 3.79 (s, 3H), 5.47e5.48 (m, 1H); 13C NMR (CDCl3,
67.8 MHz) d 15.7,16.2, 22.0, 22.9, 25.4, 29.9, 39.8, 40.1, 51.6, 53.0, 59.2,
126.7, 127.1, 128.7, 133.0, 137.1, 137.4, 140.0, 140.6, 170.6, 172.1; HRMS
8.72e8.73 (m, 1H); 13C NMR (CDCl3, 125 MHz)
d 7.8, 13.4, 22.8, 29.9,
(EI) m/z [M]þ calcd for C23H28O6 400.1886; found 400.1888.
33.6, 38.7, 40.0, 40.2, 53.0, 60.0, 122.1, 122.3, 124.5, 124.8, 133.4,
136.3, 136.4, 136.5, 137.7, 140.1, 141.8, 149.5, 149.6, 156.8, 158.1, 171.7,
209.6; HRMS (EI) m/z [M]þ calcd for C30H32N2O5 500.2311; found
500.2328.
4.4. Reaction of diyne 1 with alkynyl ketone 2a or alkynyl
ester 4b
4.4.1. Dimethyl 5-butyl-4,7-diphenyl-6-propionyl-1H-indene-2,2(3H)-
4.4.6. Trimethyl 6-pentyl-4,7-di(pyridin-2-yl)-1H-indene-2,2,5(3H)-
dicarboxylate (6a). Yellow oil; Rf¼0.51 (hexane/AcOEt¼7:3); IR
tricarboxylate (6f). Brown solid; Rf¼0.43 (hexane/AcOEt¼1:2); IR

8688
T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
(neat) 2954, 2924, 2856, 1734, 1586, 1567, 1480, 1453, 1435, 1247,
1225, 1199, 1175, 1135, 1068, 1050, 992, 965, 877, 781, 752, 707, 688,
211.7; HRMS (EI) m/z [M]þ calcd for C22H30O3 342.2195; found
342.2197.
613; mp 119.3e122.1 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 0.72 (t,
J¼7.0 Hz, 3H), 1.00e1.07 (m, 4H), 1.33e1.39 (m, 2H), 2.53 (t,
J¼8.0 Hz, 2H), 3.36 (s, 2H), 3.53 (s, 3H), 3.61 (s, 2H), 3.67 (s, 6H),
7.23e7.26 (m, 1H), 7.30e7.32 (m, 1H), 7.32e7.34 (m, 1H), 7.74e7.81
(m, 2H), 8.67e8.68 (m, 1H), 8.72e8.73 (m, 1H); 13C NMR (CDCl3,
4.4.12. Methyl 2,2-diacetyl-4,7-dimethyl-6-pentyl-2,3-dihydro-1H-
indene-5-carboxylate (6l). White solid; Rf¼0.39 (hexane/
AcOEt¼17:3); IR (neat) 2951, 2929, 2872, 1721, 1696, 1593, 1433,
1360, 1335, 1302, 1252, 1200, 1164, 1152, 1123, 1047, 1018, 964, 831,
732, 711, 624, 592, 570; mp 79.5e81.8 ꢀC; 1H NMR (CDCl3,
125 MHz)
d 13.7, 21.9, 30.4, 30.7, 31.8, 40.0, 40.1, 51.6, 53.0, 60.0,
122.05, 122.14, 123.7, 124.5, 133.1, 135.1, 136.2, 136.3, 137.5, 138.4,
141.0, 149.3, 149.6, 157.2, 157.9, 170.0, 171.6; HRMS (EI) m/z [M]þ
calcd for C30H32N2O6 516.2260; found 516.2255.
400 MHz)
2H), 2.15 (s, 3H), 2.18 (s, 6H), 2.20 (s, 3H), 2.45e2.50 (m, 2H), 3.42 (s,
2H), 3.45 (s, 2H), 3.89 (s, 3H); 13C NMR (CDCl3,100 MHz)
14.0,15.3,
d
0.90 (t, J¼6.8 Hz, 3H), 1.31e1.35 (m, 4H), 1.43e1.51 (m,
d
16.4, 22.3, 26.4, 30.2, 31.2, 32.2, 36.7, 37.3, 51.9, 73.7, 127.3, 129.7,
4.4.7. Dimethyl 5-butyl-4,7-diethyl-6-propionyl-1H-indene-2,2(3H)-
dicarboxylate (6g). Pale yellow solid; Rf¼0.50 (hexane/AcOEt¼4:1);
IR (neat) 2961, 2935, 2874, 1732, 1702, 1587, 1451, 1430, 1251, 1197,
1167, 1130, 1102, 1065, 960, 857, 714; mp 76.8e78.9 ꢀC; 1H NMR
133.7, 136.2, 136.8, 140.1, 171.2, 204.6; HRMS (EI) m/z [M]þ calcd for
C22H30O4 358.2144; found 358.2148.
4.4.13. 50-Butyl-4,4,40,70-tetramethyl-60-propionyl-10,30-dihydrospiro
[cyclohexane-1,20-indene]-2,6-dione (6m). White solid; Rf¼0.38
(hexane/AcOEt¼4:1); IR (neat) 2959, 2936, 2873, 1726, 1693, 1592,
1443, 1322, 1234, 1128, 1078, 1063, 982, 945, 927, 872, 825, 801, 671,
(CDCl3, 500 MHz)
d
0.91 (t, J¼7.5 Hz, 3H), 1.11 (t, J¼8.0 Hz, 3H), 1.14
(t, J¼8.0 Hz, 3H), 1.20 (t, J¼7.5 Hz, 3H), 1.32e1.46 (m, 4H), 2.31e2.39
(m, 4H), 2.57 (q, J¼8.0 Hz, 2H), 2.72 (q, J¼7.5 Hz, 2H), 3.54 (s, 2H),
3.56 (s, 2H), 3.76 (s, 6H); 13C NMR (CDCl3, 125 MHz)
d
7.7, 13.7, 14.4,
635, 599, 577; mp 140.9e142.1 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 0.90(t,
14.8, 22.7, 23.3, 24.3, 30.1, 34.4, 38.98, 39.0, 39.4, 53.0, 59.9, 131.8,
134.2, 136.1, 136.5, 139.3, 141.9, 172.1, 211.6; HRMS (EI) m/z [M]þ
calcd for C24H34O5 402.2406; found 402.2396.
J¼7.2 Hz, 3H),1.04 (s, 3H), 1.05 (s, 3H),1.18 (t, J¼7.2 Hz, 3H),1.31e1.43
(m, 4H), 2.03 (s, 3H), 2.16 (s, 3H), 2.32e2.35 (m, 2H), 2.67 (q, J¼7.2 Hz,
2H), 2.72 (s, 4H), 3.35 (s, 2H), 3.39 (s, 2H); 13C NMR (CDCl3, 100 MHz)
d
7.6, 13.7, 15.2, 16.0, 23.1, 28.3, 28.4, 30.5, 30.6, 33.0, 37.9, 38.1, 38.6,
4.4.8. Trimethyl
4,7-diethyl-6-pentyl-1H-indene-2,2,5(3H)-tri-
51.4, 70.1,124.9,129.6,134.9,136.1,139.0,141.9, 206.5, 211.7;HRMS(EI)
carboxylate (6h). Yellow oil; Rf¼0.42 (hexane/AcOEt¼4:1); IR
(neat) 2955, 2874, 1730, 1588, 1434, 1286, 1247, 1196, 1163, 1065,
1027, 952, 867, 780, 732, 703, 627, 600; 1H NMR (CDCl3, 500 MHz)
m/z [M]þ calcd for C25H34O3 382.2508; found 382.2514.
4.4.14. Methyl 4,4,40,70-tetramethyl-2,6-dioxo-60-pentyl-10,30-dihy-
drospiro[cyclohexane-1,20-indene]-50-carboxylate (6n). White solid;
Rf¼0.38 (hexane/AcOEt¼4:1); IR (neat) 2947, 2871, 1724, 1692,
1593, 1431, 1322, 1301, 1242, 1196, 1186, 1164, 1078, 1061, 1042, 1017,
949, 831, 737, 584, 563; mp 129.2e130.8 ꢀC; 1H NMR (CDCl3,
d
0.90 (t, J¼7.5 Hz, 3H), 1.13 (t, J¼7.5 Hz, 6H), 1.33e1.36 (m, 4H),
1.48e1.53 (m, 2H), 2.45e2.49 (m, 4H), 2.58 (q, J¼7.5 Hz, 2H), 3.55 (s,
2H), 3.57 (s, 2H), 3.75 (s, 6H), 3.88 (s, 3H); 13C NMR (CDCl3,
125 MHz)
d 13.9, 14.3, 14.5, 22.3, 22.9, 24.8, 30.5, 31.5, 32.4, 38.9,
39.5, 51.6, 52.9, 59.9, 133.4, 133.6, 135.8, 136.1, 136.2, 140.1, 171.3,
171.9; HRMS (EI) m/z [M]þ calcd for C24H34O6 418.2355; found
418.2352.
400 MHz)
d
0.89 (t, J¼7.2 Hz, 3H), 1.02 (s, 3H), 1.05 (s, 3H), 1.29e1.36
(m, 4H), 1.42e1.50 (m, 2H), 2.12 (s, 3H), 2.17 (s, 3H), 2.44e2.48 (m,
2H), 2.67e2.75 (m, 4H), 3.36 (s, 2H), 3.40 (s, 2H), 3.87 (s, 3H); 13C
NMR (CDCl3, 100 MHz) d 14.0, 15.3, 16.4, 22.3, 28.2, 28.5, 30.2, 30.5,
4.4.9. Dimethyl 5-butyl-6-propionyl-1H-indene-2,2(3H)-dicarbox-
ylate (6i). Yellow oil; Rf¼0.30 (hexane/AcOEt¼17:3); IR (neat) 2955,
2934, 2872, 1735, 1687, 1616, 1434, 1566, 1280, 1250, 1199, 1160,
31.1, 32.3, 37.9, 38.2, 51.3, 51.8, 70.1, 127.1, 129.4, 133.6, 135.8, 136.8,
140.0, 171.2, 206.4; HRMS (EI) m/z [M]þ calcd for C25H34O4
398.2457; found 398.2463.
1067, 1053, 919, 891, 813, 709; 1H NMR (CDCl3, 500 MHz)
d 0.91 (t,
J¼7.0 Hz, 3H), 1.17 (t, J¼7.5 Hz, 3H), 1.32e1.39 (m, 2H), 1.48e1.54 (m,
4.4.15. 1-(6-Butyl-2,2-bis(hydroxymethyl)-4,7-dimethyl-2,3-
dihydro-1H-inden-5-yl)propan-1-one (6o). White solid; Rf¼0.41
(hexane/AcOEt¼1:1); IR (neat) 3288, 2956, 2929, 2871, 1699, 1591,
1417, 1376, 1340, 1226, 1126, 1050, 1035, 926, 903, 701; mp
2H), 2.71e2.74 (m, 2H), 2.86 (q, J¼7.5 Hz, 2H), 3.58 (s, 4H), 3.75 (s.
6H), 7.08 (s, 1H), 7.36 (s, 1H); 13C NMR (CDCl3, 125 MHz)
d 8.4, 13.9,
22.7, 33.5, 34.2, 35.2, 40.1, 40.5, 52.9, 60.3, 123.6, 126.5, 137.1, 137.7,
141.5, 142.9, 171.7, 205.4.
84.0e86.3 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
0.91 (t, J¼9.0 Hz, 3H),1.19
(t, J¼7.0 Hz, 3H), 1.30e1.44 (m, 4H), 2.01 (s, 3H), 2.14 (s, 3H),
2.34e2.37 (m, 2H), 2.69e2.74 (m, 6H), 3.33e3.54 (br, 2H), 3.69 (s,
4.4.10. Trimethyl
6-pentyl-1H-indene-2,2,5(3H)-tricarboxylate
(6j). White solid; Rf¼0.32 (hexane/AcOEt¼4:1); IR (neat) 2955,
2921, 2854, 1733, 1715, 1622, 1573, 1428, 1281, 1244, 1227, 1180,
1155, 1128, 1067, 1054, 909, 890, 837, 798, 714, 639, 600, 572; mp
4H); 13C NMR (CDCl3, 125 MHz)
d 7.5, 13.7, 15.1, 15.9, 23.1, 30.6, 33.0,
37.6, 38.3, 38.6, 47.6, 69.2,125.4,130.2,134.1,138.3,141.1,141.3, 212.7;
HRMS (EI) m/z [M]þ calcd for C20H30O3 318.2195; found 318.2196.
82.5e84.2 ꢀC; 1H NMR (CDCl3, 500 MHz)
1.32e1.36 (m, 4H), 1.54e1.57 (m, 2H), 3.56 (s, 2H), 2.87e2.90 (m,
d
0.89 (t, J¼7.0 Hz, 3H),
4.4.16. Methyl 2,2-bis(hydroxymethyl)-4,7-dimethyl-6-pentyl-2,3-
dihydro-1H-indene-5-carboxylate (6p). White solid; Rf¼0.43 (hex-
ane/AcOEt¼1:1); IR (neat) 3236, 2951, 2928, 2871, 1717, 1590, 1436,
1378, 1308, 1243, 1201, 1166, 1107, 1090, 1041, 1016, 948, 831, 741,
2H), 3.59 (s, 2H), 3.75 (s, 6H), 3.87 (s, 3H), 7.08 (s, 1H), 7.68 (s, 1H);
13C NMR (CDCl3, 125 MHz)
d 14.0, 22.5, 31.6, 32.0, 34.4, 40.0, 40.5,
51.8, 53.0, 60.4, 126.2, 126.6, 128.4, 137.4, 144.1, 144.2, 168.2, 171.8;
HRMS (EI) m/z [M]þ calcd for C20H26O6 362.1729; found 362.1720.
728, 682; mp 101.8e103.3 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 0.90 (t,
J¼7.0 Hz, 3H), 1.32e1.35 (m, 4H), 1.45e1.51 (m, 2H), 2.10 (s, 3H), 2.14
4.4.11. 1,10-(5-Butyl-4,7-dimethyl-6-propionyl-2,3-dihydro-1H-in-
dene-2,2-diyl)diethanone (6k). White solid; Rf¼0.38 (hexane/
AcOEt¼17:3); IR (neat) 2957, 2932, 2872, 1696, 1588, 1435, 1360,
1201, 1189, 1151, 1129, 962, 947, 928, 824, 713, 624, 590; mp
(s, 3H), 2.45e2.49 (m, 2H), 2.70 (s, 2H), 2.74 (s, 2H), 3.26e3.53 (br,
2H), 3.68 (s, 4H), 3.88 (s, 3H); 13C NMR (CDCl3,125 MHz)
d 13.9,15.2,
16.3, 22.3, 30.2, 31.1, 32.2, 37.6, 38.3, 47.6, 51.8, 69.1, 127.5, 130.0,
132.9, 136.0, 138.0, 142.0, 171.8; HRMS (EI) m/z [M]þ calcd for
46.3e48.8 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
0.91 (t, J¼6.8 Hz, 3H),
C20H30O4 334.2144; found 334.2153.
1.19 (t, J¼7.2 Hz, 3H), 1.32e1.44 (m, 4H), 2.07 (s, 3H), 2.19 (s, 9H),
2.30e2.38 (m, 2H), 2.69 (q, J¼7.2 Hz, 2H), 3.41 (s, 2H), 3.45 (s, 2H);
4.4.17. 1-(6-Butyl-4,7-dimethyl-2-tosylisoindolin-5-yl)propan-1-one
(6q). White solid; Rf¼0.46 (hexane/AcOEt¼2:1); IR (neat) 2961,
2927, 2858, 2832,1699,1597,1455,1343,1158,1134,1096,1065, 948,
13C NMR (CDCl3,100 MHz)
d 7.6,13.7, 15.2, 16.0, 23.1, 26.5, 30.6, 33.0,
36.6, 37.2, 38.6, 73.7, 125.2, 129.8, 134.9, 136.4, 139.2, 142.0, 204.7,

T. Hashimoto et al. / Tetrahedron 70 (2014) 8681e8689
8689
930, 813, 710, 664, 582, 553; mp 126.2e128.6 ꢀC; 1H NMR (CDCl3,
500 MHz)
Technology of Japan. We thank Prof. Nishibayashi and Dr. Nakajima
for measuring NMR spectra of 3ac and 3aj. We thank Mr. Kouji
Itabashi for his experimental work.
d
0.89 (t, J¼7.5 Hz, 3H),1.18 (t, J¼7.0 Hz, 3H),1.33e1.38 (m,
4H),1.99 (s, 3H), 2.11 (s, 3H), 2.33e2.36 (m, 2H), 2.42 (s, 3H), 2.65 (q,
J¼7.5 Hz, 2H), 4.54 (s, 2H), 4.58 (s, 2H), 7.32 (d, J¼8.0 Hz, 2H), 7.78 (d,
J¼8.5 Hz, 2H); 13C NMR (CDCl3, 125 MHz)
d 7.5, 13.7, 15.0, 15.7, 21.5,
23.1, 30.4, 32.9, 38.5, 53.6, 53.9,124.2,127.5,128.6,129.8,133.1,133.7,
Supplementary data
135.8, 135.9, 142.6, 143.7, 210.7; HRMS (EI) m/z [M]þ calcd for
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.09.038.
C
24H31NO3S 413.2025; found 413.2025.
4.4.18. Methyl 4,7-dimethyl-6-pentyl-2-tosylisoindoline-5-carboxylate
(6r). Yellow solid; Rf¼0.53 (hexane/AcOEt¼2:1); IR (neat) 2951,
2929, 2871, 1732, 1597, 1455, 1433, 1344, 1316, 1266, 1158, 1097, 1062,
953, 814, 734, 709, 664, 589, 554; mp 97.1e99.5 ꢀC; 1H NMR (CDCl3,
References and notes
1. Smith, M. B. March’s Advanced Organic Chemistry, 7th ed.; Wiley & Sons:
Hoboken, NJ, 2013; p 569.
500 MHz)
d
0.88 (t, J¼7.0 Hz, 3H), 1.29e1.33 (m, 4H), 1.40e1.45 (m,
2. (a) Transition-metal-mediated Aromatic Ring Construction; Tanaka, K., Ed.; Wiley &
Sons: Hoboken, NJ, 2013; (b) Agenet, N.; Buisine, O.; Slowinski, F.; Gandox, V.; Au-
bert, C.; Malacria, M. Org. React. 2007, 68, 1; (c) Broere, D. L. J.; Ruijter, E. Synthesis
2012, 44, 2639; (d) Shibata, Y.;Tanaka, K. Synthesis2012, 44, 323; (e) Domínguez, G.;
2H), 2.07 (s, 3H), 2.11 (s, 3H), 2.41 (s, 3H), 2.44e2.48 (m, 2H), 3.87 (s,
3H), 4.56 (s, 2H), 4.58 (s, 2H), 7.31e7.33 (m, 2H), 7.76e7.78 (m, 2H);
13C NMR (CDCl3, 125 MHz)
d 13.9,15.1, 16.1, 21.5, 22.3, 30.1, 30.9, 32.2,
ꢀ
Perez-Catells, J. Chem. Soc. Rev. 2011, 40, 3430; (f) Chopade, P. R.; Louie, J. A. Adv.
52.0, 53.6, 54.0, 126.3, 127.5, 128.4, 129.8, 132.9, 133.7, 134.4, 136.6,
137.8, 143.7, 170.5; HRMS (EI) m/z [M]þ calcd for C24H31NO4S
429.1974; found 429.1970.
Synth. Catal. 2006, 348, 2307; (g) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org.
Chem. 2005, 4741.
3. Recent examples, see: (a) Rodrigo, S. K.; Powell, I. V.; Coleman, M. G.; Krause, J. A.;
Guan, H. Org. Biomol. Chem. 2013, 11, 7653; (b) Xi, C.; Sun, Z.; Liu, Y. Dalton Trans.
2013, 42,13327; (c) Teske, J. A.; Deiters, A. J. Org. Chem. 2008, 73, 342; (d) Turek, P.;
ꢀ
Novak, P.; Pohl, R.; Hocek, M.; Kotora, M. J. Org. Chem. 2006, 71, 8978; (e) Chang, H.-
4.4.19. Dimethyl 5-butyl-6-formyl-4,7-dimethyl-1H-indene-2,2(3H)-
dicarboxylate (8). Colorless oil; Rf¼0.50 (hexane/AcOEt¼7:3); IR
(neat) 2955, 2873,1735,1700,1580,1435,1380,1274,1249,1199,1163,
1061, 953,926,869,802,726, 664,621, 607;1HNMR(CDCl3, 500MHz)
T.; Jeganmohan, M.; Cheng, C.-H. Chem. Commun. 2005, 4955; (f) Turek, P.; Kotora,
ꢁ
ꢀ
ꢀ
ꢀ
M.; Tislerova, I.; Hocek, M.; Votruba, I.; Císarova, I. J. J. Org. Chem. 2004, 69, 9224.
4. Recent examples, see: (a) Xu, L.; Yu, R.; Wang, Y.; Chen, J.; Yang, Z. J. Org. Chem.
2013, 78, 5744; (b) Kumar, B.; King, B. T. J. Org. Chem. 2012, 77, 10617; (c) Saino,
N.; Kawaji, T.; Ito, T.; Matsushita, Y.; Okamoto, S. Tetrahedron Lett. 2010, 51, 1313;
(d) Saino, N.; Amemiya, F.; Tanabe, E.; Kase, K.; Okamoto, S. Org. Lett. 2006, 8,
1439; (e) Chouraqui, G.; Petit, M.; Aubert, C.; Malacria, M. Org. Lett. 2004, 6,
1519; (f) Gandon, V.; Leca, D.; Aechtner, T.; Vollhardt, K. P. C.; Malacria, M.;
Aubert, C. Org. Lett. 2004, 6, 3405.
d
0.95 (t, J¼7.5 Hz, 3H), 1.40e1.51 (m, 4H), 2.22 (s, 3H), 2.42 (s, 3H),
2.85e2.88 (m, 2H), 3.59 (s, 2H), 3.60 (s, 2H), 3.77 (6H),10.5 (s,1H); 13
NMR (CDCl3, 125 MHz) 13.8, 15.2, 16.6, 23.0, 28.2, 33.7, 39.9, 41.0,
C
d
53.1, 58.8,130.1,132.3,133.2,137.5,143.5,144.2,172.1,194.6;HRMS(EI)
5. Recent examples, see: (a) Mitsudo, K.; Harada, J.; Tanaka, Y.; Mandai, H.;
Nishioka, C.; Tanaka, H.; Wakamiya, A.; Murata, Y.; Suga, S. J. Org. Chem. 2013,
78, 2763; (b) Shibata, Y.; Tanaka, K. Synthesis 2012, 44, 323; (c) Iannazzo, L.;
Vollhardt, K. P. C.; Malacria, M.; Aubert, C.; Gandon, V. Eur. J. Org. Chem. 2011,
3283; (d) Alayrac, C.; Schollmeyer, D.; Witulski, B. Chem. Commun. 2009, 1464;
(e) Wang, Y.-H.; Huang, S.-H.; Lin, T.-C.; Tsai, F.-Y. Tetrahedron 2010, 66, 7136; (f)
Yoshida, K.; Morimoto, I.; Mitsudo, K.; Tanaka, H. Tetrahedron 2008, 64, 5800;
(g) Hara, H.; Hirano, M.; Tanaka, K. Org. Lett. 2008, 10, 2537.
m/z [M]þ calcd for C20H26O5 346.1780; found 346.1787.
4.5. [2D2D2] Cycloaddition of diyne 11 with alkynyl ketone
2a in the presence of (R)-BINAP ligand
A flask was charged with [Ir(cod)Cl]2 (13.6 mg, 0.02 mmol) and
(R)-BINAP (25.0 mg, 0.04 mmol). The flask was evacuated and filled
with argon. To the flask were added benzene (5 mL) and 4-nonyn-3-
one (2a) (296 mg, 2.1 mmol). Diyne 11 (256 mg,1.0 mmol) was added
to the reaction mixture. The mixture was stirred under reflux for 1 h.
The progress of the reaction was monitored by GLC. After the re-
action was complete, the solvent was evaporated in vacuo. Column
chromatography of the residue gave 12 (n-hexane/AcOEt¼20:1,
344 mg, 0.87 mmol, 87% yield, 7% ee). The ee value was determined
by HPLC analysis with a Chiralcel OZ-H column (eluant: n-hexane/2-
propanol¼99:1, flow rate: 0.4 mL/min, column temperature: 35 ꢀC,
retention time: 20.42 min (major) and 22.20 min (minor)).
6. Recent examples, see: (a) Foster, R. W.; Tame, C. J.; Hailes, H. C.; Sheppard, T. D.
Adv. Synth. Catal. 2013, 355, 2353; (b) Kawatsura, M.; Yamamoto, M.; Namioka,
J.; Kajita, K.; Hirakawa, T.; Itoh, T. Org. Lett. 2011, 13, 1001; (c) Mallagaray, A.;
ꢀ
Medina, S.; Domínguez, G.; Perez-Castells, J. Synlett 2010, 2114; (d) Cadiero, V.;
Garcia-Garrido, S. E.; Gimeno, J. J. Am. Chem. Soc. 2006, 128, 15094; (e) Yama-
moto, Y.; Ishii, J.; Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2005, 127, 9625; (f)
Yamamoto, Y.; Arakawa, T.; Ogawa, R.; Itoh, K. J. Am. Chem. Soc. 2003, 125, 12143.
ꢀ
7. Recent examples, see: (a) García-Lopez, J.-A.; Greaney, M. F. Org. Lett. 2014, 16,
2338; (b) Sato, Y.; Tamura, T.; Kinbara, A.; Mori, M. Adv. Synth. Catal. 2007, 349,
647; (c) Yamamoto, Y.; Nagata, A.; Nagata, H.; Ando, Y.; Arikawa, Y.; Tatsumi, K.;
Itoh, K. Chem.dEur. J. 2003, 9, 2469.
8. (a) Saino, N.; Kogure, D.; Kase, K.; Okamoto, S. J. Organomet. Chem. 2006, 691,
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dihydro-1H-indene-2-carboxylate (12). Yellow oil; Rf¼0.59 (hex-
ane/AcOEt¼5:1); IR (neat) 2954, 2935, 2872, 1730, 1699, 1598, 1445,
1379, 1343, 1269, 1218, 1166, 1130, 1048, 924, 862, 805, 730, 697,
634; 1H NMR (CDCl3, 500 MHz)
d
0.91 (t, J¼7.5 Hz, 3H), 1.20 (t,
J¼7.5 Hz, 3H), 1.32e1.46 (m, 4H), 2.10 (s, 3H), 2.22 (s, 3H), 2.35e2.38
(m, 2H), 2.71 (q, J¼7.5 Hz, 2H), 3.22 (d, J¼11.0 Hz, 1H), 3.26 (d,
J¼11.0 Hz, 1H), 3.62 (s, 3H), 3.93 (d, J¼16.0 Hz, 1H), 3.98 (d,
J¼16.0 Hz, 1H), 7.24e7.27 (m, 1H), 7.31e7.34 (m, 2H), 7.37e7.39 (m,
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2H); 13C NMR (CDCl3, 125 MHz)
d 7.6, 13.8, 15.2, 16.0, 23.2, 30.7, 33.1,
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ꢀ
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C
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This research was supported by Grant-in-Aid for Scientific Re-
search (C) (25410119) from the Japan Society for the Promotion of
Science and the Ministry of Education, Culture, Sports, Science, and