RhCl3/amine-catalyzed [2+2+2] cyclization of alkynes

Article abstract of DOI:10.1016/j.tet.2008.03.079

The RhCl₃·3H₂O/i-Pr₂NEt-catalyzed [2+2+2] cyclotrimerization of alkynes has been achieved. The reaction can be widely used for various alkynes and provides tri- or hexa-substituted benzenes regioselectively in high yields. The [2+2+2] cycloaddition of diynes and alkynes is also developed, and it affords benzene derivatives in moderate to high yields.

Full text of DOI:10.1016/j.tet.2008.03.079

Tetrahedron 64 (2008) 5800–5807
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Tetrahedron
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RhCl3/amine-catalyzed [2þ2þ2] cyclization of alkynes
*
*
Kenta Yoshida, Ichiro Morimoto, Koichi Mitsudo , Hideo Tanaka
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The RhCl3$3H2O/i-Pr2NEt-catalyzed [2þ2þ2] cyclotrimerization of alkynes has been achieved. The
reaction can be widely used for various alkynes and provides tri- or hexa-substituted benzenes
regioselectively in high yields. The [2þ2þ2] cycloaddition of diynes and alkynes is also developed, and it
affords benzene derivatives in moderate to high yields.
Received 27 February 2008
Received in revised form 21 March 2008
Accepted 21 March 2008
Available online 28 March 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Rh/amine catalyst
Cyclotrimerization
Hexa-substituted benzene
1. Introduction
amine-catalyzed cyclization of alkynes, which can be widely used
for internal alkynes.12 The cyclization of alkynes or diynes and al-
The transition metal-catalyzed [2þ2þ2] cyclotrimerization of
alkynes has been well known as a useful method for the con-
struction of hexa-substituted benzenes in a one step.1–9 Since the
first discovery by Reppe and co-workers,10 various transition
metals (Ni,2 Rh,3 Pd,4 Ru,5 Co,6 Ti,7 and Mo8) catalyzed [2þ2þ2]
cycloadditions have been found to date. However, it has been dif-
ficult to cyclize sterically hindered alkynes in a highly efficient and
highly regioselective manner. For instance, the efficiency of the
trimerization of internal alkynes bearing aryl and ester moieties,
such as alkyl phenylpropiolate (PhC^CCO2R), is quite low.9
Therefore, a more general and efficient catalyst has been in great
demand. In recent years, amine ligands have received considerable
attention for their unique reactivity.11 For instance, Vicic and co-
workers reported the Ni(cod)2/tert-butylterpyridine-catalyzed
cross-coupling reaction of alkyl zinc bromide and alkyl iodide.11d
The ligand system could catalyze Negishi couplings at room tem-
perature in an amide-free solvent. Okamoto and co-workers
reported that the CoCl2$6H2O/2-iminomethylpyridine-catalyzed
cycloaddition of diynes and alkynes proceeded efficiently.11c The
catalytic effect was specific to reactions with the 2-amino-
methylpyridine ligand and no effect was observed with phosphine
ligands. The reactivities in these reactions are quite different from
those in metal/phosphine ligand chemistry. These results led us to
investigate the transition metal/amine ligand-catalyzed trimeriza-
tion of internal alkynes. Recently, we performed the RhCl3$3H2O/
kynes proceeded smoothly to afford multi-substituted benzenes
regioselectively in moderate to high yields.
2. Results and discussions
The RhCl3$3H2O-catalyzed cyclotrimerization of internal al-
kynes was performed successfully by the addition of a catalytic
amount of an electron-rich and bulky alkylamine. First, using ethyl
phenylpropiolate (1a) as a model substrate, the effect of the addi-
tives in the cyclotrimerization was investigated (Table 1). In the
absence of amine, RhCl3$3H2O catalyzed the cyclotrimerization of
alkyne 1a to give cyclized product 2a in only 20% yield (entry 1). On
the other hand, the trimerization of alkyne 1a was efficiently pro-
moted by the addition of tert-amines. In the presence of Et3N,
which is a frequently used base, the yield of the products increased
to 67% (entry 2). To compare the effect of Et3N with that of other
amines, we examined the cyclotrimerization of alkyne 1a using
various electron-rich amines (entries 3–6). The trimerization of
alkyne 1a using i-Pr2NEt, Me3SiNEt2, and dicyclohexylmethylamine
(Cy2NMe), gave cycloadducts 2a and 3a in respective yields of 91,
80, and 75% (entries 3–5). Only in the case of N(C2H4)3N was the
yield of products 2a and 3a significantly reduced (24%, entry 6).
These facts indicate that the reactivity would be influenced by the
bulkiness of the tert-amines. Indeed, the yields of cyclized products
2a and 3a increased with an increase in the bulkiness of the
amines: i-Pr2NEt (91%)>Et3N (67%)>N(C2H4)3N (24%). Next, the
cyclotrimerization of 1a using PhNMe2 and Ph3N, the yields of
cycloadducts 2a and 3a dramatically decreased (entries 7 and 8).
These results suggest that such electron-deficient amines are not
* Corresponding authors. Tel.: þ81 86 251 8072; fax: þ81 86 251 8079.
E-mail addresses: mitsudo@cc.okayama-u.ac.jp (K. Mitsudo), tanaka95@cc.
okayama-u.ac.jp (H. Tanaka).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.079

K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
5801
Table 1
Table 2
Cyclotrimerization using several additives
Cyclotrimerization using several catalystsa
Ph
Ph
Ph
Ph
Ph
Ph
Catalyst (8-10 mol %)
RhCl3·3H2O (8 mol %)
R
R
Ph
R
R
R
R
R
Ph
R
R
R
i-Pr2NEt (30 mol %)
Additive (30 mol %)
Toluene, Reflux, 24 h
Toluene, Reflux, 24 h
R
Ph
Ph
Ph
Ph
R
Ph
2a
R
3a
Ph
2a
R
3a
R = CO2Et
R = CO2Et
1a
1a
Entry
Catalyst
Yieldb of 2aþ3a (%)
89
2a/3ac
Entry
Additive
Yielda of 2aþ3a (%)
2a/3ab
1
2
3
4
5
6
7
8
9
10
RhCl3
99:1
93:7
93:7
69:31
87:13
62:38
85:15
d
1
2
3
4
5
6
7
8
None
Et3N
20
67
91
80
75
24
45
26
d
69
32
17
d
d
6
99:1
98:2
96:4
96:4
97:3
95:5
96:4
97:3
d
Rh(acac)3
[Rh(OAc)2]2
[Rh(cod)2][BF4]
[RhCl(cod)]2
RhCl(PPh3)3
Rh(acac)(cod)
PdCl2
6
11
81
63
60
29
<1
10
3
i-Pr2NEt
Cy2NMe
Me3SiNEt2
N(C2H4)3N
PhNMe2
Ph3N
Pyridine
i-Pr2NH
Et2NH
t-BuNH2
TMEDA
2,20-Bipyridyl
PBu3
P(t-Bu)3
PCy3
PtCl2
IrCl3
86:14
55:45
9
10
11
12
13
14
15
16
17
18
19
20
95:5
97:3
95:5
d
a
Inactive catalysts: CoCl2, CoCl2$3H2O, NiCl2, RuCl3$nH2O, CrCl2, CrCl3,
FeCl3$6H2O, CuCl, CuCl2$2H2O, SmCl3, TiCl4, ZnCl2, PbCl2, BiCl3.
b
Isolated yield.
d
c
Determined by 1H NMR.
73:27
90:10
d
5
reaction of alkyne 1a with [Rh(cod)2][BF4] (cod¼1,5-cyclo-
octadiene) gave moderate yields of cyclized products 2a and 3a, but
exhibited poor regioselectivity less than that with RhCl3$3H2O (2a/
3a¼69:31) (entry 4). Using neutral Rh(I) catalysts such as
[RhCl(cod)]2, RhCl(PPh3)3, and Rh(acac)(cod), the yields and the
regioselectivities of the cyclized products decreased significantly
(entries 5–7). Notably, the reaction catalyzed by RhCl(PPh3)3, which
is one of the typical catalysts for the trimerization reaction, gave the
cyclized products in a yield of 60% and in the ratio of 62:38 (2a/
3a¼37:23) (entry 6). Several other metal catalysts were also
employed in the reaction. The trimerization of alkyne 1a using
PdCl2, PtCl2, and IrCl3 gave cycloadducts 2a and 3a in respective
yields of a trace,10, and 3% (entries 8–10). With other metal halides,
such as CoCl2, CoCl2$3H2O, NiCl2, RuCl3$nH2O, CrCl2, CrCl3,
FeCl3$6H2O, CuCl, CuCl2$2H2O, SmCl3, TiCl4, ZnCl2, PbCl2, and BiCl3,
cyclized products 2a and 3a were not obtained at all. Above all,
among thus far examined catalysts, the most effective catalyst is
RhCl3$3H2O/i-Pr2NEt, which can promote the cyclotrimerization
efficiently in a virtually complete regioselective manner.
<1
d
<1
d
PPh3
Dppp
(S)-BINAP
d
93:7
d
a
Isolated yield.
b
Determined by 1H NMR.
effective in cyclotrimerization. Pyridine was not effective, and
starting material 1a was recovered quantitatively, probably due to
the generation of RhCl3(py)3, which might not be an active catalyst
for the reaction (entry 9).13 In a similar manner, the RhCl3$3H2O-
catalyzed cyclotrimerization was performed with sec- and prim-
amines, affording cycloadducts 2a and 3a in yields of 17–69%
(entries 10–12). Among the examined sec- and prim-amines, elec-
tron-rich and bulky amines, e.g., i-Pr2NH, were the most effective
(entry 10). Bidentate amines such as TMEDA (N,N,N0,N0-tetrame-
thylethylenediamine) and 2,20-bipyridyl were not effective at all
(entries 13 and 14). Interestingly, commonly used phosphine li-
gands were not effective for the cyclotrimerization (entries 15–20).
With alkyl phosphines, the yields of cyclized products 2a and 3a
were lower than 6% (entries 15–17). PPh3 and bidentate phosphines
were not effective at all (entries 18–20). Above all, it has been found
that the presence of an electron-rich and bulky amine is essential
for the cyclotrimerization reaction. In particular, RhCl3$3H2O/
i-Pr2NEt is the best combination for promoting the cyclo-
trimerization of alkyne 1a, probably due to the generation of an
‘active catalyst’ in situ.
The reaction efficiency of the RhCl3$3H2O/i-Pr2NEt-catalyzed
cyclization of 1a was highly influenced by the amounts and the
ratio of RhCl3$3H2O and i-Pr2NEt (Table 3). In the presence of
RhCl3$3H2O (8 mol %) and i-Pr2NEt (30 mol %), the cyclo-
trimerization of alkyne 1a occurred smoothly to give products 2a
and 3a in 91% yield (entry 1). The ratio of the amount of RhCl3$3H2O
Table 3
To evaluate the catalytic activity of RhCl3$3H2O, several transi-
tion metal catalysts were used for the cyclotrimerization of ethyl
phenylpropiolate (1a) (Table 2). First, other Rh(III) catalysts were
employed for the reaction (entries 1 and 2). RhCl3 (anhydrous)
exhibited an activity similar to that of RhCl3$3H2O, affording
cyclized products 2a and 3a in yields of 89% and resulting in high
product selectivity (2a/3a¼99:1) (entry 1). This fact suggested that
the presence of a small amount of water might not affect the re-
action. On the other hand, Rh(acac)3 (acac¼acetylacetonate) was
not effective (entry 2), resulting in the formation of only 6% yields of
cyclized products 2a and 3a. [Rh(OAc)2]2, a Rh(II) catalyst, also
showed poor catalytic activity to afford 11% yields of cyclized
products 2a and 3a (entry 3). Next, Rh(I) catalysts were utilized for
the trimerization of 1a (entries 4–7). Among the Rh(I) catalysts
examined thus far, no catalyst showed higher activity and higher
regioselectivity than RhCl3$3H2O. Cationic Rh(I) complexes have
received great attention as useful catalysts for cycloadditions. The
Effects of the amounts and the ratio of RhCl3$3H2O/i-Pr2NEt
Ph
Ph
Ph
R
R
Ph
R
R
R
RhCl3·3H2O/i-Pr2NEt
Toluene, Reflux, 24 h
Ph
Ph
R
Ph
2a
R
3a
R = CO2Et
1a
Entry
RhCl3$3H2O (mol %)
i-Pr2NEt (mol %)
Yielda of 2aþ3a (%)
2a/3ab
1
2
3
4
5
6
7
8
3
3
3
3
2
1
30
12
9
6
3
91
84
93
74
52
71
57
96:4
96:4
97:3
96:4
95:5
95:5
95:5
6
3
a
Isolated yield.
Determined by 1H NMR.
b

5802
K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
Table 4
toluene, the cyclotrimerization of alkyne 1a afforded cycloadducts
Cyclotrimerization of alkyne 1a in several solvents
2a and 3a in 91% yields in the ratio of 96:4 (entry 1). Other aromatic
hydrocarbons such as o-xylene and benzene were used for the re-
action, resulting in a decrease in the yields of adducts 2a and 3a (87
and 67%) (entries 2 and 3). Ethers could also be used for the re-
action. When the reaction was carried out in DME (1,2-dime-
thoxyethane) or 1,4-dioxane, cycloadducts 2a and 3a were obtained
in yields of 87 and 83%, respectively (entries 4 and 5). In THF, the
yields of products 2a and 3a dramatically decreased to 47% (entry
6). Et2O was not of any use, and most of starting material 1a was
recovered (entry 7). These facts indicated that the yields of cyclo-
trimerization products 2a and 3a could be affected by the reaction
temperature (refluxing temperature of the solvents). Indeed, the
yields of the cyclized products increased with an increase in the
reaction temperature: o-xylene (144 ꢀC), toluene (111 ꢀC), 1,4-
dioxane (101 ꢀC), or DME (83 ꢀC)>benzene (80 ꢀC)>THF
(66 ꢀC)>Et2O (35 ꢀC). Alcohols could be also utilized in the trime-
rization of alkyne 1a (entries 8 and 9). The cyclotrimerization of 1a
in i-PrOH afforded products 2a and 3a in 86% yields, while the
regioselectivity was lower than that in toluene (2a/3a¼85:15)
(entry 8). In other solvents, such as CH3CN, H2O,1,2-dichloroethane,
and CH2Cl2, similar cyclotrimerization occurred to afford 18–59%
yields of adducts 2a and 3a in the ratio of 72:28–89:11 (entries 10–
13). Alkanes, e.g., hexane and heptane, were not of any use; thus,
most of starting material 1a was recovered (entries 14 and 15).
Above all, it was found that several kinds of solvents could be used
and the best choice of the solvent is toluene, in which, the best
yields and highest regioselectivity could be attained (91%,
2a/3a¼96:4). Thus, RhCl3$3H2O/i-Pr2NEt/toluene is the best com-
bination for promoting the cyclotrimerization of alkyne 1a.
Ph
Ph
Ph
RhCl3·3H2O (8 mol %)
R
R
Ph
R
R
R
i-Pr2NEt (30 mol %)
Solvent, Reflux, 24 h
Ph
Ph
R
Ph
2a
R
3a
R = CO2Et
1a
Entry
Solvent
Yielda of 2aþ3a (%)
2a/3ab
1
2
3
4
5
6
7
8
Toluene
o-Xylene
Benzene
DME
1,4-Dioxane
THF
Et2O
i-PrOH
EtOH
CH3CN
91
87
67
87
83
47
d
86
55
50
39
59
18
d
3
96:4
96:4
92:8
91:9
93:7
88:12
d
85:15
80:20
72:28
89:11
88:12
83:17
d
9
10
11
12
13
14
15
H2O
1,2-Dichloroethane
CH2Cl2
Hexane
Heptane
91:9
a
Isolated yield.
Determined by 1H NMR.
b
to that of i-Pr2NEt significantly affected the product yield (entries
2–5), and the best yields of cycloadducts 2a and 3a were obtained
with a 1:3 mixture of RhCl3$3H2O and i-Pr2NEt (entry 3). When the
amount of RhCl3$3H2O was decreased to 2 mol % and 1 mol %, the
yields of products 2a and 3a decreased to 71 and 57% yields, re-
spectively (entries 6 and 7). From these results, it was found that the
cyclotrimerization of 1a required approximately 3 equiv of i-Pr2NEt
in comparison to RhCl3$3H2O, and the yields of products 2a and 3a
decreased with an increase or decrease in the amount of i-Pr2NEt.
With 3 mol % RhCl3$3H2O and 9 mol % of the i-Pr2NEt catalyst,
cycloadducts 2a and 3a were obtained in the highest yield (93%).
The effect of the solvent on the cyclotrimerization was in-
vestigated. In several solvents, the RhCl3$3H2O/i-Pr2NEt-catalyzed
cyclotrimerization of 1a was performed at reflux (Table 4). In
Next, the RhCl3$3H2O/i-Pr2NEt catalyst was applied to the
cyclotrimerization of various alkynes (Table 5). In the presence of
RhCl3$3H2O (8 mol %) and i-Pr2NEt (30 mol %), several internal
alkynes could successfully undergo the cyclotrimerization to give
the corresponding cyclized products (entries 1–11). The cyclo-
trimerization of alkynes 1a–c bearing phenyl group smoothly
proceeded in highly regioselective manner to predominantly afford
cycloadducts 2a–c; indeed, the total yields of cycloadducts 2 and 3
were 85–91% and the ratio of 2/3 was higher than 96:4 (entries
Table 5
Cyclotrimerization of various alkynes
R1
R1
R1
RhCl3·3H2O (8 mol %)
R2
R2
R1
R2
R2
R1
R2
R1
i-Pr2NEt (30 mol %)
Toluene, Reflux
R2
R1
2
R2
3
1
Entry
R1
R2
Time (h)
Yielda of 2þ3 (%)
2/3b
96:4
>99:<1
>99:<1
76:24
d
1
2
3
4
5
6
Ph
Ph
Ph
Me
Pr
Ph
CO2Et
CO2Me
Me
CO2Et
Pr
Ph
CO2Me
2-Thienyl
5-Me-2-thienyl
5-Ac-2-thienyl
3-Thienyl
H
H
H
H
1a
24
24
24
24
24
24
24
24
24
24
24
12
12
12
12
91 (93)c
85
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
87 (91)c
95 (90)c
96
73
46
d
7
CO2Me
2-Thienyl
5-Me-2-thienyl
5-Ac-2-thienyl
3-Thienyl
Ph
p-MeC6H4
Hexane
EtO2C
d
8d
9
49
63
50
23
d
d
10d
11d
12
13
14
15
d
d
98 (94)c
97
94:6
>99:<1
67:33
74:26
87
75
a
Isolated yield.
Determined by 1H NMR.
RhCl3$3H2O (3 mol %) and i-Pr2NEt (9 mol %) were employed.
Performed in i-PrOH.
b
c
d

K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
5803
1–3). On the other hand, alkyne 1d bearing no phenyl group un-
derwent the cyclotrimerization to afford the corresponding ad-
ducts, but a slight decline in the regioselectivity was observed (2d/
3d¼76:24) (entry 4). This fact suggested that the regioselectivity of
the cyclotrimerization of alkyne was affected by the phenyl group.
Notably, in the cyclotrimerization of alkynes 1a, 1c and 1d, the
amount of RhCl3$3H2O/i-Pr2NEt could be reduced to 3/9 mol %
without an apparent change in the product yields. The cyclo-
trimerization of symmetrical internal alkynes 1e and 1f, gave
cycloadducts 2e and 2f in respective yields of 96 and 73% (entries 5
and 6). Dimethyl acetylenedicarboxylate (DMAD, 1g), an active
well-used alkyne in cycloaddition, was unsuitable for the reaction
(2g: 46% yield, entry 7). As we recently reported, dithienylacety-
lenes could be utilized in the reaction.12a The cyclotrimerization of
di(2-thienyl)acetylene and its derivatives (1h–j) afforded corre-
sponding hexakis(2-thienyl)benzenes (2h–j) in respective yields of
49, 63, and 50% (entries 8–10). Using di(3-thienyl)acetlylene (1k),
trimerized product 2k was obtained in 23% yield (entry 11). In
a similar manner, terminal alkynes 1l–o were subjected to the Rh/
amine-catalyzed trimerization (entries 12–15). The trimerization of
phenylacetylene (1l) gave cycloadducts 2l and 3l in 98% in the ratio
of 94:6 (entry 12). The reaction of p-tolylacetylene (1m) proceeded
in a highly selective manner to predominantly afford cyclized
products 2m (total yield 97%) (2m/3m¼>99:<1) (entry 13). The
trimerization of 1-octyne (1n) afforded cycloadducts 2n and 3n in
a total yield of 87%, but the ratio of 2n/3n dramatically decreased to
67:33 (entry 14). Upon the cyclotrimerization of ethyl propiolate
(1o), the yields of the corresponding adduct and the regioselectivity
were reduced to 75% and 2o/3o¼74:26 (entry 15). Above all, un-
symmetrically substituted acetylene afforded asymmetric adducts
2a–d and 2l–o as the major products in good to excellent yields.
The regioselectivity in the RhCl3$3H2O/i-Pr2NEt-catalyzed cyclo-
trimerization was highly influenced by the aryl substituents of the
alkynes; indeed, the cyclotrimerization of alkynes bearing phenyl
or tolyl groups proceeded with virtually complete regioselectivities
(entries 1–3, 12, and 13).
electron-rich Rh(I) species might interact with two alkynes by
strong p-back donation to form a rhodacyclopentadienyl complex.
The insertion of another alkyne to the complex and the subsequent
reductive elimination afford the corresponding cyclized product.
When alkynes bearing an aryl group were employed, di(a-aryl)-
rhodacyclopentadienes would be favorable than di(b-aryl) ones. It
might be the reason for the regioselective formation of the tri-
arylbenzenes (Table 5, entries 1–3, 12, and 13).
To obtain further insight into the mechanism, we attempted to
capture the in situ generated Rh(I) catalyst. To a solution of
RhCl3$3H2O in i-PrOH, i-Pr2NEt was added and the mixture was
stirred at room temperature for 0.5 h. After the solution was con-
centrated, the residual black solids were purified by GPC (gel per-
meation chromatography) to afford the colorless crystals, which
were easily deliquescent in air. In the 1H and 13C NMR spectra of the
complex, the peaks of i-Pr2NEt disappeared and new ethyl and
isopropyl peaks were observed, suggesting the coordination of i-
Pr2NEt to the Rh center (Figs. 1 and 2). Though the specific structure
of the rhodium complex is not clear at present, the existence of
a rhodium complex bearing i-Pr2NEt is strongly indicated.
The combination of RhCl3$3H2O and i-Pr2NEt was successfully
used in the [2þ2þ2] cycloaddition of diyne and various alkynes
(Table 6). In the presence of RhCl3$3H2O/i-Pr2NEt, a mixture of
diyne 4a and phenylacetylene (1l, 4 equiv) in i-PrOH was stirred at
50 ꢀC for 5 h to afford cycloadduct 5al in 81% yield and 16% of 6a
(entry 1). When the reaction was carried out at reflux, the yields of
5al and 6a were almost the same as those in the reaction at 50 ꢀC
(entry 2). Next, the RhCl3$3H2O/i-Pr2NEt-catalyzed cyclization of
diyne 4a and 1-octyne (1n) was performed at 50 ꢀC for 5 h to afford
cycloadduct 5an in 60% yield (entry 3). When the reaction was
carried out at reflux, the yield of 5an increased to 82% (entry 4). In
this case, the reaction proceeded much efficiently at a higher
temperature. Internal alkynes could also be utilized in the
RhCl3$3H2O/i-Pr2NEt-catalyzed cycloaddition (entries 5–9). Using
ethyl phenylpropiolate (1a), cyclized product 5aa was obtained in
39% yield together with 60% of 6a (entry 5). When the reaction was
carried out at reflux, the yield of 5aa was almost the same as that in
the reaction performed at 50 ꢀC, but the yield of 6a decreased,
resulting in the generation of by-products such as polymer (entry
The regioselectivity in the RhCl3/amine-catalyzed cyclo-
trimerization was highly influenced by the substituents of alkynes.
In particular, the reaction of alkynes bearing aryl groups proceeded
with virtually complete regioselectivities. A plausible mechanism
of the reaction is illustrated in Scheme 1. First, RhCl3 would be re-
duced by i-Pr2NEt to afford a Rh(I) complex. Thus generated
1.00
1.24, 1.31
Rh
N
3.01
3.46
RhCl3·3H2O
N
R
R
R
R
R
RhCl3·3H2O
NR3
2.46
2.92
1.01
1.33
R
R
R
RhI
i-Pr2NEt
RhIII
R
R
RhI
R
R
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
ppm
R
R
R
R
R
R
RhCl3·3H2O/i-Pr2NEt
RhIII
R
R
R
R
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
ppm
R
R
Scheme 1. A plausible mechanism.
Figure 1. 1H NMR analysis of i-Pr2NEt and RhCl3$3H2O/i-Pr2NEt complex.

5804
K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
20.63
Rh
N
Me
Me
16.84, 18.13
53.40, 53.37
Ph
Ph
RhCl3·3H2O (8 mol %)
Ph
Ph
Me
Me
EtO2C
EtO2C
i-Pr2NEt (30 mol %)
EtO2C
EtO2C
48.50
i-PrOH, Reflux, 24 h
RhCl3·3H2O
N
39.10
41.75
5bf (46%)
4b (0.5 mmol) 1f (10 equiv)
17.09
11.78, 11.81
Me
Me
Me
Me
EtO2C
EtO2C
Recov. 4b (45%)
CO2Et
CO2Et
i-Pr2NEt
6b (Not detected)
Scheme 2. Cycloaddition of diyne 4b and diphenylacetylene (1f).
55
50
45
40
35
30
25
20
15
10
5
ppm
3. Conclusion
The [2þ2þ2] cyclotrimerization of alkynes proceeds with high
reactivity when the combination of RhCl3$3H2O/i-Pr2NEt/toluene is
used. The reaction can be widely used for various mono- and di-
substituted acetylenes and provides tri- or hexa-substituted ben-
zenes regioselectively in high yields. The [2þ2þ2] cycloaddition of
diynes and alkynes has also been developed by using a Rh/amine
complex, and it provides benzene derivatives in moderate to high
yields.
RhCl3·3H2O/i-Pr2NEt
55
50
45
40
35
30
25
20
15
10
5
ppm
Figure 2. 13C NMR analysis of i-Pr2NEt and RhCl3$3H2O/i-Pr2NEt complex.
6). The cycloaddition of diyne 4a and alkyne 1c at 50 ꢀC or reflux
gave the cycloadduct in respective yields of 43 and 48% (entries 7
and 8). When the reaction was carried out using alkyne 1f, the yield
of 5af was 45% (entry 9). Above all, the RhCl3$3H2O/i-Pr2NEt-cat-
alyzed cyclization of diyne 4a and terminal alkynes gave the cor-
responding products in high yields. In the reaction of 4a and
internal alkynes, the yields of dimer 6a decreased under the
refluxing condition, while no significant change was observed in
the yields of 5a, probably because generated 6a would react with 1
or 4a to give other products under the refluxing conditions.
Next, the cycloaddition of diyne 4b and diphenylacetylene (1f)
was performed. In the presence of RhCl3$3H2O (8 mol %) and i-
Pr2NEt (30 mol %), to a solution of alkyne 1f in i-PrOH was added
dropwise diyne 4b at reflux, and the mixture was heated to reflux
for an additional 24 h to afford 5bf in 46% yield and 45% of 4b was
recovered (Scheme 2). While the yield of 5bf was still moderate, the
generation of 6b, the dimer of 4b, was not observed, and hexa-
substituted benzene derivative 5bf was obtained chemoselectively.
4. Experimental
4.1. General remarks
1H and 13C NMR spectra were recorded on Varian INOVA UNITY
600 (1H 600 MHz, 13C 150 MHz) spectrometers in CDCl3 using TMS
or residual chloroform as internal standard. Splitting patterns are
designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multi-
plet; dd, double doublet; and tt, triple triplet. Coupling constants
are reported in hertz (Hz). IR spectra were recorded on a JASCO FT/
IR-4100 spectrophotometer in wave number (cmꢁ1) and only major
absorption bands are compiled. Analytic thin layer chromatography
(TLC) was performed on Merck, pre-coated plate silica gel 60 F254
(0.25 mm thickness). Column chromatography was performed on
KANTO CHEMICAL silica gel 60N (40–50 mm). Preparative recycling
gel permeation chromatography (GPC) was performed with a JAI
LC-9101 instrument equipped with JAIGEL-1H/JAIGEL-2H column
using chloroform as an eluent. Elemental analysis was obtained
with Perkin–Elmer PE 2400 Series II CHNS/O analyzer. Unless
otherwise noted, all materials were obtained from commercial
suppliers and used without further purification. Diynes 4a and 4b
were prepared according to literature procedures.14 All reactions
were performed in dry solvents under argon atmosphere. Toluene,
benzene, xylene,1,4-dioxane, i-PrOH, CH3CN, dichloroethane, CH2Cl2,
hexane, and heptane were distilled from CaH2. DME, THF, Et2O, and
EtOH were distilled from sodium benzophenone ketyl under argon.
Table 6
Cycloaddition of diyne and several alkynes
R1
RhCl3·3H2O (8 mol %)
i-Pr2NEt (30 mol %)
i-PrOH
EtO2C
EtO2C
R2
4a
1 (4 equiv)
R1
EtO2C
EtO2C
EtO2C
EtO2C
CO2Et
CO2Et
R2
5a
6a
4.2. General procedure for Rh/amine-catalyzed
cyclotrimerization of internal alkyne
Entry R1
R2
Temperature (ꢀC) Time (h)
Yielda 5a/6a (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Hex
Hex
Ph
Ph
Ph
Ph
Ph
H
H
H
H
1l
1l
50
Reflux
5
2
5
2
5
2
5
2
2
5al
5al
81:16
81:18
To a suspension of RhCl3$3H2O (10 mg, 0.04 mmol) in toluene
(3.0 mL) were added i-Pr2NEt (26 mL, 0.15 mmol) and ethyl phe-
nylpropiolate 1a (87 mg, 0.50 mmol). The mixture was stirred at
reflux for 24 h. After being cooled to room temperature, the re-
action mixture was concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel
(hexane/EtOAc 5:1) to afford 1,2,4-triethoxycarbonyl-3,5,6-triphe-
nylbenzene 2a (79 mg, 91%) as colorless solids.
1n 50
1n Reflux
5an 60:27
5an 82:11
5aa 39:60
5aa 39:17
5ac 43:41
5ac 48:d
CO2Et 1a 50
CO2Et 1a Reflux
Me
Me
Ph
1c 50
1c Reflux
1f
Reflux
5af
45:d
a
Isolated yield.

K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
5805
4.2.1. 1,2,4-Triethoxycarbonyl-3,5,6-triphenylbenzene (2a)9d
4.3. General procedure for Rh/amine-catalyzed
cyclotrimerization of di(thienyl)acetylene
Colorless solids; Rf¼0.20 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 0.68 (t, J¼7.2 Hz, 3H), 0.87 (t, J¼7.2 Hz, 3H),
0.90 (t, J¼7.2 Hz, 3H), 3.65 (q, J¼7.2 Hz, 2H), 3.94 (q, J¼7.2 Hz, 2H),
3.98 (q, J¼7.2 Hz, 2H), 7.00–7.04 (m, 4H), 7.11–7.14 (m, 6H), 7.35 (s,
5H); 13C NMR (150 MHz, CDCl3): d 13.3, 13.41, 13.43, 60.9, 61.50,
61.51, 127.1, 127.3, 127.4, 127.5, 127.9, 128.0, 128.9, 129.8, 129.9, 132.0,
134.1, 137.2, 137.3, 137.4, 137.6, 139.2, 140.7, 167.29, 167.33, 167.7; IR
(KBr) 3057, 2981, 2936, 1729, 1232, 1200 cmꢁ1. Anal. Calcd for
To a solution of RhCl3$3H2O (11 mg, 0.04 mmol) in i-PrOH
(3.0 mL) were added i-Pr2NEt (26 mL, 0.15 mmol) and di(2-thienyl)-
acetylene 1h (96 mg, 0.50 mmol). The mixture was stirred at reflux
for 24 h. After being cooled to room temperature, the reaction
mixture was filtered and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel
(hexane/toluene 5:1) to afford hexa(2-thienyl)benzene 2h (47 mg,
49%) as yellow solids.
C
33H30O6: C, 75.84; H, 5.79. Found: C, 75.61; H, 5.82.
In a similar manner, the Rh/amine-catalyzed cyclotrimerization
of internal alkynes 1b–1g was carried out. The reaction conditions
and the results are illustrated in Table 5.
4.3.1. Hexa(2-thienyl)benzene (2h)
Yellow solids; Rf¼0.27 (hexane/toluene 5:1); 1H NMR (600 MHz,
CDCl3) d 6.59 (dd, J¼3.6,1.2 Hz, 6H), 6.68 (dd, J¼5.4, 3.6 Hz, 6H), 7.08
(dd, J¼5.4, 1.2 Hz, 6H); 13C NMR (150 MHz, CDCl3) d 125.8,
126.2, 129.1, 137.0, 140.7; IR (KBr) 3068, 2923, 2360, 1647, 1381,
694 cmꢁ1. Anal. Calcd for C30H18S6: C, 63.12; H, 3.18. Found: C,
63.08; H, 3.36.
4.2.2. 1,2,4-Trimethoxycarbonyl-3,5,6-triphenylbenzene (2b)9d
Colorless solids; Rf¼0.31 (hexane/EtOAc 1:1); 1H NMR
(600 MHz, CDCl3): d 3.17 (s, 3H), 3.47 (s, 3H), 3.51 (s, 3H), 7.00–7.03
(m, 4H), 7.12–7.15 (m, 6H), 7.32–7.38 (m, 6H); 13C NMR (150 MHz,
CDCl3): d 51.7, 52.3, 52.4, 127.2, 127.4, 127.51, 127.52, 128.0, 128.1,
128.5, 129.57, 129.63, 131.7, 134.1, 137.1, 137.20, 137.23, 137.3, 139.2,
140.9,167.7, 167.9, 168.1; IR (KBr) 3030, 3001, 2951, 1744, 1735,1244,
In a similar manner, the Rh/amine-catalyzed cyclotrimerization
of di(thienyl)acetylene derivatives 1i–1k was carried out. The re-
action conditions and the results are illustrated in Table 5.
1205 cmꢁ1
.
4.2.3. 1,2,4-Trimethyl-3,5,6-triphenylbenzene (2c)6g
4.3.2. Hexakis(5-methyl-2-thienyl)benzene (2i)
Colorless solids; Rf¼0.55 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 1.72 (s, 3H), 2.04 (s, 3H), 2.05 (s, 3H), 6.96–7.14
(m, 10H), 7.25 (dd, J¼7.8, 1.2 Hz, 2H), 7.35 (tt, J¼7.8, 1.2 Hz, 1H), 7.45
(tm, J¼7.8 Hz, 1H); 13C NMR (150 MHz, CDCl3): d 18.1, 18.3, 19.4,
125.6, 125.7, 126.5, 127.28, 127.31, 128.4, 129.4, 130.286, 130.294,
131.3, 131.9, 133.9, 139.2, 140.6, 141.4, 141.58, 141.61, 142.4; IR (KBr)
Yellow solids; Rf¼0.23 (hexane/toluene 5:1); 1H NMR (600 MHz,
CDCl3) d 6.33 (s, 12H), 2.30 (s, 18H); 13C NMR (150 MHz, CDCl3)
d 15.2, 123.9, 128.7, 137.0, 138.8, 140.2; IR (KBr) 3068, 2912, 2855,
2357, 1747, 1442, 1219, 800 cmꢁ1. Anal. Calcd for C36H30S6: C, 66.01;
H, 4.62. Found: C, 66.09; H, 4.53.
3055, 2956, 2918, 2849 cmꢁ1
.
4.3.3. Hexakis(5-acetyl-2-thienyl)benzene (2j)
Colorless solids; Rf¼0.07 (hexane/EtOAc 3:1); 1H NMR
(600 MHz, CDCl3) d 7.27 (d, J¼3.6 Hz, 6H), 6.67 (d, J¼3.6 Hz, 6H),
2.43 (s, 18H); 13C NMR (150 MHz, CDCl3) d 26.7, 130.9, 131.8, 136.5,
4.2.4. 1,2,4-Triethoxycarbonyl-3,5,6-trimethylbenzene (2d)2e
Colorless liquid; Rf¼0.13 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 1.35 (t, J¼7.2 Hz, 3H), 1.36 (t, J¼7.2 Hz, 3H), 1.38
(t, J¼7.2 Hz, 3H), 2.22 (s, 3H), 2.26 (s, 3H), 2.30 (s, 3H), 4.32 (q,
J¼7.2 Hz, 2H), 4.33 (q, J¼7.2 Hz, 2H), 4.40 (q, J¼7.2 Hz, 2H); 13C NMR
(150 MHz, CDCl3): d 14.0, 14.2, 16.5, 17.0, 17.3, 61.37, 61.46, 61.49,
129.9, 130.3, 132.6, 133.7, 135.8, 137.5, 167.8, 168.5, 169.4; IR (neat)
2982, 2938, 2906, 1731, 1576 cmꢁ1. Anal. Calcd for C18H24O6: C,
64.27; H, 7.19. Found: C, 64.02; H, 7.13.
145.8, 146.7, 190.7; IR (KBr) 3080, 1658, 1471, 1381, 1274 cmꢁ1
.
4.3.4. Hexa(3-thienyl)benzene (2k)
Brown solids; Rf¼0.27 (hexane/EtOAc 3:1); 1H NMR (600 MHz,
CDCl3) d 6.91 (dd, J¼4.8, 3.0 Hz, 6H), 6.58 (dd, J¼3.0, 1.5 Hz, 6H),
6.50 (dd, J¼4.8, 3.6 Hz, 6H); 13C NMR (150 MHz, CDCl3) d 123.3,
124.1, 129.7, 136.5, 140.3; IR (KBr) 3068, 2923, 2360, 1647, 1381,
1223, 694 cmꢁ1. Anal. Calcd for C30H18S6: C, 63.12; H, 3.18. Found: C,
63.08; H, 3.36.
4.2.5. 1,3,5-Triethoxycarbonyl-2,4,6-trimethylbenzene (3d)2e
Colorless liquid; Rf¼0.20 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 1.37 (t, J¼7.2 Hz, 9H), 2.23 (s, 9H), 4.38 (q,
J¼7.2 Hz, 6H); 13C NMR (150 MHz, CDCl3): d 14.2, 17.1, 61.3, 132.1,
133.5, 169.0; IR (neat) 2981, 2937,1728, 1581,1226 cmꢁ1. Anal. Calcd
for C18H24O6: C, 64.27; H, 7.19. Found: C, 64.34; H, 7.29.
4.4. General procedure for Rh/amine-catalyzed
cyclotrimerization of terminal alkyne
To a suspension of RhCl3$3H2O (11 mg, 0.04 mmol) in toluene
(3.0 mL) were added i-Pr2NEt(26 mL,0.15 mmol)andphenylacetylene
1l (55 mg, 0.50 mmol). The mixture was stirred at reflux for 12 h.
After being cooled to room temperature, the reaction mixture was
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (hexane/EtOAc 5:1) to afford
1,2,4-triphenylbenzene 2l (54 mg, 98%) as colorless solids.
4.2.6. Hexapropylbenzene (2e)4e
Colorless solids; Rf¼0.80 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 1.04 (t, J¼7.2 Hz, 18H), 1.49–1.57 (m, 12H),
2.46–2.48 (m, 12H); 13C NMR (150 MHz, CDCl3): d 15.3, 24.8, 32.2,
136.7; IR (KBr) 2952, 2928, 2890, 2869 cmꢁ1. Anal. Calcd for C24H42
C, 87.19; H, 12.81. Found: C, 87.21; H, 13.14.
:
4.2.7. Hexaphenylbenzene (2f)6g
4.4.1. 1,2,4-Triphenylbenzene (2l)7a,15
Colorless solids; Rf¼0.50 (hexane/EtOAc 5:1); 1H NMR (600 MHz,
Colorless solids; Rf¼0.57 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 7.17–7.24 (m, 10H), 7.37 (tt, J¼7.8, 1.2 Hz, 1H),
CDCl3): d 6.83–6.86 (m, 30H); 13C NMR (150 MHz, CDCl3): d 125.2,
126.5, 131.4, 140.3, 140.6; IR (KBr) 3056, 3024, 2925 cmꢁ1
.
7.45–7.48 (m, 2H), 7.51 (dd, J¼7.8, 1.2 Hz, 1H), 7.65–7.69 (m, 4H); 13
C
NMR (150 MHz, CDCl3): d 126.1, 126.5, 126.6, 127.1, 127.4, 127.89,
4.2.8. Hexamethoxycarbonylbenzene (2g)
127.92, 128.8, 129.4, 129.87, 129.90, 131.1, 139.5, 140.4, 140.6, 141.0,
Colorless solids; Rf¼0.31 (hexane/EtOAc 1:1); 1H NMR
(600 MHz, CDCl3) d 3.88 (s, 18H); 13C NMR (150 MHz, CDCl3) d 53.5,
133.9, 165.1; IR (KBr) 3009, 2958, 1739, 1445 cmꢁ1; Anal. Calcd for
141.1, 141.5; IR (KBr) 3075, 3056, 3027 cmꢁ1
.
In a similar manner, the Rh/amine-catalyzed cyclotrimerization
of terminal alkynes 1m–1o was conducted. The reaction conditions
and the results are illustrated in Table 5.
C
18H18O6: C, 50.71; H, 4.26. Found: C, 50.77; H, 3.99.

5806
K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
4.4.2. 1,2,4-Tris(4-methylphenyl)benzene (2m)3g,4e
4.6.2. Diethyl 5-hexyl-1H-indene-2,2(3H)-dicarboxylate (5an)2e
Orange liquid; Rf¼0.47 (hexane/EtOAc 5:1); 1H NMR (600 MHz,
CDCl3): d 0.87–0.89 (m, 3H), 1.24–1.33 (m, 12H), 1.54–1.60 (m, 2H),
2.54 (t, J¼7.2 Hz, 2H), 3.55 (s, 2H), 3.56 (s, 2H), 4.20 (q, J¼7.2 Hz, 4H),
6.97 (d, J¼7.2 Hz, 1H), 7.01 (s, 1H), 7.08 (d, J¼7.2 Hz, 1H); 13C NMR
(150 MHz, CDCl3): d 14.0, 14.1, 22.6, 29.0, 31.69, 31.72, 35.8, 40.1,
40.4, 60.5, 61.6, 123.8, 124.1, 127.1, 137.1, 140.0, 141.8, 171.8; IR (neat)
2957, 2928, 2856, 1735 cmꢁ1. Anal. Calcd for C21H30O4: C, 72.80; H,
8.73. Found: C, 72.79; H, 8.84.
Colorless solids; Rf¼0.60 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 2.32 (s, 3H), 2.33 (s, 3H), 2.40 (s, 3H), 7.03–7.10
(m, 8H), 7.26 (dd, J¼7.8, 0.6 Hz, 2H), 7.46 (dd, J¼7.8, 0.6 Hz, 1H),
7.56–7.62 (m, 4H); 13C NMR (150 MHz, CDCl3): d 21.11, 21.13, 125.7,
126.9, 128.6, 128.7, 129.2, 129.5, 129.68, 129.71, 131.1, 136.0, 136.1,
137.1, 137.8, 138.3, 138.7, 139.1, 140.0, 140.8; IR (KBr) 3025, 2917,
2863 cmꢁ1. Anal. Calcd for C27H24: C, 93.06; H, 6.94. Found: C,
92.67; H, 7.33.
4.4.3. 1,2,4-Trihexylbenzene (2n)4e
4.6.3. Diethyl 5-ethoxycarbonyl 6-phenyl-1H-indene-2,2(3H)-
dicarboxylate (5aa)
Colorless liquid; Rf¼0.77 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 0.87–0.91 (m, 9H), 1.28–1.39 (m, 18H), 1.54–
1.59 (m, 6H), 2.52–2.58 (m, 6H), 6.92 (dd, J¼7.8, 1.8 Hz, 1H), 6.95 (d,
J¼1.8 Hz, 1H), 7.04 (d, J¼7.8 Hz, 1H).
Colorless solids; Rf¼0.26 (hexane/EtOAc 4:1); 1H NMR
(600 MHz, CDCl3): d 0.96 (t, J¼7.2 Hz, 3H), 1.27 (t, J¼7.2 Hz, 6H), 3.63
(s, 2H), 3.65 (s, 2H), 4.04 (q, J¼7.2 Hz, 2H), 4.22 (q, J¼7.2 Hz, 2H),
7.19 (d, J¼0.6 Hz, 1H), 7.26–7.28 (m, 2H), 7.30–7.37 (m, 2H), 7.66 (s,
1H); 13C NMR (150 MHz, CDCl3): d 13.6, 14.0, 40.0, 40.4, 60.4, 60.8,
61.8, 125.5, 126.4, 126.9, 127.9, 128.3, 130.2, 139.2, 141.66, 141.74,
143.7, 168.8, 171.3; IR (KBr) 3059, 3024, 2980, 2935, 2905,
1732 cmꢁ1. Anal. Calcd for C24H26O6: C, 70.23; H, 6.38. Found: C,
70.15; H, 6.44.
4.4.4. 1,2,4-Triethoxycarbonylbenzene (2o)3d
Yellow liquid; Rf¼0.23 (hexane/EtOAc 5:1); 1H NMR (600 MHz,
CDCl3): d 1.38 (t, J¼7.2 Hz, 3H), 1.39 (t, J¼7.2 Hz, 3H), 1.41 (t,
J¼7.2 Hz, 3H), 4.39 (q, J¼7.2 Hz, 4H), 4.41 (q, J¼7.2 Hz, 2H), 7.76 (dd,
J¼8.4, 0.6 Hz, 1H), 8.19 (dd, J¼8.4, 1.2 Hz,1H), 8.40 (dd, J¼1.2, 0.6 Hz,
1H); 13C NMR (150 MHz, CDCl3): d 14.0, 14.1, 14.2, 61.7, 61.9, 62.0,
128.8,130.1,132.00,132.04,132.7,136.2,165.0,166.6,167.2; IR (neat)
2983, 2938, 1727, 1244 cmꢁ1. Anal. Calcd for C15H18O6: C, 61.22; H,
6.16. Found: C, 61.14; H, 6.60.
4.6.4. Diethyl 5-methyl 6-phenyl-1H-indene-2,2(3H)-dicarb-
oxylate (5ac)
Yellow liquid; Rf¼0.40 (hexane/EtOAc 5:1); 1H NMR (600 MHz,
CDCl3): d 1.27 (t, J¼7.2 Hz, 6H), 2.21 (s, 3H), 3.59 (s, 2H), 3.60 (s, 2H),
4.22 (q, J¼7.2 Hz, 4H), 7.05 (s, 1H), 7.10 (s, 1H), 7.28–7.33 (m, 3H),
7.37–7.40 (m, 2H); 13C NMR (150 MHz, CDCl3): d 14.0, 20.4, 40.2,
40.3, 60.5, 61.7, 125.5, 126.6, 128.0, 129.2, 134.1, 137.5, 139.1, 140.8,
142.1,171.7; IR (neat) 3057, 2980, 2935, 1733,1244 cmꢁ1. Anal. Calcd
for C22H24O4: C, 74.98; H, 6.86. Found: C, 74.93; H, 6.99.
4.4.5. 1,3,5-Triethoxycarbonylbenzene (3o)16
Colorless solids; Rf¼0.23 (hexane/EtOAc 5:1); 1H NMR
(600 MHz, CDCl3): d 1.43 (t, J¼7.2 Hz, 9H), 4.44 (q, J¼7.2 Hz, 6H),
8.85 (s, 3H); 13C NMR (150 MHz, CDCl3): d 14.3, 61.7, 131.4, 134.4,
165.1; IR (KBr) 2943, 2907, 2877, 1724, 1240 cmꢁ1. Anal. Calcd for
C
15H18O6: C, 61.22; H, 6.16. Found: C, 61.46; H, 6.28.
4.6.5. Diethyl 5,6-diphenyl-1H-indene-2,2(3H)-dicarboxylate (5af)
Colorless solids; Rf¼0.39 (hexane/EtOAc 4:1); 1H NMR
(600 MHz, CDCl3): d 1.281 (t, J¼7.2 Hz, 3H), 1.282 (t, J¼7.2 Hz, 3H),
3.68 (s, 4H), 4.240 (q, J¼7.2 Hz, 2H), 4.241 (q, J¼7.2 Hz, 2H), 7.09–
7.11 (m, 4H), 7.15–7.20 (m, 6H), 7.25 (d, J¼0.6 Hz, 2H); 13C NMR
(150 MHz, CDCl3): d 14.0, 40.3, 60.5, 61.8, 126.3, 127.8, 129.9, 139.4,
4.5. Synthesis of RhCl3$3H2O/i-Pr2NEt complex
To a solution of RhCl3$3H2O (26 mg, 0.1 mmol) in i-PrOH (6 mL)
was added i-Pr2NEt (51 mL, 0.3 mmol). The mixture was stirred at
room temperature (or reflux) for 0.5 h and was concentrated under
reduced pressure. The residue was purified by gel permeation
chromatography. Then the solid was purified by recyclization, and
colorless crystals were obtained.
139.6, 141.6, 171.7; IR (KBr) 3057, 2985, 2903, 1732, 1708 cmꢁ1
.
4.7. General procedure for cyclization of diyne 4b and
alkyne 1f
4.6. General procedure for cyclization of diyne 4a and
alkyne 1
To a solution of RhCl3$3H2O (11 mg, 0.04 mmol) and i-Pr2NEt
(26 mL, 0.15 mmol) in i-PrOH (2.0 mL) were added diphenylacetyl-
ene 1f (900 mg, 5.0 mmol) and diyne 4b (132 mg, 0.50 mmol) in i-
PrOH (3.0 mL). The mixture was stirred at reflux for 24 h. After
being cooled to room temperature, the reaction mixture was con-
centrated under reduced pressure. The residue was purified by
column chromatography on silica gel (hexane/EtOAc 5:1) to afford
diethyl 4,7-dimethyl-5,6-diphenyl-1H-indene-2,2(3H)-dicarbox-
ylate 5bf (102 mg, 46%) and 45% of 4b was recovered.
To a solution of RhCl3$3H2O (11 mg, 0.04 mmol) and i-Pr2NEt
(26 mL, 0.15 mmol) in i-PrOH (2.0 mL) were added phenylacetylene
1l (217 mg, 2.0 mmol) and diyne 4a (116 mg, 0.49 mmol) in i-PrOH
(3.0 mL). The mixture was stirred at reflux for 2 h. After being
cooled to room temperature, the reaction mixture was concen-
trated under reduced pressure. The residue was purified by column
chromatography on silica gel (hexane/EtOAc 5:1) to afford diethyl
5-phenyl-1H-indene-2,2(3H)-dicarboxylate 5al (138 mg, 81%) as
yellow liquid.
4.7.1. Diethyl 4,7-dimethyl-5,6-diphenyl-1H-indene-2,2(3H)-
dicarboxylate (5bf)
4.6.1. Diethyl 5-phenyl-1H-indene-2,2(3H)-dicarboxylate (5al)6e
Yellow liquid; Rf¼0.37 (hexane/EtOAc 5:1); 1H NMR (600 MHz,
CDCl3): d 1.25–1.28 (m, 6H), 3.63 (s, 2H), 3.66 (s, 2H), 4.26 (q,
J¼7.2 Hz, 4H), 7.26–7.27 (m, 1H), 7.32–7.34 (m, 1H), 7.39–7.43 (m,
4H), 7.55–7.56 (m, 2H); 13C NMR (150 MHz, CDCl3): d 14.0, 40.2,
40.4, 60.5, 61.7, 123.0, 124.4, 126.1, 127.0, 127.1, 128.6, 139.1, 140.3,
140.7, 141.3, 171.6; IR (neat) 3031, 2980, 2936, 1733 cmꢁ1. Anal.
Calcd for C21H22O4: C, 74.54; H, 6.56. Found: C, 74.53; H, 6.74.
In a similar manner, the Rh/amine-catalyzed cyclotrimerization
of diyne 4a and alkynes 1a, 1c, 1f, and 1n was carried out. The re-
action conditions and the results are illustrated in Table 6.
Red liquid; Rf¼0.50 (hexane/EtOAc 5:1); 1H NMR (600 MHz,
CDCl3): d 1.32 (t, J¼7.2 Hz, 6H), 2.00 (s, 6H), 3.69 (s, 4H), 4.28 (q,
J¼7.2 Hz, 4H), 6.92 (d, J¼7.2 Hz, 4H), 7.04–7.06 (m, 2H), 7.10–7.12
(m, 4H); 13C NMR (150 MHz, CDCl3): d 13.7, 19.2, 30.7, 64.4, 118.2,
128.0, 128.8, 130.2, 134.4, 144.5, 167.1; IR (neat) 3056, 3021, 2981,
2935, 1733, 1242 cmꢁ1
.
Acknowledgements
We thank the SC-NMR Laboratory of Okayama University for 1H
and 13C NMR analyses.

K. Yoshida et al. / Tetrahedron 64 (2008) 5800–5807
5807
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Supplementary data
Supplementary data and representative spectra associated with
this article can be found in the online version. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2008.03.079.
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