Efficient activation of 2-iminomethylpyridine/cobalt-based alkyne [2+2+2] cycloaddition catalyst by addition of a silver salt

Article abstract of DOI:10.1002/adsc.200700188

The addition of silver triflate (AgOTf) or silver hexafluoroantimonate (AgSbF₆) significantly increased the activity of the 2-(arylimino)methylpyridine/cobalt(II) chloride hexahydrate (CoCl ₂·6O H₂O)/zinc catalyst in alkyne cyclotrimerizations thereby accelerating the reaction and enabling the use of unactivated, simple internal alkynes as the monoyne substrate : The rate of reaction was found to be highly dependent on the nature of the counter anion (X^-) and the ligand (L) in the postulated cationic cobalt(I) complex [LCo(I)]⁺X^-.

Full text of DOI:10.1002/adsc.200700188

UPDATES
DOI: 10.1002/adsc.200700188
Efficient Activation of 2-Iminomethylpyridine/Cobalt-Based
Alkyne [2+2+2]Cycloaddition Catalyst by Addition of a Silver
Salt
Avijit Goswami,a Taichi Ito,a and Sentaro Okamotoa,*
a
Department of Material & Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama
221-8686, Japan
Fax : (+81)-45-413-9770; e-mail: okamos10@kanagawa-u.ac.jp
Received: April 17, 2007
Abstract: The addition of silver triflate (AgOTf) or
silver hexafluoroantimonate (AgSbF6) significantly
increased the activity of the 2-(arylimino)methyl-
could be generated on demand from the stable, inex-
pensive cobalt salt and easily available ligand 2-(2,6-
diisopropylphenyl)iminomethylpyridine (dipimp) or
1,2-bis(diphenylphosphino)ethane (dppe) by in situ
pyridine/cobalt(II)
chloride
hexahydrate
(CoCl2·6H2O)/zinc catalyst in alkyne cyclotrimeri-
zations thereby accelerating the reaction and en-
abling the use of unactivated, simple internal alkynes
as the monoyne substrate: The rate of reaction was
found to be highly dependent on the nature of the
counter anion (XÀ) and the ligand (L) in the postu-
lated cationic cobalt(I) complex [LCo(I)]+XÀ.
reduction
with
commercial
zinc
powder
(Scheme 1).[6a]
Keywords: catalytic cycloaddition; cobalt; iminome-
thylpyridine; silver triflate; substituted benzenes
Introduction
Research in developing the catalytic [2+2+2]cyclo-
addition of unsaturated compounds, such as alkyne
cyclotrimerization and alkyne/nitrile cycloaddition,[1]
has demonstrated the importance of cationic metal
species as a catalyst. For example, Tanaka and co-
workers have reported cationic Rh(I)/diphosphine
Scheme 1. Ligand/CoCl2·6H2O/Zn-catalyzed reaction of al-
kynes to benzene derivatives.
The catalysis cycloadds a variety of alkynes intra-
catalysts for [2+2+2]cycloaddition of alkynes, al- and intermolecularly to the corresponding substituted
kynes/nitriles and alkynes/isocycnates under mild re- benzenes; however, the production of sterically de-
action conditions, whereas, use of neutral Rh(I) com- manding benzene derivatives sometimes requires a
plexes did not exhibit any catalytic activity.[2] Kirchner long reaction time and unactivated simple internal al-
et al. documented cationic Ru complexes for [2+2+ kynes such as 4-octyne cannot be utilized as the sub-
2] and [2+2+1]cycloaddition reactions of alkynes.[3] strate 2. Inspired by the results described above, we
Hilt et al. reported the diphosphine, 1,2-diimine or assumed that by addition of a suitable additive, an
1,2-disulfide/CoX2/Zn-catalyzed intermolecular cyclo- electron-deficient cationic Co(I) species could be gen-
addition of alkynes where cationic Co species gener- erated, which may be more active and could over-
ated by the addition of ZnI2 have been proposed as come the aforementioned drawbacks to make the
an active catalyst.[4] Furthermore, there are many ex- method more general. As a result, we found that a
amples of cationic species as catalysts for [2+2] and certain silver salt exhibited a unique additive effect
[4+2]cycloaddition reactions.[5]
specific to the dipimp-Co system.
We have recently developed a highly practical and
user-friendly catalyst for alkyne cycloaddition, which
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2368 – 2374

Activation of 2-Iminomethylpyridine/Cobalt-Based Alkyne [2+2+2]Cycloaddition Catalyst
UPDATES
Results and Discussion
without an additive required 4 h (entry 1). Similar re-
sults were observed in the reactions with use of anhy-
First, the effect of an additive on the reaction of drous CoCl2 instead of CoCl2·6H2O (entries 2 and 5).
diynes 1a and 1b with alkynes 2a and 2b was investi- Addition of AgOTf (4 mol%) to a reduced amount
gated and the results are summarized in Table 1, of the catalyst (dipimp/CoCl2·6H2O/Zn=2/2/10
where the time for consumption of 1 was confirmed mol%) was also effective (entry 6). Other silver salts
by TLCanalysis of the reaction mixture.
such as AgBF4 and AgPF6 were not effective and, in
As revealed from entries 1–9, addition of AgOTf or fact, slowed down the reaction rate (entries 8 and 9).
[4]
AgSbF6 significantly increased the activity of the cata- Addition of ZnI2
to a dipimip/CoCl2·6H2O/Zn
lyst: The reaction of 1a and phenylacetylene (2a) by system resulted in no effect (entry 3).
dipimp/CoCl2·6H2O/Zn with AgOTf or AgSbF6 pro-
In general, the reaction of a diyne consisting of ter-
ceeded smoothly at room temperature and was com- minal alkynes with an unactivated aliphatic internal
plete within 0.5 h to give substituted benzene 3aa alkyne is difficult because self-dimerization and/or
quantitatively (entries 4 and 7), while the reaction -trimerization of the diyne proceeds predominantly.
The cyclotrimerization of terminally unsubstituted
diyne and 4 equivs. of 3-hexyne with an Ru catalyst
Table 1. Effect of an additive on the reaction of diyne 1a
gave only 13% of the desired product.[7] Very recent-
and alkyne 2.[a]
ly, Takeuchi and co-workers recommended a slow ad-
dition technique for such reactions to minimize the
self-addition of the diyne: thus, they employed an [Ir-
(cod)Cl]2/dppe catalyst for the cyclotrimerization
using the procedure of slow addition (7 h) of diyne to
the mixture of monoyne (3 equivs.) and catalyst to
provide the corresponding benzene derivative in good
yield.[8] In our catalytic system, slow addition of 1a
(3 h) to the reaction mixture with 2b (2 equivs.) in the
absence of AgOTf led only to self-dimerization and
-trimerization of 1a (entry 12) while, in striking con-
trast, under the same reaction conditions, addition of
AgOTf enabled the production of 3ab in 82% yield
(entry 13).
Meanwhile, the reaction of 1b consisting of internal
alkynes with an unactivated internal alkyne 2b in the
presence of the dipimp/CoCl2·6H2O/AgOTf/Zn re-
agent the catalyzed cycloaddition proceeded smoothly
to give 3bb in 72% isolated yield under the standard
reaction conditions, while the reaction without
AgOTf did not yield the corresponding product at all
after 96 h (entries 14 and 15). It is noteworthy that
the effect of AgOTf as an additive was specific to the
dipimp/CoCl2·6H2O/Zn catalyst. Although the reac-
tion with the use of dppe as a ligand instead of
dipimp gave 3aa, in the absence or presence of
AgOTf, the reaction rate was not affected by inclu-
sion of the additive (entries 10 and 11); in addition,
the reaction with dppe did not yield 3bb to any appre-
Entry 1
2
Ligand Additive Time Yield[b]
(equivs.)
1
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
dipimp -
dipimp -
dipimp ZnI2
4 h
4 h
4 h
98%
96%
87%
2[c]
3
4
dipimp AgOTf 0.5 h 97%
(92%)[d]
dipimp AgOTf 1 h 95%
dipimp AgOTf 1.5 h 94%
dipimp AgSbF6 0.5 h 94%
5[c]
6[e]
7
8
9
10
11
12[f]
13[f]
14
15
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
1a 2a (1.3)
1a 2b (2)
dipimp AgBF4
dipimp AgPF6
12 h 96%
8 h 98%
24 h 89%
dppe
dppe
-
AgOTf 24 h 91%
dipimp -
dipimp AgOTf 3 h
dipimp -
dipimp AgOTf 3 h
3 h
Trace[g]
82%
1a 2b (2)
1b 2b (2)
1b 2b (2)
96 h Trace[h]
95%
(72%)[d]
16
17
1b 2b (2)
1b 2b (2)
dppe
dppe
-
96 h Trace[h]
AgOTf 96 h Trace[h]
[a]
Reaction conditions: 1 (0.5 mmol), 2 (0.65 or 1.0 mmol),
dipimp (0.03 mmol), CoCl2·6H2O (0.025 mmol), additive
(0 or 10 mol%), Zn powder (0.05 mmol), THF (2.0 mL). ciable extent (entries 16 and 17).
[b]
1
Unless otherwise indicated, H NMR yield confirmed by
using an internal standard.
Anhydrous CoCl2 was used instead of CoCl2·6H2O.
Isolated yield.
Dipimp (2 mol%), CoCl2·6H2O (2 mol%) and AgOTf
(4 mol%) were used.
A THF solution of 1a was added dropwise over 3 h to a
mixture of 2b, dipimp, CoCl2·6H2O, AgOTf and Zn in
THF.
Similarly, an addition of AgOTf to a dppe/
CoCl2·6H2O/Zn reagent system, which has been
proved to be an efficient catalyst for the cycloaddition
of diynes and nitriles to the corresponding substituted
pyridines,[6b] did not have any advantageous effect on
the pyridine formation.
Table 2 summarizes the results of the reaction of
other diynes (1.0 equiv.) and alkynes (1.0 equiv.) cata-
lyzed by dipimp/CoCl2·6H2O/Zn in the presence or
absence of AgTOf. The data clearly reveal an acceler-
[c]
[d]
[e]
[f]
[g]
[h]
A dimer and a trimer of 1a were formed.
Substrates were recovered quantitatively.
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Avijit Goswami et al.
UPDATES
Table 2. Examples for effect of AgOTf as an additive for synthesis of hexa-substituted benzenes.[a]
Entry
R
R3
R4
AgOTf[b]
Time
Yield[c]
1
2
3
4
5
6
7
8
3bc
3bc
3bd
3bd
3ce
3ce
3df
3df
n-Bu
n-Bu
n-Bu
n-Bu
SiMe3
SiMe3
Ph
n-Bu
n-Bu
Et
CꢀC-n-Bu
CꢀC-n-Bu
À
+
À
+
À
+
À
+
96 h
2 h
48 h
3 h
96 h
2.5 h
48 h
2.5 h
Trace
62%
76%
82%
48%
91%
48%
94%
(CH2)2OH
Et
(CH2)2OH
n-Bu
n-Bu
n-Bu
n-Bu
CH2OH
CH2OH
CH2OAc
CH2OAc
Ph
[a]
E=CO2Et. Reaction conditions (equivs.): diyne 1 (1.0), alkyne 2 (1.0), dipimp (0.06), CoCl2·6H2O (0.05), Zn (0.10).
[b]
[c]
With 10 mol% of AgOTf (+) or without AgOTf (À).
Isolated yield.
ating and/or activating effect of the additive again. much faster than that without AgOTf. In contrast, a
The reactions which required several days (entries 3, dppe/CoCl2·6H2O/Zn reagent could not provide 6
5 and 7) or did not proceed (entry 1) with the dipimp/ even with AgOTf but afforded mono-cyclized com-
CoCl2·6H2O/Zn reagent were accomplished in a few pound 7 in good yields. The complementary reactivity
hours, when they were performed with AgOTf, to of dipimp and dppe ligands in the reaction of 5 and
provide the corresponding fully substituted benzene 2c might be synthetically useful. The known catalysts
(PPh3)3 and X2Ni
(dppe)/Zn[9] were uti-
N
[9]
in good to excellent yield. Similarly, fully intermolecu- such as ClRh
lar reactions were accelerated with AgOTf (Table 3). lized for the reaction under the appropriate reaction
Interestingly, reactions in the presence of the dipimp/ conditions but product 7 instead of 6 was obtained or
CoCl2·6H2O/Zn reagent and AgOTf produced more the reaction gave a complex mixture. These results
1,3,5-isomer than those without AgOTf.
demonstrate the high reactivity of the dipimp/
The catalyst activation by the addition of AgOTf CoCl2·6H2O/AgOTf/Zn catalyst.
can also be applied to the tandem cycloaddition reac-
The specificity of the additive effect to the dipimp
tions of tetrayne and monoyne as illustrated in ligand can be explained as follows: it can be assumed
Table 4. The reaction of tetrayne 5 and alkyne 2c that the Co(I) complex such as dipimp-Co(I)Cl (A),[6]
(6 equivs.) catalyzed by the dipimp/CoCl2·6H2O/Zn derived from the reaction of dipimp with CoCl2 and
reagent proceeded in a tandem fashion and gave followed by reduction with Zn, may be converted to
biaryl 6 in excellent yields, where it was observed the corresponding cationic complex of the type B by
again that the reaction in the presence of AgOTf was the reaction with AgX. The positive charge present in
the complex B can be delocalized to the pyridine
moiety of the ligand such as in the structure C
Table 3. Fully intermolecular reactions of 1-alkynes.
(Scheme 2). The specific additive effect to the dipimp
system can be addressed by the contribution of such a
resonance stabilization, while such a stabilization is
not possible in the case of the dppe-Co complex (E).
The electron-deficient nature of the cationic complex
B (or C) with a weaker s-donative dipimp ligand than
dppe in complex E may facilitate the reaction with
unactivated monoalkynes. Such an explanation may
be of interest in the research field of alkene oligome-
rization, polymerization and other synthetic reactions
based on 2-iminomethylpyridine-metal complexes as
a catalyst.[10]
R
AgOTf[a]
Time
1,2,4:1,3,5
Total Yield
n-Bu
n-Bu
Ph
À
+
À
+
15 h
0.5 h
2 h
63:37
23:77
>99:1
90:10
70%
83%
91%
94%
Ph
<0.5 h
Although there are many examples where a reason-
able explanation has been given of counter ion effects
on cationic metal complexes and their resulting effect
[a]
(À): in the absence of AgOTf, (+): in the presenece of
AgOTf (10 mol%).
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Adv. Synth. Catal. 2007, 349, 2368 – 2374

Activation of 2-Iminomethylpyridine/Cobalt-Based Alkyne [2+2+2]Cycloaddition Catalyst
UPDATES
Table 4. Tandem reaction with various catalyst systems.
Conclusions
We have found a unique additive effect of silver salts
in a ligand/CoCl2·6H2O/Zn catalyst system for the
[2+2+2]cycloaddition reaction of alkynes. The effect
was specific to reactions with the 2-iminomethylpyri-
dine ligand but no effect was observed for the phos-
hine-based system. The catalysis thus developed intro-
duces a practical and quick route to highly subsituted
benzenes from various alkynes. Further investigations
of the mechanism as well as work extending this ap-
plication to other iminopyridine-based metal com-
plexes are underway.
Catalyst
Time Product(s): Yield
dipimp/CoCl2·6H2O/Zn[a]
3 days 6: 93%[b]
dipimp/CoCl2·6H2O/Zn/AgOTf[c] 1.5 h
6: 91%[b]
dppe/CoCl2·6H2O/Zn[d]
3 days 7: 72%[e]
3 days 7: 69%[e]
3 days 7: 87%[e]
2 days 7: 42%[e]
dppe/CoCl2·6H2O/Zn/AgOTf[f]
Experimental Section
[g]
RhCl
A
RhCl(PPh3)3
General Remarks
+ complex mix.
4 days complex mix.
Br2Ni
(dppe)/Zn[i]
R
NMR spectra were recorded in CDCl3 at 600, 500 and
1
270 MHz for H and 150, 125 and 67.5 MHz for 13C, respec-
[a]
dipimp (0.06)/CoCl2·6H2O (0.05)/Zn (0.10), THF, room
temperature.
tively, on JEOL JNM-ECA600, 500 and -EX270 spectrome-
ters. Chemical shifts are reported in parts per million (ppm,
d) relative to Me4Si (d=0.00), residual CHCl3 (d=7.26 for
1H NMR), or CDCl3 (d=77.0 for 13CNMR). IR spectra
were recorded on an FT-IR spectrometer (Shimadzu, IR
Prestige-21). All reactions sensitive to oxygen and/or mois-
ture were performed under an argon atmosphere. Dry sol-
vent [tetrahydrofuran (THF)] was purchased from Kanto
Chemicals. Other chemicals which are commercially avail-
able, unless otherwise indicated, were used as received.
Starting materials 1, 2 and 6 were prepared by conventional
reaction procedures. 2-(2,6-Diisopropylphenyl)iminomethyl-
pyridine (dipimp) was prepared according to the reported
procedure with a minor modification.[10c] A mixture of 2-pyr-
idinecarboxaldehyde (30.0 mmol), 2,6-diisopropylaniline
(30.0 mmol) and anhydrous MgSO4 (ca.1–2 g) in dry THF
(40 mL) was stirred overnight at room temperature, and
then filtered through a pad of Celite. The filtrate was con-
centrated by rotary evaporation and dried under vacuum for
10 h. The resulting yellow crystalline material, which was an-
[b]
[c]
1H NMR yields.
dipimp (0.06)/CoCl2·6H2O (0.05)/AgOTf (0.10)/Zn
(0.010), THF, room temperature.
dppe (0.06)/CoCl2·6H2O (0.05)/Zn (0.10), THF, room
temperature.
Isolated yield.
dppe (0.06)/CoCl2·6H2O
[d]
[e]
[f]
(0.05)/AgOTf (0.10)/Zn (0.10),
THF, room temperatute.
RhCl
RhCl
[g]
[h]
[i]
ACHTREUNG
ACHTREUNG
Br2Ni
ACHTREUNG
1
alyzed by H NMR to confirm the formation of dipimp and
complete consumption of the starting materials, was utilized
for the Co-catalyzed reactions directly without further pu-
rification.
The crystalline ligand was stored in a sealed bottle in the
refrigerator. In addition, a catalyst precursor solution of
CoCl2·6H2O and dipimp in THF was prepared and used for
the reaction since the solution could be stored in a Schlenk
tube under argon for months.
Scheme 2. Postulated intermediate.
Procedure for the Intermolecular Cyclotrimerization
of Diynes 1 and Monoynes 2 to Annulated Benzene
Derivatives Catalyzed by a 2-(2,6-Diisopropylphen-
yl)iminomethylpyridine (dipimp)/CoCl2·6H2O/Zn
Reagent in the Presence of an Additive (Tables 1
and 2)
on reaction efficiency and selectivity,[11] the reason
why silver salts other than AgOTf and AgSbF6 were
less effective in the present catalysis is unclear at this
stage.
To a stirred mixture of zinc powder (3.5 mg, 0.05 mmol),
diyne 1 (0.5 mmol), monoyne 2 (1–2.0 equivs.) and an addi-
tive (ZnI2 or Ag salt; 10 mol%) in THF (0.5 mL) was added
Adv. Synth. Catal. 2007, 349, 2368 – 2374
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Avijit Goswami et al.
UPDATES
a solution of CoCl2·6H2O (6 mg, 0.025 mmol) and dipimp
(8 mg, 0.03 mmol) in THF (1.5 mL) at room temperature.
The reaction progress was checked by TLCanalysis. After
completion of the reaction, a small portion of Et2O was
added and the mixture was passed through a pad of Celite
with ether. The filtrate was concentrated to dryness and the
residue was chromatographed on silica gel using hexane/
Et2O (2/1) to give the corresponding annulated benzene 3.
The above-mentioned procedure was also performed with-
out an additive.
Diethyl 5-phenyl-1H-indene-2,2(3H)-dicarboxylate (3aa):
1H NMR (CDCl3, 500 MHz): d=7.55 (d, 2H, J=7.2 Hz,
Ar), 7.43–7.35 (m, 4H, Ar), 7.32 (t, 1H, J=7.2 Hz, Ar), 7.25
(d, 1H, J=7.2 Hz, Ar), 4.22 (q, 4H, J=7.2 Hz, OCH2CH3),
3.65 (s, 2H, ArCH2C), 3.63 (s, 2H, ArCH2C), 1.26 (t, 6H,
J=7.2 Hz, OCH2CH3); 13C NMR (CDCl3, 150 MHz): d=
171.6, 141.3, 140.7, 140.3, 139.1, 128.6, 127.1, 127.0, 126.1,
124.4, 123.0, 61.70, 60.53, 40.43, 40.27, 14.11. Spectroscopic
data were identical with those reported.[6]
Diethyl 4,7-dibutyl-5,6-dipropyl-1H-indene-2,2(3H)-dicar-
boxylate (3bb): 1H NMR (CDCl3, 500 MHz): d=4.20 (q,
4H, J=7.2 Hz, OCH2CH3), 3.52 (s, 4H, ArCH2C), 2.51–2.47
(m, 8H, ArCH2), 1.47–1.42 (m, 12H, methylene), 1.25 (t,
6H, J=7.2 Hz, OCH2CH3), 1.03 (t, 6H, J=7.4 Hz,
CH2CH2CH3), 0.96 (t, 6H, J=6.8 Hz, CH2 CH2CH2CH3);
13C NMR (CDCl3, 67.5 MHz): d=171.7, 137.4, 136.0, 134.0,
61.48, 59.70, 39.59, 32.59, 31.61, 30.36, 25.12, 23.36, 15.03,
14.03, 13.93; IR (neat): n=2960, 2931, 2872, 1747, 1255,
1097, 1066, 800 cmÀ1; anal. calcd. for C29H46O4 (458.67): C
75.94, H 10.11; found: C76.05, H 10.09.
500 MHz): d=7.45–7.35 (m, 6H, Ph), 7.27–7.25 (m, 4H, Ph),
4.91 (s, 2H, CH2OAc), 4.11 (q, 4H, J=7.6 Hz, OCH2CH3),
3.31 (s, 2H, ArCH2C), 3.27 (s, 2H, ArCH2C), 2.46 (t, 2H,
J=8.1 Hz, ArCH2CH2), 1.98 (s, 3H, OCOCH3), 1.32–1.29
(m, 2H, ArCH2CH2), 1.16 (t, 6H, J=7.6 Hz, OCH2CH3),
1.12–1.08 (m, 2H, ArCH2CH2CH2), 0.66 (t, 3H, J=7.8 Hz,
CH2CH2CH3); 13C NMR (CDCl3, 150 MHz): d=171.5,
170.6, 140.4, 139.89, 139.87, 139.82, 139.1, 138.2, 136.5, 129.9,
128.9, 128.38, 128.31, 127.3, 127.0, 61.99, 61.59, 59.66, 40.86,
40.55, 33.87, 29.70, 22.94, 20.94, 13.96, 13.51 (one carbon was
not differentiated); IR (neat): n=2978, 2958, 2931, 1741,
1730, 1442, 1236, 912 cmÀ1
; anal. calcd. for C34H38O6
(542.66): C75.25, H 7.06; found: C75.31, H 6.87.
Diethyl 5-butyl-6-(hydroxymethyl)-4,7-bis(trimethylsilyl)-
1H-indene-2,2(3H)-dicarboxylate (3ce): 1H NMR (CDCl3,
600 MHz): d=4.72 (d, 2H, J=4.6 Hz, ArCH2OH), 4.19 (q,
4H, J=7.0 Hz, OCH2CH3), 3.58 (s, 2H, ArCH2C), 3.57 (s,
2H, ArCH2C), 2.84 (t, 2H, J=8.0 Hz, ArCH2CH2), 1.45–
1.41 (m, 4H, methylene), 1.24 (t, 6H, J=7.0 Hz,
OCH2CH3), 0.94 (t, 3H, J=7.6 Hz, CH2CH2CH2CH3), 0.43
(s, 9H, SiMe3), 0.41 (s, 9H, SiMe3); 13C NMR (CDCl3,
150 MHz): d=171.6, 146.9, 145.8, 143.5, 142.1, 137.7, 136.3,
61.72, 61.67, 60.54, 42.03, 41.88, 36.69, 32.57, 23.15, 14.20,
14.05, 2.97, 2.74; IR (neat): n=3531, 2980, 2931, 2902, 1732,
1251, 1070, 1049, 852 cmÀ1; anal. calcd. for C26H44O5Si2
(492.80): C63.37, H 9.00; found: C63.07, H 8.67.
Procedure with the Slow Addition of Diyne (Table 1,
enrty 13)
To a stirred mixture of zinc powder (3.5 mg, 0.05 mmol), 4-
octyne (1 mmol) and AgOTf (0.05 mmol) was added a solu-
tion of CoCl2·6H2O (6 mg, 0.025 mmol) and dipimp (8 mg,
0.03 mmol) in THF (0.5 mL). A THF solution (1.5 mL) of
1a (118 mg, 0.5 mmol) was added dropwise to the reaction
mixture over 3 h by a syring pump with stirring at room
temperature. After complete addition of diyne 1a, a small
portion of Et2O was added and the mixture was passed
through a pad of Celite with ether. The filtrate was concen-
trated to dryness and the residue was chromatographed on
silica gel using hexane/Et2O (2/1) to give 3ab as a pale
yellow liquid.
Diethyl 4,5,7-tributyl-6-(hex-1-ynyl)-1H-indene-2,2(3H)-
dicarboxylate (3bc): 1H NMR (CDCl3, 500 MHz): d=4.20
(q, 4H, J=7.1 Hz, OCH2CH3), 3.52 (s, 2H, ArCH2C), 3.51
(s, 2H, ArCH2C), 2.74 (t, 2H, J=8.0 Hz, ArCH2), 2.68 (t,
2H, J=8.0 Hz, ArCH2), 2.50 (t, 2H, J=7.9 Hz, ArCH2),
2.46 (t, 2H, J=7.1 Hz, CꢀCCH2), 1.60–1.38 (m, 16H, meth-
ylene), 1.25 (t, 6H, J=7.1 Hz, OCH2CH3), 0.96–0.93 (m,
12H, CH2CH2CH2CH3); 13C NMR (CDCl3, 67.5 MHz): d=
171.5, 141.7, 137.96, 137.91, 135.3, 133.4, 122.1, 95.90, 78.41,
61.55, 59.82, 39.68, 39.26, 33.03, 32.52, 32.07, 31.78, 31.08,
30.08, 23.34, 23.18, 23.07, 21.97, 19.32, 14.02, 13.93, 13.60
(three carbons were not differentiated); IR (neat): n=2956,
2929, 2872, 2858, 1742, 1463, 1246, 1188, 1159, 1068, 1014,
862 cmÀ1; anal. calcd. for C33H50O4 (510.75): C77.60, H 9.87;
found: C77.61, H 9.98.
Diethyl
5,6-dipropyl-1H-indene-2,2(3H)-dicarboxylate
A
(3ab): 1H NMR (CDCl3, 500 MHz): d=6.97 (bs, 2H, Ar),
4.19 (q, 4H, J=7.5 Hz, OCH2CH3), 3.54 (s, 4H, ArCH2C),
2.53 (t, 4H, J=8.0 Hz, ArCH2CH2), 1.57–1.55 (m, 4H,
CH2CH2CH3), 1.25 (t, 6H, J=7.5 Hz, OCH2CH3), 0.98 (t,
6H, J=7.8 Hz, CH2CH2CH3); 13C NMR (CDCl3, 67.5 MHz):
d=171.6, 138.9, 137.2, 124.5, 61.5, 60.4, 40.2, 34.8, 24.5, 14.3,
14.0; IR (neat): n=2984, 2937, 2906, 1737, 1251, 1079, 1045,
843 cmÀ1; anal. calcd. for C21H30O4 (346.46): C72.80, H 8.73;
found: C72.91, H 8.78.
Diethyl 4,7-dibutyl-5-ethyl-6-(2-hydroxyethyl)-1H-indene-
1
2,2(3H)-dicarboxylate (3bd): mp 91–928C; H NMR (CDCl3,
600 MHz): d=4.20 (q, 4H, J=7.1 Hz, OCH2CH3), 3.74 (t,
2H, J=7.4 Hz, ArCH2CH2OH), 3.52 (bs, 4H, ArCH2C),
2.92 (t, 2H, J=7.4 Hz, ArCH2CH2OH), 2.64 (q, 2H, J=
7.5 Hz, ArCH2CH3), 2.54 (t, 2H, J=7.8 Hz, ArCH2), 2.51 (t,
2H, J=8.0 Hz, ArCH2), 1.46–1.42 (m, 8H, methylene), 1.26
(t, 6H, J=7.1 Hz, OCH2CH3), 1.13 (t, 3H, J=7.5 Hz,
CH2CH3), 0.95 (t, 6H, J=7.6 Hz, CH2CH2CH2CH3);
13CNMR (CDCl 3, 150 MHz): d=171.9, 139.8, 137.3, 136.5,
135.3, 134.4, 131.9, 63.64, 61.66, 59.75, 39.66, 39.64, 32.71,
32.66, 32.21, 30.54, 30.32, 23.38, 23.36, 22.08, 15.94, 14.05,
14.01, 13.97; IR (KBr): n=3433, 2956, 2931, 2870, 1737,
Procedure for the Intermolecular Cyclotrimerization
of 1-Alkynes to Tri-Substituted Benzenes Catalyzed
by a 2-(2,6-Diisopropylphenyl)iminomethylpyridine
(dipimp)/CoCl2.6H2O/Zn Reagent in the Presence of
AgOTf as an Additive (Table 3)
1462, 1249, 1047, 862 cmÀ1
; anal. calcd. for C27H42O5
(446.62): C72.61, H 9.48; found: C72.67, H 9.27.
To a stirred mixture of zinc powder (3.5 mg, 0.05 mmol), 1-
alkyne 2 (0.5 mmol) and AgOTf (12.8 mg, 0.05 mmol) in
THF (0.5 mL) was added a solution of CoCl2·6H2O (6 mg,
Diethyl 5-butyl-6-(ethanoyloxymethyl)-4,7-diphenyl-1H-
indene-2,2(3H)-dicarboxylate (3df): 1H NMR (CDCl3,
2372
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Adv. Synth. Catal. 2007, 349, 2368 – 2374

Activation of 2-Iminomethylpyridine/Cobalt-Based Alkyne [2+2+2]Cycloaddition Catalyst
UPDATES
0.025 mmol) and dipimp (8 mg, 0.03 mmol) in THF (1.5 mL)
at room temperature. The dark brown reaction mixture was
stirred at ambient temperature and the consumption of 2
was checked by TLCanalysis. After completion of the reac-
tion, a small portion of Et2O was added and the mixture
was passed through a pad of Celite with ether. The filtrate
was concentrated under vacuum and the crude material was
purified by column chromatography on silica gel using
hexane/Et2O (4/1) to afford the corresponding benzene de-
rivatives. The above-mentioned procedure was also per-
formed in the absence of an additive.
Tri-n-butylbenzene (4a): Selected peaks for the 1,2,4-
isomer: 1H NMR (CDCl3, 600 MHz): d=7.04 (d, 1H, J=
7.2 Hz, Ar), 6.94 (s, 1H, Ar), 6.93 (d, 1H, Ar); 13CNMR
(CDCl3, 150 MHz): d=140.3, 140.1, 137.6, 129.2, 128.9,
125.6. Identified spectroscopically by comparison with the
literature data.[3,4] Selected peaks for the 1,3,5-isomer:
1H NMR (CDCl3, 500 MHz): d=6.81 (s, 3H, Ar); 13CNMR
(CDCl3, 125 MHz): d=142.7, 125.8, 35.68, 33.78, 22.53,
14.03. Identified spectroscopically by comparison with the
literature data.[4b,12] The regioisomeric ratio was determined
by 1H NMR analysis using signals at d=7.04, 6.94, 6.93,
6.81 ppm.
74.15, 59.85, 58.99; IR (KBr): n=3402, 2926, 2854, 1055,
1012, 904 cmÀ1 (measured using a mixture of 6 and 2-
butyne-1,4-diol).
(7,7’-Diphenyl-1,1’,3,3’-tetrahydro-4,4’-biisobenzofuran-
5,5’,6,6’-tetrayl)tetrakis(methylene) tetraethanoate (tetraace-
tate of 6): mp 85–868C; 1H NMR (CDCl3, 600 MHz): d=
7.45–7.42 (m, 6H, Ph), 7.32–7.29 (m, 4H, Ph), 5.40 (bs, 2H,
ArCH2O), 5.01–4.80 (m, 14H, ArCH2O), 2.00 (s, 6H,
OCOCH3), 1.99 (s, 6H, OCOCH3); 13C NMR (CDCl3,
150 MHz): d=170.3, 170.2, 140.0, 139.1, 138.5, 137.4, 133.3,
133.0, 132.1, 128.69, 128.61, 128.1, 74.22, 74.14, 61.14, 60.88,
20.82, 20.69; IR (KBr): n=2960, 2922, 2852, 1741, 1232,
1026, 962, 908 cmÀ1; anal. calcd. for C40H38O10 (678.72): C
70.78, H 5.64; found C70.89, H 5.69.
{4-Phenyl-7-[3-(3-phenylprop-2-ynyloxy)prop-1-ynyl]-1,3-
dihydroisobenzofuran-5,6-diyl}dimethanol (7): mp 68–698C;
1H NMR (CDCl3, 600 MHz): d=7.47–7.35 (m, 6H, Ph),
7.33–7.30 (m, 3H, Ph), 7.28–7.27 (m, 1H, Ph), 5.20 (s, 2H,
ArCH2O), 5.07 (s, 2H, ArCH2O), 4.90 (s, 2H, ArCH2OH),
4.59 (s, 2H, ArCH2OH), 4.55 (bs, 4H, CꢀCCH2OCH2Cꢀ
C); 13C NMR (CDCl3, 150 MHz): d=141.9, 141.3, 138.6,
137.8, 137.7, 137.4, 131.8, 128.67, 128.62, 128.3, 127.9, 122.3,
115.8, 92.23, 87.15, 83.99, 82.04, 74.57, 74.47, 61.37, 59.75,
57.53, 57.36 (one carbon was not differentiated); IR (KBr):
n=3419, 3055, 2933, 2848, 1072, 1014, 902, 756 cmÀ1; anal.
calcd. for C28H24O4 (424.49): C79.22, H 5.70; found: C
79.02, H 5.85.
Triphenylbenzene (4b): Identification and regioisomeric
ratio of 1,2,4- and 1,3,5-triphenylbezene were carefully de-
termined by comparison of literature data[12] as well as by
1
checking the H NMR spectra of a commercially available
authentic sample (1,3,5-triphenylbenzene) using the signal at
d=7.78 ppm.
Acknowledgements
Procedure for the Cycloaddition Reactions of
Tetrayne 5 and 2-Butyne-1,4-diol to 6 and 7 (Table 4)
This study was partially supported by Scientific Frontier Re-
search Project from the Ministry of Education, Science, Sport
and Culture, Japan. We also thank the Japan Society for the
Promotion of Science (JSPS) for a grant to A.G.
To a stirred mixture of zinc powder (3.5 mg, 0.05 mmol, 10
mol%), tetrayne 5 (169 mg, 0.5 mmol) and 2-butyne-1,4-diol
(258.3 mg, 3 mmol, 6 equivs.) and AgOTf (12.8 mg,
0.05 mmol, 10 mol%) in THF (0.5 mL) was added a solution
of CoCl2·6H2O (5 mol%) and dipimp or dppe (6 mol%) in
THF (1.5 mL) at room temperature. The reaction progress
was checked by TLCanalysis. A small portion of EtOAc
was added and the mixture was passed through a pad of
Celite with EtOAc. The solvent was removed under vacuum
and the residue was chromatographed on silica gel using
hexane/EtOAc (2/1) to afford 6 or 7.
The compound 6 was contained trace amount of starting
diol which it was not possible to separate by column chro-
matography. Therefore, 6 was converted to the correspond-
ing fully acetylated compound by conventional methods
(Ac2O/Et3N/cat. DMAP/CH2Cl2) and characterized by
NMR, IR spectroscopy as well as elemental analysis.
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(7,7’-Diphenyl-1,1’,3,3’-tetrahydro-4,4’-biisobenzofuran-
5,5’,6,6’-tetrayl)tetramethanol
(6):
1H NMR
(CDCl3,
500 MHz): d=7.43–7.36 (m, 8H, Ph), 7.23–7.20 (m, 2H, Ph),
5.40 (bs, 2H, ArCH2O), 5.04 (d, 2H, J=8.2 Hz, ArCH2O),
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Adv. Synth. Catal. 2007, 349, 2368 – 2374