Iridium complex-catalyzed [2+2+2] cycloaddition of α,ω-diynes with monoynes and monoenes

Article abstract of DOI:10.1021/jo051874c

[Ir(cod)Cl]₂/DPPE was found to be a new catalyst for the cycloaddition of α,ω-diynes with monoynes to give polysubstituted benzene derivatives in high yields. Internal monoynes as well as terminal monoynes could be used. The reaction tolerates a broad range of functional groups such as alcohol, amine, alkene, ether, halogen, and nitrile. The reaction of 1,6-octadiyne derivatives with 1-alkynes gives ortho products and meta products. The regioselectivity could be controlled by the choice of ligand. The reaction with DPPE was meta selective, with meta selectivity of up to 82%. The reaction with DPPF was ortho selective, with ortho selectivity of up to 88%. We propose a mechanism to account for this regioseleetive cycloaddition. [Ir(cod)Cl]₂/DPPE also catalyzed the cycloaddition of α,ω-diynes with 2,5-dihydrofuran to give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and n-butyl vinyl ether gave benzene derivatives instead of cyclohexadiene derivatives. We also propose a mechanism to account for this novel aromatization that includes cleavage of the C-O bond.

Full text of DOI:10.1021/jo051874c

Iridium Complex-Catalyzed [2+2+2] Cycloaddition of r,ω-Diynes
with Monoynes and Monoenes
†
‡
†
‡
,†
Satoko Kezuka, Shigeru Tanaka, Toshihito Ohe, Yoshihiko Nakaya, and Ryo Takeuchi*
Department of Chemistry and Biological Science, Aoyama Gakuin UniVersity, 5-10-1 Fuchinobe,
Sagamihara 229-8558, Japan, and Department of Chemistry, Graduate School of Integrated Science,
Yokohama City UniVersity, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan
takeuchi@chem.aoyama.ac.jp
ReceiVed September 7, 2005
2
[Ir(cod)Cl] /DPPE was found to be a new catalyst for the cycloaddition of R,ω-diynes with monoynes to
give polysubstituted benzene derivatives in high yields. Internal monoynes as well as terminal monoynes
could be used. The reaction tolerates a broad range of functional groups such as alcohol, amine, alkene,
ether, halogen, and nitrile. The reaction of 1,6-octadiyne derivatives with 1-alkynes gives ortho products
and meta products. The regioselectivity could be controlled by the choice of ligand. The reaction with
DPPE was meta selective, with meta selectivity of up to 82%. The reaction with DPPF was ortho selective,
with ortho selectivity of up to 88%. We propose a mechanism to account for this regioselective
cycloaddition. [Ir(cod)Cl] /DPPE also catalyzed the cycloaddition of R,ω-diynes with 2,5-dihydrofuran
2
to give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and n-butyl vinyl ether
gave benzene derivatives instead of cyclohexadiene derivatives. We also propose a mechanism to account
for this novel aromatization that includes cleavage of the C-O bond.
Introduction
the reaction is problematic with regard to the control of
selectivity. To partially overcome this limitation, intramolecular
modes of cyclotrimerization of alkynes have been developed:
R,ω-diyne is used as one component and a monoyne is used as
Cycloaddition is one of the most efficient methods for the
synthesis of cyclic compounds from acyclic substrates. Multiple
bond formation in a single operation is possible. Transition metal
catalysts can be used for cycloadditions that would otherwise
be difficult or impossible by conventional organic chemistry.
Since Reppe first reported the nickel complex-catalyzed
cyclotrimerization of alkynes to give a benzene derivative, the
reaction has been extensively studied. Although the cyclotri-
merization of alkynes is one of the most straightforward and
atom economical routes to polysubstituted benzene derivatives,
4
another component. R,ω-Diyne oxidatively adds to a metal
center to give a metallacyclopentadiene. The reaction of the
intermediate with a monoyne gives a benzene derivative. M u¨ ller
first reported the stoichiometric reaction of rhodacyclopenta-
dienes, which were formed by the reaction of RhCl(PPh3)3 with
R,ω-diynes, and with monoynes to give benzene derivatives.5
Later, Vollhardt developed the catalytic cycloaddition of R,ω-
1
2
3
(
3) (a) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901. (b)
†
Aoyama Gakuin University.
Yokohama City University.
1) (a) Montogomery, J. Angew. Chem., Int. Ed. 2004, 43, 3890. (b)
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Abel, E. W., Stone, F. G. A., Wilkinson, W., Eds.; Pergamon: Oxford,
UK, 1995; Vol. 12, p 741. (d) Schore, N. E. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, UK, 1991;
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‡
(
Fr u¨ hauf, H.-W. Chem. ReV. 1997, 97, 523. (c) Lautens, M.; Klute, W.; Tam.
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(
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5
60, 104.
1
0.1021/jo051874c CCC: $33.50 © 2006 American Chemical Society
Published on Web 12/15/2005
J. Org. Chem. 2006, 71, 543-552
543

Kezuka et al.
diynes with monoynes to apply this chemistry to natural product
synthesis. The reaction of R,ω-diyne with monoyne has been
used as a benchmark reaction to evaluate the synthetic potential
of a metallacyclopentadiene. Several transition-metal complexes
such as those of Co, Ni, Rh, Pd, and Ru have been reported
to be catalysts for this reaction. However, new catalysts are still
valuable for expanding the reaction scope and selectivity.
In most cases, metallacycles including metallacyclopenta-
dienes are intermediates for transition metal complex-catalyzed
cycloaddition. The chemistry of metallacycles can be used to
realize various useful cycloadditions. Collman et al. first
prepared an iridacyclopentadiene by the reaction of IrCl(N2)-
(PPh3)2 with dimethyl acetylenecarboxylate.11 They found that
a tetracarbomethoxyiridacyclopentadiene was a potential catalyst
for the cyclotrimerization of dimethyl acetylenedicarboxylate.
For example, the reaction of dimethyl acetylenedicarboxylate
in the presence of a catalytic amount of a tetracarbomethoxy-
iridacyclopentadiene under refluxing toluene for 16 h gave
hexacarbomethoxybenzene in 80% yield. However, cyclotrim-
erization was limited to dimethyl acetylenedicarboxylate. Al-
though the structure and reactivity of iridacyclopentadienes have
6
7
8
9
10
1
2
been studied since their discovery, catalytic organic synthesis
via iridacyclopentadienes has been less developed than that via
rhodacyclopentadienes or cobaltacyclopentadienes. In the course
of our study on iridium complex-catalyzed carbon-carbon bond
(
5) M u¨ ller, E. Synthesis, 1974, 761.
1
3
formation, we found that [Ir(cod)Cl]2/DPPE is an efficient
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K. P. C. J. Am. Chem. Soc. 1986, 108, 856. (b) Berris, B. C.; Hovakeemian,
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catalyst for the [2+2+2] cycloaddition of R,ω-diynes with
14,15
monoynes.
We report here the full details of the [2+2+2]
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cycloaddition of R,ω-diynes with monoynes. Furthermore, we
extended this chemistry to the [2+2+2] cycloaddition of R,ω-
diynes with monoenes and found a novel aromatization reaction
of R,ω-diynes with monoenes.
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Diyne 1a reacted with 3 equiv of 1-hexyne (2a) to give an
indane derivative 3a in the presence of a catalytic amount of
[Ir(cod)Cl]2 (Ir atom 4 mol %; cod ) 1,5-cyclooctadiene). The
1
4
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544 J. Org. Chem., Vol. 71, No. 2, 2006

Ir Complex-Catalyzed Cycloaddition
TABLE 1. Effect of Ligands and Ir Complexes on the Reaction of
the yield was less than that in benzene (entry 2). A similar
2+2+2] cycloaddition catalyzed by RuCp*(cod)Cl has been
reported to proceed at room temperature in 1,2-dichloro-
a
1
a with 2a
[
1
0a-c,e
ethane.
In our reaction, 1,2-dichloroethane was less
efficient than benzene (entry 6).
Diyne 1a reacted with 3 equiv of monoynes 2 to give indane
derivatives 3 in good to excellent yields. Various functionalized
monoynes could be used. The results are summarized in Table
entry
catalyst
ligandb
conditions
yield of 3a/%c
1
2
3
4
5
6
7
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)Cl]2
[Ir(cod)OMe]2
[Ir(cod)2]BF4
Ir(cod)(acac)
[Ir(cot)2Cl]2
PPh3
50 °C 24 h
50 °C 24 h
rt 20 min
50 °C 24 h
50 °C 24 h
reflux 24 h
50 °C 24 h
50 °C 24 h
50 °C 24 h
50 °C 24 h
45
45
84
68
35
12
24
15
20
22
DPPM
DPPE
DPPP
3
. The optimal reaction conditions depended on the monoyne
component used. Diyne 1a reacted with 1-decyne (2b), 5-phen-
yl-1-pentyne (2c), and 5-chloro-1-pentyne (2d) at room tem-
perature to give 3b, 3c, and 3d in excellent yields (entries 1-3).
The reaction with phenylacetylene (2e) required more demand-
ing conditions. The reaction with 2e under refluxing dioxane
for 2 h gave 3e in 85% yield (entry 4). Conjugated enyne (2f),
propargylic ether (2g), propargylic alcohol (2h), and 3-butyn-
1-ol (2j) could each be used as a monoyne component (entries
5-7 and 9). Reactions with 2f and 2g gave the corresponding
products in decreased yields compared to those with 2a-e
P(OPh)3
DPPE
DPPE
DPPE
DPPE
d
8
d
9
e
1
0
a
A mixture of 1a (1 mmol), 2a (3 mmol), Ir complex (0.02 mmol),
ligand (P/Ir ) 2), and benzene (5 mL) was stirred under Ar. b DPPM )
bis(diphenylphosphino)methane; DPPE ) 1,2-bis(diphenylphosphino)ethane;
DPPP ) 1,3-bis(diphenylphosphino)propane. Isolated yield based on 1a.
Ir complex (0.04 mmol). cot ) cyclooctene.
c
d
e
(
entries 5 and 6). The reaction with a tertiary carbon-substituted
monoyne gave a product in high yield. The reaction with
-methyl-3-butyn-2-ol (2i) gave 3i in 86% yield (entry 8). In
TABLE 2. Effect of Solvents on the Reaction of 1a with 2aa
2
contrast, the Ni(0)-mediated reaction of 1,6-heptadiyne deriva-
tive with 2i has been reported to give the corresponding product
7
k
in 12% yield. Interestingly, the reaction with N,N-dimethyl-
propargylic amine (2l) gave 3l in 65% yield (entry 10). The
reaction of R,ω-diyne with 2l has been reported to require a
entry
solvent
benzene
EtOH
THF
dioxane
acetone
1,2-dichloroethane
conditions
yield of 3a/%b
7
h
1
2
3
4
5
6
rt 20 min
reflux 8 h
rt 20 min
rt 1 h
50 °C 5 h
rt 8 h
84
60
79
80
64
68
stoichiometric amount of a Ni(0) complex. It is well-known
that a cyano group reacts with R,ω-diyne or two molecules of
16
monoyne to give a pyridine derivative. Diyne 1a reacted
smoothly with 5-cyano-1-pentyne (2m) at the carbon-carbon
triple bond to give an indane derivative 3m exclusively. The
reaction required a longer time for completion than those with
other monoynes (entry 11). No pyridine derivative was obtained.
Internal monoynes could also be used for the reaction of 1a.
Diyne 1a reacted with 3-hexyne (2o) at room temperature to
give 3o in 15% yield. Dimer 4a and trimer 4b were obtained in
respective yields of 43% and 40%. To suppress self-dimerization
or -trimerization of 1a, diyne 1a was added to a reaction mixture
containing a catalyst and a monoyne for 7 h. Slow addition of
1a increased the yield of 3o up to 82% (entry 12). The same
reaction catalyzed by Cp*Ru(cod)Cl has been reported to give
a
A mixture of 1a (1 mmol), 2a (3 mmol), [Ir(cod)Cl]2 (0.02 mmol),
DPPE (0.04 mmol), and solvent (5 mL) was stirred under Ar. b Isolated
yield based on 1a.
ligand (entry 3). The reaction was completed in 20 min at room
temperature to give 3a in 84% yield. DPPP, DPPM, and PPh3
were all inferior to DPPE. Reactions with DPPP, DPPM, or
PPh3 as a ligand gave 3a only upon heating, and the yield of
a decreased (entries 1, 2, and 4). [Ir(cod)Cl]2 without any ligand
gave 3a in 35% yield (entry 5). We previously reported that
3
1
0b
P(OPh)3 was an efficient ligand for [Ir(cod)Cl]2-catalyzed allylic
3o in 13% yield. When 5,7-dodecadiyne (2p) was used as a
monoyne component, the reaction took place at one of two
carbon-carbon triple bonds. Alkynyl substituent was success-
substitution.1
3c-i
However, P(OPh)3 was a less efficient ligand
than DPPE for [2+2+2] cycloaddition (entry 6). The catalytic
activities of several iridium complexes combined with DPPE
as a ligand were examined (entries 7-10). The catalytic
activities of these complexes were lower than that of [Ir(cod)-
Cl]2 combined with DPPE, and the yield of 3a decreased.
The solvent also affected the reaction (Table 2). Benzene was
the solvent of choice (entry 1). Reactions with THF or dioxane
gave a slightly decreased yield of 3a compared to that with
benzene (entries 3 and 4). EtOH has been reported to be a
general solvent for RhCl(PPh3)3-catalyzed [2+2+2] cycloaddi-
7c
fully introduced to the aromatic ring. Slow addition of 1a was
effective to give indane 3p in 61% yield. The reaction with
internal monoynes gave at a yield comparable to that of the
(16) (a) Varela, J. A.; Sa a´ , C. Chem. ReV. 2003, 103, 3787. (b)
Yamamoto, Y.; Kinpara, K.; Saigoku, T.; Takagishi, H.; Okuda, S.;
Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2005, 127, 605. (c) Guntov, A.;
Heller, B.; Fischer, C.; Drexler, H.-J.; Spannenberg, A.; Sundermann, B.;
Sundermann, C. Angew. Chem., Int. Ed. 2004, 43, 3795. (d) Hoshi, T.;
Katano, M.; Nozawa, E.; Suzuki, T.; Hagiwara, H. Tetrahedron Lett. 2004,
45, 3489. (e) Varela, J. A.; Castedo, L.; Sa a´ , C. J. Org. Chem. 2003, 68,
tion.8o,p,q
However, the reaction in EtOH did not proceed at room
8
595. (f) Yong, L.; Butensch o¨ n, H. Chem. Commun. 2002, 2852. (g)
Moretto, A. F.; Zhang, H.-C.; Maryanoff, B. E. J. Am. Chem. Soc. 2001,
23, 3157. (h) Valera, J. A.; Castedo, L.; Maestro, M.; Mah ´ı a, J.; Sa a´ , C.
temperature. The reaction under refluxing EtOH gave 3a, but
1
(
14) For preliminary work described here, see: (a) Takeuchi, R.; Tanaka,
Chem. Eur. J. 2001, 7, 5203. (i) Varela, J. A.; Castedo, L.; Sa a´ , C. Org.
Lett. 1999, 1, 2141. (j) Varela, J. A.; Castedo, L.; Sa a´ , C. J. Am. Chem.
Soc. 1998, 120, 12147. (k) Varela, J. A.; Castedo, L.; Sa a´ , C. J. Org. Chem.
1997, 62, 4189. (l) Vitulli, G.; Bertozzi, S.; Vignali, M.; Lazzaroni, R.;
Salvadori, P. J. Organomet. Chem. 1987, 326, C33. (m) Parnell, C. A.;
Vollhardt, K. P. C. Tetrahedron 1985, 41, 5791. (n) Wakatsuki, Y.;
Yamazaki, H. J. Chem. Soc., Chem. Commum. 1973, 280.
S.; Nakaya, Y. Tetrahedron Lett. 2001, 42, 2991. Related reactions, see:
b) Kezuka, S.; Okado, T.; Niou, E.; Takeuchi, R. Org. Lett. 2005, 7, 1711.
c) Takeuchi, R.; Nakaya, Y. Org. Lett. 2003, 5, 3659.
(
(
(
15) Iridium complex-catalyzed enantioselective [2+2+2] cycloaddition
has been reported, see: Shibata, T.; Fujimoto, T.; Yokota, K.; Takagi, K.
J. Am. Chem. Soc. 2004, 126, 8382.
J. Org. Chem, Vol. 71, No. 2, 2006 545

Kezuka et al.
TABLE 3. The Reaction of 1a with 2a
entry
monoyne
solvent
conditions
product
yield of 3/%b
1
2
3
4
5
6
7
8
2b (R1 ) n-Oct, R2 ) H)
benzene
benzene
benzene
dioxane
benzene
benzene
dioxane
dioxane
dioxane
dioxane
dioxane
benzene
benzene
rt 20 min
rt 1 h
3b
3c
3d
3e
3f
3g
3h
3i
3j
3l
3m
3o
3p
82
81
86
85
65
66
85
86
77
65
71
82
61
2c (R1 ) CH2CH2CH2Ph, R2 ) H)
2d (R1 ) CH2CH2CH2Cl, R2 ) H)
2e (R1 ) Ph, R2 ) H)
rt 30 min
reflux 2 h
reflux 6 h
reflux 10 h
reflux 8 h
reflux 3 h
reflux 6 h
reflux 2 h
reflux 17 h
rt 7 h
2f (R1 ) 1-cyclohexenyl, R2 ) H)
2g (R1 ) CH2OMe, R2 ) H)
2h (R1 ) CH2OH, R2 ) H)
2i (R1 ) CMe2OH, R2 ) H)
2j (R1 ) CH2CH2OH, R2 ) H)
2l (R1 ) CH2NMe2, R2 ) H)
2m (R1 ) CH2CH2CH2CN, R2 ) H)
2o (R1 ) R2 ) Et)
9
c
1
1
1
1
0
1
2
3
d
d
e
2p (R1)n-Bu, R2 ) t-n-Bu)
rt 7 h
a
b
A mixture of 1a (1 mmol), 2 (3 mmol), [Ir(cod)Cl]2 (0.02 mmol), DPPE (0.04 mmol), and solvent (5 mL) was stirred under Ar. Isolated yield based
on 1a. c [Ir(cod)Cl]2 (0.03 mmol), DPPE (0.06 mmol). d Diyne 1a was added by a syringe pump for 7 h. e Dimer 4a was obtained in 5% yield. Trimer 4b
was obtained in 10% yield.
TABLE 4. The Reaction of 1b-g with 2a
entry
diyne
monoyne
conditions
rt 1 h
rt 1 h
dioxane reflux 6 h
rt 1 h
rt 4 h
dioxane reflux 12 h
rt 3 h
rt 8 h
product
yield of 3/%b
1
2
3
1b (E1 ) E2 ) Ac)
1c (E1 ) Ph, E2 ) CO2Me)
1c
1d (E1 ) SO2Me, E2 ) CO2Me)
1e (E1 ) E2 ) CH2OMe)
1e
2a (R1 ) n-Bu, R2 ) H)
3q
3r
3s
73
91
77
59
67
78
73
41
2a
c
2h (R1 ) CH2OH, R2 ) H)
4
5
2a
2a
2h
2a
2a
3t
3u
3v
3w
3x
c
6
d
7
1f (E1 ) E2 ) CH2OAc)
1g (E1 ) E2 ) H)
8
a
A mixture of 1 (1 mmol), 2 (3 mmol), [Ir(cod)Cl]2 (0.02 mmol), DPPE (0.04 mmol), and benzene (5 mL) was stirred under Ar. b Isolated yield based
on 1. c Solvent was dioxane (5 mL). A mixture of 1 (0.5 mmol), 2 (1.5 mmol), [Ir(cod)Cl]2 (0.01 mmol), DPPE (0.02 mmol), and benzene (5 mL) was
stirred under Ar.
d
reaction with terminal monoynes. Internal monoynes as well
as terminal monoynes could be used as a monoyne component.
instead of 2a, the reaction of 1c,e required heating to give a
product in good yield (entries 3 and 6).
1
,6-Heptadiyne derivatives with various functional groups at
As described above, 1,6-heptadiyne derivatives reacted
smoothly with a monoyne to give a product in good to high
yield. We examined the reaction of 2,7-nonadiyne 5 with
monoynes. The results are summarized in Table 5. Diyne 5
reacted smoothly with monoynes. Internal monoynes as well
as terminal monoynes could be used for the reaction of 5. Diyne
the 4-position were subjected to cycloaddition. The results are
summarized in Table 4. Reactions with 2a proceeded at room
temperature. The reaction of ketone 1b with 2a gave 3q in 73%
yield (entry 1). Introduction of a phenyl group at the 4-position
increased the yield up to 91% (entry 2). The reaction of sulfone
1
d with 2a gave a product in a slightly decreased yield compared
5 reacted with 1-hexyne (2a) and propargyl ether (2g) to give
6a and 6g in respective yields of 87% and 79% (entries 1 and
3). The reaction with phenylacetylene (2e) gave 6e in a
to that of 1a (entry 4). A substituent other than a carbonyl group
is also effective for this cycloaddition. Methoxymethyl- and
acetoxymethyl-substituted diynes (1e and 1f) reacted with 2a
to give 3u and 3w in respective yields of 67% and 73% (entries
and 7). Diyne with no substituent at the 4-position gave a
product in decreased yield compared to other 4,4-disubstituted-
,6-heptadiyene derivatives. The reaction of 1,6-heptadiyne (1g)
gave 3x in 41% yield (entry 8). The low yield of the product
decreased yield compared to those of 6a and 6g (entry 2).
Reactions with internal monoynes proceeded at room temper-
ature to give products in high yields (entries 4-6). The
cycloaddition of terminally disubstituted diynes with monoynes
5
1
(
17) (a) Jung, M. E.; Piizzi, G. Chem. ReV. 2005, 105, 1735. (b) Eliel,
1
7
could be due to the lack of a Thorpe-Ingold effect. When
propargylic alcohol (2h) was used as a monoyne component
E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic Compounds;
Wiley: New York, 1994; p 682.
546 J. Org. Chem., Vol. 71, No. 2, 2006

Ir Complex-Catalyzed Cycloaddition
TABLE 5. The Reaction of 5 with 2a,e,g,o,p,qa
entry
monoyne
conditions
product
yield of 6/%b
1
2
3
4
5
6
2a (R1 ) n-Bu, R2 ) H)
2e (R1 ) Ph, R2 ) H)
toluene reflux 7 h
toluene reflux 3 h
toluene reflux 5 h
benzene rt 2 h
benzene rt 30 min
benzene rt 30 min
6a
6e
6g
6o
6p
6q
87
55
79
87
86
94
2g (R1 ) CH2OMe, R2 ) H)
2o (R1 ) R2 ) Et)
2p (R1 ) n-Bu, R2 ) t-n-Bu)
2q (R1 ) R2 ) CH2OMe)
a
A mixture of 5 (1 mmol), 2 (3 mmol), [Ir(cod)Cl]2 (0.02 mmol), DPPE (0.04 mmol), and benzene (5 mL) was stirred under Ar. b Isolated yield based
on 5.
TABLE 6. The Reaction of 9a,b with 2a,o,p
entry
diyne
monoyne
conditions
product
yield of 10/%b
a
1
9a
9b
9b
9b
2a (R1 ) n-Bu, R2 ) H)
2a
2o (R1 ) R2 ) Et)
2p (R1 ) n-Bu, R2 ) t-n-Bu)
benzene reflux 2 h
toluene reflux 1 h
benzene 50 °C 1 h
benzene 40 °C 1 h
10a
10b
10c
10d
53
45
92
95
a
2
c
3
d
4
a
b
A mixture of 9 (1 mmol), 2 (6 mmol), [Ir(cod)Cl]2 (0.03 mmol), DPPE (0.06 mmol), and solvent (5 mL) was stirred under Ar. Isolated yield based
on 9. c A mixture of 9b (1 mmol), 2o (5 mmol), [Ir(cod)Cl]2 (0.02 mmol), DPPE (0.04 mmol), and benzene (5 mL) was stirred under Ar. d A mixture of 9b
1 mmol), 2p (3 mmol), [Ir(cod)Cl]2 (0.02 mmol), DPPE (0.04 mmol), and benzene (5 mL) was stirred under Ar.
(
has been studied less than that of terminally unsubstituted diynes.
The Cp*Ru(cod)Cl-catalyzed reaction of 5 with 2o has been
reported to require 15 mol % of catalyst and 10 equiv of 2o to
give 6o in 66% yield.1 Iridium catalyst is more suitable for
the cycloaddition of terminally disubstituted diyne with internal
monoynes than other transition-metal catalysts.
reacted with 3 equiv of 2a under refluxing benzene for 2 h in
the presence of 4 mol % of catalyst to give 10a in 30% yield.
Increasing the amount of catalyst and 2a improved the yield
up to 53%. The reaction of 2,8-decadiyne 9b gave good results.
The reaction of 9b with 3-hexyne (2o) and 5,7-dodecadiyne (2p)
gave 10c and 10d in respective yields of 92% and 95%. This
cycloaddition is useful for the formation of six-membered rings.
The cycloaddition of unsymmetrical R,ω-diynes with 1-alkyne
gives two isomers. The control of regioselectivity is a chal-
lenging problem. Limited examples of regioselective cycload-
dition of unsymmetrical R,ω-diyne with 1-alkyne have been
reported. The Cp*Ru(cod)Cl-catalyzed reaction of 4,4-disub-
stituted 1,6-octadiyne with 1-alkyne has been reported to be
0b
We examined the reaction of an oxygen atom-tethered diyne
(eq 1). Dipropargyl ether 7 reacted with 3 equiv of 1-hexyne
1
0b,e
meta selective.
The RhCl(PPh3)3-catalyzed reaction of
oxygen-tethered diyne with 1-alkynes has also been reported
8
n
to be meta selective. However, the RhCl(PPh3)3-catalyzed
reaction of nitrogen-tethered diyne was reported to be ortho
(
2a) at room temperature for 23 h to give 8a in 25% yield.
8
l
Increasing the amount of 1-hexyne (2a) and heating increased
the yield. The reaction of 7 with 8 equiv of 2a at 50 °C gave
8
selective, and the ortho selectivity was up to 90%. This is the
only example of ortho-selective cycloaddition. To the best of
our knowledge, there is no previous report of the selective
synthesis of either ortho or meta products from the same
substrate. It is well-known that the electronic and steric nature
of a ligand affects the catalytic activity and selectivity. The
regioselectivity of cycloaddition can be controlled by a ligand.
A systematic survey of ligands showed that regioselective
cycloaddition was controlled by the ligand. The results are
summarized in Table 7. Diyne 11a reacted with 1-hexyne (2a)
to give ortho-product 12a and meta-product 13a. DPPE and
a in 64% yield. When 3-hexyne (2o) was used instead of
-hexyne (2a), the slow addition of 7 to a reaction mixture
1
containing a catalyst and 2o for 7 h at room temperature gave
8
o in 56% yield.
As mentioned above, the [Ir(cod)Cl]2/DPPE catalyst system
is efficient for the formation of five-membered rings from either
,6-heptadiyne derivatives 1 or 2,7-nonadiyne derivatives 5. We
1
next examined the possibility of six-membered ring formation
from 1,7-octadiyne derivative 9a and 2,8-decadiyne derivative
9
9
b (Table 6).18 The results are summarized in Table 6. Diyne
a, which has two quaternary carbon centers on the tether chain,
(18) Six-membered ring formation, see ref 7i.
J. Org. Chem, Vol. 71, No. 2, 2006 547

Kezuka et al.
TABLE 7. Effect of the Ligand on the Reaction of 11a with 2aa
ligandb
conditions
yield/%c
ratio 12a/13a
d
entry
1
2
3
4
5
6
7
8
9
DPPM
DPPE
DPPP
DPPB
DPPH
benzene reflux 5 h
benzene rt 30 min
benzene reflux 1 h
benzene reflux 1 h
benzene reflux 24 h
benzene rt 3 h
benzene reflux 1 h
toluene reflux 3 h
toluene reflux 3 h
84
93
82
89
10
74
84
72
32
26/74
20/80
43/57
59/41
70/30
19/81
88/12
78/22
81/19
1,2-bis(diphenylphosphino)ethylene
DPPF
(R)-(S)-BPPFOAc
PPh3
a
A mixture of 11a (1 mmol), 2a (3 mmol), [Ir(cod)Cl]2 (0.02 mmol), ligand (0.04 mmol), and solvent (5 mL) was stirred under Ar. b DPPB ) 1,4-
bis(diphenylphosphino)butane; DPPH ) 1,6-bis(diphenylphosphino)hexane; DPPF ) 1,1′-bis(diphenylphosphino)ferrocene; (R)-(S)-BPPFOAc ) (R)-1-[(S)-
c
1
1
′,2-bis(diphenylphosphino)ferrocenyl]ethyl acetate. Isolated yield based on 11a. d Determined by H NMR.
TABLE 8. Cycloaddition of 11a,b with 2a
yield/%b
ratio 12/13
c
entry
diyne
monoyne
ligand
conditions
product
1
2
3
4
5
6
7
8
9
11a
11a
11a
11a
11a
11a
11a
11a
11a
11a
11b
11b
2a (R1 ) n-Bu, R2 ) H)
DPPE
DPPE
DPPE
DPPE
DPPE
DPPF
DPPF
DPPF
DPPF
DPPF
DPPE
DPPF
benzene rt 0.5 h
benzene rt 1 h
toluene reflux 9 h
benzene rt 12 h
toluene reflux 2 h
benzene reflux 1 h
benzene reflux 1 h
toluene reflux 8 h
benzene reflux 2 h
toluene reflux 1 h
benzene rt 3 h
12a, 13a
12b, 13b
12c, 13c
12d, 13d
12e, 13e
12a, 13a
12b, 13b
12c, 13c
12d, 13d
12e, 13e
12f, 13f
12f, 13f
92
80
92
75
74
84
83
68
86
52
76
80
20/80
19/81
39/61
18/82
42/58
88/12
86/14
76/24
84/16
74/26
14/86
59/41
2b (R1 ) n-Oct, R2 ) H)
2f (R1)1-cyclohexenyl, R2)H)
2k (R1 ) CH2CH2CH2OH, R2 ) H)
2n (R1 ) Me3Si, R2 ) H)
2a
2b
2f
2k
2n
2a
2a
1
1
1
0
1
2
toluene reflux 3 h
a
A mixture of 11 (1 mmol), 2 (3 mmol), [Ir(cod)Cl]2 (0.02 mmol), ligand (0.04 mmol), and solvent (5 mL) was stirred under Ar. b Isolated yield based
on 11. c Determined by H NMR.
1
DPPM were meta-selective ligands (entries 1 and 2). The
reaction with DPPE gave products in 93% yield with 80% meta
selectivity. Increasing the methylene length between the two
phosphorus atoms increased the ortho selectivity. DPPH gave
11a with 2a (entry 11). Meta selectivity was 86%. The reaction
with DPPF gave products in 80% yield with 59% ortho
selectivity, which is less ortho selective than the reaction of
11a with 2a (entry 12).
7
5
0% ortho selectivity, but the product yield was only 10% (entry
). The reactions with ferocenyl phosphine ligands were ortho
Cycloaddition of r,ω-Diynes with Monoenes. The cycload-
dition of R,ω-diynes with monoynes was efficiently catalyzed
by [Ir(cod)Cl]2/DPPE. If a monoene is used instead of a
monoyne, a cyclohexadiene derivative will be obtained as a
selective. The reaction with DPPF gave products in 84% yield
with 88% ortho selectivity (entry 7). (R)-(S)-BPPFOAc was less
ortho selective than DPPF (entry 8). PPh3 was an ortho-selective
ligand, but the product yield was only 32% (entry 9).
On the basis of these results, we developed the regioselective
cycloaddition of 11a with 1-alkynes. The results are summarized
in Table 8. Reactions with DPPE were meta selective, while
those with DPPF were ortho selective. Various 1-alkynes
including alcohol 2k could be used for regioselective cycload-
dition. Good meta selectivities were observed for the reaction
with 2a,b,k (entries 1, 2, and 4). Reactions with enyne 2f and
trimethylsilyacetylene 2n were less meta selective than that with
1
9
product. A polycyclic cyclohexadiene structure can be con-
structed by using iridium catalysis. Cyclohexadienes are used
in the Diels-Alder reaction, which provides a rich and diverse
20
chemistry. This cycloaddition is the simplest route to a bicyclic
cyclohexadiene framework. To examine this possibility, we
carried out the cycloaddition of R,ω-diynes with monoenes. We
examined the reaction of 1a with monoenes such as 1-octene,
acrylonitrile, styrene, and 2,5-dihydrofuran. Although diyne 1a
was consumed completely, no cyclohexadiene derivative was
obtained. Only the self-dimerization of 1a occurred. The
terminal alkyne part of 1a would be more reactive than the
monoenes used. We used 2,7-nonadiyne 5 instead of 1a to
suppress the self-dimerization of a diyne component, since
internal alkynes should be less reactive than terminal alkynes
2
a,b,k. For reactions with DPPF, good ortho selectivities were
observed in all cases (entries 6-10). The introduction of a longer
alkyl substituent to the alkyne part in the unsymmetrical diyne
affected the regioselectivity. When the ligand was DPPE, the
reaction of 11b with 2a was more meta selective than that of
548 J. Org. Chem., Vol. 71, No. 2, 2006

Ir Complex-Catalyzed Cycloaddition
TABLE 9. Effect of Molar Ratio on the Reaction of 5 with 14a
molar ratio
entry
14/5
solvent (mL)
time/h
yield of 15b
yield of 16ab
1
2
3
4
5
6
7
8
9
66
50
50
50
50
50
50
30
10
none
THF (1.2 mL)
2
2
1
6
2
1
13
2
76
79
62
54
69
67
58
58
40
13
19
24
20
20
16
17
33
36
dioxane (1.2 mL)
1,2-dimethoxyethane (1.2 mL)
benzene (1.2 mL)
1,2-dichloroethane (1.2 mL
EtOH (1.2 mL)
THF (2.7 mL)
THF (4.2 mL)
2
a
A mixture of 5 (1 mmol), 14, [Ir(cod)Cl]2 (0.01 mmol), DPPE (0.02 mmol), and solvent was stirred at 70 °C under Ar. b Isolated yield based on 5.
due to steric reasons. Diyne 5 reacted with 2,5-dihydrofuran
and diallyl ether. Reactions were carried out under reflux for
24 h. No products were obtained.
(14) under reflux in the presence of a catalytic amount of [Ir-
(
cod)Cl]2/DPPE (Ir atom 4 mol %). The results are summarized
A novel aromatization reaction including cleavage of a C-O
bond was found in the reaction of 5 with 2,3-dihydrofuran (17)
(eq 2). Diyne 5 reacted with 50 equiv of 2,3-dihydrofuran (17)
in Table 9. When 2,5-dihydrofuran was used as a solvent,
cyclohexadiene 15 was obtained in 76% yield along with the
self-dimerization product 16a in 13% yield (entry 1). Self-
trimerization product 16b was not obtained at all. The molar
ratio of 2,5-dihydrofuran (14) to diyne 5 strongly affected the
yield of 15. A molar ratio of 14 to 5 of 50 gave 15 in 79%
yield (entry 2). The effect of the solvent was examined at a
molar ratio of 50 (entries 2-7). THF gave the best result (entry
2
8
). A molar ratio of 30 or 10 decreased the yield of 15 (entries
and 9). A large excess of 2,5-dihydrofuran (14) is necessary
for a high yield of 15.
Diyne 5 reacted smoothly with 2,5-dihydrofuran (14) to give
in the presence of a catalytic amount of [Ir(cod)Cl]2/DPPE (Ir
atom 4 mol %) at 60 °C for 22 h to give aromatic alcohol 18
in 97% yield. When the amount of 17 was reduced to 10 equiv,
the yield of 18 decreased to 70%. The aromatization reaction
could be extended to the reaction with an acyclic vinyl ether
such as n-butyl vinyl ether (19) (eq 3). The reaction of 5 with
1
5. Analogous to the iridium-catalyzed reaction of 5 with 14,
the [2+2+2]cycloaddition of 1,6-heptadiyne with 2,5-dihydro-
furan catalyzed by ruthenium complex has been reported.
The coordination of the allylic oxygen atom to the ruthenium
center plays an important role. On the basis of this result, we
examined the reaction of 5 with allyl acetate, allyl n-propyl ether,
1
9d,h
2
5 equiv of 19 at 70 °C for 2 h gave 20 and ether 21. The
combined yield was nearly quantitative.
(19) Cycloaddition of diynes or two molecules of monoynes with
monoenes to give cyclohexadienes, see: (a) Wu, M.-S.; Rayabarapu. D.
K.; Cheng, C.-H. Tetrahedron 2004, 60, 10005. (b) Sambaiah, T.; Li, L.-
P.; Huang, D.-J.; Lin, C.-H.; Rayabarapu, D. K.; Cheng, C.-H. J. Org. Chem.
1
999, 64, 3663. (c) Eichberg, M. J.; Dorta, R. L.; Lamottke, K.; Vollhardt,
K. P. C. Org. Lett. 2000, 2, 2479. (d) Yamamoto, Y.; Kitahara, H.; Ogawa,
R.; Kawaguchi, H.; Tatsumi, K.; Itoh, K. J. Am. Chem. Soc. 2000, 122,
4
310. (e) Ikeda, S.; Kondo, H.; Mori, N. Chem. Commun. 2000, 815. (f)
Mori, N.; Ikeda, S.; Sato, Y. J. Am. Chem. Soc. 1999, 121, 2722. (g)
Yamamoto, Y.; Kitahara, H.; Hattori, R.; Itoh, K. Organometallics 1998,
1
7, 1910. (h) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Itoh, K. J. Org.
Chem. 1998, 63, 9610. (i) Ikeda, S.; Watanabe, H.; Sato, Y. J. Org. Chem.
1
1
1
1
998, 63, 7026. (j) Ikeda, S.; Mori, N.; Sato, Y. J. Am. Chem. Soc. 1997,
19, 4779. (k) Balaich, G. J.; Rothwell, I. P. J. Am. Chem. Soc. 1993, 115,
581. (l) Zhou, Z.; Costa, M.; Chiusoli, G. P. J. Chem. Soc., Perlin Trans.
1992, 1399. (m) Zhou, Z.; Battaglia, L. P.; Chiusoli, G. P.; Costa, M.;
Nardelli, M.; Pelizzi, C.; Predieri, G. J. Chem. Soc., Chem. Commun. 1990,
Discussion
1632. (n) Macomber, D. W.; Verma, A. G.; Rogers, R. D. Organometallics
1
988, 7, 1241. (o) Brown, L. D.; Itoh, K.; Suzuki, H.; Hirai, K.; Ibers, J.
Metallacyclopentadiene is a common intermediate in the
cyclotrimerization of alkynes. It is generally accepted that there
are two mechanisms for the reaction of metallacyclopentadiene
with alkynes (Scheme 1): a Diels-Alder type mechanism and
A. J. Am. Chem. Soc. 1978, 100, 8232. (p) Suzuki, H.; Itoh, K.; Ishii, Y.;
Simon, K.; Ibers, J. A. J. Am. Chem. Soc. 1976, 98, 8494.
3
(20) Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; John
Wiley: New York, 1990.
J. Org. Chem, Vol. 71, No. 2, 2006 549

Kezuka et al.
SCHEME 1
Regioselectivity of Cycloaddition. The regioselectivity of
the cycloaddition of 11 with 1-alkynes could be controlled by
the ligand. DPPE was a meta-selective ligand, whereas DPPF
was an ortho-selective ligand. Meta selectivity is outlined in
Scheme 2. 1-Alkyne coordinates to the vacant coordination site
above the plane of the iridacyclopentadiene formed by the
oxidative cyclization of 11a. The orientation of the incoming
1
-alkyne is directed to avoid steric interaction between the
methyl group on iridacyclopentadiene 24 and the substituent
on 1-alkyne. Therefore, meta-product 13 is obtained as a major
product. To explain the ortho selectivity, we should propose
another mechanism. Important results are shown in Table 7.
Increasing the length of the carbon chain between the two
phosphorus atoms in diphosphine increased the ortho selectivity
SCHEME 2
(Table 7, entries 2-5). Triphenylphosphine also showed high
ortho selectivity (Table 7, entry 9). The results with DPPH and
triphenylphosphine are important for considering the mechanism
of ortho selectivity (Table 7, entries 5 and 9). These ligands
gave low yields of products, but gave high ortho selectivity.
Coordination of DPPH to the iridium center forms a nine-
2
3
membered ring in which chelation is not tight. One of the
two phosphorus atoms in DPPH easily dissociates from the
iridium center to give a vacant coordination site. Triphenylphos-
phine also easily dissociates from the metal center compared
to bidentate ligands. The high ortho selectivities given by DPPH
and PPh3 suggest that the generation of a vacant coordination
site is important. Ortho selectivity is outlined in Scheme 2. DPPF
was found to be the best ligand for ortho selectivity (Table 7,
2
3d
entry 7). Since DPPF has a large bite angle, it is reasonable
to consider that similar dissociation takes place in intermediate
25 coordinated by DPPF. The steric hindrance between a methyl
group and PPh2 moiety induces the dissociation of PA to give
a vacant coordination site on the iridium center. Coordination
of a monoyne at this position followed by insertion gives
intermediate 26. Reductive elimination from 26 gives the
product. In this insertion step, the iridium moiety, which is more
bulky than the CR moiety, adds to the less-hindered site of two
2
4
25
acetylenic carbons to give iridacycloheptatriene 26. Thus,
ortho product 12 is obtained as a major product.
Cycloaddition with Monoenes to Give Cyclohexadiene
Derivatives. A possible mechanism is outlined in Scheme 3.
Coordination of 2,5-dihydrofuran (14) to a vacant coordination
site above the plane of iridacyclopentadiene 27 is followed by
a Diels-Alder type process to give 29. Reductive elimination
from 29 gives 15.
Cycloaddition with Monoenes to Give Benzene Deriva-
tives. Diyne 5 reacted with 2,3-dihydrofuran to give benzene
derivative 18 (eq 2). The reaction involves the cleavage of a
C-O bond in 2,3-dihydrofuran. A possible mechanism is
outlined in Scheme 4. Iridacyclopentadiene 27 reacts with 2,3-
dihydrofuran to give intermediate 31 via a Diels-Alder type
process. Reductive elimination of 31 gives diene intermediate
an insertion mechanism to give metallacycloheptatriene. Irida-
cyclopentadiene formed by the oxidative cyclization of R,ω-
diynes is an intermediate for cycloaddition (Scheme 2). The
catalytic activity of our iridium catalyst strongly depended on
the ligand used, and [Ir(cod)Cl]2/DPPE was the most catalyti-
cally active. The reaction of [Ir(cod)Cl]2 with DPPE gives the
mononuclear species Ir(cod)Cl(dppe). Oxidative cyclization of
diynes with Ir(cod)Cl(dppe) would give iridiacyclopentadiene
2
2. The reaction of 22 with monoyne followed by reductive
elimination gives a final product. The efficiency of DPPE
suggests that a Diels-Alder type mechanism21 is involved in
this case. Bidentate coordination of DPPE produces a vacant
coordination site above the plane of iridiacyclopentadiene 22.
Coordination of a monoyne at this position22 would facilitate a
Diels-Alder type process via intermediate 23. Coordination of
DPPE to iridium forms a five-membered ring, which gives the
most stable chelation. The stability of the intermediate coordi-
nated by DPPE would lead to high catalytic activity.
(
22) Cobaltacyclopentadiene bearing an alkyne ligand is isolated, see:
(
a) Dosa, P. I.; Whiteener, G. D.; Vollhardt, K. P. C.; Bond, A. D.; Teat,
S. J. Org. Lett. 2002, 4, 2075. (b) Diercks, R.; Eaton, B. E.; G u¨ rtzgen, S.;
Jalisatgi, S.; Matzger, A. J.; Radde, R. H.; Vollhardt, K. P. C J. Am. Chem.
Soc. 1998, 120, 8247.
(23) The effect of bite angle, see: (a) Freixa, Z.; van Leeuwen, P. W.
N. M. Dalton Trans. 2003, 1890. (b) van Leeuwen, P. W. N. M.; Kamer,
P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. ReV. 2000, 100, 2741. (c) Kamer,
P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001,
34, 895. (d) Dierkes, P.; van Leeuwen, P. W. N. M. J. Chem. Soc., Dalton
Trans. 1999, 1519.
(24) The regioselectivity of the insertion is governed by the steric
demands of both the metal center and the alkyne.
(
21) Reaction of iridacyclopentadiene with a monoyne via a Diels-Alder
type process, see: ref 12j,k. Reaction of cobaltacyclopentadiene with a
monoyne via a Diels-Alder type process, see: (a) Hardesty, J. H.; Koerner,
J. B.; Albright, T. A.; Lee, G.-Y. J. Am. Chem. Soc. 1999, 121, 6055. (b)
McAlister, D. R.; Bercaw, J. E.; Bergman, R. G. J. Am. Chem. Soc. 1977,
9
9, 1666.
550 J. Org. Chem., Vol. 71, No. 2, 2006

Ir Complex-Catalyzed Cycloaddition
SCHEME 3
32. The iridium moiety moves to an oxygen atom to give
intermediate 33. E2 elimination from 33 gives product 18 and
regenerates an iridium active species. The reaction of 5 with
n-butyl vinyl ether gave two benzene derivatives 20 and 21 (eq
3
). A possible mechanism is outlined in Scheme 5. A process
similar to that discussed above takes place in this case. The
reaction of 27 with n-butyl vinyl ether gives diene 36. The
iridium moiety moves to an oxygen atom to give intermediate
3
7. E2 elimination from 37 gives product 20 and regenerates
an iridium active species. Another reaction pathway is possible
for diene 36. The oxidative addition of the allylic C-H bond
to the iridium center gives π-allyl iridium hydride intermediate
2
6
27
3
8. Anti â-hydride elimination
assisted by n-butyl vinyl
ether gives 21 and regenerates an iridium active species.
SCHEME 4
SCHEME 5
J. Org. Chem, Vol. 71, No. 2, 2006 551

Kezuka et al.
Conclusion
dihydrofuran (14) (3.505 g, 50 mmol), and 5 (236 mg, 1.0 mmol)
was then added to the stirred solution. The reactor was immersed
in an oil bath, which was kept at 70 °C. The reaction mixture was
heated at 70 °C for 2 h. After the reaction was completed, the
solvent was evaporated in vacuo. Column chromatography of the
residue gave 15 and 16a as a mixture (n-hexane/AcOEt ) 90/10,
In conclusion, we developed the iridium complex-catalyzed
cycloaddition of diynes with monoynes and monoenes. The
reactions proceeded under mild conditions to give polysubsti-
tuted benzene derivatives and cyclohexadiene derivatives in
good to excellent yields. The experimental procedures are quite
simple. A phosphine ligand is crucial for high catalytic activity
and high selectivity. In alkyne cycloaddition chemistry, Cp or
Cp* metal complexes such as CpCo(CO)2, CpRh(ethylene)2,
and Cp*Ru(cod)Cl have been used as catalysts. In such cases,
it can be difficult to control the reaction by tuning the steric
and electronic effects of the Cp ligand since the introduction
of substituents to the Cp ligand requires considerable synthetic
operations. In contrast, our catalyst is convenient for controlling
the reaction, since various phosphine ligands are available. It
is important to note that [Ir(cod)Cl]2 is a commercially available,
air-stable, and easily handled complex. The results described
here should lead to new opportunities for the application of
organoiridium chemistry in cycloaddition.
1
289 mg). The yield of each product was determined by H NMR.
Products were purified by recycling preparative HPLC.
Cycloaddition of 5 with 17. Into a two-necked flask with a
stirring bar were placed [Ir(cod)Cl] (6.8 mg, 0.01 mmol) and DPPE
2
(8.0 mg, 0.02 mmol). The flask was evacuated and filled with Ar.
THF (1.2 mL) was added to the flask. To the stirred solution was
added 2,3-dihydrofuran (17) (3.505 g, 50 mmol), and 5 (236 mg,
1.0 mmol) was then added to the stirred solution. The reactor was
immersed in an oil bath, which was kept at 60 °C. The reaction
mixture was heated at 60 °C for 22 h. After the reaction was
completed, the solvent was evaporated in vacuo. Column chroma-
tography of the residue gave 18 (n-hexane/AcOEt ) 70/30, 297
mg, yield 97%).
Cycloaddition of 5 with 19. Into a two-necked flask with a
2
stirring bar were placed [Ir(cod)Cl] (6.8 mg, 0.01 mmol) and DPPE
(
8.0 mg, 0.02 mmol). The flask was evacuated and filled with Ar.
Experimental Section
THF (1.8 mL) was added to the flask. To the stirred solution was
added n-butyl vinyl ether (19) (2.504 g, 25 mmol), and 5 (236 mg,
General Procedure for the Cycloaddition of Diyne with
Monoyne at Room Temperature. A typical procedure is described
for the reaction of 1a with 1-hexyne (2a) (Table 1; entry 3). Into
a two-necked flask with a stirring bar were placed diyne 1a (208
1.0 mmol) was then added to the stirred solution. The reactor was
immersed in an oil bath, which was kept at 70 °C. The reaction
mixture was heated at 70 °C for 2 h. After the reaction was
completed, the solvent was evaporated in vacuo. Column chroma-
tography of the residue gave 20 and 21 as a mixture (n-hexane/
AcOEt ) 98/2, 299 mg). The yield of each product was determined
2
mg, 1.0 mmol), [Ir(cod)Cl] (13.4 mg, 0.02 mmol), and DPPE (15.9
mg, 0.04 mmol). The flask was evacuated and filled with Ar.
Benzene (5.0 mL) was added to the flask. To the stirred solution
was added 1-hexyne (2a) (246 mg, 3.0 mmol). The mixture was
stirred at room temperature for 20 min. The solvent was evaporated
in vacuo. Column chromatography (n-hexane/AcOEt ) 98/2) of
the residue gave 3a as a colorless oil (244 mg; yield 84%).
General Procedure for the Cycloaddition of Diyne with
Monoyne at Elevated Temperature. A typical procedure is
described for the reaction of 1a with propargyl alcohol (2h) (Table
1
by H NMR. Products were purified by recycling preparative HPLC.
Acknowledgment. This research was supported in part by
Grants-in-Aid for Scientific Research (C) and Scientific Re-
search on Priority Areas (A) “Exploitation of Multi-Element
Cyclic Molecules” from the Japan Society for the Promotion
of Science and the Ministry of Education, Culture, Sports, Sci-
ence and Technology of Japan. We thank Mr. Minoru Kato,
Mr. Yasushi Kawaguchi, Mr. Takeshi Kitahara, Mr. Ken Tana-
ka, and Mr, Hirokazu Shinya for their experimental assistance.
1; entry 7). Into a two-necked flask with a stirring bar were placed
diyne 1a (208 mg, 1.0 mmol), [Ir(cod)Cl] (13.4 mg, 0.02 mmol),
2
and DPPE (15.9 mg, 0.04 mmol). The flask was evacuated and
filled with Ar. Dioxane (5.0 mL) was added to the flask. To the
stirred solution was added propargyl alcohol (2h) (168 mg, 3.0
mmol) at room temperature. The reactor was immersed in an oil
bath at room temperature, and then heating was begun. The reaction
mixture was heated under refluxing dioxane for 8 h. After the
reaction was completed, the solvent was evaporated in vacuo.
Column chromatography of the residue gave 3h (n-hexane/AcOEt
Supporting Information Available: Experimental details,
1
13
compound characterization data, and H and C NMR spectra for
compounds 3a, 3e, 3l, 3t, 3w, 3x, 4a, 4b, 6p, 8a, 10b, 10d, and
16a. This material is available free of charge via the Internet at
http://pubs.acs.org.
)
70/30, 225 mg, yield 85%).
General Procedure for the Slow Addition of Diyne. A typical
JO051874C
procedure is described for the reaction of 1a with 2o (Table 3;
entry 12). Into a two-necked flask with a stirring bar were placed
(25) Iridacycloheptatriene, see: (a) Paneque, M.; Poveda, M. L.; Rendon,
N.; Mereiter, K. J. Am. Chem. Soc. 2004, 126, 1610. (b) AÄ lvarez, E.; G o´ mez,
M.; Paneque, M.; Posadas, C. M.; Poveda, M. L.; Rend o´ n, N.; Santos, L.
L.; Rojas-Lima, S.; Salazar, V.; Mereiter, K.; Ruiz, C. J. Am. Chem. Soc.
2
[Ir(cod)Cl] (13.4 mg, 0.02 mmol) and DPPE (15.9 mg, 0.04 mmol).
The flask was evacuated and filled with Ar. Benzene (3.0 mL) was
added to the flask. To the stirred solution was added 3-hexyne (2o)
2
003, 125, 1478.
(246 mg, 3.0 mmol). A benzene solution (2.0 mL) of 1a (208 mg,
(26) Oxidative addition of the allylic C-H bond to give the π-allyl
1.0 mmol) was added dropwise to the reaction mixture over 7 h by
iridium complex, see: (a) Ortmann, D. A.; Gevert, O.; Laubender, M.;
Werner, H. Organometallics 2001, 20, 1776. (b) Alvarado, Y.; Boutry, O.;
Guti e´ rrez, E.; Monge, A.; Nicasio, M. C.; Carmen; Poveda, M. L.; P e´ rez,
P. J.; Ru ´ı z, C.; Bianchini, C.; Carmona, E. Chem. Eur. J. 1997, 3, 860. (c)
Tulip, T. H.; Ibers, J. A. J. Am. Chem. Soc. 1979, 101, 4201. Oxidative
addition of the allylic C-H bond to give the π-allyl ruthenium complex,
see: (d) Itoh, K.; Masuda, K.; Ikeda, H. Organometallics 1993, 12, 2752.
Oxidative addition of the allylic C-H bond to give the π-allyl palladium
complex, see: (e) Trost, B. M.; Strege, P. E.; Weber, L.; Fullerton, T. J.;
Dietsche, T. J. J. Am. Chem. Soc. 1978, 100, 3407.
a syringe pump with stirring at room temperature. After the reaction
was completed, the solvent was evaporated in vacuo. Column
chromatography of the residue gave 3o (n-hexane/AcOEt ) 98/2,
2
5
38 mg, yield 82%), 4a (n-hexane/AcOEt ) 80/20, 11 mg, yield
%), and 4b (n-hexane/AcOEt ) 50/50, 21 mg, yield 10%).
General Procedure for the Cycloaddition of 5 with 14. A
typical procedure is described for the reaction in THF (Table 9;
entry 2). Into a two-necked flask with a stirring bar were placed
(27) Anti â-hydride elimination of the π-allyl palladium intermediate to
2
[Ir(cod)Cl] (6.8 mg, 0.01 mmol) and DPPE (8.0 mg, 0.02 mmol).
give dienes, see: (a) Schwarz, I.; Braun, M, Chem. Eur. J. 1999, 5, 2300.
(b) Takacs, J. M.; Lawson, E. C.; Clement, F. J. Am. Chem. Soc. 1997,
119, 5956. (c) Andersson, P. G.; Schab, S. Organometallics 1995, 14, 1.
The flask was evacuated and filled with Ar. THF (1.2 mL) was
added to the flask. To the stirred solution was added 2,5-
552 J. Org. Chem., Vol. 71, No. 2, 2006