RhCl3/amine-catalyzed cyclotrimerization of alkynes

Article abstract of DOI:10.1246/cl.2007.998

RhCl₃/amine was found to be an efficient catalyst for the cyclotrimerization of alkynes. The [2 + 2 + 2] cyclotrimerization of internal alkynes proceeded smoothly to afford hexa-substituted benzenes regioselectively in moderate to high yields. Copyright

Full text of DOI:10.1246/cl.2007.998

9
98
Chemistry Letters Vol.36, No.8 (2007)
RhCl /Amine-catalyzed Cyclotrimerization of Alkynes
3
ꢀ
Kenta Yoshida, Ichiro Morimoto, Koichi Mitsudo, and Hideo Tanaka
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology,
Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530
(Received May 7, 2007; CL-070485; E-mail: tanaka95@cc.okayama-u.ac.jp)
RhCl3/amine was found to be an efficient catalyst for the
Table 1. Cyclotrimerization using several additives
cyclotrimerization of alkynes. The [2 þ 2 þ 2] cyclotrimeriza-
tion of internal alkynes proceeded smoothly to afford hexa-sub-
stituted benzenes regioselectively in moderate to high yields.
Ph
Ph
Ph
R
RhCl ·3H O
3
2
R
R
Ph
R
R
R
Additive
Toluene, reflux, 24 h
Ph
Ph
Ph
2a
R
3a
R = CO Et
2
The transition-metal-catalyzed [2 þ 2 þ 2] cyclotrimeriza-
1a
tion of alkynes is a straightforward method to construct benzene
1
Additivea
Yield/%b
Entry
2a:3a
derivatives in a one-pot process. Although various transition
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
9
Et3N (8/30)
none
67
20
32
69
98:2
99:1
97:3
95:5
metals (Ni, Rh, Pd, Ru, Co, Ti, and Mo ) catalyze alkyne
cyclotrimerization, it has been not always easy to conduct inter-
molecular reactions regioselectively in high yields. In particular,
the internal alkynes, which can be applied for the trimerization,
have been often restricted to those bearing small or activated
substituents such as acetylene dicarboxylate. For instance, the
efficiency of the trimerization of internal alkynes bearing
aryl and ester moieties, such as ethyl phenylpropiolate (PhCꢁ
Et2NH (8/30)
i-Pr2NH (8/30)
i-Pr2NEt (8/30)
i-Pr2NEt (3/6)
i-Pr2NEt (3/9)
i-Pr2NEt (3/12)
Ph3N (8/30)
c
c
91 (89)
96:4 (99:1)
96:4
97:3
96:4
97:3
—
74
93
84
26
—
—
9
CCO2Et), is quite low. Therefore, a more general and efficient
trimerization method has been in great demand.
10
11
a
Pyridine (8/30)
TMEDA (8/30)
Recently, we found that the combination of RhCl3 and ter-
tiary-alkylamines works as a unique catalyst. Herein, we report
the RhCl3/amine-catalyzed cyclotrimerization of alkynes,
which can be widely applicable to internal alkynes. The cyclotri-
merization of alkynes proceeded smoothly to afford hexa-substi-
tuted benzenes regioselectively in moderate to high yields.
—
The values in parentheses are Rh/mol % and additive/
mol %. Isolated yield. RhCl3 was employed.
b
c
ities (Entries 1–5). The cyclotrimerization of alkynes 1a or 1b
was highly regioselective (Entries 1–3).
.
.
In the presence of RhCl3 3H2O (8 mol %) and Et3N
30 mol %), the cyclotrimerization of alkyne 1a at reflux in tol-
Decreasing the amount of RhCl3 3H2O (3 mol %) and
(
i-Pr2NEt (9 mol %), the yields and regioselectivities of 2 were
almost the same. By GC analysis, it was revealed that the
reaction was completed within 9 h to afford the cycloadduct
quantitatively (Entry 2). When using alkyne 1c, the cycloadduct
was obtained quantitatively, while a slight decline of the
regioselectivity was observed (Entry 4). When using symmetri-
cal internal alkynes 1d and 1e, cycloadducts were obtained in 96
and 73% yields, respectively (Entries 5 and 6). Terminal alkynes
also could be utilized in the Rh/amine-catalyzed trimerization
(Entries 7–10). The trimerization of phenylacetylene, p-tolyl-
acetylene, and 1-octyne gave the cycloadducts 2f–2h in 98, 97,
and 87% yields, respectively (Entries 7–9). Only in the case of
ethyl propiolate (1i), the yield of the corresponding products
was rather low (75%, Entry 10). In all cases, the unsymmetrical
isomers 2a–2i were obtained as the major products. The regiose-
lectivity in the RhCl3/amine-catalyzed cyclotrimerization was
highly influenced by the substituents of alkynes. Especially,
the reaction of alkynes bearing aryl groups proceeded with
virtually complete regioselectivities. Blum and co-workers
uene occurred to give 2a in 67% yield in a virtually completely
regioselective manner (Table 1, Entry 1). Without any amine,
the cyclotrimerization of alkyne 1a gave 2a only in 20% yield
(
Entry 2). Various other sec- and tert-amines were applied to
the RhCl3-catalyzed trimerization reaction (Entries 3–11), and
we found that i-Pr2NEt, a highly electron-donating amine, was
the most effective among them (Entry 5). With i-Pr2NEt, the
amount of Rh catalyst could be reduced to 3 mol % (Entry 7).
The ratio of Rh/amine influenced the reactivity (Entries 6–8).
With 1:3 of Rh/amine catalyst, the cycloadduct was obtained
in the highest yield (93%, Entry 7). On the other hand, elec-
tron-deficient amine (e.g. Ph3N) was found to be ineffective
for the trimerization reaction (Entry 9). Pyridine was ineffective,
and the starting material 1a was recovered quantitatively,
1
0
probably due to the generation of Rh(py)3Cl3 (Entry 10). Using
a bidentate amine ligand such as TMEDA, product 2a was
not obtained (Entry 11). The addition of an electron-donating
monodentate amine might be essential for generation of the
þ
ꢂ
III
‘
‘active catalyst’’ in situ.
reported trimerization using [R4N] [RhCl4] , an anionic Rh
catalyst, but the reactivity and regioselectivity of the cycload-
.
Next, the combination of RhCl3 3H2O with i-Pr2NEt was
successfully applied to the cyclotrimerization using a variety
of alkynes (Table 2). Using internal alkynes, in many cases,
the cyclotrimerization proceeded to give the corresponding cy-
clotrimerization products in high yields with good regioselectiv-
3
f
ducts were unsatisfactory and quite different from RhCl3/
i-Pr2NEt catalyst. From this result, we proposed that RhCl3
I
would be reduced by i-Pr2NEt to generate Rh complexes coor-
I
dinated by i-Pr2NEt. Rh complexes bearing ꢀ-donative trialkyl-
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.8 (2007)
999
Table 2. Cyclotrimerization of several alkynes
Synthesis, 1991, Vol. 5 (Ed.: B. M. Trost, I. Fleming), Pergamon,
Oxford, pp. 1129–1162.
R1
R1
R1
RhCl ·3H O (8 mol %)
2
a) C. M u¨ ller, R. J. Lachicotte, W. D. Jones, Organometallics
2002, 21, 1975. b) A. Jeevanandam, R. P. Korioi, I-w. Huang,
C.-H. Cheng, Org. Lett. 2002, 4, 807. c) S. Saito, T. Kawasaki,
N. Tsuboya, Y. Yamamoto, J. Org. Chem. 2001, 66, 796. d)
Y. Sato, K. Ohashi, M. Mori, Tetrahedron Lett. 1999, 40, 5231.
e) Y. Saito, T. Nishimata, M. Mori, Heterocycles 1997, 44, 443.
f) Y. Sato, T. Nishimata, M. Mori, J. Org. Chem. 1994, 59,
6133. g) G. P. Chiusoli, L. Pallini, G. Terenghi, Transition Met.
Chem. 1983, 3, 189.
a) K. Tanaka, K. Toyoda, A. Wada, K. Shirasaki, M. Hirano,
Chem. Eur. J. 2005, 11, 1145. b) L. Dufkov a´ , L. C ´ı sarov a´ , P.
Stepnicka, M. Kotora, Eur. J. Org. Chem. 2003, 2882. c) H.
Kinoshita, H. Shinokubo, K. Oshima, J. Am. Chem. Soc. 2003,
3
2
R2
R2
R1
R2
R2
R1
R2
R1
i-Pr NEt (30 mol %)
2
Toluene, reflux, 24 h
R2
R1
R2
1
2
3
Entry
R1
R2
Time/h Yield/%a
2:3
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Me
Pr
Ph
Ph
CO2Et 1a
CO2Et 1a
24
9
91 (93)b
87 (99)c
96:4
96:4
3
87 (91)b >99:<1
Me
1b
24
24
24
24
12
12
12
12
b
CO2Et 1c
95 (90)
96
73
76:24
—
—
Pr
Ph
H
1d
1e
1f
125, 7784. d) Q. Sun, X. Zhou, K. Islam, D. J. Kyle, Tetrahedron
Lett. 2001, 42, 6495. e) I. Ojima, A. T. Vu, J. V. McCullagh, A.
Kinoshita, J. Am. Chem. Soc. 1999, 121, 3230. f) I. Amer, T.
Bernstein, M. Eisen, J. Blum, K. P. C. Volhardt, J. Mol. Catal.
1990, 60, 313. g) R. Grigg, R. Scott, P. Stevenson, Tetrahedron
Lett. 1982, 23, 2691. h) E. M u¨ ller, Synthesis 1974, 761. i) J. P.
Collman, J. W. Kang, W. F. Little, M. F. Sullivan, Inorg. Chem.
98 (94)b
97
87
94:6
p-MeC6H4
Hex
EtO2C
H
H
H
1g
1h
1i
>99:<1
67:33
74:26
1
0
75
aIsolated yield. b3 mol % of RhCl3 3H2O and 9 mol % of i-
Pr2NEt were employed. GC yield.
.
1968, 7, 1298.
c
4
5
a) J. S. Cheng, H. F. Jiang, Eur. J. Org. Chem. 2004, 643. b)
M. F. N. N. Carvalho, F. M. T. Almeida, A. M. Galv a˜ o, A. J. L.
Pombeiro, J. Organomet. Chem. 2003, 679, 143. c) Y. Yamamoto,
A. Nagata, H. Nagata, Y. Ando, Y. Arikawa, K. Tatsumi, K. Itoh,
Chem. Eur. J. 2003, 9, 2469. d) J. Li, H. Jiang, M. Chen, J. Org.
Chem. 2001, 66, 3627. e) A. K. Jhingan, W. F. Maier, J. Org.
Chem. 1987, 52, 1161.
a) Y. Yamamoto, K. Kinpara, T. Saigoku, H. Takagishi, S. Okuda,
H. Nishiyama, K. Itoh, J. Am. Chem. Soc. 2005, 127, 605. b) Y.
Yamamoto, J. Ishii, H. Nishiyama, K. Itoh, J. Am. Chem. Soc.
RhCl ·3H O (8 mol %)
3
2
EtO C
i-Pr NEt (30 mol %)
EtO2C
2
2
EtO C
i-PrOH, reflux, 2 h
EtO C
2
R
2
R
4
1f:R = Ph
h:R = Hex
4 equiv.)
5f:81%
5h:82%
1
(
Scheme 1. Cycloaddition of diyne and alkynes.
2004, 126, 3712. c) Y. Ura, Y. Sato, M. Shiotsuki, T. Kondo, T.
Mitsudo, J. Mol. Catal. A: Chem. 2004, 209, 35. d) E. R u¨ ba, R.
Schmid, K. Kirchner, M. J. Calhorda, J. Organomet. Chem.
amines assumed to interact with alkynes by strong back-dona-
tion to promote the reductive cyclization to give rhodacyclopen-
tadiene. The high-regioselectivity of Rh/amine system might be
caused by the regioselective construction of the rhodacycle.
2003, 682, 204. e) Y. Yamamoto, T. Arakawa, R. Ogawa, K. Itoh,
J. Am. Chem. Soc. 2003, 125, 12143. f) J.-U. Peters, S. Blechert,
Chem. Commun. 1997, 1983.
a) N. Saino, F. Amemiya, E. Tanabe, K. Kase, S. Okamoto, Org.
Lett. 2006, 8, 1439. b) V. Gandon, C. Aubert, M. Malacria, Chem.
Commun. 2006, 2209. c) G. Hilt, T. Vogler, W. Hess, F. Galbiati,
.
Finally, the combination of RhCl3 3H2O with i-Pr2NEt was
6
applied to the [4 þ 2] cycloaddition of a diyne and alkynes
(
Scheme 1). The cycloaddition of diyne 4 and phenylacetylene
1f) or 1-octyne (1h) gave the cycloadducts 5f and 5h in 81
(
and 82% yields, respectively.
In summary, we have developed the RhCl3/amine-catalyzed
Chem. Commun. 2005, 1474. d) L. Yong, H. Butenschon, Chem.
¨
Commun. 2002, 2852. e) M. S. Sigman, A. W. Fatland, B. E.
Eaton, J. Am. Chem. Soc. 1998, 120, 5130. f) S. H. Lecker,
N. H. Nguyen, K. P. C. Vollhardt, J. Am. Chem. Soc. 1986,
[
2 þ 2 þ 2] cyclotrimerization of alkynes, which can be widely
108, 856.
applicable for various alkynes, providing tri- or hexa-substituted
benzenes regioselectively in moderate to high yields. The
7
a) F. T. Ladipo, V. Sarveswaran, J. V. Kingston, R. A. Huyck,
S. Y. Bylikin, S. D. Carr, R. Watts, S. Parkin, J. Organomet.
Chem. 2004, 689, 502. b) O. V. Ozerov, B. O. Patrick, F. T.
Ladipo, J. Am. Chem. Soc. 2000, 122, 6423. c) O. V. Ozerov,
F. T. Ladipo, B. O. Patrick, J. Am. Chem. Soc. 1999, 121, 7941.
d) E. S. Johnson, G. J. Balaich, P. E. Fanwick, I. P. Rothwell,
J. Am. Chem. Soc. 1997, 119, 11086.
[
4 þ 2] cycloaddition of diynes and alkynes has also been
developed based on the use of the Rh/amine complex, providing
benzene derivatives in high yields. Further investigation of
the structure and catalytic activity of Rh/amine complex is
currently in progress in our laboratory.
8
9
a) Y. Sato, T. Nishimata, M. Mori, J. Org. Chem. 1994, 59, 6133.
b) N. Kaneta, T. Hirai, M. Mori, Chem. Lett. 1995, 627.
a) M. Toganoh, Y. Matsuo, E. Nakamura, J. Organomet. Chem.
We thank the SC-NMR Laboratory of Okayama University
13
1
for H and C NMR analyses.
2003, 683, 295. b) H. Yan, A. M. Beatty, T. P. Fehlner, Organo-
References and Notes
metallics 2002, 21, 5029. c) P. Cioni, P. Diversi, G. Ingrosso, A.
Lucherini, P. Ronca, J. Mol. Catal. 1987, 40, 337. d) S. T. Flynn,
S. E. Hasso-Henderson, A. W. Parkins, J. Mol. Catal. 1985, 32,
101. e) R. Diercks, H. tom Dierk, Z. Naturforsch., B: Chem.
Sci. 1984, 39B, 180. f) W. H u¨ bel, C. Hoogzand, Chem. Ber.
1960, 93, 103.
1
For reviews see: a) S. Kotha, E. Brahmachary, K. Lahiri, Eur. J.
Org. Chem. 2005, 4741. b) S. Saito, Y. Yamamoto, Chem.
Rev. 2000, 100, 2901. c) D. B. Grotjahn, in Comprehensive
Organometallic Chemistry II, 1995, Vol. 12, (Eds.: E. W. Abel,
F. G. A. Stone, G. Wilkinson, L. Hegedus), Pergamon, Oxford,
pp. 741–770. d) R. Boese, A. P. V. Sickle, K. P. C. Vollhardt,
Synthesis 1994, 1374. e) N. E. Shore, in Comprehensive Organic
10 J. P. Collman, H. F. Holtzclaw Jr., J. Am. Chem. Soc. 1958, 80,
2054.
Published on the web (Advance View) June 30, 2007; doi:10.1246/cl.2007.998