Highly Chemo- and Regioselective Intermolecular Cyclotrimerization of Alkynes Catalyzed by Cationic Rhodium(I)/Modified BINAP Complexes

Article abstract of DOI:10.1021/ol035963s

(Equation presented) Cationic rhodium(I)/modified BINAP complexes are effective catalysts for highly regioselective intermolecular cyclotrimerization of terminal alkynes and highly chemo- and regioselective intermolecular cocyclotrimerization of diethyl acetylonedicarboxylate (DEAD) and terminal alkynes. It is a noteworthy example of intermolecular cocyclotrimerization of two different alkynes in terms of catalytic activity, chemo- and regioselectivity, scope of substrates, and ease of operation. The wide applicability of this new cocyclotrimerization procedure is demonstrated in the one-step synthesis of [6]metacyclophane.

Full text of DOI:10.1021/ol035963s

ORGANIC
LETTERS
2003
Vol. 5, No. 24
4697-4699
Highly Chemo- and Regioselective
Intermolecular Cyclotrimerization of
Alkynes Catalyzed by Cationic
Rhodium(I)/Modified BINAP Complexes
Ken Tanaka* and Kaori Shirasaka
Department of Applied Chemistry, Tokyo UniVersity of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received October 8, 2003
ABSTRACT
Cationic rhodium(I)/modified BINAP complexes are effective catalysts for highly regioselective intermolecular cyclotrimerization of terminal
alkynes and highly chemo- and regioselective intermolecular cocyclotrimerization of diethyl acetylenedicarboxylate (DEAD) and terminal alkynes.
It is a noteworthy example of intermolecular cocyclotrimerization of two different alkynes in terms of catalytic activity, chemo- and regioselectivity,
scope of substrates, and ease of operation. The wide applicability of this new cocyclotrimerization procedure is demonstrated in the one-step
synthesis of [6]metacyclophane.
Highly regiocontrolled synthesis of arenes is attractive
because arenes are important building blocks in organic
synthesis. Cyclotrimerization of alkynes to yield substituted
benzenes is a possible method for their synthesis. Although
various transition metals catalyze alkyne cyclotrimerization,
it has been difficult to carry out that intermolecular reaction
in a highly regioselective manner.1 In particular, catalytic
chemo- and regioselective intermolecular cocyclotrimeriza-
tion of two different alkynes has not been established yet.2-5
In general, a partially intramolecular reaction between an
R,ω-diyne and excess monoynes and a completely intra-
molecular reaction have been employed to overcome this
problem.6 The present study describes highly regioselective
intermolecular cyclotrimerization of terminal alkynes and
highly chemo- and regioselective intermolecular cocyclot-
rimerization of diethyl acetylenedicarboxylate (DEAD) and
terminal alkynes catalyzed by cationic rhodium(I)/modified
BINAP complexes (Figure 1).
Although a neutral rhodium(I) complex is an effective
catalyst for partial or complete intramolecular cyclotrimer-
(1) For reviews, see: (a) Saito, S.; Yamamoto, Y. Chem. ReV. 2000,
100, 2901-2915. (b) Fru¨hauf, H.-W. Chem. ReV. 1997, 97, 523-596. (c)
Ojima, I.; Tzamarioudaki, M.; Zhaoyang, L.; Donovan, R. J. Chem. ReV.
1996, 96, 635-662. (d) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996,
96, 46-92. (e) Boese, R.; Sickle, A. P. V.; Vollhardt, K. P. C. Synthesis
1994, 1374-1382. (f) Schore, N. E. Chem. ReV. 1988, 88, 1081-1119. (g)
Vollhardt, K. P. C. Angew. Chem., Int. Ed. 1984, 23, 536-556. (h) Grotjahn,
D. B. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone,
F. G. A., Wilkinson, G., Hegedus, L., Eds.; Pergamon Press: Oxford, 1995;
Vol. 12, pp 741-770.
Figure 1. Structures of modified BINAP ligands.
10.1021/ol035963s CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/29/2003

ization of alkynes,7,8 it generally reacts with terminal alkynes
to give linear dimers (Scheme 1).9,10 On the other hand,
Table 1. Cationic Rh(I) Complex-Catalyzed Intermolecular
Cyclotrimerization of Terminal Alkynesa
Scheme 1
yield (%) ratio
catalystb
alkyne (2 + 3)c of 2/3c
application of a cationic rhodium(I) complex in oligomer-
ization of terminal alkynes remains unexplored.11
We examined the reaction of 1-dodecyne (1a) first using
5 mol % of [Rh(cod)2]BF4/10 mol % PPh3 at room temper-
ature. The reaction was very slow, but a small amount of
cyclotrimerization products was detected (Table 1, entry 1).
Although the use of various monodentate or bidentate
phosphine ligands (Ph3P, n-Bu3P, dppe, and dcpe) furnished
cyclotrimerization products, the catalytic activities were low
(entries 1-4).
entry
1
2
3
4
5
6
7
8e
9
[Rh(cod)2]BF4/2 Ph3P
[Rh(cod)2]BF4/2 n-Bu3P
[Rh(nbd)2]BF4/dppe
1a
1a
1a
1a
1a
1a
1a
5
3
3
[Rh(cod)2]BF4/dcpe
<2
>95
<2
<2
[Rh(cod)2]BF4/Tol-BINAP
[Rh(cod)Cl]2/Tol-BINAP
[Ir(cod)2]BF4/Tol-BINAP
[Rh(cod)2]BF4/DTBM-SEGPHOS 1a
[Rh(cod)2]BF4/DTBM-SEGPHOS 1b
64:36
91d
89d
83:17
97:3
a Rh or Ir complex (0.005 mmol), phosphine (0.005 or 0.01 mmol),
1-dodecyne (0.1 mmol), and CH2Cl2 (1 mL) were employed. b The active
catalysts were prepared by mixing Rh or Ir complex and phosphine in
1
CH2Cl2 followed by hydrogenation (1 atm, rt, 0.5 h). c Determined by H
(2) Ni(0)-catalyzed cocyclotrimerization of methyl propiolate and terminal
alkynes was reported. Although the regioselectivity is high, chemoselectivity
is moderate, and the reaction requires slow addition of methyl propiolate
(over 5-60 min) and a substoichiometric amount of zinc(II) phenoxide:
Mori, N.; Ikeda, S.-I.; Odashima, K. Chem. Commun. 2001, 181-182.
(3) For Ni(0)-catalyzed cocyclotrimerization of alkynes using a large
excess of acetylene gas, see: Sato, Y.; Ohashi, K.; Mori, M. Tetrahedron
Lett. 1999, 40, 5231-5234.
(4) Palladacyclopentadiene-mediated cocyclotrimerization of two mol-
ecules of dimethyl acetylenedicarboxylate and one molecule of dipheny-
lacetylene was reported (76% yield), but this reaction proceeded in low
yield (40% yield) under catalytic conditions (regioselectivity is not relevant
to this case): Dieck, H. T.; Munz, C.; Mu¨ller, C. J. Organomet. Chem.
1990, 384, 243-255.
(5) Stoichiometric zirconium- and copper-mediated cocyclotrimerization
of alkynes, see: Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima,
K.; Kotora, M. J. Am. Chem. Soc. 1998, 120, 1672-1680.
(6) For papers on catalytic intramolecular cyclotrimerization of alkynes,
see: (a) Yamamoto, Y.; Nagata, A.; Nagata, H.; Ando, Y.; Arikawa, Y.;
Tatsumi, K.; Itoh, K. Chem. Eur. J. 2003, 9, 2469-2483. (b) Jeevanandam,
A.; Korivi, R. P.; Huang, I.; Cheng, C.-H. Org. Lett. 2002, 4, 807-810.
(c) Sugihara, T.; Wakabayashi, A.; Nagai, Y.; Takao, H.; Imagawa, H.;
Nishizawa, M. Chem. Commun. 2002, 9, 576-577. (d) Slowinski, F.;
Aubert, C.; Malacria, M. AdV. Synth. Catal. 2001, 343, 64-67. (e) Ozerov,
O. V.; Patrick, B. O.; Ladipo, F. T. J. Am. Chem. Soc. 2000, 122, 6423-
6431. (f) Yamamoto, Y.; Ogawa, R.; Itoh, K. Chem. Commun. 2000, 9,
549-550. (g) Hillard III, R. L.; Vollhardt, K. P. C. J. Am. Chem. Soc.
1977, 99, 4058-4069.
(7) For recent papers on the rhodium-catalyzed intramolecular cyclot-
rimerization of alkynes, see: (a) Kinoshita, H.; Shinokubo, H.; Oshima, K.
J. Am. Chem. Soc. 2003, 125, 7784-7785. (b) Nishiyama, H.; Niwa, E.;
Inoue, T.; Ishima, Y.; Aoki, K. Organometallics 2002, 21, 2572-2574. (c)
Witulski, B.; Zimmermann, A. Synlett 2002, 1855-1859. (d) McDonald,
F. E.; Smolentsev, V. Org. Lett. 2002, 4, 745-748. (e) Witulski, B.; Stengel,
T. Angew. Chem., Int. Ed. 1999, 38, 2426-2430. (f) Kotha, S.; Brahma-
chary, E. Tetrahedron Lett. 1997, 38, 3561-3564. (g) McDonald, F. E.;
Zhu, H. Y. E.; Homquist, C. R. J. Am. Chem. Soc. 1995, 117, 6605-6606.
(8) For pioneering work of the rhodium-catalyzed intramolecular cyclo-
trimerization of alkynes, see: Grigg, R.; Scott, R.; Stevenson, P. J. Chem.
Soc., Perkin Trans. 1 1988, 1357-1364.
NMR. d Isolated yield. e Reaction time ) 24 h.
Surprisingly, the use of Tol-BINAP dramatically improved
catalytic activity and cyclotrimerization products were
obtained in almost quantitative yield with moderate regi-
oselectivity (entry 5). The use of cationic Rh(I) complex is
essential for this reaction. The use of neutral Rh(I)/Tol-
BINAP complex or cationic Ir(I)/Tol-BINAP complex
significantly decreased the activity (entries 6 and 7). Both
high activity and regioselectivity were achieved by use of
the cationic Rh(I)/DTBM-SEGPHOS12 complex. Both non-
conjugated (1a) and conjugated (1b) terminal alkynes were
good substrates yielding 1,2,4-trisubstituted benzenes 2 in
high yield with high regioselectivity (entries 8 and 9).
Next, we investigated intermolecular cocyclotrimerization
of two different alkynes. After screening various alkynes and
cationic Rh(I)/modified BINAP complexes, we found that
the cationic Rh(I)/H8-BINAP13 complex catalyzed chemo-
and regioselective intermolecular cocyclotrimerization of
DEAD (4) and terminal alkynes. Table 2 shows that two
molecules of 1 cleanly reacted with one molecule of 4 to
yield 3,6-disubstituted diethyl phthalate 5 in high yield with
high regioselectivity upon treatment with catalytic amount
of cationic Rh(I)/H8-BINAP complex.14 Alkyl- (1a, entry
1), chloroalkyl- (1c, entry 2), methoxymethyl- (1d, entry 3),
aryl- (1e, entry 4 and 1f, entry 5), and alkenyl-substituted
(1b, entry 6) terminal alkynes were suitable substrates for
this reaction. Although the reaction of sterically demanding
trimethylsilylacetylene (1g) furnished 5g in moderate yield,
excellent regioselectivity of 5g was observed (entry 7).
(9) (a) Field, L. D.; Ward, A. J.; Turner, P. Aust. J. Chem. 1999, 52,
1085-1092. (b) Ohshita, J.; Furumori, K.; Matsuguchi, A.; Ishikawa, M.
J. Org. Chem. 1990, 55, 3277-3280.
(10) For rhodium clusters catalyzed intermolecular cyclotrimerization of
terminal alkynes, see: Baidossi, W.; Goren, N.; Blum, J. J. Mol. Catal.
1993, 85, 153-162.
(11) For recent papers on the cationic rhodium(I) complex-catalyzed
reaction of alkynes, see: (a) Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 8078-8079. (b) Chakrapani, H.; Liu, C.; Widenhoefer, R. A. Org.
Lett. 2003, 5, 157-159. (c) Tong, X.; Zhang, Z.; Zhang, X. J. Am. Chem.
Soc. 2003, 125, 6370-6371. (d) Hartung, C. G.; Tillack, A.; Trauthwein,
H.; Beller, M. J. Org. Chem. 2001, 66, 6339-6343. (e) Jeong, N.; Sung,
B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000, 122, 6771-6772.
(12) Saito, T.; Yokozawa, T.; Zhang, X.; Sayo, N. EP 850945A, 1998;
US 5872273, 1999.
(13) Zhang, X. Mashimo, K.; Koyano, K.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Takaya, H. Tetrahedron. Lett. 1991, 32, 7283-7286.
(14) In this reaction, major byproducts are 1:2 () 1/4) cocyclotrimer-
ization products.
4698
Org. Lett., Vol. 5, No. 24, 2003

Scheme 3
Table 2. Cationic Rh(I)/H8-BINAP Complex-Catalyzed
Intermolecular Cocyclotrimerization of DEAD and Terminal
Alkynesa
D followed by the coordination of terminal alkynes to form
complex B.15 Reductive elimination of rhodium gives 5 and
regenerates the rhodium catalyst.
The wide applicability of this new cocyclotrimerization
procedure is demonstrated in the synthesis of metacyclophane
(Scheme 3). The reaction of commercially available 1,9-
decadiyne (8) and 4 gave a [6]metacyclophane 9 in 50%
yield. This is the shortest (one-step) synthesis of a metacyclo-
phane starting from commercially available reagents.16
In conclusion, we discovered that cationic rhodium(I)/
modified BINAP complexes are versatile new catalysts for
highly regioselective intermolecular cyclotrimerization of
terminal alkynes, and highly chemo- and regioselective
intermolecular cocyclotrimerization of DEAD and terminal
alkynes. This catalyst system is the first example of efficient
rhodium(I)-catalyzed intermolecular cyclotrimerization of
terminal alkynes. It is a noteworthy example of intermo-
lecular cocyclotrimerization of two different alkynes in terms
of catalytic activity, chemo- and regioselectivity, scope of
substrates, and ease of operation. Work toward developing
an asymmetric variant of this process is underway and will
be reported in due course.
entry
R
yield (%) (5 + 6 + 7)b ratio of 5/6/7c
1
2
3
4
5
6
7
n-C10H21 (1a )
Cl(CH2)3 (1c)
MeOCH2 (1d )
Ph (1e)
o-Tol (1f)
1-cyclohexenyl (1b)
Me3Si (1g)
88
92
61
90
77
90
57
92:6:2
91:8:1
86:10:4
89:9:2
89:9:2
91:4:5
99:1:0
a See the Supporting Information for reaction conditions. b Isolated yield.
c Determined by H NMR.
1
Scheme 2 depicts a plausible mechanism of this cationic
rhodium(I)/H8-BINAP complex-catalyzed intermolecular co-
cyclotrimerization. Chemo- and regioselectivity is determined
by preferential formation of metallacycle A instead of C and
Acknowledgment. We thank Dr. Takao Saito of Takasa-
go International Corp. for the gift of Tol-BINAP, DTBM-
SEGPHOS, and H8-BINAP.
Scheme 2
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL035963S
(15) The use of rhodium(I)/DTBM-SEGPHOS complex for the cocy-
clotrimerization of 1 and 4 significantly lowered the yield of 5 as a result
of the generation of 2 and 3 as byproducts. The use of rhodium(I)/Tol-
BINAP complex significantly decreased the regioselectivity of 5.
(16) For the formation of cyclophanes by cyclotrimerization of bis-
terminal diynes with nitriles, see: Moretto, A. F.; Zhang, H.-C.; Maryanoff,
B. E. J. Am. Chem. Soc. 2001, 123, 3157-3158.
Org. Lett., Vol. 5, No. 24, 2003
4699