Liquid enol ethers and acetates as gaseous alkyne equivalents in Rh-catalyzed chemo- and regioselective formal cross-alkyne cyclotrimerization

Article abstract of DOI:10.1021/ol800813g

(Chemical Equation Presented) A cationic rhodium(I)/rac-BINAP complex catalyzes chemo- and regioselective formal cross-cyclotrimerizations of alkynes with enol ethers or acetates. Commercially available and cheap liquid enol ethers and acetates could be used as convenient gaseous alkyne equivalents in the present rhodium catalyses.

Full text of DOI:10.1021/ol800813g

ORGANIC
LETTERS
2008
Vol. 10, No. 12
2537-2540
Liquid Enol Ethers and Acetates as
Gaseous Alkyne Equivalents in
Rh-Catalyzed Chemo- and
Regioselective Formal Cross-Alkyne
Cyclotrimerization
Hiromi Hara, Masao Hirano, and Ken Tanaka*
Department of Applied Chemistry, Graduate School of Engineering, Tokyo UniVersity
of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received April 9, 2008
ABSTRACT
A cationic rhodium(I)/rac-BINAP complex catalyzes chemo- and regioselective formal cross-cyclotrimerizations of alkynes with enol ethers or
acetates. Commercially available and cheap liquid enol ethers and acetates could be used as convenient gaseous alkyne equivalents in the
present rhodium catalyses.
Transition-metal-catalyzed [2 + 2 + 2] cycloadditions of
alkynes have been shown to be a valuable method for the
synthesis of substituted benzenes.1 Although gaseous alkynes
such as acetylene and propyne can be used for the transition-
metal-catalyzed alkyne cyclotrimerization,2 alternative liquid
reagents are more convenient to handle than gaseous alkynes
using conventional laboratory equipment. As such, com-
Hashimoto, T.; Hattori, K.; Kikuchi, M.; Nishiyama, H. Org. Lett. 2006, 8,
3565. (e) Yamamoto, Y.; Kinpara, K.; Saigoku, T.; Nishiyama, H.; Itoh,
K. Org. Biomol. Chem. 2004, 2, 1287. (f) Yamamoto, Y.; Hata, K.; Arakawa,
T.; Itoh, K. Chem. Commun. 2003, 1290. (g) Yamamoto, Y.; Arakawa, T.;
Ogawa, R.; Itoh, K. J. Am. Chem. Soc. 2003, 125, 12143. (h) Witulski, B.;
Alayrac, C. Angew. Chem., Int. Ed. 2002, 41, 3281. (i) Witulski, B.;
Zimmermann, A. Synlett 2002, 1855. (j) Yamamoto, Y.; Ogawa, R.; Itoh,
K. Chem. Commun. 2000, 549. (k) Witulski, B.; Stengel, T. Angew. Chem.,
Int. Ed. 1999, 38, 2426. (l) Sato, Y.; Ohashi, K.; Mori, M. Tetrahedron
Lett. 1999, 40, 5231. (m) McDonald, F. E.; Zhu, H. Y. H.; Holmquist, C. R.
J. Am. Chem. Soc. 1995, 117, 6605. (n) Sato, Y.; Nishimata, T.; Mori, M.
J. Org. Chem. 1994, 59, 6133.
(1) For recent reviews of transition-metal-catalyzed [2 + 2 + 2]
cycloadditions, see: (a) Agenet, N.; Buisine, O.; Slowinski, F.; Gandon,
V.; Aubert, C.; Malacria, M. In Organic Reactions; Overman, L. E., Ed.;
John Wiley & Sons: Hoboken, 2007; Vol. 68, p 1. (b) Chopade, P. R.;
Louie, J. AdV. Synth. Catal. 2006, 348, 2307. (c) Gandon, V.; Aubert, C.;
Malacria, M. Chem. Commun. 2006, 2209. (d) Kotha, S.; Brahmachary,
E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741. (e) Yamamoto, Y. Curr.
Org. Chem. 2005, 9, 503. (f) Robinson, J. E. In Modern Rhodium-Catalyzed
Organic Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005; p
129.
(3) (a) Kezuka, S.; Tanaka, S.; Ohe, T.; Nakaya, Y.; Takeuchi, R. J.
Org. Chem. 2006, 71, 543. For their first discovery of neutral iridium(I)/
bisphosphine complex-catalyzed [2 + 2 + 2] cycloadditions, see: (b)
Takeuchi, R.; Tanaka, S.; Nakaya, Y. Tetrahedron Lett. 2001, 42, 2991.
(c) Takeuchi, R.; Nakaya, Y. Org. Lett. 2003, 5, 3659. (d) Kezuka, S.;
Okado, T.; Niou, E.; Takeuchi, R. Org. Lett. 2005, 7, 1711.
(2) For selected recent examples, see: (a) Heller, B.; Gutnov, A.; Fischer,
C.; Drexler, H.-J.; Spannenberg, A.; Redkin, D.; Sundermann, C.; Sunder-
mann, B. Chem. Eur. J. 2007, 13, 1117. (b) Ramana, C. V.; Salian, S. R.;
Gonnade, R. G. Eur. J. Org. Chem. 2007, 5483. (c) Young, D. D.; Senaiar,
R. S.; Deiters, A. Chem. Eur. J. 2006, 12, 5563. (d) Yamamoto, Y.;
10.1021/ol800813g CCC: $40.75
Published on Web 05/14/2008
2008 American Chemical Society

mercially available and cheap liquid enol ethers and acetates
are possible gaseous alkyne equivalents as shown in Scheme
1.3,4 If a [2 + 2 + 2] cycloaddition of two alkyne units with
diate, which may furnish tetrasubstituted benzene 3aa as a
sole product. We first investigated the reaction of 1a with
2a in the presence of a [Rh(cod)2]BF4/rac-BINAP complex
(5 mol %). We were pleased to find that the reaction
proceeded at room temperature to give the desired
aromatized product 3aa exclusively in high yield (Scheme
2). After screening various BINAP-type bisphosphine
Scheme 1
Scheme 2
ligands, the use of rac-BINAP furnished 3aa in the highest
yield. Although the reaction of 1a with vinyl acetate (2b)
was also examined, 3aa was obtained in lower yield than
that with 2a (Scheme 2).
Thus, we explored the scope of this process using 5 equiv
of enol ethers as shown in Table 1. Not only malonate- (1a,
entry 1) but also tosylamide- (1b, entry 2) and oxygen-linked
(1c, entry 3) 1,6-diynes could be employed for this reaction.
With respect to enol ethers, the use of n-butyl vinyl ether
(2a, entries 1-3) furnished the corresponding aromatized
products 3aa-ca in higher yields than 3ac-cc obtained from
isopropenyl methyl ether (2c, entries 4-6). Importantly,
commercially available liquid ketene acetal 2d could par-
ticipate in this reaction as a gaseous ethynyl methyl ether
equivalent, which furnished the corresponding bicyclic
methoxybenzenes 3ad-cd in high yield (entries 7, 9, and
10).8 When the amount of ketene acetal 2d reduced to 1.1
equiv, the yield of the desired product 3ad decreased to 65%
(entry 8). Although a hexane solution of ethyl ethynyl ether
is commercially available, it was unstable.9 The reaction of
unsymmetrical 1,6-diyne 1d bearing methyl and methoxy-
carbonyl at each alkyne terminus with 2c and 2d furnished
the corresponding pentasubstituted benzenes 3dc and 3dd,
respectively, with perfect regioselectivity (entries 11 and 12).
A possible mechanism for the present regioselective [2 +
2 + 2] cycloaddition of 1d with 2c or 2d is shown in Scheme
3. Diyne 1d reacts with rhodium to form rhodacyclopenta-
diene B. Subsequent regioselective insertion of 2c or 2d
forms intermediate D through intermediate C, which is
stabilized by coordination of the carbonyl group and the
methoxy group to the cationic rhodium. Reductive elimina-
tion of rhodium furnishes substituted benzene 3dc or 3dd
and methanol.
one enol ether or acetate could proceed, initially formed
cyclohexadiene A would be aromatized to the corresponding
substituted benzene through elimination of alcohol or acetic
acid.3,4 Our research group already demonstrated that cationic
rhodium(I)/BINAP-type bisphosphine complexes [BINAP )
2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl]5 are highly
effective catalysts for [2 + 2 + 2] cycloadditions of alkynes
with not only monoynes6 but also monoenes.7 In this paper,
we describe a cationic rhodium(I)/rac-BINAP complex-
catalyzed chemo- and regioselective formal cross-cyclotri-
merization of alkynes with enol ethers or acetates.
Recently, Takeuchi and co-workers reported that a neutral
iridium(I)/dppe complex catalyzes a [2 + 2 + 2] cycload-
dition of 1,6-diyne 1a with n-butyl vinyl ether (2a) at
elevated temperature (70 °C).3 However, the reaction fur-
nished two aromatized products 3aa and 4aa, and 4aa was
generated as the major product.3 We anticipated that the high
Lewis acidity of the cationic rhodium(I)/BINAP-type bis-
phosphine complexes would facilitate the elimination of
n-butanol from the initially formed cyclohexadiene interme-
(4) Although palladium-catalyzed [2 + 2 + 2] cycloadditions of dimethyl
acetylenedicarboxylate with vinyl ethers and vinyl esters were reported,
the reactions require a large excess of the vinyl compounds (100 equiv)
and a long reaction time (3-5 days), see: Stephan, C.; Munz, C.; Dieck,
H. T. J. Organomet. Chem. 1993, 452, 223
.
(5) For our accounts, see: (a) Tanaka, K. Synlett 2007, 1977. (b) Tanaka,
K.; Nishida, G.; Suda, T. J. Synth. Org. Chem. Jpn. 2007, 65, 862.
(6) For selected examples, see: (a) Tanaka, K.; Shirasaka, K. Org. Lett.
2003, 5, 4697. (b) Tanaka, K.; Nishida, G.; Wada, A.; Noguchi, K. Angew.
Chem., Int. Ed. 2004, 43, 6510. (c) Tanaka, K.; Toyoda, K.; Wada, A.;
Shirasaka, K.; Hirano, M. Chem. Eur. J. 2005, 11, 1145. (d) Tanaka, K.;
Nishida, G.; Ogino, M.; Hirano, M.; Noguchi, K. Org. Lett. 2005, 7, 3119.
(e) Tanaka, K.; Takeishi, K.; Noguchi, K. J. Am. Chem. Soc. 2006, 128,
4586. (f) Tanaka, K.; Sagae, H.; Toyoda, K.; Noguchi, K.; Hirano, M. J. Am.
Chem. Soc. 2007, 129, 1522. (g) Nishida, G.; Noguchi, K.; Hirano, M.;
Tanaka, K. Angew. Chem., Int. Ed. 2007, 46, 3951. (h) Nishida, G.; Noguchi,
K.; Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2008, 47, 3410.
(7) For examples, see: (a) Tsuchikama, K.; Kuwata, Y.; Shibata, T.
J. Am. Chem. Soc. 2006, 128, 13686. (b) Tanaka, K.; Nishida, G.; Sagae,
H.; Hirano, M. Synlett 2007, 1426. (c) Shibata, T.; Kawachi, A.; Ogawa,
M.; Kuwata, Y.; Tsuchikama, K.; Endo, K. Tetrahedron 2007, 63, 12853.
The present success in the partial intramolecular cross [2
+ 2 + 2] cycloaddition of 1,6-diynes with enol ethers
(8) The reaction of a malonate-linked terminal 1,6-diyne with ketene
acetal 2d (5 equiv) was also examined, but the yield of the desired cross-[2
+ 2 + 2] cycloaddition product was significantly decreased (ca. 30%) due
to the rapid homo-[2 + 2 + 2] cycloaddition of the diyne.
(9) A cationic rhodium(I)/BINAP complex-catalyzed [2 + 2 + 2]
cycloaddition of diynes with alkynyl ethers towards the synthesis of aryl
ethers, see: Clayden, J.; Moran, W. J. Org. Biomol. Chem. 2007, 5, 1028.
2538
Org. Lett., Vol. 10, No. 12, 2008

to react with enol ether 2c in the presence of the same
rhodium catalyst, the reaction of 5a with enol ester 2e
proceeded to give the corresponding trisubstituted benzenes
in 28% yield as a mixture of two regioisomers 6 and 7
(Scheme 4). The reactions of an electron-deficient internal
Table 1. Rh(I)+/rac-BINAP-Catalyzed [2 + 2 + 2]
Cycloaddition of 1,6-Diynes 1 with Enol Ethers 2a
Scheme 4
monoyne, dimethyl acetylenedicarboxylate (8a), with enol
ether 2c and enol ester 2e were also examined, but both 2c
and 2e failed to react with 8a in the presence of the
[Rh(cod)2]BF4/rac-BINAP catalyst.4 On the other hand, we
have already reported that two molecules of terminal
monoyne 5 react with one molecule of dialkyl acetylenedi-
carboxylate 8 in the presence of the [Rh(cod)2]BF4/
H8-BINAP catalyst to give the corresponding tetrasubstituted
benzene in high yield with high regioselectivity.6a,c
Because enol ester 2e showed no reactivity to electron-
deficient internal monoyne 8a and moderate reactivity to
terminal monoyne 5a, cross [2 + 2 + 2] cycloaddition of
2e, 8a, and 1-dodecyne (5b) was investigated in the
presence of the [Rh(cod)2]BF4/rac-BINAP catalyst.10,11
We were pleased to find that the desired three-component
coupling proceeded at room temperature to give the corre-
sponding tetrasubstituted benzene 9abe in good yield with
perfect regioselectivity (Table 2, entry 1). Thus, we explored
the scope of this process as shown in Table 2. With respect
to terminal monoynes, alkyl- (5b, entry 1), chloroalkyl- (5a,
entry 3), benzyl- (5c, entry 4), phenyl- (5d, entry 5), and
trimethylsilyl-substituted (5e, entry 6) terminal monoynes
could participate in this reaction to give the corresponding
tetrasubstituted benzenes in moderate to good yields with
perfect regioselectivity. Not only dimethyl (8a, entry 1) but
a Reactions were conducted using [Rh(cod)2]BF4 (0.015 mmol, 5 mol
%), rac-BINAP (0.015 mmol, 5 mol %), 1 (0.30 mmol), 2 (1.50 mmol, 5
equiv), and CH2Cl2 (2.0 mL) at rt for 3 h. b Isolated yield. c For 16 h. d 2d:
1.1 equiv. e At 80 °C in (CH2Cl)2. f 2c: 25 equiv.
(10) For examples of transition-metal-catalyzed intermolecular three-
component cocyclotrimerization, see: (a) Mori, N.; Ikeda, S.; Sato, Y. J. Am.
Chem. Soc. 1999, 121, 2722. (b) Mori, N.; Ikeda, S.; Odashima, K. Chem.
Commun. 2001, 181. (c) Chouraqui, G.; Petit, M.; Aubert, C.; Malacria,
M. Org. Lett. 2004, 6, 1519. (d) Yamamoto, Y.; Ishii, J.; Nishiyama, H.;
Itoh, K. J. Am. Chem. Soc. 2004, 126, 3712. (e) Ura, Y.; Sato, Y.; Tsujita,
H.; Kondo, T.; Imachi, M.; Mitsudo, T. J. Mol. Catal. A. 2005, 239, 166.
(f) Deng, L.; Giessert, A. J.; Gerlitz, O. O.; Dai, X.; Diver, S. T.; Davies,
H. M. L. J. Am. Chem. Soc. 2005, 127, 1342. (g) Yamamoto, Y.; Ishii, J.;
Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2005, 127, 9625. (h) Komagawa,
Scheme 3
S.; Saito, S. Angew. Chem., Int. Ed. 2006, 45, 2446
.
(11) For examples of intermolecular three-component cocyclotrimer-
ization using stoichiometric transition-metal complexes, see: (a) Wakatsuki,
Y.; Aoki, K.; Yamazaki, H. J. Am. Chem. Soc. 1979, 101, 1123. (b)
Takahashi, T.; Kotora, M.; Xi, Z. J. Chem. Soc., Chem. Commun. 1995,
361. (c) Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima, K.; Kotora,
M. J. Am. Chem. Soc. 1998, 120, 1672. (d) Takahashi, T.; Tsai, F.-Y.; Li,
Y.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 1999, 121, 11093. (e)
Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2001, 123, 7925. (f)
Takahashi, T.; Tsai, F.-Y.; Li, Y.; Wang, H.; Kondo, Y.; Yamanaka, M.;
Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 2002, 124, 5059. (g) Tanaka,
R.; Nakano, Y.; Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2002,
prompted our investigation into a complete intermolecular
cross [2 + 2 + 2] cycloaddition of monoynes with enol
ethers. Interestingly, although terminal monoyne 5a failed
124, 9682
.
Org. Lett., Vol. 10, No. 12, 2008
2539

Scheme 5
Table 2. Rh(I)+/rac-BINAP-Catalyzed [2 + 2 + 2]
Cycloaddition of Two Different Monoynes 8 and 5 with Enol
Esters 2a
entry
8 (E)
5 (R1)
2 (R2)
9
yieldb (%)
1
2
3
4
5
6
8a (CO2Me) 5b (n-C10H21
8b (CO2t-Bu) 5b (n-C10H21
8a (CO2Me) 5a [Cl(CH2)3] 2e (Me) 9aae
8a (CO2Me) 5c (Bn)
8a (CO2Me) 5d (Ph)
8a (CO2Me) 5e (Me3Si)
8a (CO2Me) 5e (Me3Si)
8a (CO2Me) 5e (Me3Si)
8a (CO2Me) 5b (n-C10H21
8a (CO2Me) 5e (Me3Si)
)
)
2e (Me) 9abe
2e (Me) 9bbe
69
66
41
44
51
73
60
63
49
84
2e (Me) 9ace
2e (Me) 9ade
2e (Me) 9aee
2e (Me) 9aee
2e (Me) 9aee
2b (H) 9abb
2b (H) 9aeb
7c
8d
9
in good yield,12 chemoselectivity of a [2 + 2 + 2]
cycloaddition of commercially available 1-cyanovinyl acetate
(10) with 1,6-diyne 1a is of interest. Like acrylonitrile, the
cyano group of 10 selectively reacted with 1a to give bicyclic
2-(1-acetoxyvinyl)pyridine 11 in high yield (Scheme 6).
)
10
a [Rh(cod)2]BF4 (0.030 mmol), rac-BINAP (0.030 mmol), 8 (0.30
mmol), 5 (0.33 mmol), 2 (1.50 mmol), and CH2Cl2 (2.0 mL) were used.
b Isolated yield. c 2e: 1.1 equiv. d Catalyst: 5 mol %.
also di-tert-butyl acetylenedicarboxylate (8b, entry 2) could
be employed for this reaction. Furthermore, the use of vinyl
acetate (2b) furnished the corresponding trisubstituted ben-
zenes in good yields with perfect regioselectivity (entries 9
and 10). Although the yield of the desired product decreased,
the reaction could be carried out using 1.1 equiv of enol
ester 2e (entry 7) or 5 mol % of the rhodium catalyst
(entry 8).
Scheme 6
A possible mechanism for the present chemo- and regi-
oselective cross [2 + 2 + 2] cycloaddition of two different
monoynes with enol esters is shown in Scheme 5. Terminal
monoyne 5 and electron-deficient internal monoyne 8 react
with rhodium to form rhodacyclopentadiene E due to the
steric repulsion between R1 and the BINAP ligand. Coor-
dination of enol ester 2b or 2e followed by regioselective
insertion forms intermediate F, which is stabilized by
coordination of the carbonyl groups to the cationic rhodium.
Reductive elimination of rhodium furnishes substituted
benzene 9 and acetic acid.
Future studies will focus on the further application of these
catalyses to the convenient synthesis of a wide variety of
aromatic compounds.
Acknowledgment. This work was partly supported by a
Grant-in-Aid for Scientific Research [Nos. 19350046 and
19028015 (Chemistry of Concerto Catalysis)] from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan.
As our previous report demonstrated that a chemoselective
[2 + 2 + 2] cycloaddition of the cyano group of acrylonitrile
with a 1,6-diyne proceeded to give a bicyclic 2-vinylpyridine
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.
(12) Tanaka, K.; Suzuki, N.; Nishida, G. Eur. J. Org. Chem. 2006, 3917.
OL800813G
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