Rhenium-catalyzed insertion of terminal acetylenes into a C-H bond of active methylene compounds

Article abstract of DOI:10.1021/ol0515208

(Chemical Equation Presented) A rhenium complex, [ReBr(CO) ₃(thf)]₂, catalyzed the intermolecular reactions of 1,3-dicarbonyl compounds with terminal acetylenes and gave the corresponding alkenyl derivatives in excellent yields. Thes

Full text of DOI:10.1021/ol0515208

ORGANIC
LETTERS
2005
Vol. 7, No. 22
4823-4825
Rhenium-Catalyzed Insertion of Terminal
Acetylenes into a C H Bond of Active
−
Methylene Compounds
Yoichiro Kuninobu,* Atsushi Kawata, and Kazuhiko Takai*
DiVision of Chemistry and Biochemistry, Graduate School of Natural Science and
Technology, Okayama UniVersity, Tsushima, Okayama 700-8530, Japan
kuninobu@cc.okayama-u.ac.jp; ktakai@cc.okayama-u.ac.jp
Received June 29, 2005
ABSTRACT
A rhenium complex, [ReBr(CO)3(thf)]2, catalyzed the intermolecular reactions of 1,3-dicarbonyl compounds with terminal acetylenes and gave
the corresponding alkenyl derivatives in excellent yields. These reactions could apply to an intramolecular version and gave the corresponding
cyclic compounds quantitatively.
Carbon-carbon bond formation reactions via enolate anions
or enols are fundamental transformations.1 There have been
many reports on the transition metal-mediated reactions of
enolate anions or enols with olefins or acetylenes.2 Because
the formation of enolate anions or enols and/or their reactions
with acetylenes usually requires harsh conditions,3 reactions
that do not require this step have been desired. Recently,
metal-catalyzed addition reactions of active methylene
compounds with terminal acetylenes under mild conditions
without the preparation step of enolate or enol have been
reported. For example, gold4 and nickel/ytterbium catalysts5
have been used for intramolecular cyclization of δ- and
ꢀ-acetylenic 1,3-dicarbonyl compounds, respectively. In
contrast, to our knowledge there have only been a few reports
on an intermolecular version of the reaction in which the
indium-catalyzed transformation could be carried out with
or without the addition of bases.6
(1) Caine, D. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, pp 1-63.
(2) (a) Schulte, K. E.; Ru¨cker, G.; Feldkamp, J. Chem. Ber. 1972, 105,
24. (b) Bertrand, M. T.; Courtois, G.; Miginiac, L. Tetrahedron Lett. 1974,
15, 1945. (c) Bertrand, M. T.; Courtois, G.; Miginiac, L. Tetrahedron Lett.
1975, 16, 3147. (d) Hegedus, L. S.; Williams, R. E.; McGuire, M. A.;
Hayashi, T. J. Am. Chem. Soc. 1980, 102, 4973. (e) Balme, G.; Bouyssi,
D.; Faure, R.; Gore, J.; Van Hemelryck, B. Tetrahedron 1992, 48, 3891.
(f) Badanyan, Sh. O.; Chobanyan, Zh. A.; Tirakyan, M. R.; Danielyan, A.
O. Russ. J. Org. Chem. 1997, 33, 117. (g) Nakamura, E.; Kubota, K.; Sakata,
G. J. Am. Chem. Soc. 1997, 119, 5457. (h) Kubota, K.; Nakamura, E. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2491. (i) Nakamura, E.; Kubota, K.
Tetrahedron Lett. 1997, 38, 7099. (j) McDonald, F. E.; Olson, T. C.
Tetrahedron Lett. 1997, 38, 7691. (k) Lorthiois, E.; Marek, I.; Normant, J.
F. J. Org. Chem. 1998, 63, 566. (l) Lorthiois, E.; Marek, I.; Normant, J. F.
J. Org. Chem. 1998, 63, 2442. (m) Nakamura, E.; Hara, K.; Sakata, G.;
Nakamura, E. Org. Lett. 1999, 1, 1505. (n) Kitagawa, O.; Suzuki, T.; Inoue,
T.; Watanabe, Y.; Taguchi, T. J. Org. Chem. 1998, 63, 9470. (o) Bouyssi,
D.; Monteiro, N.; Balme, G. Tetrahedron Lett. 1999, 40, 1297. (p) Koradin,
C.; Rodriguez, A.; Knochel, P. Synlett 2000, 1452. (q) Wang, X.; Pei, T.;
Han, X.; Widenhoefer, R. A. Org. Lett. 2003, 5, 2699. (r) Nakamura, M.;
Hatakeyama, T.; Hara, K.; Nakamura, E. J. Am. Chem. Soc. 2003, 125,
6362. (s) Han, X.; Wang, X.; Pei, T.; Widenhoefer, R. A. Chem. Eur. J.
2004, 10, 6333.
In the process of our investigation on the catalytic activities
of rhenium complexes,7,8 we found rhenium-catalyzed in-
(3) Strong acid: (a) Boaventura, M. A.; Drouin, J.; Conia, J. M. Synthesis
1983, 801. UV irradiation: (b) Cruciani, P.; Aubert, C.; Malacria, M.
Tetrahedron Lett. 1994, 35, 6677. (c) Cruciani, P.; Stammler, R.; Aubert,
C.; Malacria, M. J. Org. Chem. 1996, 61, 2699. (d) Renaud, J.-L.; Petit,
M.; Aubert, C.; Malacria, M. Synlett 1997, 931. (e) Renaud, J.-L.; Aubert,
C.; Malacria, M. Tetrahedron 1999, 55, 5113.
(4) (a) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 4526. (b) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D.
Angew. Chem., Int. Ed. 2004, 43, 5350.
(5) Gao, Q.; Zheng, B.-F.; Li, J.-H.; Yang, D. Org. Lett. 2005, 7, 2185.
(6) (a) Nakamura, M.; Endo, K.; Nakamura, E. J. Am. Chem. Soc. 2003,
125, 13002. (b) Nakamura, M.; Endo, K.; Nakamura, E. Org. Lett. 2005,
7, 3279.
(7) (a) Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc., in press.
(b) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.; Takai, K. Submitted for
publication.
10.1021/ol0515208 CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/30/2005

termolecular and intramolecular reactions of active methylene
compounds with terminal acetylenes under mild reaction
conditions.
Treatment of a mixture of pentane-2,4-dione (1.0 equiv)
and phenylacetylene (1.0 equiv) in the presence of a rhenium
catalyst, [ReBr(CO)3(thf)]2, at 50 °C for 24 h under solvent-
free conditions gave 1 quantitatively and regioselectively
(Table 1, entry 1). The product 1 results from the insertion
temperature conditions (90 °C and reflux), the yield of 1
decreased owing to the polymerization of acetylene. When
3-methylpentane-2,4-dione was used as the active methylene
compound, the yield was low (Table 1, entry 2). However,
the reaction proceeded in excellent yield in the case of
2-acetylcyclohexanone (Table 1, entry 3). A â-keto ester,
ethyl 3-oxobutanoate, also reacted with phenylacetylene to
give the corresponding alkenyl derivative in excellent yield
(Table 1, entry 4).9 The reaction of ethyl 2-methyl-3-
oxobutanoate and phenylacetylene gave an alkenyl derivative
5 in 70% yield (Table 1, entry 5). In this case, addition of
dysprosium triflate, Dy(OTf)3, as a co-catalyst improved the
yield markedly (Table 1, entry 6).10 Both ethyl 2-oxocyclo-
hexanecarboxylate and 2-oxocyclopentanecarboxylate could
be used as active methylene compounds, and the correspond-
ing products 6 and 7 were obtained in quantitative yields
(Table 1, entries 7 and 8).11
Table 1. Reaction of 1,3-Diketone or â-Keto Ester with
Phenylacetylene
Next, we examined reactions between several acetylenes
and pentane-2,4-dione (Table 2). As described above, the
Table 2. Reaction of Pentane-2,4-dione with Several
Acetylenes
a Isolated yield. 1H NMR yield is given in parentheses. b Acetylene (3.0
equiv), 60 °C. c The ratio of enol/1,3-diketone was 1:1. d Acetylene (2.0
equiv), 40 °C. e Acetylene (1.1 equiv). f 3-Methylpentane-2,4-dione was used
as a dicarbonyl substrate, acetylene (1.1 equiv).
a Isolated yield. 1H NMR yield is given in parentheses. b Acetylene (1.0
equiv). c Acetylene (2.0 equiv), 40 °C, 48 h. d Acetylene (1.5 equiv), 40
°C. e Acetylene (2.0 equiv), toluene was used as a solvent. f The ratio of
enol/1,3-diketone was 95:5. g Acetylene (1.5 equiv). h Dy(OTf)3 (5.0 mol
%) was used as a co-catalyst, acetylene (1.5 equiv). i Acetylene (1.1 equiv),
40 °C.
reaction of phenylacetylene and pentane-2,4-dione gave the
corresponding alkenyl compound 1 in quantitative yield
(8) For rhenium-catalyzed reactions from other groups, see: (a) Nish-
iyama, Y.; Kakushou, F.; Sonoda, N. Bull. Chem. Soc. Jpn. 2000, 73, 2779.
(b) Hua, R.; Tian, X. J. Org. Chem. 2004, 69, 5782. (c) Jiang, J.-L.; Gao,
F.; Hua, R.; Qiu, X. J. Org. Chem. 2005, 70, 381. (d) Liu, Y.; Hua, R.;
Sun, H.-B.; Qiu, X. Organometallics 2005, 24, 2819. (e) Nishiyama, Y.;
Kakushou, F.; Sonoda, N. Tetrahedron Lett. 2005, 46, 787.
of the terminal acetylene into the C-H bond of the active
methylene compound. In this reaction, a regioisomeric
product generated by C-C bond formation at the terminal
carbon atom of the acetylene was not observed. Under higher
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Org. Lett., Vol. 7, No. 22, 2005

(Table 1, entry 1). By using tert-butylacetylene as a bulky
acetylene, the desired product was formed in 94% yield
(Table 2, entry 1). However, the reaction did not proceed
with trimethylsilylacetylene or an internal acetylene (1-
phenyl-1-propyne). An ether group connected to the terminal
acetylene did not disturb the reaction, and the corresponding
compound 9 was obtained quantitatively (Table 2, entry 2).
The reaction of 1-ethynylcyclohex-1-ene with pentane-2,4-
dione also proceeded in excellent yield (Table 2, entry 3).
Also, the reaction of 1-hexyne with 3-methylpentane-2,4-
dione instead of pentane-2,4-dione gave the corresponding
alkenyl derivative 11 in quantitative yield (Table 2, entry
4).
Scheme 1. Proposed Mechanism of the Catalytic Alkenylation
To elucidate the mechanism of these reactions, we carried
out deuterium labeling experiments (eqs 1 and 2). The
reaction of ethyl 2-oxocyclohexanecarboxylate and deuter-
ated phenylacetylene afforded an alkenyl derivative 12
selectively, in which the deuterium locates anti to the â-keto
ester moiety (eq 1). On the other hand, by the reaction of
deuterated ethyl 2-oxocyclohexanecarboxylate with phenyl-
acetylene, 13 was obtained selectively, with deuterium syn
to the â-keto ester group (eq 2).
2-position, the corresponding enol is obtained as a product
after the isomerization of the olefin moiety.
The reaction can be applied in an intramolecular version,
which is the same transformation as the Conia-ene reaction
(eq 3).12 By heating a â-keto ester bearing a terminal
acetylene moiety at 50 °C for 12 h, the Conia-ene reaction
occurred and the corresponding methylenecyclopentane 14
was obtained in excellent yield.
In summary, we succeeded in the rhenium complex,
[ReBr(CO)3(thf)]2, catalyzed intermolecular nucleophilic
addition of an active methylene compound with a terminal
acetylene under mild reaction conditions. This reaction could
be applied to the intramolecular version (Conia-ene reaction),
and the corresponding cyclic compound could be obtained.
These reactions are the first examples of rhenium-catalyzed
additions of active methylene compounds with terminal acet-
ylenes, and are useful for the synthesis of 2-alkyl-substituted
2-ethenyl-1,3-dicarbonyl compounds under mild conditions.
We are now investigating C-C bond formation reactions
based on the activation of acetylenes with rhenium catalysts.
These deuterium labeling results support the proposed
mechanisms of the addition reactions of active methylene
compounds with terminal acetylenes as shown in Scheme
1. The rhenium catalyst coordinates to a terminal acetylene
and an enol, derived from a 1,3-dicarbonyl compound.5,8b
Nucleophilic addition of the enol to the rhenium-coordinated
acetylene gives an alkenylrhenium(I) intermediate (mecha-
nism A). After protonation, the rhenium catalyst is regener-
ated and a 2-alkenyl-substituted 1,3-dicarbonyl compound
is formed. The other possibility is as follows: Cyclization
of the enol-rhenium(I)-acetylene species give a rhena-
cyclopentene intermediate. Then, â-hydride elimination fol-
lowed by reductive elimination affords a 2-alkenyl-substi-
tuted 1,3-dicarbonyl compound (mechanism B). When the
1,3-dicarbonyl compound does not have a substituent at the
Acknowledgment. Financial support by a Grant-in-Aid
for Scientific Research on Priority Areas (No. 14078219,
“Reaction Control of Dynamic Complexes”) from the
Ministry of Education, Culture, Sports, Science, and Tech-
nology of Japan.
Supporting Information Available: General experimen-
tal procedure and characterization data for alkenyl deriva-
tives. This material is available free of charge via the Internet
at http://pubs.acs.org.
(9) Investigation of solvents: toluene; 22%, THF.; 1%, CH2ClCH2Cl;
45%.
(10) Dy(OTf)3 did not show the promotion activity in the reaction of
1,3-diketone and phenylacetylene (Table 1, entry 2).
(11) The reaction did not proceed by using dimethyl malonate, 1-phenyl-
2-(phenylsulfonyl)ethanone, ethyl 2-cyanoacetate, 3-pentanone and pro-
piophenone.
OL0515208
(12) For a review, see: Conia, J. M.; Le Perchec, P. Synthesis 1975, 1.
Org. Lett., Vol. 7, No. 22, 2005
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