7160
J. Am. Chem. Soc. 1999, 121, 7160-7161
compounds as substrates, since these would be expected to be
more reactive than simple carbonyl compounds. As a result, we
found that reaction 1 can be realized by the use of R-keto esters
as a substrate and Ru3(CO)12 as the catalyst. The reaction of
methyl benzoylformate (1) (2 mmol) with ethylene (initial pressure
3 atm at 25 °C in a 50-mL stainless steel autoclave) at 5 atm of
CO (initial pressure at 25 °C) at 160 °C in toluene (6 mL) in the
presence of Ru3(CO)12 (0.05 mmol) for 20 h gave tetrahydro-5-
oxo-2-phenyl-2-furancarboxylic acid methyl ester (2)6 in 23%
isolated yield, based on 1, along with 75% of 1 being recovered.
A variety of transition-metal complexes were examined for their
ability to catalyze the coupling reaction, and none of these
catalysts, which included Fe3(CO)12, Co2(CO)8, Rh4(CO)12, Ir4-
(CO)12, Os3(CO)12, [RuCl2(CO)3]2, RuCl2(PPh3)3, and CpRuCl-
(PPh3)2, were found to be active. The use of PPh3 (0.15 mmol)
as an additive in the Ru3(CO)12-catalyzed reaction of 1 increased
the yield to 61%. We then examined a variety of phosphines as
additives and found that the yields are relatively parallel to the
pKa values. Thus, the lower the pKa, the higher the yield; (PBu3
25%), (P(4-MeOC6H4)3 59%), (PPh3 61%), (P(4-FC6H4)3 64%),
(P(4-ClC6H4)3 72%), (P(4-CF3C6H4)3 94%). Finally, we found that
P(4-CF3C6H4)3 is the additive of choice (reaction 2).
Ruthenium Carbonyl-Catalyzed [2 + 2 + 1]-
Cycloaddition of Ketones, Olefins, and Carbon
Monoxide, Leading to Functionalized
γ-Butyrolactones
Naoto Chatani, Mamoru Tobisu, Taku Asaumi,
Yoshiya Fukumoto, and Shinji Murai*
Department of Applied Chemistry, Faculty of Engineering
Osaka UniVersity, Suita, Osaka 565-0871, Japan
ReceiVed April 19, 1999
Transition-metal-catalyzed cycloaddition reactions using carbon
monoxide as a one-carbon unit represent a useful method for the
synthesis of carbocyclic and heterocyclic carbonyl compounds
from acyclic building blocks.1,2 A three component [2 + 2 +
1]cycloaddition, which incorporates the ketone or the aldehyde
π-bond, the alkene π-bond, and the carbon atom of CO into the
five-membered ring represents an attractive route to γ-butyro-
lactones (reaction 1).3 However, as of 1996, such an approach
had not been reported. Crowe reported that the exposure of
titanium metallacycles, obtained by the reaction of a stoichiometric
amount of Cp2Ti(PMe3)2 with olefinic aldehydes (e.g., 5-hexenal),
with CO followed by an oxidatively induced reductive elimination
gives γ-lactones.4 Buchwald independently reported a similar
transformation in which γ-lactones are formed when the reaction
of Cp2Ti(PMe3)2 with tethered olefinic ketones is carried out in
an atmosphere of CO at 70 °C, and found that the transformation
can be catalytic, for the case of o-allylacetophenone as a substrate.5
We wish to report the use of Ru3(CO)12 as a catalyst for the
cyclocoupling of ketones (or aldehydes), olefins, and CO leading
to functionalized γ-butyrolactones. The system described here
represents the first example of the catalytic intermolecular [2 +
2 + 1] cyclocoupling of ketones (or aldehydes), olefins, and CO
(reaction 1).
A variety of ketones containing a carbonyl group at the
R-position were examined in the reaction with CO and ethylene,
as shown in Table 1. In all cases, the reactions were clean, and
no byproducts were detected by GC and TLC, even in the crude
reaction mixture. It was found that R-diketones, such as 5, 7,
and 9, undergo a cyclocoupling reaction to afford the correspond-
ing lactones, 6, 8, and 10, respectively. Similar to the case of
R-keto esters, the addition of P(4-CF3C6H4)3 gave higher yields
than were obtained in the absence of the phosphine for the reaction
of R-diketones.
The issue of whether the carbonyl group, adjacent to the ketone,
could be replaced with another electron-withdrawing group is of
interest. However, the reaction of benzoylcyanide and pentafluo-
roacetophenone did not proceed. In addition, the reaction of
benzophenone, acetophenone, 3-acetylpyridine, 2-pyridylacetone,
2-acetylpyrrole, 2-acetylfuran, and 2-acetylthiophene did not take
place. Interestingly and importantly, however, a CdN unit
adjacent to the ketone worked well. The reaction of 2-acetylpy-
ridine (11) with ethylene at 5 atm of CO at 140 °C in toluene in
the presence of Ru3(CO)12 for 20 h gave 4-methyl-4-(2-pyridyl)-
γ-butyrolactone (12) in 92% isolated yield. Curiously, the addition
of phosphine is not required in the reaction of 11. In contrast,
the addition of PPh3 had a dramatic effect on the reaction of
pyridinecarbaldehyde (13). A heteroaromatic ketone containing
a thiazole ring, as in 15, gave the corresponding lactone 16 in
nearly quantitative yield. The reaction is not limited to heteroaro-
matic ketones. An oxazoline system, such as 17 also serves as a
good substrate. The acceleration effect of the heterocyclic moiety
on this catalytic reaction can be attributed to its coordinating
ability.
In the past, we examined the reactivities of a wide variety of
aldehydes and ketones in the hope of carrying out the cyclocou-
pling reaction shown in reaction 1, but our experiments were
unsuccessful. Finally, we explored the use of R-dicarbonyl
(1) For reviews on transition-metal-catalyzed cycloaddition reactions, see:
Schore, N. E. Chem. ReV. 1988, 88, 1081. Lautens, M.; Klute, W.; Tam, W.
Chem. ReV. 1996, 96, 49. Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R.
J. Chem. ReV. 1996, 96, 635.
(2) For recent papers on [2 + 2 + 1] cycloaddition reactions using CO,
see: Chatani, N.; Morimoto, T.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc.
1998, 120, 5335. Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998,
249. Jeong, N.; Lee, S.; Sung, B. K. Organometallics 1998, 17, 3642. Kim,
J. W.; Chung, Y. K. Synthesis 1998, 142. Sugihara, T.; Yamaguchi, M. J.
Am. Chem. Soc. 1998, 120, 10782. For a recent paper on [4 + 1] cycloaddition
reactions using CO, see: Morimoto, T.; Chatani, N.; Murai, S. J. Am. Chem.
Soc. 1999, 121, 1758. Murakami, M.; Itami, K.; Ito, Y. J. Am. Chem. Soc.
1999, 121, 4130. For a recent paper on [4 + 4 + 1] cycloaddition reactions
using CO, see: Murakami, M.; Itami, K.; Ito, Y. Angew. Chem., Int. Ed. 1998,
37, 3418.
(3) γ-Butyrolactones are important precursors for the preparation of
R-methylene- γ-butyrolactones or butenolides which are found in the skeleton
of various natural products. For reviews, see: Hoffmann, H. M. R.; Rabe, J.
Angew. Chem., Int. Ed. Engl. 1985, 24, 94. Petragnani, N.; Ferraz, H. M. C.;
Silva, G. V. J. Syntheis 1986, 157. Ito, M. Pure Appl. Chem. 1991, 63, 13.
(4) Crowe, W. E.; Vu, A. T. J. Am. Chem. Soc. 1996, 118, 1557.
(5) Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 5818. Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L. J. Am. Chem.
Soc. 1997, 119, 4424.
Although the mechanism for this reaction is not clear, the
coordination of 1-aza-4-oxo-1-diene (NdC-CdO) in N-hetero-
(6) All new compounds were characterized by NMR, IR, mass spectral
data, and by elemental analyses or high-resolution mass spectra. See Supporting
Information.
10.1021/ja991223w CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/16/1999