Palladium-catalyzed carbonylation of yne esters Leading to γ-alkylidene α,β-unsaturated γ-lactones

Article abstract of DOI:10.1021/ol0514956

(Chemical Equation Presented) The reaction of yne esters with carbon monoxide (1 atm) in the presence of palladium complexes gives bicyclic unsaturated lactone derivatives in good to high yields. The 2-pyridinyloxy group is a good leaving group among leav

Full text of DOI:10.1021/ol0514956

ORGANIC
LETTERS
2005
Vol. 7, No. 20
4385-4387
Palladium-Catalyzed Carbonylation of
Yne Esters Leading to -Alkylidene
γ
r,â-Unsaturated γ-Lactones
Yasuyuki Harada, Yoshiya Fukumoto, and Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity,
Suita, Osaka 565-0871, Japan
chatani@chem.eng.osaka-u.ac.jp
Received June 27, 2005
ABSTRACT
The reaction of yne esters with carbon monoxide (1 atm) in the presence of palladium complexes gives bicyclic unsaturated lactone derivatives
in good to high yields. The 2-pyridinyloxy group is a good leaving group among leaving groups examined.
Unsaturated lactones are important subunits in naturally
occurring as well as biologically active compounds.1-3 While
Scheme 1
numerous methods have been developed for the synthesis
of such skeletons, cyclocarbonylation continues to be a
method of choice for the construction of lactone rings.3 A
variety of substrates, such as alkynols,4 allenyl alcohols,5 halo
alkenes,6 R-keto alkynes,7 and â-iodo enones,8 have been
used thus far in the preparation of unsaturated lactones via
cyclocarbonylation.3 We previously reported on the Ru3-
(CO)12-catalyzed cyclocarbonylation of 1,6-alkynals leading
to R,â-unsaturated bicyclic lactones.9 One of the proposed
mechanisms for this reaction is shown in Scheme 1. The
(1) Negishi, E.; Kotora, M. Tetrahedron 1997, 53, 6707-6738.
(2) Rao, Y. S. Chem. ReV. 1976, 76, 625-694. Ley, S. V.; Cox, L. R.;
Meek, G. Chem. ReV. 1996, 96, 423-442. Collins, I. J. Chem. Soc., Perkin
Trans. 1 1998, 1869-1888. Collins, I. J. Chem. Soc., Perkin Trans. 1 1999,
1377-1395.
(3) For a review of cyclocarbonylation reactions leading to unsaturated
lactones, see: El Ali, B.; Alper, H. Synlett 2000, 161-171. Vizer, S. S.;
Yerzhanov, K. B.; Al Quntar, A. A. A.; Dembitsky, V. M. Tetrahedron
2004, 60, 5499-5538.
(4) Norton, J. R.; Shenton, K. E.; Schwartz, J. Tetrahedron Lett. 1975,
16, 51-54. El Ali, B.; Alper, H. J. J. Org. Chem. 1991, 56, 5357-5360.
oxidative addition of an aldehyde C-H bond to ruthenium
gives acyl ruthenium species A, which undergoes carbo-
metalation, CO insertion, cyclization, and a reductive
elimination of D to afford the final product. If X, such as a
halide or pseudohalide, is the leaving group, the final step,
Tezuka, K.; Ishizaki, Y.; Inoue, Y. J. Mol. Catal. A 1998, 129, 199-206.
(5) Yoneda, E.; Zhang, S.-W.; Zhou, D.-Y.; Onitsuka, K.; Takahashi, S.
J. Org. Chem. 2003, 68, 8571-8576.
(6) Shimoyama, I.; Zhang, Y.; Wu, G.; Negishi, E. Tetrahedron Lett.
1990, 31, 2841-2844. Wu, G.; Shimoyama, I.; Negishi, E. J. Org. Chem.
1991, 56, 6506-6507.
(7) Van den Hoven, B.; El Ali, B.; Alper, H. J. Org. Chem. 2000, 65,
4131-4137.
(8) Cope´ret, C.; Sugihara, T.; Wu, G.; Shinoyama, L.; Negishi, E. J.
Am. Chem. Soc. 1995, 117, 3422-3431.
(9) Chatani, N.; Morimoto, T.; Fukumoto, Y.; Murai, S. J. Am. Chem.
Soc. 1998, 120, 5335-5336.
10.1021/ol0514956 CCC: $30.25
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Published on Web 08/31/2005

Scheme 2
Table 1. Cyclocarbonylation of Yne Esters
d, did not give satisfactory results.11 A thioester 1e was also
not a suitable substrate for the present carbonylation (23%
yield), although catalytic reactions involving the oxidative
addition of thioesters to palladium complexes are well-
known.12 We recently found that the 2-pyridinyloxy group
is a good leaving group for Pd-catalyzed cross-coupling
reactions of pyridin-2-yl esters with arylboronic acids leading
to aromatic ketones.13 We then prepared the yne ester 1f.
As expected, the reaction of 1f at 120 °C at 1 atm led to
dramatically improved yield of 2 of 84% yield. The use of
higher CO pressures, such as 5 atm decreased the product
yield to 71%. The use of a CO balloon gave 2 in 23% yield,
indicating that a slight positive CO pressure is necessary for
the reaction to proceed efficiently.
a Reaction conditions: substrate (0.5 mmol), [(η3-C3H5)PdCl]2 (0.025
mmol), PPh3 (0.075 mmol), Cy2NMe (0.5 mmol), toluene (2.5 mL) at 120
°C under CO (1 atm) for 20 h.
reductive elimination, does not proceed,10 but instead a
â-hydride elimination leading to unsaturated lactones would
be expected to occur. Herein, we report on the successful
use of this approach for the construction of unsaturated, fused
bicyclic γ-lactones via the Pd-catalyzed cyclocarbonylation
of hex-5-ynoic acid pyridin-2-yl esters (X ) a 2-pyridyloxy
group).
An intramolecular acetylene-acid chloride (X ) Cl) was
the first choice for a representative substrate to examine
because acid chlorides are well-known to generate acyl
complexes related to A via oxidative addition. Although
extensive studies were carried out using Ru3(CO)12 as the
catalyst, the expected product was not formed. However, the
use of a palladium catalyst resulted in the formation of the
expected unsaturated lactones. The reaction of 3,3-dimethyl-
oct-5-ynoyl chloride (1a) with CO (1 atm) in the presence
of a palladium catalyst gave 3-ethyl-5,5-dimethyl-4,5-dihy-
drocyclopenta[b]furan-2-one (2) in 38% yield. Other leaving
groups, which have recently been developed for Pd-catalyzed
cross coupling reactions with arylboronic acids, as in 1b-
Results for the carbonylation of various pyridinyl esters
are shown in Table 1. Substrates having alkyl-, aryl-, and
heteroaryl groups on the acetylenic carbon gave the corre-
sponding unsaturated lactones in good to high yields. Certain
additional functional groups, such as methoxy and nitro, are
compatible for the present reaction. The presence of a
geminal group at the tether is not essential for the reaction
to proceed. The formation of a cyclohexyl-fused lactone
failed to proceed smoothly.
The reaction appears to proceed in a manner consistent
with the working hypothesis proposed in Scheme 1. A
pyridinyl ester oxidatively adds to a palladium complex to
give an acyl palladium complex A.14 The complex A
undergoes carbometalation to give the vinyl palladium
complex B, in which CO is inserted to give an acyl complex
C. The cyclization of C gives the π-allyl palladium complex
(11) (a) For a recent review, see: Azpf, A. Angew. Chem., Int. Ed. 2003,
42, 5394-5399. (b) See also: Zhang, Y.; Rovis, T. J. Am. Chem. Soc.
2004, 126, 15964-15965.
(12) For a recent paper, see: Fausett, B. W.; Liebeskind, L. S. J. Org.
Chem. 2005, 70, 4851-4853. See also: Fukuyama, T.; Tokuyama, H.
Aldrichim. Acta 2004, 37, 87-96.
(10) Roy, A. H.; Hartwig, J. J. Am. Chem. Soc. 2003, 125, 13944-13945.
Roy, A. H.; Hartwig, J. F. Organometallics 2004, 23, 1533-1541.
(13) Tatamidani, H.; Kakiuchi, F.; Chatani, N. Org. Lett. 2004, 6, 3597-
3599.
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Org. Lett., Vol. 7, No. 20, 2005

D, which then undergoes a â-hydride elimination to give
the final product.15 Based on the proposed mechanism, a
catalytic amount of amine is sufficient for the reaction to
proceed. However, the use of 10 mol % (0.05 mol) of amine
decreased in the product yield to 52% yield. The exact reason
for why the 2-pyridinyloxy group is the leaving group of
choice is currently not clear. 2-Hydroxypyridine was not able
to be isolated from the reaction mixture. However, when
3-hexyne was added to a reaction of 1f under the reaction
conditions shown in Scheme 2, the hydroesterification of
2-hydroxypyridine also took place to give 12 in 56% yield,
along with 2 in 80% yield, indicating that 2-hydroxypyridine
was formed and was sufficiently stable to be trapped (Scheme
3).16,17
Scheme 3
applications of this method for generating acyl complexes
from pyridin-2-yl esters to new catalytic reactions are under
study.
In summary, we demonstrate the Pd-catalyzed cyclocar-
bonylation of yne esters leading to the formation of γ-alkyl-
idene R,â-unsaturated γ-lactones. The 2-pyridinyloxy group
was found to be a good leaving group for generating acyl
palladium complexes via oxidative addition compared with
other leaving groups in this cyclocarbonylation.18 The
Supporting Information Available: Experimental pro-
cedures and compound characterization. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL0514956
(16) When twice the amount of palladium complex was used (0.05
mmol), 2 and 13 were obtained in 97% and 74% yields, respectively.
(17) Kushino, Y.; Itoh, K.; Miura, M.; Nomura, M. J. Mol. Catal. 1994,
89, 151-158.
(18) For papers on pyridinyl esters, see: Mukaiyama, T. Chem. Lett.
1980, 709-712. Mukaiyama, T. Chem. Lett. 1980, 905-906. Mukaiyama,
T. Chem. Lett. 1981, 531-534. See also refs 11b and 13.
(14) For a stoichiometric reaction of 2-pyridinylpropionate with an
iridium complex, see: Grotjahn, D. B.; Lo, H. C.; Groy, T. L. Acta
Crystallogr. A 1996, 516-519.
(15) A similar mechanism was proposed for Pd and Rh catalysis. See
refs 7 and 8. Kamitani, A.; Chatani, N.; Murai, S. Angew. Chem., Int. Ed.
2003, 42, 1397-1399.
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