1186
LETTERS
SYNLETT
conducted so far range between 65 and 75%. Although the reaction time
was slightly longer it appears as if Pd(Po-Tol3)2Cl2 was also more
reactive than Pd(PPh3)2Cl2. These findings are in accord with recent
suggestions about the more readily formed reactive intermediate
‘Pd(Po-Tol3)’.16
(6) Chadwick, D. J.; Chambers, J.; Meakins, G. D.; Snowden, R. L. J.
Chem. Soc., Perkin Trans. 1 1973, 1766-1773.
(7) Diederich, F.; Stang, P. J., Eds. Metal-catalyzed Cross-coupling
Reactions; Wiley-VCH: Weinheim, 1998.
(8) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467-4470.
SnMe4
(9) Bach, T.; Krüger, L. Tetrahedron Lett. 1998, 39, 1729-1732.
[Pd(Po-Tol3)2Cl2]
Br
(DMA)
(10) Review: Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117-
2188.
70%
COOMe
COOMe
O
O
(11) Review: Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React.
1997, 50, 1-652.
2b
3
(12) Representative procedure: 2 mmol of ester 1 (568 mg) and 0.08
mmol of Pd(PPh3)2Cl2 (56 mg) were dissolved in 8 ml of THF at
room temperature. A solution of 4 mmol of 2-furylzinc chloride,
prepared by metalation of 4 mmol of furan (272 mg) with n-
butyllithium (4 mmol, 2.2 ml of a 1.8 M solution) and
transmetalation with ZnCl2 (6 mmol, 818 mg), in 8 ml of THF
was added via syringe. The mixture was stirred at room
temperature for 16 h and subsequently quenched with a saturated
aqueous solution of NH4Cl. After extraction with ether the
organic layers were collected, washed with brine and dried over
MgSO4. After removal of the solvent the residue was purified by
flash chromatography (pentane/t-butylmethyl ether = 98:2) to
yield 411 mg of compound 2h (76%). 1H-NMR (CDCl3, 200
MHz): δ = 3.85 (s, 3 H), 6.48 (dd, 3J = 3.5 Hz, 3J = 1.7 Hz, 1 H),
7.01 (d, 3J = 3.5 Hz, 1 H), 7.19 (s, 1 H), 7.50 (d, 3J = 1.7 Hz, 1 H).
NaOH
(H2O)
Cu, ∆T
(quinoline)
70%
91%
COOH
O
O
4
5
Scheme 3
As an application of the regioselective cross-coupling we have
completed a short synthesis of rosefuran (5).17 Saponification of the
ester 3 gave the free carboxylic acid 4 which was thermally
decarboxylated to yield the desired target compound.18,19
In summary, sequential Pd(0)-catalyzed coupling reactions on the title
compound 1 can lead to a variety of 2,3,5-tri- and 2,3-disubstituted
furans in good yields. The wide selection of organometallic reagents
which can be sucessfully employed and the fact that many functional
groups are tolerated in the course of the cross-coupling are beneficial for
synthetic applications some of which are currently being studied in our
laboratory.
(13) Amatore, C.; Broeker, G.; Jutand, A.; Khalil, F. J. Am. Chem. Soc.
1997, 119, 5176-5185 and refs. cited therein.
(14) Kada, R.; Knoppová, V.; Kovác, J.; Cepec, P. Coll. Czech. Chem.
Commun. 1984, 49, 984-991.
(15) Representative procedure: 2 mmol of compound 2b (546 mg), 4
mmol of tetramethylstannane (720 mg, 550 µl) and 0.1 mmol of
Pd(Po-Tol3)2Cl2 (70 mg) were dissolved in 10 ml of DMA and
heated to 90 °C for 16 h. – CAUTION: Tetramethylstannane is
very toxic by inhalation, in contact with skin and if swallowed.
Appropriate safety protection and utmost care is required while
handling this compound. – The mixture was cooled to room
temperature and subsequently quenched with a saturated aqueous
solution of NH4Cl. After extraction with ether the organic layers
were collected, washed with brine and dried over MgSO4. The
solvent was distilled in vacuo and the residue was purified by
flash chromatography (pentane/t-butylmethyl ether = 90:10) to
yield 290 mg of compound 3 (70%). 1H-NMR (CDCl3, 200 MHz):
δ = 1.69 (d, 4J = 1.5 Hz, 6 H), 1.96 (s, 3 H), 3.32 (d, 3J = 7.2 Hz, 2
H), 3.83 (s, 3 H), 5.23 (tsept, 3J = 7.2 Hz, 4J = 1.5 Hz, 1 H), 6.94
(s, 1 H).
Acknowledgements. This work was generously supported by the
Deutsche Forschungsgemeinschaft (Ba 1372/5-1 and Graduiertenkolleg
'Metallorganische Chemie'), and by the Fonds der Chemischen
Industrie. We thank the Degussa AG for a gift of chemicals. Thanks are
also due to Prof. Dr. P. Knochel and his group for helpful discussions.
References and Notes
(1) Rodríguez, A. D.; Shi, J-G.; Huang, S. D. J. Org. Chem. 1998, 63,
4425-4432 and refs. cited therein.
(2) Glass, R. L.; Krick, T. P.; Sand, D. M.; Rahn, C. H.; Schlenk, H.
Lipids 1975, 10, 695-702. Hannemann, K.; Puchta, V.; Simon, E.;
Ziegler, H.; Ziegler, G.; Spiteller, G. Lipids 1989, 24, 296-298 and
refs. cited therein.
(16) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969-
5970. Hartwig, J. F. Synlett 1997, 329-340.
(3) Ochi, M.; Yamada, K.; Kawakami, H.; Tatsukawa, A.; Kotsuki,
H., Shibata, K. Tetrahedron Lett. 1992, 33, 7531-7534.
(17) Büchi, G.; sz. Kovats, E.; Enggist, P.; Uhde, G. J. Org. Chem.
1968, 33, 1227-1229.
(4) Subba Rao, G. S. R.; Ravindranath, B.; Sashi Kumar, V. P.
Phytochemistry 1984, 23, 399-401 and refs. cited therein.
(18) When comparing this route with other ways to 2,3-disubstituted
furans which start from 2,3-dibromofuran, e.g. the regioselective
halogen-metal exchange,19 one should note that 2,3-dibromofuran
is prepared from ester 1.
(5) Reviews: Eberbach, W. in Houben-Weyl, 4th ed., Vol. E6a, part 1;
Kreher, R. P., Ed.; Thieme: Stuttgart, 1994; pp 16-185d. Sargent,
M. V.; Dean, F. M. in Compr. Heterocycl. Chem., Vol. 4; Katritzky,
A. R., Ed.; Pergamon: Oxford, 1984; pp. 599-656. Dean, F. M.
Adv. Heterocycl. Chem. 1982, 30, 167-238, ibid. 1982, 31, 237-
344.
(19) Zaluski, M. C.; Robba, M.; Bonhomme, M. Bull. Soc. Chim. Fr.
1970, 1838-1846. Ly, N. D.; Schlosser, M. Helv. Chim. Acta 1977,
60, 2085-2088.