LETTER
Synthesis of Cross-Conjugated Geminal Enediynes
977
(3) Nicolaou, K. C.; Smith, A. L. In Modern Acetylene
Chemistry; Stang, P. J.; Diederich, F., Eds.; VCH:
Weinheim, 1995, 253.
(4) Hird M., Gray G. W., Toyne K. J.; Mol. Cryst. Liq. Cryst.;
1991, 206: 187.
obtained with triethylamine (75%). Diethylamine and di-
isopropylamine furnished the product in lower yields
(60% and 50% yields, respectively). With pyridine, pyrro-
lidine or piperidine, no enediyne was formed.
(5) (a) Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani, H.
A. Synthesis 1997, 373. (b) Petragnani, N. Tellurium in
Organic Synthesis; Academic Press: London, 1994.
(c) Comasseto, J. V.; Barrientos-Astigarraga, R. E.
Aldrichimica Acta 2000, 33, 66.
(6) (a) Barros, S. M.; Dabdoub, M. J.; Dabdoub, V. B.;
Comasseto, J. V. Organometallics 1989, 8, 1661. (b) Tucci,
F. C.; Chieffi, A.; Comasseto, J. V.; Marino, J. P. J. Org.
Chem. 1996, 61, 4975. (c) Dabdoub, M. J.; Dabdoub, V. B.;
Comasseto, J. V.; Petragnani, N. J. Organomet. Chem. 1986,
308, 211. (d) Dabdoub, M. J.; Dabdoub, V. B.; Comasseto,
J. V. Tetrahedron Lett. 1992, 33, 2261. (e) Zeni, G.;
Formiga, H. B.; Comasseto, J. V. Tetrahedron Lett. 2000,
41, 1311. (f) Zeni, G.; Chieffi, A.; Cunha, R. L. O. R.;
Zukerman-Schpector, J.; Stefani, H. A.; Comasseto, J. V.
Organometallics 1999, 18, 803.
We also investigated the influence of the solvent in the
cross-coupling reaction. THF, dichloromethane and ben-
zene, did not give the expected enediynes. In acetonitrile
and N,N-dimethylformamide only a small amount of
cross-coupling product was observed. However, the use
of methanol afforded enediynes in higher yields.
Thus, the optimum conditions for the coupling as de-
scribed in Scheme 2 were found to be the use of PdCl2 (20
mol%), MeOH (5 mL), ketene butyltelluroacetals (1
mmol), the appropriate 1-alkyne (2 mmol) and Et3N (1
mmol) at 25 °C.12 In a next stage, we explored the gener-
ality of our method, extending the coupling reaction to
other 1-alkynes and observing that enediynes 8a–h were
obtained in good yields (Table). The reaction conditions
tolerate the use of functionalities such as hydroxyl and la-
bile acetylenic trimethyl silyl groups.
(7) (a) Silveira, C. C.; Perin, G.; Braga, A. L. Tetrahedron Lett.
1995, 36, 7361. (b) Silveira, C. C.; Perin, G.; Braga, A. L.;
Dabdoub, M. J.; Jacob, R. G. Tetrahedron 1999, 55, 7421.
(8) Dabdoub, M. J.; Cassol, T. M.; Barbosa, S. L. Tetrahedron
Lett. 1996, 37, 831.
(9) Dabdoub, M. J.; Begnini, M. L.; Guerrero, P. G. Jr.
Tetrahedron 1998, 54, 2371.
(10) Braga, A. L.; Zeni, G.; de Andrade, L. H.; Silveira, C. C.
Synlett 1997, 595.
(11) (a) Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40,
4619. (b) Zeni, G.; Menezes, P. H.; Moro, A. V.; Braga, A.
L.; Silveira, C. C.; Stefani, H. A. Synlett 2001, 1473.
(c) Zeni, G.; Panatieri, R. B.; Lissner, E.; Menezes, P. H.;
Braga, A. L.; Stefani, H. A. Org. Lett. 2001, 3, 819.
(d) Zeni, G.; Nogueira, C. W.; Panatieri, R. B.; Silva, D. O.;
Menezes, P. H.; Braga, A. L.; Silveira, C. C.; Stefani, H. A.;
Rocha, J. B. T. Tetrahedron Lett. 2001, 42, 7921. (e)Braga,
A. L.; Zeni, G.; de Andrade, L. H.; Silveira, C. C.; Stefani,
H. A. Synthesis 1998, 39. (f) Braga, A. L.; Emmerich, D. J.;
Silveira, C. C.; Martins, T. L.; Rodrigues, O. E. D. Synlett
2001, 369.
(12) Typical procedure for 8a: To a two-necked 25 mL round-
bottomed flask under argon atmosphere containing PdCl2
(0.035 g, 20 mol%) and dry methanol (5 mL) was added the
ketene butyltelluroacetal 6a (0.470g, 1 mmol). After stirring
the mixture for 15 minutes at room temperature, 1-heptyne
(0.192 g, 2 mmol) and Et3N (0.8 mL) were added. The
reaction was stirred at room temperature for 4 h. After this
time, the solids were filtered under vacuum, to the filtrate
was added brine. The organics were extracted with
dichloromethane (3 25 mL), dried over MgSO4 and
concentrated under vacuum. The residue was purified by
flash silica gel chromatography eluting with hexane; Yield
0.227 g (75%). Selected spectral and analytical data for
8a: 1H NMR (CDCl3, 200 MHz) (ppm): 7.86–7.82(m, 2 H),
7.33–7.30(m, 3 H), 6.89(s, 1 H), 2.42(t, 7.0 Hz, 2 H), 2.37(t,
7.0 Hz, 2 H), 1.75–1.20(m, 12 H), 0.96(t, 7.0 Hz, 3 H),
0.93(t, 7.0 Hz, 3 H); 13C NMR (CDCl3, 50 MHz) (ppm):
140.93, 135.99, 128.52, 128.38, 128.10, 104.08, 96.99,
88.92, 80.98, 78.61, 31.28, 31.14, 28.34, 28.01, 22.47,
22.22, 19.96, 19.80, 13.95, 13.80; IR (neat, cm–1): 3060,
2200, 2190, 1660, 786; LRMS (rel. int.) m/z 292(100),
178(80), 152(40), 91(50), 77(60).
Scheme 2
In summary, we have explored the Pd(II) catalyzed cross-
coupling reaction of ketene butyltelluroacetals with
alkynes and established a new route to synthesize ene-
diynes in good yields. Our approach is improved com-
pared to described methodologies, avoiding the
preparation of vinyl metals, haloalkynes or protection of
hydroxyl group in propargylic alcohol. In comparison to
our previously described methodology the procedure has
the advantage of easy access and great stability of ketene
butyltelluroacetals and we have shown that PdCl2 must be
used alone instead of the PdCl2–CuI mixture.
Acknowledgment
We are grateful to the FAPERGS, CNPq, CAPES, FAPESP (98/
10821-0) and UNIJUI for financial support.
References and Notes
(1) (a) Heck, R. F. Org. React. 1982, 27, 345. (b) Negishi, E.-I.
Acc. Chem.Res. 1982, 27, 345. (c) Suzuki, A. Pure Appl.
Chem. 1985, 57, 1749. (d) Stille, J. K. Angew. Chem., Int.
Ed. Engl. 1986, 25, 508; Angew. Chem. 1986, 98, 504.
(2) Sonogashira, K. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds.; Pergamon Press: New York,
1991, 521.
Synlett 2002, No. 6, 975–977 ISSN 0936-5214 © Thieme Stuttgart · New York