comitant formation of diyne byproduct 17 not only kept the
yield of 16 modest but also made purification difficult. This
result suggests that the homocoupling reaction of 15 cata-
lyzed by palladium, as has been previously reported by Lee
and co-workers,23 successfully competes with Negishi cross-
coupling. To date, this process could not be optimized to a
point that minimizes the formation of such side products.
The synthetic potential of other metal-catalyzed cross-
coupling reactions was also explored. Conjugated ynones24-26
are desirable synthetic targets because they are versatile
synthetic precursors and are also known to possess interesting
biological activity.27 After experimenting with several trans-
metalation schemes, it was established that the Stille coupling
reaction of a stannylacetylene and an acyl chloride28 provided
good results for the one-pot protocol (Table 3).
Table 3. Synthesis of Ynones 18 via a One-Pot FBW
Rearrangement and the Stille Coupling Reaction
Following the FBW rearrangement-deprotonation se-
quence of 6a in toluene, Bu3SnCl was added to the lithium-
acetylide at -40 °C, and the mixture was warmed to room
temperature to complete formation of the tin-acetylide. To
this intermediate were added the acyl chloride (in CH2Cl2)
and catalytic PdCl2(PPh3)2; the reaction was then refluxed.
The Stille coupling reaction with aryl acyl chlorides afforded
butadiynyl ketones 18a-d in good yield, while the reaction
with acetyl chloride provided only 33% yield of the unstable
diynone product 18e. Attempts to apply this method to
triynones, such as 19, were, unfortunately, not successful.
While TLC analysis of the reaction mixture suggested that
the formation of 19 would occur, it was not possible to isolate
the pure product due to the kinetic instability of 19. To the
best of our knowledge, however, the one-pot procedure
combining the FBW rearrangement and Stille coupling
a Isolated yield based on dibromoolefin. b Not isolated because of
instability.
reaction is the first example of a straightforward method for
the synthesis of diaryl butadiynyl ketones.29
(19) In situ deprotection/coupling protocols can be quite effective. See,
for example: Bell, M. L.; Chiechi, R. C.; Johnson, C. A.; Kimball, D. B.;
Matzger, A. J.; Wan, W. B.; Weakley, T. J. R.; Haley, M. M. Tetrahedron
2001, 57, 3507-3520.
(20) Negishi, E. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley-VCH: New York, 2002; pp 229-247.
(21) The use of toluene rather than hexanes allows for higher reflux
temperatures in the subsequent Negishi reaction.
In conclusion, we have developed a convenient method
for the one-pot syntheses of functionalized polyynyl com-
pounds using a carbenoid rearrangement to generate the
polyyne framework. The initially generated lithium-acetyl-
ide can be trapped in situ with electrophiles, allowing for
the formation of substituted di- and triynes. Optimized
protocols have been developed for the preparation of diaryl
polyynes via transmetalation to zinc, followed by a Negishi
coupling reaction, as well as polyynyl ketones via trans-
metalation to tin and a subsequent Stille coupling reaction.
(22) Rubin, Y.; Lin, S. S.; Knobler, C. B.; Anthony, J.; Boldi, A. M.;
Diederich, F. J. Am. Chem. Soc. 1991, 113, 6943-6949.
(23) Damle, S. V.; Seomoon, D.; Lee, P. H. J. Org. Chem. 2003, 68,
7085-7087.
(24) (a) Brown, H. C.; Racherla, U. S.; Singh, S. M. Tetrahedron Lett.
1984, 25, 2411-2414. (b) Yamaguchi, M.; Shibato, K.; Fujiwara, S.; Hirao,
I. Synthesis 1986, 421-422.
(25) Palladium-catalyzed alkynylation of acyl halides with metal acetyl-
ides. For copper: (a) Tohda, Y.; Sonogashira, K.; Hagihara, N. Synthesis
1977, 777-778. For zinc: (b) Negishi, E.; Bagheri, V.; Chatterjee, S.; Luo,
F.-T.; Miller, J. A.; Stoll, A. T. Tetrahedron Lett. 1983, 24, 5181-5184.
(c) Verkruijsse, H. D.; Heus-Kloos, Y. A.; Brandsma, L. J. Organomet.
Chem. 1988, 338, 289-294. For tin: (d) Logue, M. W.; Teng, K. J. Org.
Chem. 1982, 47, 2549-2553. (e) Ackroyd, J.; Karpf, M.; Dreiding, A. S.
HelV. Chim. Acta 1985, 68, 338-344. (f) Crisp, G. T.; O’Donoghue, A. I.
Synth. Commun. 1989, 1745-1758. For aluminum: (g) Wakamatsu, T.;
Okuda, Y.; Oshima, K.; Nozaki, H. Bull. Chem. Soc. Jpn. 1985, 58, 2425-
2426. For indium: (h) Perez, I.; Perez Sestelo, J.; Sarandeses, L. A. J. Am.
Chem. Soc. 2001, 123, 4155-4160.
(26) Palladium-catalyzed alkynylation of acyl halides with terminal
alkynes has also been reported. See: Alonso, D. A.; Na´jera, C.; Pacheco,
M. C. J. Org. Chem. 2004, 69, 1615-1619 and references therein.
(27) (a) Fukumaru, T.; Awata, H.; Hamma, N.; Komatsu, T. Agric. Biol.
Chem. 1975, 39, 519-527. (b) Nash, B. W.; Thomas, D. A.; Warburton,
W. K.; Williams, T. D. J. Chem. Soc. 1965, 2983-2988.
Acknowledgment. This work was supported by the
University of Alberta and the National Sciences and Engi-
neering Research Council of Canada (NSERC) through the
Discovery and Nano Innovation Platform (NanoIP) grant
programs. We thank Ms. Nina Cunningham for help with
the synthesis of compound 8h.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for new compounds. This
material is available free of charge via the Internet at
OL0528888
(28) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524.
(b) Marsden, J. A.; Haley, M. M. In Metal-Catalyzed Cross-Coupling
Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: New York,
2005; Chapter 6.
(29) Trimethylsilyldiynyl ketones are conveniently formed via a Friedel-
Crafts reaction. See: Walton, D. R. M.; Waugh, F. J. Organomet. Chem.
1972, 37, 45-56.
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