coupling reaction9 as a pivotal step. In this context, we report
herein the efficient synthesis of polyethynyl-substituted
aromatic compounds, hexakis[(trimethylsilyl)ethynyl]benzene
(1) and 2,4,6-tris[(trimethylsilyl)ethynyl]-1,3,5-triazine (9),
using the Negishi protocol and its application to a new route
to the differentially substituted hexaethynylbenzenes from
chloroiodobenzenes by ingenious combination with the
Sonogashira reaction.10
catalyst, proceeded smoothly at room temperature to give
triethynyltriazine 9 in 80% yield (Scheme 2).
Scheme 2
With these results in hand, we applied the Negishi coupling
reaction to the synthesis of differentially substituted hexa-
ethynylbenzenes from chloroiodobenzenes. Our plan is based
on the combination of two coupling methods, the Sonogash-
ira and Negishi cross-coupling reactions, taking advantage
of the difference between the reactivity of the halogen atoms
of aryl halides. Namely, the first Sonogashira reaction of
chloroiodobenzenes would take place selectively at iodine,
and subsequent coupling at chlorine would be achieved by
the use of the Negishi method. In general, chloroarenes are
known to exhibit significant low reactivities to palladium-
catalyzed cross-coupling in the absence of activating fac-
tors.16,17 However, we expected that the weakly electron-
withdrawing ethynyl groups introduced by the Sonogashira
coupling would activate the remaining C-Cl bonds toward
oxidative addition of Pd(0).18
To test the efficiency of the Negishi reaction in the
multiple substitution on the aromatic core, we chose hexa-
ethynylbenzene 111 and triethynyltriazine 912 as the first
targets, because (i) these compounds have not been prepared
efficiently by the Sonogashira method13 and (ii) removal of
the trimethylsilyl group of these compounds and subseguent
coupling with appropriate aromatic halides would lead to a
variety of extended π systems.
When a mixture of hexabromobenzene (5) and 10 equiv
of [(trimethylsilyl)ethynyl]zinc chloride (6), prepared by
treatment of (trimethylsilyl)acetylene with butyllithium fol-
lowed by zinc chloride,9a in the presence of Pd(PPh3)4 (20
mol %) was heated in THF14 at 80 °C for 3 days,
hexaethynylbenzene 1 was obtained in 64% isolated yield
(Scheme 1).15 The yield of 1 is much better than those
reported previously.11
We reported that the reaction of 1,3,5-trichloro-2,4,6-
triiodobenzene (11), derived from 1,3,5-trichlorobenzene (10)
by iodination with periodic acid,19 with (trimethylsilyl)-
acetylene under the Sonogashira coupling conditions gave
Scheme 1
(11) (a) Diercks, R.; Armstrong, J. C.; Boese, R.; Vollhardt, K. P. C.
Angew. Chem., Int. Ed. Engl. 1986, 25, 268. (b) Neenan, T. X.; Whitesides,
G. M. J. Org. Chem. 1988, 53, 2489.
(12) Kouvetakis, J.; Grotjahn, D.; Becker, P.; Moore, S.; Dupon, R. Chem.
Mater. 1994, 6, 636.
(13) The synthesis of 9 and its derivatives has been accomplished by
the use of expensive trifluorotriazine (with ethynyllithium reagents: ref 12
and Wortmann, R.; Glania, C.; Kra¨mer, P.; Matschiner, R.; Wolff, J. J.;
Kraft, S.; Treptow, B.; Barbu, E.; La¨ngle, D.; Go¨rlitz, G. Chem. Eur. J.
1997, 3, 1765) or a potentially toxic ethynyltin reagent (with trichlorotriazine
8: Faust, R.; Go¨belt, B. Tetrahedron Lett. 1997, 38, 8017.).
(14) We employed ca. 40% toluene as a cosolvent with THF to raise
the reflux temperature.
(15) As a byproduct, pentakis[(trimethylsilyl)ethynyl]benzene (7) was
isolated in 10% yield (see ref 11b).
(16) For reviews, see: (a) Grushin, V. V.; Alper, H. Chem. ReV. 1994,
94, 1047. (b) Grushin, V. V.; Alper, H. In ActiVation of UnreactiVe Bonds
and Organic Synthesis; Topics in Organometallic Chemistry; Murai, S.,
Ed.; Springer-Verlag: Berlin, 1999; Vol. 3, pp 193-226.
(17) For recent examples of palladium-catalyzed coupling of unactivated
chloroarenes, see: (a) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10.
(b) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722. (c) Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi,
J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 4369. (d) Mann, G.;
Incarvito, C.; Rheingold, A. L.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 3224. (e) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513.
(18) Recently the utility of zinc reagents in palladium-catalyzed cross-
coupling reactions of aryl chlorides was reported by Fu. However,
alkynylzinc reagents were reported to be unsuitable coupling partners: Dai,
C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719.
Similarly, the reaction of 2,4,6-trichloro-1,3,5-triazine (8)
with ethynylzinc chloride 6, in the presence of the palladium
(9) (a) King, A. O.; Negishi, E.-I.; Villani, F. J., Jr.; Silveira, A., Jr. J.
Org. Chem. 1978, 43, 358. For a review, see: (b) Negishi, E.-I., Liu, F. In
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: New York, 1998; pp 1-48.
(10) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467. For a review, see: (b) Sonogashira, K. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New
York, 1998; pp 203-229.
(19) Mattern, D. L. J. Org. Chem. 1984, 49, 3051.
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