Jul-Aug 2003
Palladium Catalyzed Cross-Methylation of Bromoheterocycles
567
REFERENCES AND NOTES
Author to whom correspondence should be addressed; e-mail:
[1] G. B. Buckton and W. Odling, Annalen(Suppl.), 4, 6 (1865-6);
Proc. Roy. Soc., 14, 19 (1865).
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7555 (2000).
Within the series 1a, 1b and 1c the indium reagent 1c gives
the highest yields. Dimeric bis[µ-[2-(dimethylamino)-
ethanolato-N,O:O]tetramethyl digallium (2b) and
–diindium (2c) react somewhat slower than 1b and 1c, but
ultimately afford high yields. The diindium complex has
the advantage of being fairly air insensitive and easy to
handle. The cross-methylation of the bromohetrocycles is
not associated with hydrodebromination processes
observed frequently during palladium- and nickel-
catalyzed cross-coupling of carbocylic bromoarenes with
1a. Even in the reactions of the carbocyclic substrates the
undesired hydrodehalogenation could be diminished or
eliminated by replacement of the aluminum complex by an
indium reagent [8,19].
*
EXPERIMENTAL
General Procedure for Cross-methylation of Bromoheterocyclics
with Compounds 1 and 2.
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S. Schutte, J. Kaufmann and B. C. Wassermann, J. Mol. Catal. A: Chem.,
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Eur. J. Org. Chem., 1628 (2002).
A thick walled glass tube was charged with 1 mmole of the
heterocyclic bromide, 1 mmole of the methylation reagent,
28.5 mg (0.04 mmoles) of dichlorobis(triphenylphosphine)-
palladium and 10 ml of anhydrous benzene. Except for those cases
in which 2c was employed the tube was sealed under nitrogen
atmosphere. The reaction vessel was heated at 80 °C for the desired
length of time. The cooled reaction mixture was worked up by one
of the following methods: The nitrogen containing substrates were
either concentrated and flash chromatographed on silica gel or
treated with 10 ml water, and the dried organic phase concentrated
and chromatographed. The furan derivative and the sulfur contain-
ing compounds were quenched with 5% aqueous hydrochloric acid
prior to their purification by chromotography. The reaction prod-
ucts were analyzed by gas chromatography and their mass spectra
and nmr compared with those of authentic samples. The picolines,
2-methylthiazole, 5-methylfurfural and 3-methylthiophene were
compared directly with commercial compounds. 5-Nitro-2-picol-
ine [20], 5-methoxy-3-picoline [21], 4,4-dimethyl-3,3'-bithiophene
[18], 3-methylbenzo[b]thiophene [22], 3-bromo-4-methylthio-
phene [23] and 5-methylpyrimidine [24] were compared with sam-
ples prepared according to literature procedures.
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591 (2001).
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[23] D. R. Arnold and C. P. Hadjiantoniou, Can,. J. Chem., 56,
1970 (1978).
Acknowledgement.
We thank the United States-Israel Binational Science
Foundation (BSF grant No. 2000013), the Fonds der Chemischen
Industrie (H.S.), the Deutsche Forschungsgemeinschaft (H.S.)
and the Exchange Program between the Hebrew University of
Jerusalem and the Technische Universität Berlin for financial
support of this study.
[24] H. Bredereck, H. Herlinger and J. Renner, Chem. Ber., 93, 230
(1960).