6292
Z. Lu et al. / Tetrahedron Letters 44 (2003) 6289–6292
increased the conversion of starting material but the
byproduct(s) ratios increased accordingly.
3. Muci, A. R.; Buchwald, S. L. Cross-Coupling Reactions;
Practical palladium catalysts for CꢀN and CꢀO bond
formation; 2002; Vol. 219, pp. 131–209.
The reaction conditions for a variety of haloaromatics
and amines with 10% copper metal catalyst,
K3PO4·H2O base and deanol solvent are listed in Table
3. About 1–5% of the ether byproducts of deanol were
detected for less sterically hindered substrates. Primary
aliphatic amines and small cyclic secondary amines
were readily coupled with unhindered aryl iodides.
Acyclic secondary amines worked poorly (entry 9) and
substrates containing both primary and secondary
amines gave predominant reaction at the primary site
(entry 12). Increasing the hindrance of the primary
butyl amines led to a decrease in amination yield
(entries 6, 7, 8). Aniline is not a good substrate as it
afforded only 30% of amination product (entry 10).
Amination of the heterocycle 2-iodothiophene with
pyrrolidine afforded an excellent yield (entry 13) and a
good yield with n-butylamine (entry 14).33 Notably,
palladium-mediated amination of 2-halothiophenes
with primary amines was not successful due to
diarylation34 or poor yield.35 A very good yield was also
obtained from the Cu mediated amination of 2-bro-
mothiophene with pyrrolidine on a 160 mmol scale
(entry 15, an important result as such aminothiophenes
are useful in optoelectronic materials).36 For bromides,
selectivity between the amine and ether products was
generally lower than for the comparable iodide. For
instance, in the reaction of bromobenzene with pyrro-
lidine only a 61% isolated yield of the amine adduct
was obtained and the selectivity between CꢀN and CꢀO
is about 3:1 when the reaction temperature is 80°C.
Reaction of 1,4-dibromobenzene with pyrrolidine gave
only 28% yield of the monoaminated product. If more
forcing conditions were applied none of the products
dominated.
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We have demonstrated deanol is an alternative solvent
and copper metal is a useful catalyst precursor for
amination of aromatic halides. Non-hindered primary
amines are the most reactive while acyclic secondary
amines are very unreactive so that it is possible to
differentiate them. This process has been successfully
applied to some heterocycles such as 2-iodo or 2-bro-
mothiophene and difunctional molecules such as 1,4-
diiodobenzene.
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Acknowledgements
29. Ma, D. W.; Zhang, Y. D.; Yao, J. C.; Wu, S. H.; Tao, F.
G. J. Am. Chem. Soc. 1998, 120, 12459–12467.
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Z.L. thanks KSU for a University Fellowship and also
Drs. Sampson, Gould and Gangoda for helpful
discussions.
34. Ogawa, K.; Rasmussen, S. C. J. Org. Chem. 2003, 68,
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