Organic Letters
Letter
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diarylamines are not observed in these reactions. N-Alkylanilines
are less volatile than the corresponding primary arylamines.
Therefore, isolated yields from reactions with methyl and
ethylamine hydrochloride are slightly higher than those for
reactions with ammonium sulfate.
Reactions of ethylamine hydrochloride with aryl halides occur
under conditions similar to those previously reported for the
coupling of primary alkylamines. In this case, Pd(OAc)2 is a
suitable precursor, presumably because of the more facile
reduction of the Pd(II) by ethylamine than by methylamine or
ammonia.35 Similarly, aryl halides, including bromopyridines
(4l−n), coupled with ethylamine hydrochloride to form the
corresponding N-ethylanilines (Scheme 5).
In summary, we have shown that ammonium salts are practical
alternatives to gaseous amines for the aminations of aryl halides
and can occur with distinct selectivities, distinct effects of
concentration on selectivities, and distinct resting states of the
catalyst. We observed a high selectivity for the formation of
primary arylamine over diarylamine in reactions of aryl chlorides
with ammonium sulfate, but we observed a mixture of mono- and
diarylamine in the reactions of aryl bromides with ammonium
sulfate. We attribute the difference in selectivity to the difference
in resting states in the amination reaction of ammonium sulfate
with aryl chlorides and bromides. L2Pd(Ar)(OtBu) was observed
as the major ligated palladium species during the reaction of aryl
chlorides with ammonium sulfate. However, both L2Pd(Ar)-
(OtBu) and L2Pd(Ar)(Br) were observed in reactions of aryl
bromides with ammonium sulfate. The L2Pd(Ar)(Br) reacts
selectively with primary arylamines to afford the diarylamine side
product. This method was extended to include other gaseous
amines, such as methylamine and ethylamine, to afford
N-methyl- and N-ethylanilines.
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(18) Pd[P(o-tol)3]2 is stable as a solid in air but must be handled under
inert atmosphere in solution.
(19) Singer, R. A.; Dore,
Lett. 2006, 47, 3727.
́
M.; Sieser, J. E.; Berliner, M. A. Tetrahedron
(20) See the Supporting Information.
(21) Unprotected enolizable ketones underwent aldol condensation
reactions under the basic conditions.
(22) Klinkenberg, J. L.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132,
11830.
(23) Alvaro, E.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 7858.
(24) A survey of alkoxide and phenoxide bases with various
counterions did not improve the selectivity of the reaction.
(25) Clarke, H. T.; Davis, A. W. Organic Syntheses 1922, 79.
(26) Alvarez-Builla, J.; Vaquero, J. J.; Barluenga, J. Modern Heterocyclic
Chemistry, 4th ed.; John Wiley & Sons: Weinheim, 2011.
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(28) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045.
(29) Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am.
Chem. Soc. 2008, 130, 13552.
ASSOCIATED CONTENT
* Supporting Information
■
S
(30) Lundgren, R. J.; Sappong-Kumankumah, A.; Stradiotto, M.
Chem.Eur. J. 2010, 16, 1983.
Detailed experimental procedures and compound character-
ization. This material is available free of charge via the Internet at
(31) Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 15914.
(32) Li, J. J.; Wang, Z.; Mitchell, L. H. J. Org. Chem. 2007, 72, 3606.
(33) Alsabeh, P. G.; Lundgren, R. J.; Longobardi, L. E.; Stradiotto, M.
Chem. Commun. 2011, 47, 6936.
AUTHOR INFORMATION
Corresponding Author
■
(34) Tardiff, B. J.; McDonald, R.; Ferguson, M. J.; Stradiotto, M. J. Org.
Chem. 2012, 77, 1056.
(35) Shen, Q.; Shekhar, S.; Stambuli, J. P.; Hartwig, J. F. Angew. Chem.,
Notes
Int. Ed. 2005, 44, 1371.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Dow Chemical Co. and the NIH (GM-58108) for
support and Johnson Matthey for a gift of PdCl2. R.A.G. thanks
NSERC for a graduate fellowship, Patrick S. Fier (UCB) and Dr.
Andrew T. Brusoe (UCB) for helpful discussions, and Dr. Seung
Hwan Cho (UCB) for the synthesis of substrates 1o,q,r,t
(Scheme 4).
REFERENCES
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