SCHEME 1. Synthesis of L1-L4
An Ullmann Coupling of Aryl Iodides
and Amines Using an Air-Stable
Diazaphospholane Ligand
Minghua Yang and Fei Liu*
Department of Chemistry & Biomolecular Sciences,
Macquarie UniVersity, Sydney, NSW, 2109 Australia
reported using enolates or diols as ligands.11 In this paper, we
report the use of an air-stable diazaphospholane phosphine as a
new ligand in the copper-catalyzed coupling of a range of aryl
iodides with alkyl or heterocyclic amines for synthesizing a
variety of aryl amines. While the diazaphospholane ligand
framework has seen success in transition-metal-catalyzed reac-
tions such as allylic alkylation and hydroformylation,12 its utility
in the copper-catalyzed Ullmann reaction has not yet been
demonstrated.
ReceiVed June 12, 2007
A copper-based catalytic system, using an air-stable diaza-
phospholane as the ligand, was developed for an efficient
Ullmann reaction between aryl iodides and alkyl or hetero-
cyclic amines.
A series of four diazaphospholanes, L1-L4, were synthesized
using the two-step Landis procedure from readily available
starting materials, previously utilized for the synthesis of L112b
and L412c (Scheme 1). Aldehydes and hydrazine were first
condensed to form functionalized azines, which were then
condensed with phthaloyl chloride and phenyl phosphine in one
pot to furnish the diazaphospholanes. This facile synthesis was
amenable to electron-rich aryl aldehydes, providing two new
ligands (L2 and L3) in good yields (57-63% over two steps)
as racemic mixtures. These four phosphines, L1-L4, exhibited
different chemical shifts at the phosphorus center as indicated
by 31P NMR. Electron-donating substitution on the aromatic
rings resulted in an upfield shift of the phosphorus signal by
about 12 ppm (L1 vs L3). All phosphines remained stable after
exposure to air for months at room temperature.13 The conver-
gent and facile synthesis of these stable phosphines may offer
future opportunities for rapid access of analogues by changing
the substituents of the starting aromatic aldehydes.
The Ullmann-type coupling of aryl halides with amines using
copper is recognized as an economic and versatile method for
rapidly accessing aryl amines as key synthons (Scheme 1).1
While ligand-free conditions are known, mono- and bidentate
ligands, such as phosphines,2 salicylamides,3 diamines,4 diols,5
amino alcohols,6 amino acids,7 phosphoramidites,8 oxime-
phosphine oxides,9 and phosphinidenes,10 have been shown to
significantly improve the yield and generality of this reaction.
Recently, room-temperature Ullmann reactions have also been
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All four ligands were investigated in the copper-catalyzed
coupling reaction between iodobenzene and benzylamine. Table
(3) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2003, 5, 793-796.
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Org. Chem. 2007, 72, 672-674.
(12) (a) Clark, T. P.; Landis, C. R.; Freed, S. L.; Klosin, J.; Abboud, K.
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J. S.; Clark, T. P.; Nelson, R. C. PCT Int. Appl. WO 2005042546 A2,
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(13) For an explanation of the air stability for some dialkylaryl
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(10) Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Chem. Commun.
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10.1021/jo0712291 CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/13/2007
J. Org. Chem. 2007, 72, 8969-8971
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