Scope and Limitations of Pd2(dba)3/P(i-BuNCH2CH2)3N-Catalyzed
Buchwald-Hartwig Amination Reactions of Aryl Chlorides
Sameer Urgaonkar and John G. Verkade*
Department of Chemistry, Gilman Hall, Iowa State University, Ames, Iowa 50011-3111
Received July 26, 2004
Proazaphosphatrane ligands in combination with Pd2(dba)3 generate highly active catalysts for
Buchwald-Hartwig amination of aryl chlorides. In particular, commercially available P(i-BuNCH2-
CH2)3N is a highly general and efficient ligand, allowing the coupling of an electronically diverse
set of aryl chlorides, including chloropyridines, with a wide variety of amines using 1 mol % of Pd
at 100 °C. Either a 1:1 or 2:1 ratio of ligand to Pd was found to be effective. This catalyst system
performs exceptionally well for sterically hindered substrates, even with only 0.25 mol % of Pd. It
is shown that NaOH can also be used as the base (instead of NaO-t-Bu) allowing functionalized
substrates to participate in these reactions.
Introduction
phosphine,10-13 ferrocenyldialkylphosphine,14 aryldialkyl-
phosphine,15-17 heterocyclic carbene,18-20 palladacycle,21-23
or phosphinous acid24 classes have been investigated in
these reactions.
Over the past few years, part of our research effort has
focused on the design, synthesis, and application of
proazaphosphatranes of type A to organic methodology.25
Recently, we have focused on the use of A as an ancillary
ligand in palladium-mediated coupling reactions. In this
regard, we have successfully demonstrated that in con-
trast to 1 and 2, the commercially available proazaphos-
phatrane 3 is highly active in Suzuki,26 Buchwald-
Hartwig amination,27-29 R-arylation,30,31 and Stille32
Over the past decade, one of the foremost accomplish-
ments in the field of catalysis has been the discovery of
the palladium-catalyzed carbon-nitrogen bond-forming
process commonly known as the Buchwald-Hartwig
amination reaction.1-3 This process generally involves the
coupling of aryl halides with amines mediated by a
suitable palladium complex as a catalyst to afford aryl-
amines which often are important intermediates in
organic synthesis and which occur within the molecular
framework of several natural products,4 dendrimers,5
ligands,6-8 and advanced materials.9 A major impetus to
this field was provided by the ability to activate notori-
ously unreactive but relatively cheap aryl chlorides. Not
surprisingly, a plethora of palladium catalyst systems,
featuring a palladium-bound ligand, are now accessible
for accomplishing the aforementioned transformation
involving aryl chlorides. Typically, electronically rich
sterically hindered ligands belonging to the trialkyl-
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10.1021/jo048716q CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/19/2004
J. Org. Chem. 2004, 69, 9135-9142
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