Angewandte
Chemie
DOI: 10.1002/anie.201500404
Ammonia Coupling
Nickel-Catalyzed Amination of Aryl Chlorides with Ammonia or
Ammonium Salts**
Rebecca A. Green and John F. Hartwig*
Abstract: The nickel-catalyzed amination of aryl chlorides to
form primary arylamines occurs with ammonia or ammonium
sulfate and a well-defined single-component nickel(0) preca-
talyst containing a Josiphos ligand and an h2-bound benzoni-
trile ligand. This system also catalyzes the coupling of aryl
chlorides with gaseous amines in the form of their hydrochlo-
ride salts.
tightly to transition metals,[22,23] often causing catalyst deac-
tivation. Ammonia is neither strongly basic nor acidic,
disfavoring proton exchanges to and from the reagent, and
À
À
the strong N H bond disfavors oxidative addition of the N H
bond of ammonia. In addition, the physical properties of
ammonia create challenges for conducting coupling reactions
conveniently. Because it is a corrosive gas, specialized equip-
ment is required to run reactions at high pressures. Finally, the
aniline formed during the reaction can act as a nucleophile for
subsequent amination reactions to form diarylamines. Herein,
we report a series of Ni-catalyzed monoarylations of ammo-
nia with aryl electrophiles. These studies show the value of
using a single-component catalyst for high activity and for
generating clear mechanistic information. Our mechanistic
studies strongly imply that the process occurs by shuttling
between Ni0 and arylnickel(II) halide intermediates.
T
he transition-metal-catalyzed amination of aryl halides is
a valuable tool for the construction of arylamines.[1] Many
palladium catalysts have been developed for the amination of
aryl electrophiles with a wide variety of amines. However,
there are few catalysts based on cost-effective and earth-
abundant metals for the amination of aryl electrophiles, and
little mechanistic information has been gained about the
coupling reactions of amines catalyzed by first-row metals.
Copper-catalyzed aminations of aryl halides are typically
limited to sterically unhindered aryl iodides and activated aryl
bromides.[2] Nickel catalysts for amination reactions have
been reported, but the scope of the reaction, until recently,[3,4]
was limited to secondary alkyl[5–19] and aryl[5,8,9,11,13–20] amines.
The development of a nickel catalyst for the coupling of
aryl electrophiles with primary amines and ammonia is a long-
standing challenge. Nickel-catalyzed coupling reactions of
aryl chlorides with primary alkylamines occurred, until
recently, in low yields with unactivated substrates.[5,18] Our
report of a catalyst for the coupling of unactivated aryl
chlorides with primary alkylamines demonstrated the value of
single-component catalysts to achieve high reactivity and
selectivity.[3] Despite the progress on the development of first-
The palladium-catalyzed amination of aryl electrophiles
with ammonia has been reported,[24–32] and the mechanism has
been studied.[33] These studies showed that the steric bulk of
the ligand is crucial to favor the binding of ammonia over the
binding of aniline. Nickel complexes of bidentate ligands are
known to add aryl chlorides.[3,34] Based on this information,
we investigated the coupling of chlorobenzene 1 with ammo-
nia (added to the reaction as a dioxane solution), catalyzed by
[Ni(cod)2] and a variety of bidentate phosphine ligands
(Table 1). We began our evaluation of the ligands by studying
catalysts containing common chelating bisphosphines, such as
BINAP (Table 1, entry 1), Xantphos (entry 2), and dppf
(entry 3). Because BINAP-ligated nickel complexes catalyzed
the amination of aryl chlorides with primary alkylamines,[3]
the primary arylamines formed from the coupling of ammonia
might be expected to react competitively with ammonia.
Indeed, the reaction of chlorobenzene with ammonia, cata-
lyzed by a BINAP-ligated nickel complex, occurred in low
yield with low selectivity for the primary amine 2 over the
diarylamine 2’ (Table 1, entry 1).
À
row transition-metal catalysts for C N coupling reactions, few
studies have been published on the amination of aryl electro-
philes with ammonia catalyzed by nickel. Concurrent with the
work we report here,[21] Stradiotto and co-workers reported
a Josiphos-ligated nickel catalyst for the coupling of aryl
chlorides with ammonia.[4]
The development of the nickel-catalyzed coupling of
ammonia poses several challenges. First, ammonia binds
However, reactions catalyzed by nickel complexes that
were bound by ligands of the Josiphos family occurred with
high conversions of the aryl chloride, high yields of anilines,
and varying selectivities. The nickel catalyst ligated by the
same Josiphos ligand as in a Pd catalyst for the coupling of
aryl halides with ammonia[24,27] gave high selectivity for the
primary amine. However, the conversion and yield were low
(Table 1, entry 8). Fortunately, reactions conducted with the
smaller Josiphos ligand L5 occurred with both high yields and
high selectivity (Table 1, entry 9).
[*] R. A. Green, Prof. J. F. Hartwig
Department of Chemistry, University of California, Berkeley
Berkeley, California 94720 (USA)
E-mail: jhartwig@berkeley.edu
[**] We acknowledge financial support from the NIH (GM-55382) and
the Dow Chemical Company. R.A.G. acknowledges the NSERC for
a graduate fellowship. We thank Dr. Antonio Di Pasquale for
collecting the crystallographic data and solving the structures of
complexes C2, C5, and C5A with instrumentation available from the
NIH (S10-RR027172).
We have previously shown that benzonitrile stabilizes the
Ni0 intermediate in the catalytic system, and the benzonitrile-
ligated nickel complex readily undergoes oxidative addition
of aryl chlorides.[3] To avoid the presence of cyclooctadiene in
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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