Communications
DOI: 10.1002/anie.200801427
Cross-Coupling
Aryl Halide Tolerated Electrophilic Amination of Arylboronic Acids
with N-Chloroamides Catalyzed by CuCl at Room Temperature**
Chuan He, Chong Chen, Jin Cheng, Chao Liu, Wei Liu, Qiang Li, and Aiwen Lei*
Dedicated to Professor Xiyan Lu on the occasion of his 80th birthday
À
Transition-metal-catalyzed aryl Csp2 N bond formation has
been intensively studied over the past decade because of the
importance of the amines and their derivatives in chemistry
related fields.[1–9] The Pd- or Cu-catalyzed formation of
anilines from electrophilic aryl halides and nucleophilic
primary or secondary amines, pioneered by Buchwald and
co-workers and Louie and Hartwig, as well as others,[10–14] is a
hallmark reaction in this field. In 1998, Chan et al., Evans
et al., and Lam et al. independently developed Cu-mediated
oxidative amination of nucleophilic arylboronic acids with
amines or other nucleophiles,[16–20] and the methods were later
improved to include catalytic versions.[15,17,21,22] However,
electrophilic amination of organometallic reagents by
R1R2N+ synthons,[23–31] though conceptually feasible, has
received much less attention.[32–37] The putative catalytic
cycle of this transformation is illustrated in Scheme 1:
The groups of Liebeskind and Johnson have studied this type
[32–37]
À
À
of C N bond formation employing N O derivatives.
N-Chloroamides, though attractive because of the ease of
preparation[49–51] and the high activities of the N Cl
À
bond,[23,50,51] have seldom been utilized in catalytic electro-
philic amination reactions. To the best of our knowledge,
Göttlich et al. has primarily studied the Cu-mediated reaction
of N-chloroamines with alkenes.[38,39,52] Herein, we communi-
cate our results regarding ligandless copper-catalyzed electro-
philic amination of arylboronic acids by N-chloroamides
under mild conditions.
Our initial experiments of N-chloro-N-phenylacet-
amide[49] (1a) and phenylboronic acid (2a) were carried out
by using palladium catalysts. In all attempts, biphenyl was
formed instead of the desired N-arylation product (3a).
However, copper catalysts turned out to be effective, even at
room temperature, and CuCl was found to give the best yield
when K3PO4 was used as the base (Table 1, entries 1–7).
Additional screening of different bases revealed that Na2CO3
improved the yield to 99%, whereas other bases such as
K2CO3, Li2CO3, and KF etc. were less effective (Table 1,
entries 1, and 8–12). The nonpolar solvent toluene and polar
solvents such as dioxane, acetone, and DMF all dramatically
reduced the product yields (Table 1, entries 13–16). Additives
such as TMEDA and DMEDA also did not result in improved
reaction yields (Table 1, entries 17–18).
1
2
À
(1) reaction of R R N X (as an electrophile) with the metal
catalyst (M1) would introduce the amine group to the metal
center to form R1R2N–M1–X;[34–48] (2) transmetalation of RM2
(M2 = B(OH)2) with R1R2N–M1–X to furnish R1R2N–M1R;
À
and (3) final reductive elimination to form the C N bond.
The promising results prompted us to explore the scope of
this new transformation (Table 2). Phenylboronic acids with a
methyl group at either the para, meta, or ortho positions
reacted smoothly with 1a in excellent yields (Table 2,
entries 1–3). The chloro moiety in 4-chlorophenylboronic
acid (2e) and the alkoxycarbonyl groups in 1c and 1d, which
are attached to the phenyl ring bearing the amide group, were
well tolerated (Table 2, entries 4, 6, and 7). N-Chloro-N-
phenylbenzamide (1b) and heterocyclic type 1-chloro-3,4-
dihydroquinolin-2(1H)-one (1e) were suitable substrates as
well (Table 2, entries 5 and 8). Yet, when alkyl type N-butyl-
N-chlorobutan-1-amine (1 f) was coupled with 2a under the
current conditions, only 11% of product 3j was obtained
(Table 2, entry 9), and the major components detected were
dehalogenated dibutylamine and biphenyl.
Scheme 1. Putative mechanism of transition-metal-catalyzedelectro-
philic amination of organometallic reagents by N-haloamides.
[*] C. He, C. Chen, J. Cheng, C. Liu, W. Liu, Q. Li, Prof. A. Lei
College of the Chemistry andMolecular Sciences
Wuhan University
Wuhan, Hubei, 430072 (PR China)
Fax: (+86)27-6875-4067
E-mail: aiwenlei@whu.edu.cn
main.htm
Cu-mediated N-arylation of amines or amides with aryl
halides as electrophiles have been reported, and they usually
required high temperatures.[12–14] In contrast, the reactions
described herein proceed smoothly at room temperature.
[**] This work was supportedby the National Natural Science
Foundation of China (20772093, 20502020), the Excellent Youth
Foundation of Hubei Scientific Committee, and the startup fund
from Wuhan University.
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Theoretically, addition of a N X bond to a low-valent
transition metal should be easier than that of a corresponding
Supporting information for this article is available on the WWW
[53]
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C X bond because the former is weaker in strength.
6414
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 6414 –6417