Angewandte
Chemie
DOI: 10.1002/anie.201305902
Synthetic Methods
À
Rhodium(III)-Catalyzed Azidation and Nitration of Arenes by C H
Activation**
Fang Xie, Zisong Qi, and Xingwei Li*
Organic azide and nitro compounds are important building
blocks in synthetic chemistry. In particular, organic azides
have found wide applications in synthetic chemistry, material
science, polymer chemistry, medicinal chemistry, and biol-
ogy.[1] Synthetically, azides are particularly well known for
copper-catalyzed 1,3-dipolar addition reactions.[2] Further-
more, many azide compounds exhibit valuable biological
activities.[3]
Azide groups are introduced by the following methods:
1) the Sandmeyer reaction;[4] 2) the copper-catalyzed cou-
pling of aryl halides or boronic acids with NaN3 or TMSN3;[5]
and 3) the coupling of organometallic reagents with TfN3.[6]
Despite the value of these methods, it is highly attractive to
developed an elegant system for the copper-catalyzed, NH2-
[11]
À
directed ortho C H azidation of anilines (Scheme 1c), for
which a sequence of single-electron-transfer processes has
been proposed.
À
The strategy of transition-metal-catalyzed C H activation
has allowed the development of a plethora of synthetic
methods.[12] In particular, C H activation/coupling reactions
À
catalyzed by stable [Cp*RhIII] complexes have been explored
extensively in the past several years for a broad spectrum of
arene substrates bearing a chelating group.[13] However, the
coupling partners are mostly limited to p bonds. Rhodium-
À
(III)-catalyzed C H amination has received less attention,
À
and only limited examples of intermolecular C H amination
take advantage of the ubiquity of C H bonds for more step-
reactions have been reported, with chloroamines,[14] sulfonyl
À
economical and efficient azidation.[7] To overcome the high
azides,[15] N-fluorobenzenesulfonimide (NFSI),[16] and com-
3
[17]
À
À
strength and low acidity of unreactive C(sp ) H bonds, the
pounds containing oxidizing N O bonds
reagents. No C H azidation of arenes other than electron-rich
arenes has been reported, and no related C H nitration under
rhodium catalysis has been documented. We now report
a Rh -catalyzed efficient C H azidation of arenes bearing
chelating groups under relatively mild conditions.
as aminating
À
À
strategy of homolytic C H cleavage–azidation has been
developed with rather strong hypervalent iodine reagents.[8]
Analogously, the same type of hypervalent iodine reagents
have been used for the electrophilic azidation of electron-rich
arenes, such as anisole and indoles, with and without a metal
catalyst (Scheme 1a,b).[9,10] Significantly, Jiao and Tang
À
III
À
We initiated our studies with the azidation of 2-phenyl-
À
pyridine with NaN3. We found that although essentially no C
N coupling occurred when PhI(OAc)2 (PIDA, 1.5 equiv)
alone was used as an oxidant in the presence of [{RhCp*Cl2}2]
(4 mol%; Cp* = pentamethylcyclopentadienyl; Table 1,
entry 1), the addition of TsOH·H2O (1.5 equiv) promoted
this coupling in MeCN or CH2Cl2 to give the azidation
product 2a in 20–34% yield (entries 2–4). Attempts to
improve the catalytic efficiency by employing a cationic
rhodium catalyst were to no avail (Table 1, entry 5). We
screened a number of solvents and found that the reaction
proceeded in CF3CH2OH (TFE) in slightly higher yield;
however, no reaction occurred in 1,4-dioxane, MeOH, DMF,
or (CF3)2CHOH (Table 1, entries 6–8). Gratifyingly, 2a was
isolated in high yield when the reaction was conducted in
acetone, even under mild conditions (508C; Table 1, entry 9).
However, lowering of the reaction temperature or the catalyst
loading led to a sluggish reaction (Table 1, entries 10 and 11).
Impressively, this coupling system proceeded equally well
without the extrusion of air or moisture with bench-top
acetone, which highlights the operational simplicity of the
method (Table 1, entry 13). The reaction also proceeded
smoothly when PhI(OTs)OH (Koser reagent, 1.5 equiv) was
used in place of PIDA as an oxidant in the presence of AcOH
(3 equiv; Table 1, entry 12), which appears to be an active
oxidant in the transformation, because it is readily generated
from the reaction of PIDA and TsOH.[18] The rhodium
catalyst proved necessary: a control experiment showed that
essentially no reaction occurred when it was omitted.
[9]
À
Scheme 1. C H azidation of arenes, as described by a) Kita et al.,
b) Suna and co-workers,[10] and c) Tang and Jiao.[11] TBHP=tert-butyl
hydroperoxide, TFA=trifluoroacetate, TMS=trimethylsilyl,
Ts =p-toluenesulfonyl.
[*] Dr. F. Xie,[+] Z. Qi,[+] Prof. Dr. X. Li
Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Dalian 116023 (China)
E-mail: xwli@dicp.ac.cn
[+] These authors contributed equally.
[**] This research was supported by the Dalian Institute of Chemical
Physics, the Chinese Academy of Sciences, and the NSFC (No.
21272231).
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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