Copper-catalyzed C-H azidation of anilines under mild conditions

Article abstract of DOI:10.1021/ja3089907

A novel and efficient copper-catalyzed azidation reaction of anilines via C-H activation has been developed. This method, in which the primary amine acts as a directing group by coordinating to the metal center, provides ortho azidation products regioselectively under mild conditions. This effective route for the synthesis of aryl azides is of great significance in view of the versatile reactivity of the azide products.

Full text of DOI:10.1021/ja3089907

Subscriber access provided by George Mason University Libraries & VIVA (Virtual Library of Virginia)
Communication
Copper-catalyzed C-H Azidation of Anilines under Mild Conditions
Conghui Tang, and Ning Jiao
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 06 Nov 2012
Downloaded from http://pubs.acs.org on November 6, 2012
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
Copper-catalyzed C-H Azidation of Anilines under Mild Condi-
tions
Conghui Tang † and Ning Jiao*,†,‡
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
† State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University
Xue Yuan Road 38, Beijing 100191 (China);
‡ State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences. Shanghai 200032 (China)
KEYWORDS：Azidation, Copper, C-H functionalization, Directing group.
Supporting Information Placeholder
thods suffer from narrow functional group compatibility,
atom uneconomy and harsh conditions which may in-
duce decomposition process of azides. Hence, developing
ABSTRACT: A novel and efficient copper catalyzed azi-
dation reaction of anilines via C-H activation has been
developed. This method involves primary amine as di-
recting group, by coordinating with the metal center,
ortho azidation products are regioselectively obtained
under mild conditions. This effective route to synthesis
aryl azide is of great significance in view of the versatile
reactivity of the azide product.
new ways to obtain aryl azides involving direct C-H func-
12
tionalization11,
under mild conditions would be very
fascinating while challenging at the same time.
Scheme 1. Azide group incorporation into aro-
matic rings.
The first organic azide, phenyl azide, was discovered
by Peter Griess in 1864.1 Since then, numerous syntheses
of these energy-rich molecules have been developed. In
most recent times, organic azides are widely used in or-
ganic synthesis as valuable intermediates and building
blocks due to their versatile reactivities,2 elegant perspec-
tives have been developed for the application of organic
azide, in particular in the synthesis of nitrogen-
containing heterocycles, in peptide chemistry, material
science, polymer chemistry and drug discovery.3 Moreo-
ver, aryl azide has found its biological and industrial use
as photoaffinity labeling agents.4 Thus, organic azides
have assumed an important position at the interface be-
tween chemistry, biology, medicine, and materials
science.
Conventional methods incorporation of the azide
group into aromatic rings5 include 1) classical nucleophil-
ic aromatic substitution (SNAr) reaction while this re-
quires activated aromatic systems bearing an electron-
withdrawing group (a, Scheme 1);6 2) diazotization of
aromatic amines in strong acidic condition and subse-
quent treatment with sodium azide, or diazo transfer
reaction by treatment of aromatic amines with triflyl
azide (b, Scheme 1);7 3) reactions of tosyl azide with or-
ganometallic reagents (b, Scheme 1). 8 4) copper cata-
lyzed coupling reaction of aryl halides or aryl boronic
acids (c, Scheme 1).9 More recently, a sonication-
mediated C-H azidation of anisole has been reported
through a Friedel-Crafts reaction process with the azide
at para position (d, Scheme 1).10 However, these me-
On the other hand, directed ortho functionalization of
arenes through C-H activation have emerged as an effec-
tive tool to construct substituted arenes.11,13,14 Although
various nitrogen-containing groups have been employed
as directing group, the ortho C-H functionalization of
arenes directed by primary amine is still limited. The
amine group of aniline substrates assisted vinyl C-H
bond activation and alkenylation were individually dis-
closed by the groups of You15 and Zhang.16
Herein, we report a novel and efficient Cu-catalyzed C-
H azidation of aniline derivatives directed by amino
group under mild conditions (e, Scheme 1). The signific-
-1-
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
1
2
3
4
5
6
7
8
9
ance of the present chemistry is threefold: 1) To the best
of our knowledge, this is a novel amino group directed
ortho C-H functionalization of simple and readily availa-
ble anilines. Moreover, the amino group could be con-
verted into Cl, Br, I, CN, OH and H by Sandmeyer reac-
tion; 2) Although various C-C and C-Heteroatom bond
formations via C-H activation have been successfully
achieved, the directed ortho C-H azidation of arenes has
not been realized till this work; 3) In contrast to employ-
ing expensive transition metal catalyst, this process is
simple, proceeds under mild conditions, uses inexpen-
sive copper catalysts, and forms valuable products that
would be difficult to synthesize by other methods.
Table 2. Cu-catalyzed Azidation of Anilines (1).a
N3
CuBr (10 mol %)
TBHP (2.0 eq)
CH3CN, 30 oC, Ar
R
R
+
R
TMSN3
+
NH2
NH2
NH2
N3
N3
2
3
1
entry
1
product
yield (%)b
entry
product
yield (%)b
Me
Me
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2a
2b
68
68
NH2
t-Bu
N3
2q 54
17
18
NH2
2
NH2
N3
Ph
N3
+
Me
R
R
2r 57
NH2
N3
N3
N3
N3
Table 1. Cu-catalyzed Azidation of 2, 4-Dimethyl
aniline (1a).a
NH2
NH2
Ph
Cl
73
85
75
61
63d
54
3
4
R = H, 2c:3c = 1.7:1
2s 63
19
20
R = tBu, 2d:3d = 1:1.8
R = c-Hex, 2e:3e = 1:1.4
R = OMe, 2f:3f = 1:1.7
R = CO2Me, 2g:3g = 2:1
R = COCH3, 2h:3h = 5:1
NH2
5
N3
6
7c
8
S
2t 67
R
9
2i 68
2j
2k 67
R = H
R = Me
R = F
NH2
10
11
12
13
14
53
N3
2l
2m
2n 55
64
43
R = Cl
R = OMe
R = CN
NH2
Ph
N3
Me
Ph
2u 57
21
22
2o 52
15
NH2
NH2
N3
N3
H
N
16
49e
68
2p
2v
N3
NH2
a Reaction conditions: 1a (0.5 mmol), TMSN3 (2.0 eq),
N3
o
catalyst, oxidant, CH3CN (2 mL), stirred at 30 C under
a Reaction conditions: 1 (0.5 mmol), TMSN3 (1.0 mmol,
Ar. TMS = trimethylsilyl. b Isolated yields.
2.0 eq), CuBr (0.05 mmol, 10 mol %), TBHP (1.0 mmol, 2.0
b
eq), CH3CN (2 mL), stirred at 30 oC under Ar. Isolated
We commenced our study by investigating the C-H
azidation of 2, 4-dimethyl aniline (1a). When the reac-
tion was performed in the presence of azidotrimethylsi-
lane (TMSN3) and tert-butyl hydroperoxide (TBHP) us-
c
o
d
yields. Reaction carried out at 50 C. 25% of 1g was re-
covered. e 36% of 1v was recovered.
electron-rich anilines were employed as the substrates,
both mono- and di-azidated products were obtained,
which can be easily separated by column chromatogra-
phy (Table 2, entries 3-8). One of the most readily avail-
able starting materials, aniline (1c), reacted smoothly in
a total yield of 73% (the ratio of mono- to di-azidated
product is 1.7:1). In the presence of an ortho-phenyl
substituent, a series of substrates containing electron
donating and withdrawing groups at the 2-phenyl ring of
the anilines were tolerant in this transformation with
moderate efficiencies (Table 2, entries 9-14). In addition,
ortho 2-naphthyl (1p) and 1-naphthyl (1q) substituted
anilines performed well in this transformation (Table 2,
entries 16-17). 2-Chloro substituted aniline 1s afforded
the corresponding chloro-substituted products 2s in 63%
yield (Table 2, entry 19). Heterocycle-containing sub-
strate such as 2-(thiophen-2-yl) aniline (1t) produced the
desired 2t in 67% yield (Table 2, entry 20). Moreover, 2-
(phenylethynyl) aniline (1u) containing an alkynyl group
also reacted smoothly with moderate yield (Table 2, en-
try 21).
o
ing CuBr as the catalyst at 60 C in CH3CN, 2-azido-4,6-
dimethylaniline (2a) was obtained in 28% yield (Table 1,
entry 1). Taking into consideration that high temperature
may lead to decomposition of the product, the reaction
temperature was decreased from 60 oC to 30 oC, a
slightly lower yield was obtained (Table 1, entry 2). To
our delight, when the reaction time was decreased 12 h to
1 h, the yield was promoted to 56% (Table 1, entry 3). The
highest yield appeared when the reaction time was 2 h, in
68% (Table 1, entry 4). In further step of exploring, we
tried to decrease the amount of oxidant or catalyst. How-
ever, both resulted in low efficiencies (Table 1, entries 5-
6). When the catalyst was replaced by CuCl or CuBr2, the
desired product 2a was obtained only in 48% and 34%
yield, respectively (Table 1, entries 7-8). Notably, this
reaction did not work when CuBr was removed or re-
placed by FeCl2 (Table 1, entries 9-10).
Under the optimized reaction conditions, the scope of
this copper-catalyzed C-H azidation reaction was dem-
onstrated with a series of aniline derivatives (Table 2). 2-
Tert-butyl aniline (1b) also performed well to give the
desired product 2b in 68% yield (Table 2, entry 2). Nota-
bly, when ortho- unsubstituted electron-deficient and
It’s noteworthy that when secondary amine was em-
ployed, this amino group directed ortho azidation reac-
tion also underwent well. However, the biggest obstacle
- 2 -
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
1
2
3
4
for secondary amine is that a large amount of starting
reactions (Eq. 1-2), which demonstrates that a radical
process may be involved in this process.
5
6
7
8
material remained, thus leading to relatively low yields.
Elevating the reaction time or increasing the reaction
temperature didn’t significantly promote the conversion
of the starting materials. Under the standard conditions,
diphenyl amine (1v) yielded the desired product 2v in
49% isolated yield with 36% of 1v recovery (Table 2, en-
try 22). The reaction of arylamines with a tertiary amino
group did not work under the standard conditions (See
Eq. S1-S2, SI). These results indicate that a free N-H
bond is required for this transformation.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Proposed Mechanism.
Scheme 2. Transformations of 2-Azidoaniline.
Although the mechanism of this transformation is not
completely clear yet,19 on the basis of above results, a
possible mechanism is proposed in Scheme 3. Interme-
diate A is initially generated by the coordination of cop-
per to the substrate.20 Subsequently, intermediate A
combines with an azide radical generated in situ from
TMSN3 and TBHP to form intermediate B. A single elec-
tron transfer (SET) from the aryl ring to the metal center
(from B to C) is possibly involved in this process.21 Then,
azido group transfer into the aryl ring with release of
CuBr forms intermediate D, which undergoes deproto-
nation via SET process leads to the product.
As mentioned above, aryl azides are versatile interme-
diates and building blocks in organic synthesis.17,18 After
this amino group directed ortho azidation protocol was
established, we were looking forward to applying aryl
azide in other transformations (Scheme 2). For the clas-
sical click reaction, 2-azido-4, 6-dimethylaniline (2a)
was treated with phenylacetylene in the presence of cata-
lytic amount of CuSO4, thus affording the corresponding
triazole 4 in 85% yield. When 2-azidoaniline (2c) was
treated with benzaldehyde, benzimidazole 5 was pro-
duced in 70% yield. 18a One of the advantages involving
primary amino group as directing group is its possibility
to be removed or go through other transformations. Re-
ferring to the well-known Sandmeyer Reaction, diazoti-
zation of 2c with NaNO2 followed by treatment with KI
produced 1-azido-2-iodobenzene 6 in 73%.18b The azide
group was well tolerated in this reaction, the resulting
product could be subsequently used in further conver-
sions. Moreover, 2-azidoanilines could also go through
some other transformations according to literatures. 9H-
Benzo[4,5]imidazo[1,2-d]tetrazole 7 could be easily pre-
pared by the reaction of 2c with BrCN via N-aryl cyana-
mide as the intermediate.18c Biologically important com-
pound 8-amino quinoline 8 was constructed using 2-
azido-aniline 2 as the starting material.18d In addition, 1-
azido-2-isocyanobenzene 9 which is a precursor of N-
heterocyclic carbene ligands, was synthesized from 2-
azido-aniline 2.18e
In conclusion, a novel and practical Cu-catalyzed or-
tho- C-H azidation of anilines has been developed. This
azidation reaction is regiospecific at amino group’s ortho
position with broad substrate scope. This chemistry not
only expands the scope of directing group, but also pro-
vides a novel C-H azidation approach leading to aryl
azides which are of high synthetic value. Further studies
to clearly understand the reaction mechanism and the
synthetic applications are ongoing in our laboratory.
ASSOCIATED CONTENT
Supporting Information. Experimental procedures,
analytical data for products, NMR spectra of products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
jiaoning@bjmu.edu.cn.
ACKNOWLEDGMENT
Financial support from National Basic Research Program of
China (973 Program) (Grant No. 2009CB825300) and Na-
tional Science Foundation of China (No. 21172006) are
greatly appreciated. We thank Xiang Sun for reproducing
the results of entries 2 and 4 in Table 2.
To further understand the mechanism, the reaction of
1a in the presence of 2,2,6,6-tetramethylpiperidine 1-
oxyl (TEMPO) or hydroquinone (HQ) as the radical sca-
venger were tested, 2a was completely inhibited in these
- 3 -
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
1
2
3
4
5
6
7
8
9
7330. Oximes, see: (c) Thirunavukkarasu, V. S.; Parthasarathy,
K.; Cheng, C. H. Angew. Chem., Int. Ed. 2008, 47, 9462. (d)
Sun, C. L.; Liu, N.; Li, B. J.; Yu, D. G.; Wang, Y.; Shi, Z. J. Org.
Lett. 2010, 12, 184. Carboxylic acids, see: (e) Chiong, H. A.;
Pham, Q. N.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 9879.
(f) Giry, R.; Maugel, N.; Li, J. J.; Wang, D. H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J. Q. J. Am. Chem. Soc. 2007, 129, 3510. (g)
Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362.
(h) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2009, 11, 2337.
(14) Recently, some removable or transformable directing
groups are described. For a review, see: (a) Rousseau, G; Breit,
B. Angew. Chem., Int. Ed. 2011, 50, 2450. For some examples
involing (2-pyridyl)sulfonyl, silanol, hydrazone, pyrimidyl and
amidine groups, see: (b) Rubia-Garcia, A.; Arrayas, R. G.;
Carretero, J. C. Angew. Chem., Int. Ed. 2009, 48, 6511. (c)
Huang, C.; Chattopadhyay, B.; Gevorgyan, V. J. Am. Chem. Soc.
2011, 133, 12406. (d) Ros, A.; López-Rodríguez, R.; Estepa, B.;
Álvarez, E.; Fernández, R.; Lassaletta, J. M. J. Am. Chem. Soc.
2012, 134, 4573. (e) Ackermann L.; Lygin, A. V. Org. Lett.
2012, 14, 764. (f) Pastine, S. J.; Gribkov, D. V.; Sames, D. J. Am.
Chem. Soc. 2006,128, 14220. (g) Gulevich, A. V.; Melkonyan, F.
S.; Sarkar, D.; Gevorgyan V. J. Am. Chem. Soc. 2012, 134,
5528.
(15) He, H.; Liu, W.-B.; Dai, L.-X.; You, S.-L. J. Am. Chem. Soc.
2009, 131, 8346. (b) Ye, K.-Y.; He, H.; Liu, W.-B.; Dai, L.-X.
Helmchen, G.; You, S.-L. J. Am. Chem. Soc. 2011, 133, 19006.
(16) Liang, Z.; Ju, L.; Xie, Y.; Huang, L.; Zhang, Y. Chem. Eur.
J. 2012, online, DOI: 10.1002/chem.201202672.
(17) For some selected examples, see: (a) Shen, M.; Leslie, B.
E.; Driver, T. G. Angew. Chem., Int. Ed. 2008, 47, 5056. (b)
Nguyen, Q.; Sun, K.; Driver, T. G. J. Am. Chem. Soc. 2012, 134,
7262. (c) Lu, B.; Luo, Y.; Liu, L.; Ye, L.; Wang, Y.; Zhang, L.
Angew. Chem., Int. Ed. 2011, 50, 8358. (d) Ryu, J.; Shin, K.;
Park, S. H.; Kim, J. Y.; Chang, S. Angew. Chem., Int. Ed. 2012,
51, 9904.
(18) (a) Shen, M.; Driver, T. G. Org. Lett. 2008, 10, 3367. (b)
Krasnokutskaya, E. A.; Semenischeva, N. I.; Filimonov, V. D.;
Knochel, P. Synthesis, 2007, 81. (c) Demko, Z. P.; Sharpless, K.
B. Org. Lett. 2001, 3, 4091. (d) Shan G.; Sun, X.; Xia, Q.; Rao,
Y. Org. Lett. 2011, 13, 5770. (e) Hahn, F. E.; Langenhahn, V.;
Meier, N.; Lugger, T., Fehlhammer, W. P. Chem. Eur. J. 2003,
9, 704.
(19) The mechanism of reported Cu-coupling reactions is
complicated. For Cu(I) catalyzed C-N coupling via a radical
process, see: (a) Paine, A. J. J. Am. Chem. Soc. 1987, 109, 1496.
(b) Aalten, H. L.; Vankoten, G.; Grove, D. M.; Kuilman, T.;
Piekstra, O. G.; Hulshof, L. A.; Sheldon, R. A. Tetrahedron
1989, 45, 5565. (c) Arai, S.; Hida, M.; Yamagishi, T. Bull. Chem.
Soc. Jpn. 1978, 51, 277. For Cu(I) catalyzed C-N coupling via a
Cu(III) intermediate, see: (d) Bethell, D. J.; Jenkins, I. L.; Quan,
P. M. J. Chem. Soc., Perkin Trans. 2 1985, 1789. (e) Zhang, S.-
L.; Liu, L.; Fu, Y.; Guo, Q.-X. Organometallics 2007, 26, 4546.
(f) Weingarten, H. J. Org. Chem. 1964, 29, 3624. (g) Lindley, J.
Tetrahedron 1984, 40, 1433. (h) Cohen, T.; Cristea, I. J. Am.
REFERENCES
(1) Griess, P. Phil. Trans. R. Soc. (London) 1864, 13, 377.
(2) For its use as flexible building blocks in the partial synthe-
sis of some very complex natural products, see: (a) Snider, B. B.;
Zhou, J. J. Org. Chem. 2005, 70, 1087. (b) Mascitti, V.; Corey,
E. J. J. Am. Chem. Soc. 2004, 126, 15664. (c) Cassidy, M. P.;
Özdemir, A. D.; Padwa, A. Org. Lett. 2005, 7, 1339.
(3) For some general reviews see: (a) Binder, W. H.; Sachsen-
hofer, R. Macromol. Rapid Commun. 2007, 28, 15. (b) Sletten,
E. M.; Bertozzi, C. R. Acc. Chem. Res. 2011, 44, 666.
(4) For recent examples, see: (a) Geurink, P. P.; Prely, L. M.;
Marel, G. A.; Bischoff, R.; Overkleeft, H. S. Top. Curr. Chem.
2012, 324, 85. (b) Voskresenska, V.; Wilson, R. M.; Panov, M.;
Tarnovsky, A. N.; Krause, J. A. Vyas, S.; Winter, A. H.; Hadad,
C. M. J. Am. Chem. Soc. 2009, 131, 11535.
(5) For reviews, see: (a)Scriven, E. F. V.; Turn-bull, K. Chem.
Rev. 1988, 88, 297. (b) Bräse, S.; Gil, C.; Knepper, K.; Zim-
mermann, V. Angew. Chem., Int. Ed. 2005, 44, 5188.
(6) (a) Keana, J. F. W.; Cai, S. X. J. Org. Chem. 1990, 55,
3640. (b) Chehade, K. A. H.; Spielmann, H. P. J. Org. Chem.
2000, 65, 4949.
(7) (a) Ritchie, C. D.; Wright, D. J. J. Am. Chem. Soc. 1971, 93,
2429. (b) Ritchie, C. D.; Virtanen, P. O. I. J. Am. Chem. Soc.
1972, 94, 4966. (c) Avemaria, F.; Zimmermann, V.; Bräse, S.
Synlett, 2004, 1163. (d) Liu, C.-Y.; Knochel, P. J. Org. Chem.
2007, 72, 7106. (e) Liu, Q.; Tor, Y. Org. Lett. 2003, 5, 2571.
(8) (a) Smith, P. A. S.; Rowe, C. D.; Bruner, L. B. J. Org. Chem.
1969, 34, 3430. (b) Gavenonis, J.; Tilley, T. D. Organometal-
lics 2002, 21, 5549.
(9) (a) Zhu, W.; Ma, D. Chem. Commun. 2004, 888. (b) Tao,
C.-Z.; Cui, X.; Li, J.; Liu, A.-X.; Liu, L.; Guo, Q.-X. Tetrahedron
Lett. 2007, 48, 3525. (c) Li, Y.; Gao, L.-X.; Han, F.-S. Chem.
Eur. J. 2010, 16, 7969.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) Telvekar, V. N.; Sasane, K. A. Synth. Commun. 2012, 42,
1085.
(11) For some recent reviews on C-H functionalization, see: (a)
Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (b)
Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Chem. Soc.
Rev. 2011, 40, 4740. (c) Lu, H.; Zhang, X. P. Chem. Soc. Rev.
2011, 40, 1899. (d) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011,
111, 1215. (e) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110,
1147. (f) Daugulis, O. Top. Curr. Chem. 2010, 292, 57. (g) Sa-
toh, T.; Miura, M. Chem. Eur. J. 2010, 16, 11212. (h) Colby, D.
A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (i)
Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. Chem. Rev. 2010, 110, 890. (j) Chen, X.; Engle,
K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48,
5094. (k) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew.
Chem., Int. Ed. 2009, 48, 9792.
(12) For an example of indirect C-H azidation of heterocycle
C-H bond, see: (a) Lubriks, D.; Sokolovs, I.; Suna, E. J. Am.
Chem. Soc. 2012, 134, 15436. For direct azidation of aliphatic
substrates, see: (b) Harschneck, T.; Hummel, S.; Kirsch, S. F.;
Klahn, P. Chem. Eur. J. 2012, 18, 1187. (c) Zhdankin, V. V.;
Krasutsky, A. P.; Kuehl, C. J.; Simonsen, A. J.; Woodward, J. K.;
Mismash, B.; Bolz, J. T. J. Am. Chem. Soc. 1996, 118, 5192. (d)
Kashinath, D.; Budin, G.; Baati, R.; Meunier, S.; Wagner,
A. Tetrahedron Lett. 2009, 50, 5379.
Chem. Soc. 1976, 98, 748. For
a Cu(II) catalyzed C-H
functionalization via a Cu(III) intermediate, see: (i) King, A. E.;
Huffman, L. M.; Casitas, A.; Costas, M.; Ribas, X.; Stahl, S. S. J.
Am. Chem. Soc. 2010, 132, 12086, and references therein.
(20) Tsuda, T.; Watanabe, K.; Miyata, K.; Yamamoto, H.;
Saegusa, T. Inorg. Chem. 1981, 20, 2728. (b) Giri, R.; Hartwig,
(13) Numerous functional groups containing nitrogen or oxy-
gen have been reported as directing groups, such as amides, see:
(a) Shabashov, D.; Daugulis, O. Org. Lett. 2006, 8, 4947. Ni-
trogen-containing heterocycles, see: (b) Kaliani, D.; Deprez, N.
R.; Desai, L. V.; Sanford, M. S. J. Am.Chem. Soc. 2005, 127,
J. F. J. Am. Chem. Soc. 2010, 132, 15860.
(21) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am.
Chem. Soc. 2006, 128, 6790.
- 4 -
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment