Transition-metal-free direct amination of simple arenes with sulfonyl azides

Article abstract of DOI:10.1016/j.tetlet.2015.02.009

A metal-free green protocol has been developed for amination of simple arenes using arylsulfonyl azides via a nitrene transfer process under solvent free conditions at 130 °C releasing N₂ gas as the sole by-product.

Full text of DOI:10.1016/j.tetlet.2015.02.009

Tetrahedron Letters xxx (2015) xxx–xxx
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Tetrahedron Letters
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Transition-metal-free direct amination of simple arenes with
sulfonyl azides
⇑
Lianggui Wang , Arun Jyoti Borah , Guobing Yan
Department of Chemistry, Lishui University, Lishui 323000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A metal-free green protocol has been developed for amination of simple arenes using arylsulfonyl azides
via a nitrene transfer process under solvent free conditions at 130 °C releasing N2 gas as the sole by-
product.
Received 2 December 2014
Revised 22 January 2015
Accepted 2 February 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Metal-free
Amination
Arene
Arylsulfonyl azide
Nitrogen-containing compounds are broadly present in natural
products and synthetic intermediates. Aryl amines are very impor-
tant key components displaying important chemical, biological,
and medicinal properties.1 Therefore efforts are continuously
driven toward the development of efficient reactions to carry out
C–N bond formation over arene molecules. Particularly, the Cu
and Pd mediated N-arylation of aryl(pseudo)halides is extensively
reported. However, it suffers from the drawbacks of using prefunc-
tionalized arene and formation of unnecessary by-products.2
Amination through C–H activation of arenes (inner-sphere mecha-
nism)3 has received special attention as the process does not
require prefunctionalized arene. Though transition metal catalyzed
C–H bond offers notable advantages in terms of reaction conditions
and selectivity, substrate scope is rather limited. The nature of
aminating source is crucial in these reactions. Parent amines can
be used in the presence of external oxidants.4 The use of preacti-
vated amino precursors like halogenated amine5 allows an external
oxidant-free method for the amination. However, the generation of
stoichiometric byproducts from the use of oxidants and bases
aliphatic, benzylic or allylic positions.7 Organic azides are widely
used for transition-metal catalyzed intermolecular C–H amination
of sp3 C–H bonds.8 However, most of them are based on nitrene
insertion reaction at allylic and benzylic positions.8a–k Recently, a
number of azide mediated sp2 C–H amination, particularly in arene
systems have been reported in the presence of various catalytic
systems.6,8k,9 These chelation-guided direct C–N bond formation
reactions occur in the absence of external oxidants. Literature
using azides as nitrene precursor for sp2 C–H activation is very
rare.10 While intramolecular case is limited to arene C–H activa-
tion,10a,c,d,f,g intermolecular sp2 C–H activation is confined to acyl
C–H bond.10h–j
This field of oxidative C–H activation process has been boosted
by the advent of several metal free protocols.11 Efforts are contin-
uously being devoted for metal free oxidative amination process
using various aminating agents.12 Ayyangar and co-workers
reported the generation of sulfonyl nitrene from azides via ther-
molysis process. These reports mainly revealed the formation of
azepines.13 Although the synthesis of sulfonanilde from benzene
has been reported during the course of such reactions, the amina-
tion process of arene is not explored widely and is very limited.
Here we wish to report an intermolecular metal free nitrene trans-
fer to arene C–H bond using arylsulfonyl azide as the source of
nitrogen.
6
cannot be avoided under these conditions. Use of organic azides
provides another oxidant-free method that releases nitrogen gas
as the only by-product. Nitrene insertion reaction (outer sphere
mechanism) is an alternative tool for introducing a functional
group in the presence of a transition metal catalyst.3f,7 Nitrene-
transfer process is successfully applied for sp3 C–H bonds at
Initially, our study focused on the C–H amination process of
mesitylene as a model substrate with different arylsulfonyl azides
as the nitrene source. To evaluate the scope of the azides, we used
4-methylbenzenesulfonyl azide (Scheme 1, 2a, 0.3 mmol) with
0.5 mL of mesitylene (Scheme 1, 1a) at 80 °C. The reaction was
allowed to run for 24 h.
⇑
Corresponding author. Tel./fax: +86 578 2271308.
E-mail address: gbyan@lsu.edu.cn (G. Yan).
These authors contributed equally.
http://dx.doi.org/10.1016/j.tetlet.2015.02.009
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wang, L.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.02.009

2
L. Wang et al. / Tetrahedron Letters xxx (2015) xxx–xxx
After successful investigation with TsN3, we extended the C–H
SO2N3
amination of mesitylene with various sulfonyl azides (Table 1,
2a–m). It was observed that, the substituents on the aromatic ring
of azides have slight impact on the nitrene transfer process. Elec-
tron withdrawing substituents were found to be effective in terms
of yields of the reaction (entries 5–12, 80–96% yield) in comparison
with electron donating substituents (entries 1–3, 67–80% yield).
The azide, 2m bearing heteroarene group also facilitates the
nitrene transfer to mesitylene effectively under the reaction
conditions and 88% of the aminated product (3m) was isolated.
We also observed the efficacy of the nitrene transfer process
with different arenes (Table 2). For this purpose we have chosen
TsN3 as the suitable precursor and all the reactions were carried
out at 130 °C under solvent free conditions. Although the arenes
(Table 2, entries 1–5) were aminated under the standard condition,
selectivity was found to be poor with unsymmetrical arenes
(Table 2, entries 3–5), leading to the formation of regiomers, as
detected via 1H NMR spectral data. The isomers were found to be
NHSO2C6H4CH3
+
T (o C)
1a
2a
3a
Scheme 1.
But its progress was found to be disappointing and trace
amount of C–H aminated product 3a (Scheme 1) was detected
through GC–MS. Changing the temperature to 120 °C, 40% of the
product 3a was isolated. The product was characterized through
NMR spectral data. Further increasing the temperature to 130 °C,
the product yield increased to 67% within a period of 12 h. These
observations lead us to believe that the temperature is very crucial
for the amination process. To our delight, all the reactions were
found to be effective under solvent free conditions.14
non-separable and isolated as
a mixture. While 1-bromo-4-
methoxybenzene (Table 2, entry 3) provided 1:1 ortho product
(4c:4c0, 75% combined yield), ortho-xylene provided 1:1 2,3-
dimethyl-N-tosylbenzenamine and 3,4-dimethyl-N-tosylbenzen-
amine products (4d:4d0, 78% combined yield) and toluene provided
1:1 N-(2-methylphenyl)-4-methylbenzenesulfonamide and N-(4-
methylphenyl)-4-methylbenzenesulfonamide products (4e:4e0,
80% combined yield). We have not detected formation of over ami-
nated product with any kind of arene under the reaction condi-
tions. However, with heteroarenes, the scope of the nitrene
transfer process is limited (Table 2, entries 6 and 7). While with
thiophene, trace amount of aminated product was detected, with
Table 1
Reactions of different azides with mesitylenea
NHSO2Ar1
Ar1SO2N3
+
130 oC
1a
2a-m
3a-m
Entry
Ar1SO2N3 (2a–m)
Products
(3a–m)
Yieldb
(%)
2a
1
2
3
4
5
6
SO2N3
3a
3b
3c
3d
3e
3f
67
78
76
83
80
86
Table 2
2b
2c
SO2N3
SO2N3
2d
a
Amination of different arenes with TsN3
SO2NHAr2
Ar2H
MeO
Br
+
SO2N3
130 o
C
2a
Ar2H
4a-g
Product
SO2N3
Entry
Yieldb
(4a–g)
(%)
2e
SO2N3
SO2N3
1
2
4a
76
2f
F
F
4b
53
7
8
3g
3h
85
80
2g
SO2N3
4c
4c'
F
Br
3
4
4c:4c0 (1:1)c
75d,e
2h
SO2N3
Br
OMe
Cl
4d:4d0 (1:1)c
78d
9
3i
89
96
89
2i
SO2N3
2j
2l
10
11
F3C
F3C
SO2N3
3j
5
6
4e:4e0 (1:1)c
80d
3k
4f
Trace
2k
S
SO2N3
7
4g
—
12
13
O2N
S
SO2N3
3l
86
88
N
a
b
c
Reaction condition: Arene (0.5 mL), TsN3 (0.3 mmol), 130 °C, 12 h.
Isolated yield.
2m
SO2N3
3m
Ratio determined from 1H NMR integration.
Combined yield.
a
d
e
Reaction condition: 1a (0.5 mL), 2a-m (0.3 mmol), 130 °C, 12 h.
Isolated yield.
b
4c:4c0 can be isolated by performing thin layer chromatography twice.
Please cite this article in press as: Wang, L.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.02.009

L. Wang et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
659; (c) Ng, K.-H.; Zhou, Z.; Yu, W.-Y. Chem. Commun. 2013, 7031–7033; (d)
Boursalian, G. B.; Ngai, M.-Y.; Hojczyk, K. N.; Ritter, T. J. Am. Chem. Soc. 2013,
135, 13278–13281.
D
D
D
D
TsN3
+
6. (a) Ryu, J.; Shin, K.; Park, S. H.; Kim, J. Y.; Chang, S. Angew. Chem., Int. Ed. 2012,
51, 9904–9908; (b) Kim, J. Y.; Park, S. H.; Ryu, J.; Cho, S. H.; Kim, S. H.; Chang, S.
J. Am. Chem. Soc. 2012, 134, 9110–9113; (c) Shin, K.; Baek, Y.; Chang, S. Angew.
Chem., Int. Ed. 2013, 52, 8031–8036; (d) Ryu, J.; Kwak, J.; Shin, K.; Lee, D.; Chang,
S. J. Am. Chem. Soc. 2013, 135, 12861–12868.
7. (a) Díaz-Requejo, M. M.; Pérez, P. J. Chem. Rev. 2008, 108, 3379–3394; (b)
Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417–424; (c) Collet, F.; Dodd,
R. H.; Dauban, P. Chem. Commun. 2009, 5061–5074; (d) Simone, F.; Alessandro,
C.; Emma, G. Dalton Trans. 2009, 5434–5443; (e) Collet, F.; Lescot, C.; Dauban, P.
Chem. Soc. Rev. 2011, 40, 1926–1936; (f) Chang, J. W. W.; Ton, T. M. U.; Chan, P.
W. H. Chem. Rec. 2011, 11, 331–357; (g) Che, C.-M.; Lo, V. K.-Y.; Zhou, C.-Y.;
Huang, J.-S. Chem. Soc. Rev. 2011, 40, 1950–1975; (h) Ramirez, T. A.; Zhao, B.;
Shi, Y. Chem. Soc. Rev. 2012, 41, 931–942; (i) Roizen, J. L. Harvey; M. E.; Bois, J. D
Acc. Chem. Res. 2012, 45, 911–922.
8. (a) Katsuki, T. Chem. Lett. 2005, 34, 1304–1309; (b) Cenini, S.; Gallo, E.; Caselli,
A.; Ragaini, F.; Fantauzzi, S.; Piangiolino, C. Coord. Chem. Rev. 2006, 250, 1234–
1253; (c) Badiei, Y. M.; Dinescu, A.; Dai, X.; Palomino, R. M.; Heinemann, F. W.;
Cundari, T. R.; Warren, T. H. Angew. Chem., Int. Ed. 2008, 47, 9961–9964; (d)
Fantauzzi, S.; Gallo, E.; Caselli, A.; Ragaini, F.; Casati, N.; Macchic, P.; Cenini, S.
Chem. Commun. 2009, 3952–3954; (e) Lu, H.; Subbarayan, V.; Tao, J.; Zhang, X.
P. Organometallics 2010, 29, 389–393; (f) Driver, T. G. Org. Biomol. Chem. 2010,
8, 3831–3846; (g) Liu, Y.; Che, C.-M. Chem. Eur. J. 2010, 16, 10494–10501; (h)
Lyaskovskyy, V.; Suarez, A. I. O.; Lu, H.; Jiang, H.; Zhang, X. P.; de Bruin, B. J. Am.
Chem. Soc. 2011, 133, 12264–12273; (i) Nishioka, Y.; Uchida, T.; Katsuki, T.
Angew. Chem., Int. Ed. 2013, 52, 1739–1742; (j) Suárez, J. R.; Chiara, J. L. Chem.
Commun. 2013, 9194–9196; (k) Intrieri, D.; Zardi, P.; Caselli, A.; Gallo, E. Chem.
Commun. 2014, 11440–11453; (l) Kang, T.; Kim, Y.; Lee, D.; Wang, Z.; Chang, S.
J. Am. Chem. Soc. 2014, 136, 4141–4144; (m) Wang, N.; Li, R.; Li, L.; Xu, S.; Song,
H.; Wang, B. J. Org. Chem. 2014, 79, 5379–5385.
9. (a) Shi, J.; Zhou, B.; Yang, Y.; Li, Y. Org. Biomol. Chem. 2012, 10. 8953-5388; (b)
Kim, J.; Kim, J.; Chang, S. Chem. Eur. J. 2013, 19, 7328–7333; (c) Yadav, M. R.; Rit,
R. K.; Sahoo, A. K. Org. Lett. 2013, 15, 1638–1641; (d) Bhanuchandra, M.; Yadav,
M. R.; Rit, R. K.; Kuram, M. R.; Sahoo, A. K. Chem. Commun. 2013, 5225–5227; (e)
Zheng, Q.-Z.; Liang, Y.-F.; Qin, C.; Jiao, N. Chem. Commun. 2013, 5654–5656; (f)
Yu, D.-G.; Suri, M.; Glorius, F. J. Am. Chem. Soc. 2013, 135, 8802–8805; (g) Lee,
D.; Kim, Y.; Chang, S. J. Org. Chem. 2013, 78, 11102–11109; (h)
Thirunavukkarasu, V. S.; Raghuvanshi, K.; Ackermann, L. Org. Lett. 2013, 15,
3286–3289; (i) Tang, C.; Yuan, Y.; Cui, Y.; Jiao, N. Eur. J. Org. Chem. 2013, 7480–
7483; (j) Zhou, B.; Yang, Y.; Shi, J.; Feng, H.; Li, Y. Chem. Eur. J. 2013, 19, 10511–
10515; (k) Park, S. H.; Kwak, J.; Shin, K.; Ryu, J.; Park, Y.; Chang, S. J. Am. Chem.
Soc. 2014, 136, 2492–2502; (l) Kim, J.; Chang, S. Angew. Chem., Int. Ed. 2014, 53,
2203–2207; (m) Park, S. H.; Park, Y.; Chang, S. Org. Synth. 2014, 91, 52–59; (n)
Kim, H. J.; Ajitha, M. J.; Lee, Y.; Ryu, J.; Kim, J.; Lee, Y. J.; Chang, S. J. Am. Chem.
Soc. 2014, 136, 1132–1140; (o) Wang, H.; Yu, Y.; Hong, X.; Tan, Q.; Xu, B. J. Org.
Chem. 2014, 79, 3279–3288; (p) Shin, K.; Ryu, J.; Chang, S. Org. Lett. 2014, 16,
2022–2025; (q) Jia, X.; Han, J. J. Org. Chem. 2014, 79, 4180–4185.
+
130 o
C
D
KH/KD=1
D
0.25ml
0.25ml
D
D
NHTs
D
NHTs
+
D
D
75%
Scheme 2. Isotope effect.
pyridine, this approach did not lead to the formation of the desired
product.
The mechanism of this reaction is not clear. The kinetic isotope
effect (kH/kD = 1.0) was determined by an intermolecular competi-
tion experiment, indicating that the cleavage of C–H bond in this
amination is not included in the rate-determining step (Scheme 2).
In conclusion, we have developed an efficient nitrene transfer
process to arenes using azides under metal free conditions. Various
sulfonyl azides were found to be effective under the protocol.
While unsymmetrical arenes provided regiomeric mixture of ami-
nated products, heteroarene could not be carried out for amination.
Acknowledgments
We thank the Natural Science Foundation of Zhejiang Province
of China (No. LY12B02006 and LY13B020005) for financial support.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.02.
009.
10. (a) Stokes, B. J.; Dong, H.; Leslie, B. E.; Pumphrey, A. L.; Driver, T. G. J. Am. Chem.
Soc. 2007, 129, 7500–7501; (b) Dong, H.; Shen, M.; Redford, J. E.; Stokes, B. J.;
Pumphrey, A. L.; Driver, T. G. Org. Lett. 2007, 9, 5191–5194; (c) Shen, M.; Leslie,
B. E.; Driver, T. G. Angew. Chem., Int. Ed. 2008, 47, 5056–5059; (d) Shou, W. G.;
Li, J.; Guo, T.; Lin, Z.; Jia, G. Organometallics 2009, 28, 6847–6854; (e) Liu, Y.;
Wei, J.; Che, C.-M. Chem. Commun. 2010, 6926–6928; (f) Dong, H.; Latka, R. T.;
Driver, T. G. Org. Lett. 2011, 13, 2726–2729; (g) Pumphrey, A. L.; Dong, H.;
Driver, T. G. Angew. Chem., Int. Ed. 2012, 51, 5920–5923; (h) Xiao, W.; Zhou, C.-
Y.; Che, C.-M. Chem. Commun. 2012, 5871–5873; (i) Wei, J.; Xiao, W.; Zhou, C.-
Y.; Che, C.-M. Chem. Commun. 2014, 3373–3376; (j) Jin, L.-M.; Lu, H.; Cui, Y.;
Lizardi, C. L.; Arzua, T. N.; Wojtas, L.; Cui, X.; Zhang, X. P. Chem. Sci. 2014, 5,
2422–2427.
References and notes
1. (a) Ricci, A. Amino Group Chemistry: From Synthesis to the Life Sciences; Wiley-
VCH: Weinheim, 2008; (b) Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2, 284–
287; (c) Candeias, N. R.; Branco, L. C.; Gois, P. M. P.; Afonso, C. A. M.; Trindade,
A. F. Chem. Rev. 2009, 109, 2703–2802.
2. (a) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969–5970; (b)
Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901–7902; (c) Evano,
G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054–3131; (d) Ley, S. V.;
Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400–5449; (e) Hartwig, J. F. Acc.
Chem. Res. 2008, 41, 1534–1544; (f) Monnier, F.; Taillefer, M. Angew. Chem., Int.
Ed. 2009, 48, 6954–6971.
11. (a) Samanta, R.; Matcha, K.; Antonchick, A. P. Eur. J. Org. Chem. 2013, 5769–
5804; (b) Mehta, V. P.; Punji, B. RSC Adv. 2013, 3, 11957–11986.
12. (a) Fan, R.; Li, W.; Pu, D.; Zhang, L. Org. Lett. 2009, 11, 1425–1428; (b) Kim, H. J.;
Kim, J.; Cho, S. H.; Chang, S. J. Am. Chem. Soc. 2011, 133, 16382–16385; (c)
Yoshimura, A.; Nemykin, V. N.; Zhdankin, V. V. Chem. Eur. J. 2011, 17, 10538–
10541; (d) Kantak, A. A.; Potavathri, S.; Barham, R. A.; Romano, K. M.; DeBoef, B.
J. Am. Chem. Soc. 2011, 133, 19960–19965; (e) Ochiai, M.; Miyamoto, K.;
Kaneaki, T.; Hayashi, S.; Nakanishi, W. Science 2011, 332, 448–451; (f) Borah, A.
J.; Phukan, P. Chem. Commun. 2012, 5491–5493; (g) Souto, J. A.; Becker, P.;
Iglesias, Á.; Muñiz, K. J. Am. Chem. Soc. 2012, 134, 15505–15511; (h) Xue, Q.;
Xie, J.; Li, H.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 3700–3702.
13. (a) Ayyangar, N. R.; Bambal, R. B.; Nikalje, D. D.; Srinivasan, K. V. Can. J. Chem.
1985, 63, 887–890; (b) Ayyangar, N. R.; Bambal, R. B.; Lugade, A. G. Heterocycles
1982, 18 (Spec. 1), 77–82; (c) Ayyangar, N. R.; Bambal, R. B.; Lugade, A. G. J.
Chem. Soc., Chem. Commun. 1981, 15, 790–791; (d) Ayyangar, N. R.; Phatak, M.
V.; Purchit, A. K. Chem. Ind. (London) 1979, 23, 853–854.
3. (a) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007,
107, 5318–5365; (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147–
1169; (c) Armstrong, A.; Collins, J. C. Angew. Chem., Int. Ed. 2010, 49, 2282–
2285; (d) Cho, S. H. J.; Kim, Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40,
5068–5083; (e) Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev.
2011, 40, 4740–4761; (f) Stokes, B. J.; Driver, T. G. Eur. J. Org. Chem. 2011, 4071–
4088; (g) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651–3678; (h)
Louillat, M.-L.; Patureau, F. W. Chem. Soc. Rev. 2014, 43, 901–910.
4. (a) Thu, H.-Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048–9049; (b)
Wang, Q.; Schreiber, S. L. Org. Lett. 2009, 11, 5178–5180; (c) Monguchi, D.;
Fujiwara, T.; Furukawa, H.; Mori, A. Org. Lett. 2009, 11, 1607–1610; (d) Xiao, B.;
Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 1466–1474; (e)
Zhao, H.; Shang, Y.; Su, W. Org. Lett. 2013, 15, 5106–5109; (f) Shrestha, R.;
Mukherjee, P.; Tan, Y.; Litman, Z. C.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135,
8480–8483.
14. Using a solid arene, for example, dimethoxybenzene, 1,3,5-trimethoxybenzene
or 1,2,4,5-tetramethylbenzene with TsN3 in the presence of different solvents
like DCE, DMSO and DMF, the reaction failed.
5. (a) Sun, K.; Li, Y.; Xiong, T.; Zhang, J.; Zhang, Q. J. Am. Chem. Soc. 2011, 133,
1694–1697; (b) Grohmann, C.; Wang, H.; Glorius, F. Org. Lett. 2012, 14, 656–
Please cite this article in press as: Wang, L.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.02.009