Sodium chlorate as a viable substoichiometric oxidant for cobalt-catalyzed oxidative annulation of aryl sulfonamides with alkynes

Article abstract of DOI:10.1016/j.tetlet.2016.06.059

In this work, NaClO₃is demonstrated for the first time as an efficient and versatile oxidant in the catalytic C–H activation reaction. By using sodium chlorate as the oxidant, a highly regioselective cobalt-catalyzed oxidative annulation of ary

Full text of DOI:10.1016/j.tetlet.2016.06.059

Accepted Manuscript
Sodium chlorate as a viable substoichiometric oxidant for cobalt-catalyzed ox-
idative annulation of aryl sulfonamides with alkynes
You Ran, Yudong Yang, Luoqiang Zhang
PII:
S0040-4039(16)30728-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.059
TETL 47786
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
20 April 2016
7 June 2016
14 June 2016
Please cite this article as: Ran, Y., Yang, Y., Zhang, L., Sodium chlorate as a viable substoichiometric oxidant for
cobalt-catalyzed oxidative annulation of aryl sulfonamides with alkynes, Tetrahedron Letters (2016), doi: http://
dx.doi.org/10.1016/j.tetlet.2016.06.059
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Sodium chlorate as a viable
Leave this area blank for abstract info.
substoichiometric oxidant for cobalt-
catalyzed oxidative annulation of aryl
sulfonamides with alkynes
You Ran, Yudong Yang*, Luoqiang Zhang

1
Tetrahedron Letters
Sodium chlorate as a viable substoichiometric oxidant for cobalt-catalyzed oxidative
annulation of aryl sulfonamides with alkynes
You Ran, Yudong Yang and Luoqiang Zhang
,
College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
In this work, NaClO3 is demonstrated for the first time as an efficient and versatile oxidant in the
catalytic C−H activation reaction. By using sodium chlorate as the oxidant, a highly
regioselective cobalt-catalyzed oxidative annulation of aryl sulfonamides with alkynes has been
developed and can be extended to the annulation of benzamide.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Cobalt catalysis
Sultam
C−H activation
Oxidative annulation
Recently, transition-metal-catalyzed C−H functionalization has
emerged as an efficient and powerful strategy for the
construction of carbon−carbon and carbon−heteroatom bonds.1 In
particular, transition-metal-catalyzed oxidative C−H activation
has attracted much attention due to their high atom- and step-
economy and versatility in organic transformations.2 In these
reactions, oxidation represents a fundamental and important step
to constitute the catalytic cycle, in which reoxidation of the
catalytic metal center from a relatively low oxidation state to a
higher oxidation state is accomplished. Furthermore, oxidant
could work as an important variant to dictate the reaction
selectivity as well.3 Thus, various external oxidants, including
metal salts (e.g., Cu(OAc)2, Ag2CO3, etc.), peroxides,
hypervalent iodine(III) reagents, DDQ, and O2 or air, are often
employed. Although these common oxidants could support most
of the currently developed reactions, they still suffer from some
limitations, including: 1) The concomitant side-reactions caused
by these oxidants complicate the transformations. For example,
undesired acetoxylation could occur when PhI(OAc)2 and
Cu(OAc)2 are employed4 and N-oxidation of the nitrogen-
containing substrates could take place in the presence of
peroxides;5 2) The wastes released from oxidants, such as heavy
metals and aromatic iodides, would be harmful to environment;
and 3) Stoichiometric or excess amounts of oxidants are required
in most cases, thus diminishing the appeal of oxidative C−H
activation. Therefore, exploitation of lowly toxic, inexpensive
and environmentally benign oxidants that could work operatively
with the catalytic system remains an important task in oxidative
C−H activation.
Sodium chlorate is usually used in metal extraction and paper
bleaching in modern chemical industry.6 Despite its good
oxidative ability, NaClO3 is seldom used as an oxidant in organic
synthesis. To the best of our knowledge, whether NaClO3 can be
applicable as an oxidant in transition-metal-catalyzed oxidative
C−H functionalization has never been reported. We envisioned
that NaClO3 would be an ideal oxidant in catalytic C−H
activation on the basis of the following considerations: 1) The
high oxidation state of Cl (potential reduction from Cl(+5) to
Cl(−1)) may minimize the amount of oxidant used; and 2)
NaClO3 is an inexpensive, easily-available and -handling oxidant,
hence improving the reaction practicality.
On another hand, transition-metal-catalyzed oxidative C−H
activation/annulation of arenes with alkynes is regarded as a
highly efficient and expedient tactics to construct diverse
carbocycles and heterocycles. In the past decade, numerous noble
metals,7,8 including Pd, Rh, and Ru, have been successfully
employed in these catalytic annulation reactions. From the
viewpoint of economy and sustainable chemistry, using an
inexpensive and abundant metal to accomplish these catalytic
annulations should be more attractive and practical.9 Herein, we
disclose
a regioselective cobalt-catalyzed oxidative C−H
activation/annulation of sulfonamides with alkynes by using
NaClO3 as the oxidant to synthesize sultams which are common
motifs in pharmaceuticals and biologically active compounds
(Scheme 1).10,11 Notably, this is the first demonstration of
NaClO3 as an efficient and versatile oxidant in the catalytic C−H
activation reactions.
———
 Corresponding author. Tel.: +86-28-85412285; e-mail: yangyudong@scu.edu.cn (Y. Yang).

2
Tetrahedron
a
1a (0.2 mmol, 1.0 equiv), 2a (2.0 equiv), oxidant (1.5 equiv), catalyst (20
mol%) and PivOH (1.0 equiv) were stirred in 1,4-dioxane (1.0 mL) at 120 °C
for 24 hours under an atmosphere of N2.
b Isolated yields.
c Without PivOH.
d NaClO3 (1.2 equiv) was used.
e Co(OAc)2∙4H2O (10 mol%) was used.
f NaClO3 (0.75 equiv) was used.
g Reaction was performed under air. n.d. = not detected. n.r. = no reaction.
Scheme 1 Oxidative annulation of aryl sulfonamides with both
terminal and internal alkynes by using NaClO3 as the oxidant.
With the optimized conditions in hand, we next examined the
scope of this catalytic system with respect to sulfonamide
derivatives as summarized in Table 2. Both the sulfonamides
with electron-donating and -withdrawing groups worked
smoothly under the standard conditions, giving the corresponding
products with an excellent regioselectivity in moderate to
excellent yields (Table 2， 3b-h). The positions of substituents
on the aromatic rings did not show significant influence on the
yields (3f and 3g). Sulfonamide with a trifluoromethyl group at
the ortho position could also afford the desired product 3h in
79% yield, indicating that the reaction seems insensitive to the
steric hindrance. It is notable that heteroaromatic and condensed
aromatic substrates also displayed good reactivity and excellent
regioselectivity under the current reaction conditions (3i and 3j).
In addition, the absolute configuration of 3a was confirmed by
single crystal X-ray analysis (Table 2).13
Our initial optimization focused on the effect of oxidants on
the cobalt-catalyzed annulation of aryl sulfonamide 1a and
phenyl acetylene 2a (Table 1). It was found that a mixture of
regioisomers 3a and 3a' (67/29) could be obtained in the
presence of Co(OAc)2 (20 mol%), Ag2CO3 (1.5 equiv), and
PivOH (1.0 equiv) in 1,4-dioxane at 120 °C (Table 1， entry 1).
The replacement of Ag2CO3 with Ag2O could slightly improve
the selectivity of products, while AgOAc gave a diminished ratio
of 3a/3a' (entries 2 and 3). All the other common oxidants in our
tests, including Mn(OAc)2/O2, Cu(OAc)2, PhI(OAc)2, Na2S2O8,
failed to promote this reaction (entries 4−7). To our delight, 3a
was afforded in 87% yield as a single regioisomeric product
when NaClO3 was employed as the oxidant (entry 8). No
annulated product 3a or 3a' was detected in the absence of
PivOH, which indicated the essential role of PivOH in this
reaction (entry 9). [Cp*Co(CO)I2] gave a comparable yield (entry
10). Other cobalt salts exhibited inferior efficiency in the
catalysis of annulation of sulfonamide 1a with phenyl acetylene
2a (entries 11 and 12). 1,4-Dioxane was found to be the best
solvent for this transformation (Table S1, entry 11, see the
Supporting Information). Interestingly, only 0.75 equiv of
NaClO3 was required under our conditions, which implied that
Table 2 Scope of aryl sulfonamidesa,b
−
−
the reductive intermediates of ClO3 , such as ClO2 and ClO−,
could also act as the oxidant for the regeneration of Co(III)
species (entry 15).12 No decrease in the yield was detected when
cobalt(II) acetate tetrahydrate was used instead of anhydrous salt
under air (entry 16).
Table 1.Optimization of the Reaction Conditionsa,b
a
1 (0.2 mmol, 1.0 equiv), 2a (2.0 equiv), Co(OAc)2∙4H2O (10 mol%),
NaClO3 (0.75 equiv) and PivOH (1.0 equiv) were stirred in 1,4-dioxane (1.0
mL) at 120 °C for 24 hours under air.
b Isolated yields.
Entry
Catalyst
Oxidant
3a/3a' Yieldb (%)
1
2
Co(OAc)2
Co(OAc)2
Ag2CO3
Ag2O
67/29
79/16
We next investigated the generality of alkynes 2 with various
substitutions as depicted in Table 3. Both aromaric and aliphatic
terminal alkynes reacted smoothly with sulfonamide 1a to give
the corresponding sultam products with excellent regioselectivity
in moderate to excellent yields. It is noteworthy that an array of
functional groups, including alkoxy, halide, ester, alkenyl and
trimethylsilyl, were tolerant with the reaction conditions, which
could offer an opportunity for further transformations (Table 3,
4b-k). The reaction could also be extended to internal alkynes.
Symmetrical alkynes such as diaryl- and dialkyl-substituted
acetylenes could be efficiently converted to the desired sultams
(4l-t). However, unsymmetrical aryl alkyl alkynes gave a mixture
of regioisomers, but with an obvious preference having the
phenyl substituent proximal to nitrogen (4u and 4v), which could
be separated by column chromatography and crystallization.
3
Co(OAc)2
AgOAc
57/28.
trace
4
Co(OAc)2
Mn(OAc)2/O2
Cu(OAc)2
PhI(OAc)2
Na2S2O8
NaClO3
Ag2CO3
NaClO3
NaClO3
NaClO3
NaClO3
NaClO3
NaClO3
NaClO3
5
Co(OAc)2
n.d.
6
Co(OAc)2
n.d.
7
Co(OAc)2
n.r.
8d
Co(OAc)2
87/trace
n.r.
9c
Co(OAc)2
10d
11d
12d
13 d
14d,e
15e,f
16e,f,g
Co(acac)2
57/trace
30/trace
88/trace
88/trace
89/trace
92/trace
92/trace
CoCl2
[Cp*Co(CO)I2]
Co(OAc)2∙4H2O
Co(OAc)2∙4H2O
Co(OAc)2∙4H2O
Co(OAc)2∙4H2O

3
To further examine the generality of our methodology,
benzamide 5 was subjected to the standard conditions, giving a
single regioisomer 6 in 82% yield (eqn (1)). In addition, NaClO3
was also successfully employed as an oxidant in the cobalt-
catalyzed oxidative annulation of benzamide 5 with styrene (eqn
(2)), rhodium-catalyzed oxidative annulation of azobenzene with
diphenylacetylene (eqn (3)) and cobalt-catalyzed homo-coupling
of benzamide 5 (eqn (4)), which further proved the efficiency and
versatility of NaClO3 as an oxidant in oxidative C−H activation.
Table 3. Scope of Alkynesa,b
To further gain insight of the reaction mechanism, several
common radical inhibitors were added, including 2,2,6,6-
tetramethylpiperidine-N-oxyl (TEMPO), 2,6-di-tert-butyl-p-
cresol (BHT) and ascorbic acid (Table S3 in SI). All of these
radical scavengers exhibited significant suppression effect on the
reaction, thus indicating that a radical process might be involved.
Based on the above results as well as previous reports, a
proposed reaction mechanism was illustrated in Scheme
2.9b,11b,c,14 Initial coordination of cobalt complex to 1a leads to a
Co(III) species 7, which then undergoes C−H metallation and
alkyne insertion to deliver a seven-membered metallacycle
intermediate 9. Subsequent reductive elimination affords the
desired sultam product 3a and releases the Co(I) species. Finally,
−
the reoxidation of Co(I) to the reactive Co(III) species by ClOn
completes the catalytic cycle.
a
1a (0.2 mmol, 1.0 equiv), 2 (2.0 equiv), Co(OAc)2∙4H2O (10 mol%),
NaClO3 (0.75 equiv) and PivOH (1.0 equiv) were stirred in 1,4-dioxane (1.0
mL) at 120 °C for 24 hours under air.
b Isolated yields.
c NaClO3 (1.0 equiv), Co(OAc)2∙4H2O (20 mol%) and PivOH (2.0 equiv).
Scheme 2 Proposed mechanism.
In conclusion,
a
cobalt-catalyzed annulation of aryl
sulfonamides with both terminal and internal alkynes to
synthesize sultams has been developed. A broad set of
sulfonamides and alkynes could be converted to the desired
products with high regioselectivity in moderate to excellent
yields. For the first time, NaClO3 has been proved to be an
efficient and versatile oxidant to sustain the transition-metal-
catalyzed oxidative C−H activation reaction.

4
Tetrahedron
1007; (e) Yang, Y.; Li, K.; Cheng, Y.; Wan, D.; Li, M.; You, J.
Chem. Commun. 2016, 58, 2872.
Acknowledgments
8. For selected examples on noble metal-catalyzed oxidative
annulation of arenes with alkynes, see: (a) Shi, Z.; Zhang, C.; Li,
S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed. 2009,
48, 4572; (b) Shi, Z.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int.
Ed. 2009, 48, 7895; (c) Ackermann, L.; Lygin, A. V.; Hofmann, N.
Angew. Chem., Int. Ed. 2011, 50, 6379; (d) Zhang, G.; Yang, L.;
Wang, Y.; Xie, Y.; Huang, H. J. Am. Chem. Soc. 2013, 135, 8850;
(e) Kathiravan, S.; Nicholls, I. A. Chem. Commun. 2014, 50, 14964;
(f) Li, D. Y.; Chen, H. J.; Liu, P. N. Org. Lett. 2014, 16, 6176; (g)
Qi, Z.; Tang, G.-D.; Pan, C.-L.; Li, X. Org. Biomol. Chem. 2015,
13, 10977; (h) Mo, J.; Wang, L.; Cui, X. Org. Lett. 2015, 17, 4960.
9. For selected examples on cheap transition-metal-catalyzed
oxidative annulation of arenes with alkynes, see: (a) Shiota, H.;
Ano, Y.; Aihara, Y.; Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc.
2011, 133, 14952; (b) Grigorjeva, L.; Daugulis, O. Angew. Chem.,
Int. Ed. 2014, 53, 10209; (c) Sun, B.; Yoshino, T.; Kanai, M.;
Matsunaga, S. Angew. Chem., Int. Ed. 2015, 54, 12968; (d) Castro,
L. C. M.; Obata, A.; Aihara, Y.; Chatani, N. Chem.–Eur. J. 2016,
22, 1362; (e) Prakash, S.; Muralirajan, K.; Cheng, C.-H. Angew.
Chem., Int. Ed. 2016, 55, 1844.
10. (a) Drews, J. Science 2000, 287, 1960. (b) DeSantis, L. Surv.
Ophthalmol. 2000, 44, 119; (c) Wells, G. J.; Tao, M.; Josef, K. A.;
Bihovsky, R. J. Med. Chem. 2001, 44, 3488; (d) Brooke, E. W.;
Davies, S. G.; Mulvaney, A. W.; Okada, M.; Pompeo, F.; Sim, E.;
Vickers, R. J.; Westwood, I. M. Biorg. Med. Chem. 2003, 13, 2527.
11. (a) Pham, M. V.; Ye, B.; Cramer, N. Angew. Chem., Int. Ed. 2012,
51, 10610; (b) Planas, O.; Whiteoak, C. J.; Company, A.; Ribas, X.
Adv. Synth. Catal. 2015, 357, 4003; (c) Kalsi, D.; Sundararaju, B.
Org. Lett. 2015, 17, 6118.
This work was supported by grants from the National NSF of
China (No. 21502123), and Comprehensive Training Platform of
Specialized Laboratory, College of Chemistry, Sichuan
University.
References and notes
1. (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2009, 48, 5094; (b) Lyons, T. W.; Sanford, M. S. Chem.
Rev. 2010, 110, 1147; (c) Zhao, D.; You, J.; Hu, C. Chem.–Eur. J.
2011, 17, 5466; (d) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Rev.
2011, 111, 1293; (e) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord,
J.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 10236; (f)
Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012,
112, 5879; (g) Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013, 5,
369; (h) Shang, X.; Liu, Z.-Q. Chem. Soc. Rev. 2013, 42, 3253; (i)
Huang, Z.; Dong, G. Tetrahedron Lett. 2014, 55, 5869; (j) Kuhl,
N.; Schröder, N.; Glorius, F. Adv. Synth. Catal. 2014, 356, 1443;
(k) Yang, L.; Huang, H. Chem. Rev. 2015, 115, 3468.
2. (a) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev.
2011, 40, 5068; (b) Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem.
Soc. Rev. 2012, 41, 3381; (c) Song, G.; Wang, F.; Li, X. Chem. Soc.
Rev. 2012, 41, 3651; (d) Louillat, M.-L.; Patureau, F. W. Chem.
Soc. Rev. 2014, 43, 901; (e) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.;
Liu, Z.; Zhang, Y. Org. Chem. Front. 2015, 2, 1107.
3. (a) Stuart, D. R.; Villemure, E.; Fagnou, K. J. Am. Chem. Soc.
2007, 129, 12072; (b) Potavathri, S.; Dumas, A. S.; Dwight, T. A.;
Naumiec, G. R.; Hammann, J. M.; DeBoef, B. Tetrahedron Lett.
2008, 49, 4050; (c) Check, C. T.; Henderson, W. H.; Wray, B. C.;
Eynden, M. J. V.; Stambuli, J. P. J. Am. Chem. Soc. 2011, 133,
18503; (d) Juwaini, N. A. B.; Ng, J. K. P.; Seayad, J. ACS Catal.
2012, 2, 1787; (e) Pereira, K. C.; Porter, A. L.; Potavathri, S.;
LeBris, A. P.; DeBoef, B. Tetrahedron 2013, 69, 4429.
12. In the presence of NaClO2 or Ca(ClO)2, the desired product could
be obtained in 45% and 5% yield, respectively (Table S2 in SI).
13. Crystallographic data for the compound 3a (CCDC 1444380 for 3a)
in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication. These
data can be obtained free of charge from The Cambridge
Crystallographic
Data
Center
via
4. (a) Tang, S.; Peng, P.; Pi, S.-F.; Liang, Y.; Wang, N.-X.; Li, J.-H.
Org. Lett. 2008, 10, 1179; (b) He, G.; Zhao, Y.; Zhang, S.; Lu, C.;
Chen, G. J. Am. Chem. Soc. 2012, 134, 3.
www.ccdc.cam.ac.uk/data_request/cif.
14. Hyster, T. K. Catal. Lett. 2015, 145, 458.
5. Desai, L. V.; Malik, H. A.; Sanford, M. S. Org. Lett. 2006, 8, 1141.
6. (a) Uçar, G. Hydrometallurgy 2009, 95, 39; (b) Kariuki, S.; Moore,
C.; McDonald, A. M. Hydrometallurgy 2009, 96, 72; (c) Xian, Y.
J.; Wen, S. M.; Deng, J. S.; Liu, J.; Nie, Q. Can. Metall. Q. 2012,
51, 133; (d) Abdollahi, H.; Noaparast, M.; Shafaei, S. Z.; Manafi,
Z.; Erust, C.; Akcil, A. Sep. Sci. Technol. 2015, 50, 2396.
Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at XXX.
7. For selected reviews on noble metal-catalyzed oxidative annulation
of arenes with alkynes, see: (a) Satoh, T.; Miura, M. Chem.–Eur. J.
2010, 16, 11212; (b) He, R.; Huang, Z.-T.; Zheng, Q.-Y.; Wang, C.
Tetrahedron Lett. 2014, 55, 5705; (c) Ackermann, L. Acc. Chem.
Res. 2014, 47, 281; (d) Song, G.; Li, X. Acc. Chem. Res. 2015, 48,
Click here to remove instruction text...

Highlights
Title: Sodium Chlorate as a Viable Substoichiometric Oxidant for Cobalt-Catalyzed
Oxidative Annulation of Aryl Sulfonamides with Alkynes
(1) Synthesis of sultams through cobalt-catalyzed oxidative annulation.
(2) NaClO3 proved to be a versatile oxidant in C−H activation reaction.
(3) Moderate to excellent yields with excellent regioselectivity could be obtained.
(4) A broad scope of functional groups could be tolerant.