Copper-Catalyzed Aerobic Oxidation of Amines to Benzothiazoles via Cross Coupling of Amines and Arene Thiolation Sequence

Article abstract of DOI:10.1002/adsc.202000598

A one-pot three-component synthesis of benzothiazoles has been developed using the copper-catalyzed aerobic cross coupling of amines followed by arene thiolation using elemental sulfur. The dual roles of elemental sulfur and CuCl(OH)-TMEDA in the aerobic amine oxidation and the aniline thiolation enable the facile access to benzothiazole derivatives from readily available starting materials. The operational simplicity of the current promiscuous catalyst system suggests the high synthetic potential in the preparation of heterocyclic compounds. (Figure presented.).

Full text of DOI:10.1002/adsc.202000598

Title: Copper-Catalyzed Aerobic Oxidation of Amines to
Benzothiazoles via Cross Coupling of Amines and Arene
Thiolation Sequence
Authors: Kyungsoo Oh and Jihyeon Kim
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000598
Link to VoR: https://doi.org/10.1002/adsc.202000598

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper-Catalyzed Aerobic Oxidation of Amines to
Benzothiazoles via Cross Coupling of Amines and Arene
Thiolation Sequence
Jihyeon Kima and Kyungsoo Oha*
a
Center for Metareceptome Research, Graduate School of Pharmaceutical Sciences, Chung-Ang University, 84
Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea
E-mail: kyungsoooh@cau.ac.kr
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
cyclization precursors. Thus, the utilization of pre-
Abstract.
A one-pot three-component synthesis of
benzothiazoles has been developed using the copper- functionalized aniline derivatives such as 2-
aminobenzenethiol derivatives[8] and 2-haloanilines[9]
catalyzed aerobic cross coupling of amines followed by
arene thiolation using elemental sulfur. The dual roles of
elemental sulfur and CuCl(OH)-TMEDA in the aerobic
amine oxidation and the aniline thiolation enable the facile
access to benzothiazole derivatives from readily available
starting materials. The operational simplicity of the current
promiscuous catalyst system suggests the high synthetic
potential in the preparation of heterocyclic compounds.
provides the synthetically useful bimolecular reaction
approaches to benzothiazole derivatives (Scheme 1b).
While the direct functionalization of benzothiazole
allows the introduction of various substituents at the
C-2 position,[10] the structural diversity in the
benzothiazole skeleton greatly benefits from the
three-component reaction approaches (Scheme 1c),
where the pre-functionalized aniline derivatives[11] or
2-halonitrobenzene derivatives[12] in combination
with aldehyde precursors and sulfur source work in
concert to deliver the desired synthetic
transformations. However, except a few cases of
iodine-promoted in situ functionalization of
aniline,[13] the use of unfunctionalized anilines has not
been exploited in the catalytic approaches to
benzothiazoles. In addition, while the benzylamines
are known to be aldehyde precursors in combination
of 2-iodoanilines[11c] or 2-halonitrobenzenes,[12b] the
Keywords: Amines; Aerobic Oxidation; Benzothiazoles;
Copper Catalysis; Cross Coupling
The development of a promiscuous catalyst, capable
of activating multiple reaction pathways, significantly
diversifies the synthetic toolbox, allowing the
utilization of multiple reaction partners in a one-pot
or tandem fashion.[1] While the intrinsic reactivity of
functional groups can guide the execution of
sequential catalyst systems,[2] the development of a
promiscuous catalyst system remains a elusive goal
direct
combination
of
benzylamines
and
unfunctionalized anilines toward the synthesis of
benzothiazoles is yet to be explored. With an aim to
despite of the advent of well-defined catalyst systems. push promiscuous catalyst systems beyond current
The continuous challenge in the utilization of
promiscuous catalyst systems lies in the fact that the
catalyst-substrate interactions become more complex
as the number of reaction components increases. In
order to investigate the feasibility of a promiscuous
catalyst in a multi-component reaction setting, the
copper catalyst system has been chosen as a model
catalyst due to the catalytic versatility in various
organic transformations.[3]
Benzothiazoles represent one of the privileged
heterocyclic compounds with a diverse biological
activity.[4] The conventional synthetic approaches to
benzothiazole derivatives include the intramolecular
thiolation of N-phenylthioamide derivatives under the
photoredox catalysis[5] and the metal catalysis[6]
(Scheme 1a). While the imino thiols and 2-thioaniline
derivatives undergo the oxidative cyclization,[7] such
unimolecular reactions demand the preparation of
knowledge boundaries, the oxidative cross-coupling
of amines[14] and the electron-rich arene thiolation[15]
have been envisioned under the aerobic copper
catalysis (Scheme 1d). The potential pitfalls of the
three-component approach are apparent since
benzylamines are transformed to thioamides by the
elemental sulfur[16] and anilines are aerobically
oxidized to diazo compounds in the presence of
copper catalyst.[17] Given the multifaceted nature of
copper
catalyst
system,
the
successful
implementation of the proposed three-component
reaction approach to benzothiazoles should help
better understand the promiscuous catalyst systems
and entangle the primary catalyst-substrate
interactions.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
(entries 16-17) and the critical needs of molecular
oxygen for the catalytic cycle (entry 18).
Table 1. Optimization of copper-catalyzed three-
component reaction to benzothiazole.[a]
entry Cu cat. (mol %)
solvent yield
(%)[b]
1
CuOAc (20)
CuCl (20)
DMSO 22
2
DMSO 50
DMSO 40
DMSO 53
DMSO 47
DMSO 49
DMSO 38
DMSO 57
DMSO 35
DMSO 63
3
CuBr (20)
4
CuI (20)
5
Cu(OAc)2 (20)
CuO (20)
6
7
Cu(OTf)2 (20)
CuCl2 (20)
CuBr2 (20)
8
9
10
11
12
13[c]
14[d]
15[d]
16[d]
17[d]
18[d,e]
CuCl(OH)TMEDA (20)
CuCl(OH)TMEDA (20)
CuCl(OH)TMEDA (20)
CuCl(OH)TMEDA (20)
CuCl(OH)TMEDA (20)
CuCl2 (20)
DMF
NMP
20
7
PhCl/
39
Scheme 1. Synthetic strategies to benzothiazoles.
DMSO
DMSO 76
DMSO 37
DMSO 45
DMSO 51
DMSO < 3
The feasibility of copper-catalyzed three-
component approach to benzothiazoles was examined
using p-anisidine 1a, benzylamine 2a, and elemental
sulfur S8 (Table 1). A quick survey of solvents
revealed that the use of DMSO at 100 °C was a
critical reaction parameter for the successful
formation of benzothiazole 3a in 22% yield upon
using 20 mol% CuOAc (entry 1).[18] The change of
copper catalyst improved the catalytic activity,
demonstrating the importance of copper counter
anions in the formation of benzothiazole 3a (entries
2-4). The investigation into the oxidation state of
copper salts also revealed the better catalytic property
of copper (II) salts (entries 5-10), culminating to the
synthetically useful levels of benzothiazole 3a in 57-
63% yields in the presence of chloride anion-
containing copper salts (entries 8 and 10). The
superiority of DMSO solvent was further
demonstrated under the catalysis of chloride anion-
containing copper salts (entries 11-13), and the final
fine-tuning of the reaction parameters was achieved
to 76% yields of 3a by using different ratios of p-
anisidine 1a, benzylamine 2a, and S8 (entries 14-15).
The control experiments confirmed the optimal
catalyst amount of CuCl(OH)TMEDA as 20 mol%
CuCl(OH)TMEDA (10)
CuCl(OH)TMEDA (30)
CuCl(OH)TMEDA (20)
[a]Reaction using 1a (0.75 mmol), 2a (0.50 mmol), S8 (0.25
mmol; 4 equiv of elemental sulfur), copper catalyst (X
mol%) in 1 mL solvent (0.5 M) at 100 °C under oxygen
balloon for 20 h. [b]Isolated yields after column
chromatography. [c]Reaction in 1:1 PhCl:DMSO. [d]Use of
1a (0.60 mmol). [e]Reaction under air.
The optimized three-component aerobic
oxidation condition to benzothiazoles was applied to
aniline derivatives with varied electronic and steric
character (Scheme 2). The use of alkyl substituents at
the para-position of anilines provided the
corresponding benzothiazoles 3b-3c in 62-88% yields.
The electronic effect of anilines was substantial in the
current aerobic oxidation protocol; thus aniline
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
without any electron-donating substituent provided
the benzothiazole 3d in 12% yield. Likewise, the
halogen substituted anilines only led to the formation
of benzothiazoles 3e-3g in 40-43% yields. However,
in the case of p-chloroaniline, the addition of
dehydrating agent, 3Å MS, to the reaction mixture
significantly improved the formation of 3f to 80%
yield. This molecular sieve effect was not evident in
the case of aniline 2d and p-bromoaniline 2g, where
the products 3d and 3g were obtained in lower yields
of 10% and 33%, respectively. The steric effect of p-
anisidine derivatives revealed that the methoxy group
at ortho- or meta-position did not deter the formation
of benzothiazole 3h and the regioselective formation
of 3i. However, the methyl group at meta-position in
3,4-dimethylaniline did not show high regiocontrol,
providing a 2.5:1 mixture of 3j and 3j’. The use of 3-
chloroaniline under the optimized reaction condition
also provided a mixture of benzothiazoles 3k and 3k’.
The lack of a para-substituent in 3,5-dimethylaniline
caused the formation of 3l in 38% yield since the use
of para-substituted pyridine and quinoline derivatives
smoothly underwent the regioselective formation of
benzothiazoles 3m-3o in 48-80% yields. The current
three-component aerobic oxidation protocol to
benzothiazoles could not be extended to allyl and
alkylamines, since the reaction stopped at the
corresponding aldehyde products.[19]
group at the para-position of benzylamines lowered
the yields of benzothiazoles 3t-3v to 14-46%. Such
electronic effect was significantly attenuated for the
ortho- or meta-substituted benzylamines, where the
various benzothiazoles 3w-3zd were obtained in 68-
94% yields. Additionally, the use of 2-
thiophenemethylamine was possible, providing the
corresponding benzothiazole 3ze in 88% yield.
Scheme 3. Benzylamine substrate scope for aerobic
oxidation sequence to benzothiazoles.
In order to better understand the interplay
between the catalyst and substrates, the control
experiments were performed under the optimized
reaction conditions (Scheme 4). The subjection of p-
anisidine 1a under the CuCl(OH)TMEDA catalysis
primarily led to the formation of azobenzene
derivative 4a in 33% yield, while no reaction took
place in the presence of elemental sulfur. The
combination of CuCl(OH)TMEDA and elemental
sulfur
mirrored
the
reaction
result
of
CuCl(OH)TMEDA catalyst. The benzylamine 2a
under CuCl(OH)TMEDA catalysis was prominently
oxidized to the corresponding imine 5a and
dibenzylimine 5b in 32% and 36% yield, respectively.
The use of elemental sulfur also led to the formation
of 5a and 5b. Although the NMR yields of
benzaldehyde, from the hydrolysis of imines 5a and
5b, was in the range of 60-70% yields, the crude
reaction mixtures were clean without any by-products.
The reaction of 1a and 2a in the presence of
CuCl(OH)TMEDA reflected the respective reaction
outcome without the dibenzylimine 5b, providing the
azobenzene derivative 4a and benzylimine 5a.[20]
However, the elemental sulfur promoted the
formation of benzothiazole 3a in <5% yield and the
dibenzylimine 5b and the crossed imine 6a in 10%
and 60% yield, respectively. The substantial
difference in the reaction outcome between copper
catalyst and S8 illustrates the importance of coupling
between three components; 1a, 2a, and S8.
Scheme 2. Aniline substrate scope for aerobic oxidation
sequence to benzothiazoles ([a]Using 3Å MS (250 mg). [b]Using
20 mol% of CuCl2 instead of CuCl(OH)TMEDA. [c]Using 3Å MS
(250 mg) and 20 mol% of CuCl2).
The necessity of a para-substituent in aniline
derivatives in the current three-component aerobic
oxidation protocol prompted the use of 2-
naphthylamine 1p for the substrate scope for
benzylamine derivatives
2
(Scheme 3). The
regioselective CS bond formation has been observed
for various benzylamine derivatives, providing the
corresponding benzothiazoles 3p-3s in 77-91% yields.
However, the presence of chloro, bromo, and nitro
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
preferential insertion to the Csp2-Br bond over Csp2-H
bond, where the formation of imine 6b was only
observed in 36% yield from the reaction of 2-bromo-
4-methylaniline 1q. The possible involvement of
thioamide intermediate, that could be derived from
the oxidation of amines 1 and 2 by S8,[16] was ruled
out, where the authentic sample of N-(4-
methoxyphenyl)benzothioamide did not undergo the
intramolecular thiolation under the optimized reaction
condition.
Scheme 4. Control experiments.
Mechanistically,
it
appears
that
the
benzylamines 2 react with S8 to give benzylamine
polysulfides.[21] While the formation of benzylamine
polysulfides is difficult to confirm during the reaction
at 100 °C, the GC-MS analysis of the reaction
mixture indicated the presence of a benzylamine
disulfide 2a’ peak at 277.0828, corresponding to the
molecular ion of [M+H]+. Thus the molecular ion
peak at 277.0828 indirectly supports the formation of
benzylamine polysulfides during the reaction. It is
also possible to generate the benzylimines 5a from
benzylamines 2 via copper catalysis, and then the
formation of benzylamine polysulfides by the action
of S8. Given that the facile vulcanization of natural
sulfur is accelerated by aniline, the attack of anilines
1 to either 2’ or benzylimines 5a should provide the
N,S-acetal intermediate A. The concomitant action of
copper catalyst and S8 converts the N,S-acetal A to
the copper thiolate B, and the following oxidative
CH activation leads to the aryl copper species C.[15]
The reductive elimination of aryl copper C provides
the benzothiazoline D, which spontaneously
undergoes the aerobic oxidation into the
benzothiazole 3.[22] The aerobic oxidation of
copper(0) metal to copper (II) species should
complete the catalytic cycle. The formation of N,S-
acetal intermediate A appears to be sensitive to the
electronic nature of anilines 1 and benzylamines 2 as
shown in Scheme 2-3, but ultimately influenced by
the water content in the reaction mixture. Thus, the
control experiments using 0.5 equiv of water lowered
the yield of 3a to 71% (versus 76%), and the reaction
did not proceed in the presence of 1 equiv of water.
Thus, the employment of benzaldehyde or crossed
imine 6a under the optimized conditions provided the
benzothiazole 3a in diminished yields of 20-30%
(Scheme 5). The appropriate choice of copper
catalysts such as CuCl2 and CuCl(OH)TMEDA
indicated the less oxidizing power in the conversion
of anilines and benzylamines to the corresponding
azobenzene derivatives[17a] and dibenzylimine,[23]
respectively. The copper thiolate B did not show the
Scheme 5. Proposed mechanism for tandem aerobic
oxidation Protocol.
In summary, we have developed a three-
component
aerobic
oxidation
pathway
to
benzothiazoles in the presence of copper (II) catalysts.
The promiscuous catalytic behavior of copper salts
has been tamed by the combination of three reaction
components; anilines, benzylamines, and elemental
sulfur, where the unwanted oxidation pathways of
anilines and benzylamines to azobenzenes and
aldehydes were avoided. The multiple roles of
molecular oxygen are particularly noteworthy in the
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
government (MSICT) (NRF-2015R1A5A1008958, and NRF-
2019R1A2C2089953).
current
three-component
reaction,
clearly
demonstrating the control powers of oxygen for
various intermediates and catalytic species. Given
that the copper species possess promiscuous catalytic
behaviors for various functional groups, the further
development of multi-component aerobic oxidation
approaches should warrant the facile synthesis of
heterocyclic compounds in a one-pot. Thus, our
current research efforts are directed to the synthetic
utilization of copper catalystselemental sulfur
system, and these results will be reported in near
future.
References
[1] For reviews, see: a) D. E. Fogg, E. N. dos Santos,
Coord. Chem. Rev. 2004, 248, 2365-2379; b) J.-C.
Wasilke, S. J. Obrey, R. T. Baker, G. C. Bazan, Chem.
Rev. 2005, 105, 1001-1020; c) C. M. Marson, Chem
Soc. Rev. 2012, 41, 7712-7722; d) C. A. Denard, J. F.
Hartwig, H. Zhao, ACS. Catal. 2013, 3, 2856-2864; e)
M. J. Climent, A. Corma, S. Iborra, M. J. Sabater, ACS
Catal. 2014, 4, 870-891; f) F. R. Bisogno, M. G.
Lopez-Vidal, G. de Gonzalo, Adv. Synth. Catal. 2017,
359, 2026-2049.
Experimental Section
General Procedure for the Synthesis of Benzothiazoles
[2] For examples, see: a) H.-C. Guo, J.-A. Ma, Angew.
Chem. Int. Ed. 2006, 45, 345-366; b) A. Grossmann, D.
Ender, Angew. Chem. Int. Ed. 2012, 51, 314-325; c) S.
Afewerki, A. Córdova, Chem. Rev. 2016, 116, 13512-
13570; d) A. Corma, J. Navas, M. J. Sabater, Chem.
Rev. 2018, 118, 1410-1459.
An oven dried round-bottom flask was charged with
[Cu(OH)TMEDA]2Cl2 (48 mg, 0.1 mmol, 20 mol%),
substituted aniline 1 (0.6 mmol), sulfur powder (65 mg, 2
mmol) and 1.0 mL of DMSO under oxygen balloon.
Benzylamine 2a
and then the solution was stirred at 100 °C until the
reaction was complete by TLC (20-28 h). The crude
mixture was purified by silica gel column chromatography
using 1 to 20% ethyl acetate in hexanes to afford the
desired compound 3.
[3] a) S. E. Allen, R. R. Walvoord, R. Padilla-Salinas, M.
C. Kozlowski, Chem. Rev. 2013, 113, 6234-6458; b) S.
D. McCann, S. S. Stahl, Acc. Chem. Res. 2015, 48,
1756-1766; c) X. Tang, W. Wu, W. Zeng, H. Jiang. Acc.
Chem. Res. 2018, 51, 1092-1105.
6-Methoxy-2-phenylbenzo[d]thiazole (3a): Purification
of the product was performed by column chromatography
using hexanes/EtOAc = 95:5. White solid (92.3 mg, 76%);
[4] a) R. S. Keri, M. R. Patil, S. A. Patil, S. Budagumpi,
Eur. J. Med. Chem. 2015, 89, 207-251; b) A. Rouf, C.
Tanyeli, Eur. J. Med. Chem. 2015, 97, 911-927; c) N. P.
Prajapati, R. H. Vekariya, M. A. Borad, H. D. Patel,
RSC Adv. 2014, 4, 60176-60208; d) X. Liu, Z.-B. Dong,
Eur. J. Org. Chem. 2020, 408-419.
1
The H NMR and 13C NMR spectra for this compound are
consistent with previously reported literature data.[8f] 1
H
NMR (CDCl3, 600 MHz): δ 8.04-8.03 (m, 2H), 7.96 (d, J =
9.0 Hz, 1H), 7.49-7.46 (m, 3H), 7.34-7.33(m, 1H), 7.09 (dd,
J = 9.0, 2.1 Hz, 1H), 3.88 (s, 3H); 13C NMR (150 MHz,
CDCl3): δ165.5, 157.7, 148.6, 136.4, 133.7, 130.5, 128.9,
127.2, 123.7, 115.6, 104.1, 55.7.
[5] a) Y. Cheng, J. Yang, Y. Qu, P. Li, Org. Lett. 2012, 14,
98-101; b) G. Zhang, C. Liu, H. Yi, Q. Meng, C. Bian,
H. Chen, J.-X. Jian, L.-Z. Wu, A. Lei, J. Am. Chem.
Soc. 2015, 137, 9273−9280; c) Z.-M. Xu, H.-X. Li, D.
J. Young, D.-L. Zhu, H.-Y. Li, J.-P. Lang, Org. Lett.
2019, 21, 237−241; d) L. M. Bouchet, A. A. Heredia, J.
E. Argüello, L. C. Schmidt, Org. Lett. 2020, 22, 610-
614.
2-Phenylthiazolo[4,5-c]quinoline (3n): Purification of the
product was performed by column chromatography using
hexanes/EtOAc = 90:10. Yellow solid (63.4 mg, 48%),
1
m.p. 149-150 °C; H NMR (CDCl3, 600 MHz): δ 9.53 (s,
1H), 8.25 (d, J = 8.6 Hz, 1H), 8.14-8.12 (m, 2H), 8.01 (d, J
= 8.3 Hz, 1H), 7.75-7.73 (m, 1H), 7.66-7.63 (m, 1H), 7.53
(m, 3H); 13C NMR (150 MHz, CDCl3): δ 168.6, 148.7,
146.1, 144.2, 140.2, 132.9, 131.4, 130.5, 129.2, 128.9,
127.6(2C), 124.9, 123.4; IR (neat): 3066, 2928, 2857, 1560,
1502, 1474, 1441, 1364, 1329, 1258, 1223, 954, 934, 759,
690 cm-1; HRMS (ESI): m/z calcd for C16H11N2S+ (M+H)+
263.0637 Found 263.0639.
[6] a) G. Evindar, R. A. Batey, J. Org. Chem. 2006, 71,
1802−1808; b) H. C. Ma, X. Z. Jiang, Synlett. 2008,
1335-1340; c) L. L. Joyce, R. A. Batey, Org. Lett. 2009,
11, 2792−2795; For C-H activation strategies, see: d) A.
Banerjee, S. K. Santra, S. K. Rout, B. K. Patel,
Tetrahedron 2013, 69, 9096-9104; e) Y. Cheng, Q.
Peng, W. Fan, P. Li, J. Org. Chem. 2014, 79,
5812−5819; f) S. Sharma, R. S. Pathare, A. K. Maurya,
K. Gopal, T. K. Roy, D. M. Sawant, R. T. Pardasani,
Org. Lett. 2016, 18, 356−359.
2-(4-Fluorophenyl)naphtho[2,1-d]thiazole
(3s):
Purification of the product was performed by column
chromatography using hexanes/EtOAc = 98:2. Light
1
yellow solid (94.0 mg, 84%), m.p. 140-141 °C; H NMR
(CDCl3, 600 MHz): δ 8.12-8.10 (m, 2H), 8.07 (d, J = 8.3
Hz, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.3 Hz, 1H),
7.87 (d, J = 9.0 Hz, 1H), 7.59 (t, J = 7.9 Hz, 1H), 7.55-7.53
(m, 1H), 7.20-7.17 (m, 2H); 13C NMR (150 MHz, CDCl3):
δ 165.7, 164.2 (d, J = 249.9 Hz), 152.1, 132.1, 131.0,
130.0 (d, J = 2.8 Hz), 129.2 (d, J = 8.5 Hz), 128.9, 128.0,
127.4, 127.0, 125.9, 125.0, 121.5, 116.1 (d, J = 21.6 Hz);
IR (neat): 3058, 2930, 2861, 1597, 1523, 1470, 1441, 1440,
1390, 1351, 1299, 1234, 1159, 1105, 1023, 954837, 807,
740 cm-1; HRMS (ESI): m/z calcd for C17H11FNS+ (M+H)+
280.0591 Found 280.0598.
[7] a) D. S. Bose, M. Idrees, J. Org. Chem. 2006, 71,
8261−8263; b) D.-Y. Zhao, X.-K. Guo, J.-H. Li, R.-Y.
Tang, Synthesis 2012, 44, 927−933.
[8] a) J. A. Seijas, M. P. Vázquez-Tato, M. R. Carballido-
Reboredo, J. Crecente-Campo, L. Romar-López,
Synlett 2007, 2, 313−317; b) K. Bahrami, M. M.
Khodaei, F. Naali, J. Org. Chem. 2008, 73, 6835−6837;
c) G. Bastug, C. Eviolitte, I. E. Markó, Org. Lett. 2012,
Acknowledgements
This research was supported by the National Research
Foundation of Korea (NRF) grants funded by the Korean
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
14, 3502−3505; d) Y.-P. Zhu, F.-C. Jia, M.-C. Liu, A.-
[14] For reviews, see: a) B. Chen, L. Wang, S. Gao, ACS
Catal. 2015, 5, 5851-5876; b) A. E. Wendlandt, S. S.
Stahl, Angew. Chem. Int. Ed. 2015, 54, 14638-14658;
c) M. Largeron, Org. Biomol. Chem. 2017, 15, 4722-
4730; d) R. Zhang, S. Luo, Chin. Chem. Lett. 2018, 29,
1193-1200; For our recent contributions, see: e) Y.
Goriya, H. Y. Kim, K. Oh, Org. Lett. 2016, 18, 5174-
5177; f) G. Golime, G. Bogonda, H. Y. Kim, K. Oh,
ACS Catal. 2018, 8, 4986-4990; g) J. Kim, G. Golime,
H. Y. Kim. K. Oh, Asian J. Org. Chem. 2019, 8, 1674-
1679; h) K. Kim, H. Y. Kim, K. Oh, Org. Lett. 2019,
21, 6731-6735; i) T. Si, H. Y. Kim, K. Oh, ACS Catal.
2019, 9, 9216-9221.
X. Wu, Org. Lett. 2012, 14, 4414−4417; e) T. B.
Nguyen, L. Ermolenko, W. A. Dean, A. Al-Mourabit,
Org. Lett. 2012, 14, 5948−5951; f) Y. Liao, H. Qi, S.
Chen, P. Jiang, W. Zhou, G.-J. Deng, Org. Lett. 2012,
14, 6004-6007; g) Y. Sun, H. Jiang, W. Wu, W. Zeng,
X. Wu, Org. Lett. 2013, 15, 1598−1601; h) P. B.
Gorepatil, Y. D. Mane, V. S. Ingle, Synlett 2013, 24,
2241−2244; i) M. S. Mayo, X. Yu, X. Zhou, X. Feng,
Y. Yamamoto, M. Bao, Org. Lett. 2014, 16, 764−767;
j) G. Naresh, R. Kant, T. Narender, J. Org. Chem. 2014,
79, 3821-3829; k) R. Hu, X. Li, Y. Tong, D. Miao, Q.
Pan, Z. Jiang, H. Gan, S. Han, Synlett 2016, 27,
1387−1390.
[15] For a recent review, see: C. Shen, P. Zhang, Q. Sun, S.
Bai, T. S. A. Hor, X. Liu, Chem. Soc. Rev. 2015, 44,
291-314.
[9] a) T. Itoh, T. Mase, Org. Lett. 2007, 9, 3687−3689; b)
D. Ma, S. Xie, P. Xue, X. Zhang, J. Dong, Y. Jiang,
Angew. Chem. Int. Ed. 2009, 48, 4222-4225; c) F.
Wang, S. Cai, Z. Wang, C. Xi, Org. Lett. 2011, 13,
3202−3205; d) H. Yu, M. Zhang, Y. Li, J. Org. Chem.
2013, 78, 8898−8903; e) X. Zhang, W. Zeng, Y. Yang,
H. Huang, Y. Liang, Org. Lett. 2014, 16, 876−879; f) Y.
Huang, P. Zhou, W. Wu, H. Jiang, J. Org. Chem. 2018,
83, 2460−2466.
[16] a) T. B. Nguyen, L. Ermolenko, A. Al-Mourabit, Org.
Lett. 2012, 14, 4274-4277; For a comprehensive review
on elemental sulfur, see: b) T. B. Nguyen, Adv. Synth.
Catal. 2017, 359, 1066-1130; c) T. B. Nguyen, Adv.
Synth. Catal. 2020, 362, DOI: 10.1002/adsc.202000535.
[17] a) W. Lu, C. Xi, Tetrahedron Lett. 2008, 49, 4011-
4015; b) C. Zhang, N. Jiao, Angew. Chem. Int. Ed.
2010, 49, 6174-6177; c) Z. Hu, F. M. Kerton, Org.
Biomol. Chem. 2012, 10, 1618-1624; d) Y. Zhu, Y. Shi,
Org. Lett. 2013, 15, 1942-1945.
[10] a) J. Huang, J. Chan, Y. Chen, C. J. Borths, K. D.
Baucom, R. D. Larsen, M. M. Faul, J. Am. Chem. Soc.
2010, 132, 3674−3675; b) O. Vechorkin, N. Hirt, X.
Hu, Org. Lett. 2010, 12, 3567−3569; c) Z. Yang, X.
Chen, S. Wang, J. Liu, K. Xie, A. Wang, Z. Tan, J. Org.
Chem. 2012, 77, 7086−7091; d) Q. Song, Q. Feng, M.
Zhou, Org. Lett. 2013, 15, 5990−5993; e) P. Lassalas,
F. Marsais, C. Hoarau, Synlett 2013, 24, 2233−2240; f)
K. R. Babu, N. Zhu, H. Bao, Org. Lett. 2017, 19,
46−49.
[18] For optimization details, see the Supporting
Information.
[19] The current three-component approach to
benzothiazoles is not applicable to aliphatic amines due
to the rapid hydrolysis tendency of the N,S-acetal
intermediate A into imines and aldehydes, where the
three-component reactions of aliphatic amines only
provided the corresponding aldehydes in 70-80% yields
(see the Supporting Information for details).
[11] a) H. Deng, Z. Li, F. Ke, X. Zhou, Chem. Eur. J. 2012,
18, 4840-4843; b) N. Park, Y. Heo, M. R. Kumar, Y.
Kim, K. H. Song, S. Lee, Eur. J. Org. Chem. 2012,
1984-1993; c) R. Wang, Y.-l. Ding, H. Liu, S. Peng, J.
Ren, L. Li, Tetrahedron Lett. 2014, 55, 945-949; d) Z.
Yang, R. Hu, X. Li, X. Wang, R. Gu, S. Han,
Tetrahedron Lett. 2017, 58, 2366-2369; e) W. Yu, W.
Wu, H. Jiang, Chin. J. Chem. 2019, 37, 1158-1166.
[20] The benzylimine 5a was rapidly hydrolyzed to
benzaldehyde in the reaction mixture, thus the crude
NMR only showed the benzaldehyde.
[21] a) Y. Sasaki, F. P. Olsen, Can. J. Chem. 1971, 49,
283-293; b) T. B. Nguyen, L. P. A. Nguyen, T. T. T.
Nguyen, Adv. Synth. Catal. 2019, 361, 1787-1791.
[12] a) J. Liu, Q. Gui, Z. Yang, Z. Tan, R. Guo, J.-C. Shi,
Synthesis 2013, 45, 943−951; b) T. B. Nguyen, L.
Ermolenko, P. Retailleau, A. Al-Mourabit, Angew.
Chem. Int. Ed. 2014, 53, 13808-13812; c) T. Guntreddi,
R. Vanjari, K. N. Singh, Org. Lett. 2015, 17, 976−978;
d) T. B. Nguyen, K. Pasturaud, L. Ermolenko, A. Al-
Mourabit, Org. Lett. 2015, 17, 2562−2565; e) L. A.
Nguyen, Q. A. Ngo, P. Retailleau, T. B. Nguyen, Green
Chem. 2017, 19, 4289-4293; f) X. Wang, X. Li, R. Hu,
Z. Yang, R. Gu, S. Ding, P. Li, S. Han, Synlett 2018, 29,
219−224; g) Q. Xing, Y. Ma, H. Xie, F. Xiao, F. Zhang,
G.-J. Deng, J. Org. Chem. 2019, 84, 1238-1246.
[22] M. A. Lynn, L. J. Carlson, H. Hwangbo, J. M. Tanski,
L. A. Tyler, J. Mol. Struct. 2012, 1011, 81-93.
[23] R. D. Patil, S. Adimurthy, Adv. Synth. Catal. 2011,
353, 1695-1700.
[13] a) X. Che, J. Jiang, F. Xiao, H. Huang, G.-J. Deng,
Org. Lett. 2017, 19, 4576-4579; b) J. Jiang, G. Li, F.
Zhang, H. Xie, G.-J. Deng, Adv. Synth. Catal. 2018,
360, 1622-1627; c) A. Dey, A. Hajra, Org. Lett. 2019,
21, 1686-1689; d) J. Zhang, X. Zhao, P. Liu, P. Sun, J.
Org. Chem. 2019, 84, 12596-12605.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000598
Advanced Synthesis & Catalysis
COMMUNICATION
Copper-Catalyzed Aerobic Oxidation of Amines to
Benzothiazoles via Cross Coupling of Amines and
Arene Thiolation Sequence
Adv. Synth. Catal. Year, Volume, Page – Page
Jihyeon Kimand Kyungsoo Oh*
7
This article is protected by copyright. All rights reserved.