Visible Light-Mediated Coupling of Thioureas and 1,3-Dicarbonyls: Towards a Leaving Group-Free Synthesis of Aminothiazoles

Article abstract of DOI:10.1002/adsc.201701565

A synthesis of aminothiazoles from various 1,3-dicarbonyls and thioureas without a leaving group has been developed. The reaction is photocatalyzed by tetraiodofluorescein, an organic dye. Under irradiation with green LEDs, a sulfur radical is generated in situ from thiourea, followed by addition to the enol tautomer, forming the aminothiazole backbone. This novel strategy provides a greener alternative to the traditional leaving group protocols, with excellent atom economy. (Figure presented.).

Full text of DOI:10.1002/adsc.201701565

Title: Visible Light-Mediated Coupling of Thioureas and 1,3-
Dicarbonyls: Towards a Leaving Group-Free Synthesis of
Aminothiazoles
Authors: Irwan Iskandar Roslan, Kian Hong Ng, Mohammad Ashraf
Gondal, Chanbasha Basheer, Mohammed Abdulkader
Dastageer, Stephan Jaenicke, and Gaik-Khuan Chuah
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.201701565
Link to VoR: http://dx.doi.org/10.1002/adsc.201701565

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Visible Light-Mediated Coupling of Thioureas and 1,3-
Dicarbonyls: Towards a Leaving Group-Free Synthesis of
Aminothiazoles
Irwan Iskandar Roslan,a Kian-Hong Ng,a Mohammed Ashraf Gondal,b* Chanbasha
Basheer,c Mohamed A. Dastageerb, Stephan Jaenickea and Gaik-Khuan Chuaha*
a
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
Fax: +65-6779-1691; phone: +65-6516-2839; e-mail: chmcgk@nus.edu.sg;
Physics Department, King Fahd University of Petroleum & Minerals, Dhahran, 31261, Saudi Arabia
b
Fax: +96613-8604281; phone: +96613-8602351/8603274; e-mail: magondal@kfupm.edu.sa
Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran, 31261, Saudi Arabia
c
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######.((Please
delete if not appropriate))
Abstract. A synthesis of aminothiazoles from various 1,3-
dicarbonyls and thioureas without a leaving group has been
developed. The reaction is photocatalyzed by
tetraiodofluorescein, an organic dye. Under irradiation with
green LEDs, a sulfur radical is generated in situ from
thiourea, followed by addition to the enol tautomer,
forming the aminothiazole backbone. This novel strategy
provides a greener alternative to the traditional leaving
group protocols, with excellent atom economy.
Keywords: Photocatalysis; Radicals; Green chemistry;
Heterocycles; Cyclization
The traditional method of coupling α-halo 1,3-
dicarbonyls or α-halo acetophenones with various
dinucleophiles is a popular protocol used in the
synthesis of a wide array of heteroaromatic
backbones including imidazo[1,2-a]pyridines,[1]
thiazoles,[2] oxazoles[3] and (benzo[d])imidazo[2,1-b]-
thiazoles[4] (Scheme 1A). A leaving group at the α-
carbon of the 1,3-dicarbonyls or acetophenones is
necessary to switch the polarity of the α-carbon from
Scheme 1. Existing strategies for heteroaromatic synthesis
via coupling of dinucleophiles and α-halo dielectrophiles
and proposed leaving group-free protocol.
nucleophilic to electrophilic and also to direct the
nucleophilic attack by the respective dinucleophilic
coupling partners.
As most of the α-halo 1,3-dicarbonyls and
acetophenones are not commercially available and
imidazo[1,2-a]pyridines and thiazoles using CBrCl3
as the α-brominating agent.[11]
thus require prior prefunctionalization, it is not
surprising that recent protocols have employed in situ
α-halogenation strategies for the synthesis of the
aforementioned heteroaromatics (Scheme 1B). These
protocols use various halogenating reagents including
N-bromo and iodosuccinimide (NBS and NIS),[5]
[12]
It is known that in the presence of Mn(OAc)3,
peroxides and/or I2, radicals can form at the α-carbon
of 1,3-dicarbonyls[13] and undergo radical addition
with unsaturated alkyne or alkene moieties.[14] We
wanted to investigate if it is possible to reverse the
roles, with a thiol radical formed in situ from thiourea
undergoing a radical addition with the enol tautomer
of 1,3-dicarbonyls instead. This will allow the
[6]
CBr4, molecular iodine,[7] tetra n-butylammonium
iodide (TBAI),[8] metal halides[9] and hypervalent
iodine compounds.[10] We have previously applied an
in situ α-halogenation strategy in the synthesis of
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
synthesis of aminothiazoles from the coupling of 1,3-
dicarbonyls and thiourea without the need of a
leaving group (Scheme 1C), a superior strategy to
that of traditional and in situ halogenation protocols.
Yadav’s group reported that a thiol radical could
be formed in situ from thiobenzamide under visible
light using eosin Y as a photosensitizer.[15] Eosin Y
belongs to a group of organic dyes known as
fluorescein.[16] Eosin Y and its fluorescein derivatives
eosin B, Rose Bengal, and erythrosin B are attractive
photoredox catalyst options because they are cheap,
commercially available, and are often considered to
be less toxic and more environmentally benign
compared to transition metal photocatalysts.[17] In
recent years, these fluorescein-based photocatalysts
have been used in a wide range of photoredox
reactions,[18] including the synthesis of heterocycles
such as 1,2,4 thiadiazoles,[15] benzothiophenes,[19]
pyrroloindolines,[20] coumarins,[21] benzofurans,[22]
Table 1. Optimization parameters.[a]
Entry Photocatalyst
Solvent
Yield 3a
(%)[b]
phenanthridines,[23]
pyrroloisoquinolines[24]
and
quinazolinones.[25]
1
2
3
4
Na2-eosin Y
Erythrosin B
Phloxine B
Rose Bengal
Eosin Y
MeCN
MeCN
MeCN
MeCN
MeCN
10
The aminothiazole backbone is widely found in
natural products, pharmaceuticals, and agro-
chemicals.[26] It is present in compounds possessing
diverse and important medicinal and biological
properties, including anticancer, anticonvulsant,
antidiabetic, antiviral, antituberculosis, among many
others.[27] Drugs with the aminothiazole motif that are
currently in the market include Famotidine, Cefdinir,
17
10
12
83
98
0
5
6
7
Tetraiodofluorescein MeCN
— MeCN
8[c]
9
Tetraiodofluorescein MeCN
Tetraiodofluorescein DMF
Tetraiodofluorescein EtOH
Tetraiodofluorescein DCE
Tetraiodofluorescein MeCN
0
69
93
43
0
Meloxcam,
Abafungin,
Meloxicam,
and
10
11
12[d]
Sudoxicam.[28] In addition, aminothiazoles and its
derivatives have also found use as dyes, films and in
biophysical binding assays.[29] Herein, we report a
leaving group-free synthetic protocol to access
[a]Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol) and
photocatalyst (2 mol %), solvent (6 mL), 8 h, rt in open air
and under irradiation of 5050 SMD green LED strips (λ =
525 nm). [b]Isolated yield. [c]Reaction performed in the dark.
[d]Under argon.
aminothiazoles using tetraiodofluorescein as
a
photocatalyst, under irradiation with green LED at
ambient conditions.
The optimization studies were conducted by
reacting 1 mmol each of methyl acetoacetate 1a and
thiourea 2a using 2 mol % of the photocatalyst in
acetonitrile as the solvent in a system open to air.
Irradiation was by green LED strips (λ = 525 nm) for
8 h (Table 1). With the disodium salt of fluorescein
dye, Na2-eosin Y, as photocatalyst, the yield of the
aminothiazole product 3a was only 10 % (Table 1,
entry 1). Other disodium salt derivatives of
fluorescein including erythrosin B, phloxine B and
Rose Bengal also exhibited low yields of 3a (Table 1,
entries 2-4). On the other hand, reactions using the
free acid fluorescein derivatives, eosin Y and
tetraiodofluorescein, as photocatalyst proceeded with
product yields of 83 % and 98 %, respectively (Table
1, entries 5 and 6). No product 3a was formed in the
absence of a photocatalyst (Table 1, entry 7). 3a was
also not formed when the reaction was conducted in
the dark in the presence of tetraiodofluorescein
(Table 1, entry 8). These results confirm that the
reaction is photocatalytic in nature. Besides studying
the effects of different photocatalysts, various
solvents were also screened for the reaction with
tetraiodofluorescein as photocatalyst but none were
as good as MeCN (Table 1, entries 9-11). The
product 3a was not observed when the reaction was
conducted under argon, implying that the presence of
O2 (air) is essential for the reaction (Table 1, entry
12).To the best of our knowledge, the employment of
tetraiodofluorescein in a photochemical reaction has
not been reported before.
Using the optimized conditions, a variety of 1,3-
dicarbonyls were screened for their suitability in the
reaction (Table 2). Various linear and branched alkyl
acetoacetates including isopropyl, tert-butyl, amyl,
and isoamyl reacted smoothly with thiourea 2a giving
excellent yields of 3a-3e. It was gratifying to see that
both allyl and methoxyethyl acetoacetate were
suitable for the reaction with excellent yields as well
(Table 2, 3f and 3g). β-ketoesters containing n-propyl
and isopropyl moieties were also well tolerated under
the optimized conditions with good yields of products
3h and 3i. Both aliphatic and cyclic diketones
proceeded smoothly to afford good yields of 3j and
3k. β-Ketoamide was also a suitable coupling partner
with thiourea, forming 83 % of 3l.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
Table 2. Scope of reaction.[a]
[a] Molecular weight determined by GC-MS. [b] Isolated yield
Scheme 2. Control experiments
enol tautomer plays an important part in this reaction.
In general, N-arylthioureas bearing electron donating
substituents on the phenyl ring, including methyl and
methoxy (Table 2, 3s - 3u), fared significantly poorer
than those bearing electron donating substituents and
halogens (Table 2, 3v - 3x). N-substituted naphthyl
and benzyl derivatives were also screened as coupling
partners to acetylacetone and formed moderate yields
of 3y and 3z respectively.
To obtain insights into the reaction mechanism, a
series of control experiments were conducted
(Scheme 2). First,
1
equiv of 2,2,6,6-
tetramethylpiperidin-1-yl oxyl (TEMPO) was added
as a radical scavenger to a reaction mixture under
optimized conditions (Scheme 2a). After 8 h, no 3a
was detected, indicating that radical intermediates are
involved in its formation. An addition product
between TEMPO and the thio radical form of 2a
could be identified by GCMS (Scheme 2a), providing
evidence of a radical intermediate. Another radical
quenching experiment was conducted under the
optimized conditions but with a different radical
scavenger, hydroquinone (Scheme 2a). Again, no 3a
was detected, supporting the hypothesis that the
reaction proceeds via a radical pathway. As it was
demonstrated that O2 was necessary for the reaction
(Table 1, entry 12), a singlet O2 scavenger, 2,3-
dimethyl-2-butene, was added to the reaction mixture
(Scheme 2c).[30] The reaction was not quenched,
suggesting that singlet O2 does not participate in the
reaction but rather the involvement of triplet O2 is
indicated. An experiment was also conducted using
the optimized conditions with light alternately
switched on/off to prove that a continuous light
irradiation is necessary.[31] The concentration of 3a
grew during each irradiation period, but remained
unchanged when the light was switched off. This
demonstrated that the formation of the desired
[a]Reaction conditions: 1 (1.0 mmol), 2 (1.0 mmol) and
tetraiodofluorescein (2 mol %), MeCN (6 mL), 8 h, rt in
open air and under irradiation of 5050 SMD green LED
strips (λ = 525 nm). Isolated yield. [b]After 10 h. [c]1.5
mmol of 1,3-dicarbonyl and 16 h instead.
A wide array of N-substituted thioureas was also
screened for the reaction. N-methyl and N-
ethylthioureas reacted smoothly with methyl
acetoacetate 1a with good yields, albeit with longer
reaction times (Table 2, 3m and 3n). Reaction of 1a
with N-acetyl and guanidyl thiourea derivatives gave
moderate yields of 3o and 3p respectively. On the
other hand, N-phenylthiourea fared poorly with 31 %
yield of 3q, even with excess of methyl acetoacetate
1a. This was due to the competing decomposition
reaction of N-phenylthiourea into ammonia and
phenyliso-thiocyanate, which were detected by GC-
MS. It was gratifying to see that acetylacetone fared
significantly better, with 53 % yield of 3r when
reacted with N-phenylthiourea. Acetylacetone is a
more reactive coupling partner than methyl
acetoacetate 1a, presumably because it forms the enol
more readily compared to 1a. This suggests that the
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
product occurred only under continuous light
irradiation.
constituting a green and atom economical synthesis.
Tetraiodofluorescein was employed as a photoredox
catalyst to generate a thio radical in situ from thiourea.
This then adds to the enol tautomer, forming the
aminothiazole backbone in a series of cascade steps.
Based on the results obtained from optimization,
scope of reaction and control experiments, a plausible
mechanism is proposed (Scheme 3). Upon visible
light
irradiation,
the
photoredox
catalyst
tetraiodofluorescein (TIF) goes to its excited state
(TIF*).[32] Single electron transfer (SET) from the
thiol tautomer of thiourea to TIF* and generates a
TIF radical anion (TIF•–) and a radical cation A.[15]
Aerobic oxygen then oxidizes TIF•– back to the
ground state, completing the reductive quenching
Experimental Section
Typical procedure for the synthesis of aminothiazoles
A test tube was charged with methyl acetoacetate 1a (108
μL, 1.0 mmol), thiourea 2a (76 mg, 1.0 mmol) and
tetraiodofluorescein E (17 mg, 0.02 mmol) in 6 mL of
MeCN. The test tube was placed in a 8-port holder of the
photoreactor (Figure S1, supplementary information). The
reaction mixture was stirred in open air under irradiation
from 5050 SMD green LED strips [60.0 W at 0.2 W/LED
chip, λ = 525 nm] at room temperature. After 8 h, the
reaction mixture was diluted with H2O (10 mL) and
extracted with EtOAc (3 × 10 mL). The combined organic
layers were dried with anhydrous Na2SO4. After filtration,
the solvents were removed by rotary evaporation and the
residue was purified by column chromatography (ethyl
acetate/hexane, 3:2 v/v) to afford 3a in 98 % yield.
•–
cycle and generating a superoxide radical anion O2
in the process.[33] This radical anion then abstracts a
hydrogen atom from A, forming the thiol radical
intermediate B. Next, B undergoes a radical addition
reaction with the enol tautomer of 2, generating C
and releasing H2O2 in the process.[34] The presence of
H2O2 was detected with potassium iodide/starch paper,
which turned dark blue when a drop from the
concentrated reaction mixture was applied on it.[30]
Cycloisomerization of C then forms D, which
undergoes dehydration to form the desired product 3
Methyl 2-amino-4-methylthiazole-5-carboxylate (3a).
1
Obtained as a white solid (168 mg, 98 %); H NMR (300
MHz, DMSO-d6) δ 7.71 (s, 2H), 3.67 (s, 3H), 2.37 (s, 3H);
13C NMR (300 MHz, CDCl3) δ 170.3, 162.3, 159.6, 106.9,
51.2, 17.1. HRMS (ESI) calcd for C6H7N2O2S [M-H]-
171.0234; found 171.0231.
Acknowledgements
Financial support from KFUPM-NUS Collaborative Grants R-
143-001-617-597, NUS 15109 and NUS 15110 is gratefully
acknowledged.
References
[1] a) A. K. Bagdi, S. Santra, K. Monir, A. Hajra, Chem.
Commun. 2015, 51, 1555-1575; b) S. Ponnala, S. T. V.
S. K. Kumar, B. A. Bhat, D. P. Sahu, Synth. Commun.
2005, 35, 901-906; c) A. J. Stasyuk, M. Banasiewicz,
M. K. Cyranski, D. T. Gryko, J. Org. Chem. 2012, 77,
5552-5558; d) Y.-Y. Xie, Z.-C. Chen, Q.-G. Zheng,
Synthesis 2002, 1505-1508; e) K. C. Chunavala, G.
Joshi, E. Suresh, S. Adimurthy, Synthesis 2011, 635-
641; f) I. G. Ribeiro, K. C. M. da Silva, S. C. Parrini, A.
L. P. de Miranda, C. A. M. Fraga, E. J. Barreiro, Eur. J.
Med. Chem. 1998, 33, 225-235; g) L. Cai, C. Brouwer,
K. Sinclair, J. Cuevas, V. W. Pike, Synthesis 2006,
133-145; h) J. S. Yadav, B. V. S. Reddy, Y. G. Rao, M.
Srinivas, A. V. Narsaiah, Tetrahedron Lett. 2007, 48,
7717-7720.
Scheme 3. Proposed mechanism
[2] a) R.-P. Moldovan, R. Teodoro, Y. Gao, W. Deuther-
Conrad, M. Kranz, Y. Wang, H. Kuwabara, M. Nakano,
H. Valentine, S. Fischer, M. G. Pomper, D. F. Wong, R.
F. Dannals, P. Brust, A. G. Horti, J. Med. Chem.
2016, 59, 7840-7855; b) M. R. Ali, S. Kumar, O. Afzal,
In summary, we have developed a novel leaving
group-free protocol for the radical coupling of 1,3-
dicarbonyls and thioureas to access a wide array of
aminothiazoles. The use of photon energy replaces
the need for a leaving group and thermal energy,
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
N. Shalmali, M. Sharma, S. Bawa, Chem. Biol. Drug
Pericherla, P. Kaswan, P. Khedar, B. I. Khungar, K.
Parang, A. Kumar, RSC Adv. 2013, 3, 18923-18930; d)
Z.-J. Cai, S.-Y. Wang, S.-J. Ji, Adv. Synth. Catal. 2013,
355, 2686-2692; e) Y. Zhang, Z. Chen, W. Wu, Y.
Zhang, W. Su, J. Org. Chem. 2013, 78, 12494-12504;
f) W. Ge, X. Zhu, Y. Wei, Eur. J. Org. Chem. 2013,
6015-6020.
Des. 2016, 87, 508-516; c) P. Pal, H. P. Gandhi, A. M.
Kanhed, N. R. Patel, N. N. Mankadia, S. N. Baldha, M.
A. Barmade, P. R. Murumkar, M. R. Yadav, Eur. J.
Med. Chem. 2017, 130, 107-123; d) A. Kamal, M.
Balakrishna, V. L. Nayak, T. B. Shaik, S. Faazil, V. D.
Nimbarte, ChemMedChem 2014, 9, 2766-2780; e) S.
Balalaie, S. Nikoo, S. Haddadi, Synth. Commun. 2008,
38, 2521-2528; f) P. Starkov, F. Rota, J. M. D'Oyley, T.
D. Sheppard, Adv. Synth. Catal. 2012, 354, 3217-3224;
g) D. Zhu, J. Chen, H. Xiao, M. Liu, J. Ding, H. Wu,
Synth. Commun. 2009, 39, 2895-2906.
[10] X. Wang, L. Ma, W. Yu, Synthesis 2011, 2445-2453.
[11] a) I. I. Roslan, K.-H. Ng, G.-K. Chuah, S. Jaenicke,
Adv. Synth. Catal. 2016, 358, 364-369; (b) I. I.
Roslan, K.-H. Ng, J.-E. Wu, G.-K. Chuah, S. Jaenicke,
J. Org. Chem. 2016, 81, 9167-9174; c) I. I. Roslan,
K.-H. Ng, G.-K. Chuah, S. Jaenicke, Eur. J. Org.
Chem. 2017, 704-709; d) I. I. Roslan, G.-K. Chuah, S.
Jaenicke, Eur. J. Org. Chem. 2017, 671-675; e) I. I.
Roslan, K.-H. Ng, G.-K. Chuah, S. Jaenicke, Beilstein
J. Org. Chem. 2017, 13, 2739-2750.
[3] a) S. Lee, K. Y. Yi, S. J. Youn, B. H. Lee, S.-E. Yoo,
Bioorg. Med. Chem. Lett. 2009, 19, 1329-1331; b) W.
Goehring, U. Hoffmann, M. Scalone, H. Stahr, S.
Wang, Novel process for the preparation of the insulin
sensitizer, 2004, US Patent US20040267023 A1.
[4] a) G. Samala, P. B. Devi, S. Saxena, N. Meda, P.
Yogeeswari, D. Sriram, Bioorg. Med. Chem. 2016, 24,
1298-1307; b) J. Singh, A. Mishra, M. Srivastava, P.
Rai, S. Yadav, B. P. Tripathi, J. Singh, RSC Adv. 2016,
6, 49164-49172; c) R. Aggarwal, G. Sumran, Synth.
Commun. 2006, 36, 875-879.
[12] a) M. Mondala, U. Bora, RSC Adv. 2013, 3, 18716-
18754; b) Y.-F. Wang, K. K. Toh, S. Chiba, K.
Narasaka, Org. Lett. 2008, 10, 5019-5022; c) T.
Linker, J. Prakt. Chem. 1997, 339, 488-492.
[13] a) X. Guo, R. Yu, H. Li, Z. Li, J. Am. Chem. Soc.
2009, 131, 17387-17393; b) S. Tang, K. Liu, Y. Long,
X. Gao, M. Gao, A. Lei, Org. Lett. 2015, 17, 2404-
2407; c) S. Tang, K. Liu, Y. Long, X. Qi, Y. Lan, A.
Lei, Chem. Commun. 2015, 51, 8769-8772; d) S.
Tang, X. Gao, A. Lei, Adv. Synth. Catal. 2016, 358,
2878-2882.
[5] a) M. Narender, M. S. Reddy, V. P. Kumar, B. Srinivas,
R. Sridhar, Y. Venkata, D. Nageswar, K. R. Rao,
Synthesis 2002, 22, 3469-3472; b) M. H. Shinde, U. A.
Kshirsagar, Green Chem. 2016, 18, 1455-1458; c) Y.
Yan, Y. Zhang, Z. Zha, Z. Wang, Org. Lett., 2013, 15,
2274-2277; d) S. K. Lee, J. K. Park, J. Org. Chem.
2015, 80, 3723-3729; e) B. S. Kuarm, J. V. Madhav, B.
Rajitha, Lett. Org. Chem. 2011, 8, 549-553; f) M.
Narender, M. S. Reddy, V. P. Kumar, B. Srinivas, R.
Sridhar, Y. V. D. Nageswar, K. R. Rao, Synthesis 2007,
22, 3469- 3472; g) S. B. Bhagat, V. N. Telvekar,
Tetrahedron Lett. 2017, 58, 3662-3666.
[14] H. Yi, G. Zhang, H. Wang, Z. Huang, J. Wang, A. K.
Singh, A. Lei, Chem. Rev. 2017, 117, 9016-9085.
[15] V. P. Srivastava, A. K. Yadav, L. D. S. Yadav, Synlett
2013, 24, 465-470.
[16] G. Wei, C. Basheer, C.-H. Tan, Z. Jiang, Tetrahedron
Lett. 2016, 57, 3801-3809.
[6] a) X. Zhou, H. Ma, C. Shi, Y. Zhang, X. X. Liu, G.
Huang, Eur. J. Org. Chem. 2017, 237-240; b) C. Huo, J.
Tang, H. Xie, Y. Wang, J. Dong, Org. Lett. 2016, 18,
1016-1019; c) T. Keshari, R. Kapoorr, L. D. S. Yadav,
Tetrahedron Lett. 2015, 56, 5623-5627.
[17] D. P. Hari, B. Kӧnig, Chem. Commun. 2014, 50,
6688-6699.
[18] a) Y. Pan, C. W. Kee, L. Chen, C.-H. Tan, Green
Chem. 2011, 13, 2682-2685; b) D.-T. Yang, Q.-Y.
Meng, J.-J. Zhong, M. Xiang, Q. Liu, L.-Z. Wu, Eur.
J. Org. Chem. 2013, 7528-7532; c) S. P. Pitre, C. D.
McTiernan, H. Ismaili, J. C. Scaiano, ACS Catal.
2014, 4, 2530-2535; d) D. P. Hari, B. König, Chem.
Commun. 2014, 50, 6688-6699; e) W. Guo, L.-Q. Lu,
Y. Wang, Y.-N. Wang, J.-R. Chen, W.-J. Xiao,
Angew. Chem. Int. Ed. 2015, 54, 2265-2269;
Angew.Chem. 2015, 127, 2293-2297; f) S. Chen, P.
Slattum, C. Wang, L. Zang, Chem. Rev. 2015, 115,
11967-11998; g) S. P. Pitre, C. D. McTiernan, J. C.
Scaiano, Acc. Chem. Res. 2016, 49, 1320-1330; h) M.
Majek, A. Jacobi von Wangelin, Acc. Chem. Res.
2016, 49, 2316-2327; i) N. A. Romero, D. A.
Nicewicz, Chem. Rev. 2016, 116, 10075-10166; j) D.
A. Nicewicz, T. M. Nguyen, ACS Catal. 2013, 4,
355-360; k) D. Ravelli, M. Fagnoni, ChemCatChem
2012, 4, 169-171; l) Y. C. Teo, Y. Pan, C.-H. Tan,
ChemCatChem 2013, 5, 235-240; m) D. Cantillo, O.
de Frutos, J. A. Rincon, C. Mateos, C. O. Kappe, Org.
Lett. 2014, 16, 896-899.
[7] a) Y.-P. Zhu, J.-J. Yuan, Q. Zhao, M. Lian, Q.-H. Gao,
M.-C. Liu, Y. Yang, A.-X. Wu, Tetrahedron 2012, 68,
173-178; b) Q. Cai, M.-C. Liu, B.-M. Mau, X. Xie, F.-
C. Jia, Y.-P. Zhu, A.-X. Wu, Chin. Chem. Lett. 2015,
26, 881-884; c) Y. Xie, J. Wu, X. Che, Y. Chen, H.
Huang, G.-J. Deng, Green Chem. 2016, 18, 667-671; d)
J. Zhou, H. Huang, W. Wu, H. Chen, H. Hiang, Org.
Lett. 2013, 15, 2604-2607; e) S. Liu, H. Xi, J. Zhang, X.
Wu, Q. Gao, A. Wu, Org. Biomol. Chem. 2015, 13,
8807-8811; f) T. J. Donohoe, M. A. Kabeshov, A. H.
Rathi, I. E. D. Smith, Org. Biomol. Chem. 2012, 10,
1093-1101.
[8] a) L. Ma, X. Wang, W. Yu, B. Han, Chem. Commun.
2011, 47, 11333-11335; b) J. Xie, H. Jiang, Y. Cheng,
C. Zhu, Chem. Commun. 2012, 48, 979-981.
[9] a) A. K. Bagdi, M. Rahman, S. Santra, A. Majee, A.
Hajra, Adv. Synth. Catal. 2013, 355, 1741-1747; b) D.
C. Mohan, R. R. Donthiri, S. N. Rao, S. Adimurthy,
Adv. Synth. Catal. 2013, 355, 2217-2221; c) K.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
[19] D. P. Hari, T. Hering, B. König, Org. Lett. 2012, 14,
Chang, J. Y. N. Lau, J.-J. Huang, J. Med. Chem. 2014,
57, 4098-4110; f) T. Iino, D. Tsukahara, K. Kamata,
K. Sasaki, S. Ohyama, H. Hosaka, T. Hasegawa, M.
Chiba, Y. Nagata, J. Eiki, T. Nishimura, Bioorg. Med.
Chem. 2009, 17, 2733-2743. g) P. Makam, T. Kannan,
Eur. J. Med. Chem. 2014, 87, 643-656; h) A. Khalil, J.
A. Edwards, C. A. Rappleye, W. Tjarks, Bioorg. Med.
Chem. 2015, 23, 532-547; i) H. Lu, J. Rogowskyj, W.
Yu, A. Venkatesh, N. Khan, S. Nakagawa, N.
Goossens, A. P. Koh, T. Higashi, G. Gunasekaran, M.
E. Schwarz, S. P. Hiotis, X. Xu, W. Kinney, Y.
Hoshida, T. Block, A. Cuconati, Y. Du, Bioorg. Med.
Chem. Lett. 2016, 26, 5819-5824.
5334-5337.
[20] K. Wu, Y. Du, T. Wang, Org. Lett. 2017, 19, 5669-
5672.
[21] W. Yang, S. Yang, P. Lia, L. Wang, Chem. Commun.
2015, 51, 7520-7523.
[22] W. Guo, L.-Q. Lu, Y. Wang, Y.-N. Wang, J.-R. Chen,
W.-J. Xiao, Angew. Chem. Int. Ed. 2015, 54, 2265-
2269; Angew. Chem. 2015, 127, 2293 -2297.
[23] a) L. Gu, C. Jin, J. Liu, H. Ding, B. Fan, Chem.
Commun. 2014, 50, 4643-4645; b) T. Xiao, L. Li, G.
Lin, Q. Wang, P. Zhang, Z.-W. Mao, L. Zhou, Green
Chem. 2014, 16, 2418-2421; c) X. Liu, Z. Qing, P.
Cheng, X. Zheng, J. Zeng, H. Xie, Molecules 2016,
21, 1690-1701.
[28] a) L. Laine, A. J. Kivitz, A. E. Bello, A. Y. Grahn, M.
H. Schiff, A. S. Taha, Am. J. Gastroenterol. 2012,
107, 379-386; b) C. Borelli, M. Schaller, M. Niewerth,
K. Nocker, B. Baasner, D. Berg, R. Tiemann, K.
Tietjen, B. Fugmann, S. Lang-Fugmann, H. C.
Korting, Chemotherapy. 2008, 54, 245-259; c) P. D.
R. Guay, Clin. Ther. 2002, 24, 473-489; d) R. S.
Obach, A. S. Kalgutkar, T. F. Ryder, G. S. Walker,
Chem. Res. Toxicol. 2008, 21, 1890-1899; e) G.
Engelhardt, D. Homma, K. Schlegel, R. Utzmann, C.
Schnitzler, Inflamm. Res. 1995, 44, 423-433.
[24] C. Vila, J. Lau, M. Rueping, Beilstein J. Org. Chem.
2014, 10, 1233-1238.
[25] P. Qian, Y. Deng, H. Mei, J. Han, J. Zhou, Y. Pan,
Org. Lett. 2017, 19, 4798-4801.
[26] a) F. Haviv, J. D. Ratajczyk, R. W. DeNet, F. A.
Kerdesky, R. L. Walters, S. P. Schmidt, J. H. Holms,
P. R. Young, G. W. Carter, J. Med. Chem. 1988, 31,
1719-1728; b) F. Clemence, O. L. Martret, F.
Delevallee, J. Benzoni, A. Jouanen, S. Jouquey, M.
Mouren, R. Deraedt, J. Med. Chem. 1988, 31, 1453-
1462; c) J. C. Jaen, L. D. Wise, B. W. Caprathe, H.
Tecle, S. Bergmeier, C. C. Humblet, T.G. Heffner, L.
T. Meltzner, T. A. Pugsley, J. Med. Chem. 1990, 33,
311-317; d) K. Tsuji, H. Ishikawa, Bioorg. Med.
Chem. Lett. 1994, 4, 1601-1606; e) D. J. Hu, S. F Liu,
T. H. Huang, H. Y. Tu, A. D. Zhang, Molecules 2009,
14, 1288-1303; f) M. A. Metwally, E. Abdel-Latif, F.
A. Amer, G. Kaupp, J. Sulfur Chem. 2004, 25, 63-
85; g) W.-L. Wang, D.-Y. Yao, M. Gu, M.-Z. Fan, J.-
Y. Li, Y.-C. Xing, F.-J. Nan, Bioorg. Med. Chem.
Lett. 2005, 15, 5284-5287; h) J. R. Lewis, Nat. Prod.
Rep. 1999, 16, 389-416; i) B. A. Fink, D. S.
Mortensen, S. R. Stauffer, Z. D. Aron, J. A.
Katzenellenbogen, Chem. Biol. 1999, 6, 205-219.
[29] a) S. M. Devine, M. D. Mulcair, C. O. Debono, E. W.
W. Leung, J. W. M. Nissink, S. S. Lim, I. R.
Chandrashekaran, M. Vazirani, B. Mohanty, J. S.
Simpson, J. B. Baell, P. J. Scammells, R. S. Norton,
M. J. Scanlon, J. Med. Chem. 2015, 58, 1205-1214;
b) H. R. Maradiya, V. S. Patel, Chem. Hetero. Comp.
2003, 39, 357-363; c) K. K. Roy, S. Singh, S. K.
Sharma, R. Srivastava, V. Chaturvedi, A. K. Saxena,
Bioorg. Med. Chem. Lett. 2011, 21, 5589-5593.
[30] T. Keshari, V. K. Yadav, V. P. Srivastava, L. D. S.
Yadav, Green Chem. 2014, 16, 3986-3992.
[31] See supporting information (Fig. S2, page S40) for
more information regarding the On-Off experiment.
[32] A. Penzkofer, A. Beidoun, Chem. Phys. 1993, 177,
203-216.
[33] V. Srivastava, P. P. Singh, RSC Adv. 2017, 7, 31377-
31392.
[27] a) A. Meissner, H. Boshoff, M. Vasan, B. P.
Duckworth, C. E. Barry, C. C. Aldrich, Bioorg. Med.
Chem. 2013, 21, 6385-6397; b) T. Suzuki, S.
Hisakawa, Y. Itoh, N. Suzuki, K. Takahashi, M.
Kawahata, K. Yamaguchi, H. Nakagawa, N. Miyata,
Bioorg. Med. Chem. Lett. 2007, 17, 4208-4212; c) F.
W. Bell, A. S. Cantrell, M. Högberg, S. R. Jaskunas,
N. G. Johansson, C. L. Jordan, M. D. Kinnick, P.
Lind, J. M. Morin Jr., R. Noréen, B. Öberg, J. A.
Palkowitz, C. A. Parrish, P. Pranc, C. Sahlberg, R. J.
Ternansky, R. T. Vasileff, L. Vrang, S. J. West, H.
Zhang, X.-X. Zhou, J. Med. Chem. 1995, 38, 4929-
4936; d) R. Romagnoli, P. G. Baraldi, M. K. Salvador,
M. E. Camacho, D. Preti, M. A. Tabrizi, M. Bassetto,
A. Brancale, E. Hamel, R. Bortolozzi, G. Basso, G.
Viola, Bioorg. Med. Chem. 2012, 20, 7083-7094; e)
Y.-S. Lee, S.-H. Chuang, L. Y. L. Huang, C.-L. Lai,
Y.-H. Lin, J.-Y. Yang, C.-W. Liu, S.-C. Yang, H.-S.
Lin, C.-C. Chang, J.-Y. Lai, P.-S. Jian, K. Lam, J.-M.
[34] L. Huang, J. Zhao, RSC Adv. 2013, 3, 23377-23388.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201701565
Advanced Synthesis & Catalysis
COMMUNICATION
Visible Light-Mediated Coupling of Thioureas with
1,3-Dicarbonyls: Towards a Leaving Group-Free
Synthesis of Aminothiazoles
Adv. Synth. Catal. Year, Volume, Page – Page
Irwan Iskandar Roslan, Kian-Hong Ng,
Mohammed Ashraf Gondal,* Chanbasha Basheer,
Mohamed A. Dastageer, Stephan Jaenicke and
Gaik-Khuan Chuah*
7
This article is protected by copyright. All rights reserved.