Photocatalyst- And Transition-Metal-Free Visible-Light-Promoted Intramolecular C(sp2)-S Formation

Article abstract of DOI:10.1021/acs.orglett.1c00235

A photocatalyst- and transition-metal-free visible-light-induced cyclization of ortho-halothiobenzanilides has been developed. Upon irradiation with visible light, substrates undergo dehalogenative cyclization to 2-aryl benzothiazoles with high efficiency and selectivity. This photocyclization exhibits a high tolerance to various functional groups, is applicable for the synthesis of 2-alkyl benzothiazoles, and is easy to set up for gram-scale reaction.

Full text of DOI:10.1021/acs.orglett.1c00235

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Letter
Photocatalyst- and Transition-Metal-Free Visible-Light-Promoted
Intramolecular C(sp2)−S Formation
Hao Wang, Qi Wu, Jian-Dong Zhang,* Hai-Yan Li, and Hong-Xi Li*
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ABSTRACT: A photocatalyst- and transition-metal-free visible-light-
induced cyclization of ortho-halothiobenzanilides has been developed.
Upon irradiation with visible light, substrates undergo dehalogenative
cyclization to 2-aryl benzothiazoles with high efficiency and selectivity. This
photocyclization exhibits a high tolerance to various functional groups, is
applicable for the synthesis of 2-alkyl benzothiazoles, and is easy to set up
for gram-scale reaction.
Scheme 1. Photosynthesis of 2-Aryl Benzothiazoles
s in the past years, visible-light photoredox catalysis has
Abecome an efficient protocol to forge C−C, C−O, C−N,
and C−S bonds.1,2 Most of the visible-light-induced
conversions require the use of exogenous photosensitizers
(e.g., polypyridyl Ru/Ir complexes or organic dyes) because
common organic molecules do not absorb light in the visible
region.3,4 In recent years, noncovalent interaction of electron
donor−acceptor (EDA) complexes can mediate photocatalyst-
free transformations under visible light.5−9 However, the direct
visible-light irradiation of donor−acceptor complexes to induce
intramolecular cross couplings remains underexplored in the
absence of photoredox catalysts.
2-Aryl benzothiazoles are common building blocks found in
pharmaceuticals, natural products, agrochemical complexes,
and functional materials.10 Consequently, their synthesis has
attracted much attention (Scheme 1).11−16 Apart from thermal
reactions,17,18 visible-light-triggered construction of 2-aryl
benzothiazoles, including (i) oxidative condensation of 2-
aminothiophenols with aromatic aldehydes,19,20 (ii) intra-
molecular C(sp2)−H thiolation of thiobenzanilides,21 (iii) Cu-
catalyzed C−H arylation of benzothiazole with iodobenzene,22
(iv) oxidative coupling of thiophenols and arylnitriles,23 and
(v) thia−Wolff rearrangement of alkynyl sulfide,24 have been
developed. The above photoreactions necessitate expensive or/
and toxic photoredox catalysts such as [Ru(bpy)3]2+ and
[Ir(ppy)3], which play a key role in the formation of
benzothiazoles but may contaminate the final products.
Using a photocatalyst-free strategy could be an efficient
alternative to avoid their cost, toxicity, and contamination.
Ultraviolet (UV)-light-induced intramolecular aromatic sub-
stitutions of 2-bromo/iodo-thiobenzanilides to benzothiazoles
with a strong base in liquid ammonia were reported.25 The
application of high-energy UV light and harsh conditions limits
the substrate scope and causes unwanted side reactions.
Herein, we reported the visible-light-induced dehalogenative
cyclization of 2-halothiobenzanilides into benzothiazoles at
Received: January 21, 2021
Published: February 26, 2021
https://dx.doi.org/10.1021/acs.orglett.1c00235
Org. Lett. 2021, 23, 2078−2083
© 2021 American Chemical Society
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ambient temperature. Notably, these reactions avoid the use of
an external photosensitizer and transition-metal catalyst
typically required to effect C−S cross couplings.26
solvent (Table S1, entries 3−10). DSMO was the optimal
solvent (entry 1). DMF, MeOH, and EtOH were less effective
than DMSO. MeCN, THF, or 1,4-dioxane offered 15−39%
yield of B1. Only a trace of products was observed when the
reaction was carried out in CH2Cl2 or toluene. Gratifyingly,
high product yield (98%) was obtained after 5 h of sunlight
irradiation (entry 12). No desired product was formed in the
dark (entry 13), displaying that visible-light irradiation was
essential for this debrominative cyclization. The reaction was
performed in air to afford the desired product B1 in 61% yield
and a desulfurizated product N-(2-bromophenyl)benzamide in
17% yield (entry 14). Thus, the optimized conditions were
found to be 50 mol % of Na3PO4 as base and DMSO as solvent
under the irradiation of visible light at ambient temperature.
Notably, this photocyclization proceeded effectively without
the addition of transition metal and photoredox catalyst.
After determining the optimized reaction conditions (Table
1, entry 1), we explored the photocyclization of other
substrates with an ortho C(sp2)−Br bond. As shown in
Scheme 2, a range of N-(2-bromophenyl)benzothioamides
In 2017, Miyake et al. developed a visible-light-promoted
protocol for C(sp2)−S cross coupling of thiols and aryl halides
via intermolecular charge transfer without photoredox catalysts
and transition-metal catalysts.27 Very recently, we found that
thiobenzanilide derivatives can absorb visible light, and their
photoexcited states undergo cyclization to benzothiazoles
using stoichiometric 2,2,6,6-tetramethylpiperidine N-oxyl as
the hydrogen atom transfer reagent.28 The oxidative
conversion required a relatively expensive oxidant and
displayed low positional selectivity. For meta-substituted
thioanilides, a mixture of two regioisomers was formed.
These above results stimulated us to explore the direct
visible-light irradiation of ortho-halothiobenzanilides into 2-aryl
benzothiazole through intramolecular electron transfer under
catalyst-free conditions.
We initially chose N-(2-bromophenyl)benzothioamide (A1)
as the model substrate to optimize reaction conditions (Tables
1 and S1). The irradiation of A1 with Na3PO4 in DMSO was
a
Scheme 2. Synthesis of 2-Substituted Benzothiazoles
a
Table 1. Parameters for Intramolecular Cyclization
entry
base
conversion (%)
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
Na3PO4
KHCO3
NaOAc
Na2HPO4
Na2CO3
K2CO3
KOH
NaOH
Et3N
(i-Pr)2EtN
>99
99
99
>99
99
99
>99
>99
92
93
92
99
89
88
94
86
88
99
99
87
88
76
98
0
b
Na3PO4
Na3PO4
Na3PO4
>99
8
84
c
d
14
61
a
Reaction conditions: A1 (0.2 mmol), Na3PO4 (0.1 mmol, 0.5 equiv),
DMSO (2 mL), N2, irradiation under a 45 W CFL for 5 h with
b
cooling by a fan, HPLC assay conversion, and yield. Under sunlight
c
d
(the maximum power density is about 5 mW cm−2). In the dark. In
air, N-(2-bromophenyl)benzamide was formed in 17% yield.
carried out under visible light from a 45 W compact
fluorescent lamp (CFL) (Figure S1). Pleasingly, after 5 h of
CFL irradiation, we isolated the desired product 2-
phenylbenzo[d]thiazole (B1) in 99% HPLC assay yield
(entry 1; HPLC = high performance liquid chromatography)
with high selectivity. A series of bases (e.g., KHCO3, NaOAc,
Na2HPO4, Na2CO3, K2CO3, KOH, NaOH, Et3N, and (i-
Pr)2EtN) were screened (entries 2−10). Na3PO4, KOH, and
NaOH are excellent bases for this transformation (entries 1, 7,
and 8). Good conversions were observed using others. We
obtained lower yield (91%), as the Na3PO4 loading was
decreased from 0.5 equiv to 0.2 equiv (Table S1, entry 1). The
reaction proceeded in 76% yield in the absence of base (Table
S1, entry 2). The process was largely sensitive to the used
a
Reaction condition: A (0.2 mmol), Na3PO4 (0.1 mmol, 0.5 equiv),
DMSO (2 mL), N2, irradiation of 45 W CFL, and isolated yields.
with electron-donating or electron-withdrawing substituents on
the 3-, 4-, 5-, or 6- position of N-phenyl rings were compatible
to afford the corresponding 2-aryl benzothiazoles B1−B10 in
high yields (90−98%) after the 3−10 h irradiation. The
photocyclization of N-(2-bromophenyl)benzothioamide deriv-
atives bearing various 2-aryl groups was also investigated
(B11−B31). The electronic and steric effects of substitutes on
the 2-aryl ring affect product outcomes. Sterically encumbered
benzothioamides with methyl, methoxyl, and fluoride groups at
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the ortho position of the 2-phenyl ring (B24−B26) showed
lower activities than the corresponding ones bearing groups on
the 3- and 4-postion (B11, B13−B14, and B19−B21). The
reaction was performed with substrates bearing electron-
donating substituents at the p-position of the 2-aryl ring with
excellent yield (98% for B11−B13) after 2−3 h of CFL
irradiation. Electron-deficient 2-aryls with F, Cl, Br, I, or CF3 at
the 4-position were also tolerated in this photocyclization
process, but extended irradiation time (5 or 24 h) was
necessary to reach 86−94% yields (B14−B18). To our delight,
benzothioamides with other halo groups (F, Cl, Br, and I),
which have proven to be challenging substrates using other
reaction conditions, readily underwent debrominative cycliza-
tion to deliver halogenated products (B14−B17, B21−B23,
and B26), facilitating further functionalization of products.
The optimized conditions were also suitable for N-(2-
bromophenyl)-3,4-dimethoxybenzothioamide and N-(2-
bromophenyl)naphthalene-2-carbothioamide to provide the
expected products B27 and B28 in 80−98% yields. Substrates
A29−A31 bearing the pyridine, furan, or thiophene moiety
were converted to B29−B31 in 67−92% yields. N-(2-
Bromophenyl)alkanethioamides A32−A39 were also found
to be the competent substrates for this photocyclization,
producing the corresponding products 2-alkylbenzothiazoles
B32−B39 in moderate to good yields. N1,N4-Bis(2-
bromophenyl)benzene-1,4-bis(carbothioamide) A40 under-
went the double-cyclization reaction in one step to give B40
in 82% yield under standard reaction conditions.
(1.17 g, 4 mmol) was performed to deliver B1 in 73% yield
(0.85 g) under natural sunlight for 8 h (Scheme 3b, see the
Supporting Information). Moreover, we explored some
synthetic applications of this photocyclization protocol. The
cross coupling of 2-(4-bromophenyl)-benzo[d]thiazole (B16)
with diethyl phosphonate by thioxanthen-9-one/(dtbbpy)-
NiBr2 (dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine) dual
catalysis under visible light yielded calcium antagonist
diethyl(4-(benzo[d]thiazol-2-yl)phenyl)-phosphonate (C1)
with good yield (Scheme 3c(I) and see the Supporting
Information). Due to this simple photochemical reaction
system, it is possible to dispense with a workup and isolation
procedure before carrying out further derivatization of the
produced benzothiazole compounds. For example, PhB(OH)2
and a catalytic amount of Pd(OAc)2 were added to the same
reaction flask after the photoirradiation of A17 for 5 h, and the
resulting mixture was heated at 110 °C for 5 h. 2-([1,1′-
Biphenyl]-4-yl)benzo[d]thiazole (C2) was isolated in 84%
yield (Scheme 3c(II)).
The UV/vis absorption spectra of some substrates were
recorded at room temperature (Figure S2). The absorption
spectra of A1, A4, A14, A24, A28, A31, A35, and A41 in
DMSO each indicated the absorption range from UV to visible
wavelengths with the absorption edge at about 450−500 nm.
The cyclization of A1 was carried out upon the irradiation of
CFL, and blue LED, green LED, and red LED afforded B1 in
99%, 95%, 4%, and trace yields, respectively (Scheme 4).
Scheme 4. Control Experiments
With an extensive exploration of the scope of substrates, we
turned our attention to the applications of this catalyst-free
photoreaction (Scheme 3). The cyclization of N-(2-bromo-5-
fluorophenyl)-3,4-dimethoxybenzothioamide A41 afforded 2-
(3,4-dimethoxyphenyl)-5-fluorobenzo[d]thiazole B41 as a
potent antitumor agent, which avoids transition-metal
contamination (Scheme 3a). A gram-scale reaction of A1
Scheme 3. Gram-Scale Reaction and Applications
These yields are correlated with the spectral overlap between
the emission of radiation light and the absorbance of A1
(Figure S3). As depicted in Figure S4, the cyclization
progressed smoothly under the CFL irradiation, but no further
transformation was observed when the light source was moved
away. Even when heated at 80 °C, no desired product was
detected in the dark. These above results confirmed that this
present intramolecular cyclization was a photochemical
process.
To further elucidate the mechanism of this reaction, several
control experiments were conducted. When 1,3-dinitrobenzene
as a strong electron acceptor was added into the photoreaction
system, inhibition of the cyclization was not observed (Scheme
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4). An intermolecular electron transfer process was ruled out.
We also studied the effect of radical inhibitors on this
photoreaction. The addition of 2,2,6,6-tetramethyl-1-piperidi-
nyloxy (TEMPO) into the model reaction hardly suppressed
the cyclization. The reaction could be performed in the
presence of 1,1-diphenylethylene without a significant loss of
yield of B1. Under the standard conditions, N-(3-
bromophenyl)benzothioamide or N-(4-bromophenyl)-
benzothioamide did not undergo photocyclization to B1 or
cross coupling (Scheme 5a). These results display that no aryl
free radicals are involved in the reaction process.
(sp2)−S cross coupling is proposed (Scheme 6). Substrate I or
its anion accepts a photon to generate its excited state II. The
Scheme 6. Proposed Mechanism
Scheme 5. Reactivity of Different Halogenated Substrates
species II then undergoes an intramolecular electron transfer
from the thiolate anion to the N-aryl ring, forming III
possessing the thiyl free radical and aryl halide radical anion.
The intermediate III undergoes debrominative cyclization to
give the desired product.
In summary, we have developed a highly efficient method for
visible-light-promoted intramolecular C(sp2)−S bond forma-
tion in the absence of a photosensitizer and transition metal
catalyst. Under the irradiation of compact fluorescent lamp
light, blue LED, or natural sunlight, 2-halothiobenzanilide
derivatives undergo smoothly intramolecular cross coupling
into 2-aryl benzothiazoles through photon absorption, electron
transfer, and dehalogenative cyclization. Such a photoreaction
has a broad substrate scope, proceeds efficiently on a gram
scale, and is applicable to the synthesis of 2-alkyl
benzothiazoles. It is anticipated that the photocatalyst- and
transition-metal-free methodology may be applied to forge
carbon−carbon/heteroatom bonds under visible light. These
studies are under investigation in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00235.
1
Experimental procedures, H, 13C, 19F, and 31P NMR
The oxidative cyclization of A1 over time was monitored
using HPLC (Figure S5). Product B1 got accumulated at the
same rate as the consumption of A1. Substrate A1 was totally
converted in 4 h. A plot of the percentage of residual substrate
(c/c0) with irradiation time (t) showed that the kinetics of this
reaction obeyed a zero-order rate law. The conversions of A1
and its iodo, chloro, and fluoro derivatives into B1 were also
monitored over time using HPLC as shown in Figure S6. The
order of reactivity was N-(2-iodophenyl)benzothioamide > A1
> N-(2-chlorophenyl)benzothioamide > N-(2-fluorophenyl)-
benzothioamide. N-(2-Bromo-6-fluorophenyl)benzothioamide
A42 afforded a mixture of 4-fluoro-2-phenylbenzothiazole B42
(85%) and 4-bromo-2-phenylbenzothiazole B10 (7%)
(Scheme 5c). The yield of two isomers is consistent with the
halogen activity.
spectra, and characterization data for all products (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Hong-Xi Li − College of Chemistry, Chemical Engineering and
Materials Science, Soochow University, Suzhou 215123,
China; orcid.org/0000-0001-8299-3533; Email: lihx@
suda.edu.cn
Jian-Dong Zhang − College of Chemistry, Chemical
Engineering and Materials Science, Soochow University,
Suzhou 215123, China; Email: zhangjiandong@
suda.edu.cn
Authors
This C−S cross coupling photoreaction was also inves-
tigated through density functional theory (DFT) calculations.
The molecular geometry was optimized using the DFT method
of wB97XD with the basis set of def2-tzvp (see Supporting
Information). The activation barriers of iodo, bromo, and
chloro derivatives are 30.7, 31.8, and 33.3 kcal mol−1,
respectively, which are in agreement with the experimental
results.
Hao Wang − College of Chemistry, Chemical Engineering and
Materials Science, Soochow University, Suzhou 215123,
China
Qi Wu − College of Chemistry, Chemical Engineering and
Materials Science, Soochow University, Suzhou 215123,
China
Hai-Yan Li − Analysis and Testing Center, Soochow
University, Suzhou 215123, China
On the basis of the above results and evidence, a plausible
mechanism for this visible-light-induced intramolecular C-
Complete contact information is available at:
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Noble, A.; Aggarwal, V. K. Catalyst-Free DeaminativeFunctionaliza-
tions of Primary Amines by Photoinduced Single-Electron Transfer.
Angew. Chem., Int. Ed. 2019, 58, 5697−5701.
https://pubs.acs.org/10.1021/acs.orglett.1c00235
Notes
(7) (a) Fu, M.-C.; Shang, R.; Zhao, B.; Wang, B.; Fu, Y.
Photocatalytic Decarboxylative Alkylations Mediated by Triphenyl-
phosphine and Sodium Iodide. Science 2019, 363, 1429−1434.
(b) Mao, T.; Ma, M.-J.; Zhao, L.; Xue, D.-P.; Yu, Y.; Gu, J.; He, C.-Y.
A General and Green Fluoroalkylation Reaction Promoted via
Noncovalent Interactions Between Acetone and Fluoroalkyl Iodides.
Chem. Commun. 2020, 56, 1815−1818. (c) Liang, K.; Li, N.; Zhang,
Y.; Li, T.; Xia, C. Transition-Metal-Free α-Arylation of Oxindoles via
Visible-Light-Promoted Electron Transfer. Chem. Sci. 2019, 10,
3049−3053. (d) Cheng, Y.; Yu, S. Hydrotrifluoromethylation of
Unactivated Alkenes and Alkynes Enabled by an Electron-Donor−
Acceptor Complex of Togni’s Reagent with a Tertiary Amine. Org.
Lett. 2016, 18, 2962−2965.
(8) (a) Bosque, I.; Bach, T. 3-Acetoxyquinuclidine as Catalyst in
Electron Donor−Acceptor Complex-Mediated Reactions Triggered
by Visible Light. ACS Catal. 2019, 9, 9103−9109. (b) McClain, E. J.;
Monos, T. M.; Mori, M.; Beatty, J. W.; Stephenson, C. R. J. Design
and Implementation of a Catalytic Electron Donor−Acceptor
Complex Platform for Radical Trifluoromethylation and Alkylation.
ACS Catal. 2020, 10, 12636−12641. (c) Guo, Q.; Wang, M.; Liu, H.;
Wang, R.; Xu, Z. Visible-Light-Promoted Dearomative Fluoroalkyla-
tion of β-Naphthols through Intermolecular Charge Transfer. Angew.
Chem., Int. Ed. 2018, 57, 4747−4751.
(9) (a) Jung, S.; Shin, S.; Park, S.; Hong, S. Visible-Light-Driven C4-
Selective Alkylation of Pyridinium Derivatives with Alkyl Bromides. J.
Am. Chem. Soc. 2020, 142, 11370−11375. (b) Guo, W.; Zhao, M.;
Tan, W.; Zheng, L.; Tao, K.; Liu, L.; Wang, X.; Chen, D.; Fan, X.
Visible Light-Promoted Three-Component Tandem Annulation for
the Synthesis of 2-Iminothiazolidin-4-ones. J. Org. Chem. 2018, 83,
1402−1413. (c) Ge, Q.-Q.; Qian, J.-S.; Xuan, J. Electron Donor−
Acceptor Complex Enabled Decarboxylative Sulfonylation of
Cinnamic Acids under Visible-Light Irradiation. J. Org. Chem. 2019,
84, 8691−8701. (d) Lee, J.; Hong, B.; Lee, A. Visible-Light-
Promoted, Catalyst-Free Gomberg−Bachmann Reaction: Synthesis
of Biaryls. J. Org. Chem. 2019, 84, 9297−9306.
(10) (a) Chugunova, E.; Boga, C.; Sazykin, I.; Cino, S.; Micheletti,
G.; Mazzanti, A.; Sazykina, M.; Burilov, A.; Khmelevtsova, L.; Kostina,
N. Synthesis and Antimicrobial Activity of Novel Structural Hybrids
of Benzofuroxan and Benzothiazole Derivatives. Eur. J. Med. Chem.
2015, 93, 349−359. (b) Wang, R.-L.; Jin, X.-Y.; Kong, D.-L.; Chen,
Z.-G.; Liu, J.; Liu, L.; Cheng, L. Visible-Light Facilitated Fluorescence
“Switch-On” Labelling of 5-Formylpyrimidine RNA of 5-Formylpyr-
imidine RNA. Adv. Synth. Catal. 2019, 361, 5406−5411. (c) Cheng,
J.; Liu, D.; Li, W.; Bao, L.; Han, K. Comprehensive Studies on
Excited-State Proton Transfer of A Series of 2-(2′-Hydroxyphenyl)
Benzothiazole Derivatives: Synthesis, Optical Properties, and
Theoretical Calculations. J. Phys. Chem. C 2015, 119, 4242−4251.
(11) (a) Zhang, W.; Yue, Y.; Yu, D.; Song, L.; Xu, Y.; Tian, Y.; Guo,
Y. 1,10-Phenanthroline Catalyzed Tandem Reaction of 2-Iodoanilines
with Isothiocyanates in Water. Adv. Synth. Catal. 2012, 354, 2283−
2287. (b) Sethiya, A.; Sahiba, N.; Teli, P.; Soni, J.; Agarwal, S. Current
advances in the synthetic strategies of 2-arylbenzothiazole. Mol.
Diversity 2020, DOI: 10.1007/s11030-020-10149-4.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the financial support provided by the
National Natural Science Foundation of China (21771131 and
21971182), the “Priority Academic Program Development” of
Jiangsu Higher Education Institutions, and Scientific and
Technologic Infrastructure of Suzhou (SZS201708).
REFERENCES
■
(1) (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Visible Light
Photoredox Catalysis with Transition Metal Complexes: Applications
in Organic Synthesis. Chem. Rev. 2013, 113, 5322−5363. (b) Cong,
F.; Lv, X.-Y.; Day, C. S.; Martin, R. Dual Catalytic Strategy for
Forging sp2−sp3 and sp3−sp3 Architectures via β-Scission of Aliphatic
Alcohol Derivatives. J. Am. Chem. Soc. 2020, 142, 20594−20599.
(c) Chen, B.; Wu, L.-Z.; Tung, C.-H. Photocatalytic Activation of
Less Reactive Bonds and Their Functionalization via Hydrogen-
Evolution Cross-Couplings. Acc. Chem. Res. 2018, 51, 2512−2523.
(2) (a) Zhang, J.; Li, Y.; Xu, R.; Chen, Y. Donor−Acceptor Complex
Enables Alkoxyl Radical Generation for Metal-Free C(sp3)−C(sp3)
Cleavage and Allylation/Alkenylation. Angew. Chem., Int. Ed. 2017,
56, 12619−12623. (b) Veatch, A. M.; Alexanian, E. J. Cobalt-
Catalyzed Aminocarbonylation of (Hetero)aryl Halides Promoted by
Visible Light. Chem. Sci. 2020, 11, 7210−7213. (c) Kariofillis, S. K.;
Shields, B. J.; Tekle-Smith, M. A.; Zacuto, M. J.; Doyle, A. G. Nickel/
Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using
Trimethyl Orthoformate as a Methyl Radical Source. J. Am. Chem.
Soc. 2020, 142, 7683−7689.
(3) (a) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Dual Catalysis
Strategies in Photochemical Synthesis. Chem. Rev. 2016, 116, 10035−
10074. (b) Ghosh, I.; Khamrai, J.; Savateev, A.; Shlapakov, N.;
Antonietti, M.; König, B. Organic Semiconductor Photocatalyst Can
Bifunctionalize Arenes and Heteroarenes. Science 2019, 365, 360−
366. (c) Inial, A.; Morlet-Savary, F.; Lalevée, J.; Gaumont, A.−C.;
Lakhdar, S. Visible-Light-Mediated Access to Phosphate Esters. Org.
Lett. 2020, 22, 4404−4407. (d) Yu, X.-Y.; Chen, J.-R.; Xiao, W.-J.
Visible Light-Driven Radical-Mediated C−C Bond Cleavage/
Functionalization in Organic Synthesis. Chem. Rev. 2021, 121, 506−
561.
(4) (a) Wang, N.; Gu, Q.-S.; Li, Z.-L.; Li, Z.; Guo, Y.-L.; Guo, Z.;
Liu, X.-Y. Direct PhotocatalyticSynthesis of Medium-SizedLactams by
C-C Bond Cleavage. Angew. Chem., Int. Ed. 2018, 57, 14225−14229.
(b) Yang, S.; Li, P.; Wang, Z.; Wang, L. Photoinduced Oxidative
Formylation of N,N-Dimethylanilines with Molecular Oxygen without
External Photocatalyst. Org. Lett. 2017, 19, 3386−3389.
(5) (a) Crisenza, G. E. M.; Mazzarella, D.; Melchiorre, P. Synthetic
Methods Driven by the Photoactivity of Electron Donor−Acceptor
Complexes. J. Am. Chem. Soc. 2020, 142, 5461−5476. (b) Lima, C. G.
S.; Lima, T. d. M.; Duarte, M.; Jurberg, I. D.; Paixao, M. W. Organic
̃
Synthesis Enabled by Light-Irradiation of EDA Complexes:
Theoretical Background and Synthetic Applications Organic Synthesis
Enabled by Light-Irradiation of EDA Complexes: Theoretical
Background and Synthetic Applications. ACS Catal. 2016, 6, 1389−
1407. (c) Li, Z.; Ma, P.; Tan, Y.; Liu, Y.; Gao, M.; Zhang, Y.; Yang, B.;
Huang, X.; Gao, Y.; Zhang, J. Photocatalyst- and Transition-Metal-
Free α-Allylation of N-Aryl Tetrahydroisoquinolines Mediated by
Visible Light. Green Chem. 2020, 22, 646−650.
(12) (a) Folgueiras-Amador, A. A.; Qian, X.-Y.; Xu, H.-C.; Wirth, T.
Catalyst- and Supporting-Electrolyte-Free Electrosynthesis of Benzo-
thiazoles and Thiazolopyridines in Continuous Flow. Chem. - Eur. J.
2018, 24, 487−491. (b) Zhu, X.; Yang, Y.; Xiao, G.; Song, J.; Liang,
Y.; Deng, G. Double C−S Bond Formation via C−H Bond
Functionalization: Synthesis of Benzothiazoles and Naphtho[2,1-
d]thiazoles from N-Substituted Arylamines and Elemental Sulfur.
Chem. Commun. 2017, 53, 11917−11920.
(6) (a) Wei, Y.; Zhou, Q.-Q.; Tan, F.; Lu, L.-Q.; Xiao, W.-J. Visible-
Light-Driven Organic Photochemical Reactions in the Absence of
External Photocatalysts. Synthesis 2019, 51, 3021−3054. (b) Guille-
mard, L.; Colobert, F.; Wencel-Delord, J. Visible-Light-Triggered,
Metal- and Photocatalyst-Free Acylation of N-Heterocycles. Adv.
Synth. Catal. 2018, 360, 4184−4190. (c) Wu, J.; Grant, P. S.; Li, X.;
(13) (a) Rey, V.; Soria-Castro, S. M.; Arguello, J. E.; Penénory, A. B.
̈ ̃ ̃
Photochemical Cyclization of Thioformanilides by Chloranil: An
Approach to 2-Substituted Benzothiazoles. Tetrahedron Lett. 2009, 50,
4720−4723. (b) He, W.-B.; Gao, L.-Q.; Chen, X.-J.; Wu, Z.-L.;
Huang, Y.; Cao, Z.; Xu, X.-H.; He, W.-M. Visible-Light-Initiated
2082
https://dx.doi.org/10.1021/acs.orglett.1c00235
Org. Lett. 2021, 23, 2078−2083

Organic Letters
pubs.acs.org/OrgLett
Letter
Malic Acid-Promoted Cascade Coupling/Cyclization of Aromatic
Amines and KSCN to 2-Aminobenzothiazoles Without Photocatalyst.
Chin. Chem. Lett. 2020, 31, 1895−1898.
(sp)−S Coupling Reaction: Synthesis of Substituted 2-Phenyl-
benzothiazoles via thia-Wolff Rearrangement. Chem. Commun. 2020,
56, 3781−3784.
(25) (a) Bowman, W. R.; Heaney, H.; Smith, P. H. G.
Intramolecular Aromatic Substitution (SRN1) Reactions; Use of
Entrainment for the Preparation of Benzothiazoles. Tetrahedron Lett.
1982, 23, 5093−5096. (b) Jayanthi, G.; Muthusamy, S.; Paramasivam,
R.; Ramakrishnan, V. T.; Ramasamy, N. K.; Ramamurthy, P.
Photochemical Synthesis of s-Triazolo[3,4-b]benzothiazole and
Mechanistic Studies on Benzothiazole Formation. J. Org. Chem.
1997, 62, 5766−5770.
(14) (a) Gan, Z.; Li, G.; Yang, X.; Yan, Q.; Xu, G.; Li, G.; Jiang, Y.-
Y.; Yang, D. Visible-Light-Induced Regioselective Cross-Dehydrogen-
ative Coupling of 2-Isothiocyanatonaphthalenes With Amines Using
Molecular Oxygen. Sci. China: Chem. 2020, 63, 1652−1658. (b) Dinh,
A. N.; Nguyen, A. D.; Aceves, E. M.; Albright, S. T.; Cedano, M. R.;
Smith, D. K.; Gustafson, J. L. Photocatalytic Oxidative C−H
Thiolation: Synthesis of Benzothiazoles and Sulfenylated Indoles.
Synlett 2019, 30, 1648−1655.
(26) (a) Wang, X.; Cuny, G. D.; Noel, T. A Mild, One-Pot Stadler−
Ziegler Synthesis of Arylsulfides Facilitated by Photoredox Catalysis
in Batch and Continuous-Flow. Angew. Chem., Int. Ed. 2013, 52,
7860−7864. (b) Oderinde, M. S.; Frenette, M.; Robbins, D. W.;
Aquila, B.; Johannes, J. W. Photoredox Mediated Nickel Catalyzed
Cross-Coupling of Thiols With Aryl and Heteroaryl Iodides via Thiyl
Radicals. J. Am. Chem. Soc. 2016, 138, 1760−1763. (c) Jouffroy, M.;
Kelly, C. B.; Molander, G. A. Thioetherification via Photoredox/
Nickel Dual Catalysis. Org. Lett. 2016, 18, 876−879. (d) Jiang, M.; Li,
H.; Yang, H.; Fu, H. Room-Temperature Arylation of Thiols:
Breakthrough with Aryl Chlorides. Angew. Chem., Int. Ed. 2017, 56,
874−879.
(15) Liu, Y.; Chen, X.-L.; Sun, K.; Li, X.-Y.; Zeng, F.-L.; Liu, X.-C.;
Qu, L.-B.; Zhao, Y.-F.; Yu, B. Visible-Light Induced Radical
Perfluoroalkylation/Cyclization Strategy To Access 2-Perfluoroalkyl-
benzothiazoles/Benzoselenazoles by EDA Complex. Org. Lett. 2019,
21, 4019−4024.
(16) (a) Zhang, G.; Liu, C.; Yi, H.; Meng, Q.; Bian, C.; Chen, H.;
Jian, J.-X.; Wu, L.-Z.; Lei, A. External Oxidant-Free Oxidative Cross-
Coupling: A Photoredox Cobalt-Catalyzed Aromatic C−H Thiolation
for Constructing C−S Bonds. J. Am. Chem. Soc. 2015, 137, 9273−
9280. (b) Ye, L.-m.; Chen, J.; Mao, P.; Mao, Z.-f.; Zhang, X.-j.; Yan,
M. Visible-Light-Promoted Synthesis of Benzothiazoles from 2-
Aminothiophenols And Aldehydes. Tetrahedron Lett. 2017, 58,
874−876.
(17) (a) Evindar, G.; Batey, R. A. Parallel Synthesis of a Library of
Benzoxazoles and Benzothiazoles Using Ligand-Accelerated Copper-
Catalyzed Cyclizations of ortho-Halobenzanilides. J. Org. Chem. 2006,
71, 1802−1808. (b) Gan, F.; Luo, P.; Lin, J.; Ding, Q. Recent
Advances in the Synthesis and Applications of 2-Arylbenzothiazoles.
Synthesis 2020, 52, 3530−3548.
(27) Liu, B.; Lim, C.-H.; Miyake, G. M. Visible-Light-Promoted C−
S Cross-Coupling via Intermolecular Charge Transfer. J. Am. Chem.
Soc. 2017, 139, 13616−13619.
(28) Xu, Z.-M.; Li, H.-X.; Young, D. J.; Zhu, D.-L.; Li, H.-Y.; Lang,
J.-P. Exogenous Photosensitizer-, Metal-, and Base-Free Visible-Light-
Promoted C−H Thiolation via Reverse Hydrogen Atom Transfer.
Org. Lett. 2019, 21, 237−241.
(18) (a) Gao, M.-Y.; Li, J.-H.; Zhang, S.-B.; Chen, L.-J.; Li, Y.-S.;
Dong, Z.-B. A Mild Synthesis of 2-Substituted Benzothiazoles via
NickelCatalyzed Intramolecular Oxidative C−H Functionalization. J.
Org. Chem. 2020, 85, 493−500. (b) Benedí, C.; Bravo, F.; Uriz, P.;
Fernández, E.; Claver, C.; Castillón, S. Synthesis of 2-Substituted-
Benzothiazoles by Palladium-Catalyzed Intramolecular Cyclization of
o-Bromophenylthioureas and o-Bromophenylthioamides. Tetrahedron
Lett. 2003, 44, 6073−6077.
(19) (a) Yu, C.; Lee, K.; You, Y.; Cho, E. J. Synthesis of 2-
Substituted Benzothiazoles by Visible Light-Driven Photoredox
Catalysis. Adv. Synth. Catal. 2013, 355, 1471−1476. (b) Samanta,
S.; Das, S.; Biswas, P. Photocatalysis by 3,6-Disubstituted-s-Tetrazine:
Visible-Light Driven Metal-Free Green Synthesis of 2-Substituted
Benzimidazole and Benzothiazole. J. Org. Chem. 2013, 78, 11184−
11193.
(20) (a) Wade, A. R.; Pawar, H. R.; Biware, M. V.; Chikate, R. C.
Synergism in Semiconducting Nanocomposites: Visible Light Photo-
catalysis Towards the Formation of C-S and C-N Bonds. Green Chem.
2015, 17, 3879−3888. (b) Das, S.; Samanta, S.; Maji, S. K.; Samanta,
P. K.; Dutta, A. K.; Srivastava, D. N.; Adhikary, B.; Biswas, P. Visible-
Light-Driven Synthesis of 2-Substituted Benzothiazoles Using CdS
Nanosphere as Heterogenous Recyclable Catalyst. Tetrahedron Lett.
2013, 54, 1090−1096.
(21) (a) Cheng, Y.; Yang, J.; Qu, Y.; Li, P. Aerobic Visible-Light
Photoredox Radical C-H Functionalization: Catalytic Synthesis of 2-
Substituted Benzothiazoles. Org. Lett. 2012, 14, 98−101. (b) Bouchet,
L. M.; Heredia, A. A.; Arguello, J. E.; Schmidt, L. C. Riboflavin as
̈
Photoredox Catalyst in the Cyclization of Thiobenzanilides: Synthesis
of 2-Substituted Benzothiazoles. Org. Lett. 2020, 22, 610−614.
(22) Yang, F.; Koeller, J.; Ackermann, L. Photoinduced Copper-
Catalyzed C-H Arylation at Room Temperature. Angew. Chem., Int.
Ed. 2016, 55, 4759−4762.
(23) Natarajan, P.; Manjeet, M.; Muskan, M.; Brar, N. K.; Jot Kaur,
J. Visible Light Photoredox Catalysis: Conversion of a Mixture of
Thiophenols and Nitriles into 2-Substituted Benzothiazoles via
Consecutive C−S and C−N Bond Formation Reactions. Org. Chem.
Front. 2018, 5, 1527−1531.
(24) Reddy, M. B.; Anandhan, R. Visible Light Initiated Amino
Group ortho-Directed Copper(I)-Catalysed Aerobic Oxidative C-
2083
https://dx.doi.org/10.1021/acs.orglett.1c00235
Org. Lett. 2021, 23, 2078−2083