S-Tetrazine Dyes: A Facile Generation of Photoredox Organocatalysts for Routine Oxidations

Article abstract of DOI:10.1021/acs.joc.9b02454

A series of organic dyes derived from s-tetrazine have been synthesized, and their photophysical and electrochemical properties are systematically investigated. Testing these compounds as photoredox catalysts in a model oxidative C-S bond cleavage of thioethers has led us to identify new classes of active s-tetrazines. Moreover, some of them can be formed in situ from commercially available 3,6-dichlorotetrazine, making this photocatalyzed C-S bond functionalization simple and highly practical.

Full text of DOI:10.1021/acs.joc.9b02454

Subscriber access provided by - Access paid by the | UCSF Library
Article
s-Tetrazine Dyes: a facile generation of
photoredox organocatalysts for routine oxidations
Tuan Le, Thibaut Courant, Jérémy Merad, Clémence Allain, Pierre Audebert, and Géraldine Masson
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02454 • Publication Date (Web): 13 Nov 2019
Downloaded from pubs.acs.org on November 14, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
s-Tetrazine Dyes: a facile generation of photoredox
organocatalysts for routine oxidations
§†
§‡
‡
†
†
Tuan Le, Thibaut Courant, Jérémy Merad, Clémence Allain, * Pierre Audebert and
Géraldine Masson‡*
‡
Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université
Paris-Saclay, 1, av. de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
†
PPSM, ENS Paris-Saclay, CNRS, Université Paris-Saclay, 94235 Cachan, France.
New organic
photocatalysts
N
N
N
N
s-tetrazines
X
X
(Tz)
Tz
NHCOR2
R1 SR3
NHCOR2
R1 Nu
singlet photo-oxidants
tunable redox potentials
generation in situ
Nu
low molecular weight
ABSTRACT: A series of organic dyes derived from s-tetrazine have been synthesized, and their photophysical
and electrochemical properties systematically investigated. Testing these compounds as photoredox catalysts
in a model oxidative C-S bond cleavage of thioethers has led us to identify new classes of active s-
tetrazines. Moreover, some of them can be formed in situ from commercially available 3,6-dichlorotetrazine
making this photocatalyzed C-S bond functionalization simple and highly practical.
high electron affinity and can be reversibly
reduced into their anion-radical counterpart.
Their reduction potential can be tuned by the
INTRODUCTION
In recent years, visible light photoredox
catalysis has turned out to become a powerful ally
nature of the aromatic substituents. In addition,
to drive ion-radical redox reactions under mild
1
we6 and others
7
have demonstrated that
reaction conditions. In this context, Ru(II) and
Ir(III) polypyridyl complexes, have been
appropriately substituted tetrazines absorb
visible light while displaying long fluorescence
lifetimes and high quantum yields. Despite this
attractive profile, as far as we are aware, only
extensively used as sensitizers, owing to their
exceptional photophysical properties (Scheme 1,
a).1,2 On the other hand, this unique reactivity
is offset by high costs, toxicity and scarcity in
metal resources, a situation responsible for the
limited exports of photoredox catalysis out of
academic laboratories. An alternative is provided
by the use of naturally occurring dyes as
sensitizers (such as methylene blue and eosin Y,
Scheme 1, b).3 Consequently, identifying new
organic scaffolds as non-toxic, inexpensive and
eco-friendly photocatalysts has recently become a
3
,6-di(pyridin-2-yl)-1,2,4,5-tetrazine 1 has been
employed as a photocatalyst by Biswas et al.
8
(
this
Scheme 1, b). However, the imposed structure of
Scheme 1. Selected photocatalysts. Oxidative C-S
bond functionalizations
dynamic research area. As
a result of these
extensive investigations, original structures
like cyanoarenes (i.e. 4CzIPN) and acridinium
+
salts (i.e. Mes-Acr ) have been brought to light
4
(
Scheme 1, b). Although these examples of organic
sensitizers represent important advances, the
development of accessible and cheap metal-free
photocatalysts is still highly desirable.
As part of our continuing efforts to develop novel
photocatalytic processes5 and design new organic
fluorophores,6 we have recently turned our
attention to s-tetrazines (1,2,4,5-tetrazines 2,
Scheme 1). These electroactive heterocycles show
ACS Paragon Plus Environment

The Journal of Organic Chemistry
The study started with the synthesis of several
substituted s-tetrazines 2, easily prepared by a
Page 2 of 12
a) TM-based photocatalysts2
+
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
single nucleophilic aromatic substitution step
N
N
N
N
N
N
N
between
dichlorotetrazine
such as alcohols and pyrazole, Scheme 2).6
commercially
available
3,6-
Ru
N
Ir
3
and various nucleophiles
(
N
Etherification process was efficiently conducted
in the presence of 2,4,6-collidine with phenols
and aliphatic alcohols, then affording tetrazines
Ru(bpy)32+
fac-Ir(ppy)33+
b) Organic dyes
2
a-d with moderate to good yields. Sterically
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N
CO2H
Br
demanding adamantan-1-ylmethanol gave only mono-
substituted product and the addition of DMAP was
required to promote the second substitution and
deliver 2e with 33% yield. The synthesis of 3,6-
di(1H-pyrazol-1-yl)-tetrazine 2g can be achieved
Br
+
N
S
N
-
Cl
HO
O
OH
Br
Methylene blue
Me
Br
Eosin Y
3
by refluxing pyrazole and 3 in CH CN.
R
Scheme 2. Synthesis of 3,6-dialkoxy-tetrazines from
3,6-dichloro 1,2,4,5-tetrazine 3
Me
Me
NC
R
CN
R
R =
N
NuH (2 equiv)
N
N
N
N
N
2,4,6-collidine (2 equiv)
N
N
N
N
ClO4-
R
Me Mes-Acr+
4CzIPN
Cl
Cl
O
Nu
R
CH2Cl2, 40 °C
3
2
N
N
N
N
N
N
N
RO
OR
O
F3C
O
R, Nu=
Cl
O
N
N
N
1
2
t-Bu
c) Photocatalyzed NDA reaction
Cl
CF3
N
N
N
N
2a 74%
2b 74%
2c 76%
2d 64%
O
R
R
O
Pcat 1-3
R, Nu=
O
R2
NH
SR3
R2
NH
R= Cl, Nu =
+
Nu
O
O
N
N
R1
R1
Nu
F3C
5
N
N
4
R2
6
NH
SR3
2e 33%c
39%d
2h 79%e
2g
7
2f 61%
R1
a
Reaction conditions: 3 (1.6 mmol), NuH (3.2 mmol), collidine
(20 mL) at reflux. b Isolated yields. c
(
3.2 mmol) in CH
2
Cl
2
3
(1.6 mmol), NuH (3.2 mmol), collidine (1.6 mmol, 1 equiv.) in
CH Cl (20 mL) at reflux followed by addition of DMAP (3.2
mmol). d with CH CN as solvent.e (1.6 mmol), NuH ( 1.6 mmol,),
collidine (1.6 mmol) in CH Cl (20 mL) at reflux
compound only offers a poor modularity of its
photoredox performances. Since 3,6-dialkoxy and
2
2
3
3
,6-diaryloxy tetrazines 2 exhibit significantly
improved fluorescence quantum yields compared to
,6c,6f we have assumed that this general scaffold
2
2
The photophysical and electrochemical properties
of synthesized s-tetrazines 2 were then recorded
1
could be the starting point to design original,
cheap and highly efficient photocatalysts. Herein
is reported a comparative study accounting for the
ability of various 3,6- dialkoxy and 3,6-diaryloxy
tetrazines 2 to catalyze the C−S bonds cleavage
of α-carbamoylsulfides under visible-light
irradiation (Scheme 1, c). In addition, to their
(
Table
1).
Dichloromethane
solutions
of
tetrazines 2a to 2g display a strong absorption
band in the UV region, corresponding to a *
allowed transition (See the UV–vis spectra,
Figure S1 in Supporting Information). More
interestingly, a less intense band was observed
in the green region (520-530 nm) resulting from a
mainly forbidden n-* transition. Modifying the
electronic properties of the substituents of s-
tetrazines only had a small impact on the λmax of
this last band and all compounds showed decent
synthesis,
their
electrochemical
and
spectroscopic properties were investigated and
compared to tetrazine 1. Following this studies,
we found that an active photocatalyst can be
formed in situ from commercially available 3,6-
dichlorotetrazine, improving the practical aspect
of using tetrazines as photocatalysts.
-
1
1
molar extinction coefficient (>500 cm .L.mol- ).
Irradiation of 2 in the green region produces
fluorescence emission between 549 and 577 nm
RESULTS AND DISCUSSION
(recorded
in
dichloromethane)
with
high
ACS Paragon Plus Environment

Page 3 of 12
The Journal of Organic Chemistry
electron transfer from the radical ionic product
fluorescence quantum yields (See the fluorescence
spectra, Figure S2 in Supporting Information).
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
is faster in the case of singlet state.10 This
feature pushed us to believe that highly
fluorescent s-tetrazines with long lifetime of
excited state could emerge as unique singlet
photoredox catalysts suitable for wide-range
oxidations.
Table 1. Photophysical data for tetrazines 2a to 2h
2 2
and 3 in CH Cl .

abs


em nm
577

f
 ns
entry
Pcat 2
nm
31,
340,
32
25,
5
600
0.14
60
1
2
2aa
Electrochemical data for s-tetrazines 2a to 2g in
dichloromethane and using ferrocene as internal
reference are reported in Table 2 (See the cyclic
2
5
600
640
567
0.27
0.31
130
165
2ba
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
350
voltammograms,
Information). Measured reduction potentials from
0.21V to –0.86V vs SCE for tetrazines 2a to 2g
Figure
S4
in
Supporting
2
c
528,
335,
563,
573
3
4
2
58
530,
45,
‒
2da
500
575
574
0.005
n.d.
confirmed their high electron affinity as well as
the opportunity to finely tune their reduction
potential by modifying lateral chains. The
geometry of tetrazines has been optimized using
DFT/B3LYP/6-31G(d) method and their electronic
properties as HOMO, LUMO levels were examined (see
Figure S10 to S17 in Supporting Information). It
3
232
2eb
523,
588
680
0.07
0.32
5
6
32
3
33
2f
520,
331,
556,
566
133
2
72
520,
71,
90
517,
48,
70
515,
07
7
8
9
2g
2h
3d
600
420
556
553
555
0.02
0.15
0.14
8c
is worth noting that
obtained between the
a
good correlation was
reduction potential
3
2
determined experimentally and the LUMO level
obtained from DFT calculations.6c An optical gap
of 2.17V was then applied to calculate the
reduction potential of the singlet excited state.
The resulting values proved to be significantly
higher than that displayed by the excited state
of some benchmark photoredox catalysts such as
94
3
2
460
58
3

abs absorption wavelength.

molar absorption coefficient
emission wavelength,
fluorescence quantum yield, measured using rhodamine 6G in



(M cm  for first

abs value em
,

f
Ru(bpy)
3
2+, eosin Y, fluorescein, 4CzIPN and
similar to that of excited mesitylacridinium (E*=
a
EtOH as a reference (f_ref =0.95), fluorescence lifetime.
b
c
2.06V vs SCE) (figure 1).
Data from ref 6f. Data from 6g Pure at >95% contaminated
by inseparable amount of 2h. dData from ref 6b
Table 2. Electrochemical data for tetrazines 2a to
However, the presence of electron donor groups on
the phenoxy moiety led to complete extinction of
the fluorescence for tetrazines 2d with no
measurable quantum yield, this presumably due to
an intramolecular electron-transfer from the
electron-rich substituent to the tetrazine core.
Similar results were observed with aliphatic alkyl
groups such as the adamantyl. Interestingly, 3,6-
bis-(2,2,2-trifluoroethoxy)-1,2,4,5-tetrazine
2 2
2h and 3 in CH Cl .
E0(Tz
E0(
Tz-.
/
vs
Tz*
/Tz
E0(Tz
*/Tz-
Pcat
2
E0(Tz/
Tz-. vs
-.
entry
SCE)
.
vs
vs
Fc+/Fc
-)
Fc+/
Fc -)
SCE
)
2aa
2ba
-0.92
-0.92
-0.61
-0.99
-0.52
-0.52
-0.21
-0.59
1.25
1.25
1.56
1.18
1.65
1.65
1.96
1.58
1
2
3
4
5
6
7
8
9
(
2c) is highly fluorescent. Excited state
lifetimes were extrapolated from the rates of
fluorescence decays and turned out to be long for
compounds 2a-c, 2f (60-165 ns, Figure S3, in
Supporting Information). It is important to notice
that commonly employed photoredox catalysts
usually perform SET from their long living (up to
ms) triplet excited state. However, it is
established that direct photoexcitation of s-
tetrazines does not lead to intersystem crossing
2c
2da
2eb
2f
-1.26
- 0.98
- 0.90
-0.78
-0.68
-0.86
-0.58
-0.50
-0.38
-0.28
0.91
1.19
1.27
1.39
1.49
1.31
1.59
1.67
1.79
1.89
2g
2h
3c
0
.-
E (Tz/Tz ) measured in DCM with 1mM concentration of 2,
a
(
ISC) and phosphorescence is only observed in
0.1M TBAPF6 and ferrocene as internal reference. data
from reference 6f. b Data from ref 6g c Data from ref 6c.
specific cases.9 Theoretically, SET from singlet
or triplet states are equally fast, only back
Figure 1. Electrochemical scale
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 12
Mes-Acr+
4CzIPN
Fluorescein
Pcat 1, 2 or 3 (10% mol),
solvent, additive (10 equiv)
t
t
t
NHBoc
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
E = 2.06V
E = 1.49V
E = 0.78V
NHBoc
SEt
NH
N
N
N
+2.5
0
E* (V vs SCE)
Ph
Ph
O2 (1 atm), rt, 20 h
green LEDs
4a
5a
6a
Eosin Y Ru(bpy)32+
E = 0.79V ERu(II)*/Ru(I)= 0.77V
yield (%)b
Tetrazines
entry
Pcat
solvent
additive
-
t
t
E = 1.96 to 1.65 V
1
2
1
2a
2b
2c
2d
2e
2f
2g
2c
2g
3
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
trace
33
Ir[dF(CF3)ppy]2(dtbpy)3+
EIr(III)*/Ir(II)= 1.21V
-
3
-
43
In 2016, our group developed a Ru(bpy)
catalyzed coupling reaction of azoles with α -
carbamoylsulfides through single-electron
oxidation of sulfides.5b,c In this studies, organic
dyes such as eosin and 9-mesityl-10-
methylacridinium provided disappointing results
comparatively to Ru(bpy) (PF Therefore,
3 6
(PF) -
4
-
75
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
-
33
a
6
-
70
7
-
10
Y
8
-
69
)
2
.
9
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
93
3
6
identifying efficient organic dyes able to compete
with Ru complexes in oxidative C-S bond
functionalization is still highly motivating.
This reaction was then selected as a model to
evaluate the performances of s-tetrazine dyes
2.5b,c,g,11
10
11
12
93
CH CN
3
79
2h
3
CH CN
3
86
0c
1
1
1
3
4
5
CH
CH
CH
3
3
3
CN
CN
CN
0d
8e
-
3
Based on the singlet excited-state oxidation
potentials shown in Table 2, most of s-tetrazines
16
4CzIPN
CH CN
3
42
72
1
1
1
2
2
7
8
9
0
1
Ru(bpy)
3
Cl
2
CH
CH
3
3
CN
CN
2
should be able to oxidize the
α -
Mes-acr
60
carbamoylsulfides (Eox = +1.18 V vs SCE)5c through
2g
2g
2g
CH
THF
CH CN
2
Cl
2
25
a SET oxidation. As a matter of fact, irradiation
trace
78f
with green LEDs of 2a (10 mol%) under O
in CH CN in the presence of tert-butyl-(1-
ethylthio)-3-phenylpropyl)carbamate (4a) with
2
atmosphere
3
3
a
General conditions: 4a (0.10 mmol, 1 equiv.), 5a (0.15 mmol),
2 (0.10 equiv), in CH CN (1 mL) irradiated with 5 W green LEDs
at rt for 20 h. b Isolated yields. c Reaction performed in the
(
3
pyrazole (5a) led to the formation of desired
adduct 6a with 33% yield after 20 h. (Table 3,
dark. d Reaction conducted without Pcat. e Reaction conducted
entry 2). Meanwhile, tetrazine
1
was nearly
under argon atmosphere.
chlorocyclohexane.
f
Reaction conducted with
unreactive under these conditions (entry 1). As
speculated, dye 2b (entry 3) with comparable
photoredox properties gave a similar yield. s-
Tetrazine 2c (with higher quantum yield)
(entries 9 and 10). To our delight, the use of
commercially fluorescent 3,6-dichlorotetrazine 3
results in an efficient C-N bond formation (entry
incorporating
m-bis-(trifluoromethyl)-group
1
1). However, a careful analysis of the reaction
progress allows us to detect the in situ formation
of 3-chloro-6-(1H-pyrazol-1-yl)-1,2,4,5-
tetrazine (2h), resulting from a nucleophilic
mono-substitution by pyrazole. We then
afforded 6a with the higher yield (entry 4) while
weakly fluorescent compound 2d provided 33% yield
of 6a (entry 5). Surprisingly, better conversion
was observed when using less fluorescent compound
2e comparted to 2f and 2g (entry 6 vs. entry 7).
Bis-pyrazole tetrazine 2g showed also promising
results as photocatalyst for the coupling reaction
synthesized this compound (See Supporting
Information) and demonstrated it was the active
catalytic species when the reaction was conducted
with 3 (entry 12). As a confirmation, compound 2h
(
entry 8). We then imagine that the addition of
an acidic additive able to stabilize radical
anions could improve the reaction
displayed
(
similar
excited-state lifetime, absorption spectral
photophysical
properties
efficiency.5b,c,g,11 Indeed, in the presence of
2,2,2-trifluoroethanol (TFE), 2c and 2g catalyze
the formation of 6a with an excellent yield of 93%
features and fluorescence, Table 1) to 2c while
with a lower oxidation potential (Table 2). Other
solvents and additives have been tested in
Table 3. Optimization of the oxidative C-S bond
functionalization.a
combination with
3
without any significant
improvement of the yields was observed (See
Supporting information). Under these conditions,
catalyst 4CzIPN, Ru(bpy) Cl
methylacridinium tetrafluoroborate
3
2
and 9-mesityl-10-
(Mes-acr)
ACS Paragon Plus Environment

Page 5 of 12
The Journal of Organic Chemistry
afforded the adduct 6a in lower yields (entries
6-18) thus clearly demonstrating the superiority
branched alkyl chains or silyl ethers reacted
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
smoothly to deliver 56 to 80% of the desired
adducts 6h-6l. As expected, tetrazines 2c and 2g
efficiently catalyze the C-N bond formation (6c,
6d, 6f, 6h, 6j, 6h and 6l). To our delight, when
1 equiv of chlorocyclohexane was added in the
reaction of 4a and 5a, the desired coupling
product was exclusively formed in similar yield,
showing thus satisfactory tolerance with halogen
groups (Table 3, entry 21).12 The reaction of C-C
bonds is also promoted by tetrazines 2g and 3 when
trimethoxybenzene was used instead of pyrazole
of tetrazines over other photocatalysts in C-S
bond functionalization (entry 16, Table 3). We
also briefly screened other solvents for the
process. However, the yield was substantially
decreased when the reaction was conducted in
CH
2
Cl
2
, or THF instead of CH
3
CN (entries 19 and
2
0).
With the optimized reaction conditions, the scope
of the photo-catalyzed oxidative C-S bond
functionalization was next investigated (Scheme
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
6m). Surprisingly, nearly no product 6m was
3
). In order to propose a turnkey process, the
observed when using 2c as a catalyst. To our
delight, the photocatalytic aza-Friedel–Craft
reaction can be applied to aromatic and aliphatic
α-amidosulfides (6n and 6p). Finally, thiophene
and indole readily participate in nucleophilic
addition giving rise, respectively, to 6o and 6p
in descent yield. The model reaction could also
be scaled-up to 1 mmol scale giving 89% of desired
compound 6a showing that tetrazine photocatalysis
reaction scope was first explored by using the
commercially available pre-catalyst 3. Electron-
rich and poor pyrazoles, as well as benzopyrazole
and benzoimidazole are effective reaction
partners since they afford the corresponding
coupling products 6b-g in moderate to good yields.
In addition, α-carbamoyl sulfides bearing either
linear and
Scheme 3 Scope of the reaction for oxidative C-S
bond functionalizationa
could be
a very inexpensive way to perform
photoredox reaction on large scale (see Supporting
information).
O
Pcat (10 mol%)
TFE (10 equiv)
O
R2
NH
NuH
5
R2
+
NH
Scheme 4. Suggested reaction mechanism for electron
rich substrates
CH3CN, rt, 20 h
green LEDs
R1
SR3
R1
Nu
6
4
N
Cl
N
NHBoc
NHCbz
NHBoc
N
Cl
N
3
N
N
N
Ph
N
Ph
N
Ph
Ph
N
H
6c 80%c
6d 97%b
N
6b 70%d
N
d
76%d
80%
R4
N
R4
5
NHBoc
NHBoc
N
NHCO2R3
NHBoc
N
N
N
N
N
R4
N
Ph
N
Ph
6g
R1
N
N
N
N
2h
c
O2
6
e 63%d
6f 88%
79%d
7%d
Cl
N
5
6
NO2
O2.-
R4
R4
NHBoc
NHBoc
NHBoc
NHBoc
H
N
N
N
N
(
)6
N
N
N
N
N
( )6
N
N
N
N
N
N
N
N
HOO
N
N
R4
c
b
6
h 99%
71%
6j
N
N
8
75%
4%
6k 56%d
6i 80%d
Cl
N
5
d
d
Cl
9
8
1/2 H2O2 + 1/2 O2
BocHN
OMe
SET
NHBoc
BocHN
MeO
OMe
TBDPSO
N
(
)3
N
Ph
NHCO2R3
NHCO2R3
NHCO2R3
6
l 83%c
OMe
MeO
OMe
d
c
c
R1
SR2
R1
SR2
R1
80%
6m 90%
55%d
6n
9
7%
11
d
97%
SR2
4
10
BocHN
BocHN
H
N
R2SSR2
S
Ph
6p 55%d
Ph
OMe
6o 58%d
In view to clarify the reaction mechanism, control
experiments were conducted. They have pointed out
that the reaction does not proceed in the absence
of light (Table 3, entry 13) or photocatalyst
(entry 14) while working under an oxygen
atmosphere is essential to regenerate the ground
a
Reaction conditions: 4 (0.10 mmol), 5 (0.15 mmol), Pcat
10 mol%), in CH CN (1 mL) irradiated with 5 W green LEDs
(
3
at rt for 20h. b Isolated yieldswith 2c. c Isolated yields
with 2g. d Isolated yields with 3.
state
catalyst
(entry
15).
Stern−Volmer
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 12
fluorescence quenching experiments (see Figure S5 HPLC grade solvents purchased from Sigma-Aldrich or
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
and S6 in Supporting Information) established that
α-carbamoylsulfides is the fluorescence quencher
for the excited state of s-tetrazine dye 2h.
freshly distilled solvents were used for flash
chromatography for compounds undergoing full
characterization. Reaction solvents were purchased
from ACROS 99.8% grade on molecular sieves. All
Based on our previous studies and the above
results,5b,c
other
commercially
available
reagents
were
a
possible reaction mechanism is
proposed in Scheme 4.1 Upon irradiation, s-
purchased from Acros, Aldrich, Fluka, VWR, Aplichem
or Merck and used without any further purification.
tetrazine 2h in situ generated from 3, is excited
to its singlet state 8 and reductively quenched
by α-carbamoylsulfides 4 to generate tetrazine
radical anion 9 and sulfur radical cation 10 via
single electron transfer (SET) oxidation.
Subsequent C-S bond cleavage affords N-carbamoyl
iminium 11 and thiyl radical 12 which dimerizes
fast (isolation of disulfide supports the
3
,6-dichloro-1,2,4,5-s-tetrazine was purchased from
Sigma-Aldrich. Chromatography was performed on
silica gel (60-240 mesh) unless otherwise
specified. Analytical thin layer chromatography
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
6
TLC) was performed on silica gel plates (Merck
0F254) visualized either with a UV lamp (254 nm) or
by using permanganate, phosphomolbdic acid or
ninhydrin stain. Organic extracts were dried over
mechanism,
Information). Meanwhile, photocatalyst 2h is
See
Figure
S7
in
Supporting
anhydrous MgSO
4
.
1H NMR and 13C NMR spectra were
1
recorded on Bruker DPX-500, at 500 MHz ( H value)
regenerated by the reduction of oxygen to
1
3
●−). Nucleophilic
or 125 MHz ( C value) in CDCl
referenced to residual chloroform (7.26 ppm, 1H;
7.0 ppm, 13C) or TMS. Chemical shifts are reported
3
. Spectra were
superoxide radical anion (O
addition of pyrazole 5 and deprotonation by O
ultimately afford the desired product 6. To
●−, the reactions
confirm the formation of
between 4 and 5 were conducted in the presence of
p-benzoquinone (p-BQ), as superoxide
2
●
−13
2
7
in ppm, multiplicities are indicated by s (singlet),
d (doublet), t (triplet), q (quartet), qt (quintet),
and m (multiplet or unresolved), br (broad signal).
Coupling constants, J, are reported in hertz (Hz).
All NMR spectra were obtained at 300K unless
otherwise specified. High-resolution mass spectra
(HRMS) were recorded using electrospray ionization
O
2
a
scavenger.14 Coupling product 6a was obtained in
only 20% yield (see Figure S8 in Supporting
Information), indicating that the formation of a
superoxide radical is crucial step in this
(ESI) and
a
time-of-flight (TOF) analyzer in
photocatalyzed process.
using iodine-starch indicator (see Figure S9 in
A
control experiment
positive-ion or negative-ion detection mode.
Reaction were irradiated using Flexled INSPIRE LED
lamp (45 LEDs, 7.2W, λ = 535 nm) at a 5cm distance
and using a cooling fan to keep temperature at
Information),15
Supporting
highlighted
the
2 2
presence of H O (see Scheme 4) at the end of the
reaction probably generated by disproportionation
●).“
25°C.
Amidosulfides starting materials were
of hydroperoxyl radical (HO
2
synthesized according literature procedure.16
CONCLUSION
General Protocol for azoles coupling. To a solution
of amidosulfide (0.1 mmol, 1eq) in acetonitrile
In conclusion, we have designed and prepared new s-
tetrazine dyes displaying high oxidative ability.
These compounds are among the smallest photoredox
catalysts reported in the literature and can be
generated in situ from commercially available
compounds. Moreover, their redox properties can be
tuned by modifying the substitution patterns. These
advantages make them easy to handle and quickly
accessible. Their efficiency has been demonstrated
in a model C-S bond functionalization where they
competed efficiently with benchmark catalysts like
(
1
1
0.1M), was added suitable nucleophile (0.15 mmol,
.5eq) and s-tetrazine photocatalyst (0.01 mmol,
0% Mol) followed by TFE (1 mmol, 10eq, 80ul). The
reaction was flushed with O
minutes and then stirred at room temperature
overnight under O atmosphere. The reaction was
2
(bubbling) for 5
2
irradiated with green leds (535 nm) for 20h.
Completion of the reaction was checked by TLC.
Solvents were removed in vacuo and the residue was
purified by flash chromatography (Pet. Ether / Ethyl
acetate) to give desired product.
2+. Finally, we expect this work could be the
Ru(bpy)
3
Compounds 6a to 6p except 6l were previously
described in literature. Data are in accordance with
literature values.5a,b
starting point of an increased use of simple
tetrazines to perform routine day-to-day chemical
oxidations.
tert-butyl
(3-phenyl-1-(1H-pyrazol-1-
yl)propyl)carbamate (6a)5b was obtained following
general protocol for azoles coupling. With 2c 28
mg, 93%, 2g 28 mg, 93%, 3 24 mg, 79%, (Pet. Ether /
EXPERIMENTAL SECTION
Materials and methods. Technical grade solvents
were used for quantitative flash chromatography.
1
13
3
Ethyl acetate 4:1 as eluent) H{ C} NMR (CDCl , 300
ACS Paragon Plus Environment

Page 7 of 12
1
The Journal of Organic Chemistry
MHz) δ (ppm): 7.63 (s, 1H), 7.57 (s,1H), 7.31 (t,
J= 7.2 Hz, 2H), 7.22 (t, J= 7.1 Hz, 1H), 7.15 (d,
J= 7.6Hz, 2H), 6.26 (s, 1H), 5.84 (d, J= 9.2 Hz,
tert-butyl
phenylpropyl)carbamate
(1-(1H-indazol-1-yl)-3-
5b
(6f)
following general protocol for azoles coupling.
was
obtained
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
1
(
(
(
H), 5.77 (m, 1H), 2.54-2.51 (m, 3H), 2.43-2.36 (m,
13
With 2g 31 mg, 88%, 3 28 mg, 79%, (Pet. Ether /
1
1
13
H), 1.42 (s, 9H). C{ H} NMR (CDCl
3
, 75MHz) δ
3
Ethyl acetate 3:1 as eluent) H{ C} NMR (CDCl , 300
ppm): 154.7, 140.3, 140.2, 130.0, 128.6 (2C), 128.5
2C), 126.3, 104.9, 80.3, 66.4, 36.0, 31.5, 28.3
3C).
MHz) δ(ppm): 8.14 (s br,1H), 7.79 (dd, J= 8.8 and
0.9 Hz, 1H), 7.72 (dt, J= 8.4 and 1.0 Hz, 1H),
7.38−7.20 (m, 4H), 7.16−7.11 (m, 3H), 6.49 (d br,J=
9.0 Hz,1H), 6.07 (m, 1H), 2.72−2.48 (m, 4H), 1.39
benzyl
(3-phenyl-1-(1H-pyrazol-1-
yl)propyl)carbamate (6b)5b was obtained following
13
1
3
(s, 9H). C{ H} NMR (CDCl , 75 MHz) δ(ppm): 154.7,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
general protocol for azoles coupling. With 3 23 mg,
7
143.6, 141.3, 139.5, 132.5, 128.7(2C), 128.4 (2C),
126.6, 123.2, 122.6, 120.3, 110.8, 80.8, 62.4,
36.0,31.7, 28.2 (3C).
0%, (Pet. Ether / Ethyl acetate 4:1 as eluent)
13
1
H{ C} NMR (CDCl , 300 MHz) δ (ppm): 7.65 (s, 1H),
3
tert-butyl
(1-(1H-benzo[d]imidazol-1-yl)-3-
carbamate was obtained
(6g)5b
following general protocol for azoles coupling.
7
.60 (s, 1H), 7.40-7.20 (m, 8H), 7.14-7.11 (m, 2H),
.41 (d br, J = 9.2 Hz, 1H), 6.28 (s, 1H), 5.81 (t,
phenylpropyl)
6
J = 8.1 Hz, 1H), 5.16 (d, J = 12.1 Hz, 1H), 5.00
(d, J = 12.3 Hz, 1H), 2.63-2.32 (m, 4H). 13C{1H} NMR
With 2g 21 mg, 59%, (Pet. Ether / Ethyl acetate 1:1
1
13
as eluent) H{ C} NMR (CD
3
CN + D
.08 (s, 1H), 7.73-7.56 (m, 2H), 7.36-7.16 (m, 7H),
.56 (bs, 1H), 5.92 (q, J=7.1Hz, 1H), 2.78-2.40 (m,
2
O, 500 MHz) δ(ppm):
(CDCl , 75 MHz) δ (ppm): 155.5, 140.4, 140.1,
3
8
6
4
1
1
3
36.0, 130.1, 128.6 (2C), 128.5 (2C), 128.4 (2C),
28.2, 128.1, 126.3, 126.1, 105.0, 67.1, 66.8, 35.8,
1.4.
1
3
1
H), 1.36 (s, 9H),
3
C{ H} NMR (CDCl , 75 MHz)
δ(ppm): 154.7, 143.6,141.3, 139.5, 132.5, 128.7
tert-butyl
phenylpropyl) carbamate (6c)
(1-(3-methyl-1H-pyrazol-1-yl)-3-
5b
(
8
2C), 128.4 (2C), 126.6, 123.2, 122.6, 120.3, 110.8,
0.8, 62.4, 36.0, 31.7, 28.2 (3C).
was obtained
following general protocol for azoles coupling.
tert-butyl (1-(1H-pyrazol-1-yl)octyl)carbamate
With 2c 25 mg, 80%, 3 25 mg, 80%,(Pet. Ether / Ethyl
1
(6h)5b was obtained following general protocol for
azoles coupling. With 2g 29 mg, 99%, 3 21 mg, 71%,
(Pet. Ether / Ethyl acetate 4:1 as eluent) 1H{ C}
13
acetate 4:1 as eluent) H{ C} NMR (CDCl
3
, 300 MHz)
δ (ppm): 7.47−7.40 (m, 1H), 7.28−7.24 (m, 2H),
13
7
1
2
9
1
1
1
.20−7.15 (m, 1H), 7.12−7.09 (m, 2H), 5.98-5.96 (m,
H), 5.82-5.75 (m, 1H), 5.63-5.56 (m, 1H), 2.56-
.40 (m, 3H), 2.29 (s, 3H), 2.25 (m, 1H), 1.38 (s,
3
NMR (CDCl , 300 MHz) δ(ppm): 7.48 (s, 2H), 6.13 (s,
1H), 5.72(br s, 1H), 5.52 (br s, 1H), 2.12 (br s,
1H), 1.98 (br s, 1H), 1.33 (s, 9H), 1.28−1.08 (m,
1
3
1
3
H). C{ H} NMR (CDCl , 75 MHz) δ (ppm): 149.5,
1
3
1
3
10H), 0.78 (t, J= 6.7 Hz, 3H). C{ H} NMR (CDCl , 75
39.5, 130.9, 128.6 (2C), 128.5, 126.3, 104.9,
04.5, 66.3, 62.5, 36.1, 31.6, 28.4 (3C), 13.9,
0.8;
MHz) δ(ppm): 154.8, 140.0, 129.6, 104.7, 80.2,
67.2, 34.7, 31.6, 29.1, 29.0, 29.0, 28.3 (×3),
2
5.3, 22.5, 14.0;
tert-butyl
tert-butyl (1-(3,5-dimethyl-1H-pyrazol-1-yl)-3-
b
(1-(3,5-dimethyl-1H-pyrazol-1-
5
phenylpropyl) carbamate (6d) was obtained
following general protocol for azoles coupling.
yl)octyl) carbamate (6i)5b was obtained following
general protocol for azoles coupling. With 3 26 mg,
8
With 2c 32 mg, 97%, 3 25 mg, 76%, (Pet. Ether /
0%, (Pet. Ether / Ethyl acetate 4:1 as eluent)
1
13
3
Ethyl acetate 4:1 as eluent) H{ C} NMR (CDCl , 300
1
13
H{ C} NMR (CDCl
3
, 300MHz) δ (ppm): 5.74 (s, 1H),
.71−5.59 (m, 2H), 2.35 (s, 3H), 2.23(s, 3H),
.16−1.88 (m, 2H), 1.41 (s, 9H), 1.34−0.99 (m, 10H),
MHz) δ(ppm): 7.32−7.13 (m, 5H), 6.10 (d br, J= 9.2
Hz, 1H), 5.77 (s, 1H), 5.70 (m, 1H), 2.52−2.33 (m,
4
5
2
0
1
3
1
H), 2.27(s, 3H), 2.24 (s, 3H), 1.42 (s, 9H). C{ H}
13
1
3
.87 (t, J= 6.7 Hz, 3H). C{{ H} NMR (CDCl , 75 MHz)
NMR (CDCl , 75 MHz) δ(ppm): 154.8, 148.4, 140.7,
3
δ (ppm): 154.8,148.2, 134.4, 104.4, 79.8, 62.8,
139.6, 128.5 (2C), 128.4 (2C), 126.1, 104.7, 79.0,
62.2, 36.4, 31.5, 28.3 (3C), 13.7, 10.7;
3
1
5.3, 31.6, 29.0, 28.7, 28.2 (3C), 25.2, 22.5, 13.9,
3.6, 10.7;
tert-butyl (2-methyl-1-(1H-pyrazol-1-yl)propyl)
tert-butyl (1-(4-nitro-1H-pyrazol-1-yl)-3-
(6e)5b
phenylpropyl) carbamate was obtained
following general protocol for azoles coupling.
carbamate (6j)5b was obtained following general
protocol for azoles coupling. With 2c 20 mg, 84%, 3
8 mg, 75%, (Pet. Ether / Ethyl acetate 4:1 as
With 3 22 mg, 63%, (Pet. Ether / Ethyl acetate 4:1
1
1
13
3
as eluent) H{ C} NMR (CDCl , 300 MHz) δ(ppm): 8.29
1
13
eluent) H{ C} NMR (CDCl
3
, 300 MHz) δ(ppm): 7.55
(s br, 1H), 8.15 (s, 1H), 7.36−7.23 (m, 3H),
7.16−7.13 (m, 2H), 5.73−5.57 (m, 2H), 2.67−2.32 (m,
4
(
(
(
s, 1H),7.51 (s, 1H), 6.21 (s, 1H), 5.52 (d, J= 7.7
Hz, 1H), 5.37 (t, J= 9.0 Hz,1H), 2.38 (h, J= 6.5
Hz, 1H), 1.40 (s, 9H), 1.06 (d, J= 6.6 Hz, 3H), 0.70
13
1
3
H), 1.44 (s, 9H). C{ H} NMR (CDCl , 75 MHz) δ
ppm):154.3, 139.3, 136.4, 135.3, 128.8 (2C), 128.3
2C), 126.7 (2C), 81.4, 68.2, 35.1, 31.3, 28.2 (3C).
1
3
1
(
3
d, J= 6.6 Hz, 3H). C{ H} NMR (CDCl , 75 MHz)
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 12
1
13
δ(ppm): 155.2, 140.0, 130.0, 104.4, 80.1, 72.8,
3
as eluent) H{ C} NMR (CDCl , 300 MHz) δ(ppm) :
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3.1, 28.2 (3C), 18.8, 18.6.
tert-butyl (1-(3,5-dimethyl-1H-pyrazol-1-yl)-2-
7.22-7.07 (m, 5H), 6.49 (s, 1H), 5.95-5.93 (m, 1H),
4.74-4.59 (m, 2H), 3.78 (s, 3H), 2.65-2.55 (m, 2H),
1
methyl
propyl)carbamate
(6k)5b
was
obtained
2.05-1.97 (m, 2H), 1.37 (s, 9H); 13C{ H} NMR (CDCl
3
following general protocol for azoles coupling.
With 15 mg, 56%, (Pet. Ether / Ethyl acetate 4:1 as
,75 MHz) δ 165.4, 155.2, 141.5, 132.5, 128.6 (2C),
128.4 (2C), 126.1, 121.8, 103.1, 80.1, 60.4, 50.9,
38.5, 32.5, 28.5 (3C);
13
eluent). 1H{ C} NMR (CDCl
3
, 300 MHz) δ(ppm): 5.73
s, 1H), 5.70 (s, 1H), 5.27 (t, J= 9.9 Hz, 1H),
(
2
(
tert-butyl
phenylpropyl)
(1-(3-methyl-1H-indol-2-yl)-3-
carbamate was obtained
(6p)5c
following general protocol for azoles coupling.
.42−2.26 (m, 4H), 2.22 (s, 3H), 1.40 (s, 9H), 1.08
d, J= 6.6 Hz, 3H), 0.64 (d, J= 6.6 Hz, 3H). 13C{ H}
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR (CDCl
3
, 75 MHz) δ(ppm): 155.3, 148.3, 139.8,
With 3 20 mg, 55%, (Pet. Ether / Ethyl acetate 2:1
13
1
1
1
04.4, 79.9, 68.6, 33.9, 28.4 (3C), 19.2, 18.7,
3.8, 11.0.
3
as eluent) H{ C} NMR (CDCl , 300 MHz) δ (ppm) 8.46
(s, 1H, NHindole), 7.47 (d, J = 7.7Hz, 1H), 7.26–
7.01 (m, 8H), 4.97 (br. s, 1H) 4.71-4.64 (m, 1H,),
2.65-2.48 (m, 2H), 2.36-2.12 (m, 2H), 2.19 (s, 3H),
tert-butyl (4-((tert-butyldiphenylsilyl)oxy)-1-
1H-pyrazol-1-yl)butyl)carbamate (6l) was obtained
following general protocol for azoles coupling.
(
1
3
1
1.37 (s, 9H); C{ H} NMR (CDCl3, 75 MHz) δ (ppm)
156.0, 141.2, 135.5, 134.7, 129.1, 128.6 (2C), 128.5
(2C), 126.2, 121.9, 119.2, 118.7, 110.9, 107.8,
80.2, 48.0, 32.7, 28.5 (3C), 28.1, 8.8.
Colorless oil. With 2g 41 mg, 83%, 3 39 mg, 80%,
(
Pet. Ether / Ethyl acetate 4:1 as eluent)
1
13
H{ C} NMR (CDCl
3
, 300 MHz) δ(ppm) : 7.74-7.18 (m,
2H), 6.11 (t, J= 1.8Hz, 1H), 5.79-5.40 (m, 2H),
.55 (t, J= 6.2Hz, 2H), 2.25-1.91 (m, 2H), 1.46-
1
3
1
(
1
Synthesis and data for s-tetrazines 2c and 2e to 2h
s-tetrazines 2a, 2b, 2d were prepared according
reported procedures.6f
1
3
1
.19 (m + s, 2H + 9H), 0.96 (s, 9H); C{ H} NMR
CDCl , 75 MHz) δ(ppm): 154.7, 139.9, 135.5 (4C),
33.7, 129.6 (4C), 129.5, 127.7 (4C), 104.7, 80.2,
3
Procedure A: To a solution of 3,6-dichlorotetrazine
(1.0 equiv) in anhydrous CH Cl
2 2
(8 x 10-2 M) were
67.1, 63.0, 31.3, 28.3 (3C), 26.8 (3C), 19.2. IR
(neat) cm-1 : 3217, 2947, 2858, 1697, 1532, 1366,
1268, 1254, 1109, 734; HRMS (ESI-TOF) anal. for
added a phenol derivative (2 equiv), then 2,4,6-
collidine (2 equiv). The resulting mixture was then
stirred and heated under reflux until complete
conversion (monitored by TLC). The solvent was then
removed under reduce pressure and the residue was
C
28
H
39
N
3
O
3
SiNa [M+Na] calc : 516.2653 found : 516.2663
tert-butyl (3-phenyl-1-(2,4,6-
trimethoxyphenyl)propyl) carbamate was
(6m)5c
purified by silica gel flask chromatography (CH
2 2
Cl
obtained following general protocol for azoles
/AcOEt or petroleum ether/CH Cl gradient). In some
2
2
coupling. With 2g 36 mg, 90%, (Pet. Ether / Ethyl
1
cases, the desired product as a precipitate was
filtered, washed with cold dichloromethane and used
without further purification.
13
3
acetate 4:1 as eluent) H{ C} NMR (CDCl , 300 MHz,)
δ (ppm) 7.28-7.16 (m, 5H), 6.15 (s, 2H), 5.86 (br.
d, J= 10.2 Hz, 1H), 5.43 (dd, 1H, J= 9.9 and 15.3
Hz), 3.84 (s, 3H), 3.83 (s, 6H), 2.75-2.65 (m, 1H),
Procedure B: To a solution of 3,6-dichlorotetrazine
(8 x 10-2 M) were
2 2
(1.0 equiv) in anhydrous CH Cl
2
13
.53-2.43 (m, 1H), 2.19-1.92 (m, 2H), 1.46 (s, 9H).
added a phenol derivative (2 equiv), then 2,4,6-
collidine (1 equiv). The resulting mixture was then
stirred and heated under reflux until complete
conversion into monosubstituted product (monitored
by TLC). DMAP (1 equiv) was added and the reaction
was kept running for 1 hours. The solvent was then
removed under reduce pressure and the residue was
1
C{ H} NMR (CDCl3, 75 MHz) δ(ppm): 160.2, 158.6,
1
9
2
55.5, 128.3 (3C), 128.1 (2C), 125.4 (2C), 111.0,
1.1, 91.0 (2C), 78.6, 55.8, 55.2, 45.9, 37.6, 32.9,
8.5 (3C);
tert-butyl
trimethoxyphenyl)methyl)
(phenyl(2,4,6-
(6n)5c
was
carbamate
obtained following general protocol for azoles
coupling. With 2g 36 mg, 97%, 3 36 mg, 97%, (Pet.
purified by silica gel flash chromatography (CH
/AcOEt or petroleum ether/CH Cl gradient).
3,6-bis(4-chlorophenoxy)-1,2,4,5-tetrazine
(2a)6f Pink solid (397 mg, 74% yield). Reported (287
2 2
Cl
2
2
1
13
Ether / Ethyl acetate 5:1 as eluent) H{ C} NMR
(
(
1
(
1
1
3
CDCl , 300 MHz) δ (ppm) 7.26-7.11 (m, 5H), 6.59
1
13
br. d, J= 10.1 Hz, 1H), 6.25 (br. d, J= 10.2 Hz,
H) 6.15 (s, 2H), 3.81 (s, 3H), 3.77 (s, 6H), 1.47
3
mg, 52% yield). H{ C} NMR (300 MHz, CDCl ) δ (ppm):
7.43 (d, J = 8.9 Hz, 4H), 7.22 (d, J = 8.9 Hz, 4H);
Mp: 165-166°C.
1
3
1
s, 9H). C{ H} NMR (CDCl3, 75 MHz) δ (ppm) 160.6,
58.6, 155.7, 127.8 (3C), 126.0 (2C), 126.0 (2C),
11.0 (3C), 91.2, 79.0, 55.9, 55.3, 48.2, 28.5 (3C).
3,6-bis(3-chlorophenoxy)-1,2,4,5-tetrazine
(2b)6f Pink solid (397 mg, 74% yield). Reported (110
1
13
tert-butyl
phenylpropyl)
(1-(5-methoxythiophen-2-yl)-3-
carbamate was obtained
(6o)5c
3
mg, 33% yield). H{ C} NMR (300 MHz, CDCl ) δ (ppm):
7.44 (t, J = 8.0 Hz, 2H), 7.37-7.31 (m, 4H), 7.20-
7.18 (d, J = 8.0 Hz, 2H); Mp:128-130°C.
following general protocol for azoles coupling.
With 3 20 mg, 58%, (Pet. Ether / Ethyl acetate 3:1
ACS Paragon Plus Environment

Page 9 of 12
The Journal of Organic Chemistry
3
,6-bis(3,5-bis(trifluoromethyl)phenoxy)-
,2,4,5-tetrazine (2c) Prepared according to
in hours from 3,6-
with cold acetonitrile. The solid was purified by
chromatography over silica gel (CH Cl Ethyl
1
2
1
2
2
/
general procedure
A
4
acetate 99/1 to 1/1) to give pure product as an
orange solid (102 mg, 48% yield, 97% purity with 3%
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
dichlorotetrazine (242 mg, 1.6 mmol), 3,5-
bis(trifluoromethyl)phenol (0.6 mL, 3.2 mmol) and
1
13
of 2h). H{ C} NMR (300 MHz, CDCl
(m, 2H), 8.06 (m, 2H), 6.71 (m, 2H); 13C{ H} NMR (75
MHz, CDCl ) δ (ppm); 158.8 (2C), 146.1 (2C), 129.6
3
) δ (ppm) : 8.75
1
2
,4,6-collidine (0.4 mL, 3.2 mmol) in CH
2 2
Cl (20 mL).
no purification needed. Pink solid (655 mg, 76%
3
1
13
-1
yield). H{ C} NMR (300 MHz, CD
3
CN) δ (ppm): 8.02
s, 2H), 7.98 (s, 4H); 19F NMR (282 MHz, CD
CN) δ
CN) δ (ppm):
67.0 (2C), 152.9 (2C), 132.9 (4C), 122.0 (4C),
(2C), 110.1 (2C). IR (neat) ν (cm ): 3676, 3146,
2988, 1524, 1475, 1397, 1255, 1185, 1165, 1075,
1027, 953, 918, 888, 773; Mp: 256-259°C. HRMS
(
(
1
1
1
7
3
ppm): -63.54; 13C{ H} NMR (75 MHz, CD
1
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
+
(ESI-TOF) m/z: [M+CH
C H N
8 7 8
3
CN+Na] m/z: [M+H] Calcd for
215.0794; Found 215.0794.
3-chloro-6-(1H-pyrazol-1-yl)-1,2,4,5-tetrazine
(2h) To a solution of 3,6-dichlorotetrazine (150
mg, mmol) in acetonitrile 10 mL, was added
-
1
+
20.2 (4C), 117.0 (2C); IR (neat) ν (cm ): 3055,
406, 1347, 1264, 1174, 1133, 956, 902, 847, 732,
02; Mp: 215-217°C. HRMS (ESI-TOF) m/z: [M+Cl]-
-
1
Calcd for C18
H
6
F
12
N
4
O
2
Cl 572,9988; Found 572.9983
,6-bis(4-(tert-butyl)phenoxy)-1,2,4,5-
3
pyrazole (68 mg, 1 mmol). The reaction was stirred
at reflux for 1h. Solvents were removed in vacuo
and the resulting solid was purified by
tetrazine (2d) 6f Pink solid (387 mg, 64% yield).
1
13
Reported (403 mg, 93% yield). H{ C} NMR (500 MHz,
DMSO-d6) δ (ppm): 7.51 (d, J = 8.7 Hz, 4H), 7.29
chromatography over silica gel (CH
2
Cl
2
/ Ethyl
(
d, J = 8.7 Hz, 4H), 1.32 (s, 18H); Mp: 267-269°C;
,6-bis(((1s,3s)-adamantan-1-yl)methoxy)-
,2,4,5-tetrazine (2e) Prepared according to
acetate 99/1 to 2/1) to give pure product as an
1
13
3
orange solid (73 mg, 40% yield). H{ C} NMR (300 MHz,
CDCl ) δ (ppm) : 8.70-8.69 (m, 2H), 8.05-8.04 (m,
2H), 6.72-6.70 (m, 2H) ; C{ H} NMR (75 MHz, CD
δ (ppm) ; 166.4, 146.0, 130.0, 117.0, 110.7; IR
1
3
1
3
1
general procedure
dichlorotetrazine
B
(242
under reflux from 3,6-
mg, 1.6 mmol), 1-
3
CN)
-
1
adamantanemethanol (531 mg, 3.2 mmol), 2,4,6-
collidine (0.2 mL, 1.6 mmol) and DMAP (195 mg, 1.6
(neat) ν (cm ) : 3676, 3152, 2988, 2901, 1532,
1499, 1478, 1393, 1259, 1210, 1066, 922, 781 ; Mp :
117-119°C HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
mmol) in CH
2 2 2 2
Cl (20 mL). (CH Cl / Ethyl acetate 99/1
+
C
5
H
4
ClN
6
183.0186; Found 183.0172.
to 1/1 as eluent) Pink solid (216 mg, 33%
1
13
yield). H{ C} NMR (300 MHz, CDCl
(s, 4H), 2.04 (m, 6H), 1.79-1.69 (m, 24H); 13C{ H}
NMR (75 MHz, CDCl ) δ (ppm): 166.4 (2C), 79.4 (2C),
39.1 (6C), 36.9 (6C), 33.7 (2C), 28.0 (6C); IR
3
) δ (ppm): 4.12
ASSOCIATED CONTENT
1
The Supporting Information is available free of
charge via the Internet at http://pubs.acs.org.
Control experiments, Electrochemical Data, UV-Vis
3
-
1
(neat) ν (cm ): 3676, 2988, 2902, 1451, 1407, 1394,
1242, 1230, 1075, 1066, 1057, 892, 880; Mp: 175-
76°C. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
1
13
data, DFT Calculation and H, C NMR data.
1
C
+
24
H
35
N
4
O
2
411.2760; Found 411.2752.
3
,6-bis(2,2,2-trifluoroethoxy)-1,2,4,5-
AUTHOR INFORMATION
tetrazine (2f) Prepared according to general
procedure A under reflux from 3,6-dichlorotetrazine
Corresponding Author
(
242 mg, 1.6 mmol), TFE (0.5 mL, 6 mmol), 2,4,6-
collidine (0.4 mL, 3.2 mmol) in CH Cl (20 mL)
collection by filtration no purification needed.
*
clemence.allain@ens-paris-saclay.fr
geraldine.masson@cnrs.fr
T.L and T.C contributed equally to this work.
2
2
*
§
1
13
Pink solid (271 mg, 61% yield). H{ C} NMR (300 MHz,
) δ (ppm): 5.01 (q, J = 7.9 Hz, 2H); 13C{ H}
1
CDCl
3
ACKNOWLEDGMENT
NMR (75 MHz, CDCl ) δ (ppm): 166.7, 122.4 (q, J =
), 65.1 (q, J = 37.7 Hz); 19F NMR (282
3
We thank ICSN for funding. T.C and J.M thanks the
Labex Charm3at for postdoctoral fellowships and T.L
thanks for a financial support of Master. P.A thanks
the Institut Universitaire de France for personal
and financial support. This work was granted access
to the computing resources of CINES (Montpellier,
allocation A0050810547 awarded by GENCI). We thank
Arnaud Brosseau (PPSM) for his help with the
fluorescence lifetime measurements.
2
77.6 Hz, CF
3
-
1
MHz, CDCl
3
) δ (ppm): -73.8; IR (neat) ν (cm ):
676, 2988, 2902, 1406, 1394, 1250, 1230, 1075,1066,
92, 879; Mp: 80-82°C. HRMS (ESI-TOF) m/z: [M-
3
8
]+ Calcd for C
+
CF
3
5
H
4
F
3
N
4
O
2
209.0286; Found 209.295
3
,6-di(1H-pyrazol-1-yl)-1,2,4,5-tetrazine (2g)
To a solution of 3,6-dichlorotetrazine (150 mg, 1
mmol) in acetonitrile 10 mL, was added pyrazole (136
mg, 2 mmol) The reaction was heated to reflux for
2
h. Reaction was cooled to 0°C and the orange-pink
precipitate was collected by filtration and washed
REFERENCES
ACS Paragon Plus Environment

The Journal of Organic Chemistry
1) For selected recent reviews on photoredox Light Photocatalysis
Page 10 of 12
Chemistry;
(
in
Organic
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
catalysis, see: (a) Prier, C. K.; Rankic, D. A.;
MacMillan, D. W. Visible Light Photoredox Catalysis
with Transition Metal Complexes: Applications in
Organic Synthesis. Chem. Rev. 2013, 113, 5322. (b)
Schultz, D. M.; Yoon, T. P. Solar Synthesis:
Prospects in visible light Photocatalysis Science
Stephenson, C. R. J., Yoon, T. P., MacMillan, D. W.
C., Eds.; Wiley-VCH: Weinheim, 2018. (g) Sideri, I.
K.;
Voutyritsa,
E.;
Kokotos,
C.
G.
Photoorganocatalysis, Small Organic Molecules and
Light in the Service of Organic Synthesis: the
Awakening of a Sleeping Giant Org. Biomol. Chem.
2018, 16, 4596. (h) Ray, S.; Samanta, P. K.; Biswas,
P. Recent Developments on Visible‐Light Photoredox
Catalysis by Organic Dyes for Organic Synthesis. In
2014, 343, 1239176. (c) Kärkäs, M. D.; Matsuura, B.
S.; Stephenson, C. R. J. Enchained by Visible Light-
Mediated Photoredox Catalysis Science, 2015, 349,
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
285. (d) Shaw, M. H.; Twilton, J.; MacMillan, D.
Visible
Light‐Active
Photocatalysis:
W. C. Photoredox Catalysis in Organic Chemistry. J.
Org. Chem. 2016, 81, 6898. (e) Courant, T.; Masson,
G. Recent Progress in Visible-Light Photoredox-
Catalyzed Intermolecular 1,2-Difunctionalization of
Double Bonds via an ATRA-Type Mechanism J. Org.
Chem. 2016, 81, 6945. (f) Skubi, K. L.; Blum, T.
R.; Yoon, T. P. Dual catalysis Strategies in
Photochemical Synthesis Chem. Rev. 2016, 116,
Nanostructured Catalyst Design, Mechanisms, and
Applications; Ghosh, S., Ed.; Wiley-VCH: Weinheim,
2018.
(4)Selected examples: (a) Fukuzumi, S.; Ohkubo, K.
Organic Synthetic Transformations Using Organic
Dyes as Photoredox Catalysts Org. Biomol. Chem.
2014, 12, 6059. (b) Nicewicz, D. A.; Nguyen, T. M.
Recent Applications of Organic Dyes as PhotoRedox
Catalysts in Organic Synthesis ACS Catal. 2014, 4,
355. (c) Yang, C.; Yang, J. D.; Li, Y. H.; Li, X.;
Cheng, J. P. 9,10-Dicyanoanthracene Catalyzed
Decarboxylative Alkynylation of Carboxylic Acids
under Visible-Light Irradiation J. Org. Chem. 2016,
81, 12357. (d) Joshi-Pangu, A.; Roth, H. G.; Oliver,
S. F.; Campeau, L.-C.; Nicewicz, D. A.; DiRocco, D.
A. Acridinium-Based Photocatalysts: A Sustainable
Option in Photoredox Catalysis. J. Org. Chem. 2016,
81, 7244. (e) Le Vaillant, F.; Garreau, M.; Nicolai,
S.; Gryn'ova, G.; Corminboeuf, C.; Waser, J. Fine-
10035. (g) Ravelli, D.; Protti, S.; Fagnoni, M.
Carbon-Carbon Bond Forming Reactions via
Photogenerated Chem. Rev. 2016, 116, 9850. (h)
Marzo, L.; Pagire, S.K.; Reiser, O.; Konig, B.;
Visible-Light Photocatalysis: Does it Make
a
Difference in Organic Synthesis Angew. Chem. Int.
Ed. 2018, 57, 10034.
(2) (a) Juris, A.; Balzani, V.; Barigelletti, F.;
Campagna, S.; Belser, P.; von Zelewsky, A. Ru(II)
Polypyridine
Photochemistry,
Complexes:
Photophysics,
and
Electrochemistry,
Chemiluminescence. Coord. Chem. Rev. 1988, 84, 85.
(b) Tucker, J. W.; Stephenson, C. R. J. Shining
Light on Photoredox Catalysis: Theory and Synthetic
Applications. J. Org. Chem. 2012, 77, 1617. (c)
Teegardin, K.; Day, J. I.; Chan, J.; Weaver, J.
Tuned
Organic
Photoredox
Catalysts
for
Fragmentation-Alkynylation Cascades of Cyclic Oxime
Ethers, Chem. Sci. 2018, 9, 5883. (f) Speckmeier,
E.; Fischer, T.; Zeitler, K. J. A Toolbox Approach
to
Construct
Broadly
Applicable
Metal-Free
Advances in Photocatalysis:
A
Microreview of
Catalysts for Photoredox Chemistry – Deliberate
Tuning of Redox Potentials and Importance of
Halogens in Donor-Acceptor Cyanoarenes J. Am. Chem.
Soc. 2018, 140, 15353.
Visible Light Mediated Ruthenium and Iridium
Catalyzed Organic Transformations. Org. Process
Res. Dev. 2016, 20, 1156. (d) Blakemore, J. D.;
Crabtree; R. H.; Brudvig, G. W. Molecular Catalysts
for Water Oxidation. Chem. Rev. 2015, 115, 12974.
(5) (a) Courant, T.; Masson, G. Photoredox Initiated
α-Alkylation of Imines via
a
Three-Component
(
3) For selected reviews, see: (a) Ravelli, D.;
Radical/Cationic Reaction Chem. Eur. J. 2012, 18,
423. (b) Jarrige, L.; Levitre, G.; Masson, G.
Fagnoni, M.; Albini, A. Photoorganocatalysis. What
For? Chem. Soc. Rev. 2013, 42, 97. (b) Nicewicz,
D.A. and Nguyen, T.M. Recent Applications of Organic
Dyes as Photoredox Catalysts in Organic Synthesis.
ACS Catal., 2014, 4, 355. (c) Romero, N. A.;
Nicewicz, D. A. Organic Photoredox Catalysis Chem.
Rev. 2016, 116, 10075. (d) Ghosh, I.; Marzo, L.;
Das, A.; Shaikh, R.; König, B. Visible Light
Mediated Photoredox Catalytic Arylation Reactions
Acc. Chem. Res. 2016, 49, 1566. (e). Pitre, S. P.;
McTiernan, C. D.; Scaiano, J. C. Library of Cationic
Organic Dyes for Visible-Light-Driven Photoredox
Transformations ACS Omega 2016, 1, 66. (f) Zeitler,
K. Metal-free Photo(redox) Catalysis. In Visible
Visible-Light
Photoredox-Catalyzed
Coupling
Reaction of Azoles with α-Carbamoyl Sulfides. J.
Org. Chem. 2016, 81, 7230. (c) Lebée, C.; Languet,
M.; Allain, C.; Masson, G. α-Carbamoylsulfides as
N-Carbamoylimine Precursors in the Visible Light
Photoredox-Catalyzed
Synthesis
of
α,α-
Disubstituted Amines. Org. Lett. 2016, 18, 1478.
(d) Lanzi, M.; Merad, J.; Boyarskaya, D.V., Maestri,
G.; Allain, C.; Masson, G. Visible Light-Triggered
C-C and C-N Bonds Formation by C-S Bonds Cleavage
of Benzylic Thioethers Org. Lett. 2018, 20, 5247.
(6) For a review, see: (a) Clavier, G.; Audebert,
P. s-Tetrazines as Building Blocks for New
ACS Paragon Plus Environment

Page 11 of 12
The Journal of Organic Chemistry
Functional Molecules and Molecular Materials. Chem.
Rev. 2010, 110, 3299. For selected examples, see
b) Audebert, P.; Miomandre, F.; Clavier, G.;
Di(pyridin-2-yl)-1,2,4,5-tetrazine
(pytz)
as
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
catalyst RSC Adv. 2015, 5, 84328. (c) Samanta, S.;
Ray, S.; Ghosh, A. B.; Biswas, P. 3,6-Di(pyridin-2-
yl)-1,2,4,5-tetrazine (pytz) Mediated Metal-Free
Mild Oxidation of Thiols to Disulfides in Aqueous
Medium RSC Adv. 2016, 6, 39356.
(
Vernieres, M. C.; Badré, S.; Meallet-Renault, R.
Synthesis and Properties of New Tetrazines
Substituted by Heteroatoms: Towards the World’s
Smallest Organic Fluorophores. Chem. - Eur. J. 2005,
(9) (a) Chowdhury, M.; Goodman, L. Nature of
s‐Tetrazine Emission Spectra, J. Chem. Phys. 1963,
38, 2979. (b) Ågren, H.; Vahtras, O.; Knuts, S.
Jørgensen, P. Radiative Lifetimes of Triplet Spin
Sublevels of the Azabenzenes, J. Chem. Phys. 1994,
181, 291
1
1, 5667. (c) Gong, Y. H.; Miomandre, F.; Meallet-
Renault, R.; Badre, S.; Galmiche, L.; Tang, J.;
Audebert, P.; Clavier, G., Synthesis and Physical
Chemistry of s-Tetrazines: Which Ones are
Fluorescent and Why? Eur. J. Org. Chem. 2009, 6121.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
d) Jullien-Macchi, E.; Allain, C.; Alain-Rizzo,
(10) (a) Yasunao, K.; Tatsuo, A.; Hirochika, S.;
Katsumi, T. Effects of Sensitizer Spin Multiplicity
on Electron-Transfer Initiated Isomerization of
cis-Stilbene Chem. Lett. 1988, 17, 1193. (b) Akaba,
R.; Ohshima, K.; Kawai Y.; Obuchi, Y.; Negishi, A.;
Sakuragi, H.; Tokumaru, K. Triplet-Mediated
V.; Dumas-Verdes, C.; Galmiche, L.; Audibert, J.-
F.; Berhe Desta, M.; Pansu, R. B.; Audebert, P. New
Highly
Tetrazines: a Step Toward the Strongest Purely
Electrodeficient
Cationic
Fluorescent
Organic Photooxidants. New J. Chem. 2014, 38, 3401..
(
e)Qing, Z.; Audebert, P.; Clavier, G.; Miomandre,
Electron
Derivatives
Transfer
with
Oxygenation Stilbene
2,4,6-Triphenylpyrylium
of
F.; Tang, J.; Vu, T. T.; Méallet-Renault, R.
Tetrazines with Hindered or Electron Withdrawing
Tetrafluoroborate Tetrahedron Lett. 1991, 32, 109.
(11) Wever, W. J.; Cinelli, M. A.; Bowers, A. A.
Substituents:
Fluorescence Properties, J. Electroanal. Chem.
009, 632, 39.
(7) (a) Gückel, F.; Maki, A. H.; Neugebauer, F. A.;
Schweitzer, D.; Vogler, H., Spectroscopic
Synthesis,
Electrochemical
and
Visible
Light
Mediated
activation
and
O-
2
Glycosylation of Thioglycosides Org. Lett. 2013,
15, 30.
(12) Chlorocyclohexane was totally recovered at the
end of the reaction.
Investigations of the Lowest Triplet-State of s-
Tetrazines. Chem. Phys. 1992, 164, 217. (b) Myers,
T. W. ; Snyder, C. J.; Chavez, D. E.; Scharff, R.
J.; Veauthier, J. M.: Synthesis and Electrochemical
Behavior of Electron-Rich s-Tetrazine and Triazolo-
tetrazine Nitrate Esters, Chem. Eur. J. 2016, 22,
10590. (c) Chavez, D. E. ; Parrish, D. A.; Mitchell,
L.: Energetic Trinitro- and Fluorodinitroethyl
Ethers of 1,2,4,5-Tetrazines Angew. Chem. Int. Ed.
(13) For a selected review on superoxide anion
radical acting as a base, see: Hayyan, M.; Hashim,
M. A.; AlNashef, I. M. Superoxide Ion: Generation
and Chemical Implications Chem. Rev. 2016 116, 3029.
(14) Samoilova, R. I.; Crofts, A R.; Dikanov S. A.
Reaction of Superoxide Radical with Quinone
Molecules Phys. Chem. A, 2011, 115, 11589.
(15) Hsu, C.W.; Sundén, H. α‑Aminoalkyl Radical
Addition to Maleimides via Electron Donor−Acceptor
Complexes Org. Lett. 2018, 20, 2051.
2
016, 55, 8666.
8) (a) Samanta, S.; Das, S. Biswas, P.
(
Photocatalysis by 3,6-Disubstituted-s-Tetrazine:
Visible-Light Driven Metal-Free Green Synthesis of
(16) George, N.; Bekkaye, M.; Masson, G.; Zhu, J. A
Practical, One‐Pot Multicomponent Synthesis of
α‐Amidosulfides and Their Application as Latent
N‐Acylimines in the Friedel–Crafts Reaction Eur.
J. Org. Chem. 2011, 3695
2
-Substituted Benzimidazole and Benzothiazole J.
Org. Chem. 2013, 78, 11184. (b) Samanta, S.; Biswas,
P. Metal Free Visible Light Driven Oxidation of
Alcohols to Carbonyl Derivatives Using 3,6-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 12
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
ACS Paragon Plus Environment