Strain-Promoted 1,3-Dithiolium-4-olates–Alkyne Cycloaddition

Article abstract of DOI:10.1002/anie.201908052

Reported here is the reactivity of mesoionic 1,3-dithiolium-4-olates towards strained alkynes, leading to thiophene cycloaddition products. In the process, the potential of these dipoles towards orthogonal reaction with azides, allowing efficient double ligation reactions, was discovered. A versatile process to access benzo[c]thiophenes, in an unprecedented divergent fashion, was developed and provides a new entry to unconventional polyaromatic thiophenes.

Full text of DOI:10.1002/anie.201908052

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Strain-Promoted 1,3-Dithiolium-4-olates/Alkyne Cycloaddition
Authors: Ramar Arun Kumar, Manas R Pattanayak, Expédite Yen-Pon,
Jijy Elyian, Karine Porte, Sabrina Bernard, Margaux Riomet,
Pierre Thuéry, Davide Audisio, and Frédéric Taran
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: Angew. Chem. Int. Ed. 10.1002/anie.201908052
Angew. Chem. 10.1002/ange.201908052
Link to VoR: http://dx.doi.org/10.1002/anie.201908052
http://dx.doi.org/10.1002/ange.201908052

10.1002/anie.201908052
Angewandte Chemie International Edition
COMMUNICATION
Strain-Promoted 1,3-Dithiolium-4-olates--Alkyne Cycloaddition
Ramar Arun Kumar,[a],[c] Manas R. Pattanayak,[a] Expédite Yen-Pon,[a] Jijy Elyian,[a] Karine Porte,[a]
Sabrina Bernard,[a] Margaux Riomet,[a] Pierre Thuéry,[b] Davide Audisio[a],* and Frédéric Taran[a],*
Abstract: We report the reactivity of mesoionic 1,3-dithiolium-4-
olates towards strained alkynes leading to thiophene cycloaddition
products. In the process, we discovered the potential of these dipoles
towards orthogonal reaction with azides allowing efficient double
ligation reactions. We also developed a versatile process to access
benzo[c]thiophenes in an unprecedented divergent fashion, which
provides a new entry to unconventional poly-aromatic thiophenes.
Mesoionics are an exotic class of dipoles holding much
promise in cycloaddition reactions. Although their synthesis and
reactivity have been reported since the 60’s, their potential is far
from been fully explored.1 Mesoionic compounds represent a
large family of five-membered heterocycles that cannot be
represented by Lewis structures not involving charge separation.
Over the last decade, the popularity of this exotic family of
heterocycles has suddenly increased and caught much attention.2
In particular, nitrogen-containing mesoionics such as
münchnones and sydnones were reported to be competent dipole
partners for strain-promoted cycloaddition reactions. Their
reactivity with arynes, described by Larock and Shi,3 Garg and
Houk,4 and others,5 offered novel synthetic opportunities to
access substituted pyrazoles and pyrroles, not trivial to assemble
by traditional synthetic methodologies. Moreover, the use of the
aryne-sydnone cycloaddition was recently described for the
unconventional, direct assembly of helicene scaffolds.6 In recent
years, sydnones and imino-sydnones were identified as
importance of thiophenes in organic chemistry, in particular
medicinal and material science, we decided to investigate in detail
the reactivity of DTOs. In this report, we describe the cycloaddition
between DTOs and strained alkynes, focusing on cyclooctynes
and arynes. In the event, we unveil a novel ligation strategy, which
is orthogonal to the well-established azide-cycloalkyne click
reaction, as well as a complementary pathway to access a variety
of substituted benzo[c]thiophenes with possible implications in
material science (Scheme 1).
promising
dipoles
for
strain-promoted
ligation
with
cyclooctynes.7,8 These transformations hold much promise for
click and bioorthogonal chemistry and a variety of applications
were reported in living cells9 and organisms.10
While the community has accepted nitrogen-containing
mesoionics as versatile platform in synthetic organic chemistry,
sulfur-based derivatives remain a mere textbook curiosity and
their reactivity is only partially explored. First reported in 1964,11
1,3-dithiolium-4-olates (DTOs) are essentially known to undergo
thermal 1,3-dipolar cycloaddition in presence of activated alkynes
followed by a retro-Diels Alder to deliver substituted thiophenes.12
This thermal process has received limited attention, probably due
to the poor regioselectivity, the limited scope and the drastic
conditions required to assemble the thiophene unit. Their
reactivity with activated alkenes such as fulvenes,13 azirines,14
maleimides15 and acenaphthylene16 has also been sporadically
reported. Surprisingly, less than twenty articles describe
cycloaddition reactions with these dipoles. Given the fundamental
Scheme 1. Reactivity of 1,3-dithiolium-4-olates (DTOs) with strained alkynes.
At the outset, we prepared a library of DTOs, according to
previous synthetic protocols developed by Potts17 and Gotthardt18
in a three-step procedure. Grignard reagents were reacted in
presence of carbon disulphide at room temperature. The
corresponding dithioic acids underwent nucleophilic substitution
in presence of α-bromophenyl acetic acids under aqueous
conditions. Without further purification, the phenyl acetic acid
derivatives were cyclized in presence of acetic anhydride and
triethylamine, to deliver the desired DTOs 1-12 as dark blue solids
in 44 to 88% yields (Scheme 2). Products are bench-stable and
display strong absorbance properties. With this series of DTOs,
we next started the investigation of their reactivity with
cyclooctynes. When 2,5-diphenyl DTO 1 was mixed with
bicyclo[6.1.0]non-4-yne-9,9-diyldimethanol (BCNDM)19 a smooth
conversion was observed at room temperature in chloroform, and
the thiophene cycloadduct 13 was isolated in quantitative yield. It
should be noted that the retro-Diels Alder step generates the
desired thiophene with equimolar amounts of carbonyl sulfide
(COS), whose relevance has been recently described for the
therapeutic delivery of H2S.20 The evolution of the reaction could
be easily visualized by the discoloration of the dark mesoionic
[a]
Dr. R. A. Kumar, Dr. M. R. Pattanayak, Dr. E. Yen-Pon, Dr. J. Elyian,
K. Porte, Dr. S. Bernard, Dr. M. Riomet, Dr. D. Audisio, Dr. F. Taran
Service de Chimie Bio-organique et Marquage (SCBM),
CEA/DRF/JOLIOT, Université Paris-Saclay, F-91191, Gif-sur-Yvette,
France
E-mail: davide.audisio@cea.fr, frederic.taran@cea.fr
Dr. P. Thuéry
NIMBE, CEA, CNRS, Université Paris-Saclay, 91191 Gif-sur-Yvette,
France
SRM Research Institute, Department of Chemistry, SRM Institute of
Science and Technology, Kattankulathur, 603203 Chennai, India
[b]
[c]
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201908052
Angewandte Chemie International Edition
COMMUNICATION
solution: while DTO 1 has characteristic dark color but displays
no fluorescence, thiophene 13 is a colorless fluorescent molecule.
Table 1. Photophysical data of compounds DTOs and cycloadducts and kinetic
studies on cycloaddition reactions.[a]
Adduct:
Ar
Ar’
DTO: max ()[b]

yield[c]
k[e]

[d]
ex/em
13:97%
296/381
14:99%
312/397
15:96%
293/379
16:98%
324/424
17:90%
299/390
18:99%
316/401
19:96%
303/396
20:97%
316/392
21:96%
310/392
0.071  0.005
0.099  0.002
0.128  0.004
0.030  0.004
0.082  0.002
0.016  0.001
0.054  0.001
nd
1: 543 (10200)
2: 559 (20200)
3: 548 (8400)
4: 560 (11800)
5: 557 (12600)
6: 595 (22700)
7: 563 (11900)
8: 595 (17900)
Scheme 2. Synthesis of 1,3-dithiolium-4-olates. Yields based on α-
bromophenyl acetic acids as limiting reagents.
Turn-on probes based on bioorthogonal ligation and click
reactions are remarkable chemical tools to label, visualize and
study drugs and biomolecules. These transformations have been
extensively studied and several fluorogenic azide,21 tetrazine22
and sydnone probes23 have been developed. In light of their
promising optical properties, DTOs 1-12 were reacted with
BCNDM to afford quantitatively the corresponding thiophene
products (see Table 1 and Figure S6). The photo-physical
properties of both DTOs and thiophenes were measured and the
second-order kinetics were determined. All tested reactions were
found fluorogenic showing high fluorescence enhancement upon
formation of the thiophene products. Comparative kinetics (Table
1) highlighted the importance of both substituents on positions 2
and 5 of the mesoionic core. Kinetic values of the strain-promoted
1,3-dithiolium-4-olates/alkyne cycloaddition (SPDAC) reaction,
ranging from 0.016 to 0.180 M-1 sec-1, are comparable to the well-
known strain-promoted azide-alkyne cycloaddition (SPAAC) click
reaction. While for azides and sydnones the use of highly strained
cyclooctynes increases the reaction rates, in striking contrast, no
reaction occurred between 4 and DIBAC at room temperature,
even after prolonged stirring. This unexpected lack of reactivity
might be rationalized by the steric hindrance resulting from the
2,5-diaryl substituents of the mesoionic and the aromatic rings
adjacent to the alkyne (Scheme 3). Given this peculiar orthogonal
behaviour, we designed the dual probe 26,24 bearing an alkyl
azide connected to the DTO, which was synthetized in 67% yield
from 25. In a proof-of-concept experiment, 26 reacted exclusively
at the azide moiety in presence of DIBAC, the sequential addition
of BCN allowing the clean formation of 27 in a quantitative
fashion.24 Similar results were obtained with functionalized
cyclooctynes: complete orthogonal ligations after sequential
addition of a DIBAC-biotin conjugate and a BCN bearing the cyclic
RGD peptide affording selectively 28. This experiment shows the
potential of DTO as competent dipoles for orthogonal ligations
with azides (Scheme 4).
0.071  0.001
9: 566 (17300)
22:99%
310/387
0.101  0.001
10: 568 (16300)
11: 576 (10800)
12: 625 (12300)
23:97%
311/411
24:98%
361/460
0.184  0.003
nd
[a] Kinetics were conducted with 150 µM of DTO and BCNDM in CHCl3. [b]max
:
nm  :M-1.cm-1. [c] Isolated yields. [d] ex and em of thiophene cycloadduct (nm),
see Figures S7 and S8 for fluorescence spectra. [e] M-1.sec-1.
Scheme 3. Reactivity of DTO 4 with cyclic alkynes. [a] Reaction between DTOs
and DIBAC could only be observed when the temperature was higher than 90 °C.
This article is protected by copyright. All rights reserved.

10.1002/anie.201908052
Angewandte Chemie International Edition
COMMUNICATION
such as 43, whose synthesis has so far only been preliminarily
explored.33
Scheme 4. Orthogonality between dithiolium-SPDAC and azide-SPAAC
cycloaddition reactions (only one regioisomer of triazole product is
represented). a Isolated yield after HPLC purification.
After showcasing the SPDAC as potential tool for orthogonal
cycloadditions with cyclooctynes, we next explored the reactivity
of these sulphur-based mesoionics with arynes.25 The importance
of benzo[c]thiophenes in material science, in particular for their
non-linear optical (NLO) properties,26 low bandgap conjugated
polymers27 and their use as near-infrared fluorophore subunits is
well-established.28
Nonetheless,
synthetic
access
to
Scheme 5. Exploring the SPDAC for the synthesis of benzo[c]thiophenes.
benzo[c]thiophenes and derived S-heteroacenes still remains
challenging and requires time-consuming, multi-step convergent
approaches. It is somehow surprising that the most common
strategy still relies on the venerable Paal-Knorr cyclization, from
the corresponding 1,4-diketone precursors in presence of excess
of a source of sulphur.29 In this context, the SPDAC with arynes
would provide a divergent entry to benzo[c]thiophenes and
streamline the access to unconventional derivatives. After careful
optimization,24 29 could be isolated in 82% yield from 1 and 2-
(trimethylsilyl)phenyl trifluoromethanesulfonate, in presence of KF
(4 equiv.) and 18-crown ether (4.5 equiv.) in THF.30 With this
optimized set of conditions, benzo[c]thiophenes 29-37 were
isolated in 53 to 82% yields from the corresponding DTOs. To
investigate the versatility of the transformation, we next reacted
the mesoionics with previously reported polyaromatic arynes.31 In
presence of 2,3-naphthyne precursor, the desired S-
heteroacenes 38 and 39 were isolated in 55% and 59% yield.
Interestingly, acenothiophenes 29 and 38 were recently reported
by the group of Chi, by means of a Paal-Knorr sequence in 65%
and 50% yield, respectively, from the corresponding diketones.32
These results show the divergence of SPDAC over current
available methods. The reaction with ortho-fused 1,2-naphthyne
and 3,4-phenanthryne precursors delivered the helical derivatives
40 and 41 in good yield. Finally, thiophenes 42-44 were isolated
in 47 to 63% yield. The use of 9,10-phenanthryne is particularly
interesting because it generates phenanthro[9,10-c]thiophenes
Scheme 6. Synthesis of 45 from DTO 1 and the Sonheimer-Wong diyne.
Finally, we investigated double SPDAC reaction of DTO 1 with
the Sondheimer-Wong diyne (Scheme 6).34 Similarly to DIBAC,
the reaction with this diyne was slower than with BCNDM,
however a clean formation of dithiophene-diphenylene 45 was
observed, upon heating at 90 °C during 48 hours. As highlighted
by X-ray analysis, 45 adopts a unique saddle-shaped structure
This article is protected by copyright. All rights reserved.

10.1002/anie.201908052
Angewandte Chemie International Edition
COMMUNICATION
[8]
[9]
S. Bernard, D. Audisio, M. Riomet, S. Bregant, A. Sallustrau, L.
Plougastel, E. Decuypere, S. Gabillet, R. A. Kumar, J. Elyian, M. N. Trinh,
O. Koniev, A. Wagner, S. Kolodych, F. Taran, Angew. Chem. Int.
Ed. 2017, 56, 15612-15616; Angew. Chem. 2017, 129, 15818-15822, b)
M. Riomet, E. Decuypere, K. Porte, S. Bernard, L. Plougastel, S.
Kolodych, D. Audisio, F. Taran, Chem. Eur. J. 2018, 24, 8535-8541.
L. Plougastel, M. R. Pattanayak, M. Riomet, S. Bregant, A. Sallustrau, M.
Nothisen, A. Wagner, D. Audisio, F. Taran. Chem. Commun. 2019, 55,
4582-4585.
with the two thiophene moieties on the same side of the
molecule.35 This new skeleton might therefore represent a
promising candidate for the development of chiral functional
molecules.36
In conclusion, we have studied the virtually unexplored
reactivity of DTO towards strained alkynes. These mesoionics
can be successfully used for orthogonal double click reactions
and provide a versatile platform to access benzo[c]thiophenes
and dithiophene-diphenylene structures in an unprecedented
[10] K. Porte, B. Renoux, E. Péraudeau, J. Clarhaut, B. Eddhif, P. Poinot, E.
Gravel, E. Doris, A. Wijkhuisen, D. Audisio, S. Papot, F. Taran. Angew.
Chem. Int. Ed. 2019, 58, 6366-6370.
[11] a) E. Campaigne, N. W. Jacobsen, J. Org. Chem. 1964, 29, 1703-1708,
b) H. Gotthardt, B. Christl, Tet. Lett. 1968, 9, 4743-4745.
[12] a) H. Gotthardt, B. Christl, Tetrahedron Letters 1968, 9, 4747-4749, b) H.
Gotthardt, C. M. Weisshuhn, Chemische Berichte 1978, 111, 3178-3182,
c) G. Meazza, G. Zanardi, G. Guglielmetti, P. Piccardi, J. Fluorine Chem.
1997, 82, 175-180.
divergent fashion, which will provide
a
new entry to
unconventional poly-aromatic thiophenes. Further work on these
molecules is currently ongoing.
[13] H. Kato, N. Aoki, Y. Kawamura, K. Yoshino, J. Chem. Soc., Perk. Trans.
1 1985, 1245-1247.
Acknowledgements
[14] K. T. Potts, D. R. Choudhury, A. J. Elliott, U. P. Singh, J. Org. Chem.
1976, 41, 1724-1728.
This work was supported by the French Research National
Agency (ANR-14-CE06-0004 and ANR-17-CE07-0035-01) and
CEA. RAK, MRP and JE thank Enhanced Eurotalents for financial
support. The authors thank Elodie Marcon and David-Alexandre
Buisson for excellent analytical support, Dr. Sarah Bregant for
helpful discussions and Dr. Simon Specklin for preliminary
experiments.
[15] H. Gotthardt, B. Christl, Chem. Ber. 1978, 111, 3029-3036.
[16] a) H. Gotthardt, B. Christl, Tet. Lett. 1968, 9, 4751-4756. b) H. Gotthardt,
C. M. Weisshuhn, B. Christl, Chem. Ber. 1978, 111, 3037-3047.
[17] K. T. Potts, U. P. Singh, J. Chem. Soc. D: Chem. Commun. 1969, 569-
570.
[18] H. Gottardt, M. C. Weisshuhn, B. Christl, Chem. Ber. 1976, 109, 740-752.
[19] S. Bernard, R. A. Kumar, K. Porte, P. Thuéry, F. Taran, D. Audisio, Eur.
J. Org. Chem. 2018, 2018, 2000-2008.
[20] a) C. R. Powell, J. C. Foster, B. Okyere, M. H. Theus, J. B. Matson, J.
Am. Chem. Soc. 2016, 138, 13477-13480, b) Y. Zhao, M. D. Pluth,
Angew. Chem. Int. Ed. 2016, 55, 14638-14642; Angew. Chem. 2016, 128,
14858-14862, c) A. K. Steiger, S. Pardue, C. G. Kevil, M. D. Pluth, J. Am.
Chem. Soc. 2016, 138, 7256-7259.
Keywords: Mesoionics • Click chemistry • Screening •
Cycloaddition • Thiophene
[1]
a) J M. Lopchuk Top. Heterocycl. Chem. 2012, 29, 381–414. b) G. W.
Gribble The Chemistry of Heterocyclic Compounds, Volume 59:
Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry, 2002,
Chapter 10: Mesoionic Ring Systems Toward Heterocycles and Natural
Products. C) W. D. Ollis, S. P. Stanforth, C. A. Ramsden, Tetrahedron
1985, 41, 2239-2329.
[21] a) P. Shieh, M. J. Hangauer, C. R. Bertozzi, J. Am. Chem. Soc., 2012,
134, 17428-17431, b) P. Shieh, V. T. Dien, B. J. Beahm, J. M. Castellano,
T. Wyss-Coray, C. R. Bertozzi, J. Am. Chem. Soc., 2015, 137, 7145-
7151.
[22] a) L. G. Meimetis, J. C. T. Carlson, R. J. Giedt, R. H. Kohler, R.
Weissleder, Angew. Chem., Int. Ed., 2014, 53, 7531-7534, b) A.
Wieczorek, P. Werther, J. Euchner, R. Wombacher, Chem. Sci., 2017, 8,
1506-1510.
[2]
[3]
[4]
[5]
a) D. L. Browne, J. P. A. Harrity, Tetrahedron 2010, 66, 553-568. b) E.
Decuypère, L. Plougastel, D. Audisio, F. Taran, Chem. Commun. 2017,
53, 11515-11527.
a) Y. Fang, C. Wu, R. C. Larock, F. Shi, J. Org. Chem. 2011, 76, 8840-
8851. b) C. Wu, Y. Fang, R. C. Larock, F. Shi, Org. Lett. 2010, 12, 2234-
2237.
[23] a) E. Decuypère, M. Riomet, A. Sallustrau, S. Bregant, R. Thai, G.
Pieters, G. Clavier, D. Audisio, F. Taran, Chem. Commun. 2018, 54,
10758-10761, b) C. Favre, F. Friscourt, Org. Lett. 2018, 20, 4213-4217.
[24] See Supporting Information for experimental details.
[25] To the best of our knowledge, we are aware of one single example of
cycloaddition between DTO 1 and benzyne. The product was obtained
in 36% yield and the aryne generated from 1-aminobenzotriazole with
Pb(OAc)4. See: H. Kato, S. Nakazawa, T. Kiyosawa, K. Hirakawa, J.
Chem. Soc., Perk. Trans. 1 1976, 672-675.
a) J. M. Medina, T. C. McMahon, G. Jiménez-Osés, K. N. Houk, N. K.
Garg, J. Am. Chem. Soc. 2014, 136, 14706-14709. b) T. K. Shah, J. M.
Medina, N. K. Garg, J. Am. Chem. Soc. 2016, 138, 4948-4954.
a) T. Ikawa, S. Masuda, A. Takagi, S. Akai, Chem. Sci. 2016, 7, 5206-
5211. b) J. Shi, H. Xu, D. Qiu, J. He, Y. Li, J. Am. Chem. Soc. 2017, 139,
623-626. c) T. Ikawa, S. Masuda, H. Nakajima, S. Akai, J. Org. Chem.
2017, 82, 4242-4253.
[26] T. J. L. Silva, P. J. Mendes, M. H. Garcia, M. P. Robalo, J. P. Prates
Ramalho, A. J. Palace Carvalho, M. Büchert, C. Wittenburg, J. Heck, Eur.
J. Inorg. Chem. 2013, 2013, 3506-3517.
[6]
[7]
E. Yen-Pon, P. A. Champagne, L. Plougastel, S. Gabillet, P. Thuéry, M.
Johnson, G. Muller, G. Pieters, F. Taran, K. N. Houk, D. Audisio, J. Am.
Chem. Soc. 2019, 141, 1435-1440.
[27] Y. Qin, J. Y. Kim, C. D. Frisbie, M. A. Hillmyer, Macromolecules 2008,
41, 5563-5570.
a) L. Plougastel, O. Koniev, S. Specklin, E. Decuypere, C. Créminon, D.-
A. Buisson, A. Wagner, S. Kolodych, F. Taran, Chem. Commun. 2014,
50, 9376-9378, b) S. Wallace, J. W. Chin, Chem. Sci. 2014, 5, 1742-
1744, c) M. K. Narayanam, Y. Liang, K. N. Houk, J. M. Murphy, Chem.
Sci. 2016, 7, 1257-1261, d) H. Liu, D. Audisio, L. Plougastel, E.
Decuypere, D.-A. Buisson, O. Koniev, S. Kolodych, A. Wagner, M.
Elhabiri, A. Krzyczmonik, S. Forsback, O. Solin, V. Gouverneur, F. Taran,
Angew. Chem. Int. Ed. 2016, 55, 12073-12077; Angew. Chem. 2016, 128,
12252–12256.
[28] S. T. Meek, E. E. Nesterov, T. M. Swager, Org. Lett. 2008, 10, 2991-
2993.
[29] a) W. Volz, J. Voss Synthesis, 1990, 8, 670-674, b) K. Baumgärtner, T.
Kirschbaum, F. Krutzek, A. Dreuw, F. Rominger, M. Mastalerz, Chem.
Eur. J. 2017, 23, 17817-17822.
[30] Please note that benzo[c]thiophenes might sensitive to the light (see ref
27 and 29). As a general procedure, we have performed all synthesis
and purifications by limiting light exposure. See Supporting Information
for experimental details.
This article is protected by copyright. All rights reserved.

10.1002/anie.201908052
Angewandte Chemie International Edition
COMMUNICATION
[31] D. Pena, D. Pérez, E. Guitiàn, L. Castedo J. Org. Chem. 2000, 65, 6944-
6950.
Rossmann, B. X. Tan, P. de Andrade, Y. S. Tan, C. Verma, G. J.
McKenzie, A. R. Venkitaraman, M. Hyvönen, D. R. Spring, Angew. Chem.
Int. Ed. 2015, 54, 15410-15413; Angew. Chem., 2015, 127, 15630-
15633.
[32] X. Shi, T. Y. Gopalakrishna, Q. Wang, C. Chi, Chem. Eur. J. 2017, 23,
8525-8531.
[33] a) I. Nagao, M. Shimizu, T. Hiyama, Angew. Chem. Int. Ed. 2009, 48,
7573-7576. b) I. Schnapperelle, T. Bach, Chem. Eur. J. 2014, 20, 9725-
9732 and references cited therein.
[35] The structure of 45 was confirmed by X-ray analysis. CCDC-1937085
contains the supplementary crystallographic data. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[34] a) A. Orita, D. Hasegawa, T. Nakano, J. Otera, Chem. Eur. J. 2002, 8,
2000-2004, b) F. Xu, L. Peng, K. Shinohara, T. Nishida, K. Wakamatsu,
M. Uejima, T. Sato, K. Tanaka, N. Machida, H. Akashi, A. Orita, J. Otera,
Org. Lett. 2015, 17, 3014-3017, c) D. A. Sutton, S.-H. Yu, R. Steet, V. V.
Popik, Chem. Commun. 2016, 52, 553-556, d) Y. H. Lau, Y. Wu, M.
[36] J.-W. Han, J.-X. Chen, X. Li, X.-S. Peng, H. N. C. Wong, Synlett 2013,
24, 2188-2198.
This article is protected by copyright. All rights reserved.

10.1002/anie.201908052
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Ramar Arun Kumar, Manas R.
Pattanayak, Expédite Yen-Pon, Jijy
Elyian, Karine Porte, Sabrina Bernard,
Margaux Riomet, Pierre Thuéry, Davide
Audisio and Frédéric Taran
Page No. – Page No.
Fluorogenic Thiophene Click: 1,3-dithiolium-4-olates reacted with strained alkynes
in very clean processes affording poly-aromatic thiophene structures in high yields.
Their use for ligation applications has also been investigated with cyclooctynes
offering a new orthogonal reaction to the strain-promoted azide/alkyne reaction.
Strain-Promoted 1,3-Dithiolium-4-
olate--Alkyne Cycloaddition
This article is protected by copyright. All rights reserved.