Vinyl Thianthrenium Tetrafluoroborate: A Practical and Versatile Vinylating Reagent Made from Ethylene

Article abstract of DOI:10.1021/jacs.1c06632

The use of vinyl electrophiles in synthesis has been hampered by the lack of access to a suitable reagent that is practical and of appropriate reactivity. In this work we introduce a vinyl thianthrenium salt as an effective vinylating reagent. The bench-stable, crystalline reagent can be readily prepared from ethylene gas at atmospheric pressure in one step and is broadly useful in the annulation chemistry of (hetero)cycles, N-vinylation of heterocyclic compounds, and palladium-catalyzed cross-coupling reactions. The structural features of the thianthrene core enable a distinct synthesis and reactivity profile, unprecedented for other vinyl sulfonium derivatives.

Full text of DOI:10.1021/jacs.1c06632

pubs.acs.org/JACS
Communication
Vinyl Thianthrenium Tetrafluoroborate: A Practical and Versatile
Vinylating Reagent Made from Ethylene
Fabio Juliá, Jiyao Yan, Fritz Paulus, and Tobias Ritter*
Cite This: J. Am. Chem. Soc. 2021, 143, 12992−12998
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: The use of vinyl electrophiles in synthesis has been hampered by the lack of access to a suitable reagent that is
practical and of appropriate reactivity. In this work we introduce a vinyl thianthrenium salt as an effective vinylating reagent. The
bench-stable, crystalline reagent can be readily prepared from ethylene gas at atmospheric pressure in one step and is broadly useful
in the annulation chemistry of (hetero)cycles, N-vinylation of heterocyclic compounds, and palladium-catalyzed cross-coupling
reactions. The structural features of the thianthrene core enable a distinct synthesis and reactivity profile, unprecedented for other
vinyl sulfonium derivatives.
wing to the rich chemistry of alkenes, the presence of a
terminal alkenyl (vinyl, C2H3) substituent enables a
equipment (high-pressure reactors or UV-photoreactors) has
traditionally restricted the use of ethylene as a reagent in
organic synthesis involving complex small molecules.
O
myriad of opportunities for diversification and elaboration via
dihydroxylation, carbofunctionalization, Heck-type arylation,
hydroamination, and metathesis, among others.1−6 However,
the introduction of a vinyl group as a C-2 building block is
currently difficult, in contrast to the extended use of other
substituted alkenyl electrophiles, in view of the lack of suitable
reagents with the desired properties and reactivity profile. Here
we report the reagent vinyl thianthrenium tetrafluoroborate
(vinyl-TT+, 1) that functions as a versatile reagent for different
synthetic transformations. Reagent 1 is accessible directly from
ethylene (1 atm) in a single step from commercially available
material on multigram scale and is a bench-stable, non-
hygroscopic solid that can be stored at room temperature in air
without signs of decomposition for at least one year. Despite
its high stability, 1 displays a rich reactivity profile and has
been implemented in several polar and palladium-catalyzed
cross-coupling reactions, which differentiates it from all other
vinylating reagents reported to date. The unusual direct
conversion of ethylene into a versatile building block for
organic synthesis sets the approach apart from previous
syntheses of alkenylsulfonium salts; in addition, 1 can
participate in useful reactions such as a Suzuki cross-coupling
that have not been realized with other alkenylthianthrenium
salts.
Ethylene is an inexpensive gas (annual production >100
million tons),7 but its use in organic synthesis is rare and
typically limited to simple substrates without high levels of
complexity.8 One of the main drawbacks of the use of ethylene
is the high temperature and pressures that are generally
required for its conversion. In fact, reactions engaging ethylene
at atmospheric pressure (1 atm) are uncommon and almost
exclusive to metal-mediated reactions, owing to the ability of
metal centers to activate ethylene via coordination.9−14 Metal-
free reactions utilizing ethylene at 1 atm are manily restricted
to photochemical cycloadditions with high-energy UV
light.15−17 Overall, the general requirement for specialized
The development of palladium-catalyzed cross-coupling
reactions has allowed researchers to reliably construct C−
Csp2 bonds (Figure 1A).18,19 However, in contrast to the
widespread use of alkenyl (substituted vinyl) derivatives, the
use of vinyl halides as electrophiles (e.g., vinyl bromide) is
challenging owing to the difficulty of handling the gaseous
compounds that are acutely toxic and carcinogenic, which has
historically thwarted their utilization in synthesis.20 Alter-
natively, numerous nucleophilic vinyl-[M] reagents ([M] =
SnBu3, SiMe3, B(OR)2, etc.) have been developed over the
years,21 but most of them are prepared in several steps from
vinyl bromide itself, display high toxicity and low stability, or
are poorly reactive (Figure 1B). Moreover, while significant
advances have been accomplished with vinyl nucleophiles, the
development of electrophilic derivatives that can effectively
display the reactivity profile of vinyl halides is significantly less
accomplished, and none of them are suitable as Michael
acceptors for the direct polar addition of nucleophiles.
Jimenez,22 Mukaiyama,23 and Aggarwal24 have developed the
use of vinyl diphenylsulfonium salts25 as a 1,2-ethane dication
synthon. This hygroscopic oil, prepared in three steps from
bromoethanol, displays some practicality issues26 and is often
generated in situ from its precursor bromoethyl diphenylsulfo-
nium triflate.27 Over the past two decades, Aggarwal and
others have reported a series of elegant transformations
applying this reagent to the synthesis of (hetero)cycles.24,28−34
However, neither the reagent nor its precursors have ever been
Received: June 26, 2021
Published: August 10, 2021
© 2021 The Authors. Published by
American Chemical Society
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998
12992

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
Figure 2. (A) Synthesis of 1 from ethylene, proceeding through a
formal [4 + 2] cycloadduct (3) as intermediate. (B) Crystal structures
of 1 and 3 obtained by X-ray diffraction (counterions omitted for
simplicity).
a crystalline solid can be carried out by simple precipitation, to
afford an analytically pure compound without the need for
further purification. An alternative lab-scale synthetic route
from vinyl-SiMe3 (2 equiv) was similarly effective (96% yield,
see Supporting Information). The salt 1 is a nonhygroscopic
solid that can be stored in the presence of air and moisture
without signs of decomposition for at least one year, which
makes it practical and easy-to-handle. DSC-TGA reveals that 1
does not decompose at temperatures lower than 280 °C, which
underscores a desirable safety profile (Figure S6). In contrast,
attempts of implementing this protocol using other sulfoxides
such as dibenzothiophene-S-oxide or diphenylsulfoxide were
unsuccessful (Figures S7 and S8). The structural features of
thianthrene that allow the formation of a [4 + 2] adduct with
ethylene seem crucial for a productive reaction, and indeed has
enabled the first report on the formation of sulfonium salts
directly from ethylene gas. To further confirm the key role of
the [4 + 2] cycloadduct under the reaction conditions, we
isolated and characterized intermediate 3, the crystal structure
of which shows the “snapshot” of ethylene activation by the
formal thianthrenium dication (Figure 2B). No other known
vinylating reagent can currently be accessed directly from
ethylene, and the practical and conceptual advantages of 1
allow a rich and divergent chemistry (see below) while
avoiding certain limitations associated with other reagents.
To evaluate the reactivity profile of 1 we started
benchmarking the reagent in annulation reactions reported
for vinyl-SPh2(OTf) or its precursor, which proceed via
sulfonium ylide intermediates.25 As depicted in Figure 3, we
can access (hetero)cyclic motifs that are prevalent in bioactive
compounds and pharmaceuticals. Selected examples include a
cyclopropanation reaction (4 → 5),28 the assembly of
morpholine (6 → 7)24 and azetidine (8 → 9)31 scaffolds,
and a tandem N-nucleophilic addition/Corey−Chaykovsky
epoxidation (10 → 11).32 In all cases, the isolated yields were
comparable or superior to those obtained with vinyl-
SPh2(OTf) under the same conditions.
Figure 1. (A) Use of alkenyl electrophiles in cross-coupling reactions.
(B) Commonly used vinylating reagents. (C) Vinyl thianthrenium salt
1 can be accessed directly from ethylene and is a versatile C-2
building block.
reported as suitable electrophiles in cross-coupling reactions
owing to their fundamental reactivity profile (vide infra). In
fact, only a few substituted alkenyl sulfonium salts have been
successfully engaged in cross-couplings,35−37 but no examples
of vinylations have been reported. Our group recently reported
the synthesis of alkenyl thianthrenium salts,38 but a general
reactivity profile in polar and cross-couling reactions has not
been explored yet. Moreover, we were unsuccessful in engaging
these salts in efficient couplings with aryl boronic acids via
Suzuki-type reactions.
We recently aimed to design a strategy to trap ethylene
efficiently and convert it into a practical and crystalline reagent
(Figure 1C). Ideally, this new species should be stable and easy
to handle, while simultaneously exhibiting a rich reactivity
profile. We questioned whether vinyl thianthrenium salts
(vinyl-TT+) could provide a valuable solution to this task. The
perchlorate salt of vinyl-TT+ was published three decades ago
while exploring the reactivity of thianthene radical cation
(TT•+) with (vinyl)4Sn,39 but only milligram quantities were
accessed owing to the involvement of potentially explosive
perchlorate salts,40 and its synthetic use has never been
reported. While, in comparison with other olefins, ethylene gas
typically requires high pressure and an autoclave for cyclo-
addition reactions,8,41 we sought to capitalize on the high
reactivity of the highly electrophilic thianthrenium dication
species generated by treatment of thianthrene-S-oxide (2) with
activating reagents such as Tf2O (Figure 2A). Following our
new protocol, vinyl thianthrenium tetrafluoroborate (1) can
now be prepared on multigram scale (50 mmol) with a simple
balloon of ethylene (1 atm) in 86% yield. The isolation of 1 as
Next, we aimed to implement 1 in new reactions to
effectively transfer the vinyl moiety to nucleophilic nitrogen.
During his studies on annulation reactions, Aggarwal reported
12993
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
an annulation−vinylation sequence on 1,2-aminoalcohols42
only when Cbz is the N-protecting group, but, beyond these
examples, a general platform for N-vinylation of heterocycles
using sulfonium salts is not yet established43 and current
methods require harsh conditions44−47 or metal-mediated
reactions (85−100 °C).48−51 We developed a simple protocol
that uses 1 in the presence of a base at room temperature
(Table 1). A diverse set of N-vinylated nitrogen heterocycles
can now be accessed under mild conditions including
azacarbazole (12), indole (13 and 14), imidazole (19),
pyrazole (15 and 16), triazole (17), and pyridone (18). A
broad tolerance to an array of polar groups was displayed as
demonstrated by the compatibility of nitro (13) and aldehyde
groups (14), which are not tolerated using calcium carbide,47
or aryl halides (16, 20) that are reactive in SNAr and cross-
coupling reactions. Other scaffolds of relevance such as
deazapurine (20) or theophylline (21) were also vinylated,
as well as the amino acids tryptophan and histidine (22 and
23). Finally, we explored the use of 1 for late-stage N-
vinylation. The mild conditions and fast reaction times enabled
modification of the drugs metaxalone (24), carvedilol (25),
lansoprazole (27), and the laser dye coumarin 7 (26), further
showcasing the compatibility with groups such as alcohols,
alkylamines, and sulfoxides.
Figure 3. Application of 1 in the annulation of hetero- and
carbocycles.
Vinylated arenes (styrenes) are activated alkenes with
widespread use in transition-metal catalysis,52,53 radical
chemistry,54,55 and electrophilic reactions.56,57 In contrast to
alkenylation, the assembly of styrenes using vinylating reagents
a
Table 1. Vinylation of N-Heterocycles Using 1
a
b
Reaction conditions: 0.300 mmol of N-heterocycle, 1.7 equiv of 1, 2.0 equiv of DBU in CH2Cl2 (3.0 mL, c = 0.10 M), 25 °C, 3 h. DMSO was
c
d
used as solvent. 1.2 equiv of 1 were added to a solution of N-heterocycle and DBU. 30 min at 0 °C, then 2.5 h at 25 °C. * denotes the site of
vinylation on the constitutional isomer not shown.
12994
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
a
Table 2. Suzuki-Type Vinylation of Organoboron Compounds
(A) Scope of the transformation. (B) Competition experiment between 1-d3 and vinyl bromide; analysis by NMR spectroscopy and mass
a
spectrometry. (C) Comparison of the reactivity of 1 and vinyl-SPh2(OTf). Reaction conditions: 0.300 mmol of ArB(OH)2, 1.5 equiv of 1, 0.050
b
c
equiv of Pd(dba)2, 0.11 equiv of P(o-tol)3, 1.5 equiv of t-BuOLi in THF (6.0 mL, c = 0.05 M), 60 °C, 16 h. NMR yield. K2CO3 was used as base.
d
e
f
1.7 equiv of 1, 50 °C, 24 h. From ArBpin. From ArBF3K.
in metal-catalyzed cross-couplings often face several additional
challenges,21 such as undesired Heck-type reactivity on the
vinyl−[M] reagent or polymerization styrene-type products.
Vinyl sulfonium salts are ideally positioned to undergo metal-
catalyzed vinylations, but no examples have been reported.
One of the main reasons is the unselective cleavage of the
different C−S bonds in sulfonium salts,37 which can result in
mixtures of products. We conceived 1 as a suitable coupling
partner that could overcome the above-mentioned challenges
and enable fast oxidative addition in view of its electropositive
character (Ered = −1.13 V vs SCE). Moreover, in line with what
has been observed in palladium-catalyzed reactions of aryl
thianthrenium salts,58−63 cleavage of the Cvinyl−S bond
selectively over the two Caryl−S bonds may be explained by
irreversible oxidative addition into the vinyl bond but
reversible oxidative addition into the aryl bond64,65 of the
annulated structure of the thianthrene core (see Supporting
Information for a discussion). To demonstrate the perform-
ance of 1 in cross-coupling reactions, we developed a Suzuki-
type vinylation of aryl boronic acids (Table 2A). The scope of
aryl boronic acids encompasses a wide range of (hetero)arenes
with different functional groups and substitution patterns (28−
36), including electrophilic groups that are not tolerated by
Wittig olefination-based synthesis66 (34, 39), with proto-
deborylation observed as the main side reaction in those
examples with lower yields. The fast rate of oxidative addition
of the C−S bond allowed the vinylation of substrates
containing C−Br bonds (33) that are otherwise reactive in
Suzuki reactions.19 Likewise, a competition experiment
between vinyl thianthrenium 1-d3 and vinyl bromide
established that the thianthrenium compound reacts substan-
tially faster than vinyl bromide; less than 1% of reaction
product based on vinyl bromide could be detected by either
NMR spectroscopy or mass spectrometry analysis (Table 2B).
Extension of the methodology to other organoboron
compounds, such as boronic esters (38) and trifluoroborates
12995
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
(39), is possible. Alkenyl boronic acids were also suitable
substrates, yielding valuable dienes (40) that can be employed
for further elaboration (e.g., Diels−Alder reactions).
https://pubs.acs.org/10.1021/jacs.1c06632
Funding
In contrast, the use of vinyl-SPh2(OTf) under the same
reaction conditions did not afford the desired products or
resulted in <15% yield in all the cases studied (Table 2C). For
example, while styrene 42 was isolated in 68% yield when using
reagent 1, only a 4% yield could be detected by NMR when
using vinyl-SPh2(OTf), which may be the result of a faster
reagent decomposition or catalyst poisoning. Moreover,
analysis of the reaction mixture revealed the presence of
equimolar amounts of side-product 43, arising from aryl−Ph
instead of aryl−vinyl bond formation, while no related product
resulting from aryl−aryl coupling could be detected in the
reaction with 1. A similar outcome was observed with substrate
44. These results underline the key benefits of the structural
design of thianthrene electrophiles, effectively channelling the
oxidative addition process toward the desired C−S bond and
allowing, for the first time, a vinylation reaction based on cross-
coupling with vinyl sulfonium salts.
Open access funded by Max Planck Society.
Notes
The authors declare the following competing financial
interest(s): T.R. may benefit from royalty payments on sales
of thianthrene-related compounds.
ACKNOWLEDGMENTS
■
We thank Dr. Markus Leutzsch and Ms. Petra Philipps for
assistance with NMR experiments, Ms. Fei Wang for DSC
analysis, Dr. Qiang Cheng and Aboubakr Hamad for helpful
discussions, and Dr. Florian Berger for the development of a
synthesis of 1 from trimethylvinylsilane. We thank the MPI fur
̈
Kohlenforschung for their financial support.
REFERENCES
■
(1) Patai, S. The Chemistry of Alkenes; Wiley: New York, 1964; Vol.
1. DOI: DOI: 10.1002/9780470771044.
In summary, we have developed a convenient vinyl
electrophile reagent that is prepared directly from ethylene
and can be stored in the presence of air and moisture. The salt
has proven to be an effective vinylating reagent and C-2
synthon for the synthesis of carbo- and heterocycles, N-
vinylated products, styrenes, and dienes. The distinct structural
features of thianthrenium salts in comparison with other
sulfonium salts enable both its unique synthesis from ethylene
and its superior performance in cross-coupling reactions. Its
one-step synthesis, easy-to-handle features, and robust
reactivity make it a valuable and versatile reagent that will
find synthetic utility in further organic and transition-metal
catalyzed transformations.
(2) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Catalytic
Asymmetric Dihydroxylation. Chem. Rev. 1994, 94 (8), 2483−2547.
(3) McDonald, R. I.; Liu, G.; Stahl, S. S. Palladium(II)-Catalyzed
Alkene Functionalization via Nucleopalladation: Stereochemical
Pathways and Enantioselective Catalytic Applications. Chem. Rev.
2011, 111 (4), 2981−3019.
(4) Beletskaya, I. P.; Cheprakov, A. V. The Heck Reaction as a
Sharpening Stone of Palladium Catalysis. Chem. Rev. 2000, 100 (8),
3009−3066.
(5) Pirnot, M. T.; Wang, Y.-M.; Buchwald, S. L. Copper Hydride
Catalyzed Hydroamination of Alkenes and Alkynes. Angew. Chem., Int.
Ed. 2016, 55 (1), 48−57.
(6) Grubbs, R. H.; Chang, S. Recent advances in olefin metathesis
and its application in organic synthesis. Tetrahedron 1998, 54 (18),
4413−4450.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c06632.
■
(7) Zimmermann, H.; Walzl, R.; Ethylene. Ullmann’s Encyclopedia of
Industrial Chemistry 2009, DOI: 10.1002/14356007.a10_045.pub3.
(8) Crimmins, M. T.; Kim-Meade, A. S. Ethylene. Encyclopedia of
Reagents for Organic Synthesis 2001, 1−4.
sı
Experimental procedures and spectral data (PDF)
(9) Saini, V.; Stokes, B. J.; Sigman, M. S. Transition-Metal-Catalyzed
Laboratory-Scale Carbon−Carbon Bond-Forming Reactions of Ethyl-
ene. Angew. Chem., Int. Ed. 2013, 52 (43), 11206−11220.
(10) RajanBabu, T. V.; Adam Cox, G.; Lim, H. J.; Nomura, N.;
Sharma, R. K.; Smith, C. R.; Zhang, A. 5.32 Hydrovinylation
Reactions in Organic Synthesis. In Comprehensive Organic Synthesis II,
2nd ed.; Knochel, P., Ed.; Elsevier: Amsterdam, 2014; pp 1582−1620.
(11) Hilt, G. Hydrovinylation Reactions − Atom-Economic
Transformations with Steadily Increasing Synthetic Potential. Eur. J.
Org. Chem. 2012, 2012 (24), 4441−4451.
Accession Codes
CCDC 2075820−2075821 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(12) Vaughan, B. A.; Webster-Gardiner, M. S.; Cundari, T. R.;
Gunnoe, T. B. A rhodium catalyst for single-step styrene production
from benzene and ethylene. Science 2015, 348 (6233), 421−424.
(13) Harper, M. J.; Emmett, E. J.; Bower, J. F.; Russell, C. A.
Oxidative 1,2-Difunctionalization of Ethylene via Gold-Catalyzed
Oxyarylation. J. Am. Chem. Soc. 2017, 139 (36), 12386−12389.
(14) Tang, S.; Wang, D.; Liu, Y.; Zeng, L.; Lei, A. Cobalt-catalyzed
electrooxidative C−H/N−H [4 + 2] annulation with ethylene or
ethyne. Nat. Commun. 2018, 9 (1), 798.
AUTHOR INFORMATION
Corresponding Author
■
Tobias Ritter − Max-Planck-Institut fu
45470 Mulheim an der Ruhr, Germany; orcid.org/0000-
0002-6957-450X; Email: ritter@kofo.mpg.de
̈
r Kohlenforschung, D-
̈
Authors
Fabio Juliá − Max-Planck-Institut fu
45470 Mulheim an der Ruhr, Germany; orcid.org/0000-
0001-8903-4482
Jiyao Yan − Max-Planck-Institut fu
45470 Mulheim an der Ruhr, Germany
Fritz Paulus − Max-Planck-Institut fur Kohlenforschung, D-
45470 Mulheim an der Ruhr, Germany
Complete contact information is available at:
̈
r Kohlenforschung, D-
̈
(15) Cargill, R. L.; Dalton, J. R.; Morton, G. H.; Caldwell, W. W.
Photocyclization of an enone to an alkene. Org. Synth. 2003, 62, 118.
(16) Meyers, A. I.; Fleming, S. A. Efficient asymmetric (2 + 2)
photocycloaddition leading to chiral cyclobutanes. Application to the
total synthesis of (−)-grandisol. J. Am. Chem. Soc. 1986, 108 (2),
306−307.
̈
r Kohlenforschung, D-
̈
̈
̈
(17) Hoffmann, N.; Scharf, H.-D.; Runsink, J. Chiral induction in
photochemical reactions-XII. Synthesis of chiral cyclobutane deriva-
12996
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
tives from (+)-5-menthyloxy-2-[5H]-furanone and ethylene. Tetrahe-
dron Lett. 1989, 30 (20), 2637−2638.
(18) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;
Snieckus, V. Palladium-Catalyzed Cross-Coupling: A Historical
Contextual Perspective to the 2010 Nobel Prize. Angew. Chem., Int.
Ed. 2012, 51 (21), 5062−5085.
(19) Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling
Reactions of Organoboron Compounds. Chem. Rev. 1995, 95 (7),
2457−2483.
(20) World Health Organization International Agency for Research
on Cancer. Vinyl bromide. IARC Monogr. Eval. Carcinog. Risks Hum.
1999, 71 Pt 2: 923−8. https://publications.iarc.fr/115.
(21) Denmark, S. E.; Butler, C. R. Palladium- (and nickel-) catalyzed
vinylation of aryl halides. Chem. Commun. 2009, 1, 20−33.
(22) Wang, Y.; Zhang, W.; Colandrea, V. J.; Jimenez, L. S. Reactivity
and rearrangements of dialkyl- and diarylvinylsulfonium salts with
indole-2- and pyrrole-2-carboxaldehydes. Tetrahedron 1999, 55 (35),
10659−10672.
(36) Aukland, M. H.; Talbot, F. J. T.; Fernández-Salas, J. A.; Ball,
M.; Pulis, A. P.; Procter, D. J. An Interrupted Pummerer/Nickel-
Catalysed Cross-Coupling Sequence. Angew. Chem., Int. Ed. 2018, 57
(31), 9785−9789.
(37) Lin, H.; Dong, X.; Li, Y.; Shen, Q.; Lu, L. Highly Selective
Activation of Vinyl C−S Bonds Over Aryl C−S Bonds in the Pd-
C a t a l y z e d C o u p l i n g o f (E )- ( β - T r i f l u o r o m e t h y l ) -
vinyldiphenylsulfonium Salts: Preparation of Trifluoromethylated
Alkenes and Dienes. Eur. J. Org. Chem. 2012, 2012 (25), 4675−4679.
(38) Chen, J.; Li, J.; Plutschack, M. B.; Berger, F.; Ritter, T. Regio-
and Stereoselective Thianthrenation of Olefins To Access Versatile
Alkenyl Electrophiles. Angew. Chem., Int. Ed. 2020, 59 (14), 5616−
5620.
(39) Lochynski, S.; Boduszek, B.; Shine, H. J. Oxidation of
organotins (R4Sn, RSnMe3, and R3SnSnR3) by the thianthrene
cation radical. J. Org. Chem. 1991, 56 (3), 914−920.
(40) Blauvelt, M. L. 5-Thianthrenyl-5-ylium Perchlorate. Encyclope-
dia of Reagents for Organic Synthesis 2009, 1−6.
(23) Yamanaka, H.; Yamane, Y.; Mukaiyama, T. A New Method for
the Preparation of Nitrogen-containing Heterocycles Using Diphe-
nylsulfonium Triflates. Heterocycles 2004, 63 (12), 2813−2826.
(24) Yar, M.; McGarrigle, E. M.; Aggarwal, V. K. An Annulation
Reaction for the Synthesis of Morpholines, Thiomorpholines, and
Piperazines from β-Heteroatom Amino Compounds and Vinyl
Sulfonium Salts. Angew. Chem., Int. Ed. 2008, 47 (20), 3784−3786.
(25) Yar, M.; McGarrigle, E. M.; Aggarwal, V. K. Sulfonium,
Ethenyldiphenyl-, 1,1,1-Trifluoromethanesulfonate. Encyclopedia of
Reagents for Organic Synthesis 2012, 1−6.
(26) “While a large amount of methodology has been developed
using diphenylvinylsulfonium triflate, some practical issues remain.
Diphenylvinylsulfonium triflate is a slightly hygroscopic brown oil that
must be stored under inert atmosphere and kept at low temperature
(fridge at 4° C). For this reason, the reagent is difficult to manipulate
and hard to synthesize on large scales.” J. V. Matlock, V. K. Aggarwal,
E. M. McGarrigle, ref 27.
(41) Fannes, C.; Meerpoel, L.; Toppet, S.; Hoornaert, G.
Cycloaddition of Olefinic Compounds to 2H-1,4-Oxazin-2-ones:
Synthesis of 2-Oxa-5-azabicyclo[2.2.2]oct-5-en-3-ones. Synthesis
1992, 1992 (07), 705−709.
(42) Yar, M.; Fritz, S. P.; Gates, P. J.; McGarrigle, E. M.; Aggarwal,
V. K. Synthesis of N-Vinyloxazolidinones and Morpholines from
Amino Alcohols and Vinylsulfonium Salts: Analysis of the Outcome’s
Dependence on the N-Protecting Group by Nanospray Mass
Spectrometry. Eur. J. Org. Chem. 2012, 2012 (1), 160−166.
(43) Alkenylation of nitrogen heterocycles has only been reported
for styrenyl sulfonium salts: Zhou, M.; Tan, X.; Hu, Y.; Shen, H. C.;
Qian, X. Highly Chemo- and Regioselective Vinylation of N-
Heteroarenes with Vinylsulfonium Salts. J. Org. Chem. 2018, 83,
8627−8635.
(44) Lan, T.; Chen, X.; Liu, Z.; Mao, Z. A Novel Facile Synthesis
Method of N-Vinylpyrroles. J. Heterocycl. Chem. 2013, 50 (5), 1094−
1098.
(27) Matlock, J. V.; Aggarwal, V. K.; McGarrigle, E. M. (2-
Bromoethyl)diphenylsulfonium Trifluoromethanesulfonate. Encyclo-
pedia of Reagents for Organic Synthesis 2016, 1−5.
(28) Zhou, M.; En, K.; Hu, Y.; Xu, Y.; Shen, H. C.; Qian, X. Zinc
triflate-mediated cyclopropanation of oxindoles with vinyl diphenyl
sulfonium triflate: a mild reaction with broad functional group
compatibility. RSC Adv. 2017, 7 (7), 3741−3745.
(29) Yar, M.; McGarrigle, E. M.; Aggarwal, V. K. Bromoethylsulfo-
nium SaltA More Effective Annulation Agent for the Synthesis of 6-
and 7-Membered 1,4-Heterocyclic Compounds. Org. Lett. 2009, 11
(2), 257−260.
(30) Karahan, S.; Tanyeli, C. Organocatalytic enantioselective
construction of isatin-derived N-alkoxycarbonyl 1,3-aminonaphthols
via sterically encumbered hydrocarbon-substituted quinine-based
squaramide. New J. Chem. 2017, 41 (17), 9192−9202.
(31) Fritz, S. P.; Moya, J. F.; Unthank, M. G.; McGarrigle, E. M.;
Aggarwal, V. K. An Efficient Synthesis of Azetidines with (2-
Bromoethyl)sulfonium Triflate. Synthesis 2012, 44 (10), 1584−1590.
(32) Unthank, M. G.; Hussain, N.; Aggarwal, V. K. The Use of Vinyl
Sulfonium Salts in the Stereocontrolled Asymmetric Synthesis of
Epoxide- and Aziridine-Fused Heterocycles: Application to the
Synthesis of (−)-Balanol. Angew. Chem., Int. Ed. 2006, 45 (42),
7066−7069.
(33) Yar, M.; Unthank, M. G.; McGarrigle, E. M.; Aggarwal, V. K.
Remote Chiral Induction in Vinyl Sulfonium Salt-Mediated Ring
Expansion of Hemiaminals into Epoxide-Fused Azepines. Chem. -
Asian J. 2011, 6 (2), 372−375.
(34) Xie, C.; Han, D.; Hu, Y.; Liu, J.; Xie, T. Synthesis of pyrrolidin-
2-ones via tandem reactions of vinyl sulfonium salts under mild
conditions. Tetrahedron Lett. 2010, 51 (40), 5238−5241.
(35) Srogl, J.; Allred, G. D.; Liebeskind, L. S. Sulfonium Salts.
Participants par Excellence in Metal-Catalyzed Carbon−Carbon
Bond-Forming Reactions. J. Am. Chem. Soc. 1997, 119 (50),
12376−12377.
(45) Martín-Escolano, R.; Aguilera-Venegas, B.; Marín, C.; Martín-
Montes, A.; Martín-Escolano, J.; Medina-Carmona, E.; Arán, V. J.;
́
Sánchez-Moreno, M. Synthesis and Biological in vitro and in vivo
Evaluation of 2-(5-Nitroindazol-1-yl)ethylamines and Related Com-
pounds as Potential Therapeutic Alternatives for Chagas Disease.
ChemMedChem 2018, 13 (19), 2104−2118.
(46) Shmidt, E. Y.; Protsuk, N. I.; Vasil’tsov, A. M.; Ivanov, A. V.;
Mikhaleva, A. I.; Trofimov, B. A. Improved method for the synthesis
of 1-vinylindole. Chem. Heterocycl. Compd. 2013, 49 (3), 404−407.
(47) Rattanangkool, E.; Vilaivan, T.; Sukwattanasinitt, M.;
Wacharasindhu, S. An Atom-Economic Approach for Vinylation of
Indoles and Phenols Using Calcium Carbide as Acetylene Surrogate.
Eur. J. Org. Chem. 2016, 2016 (25), 4347−4353.
(48) Lebedev, A. Y.; Izmer, V. V.; Kazyul’kin, D. N.; Beletskaya, I. P.;
Voskoboynikov, A. Z. Palladium-Catalyzed Stereocontrolled Vinyl-
ation of Azoles and Phenothiazine. Org. Lett. 2002, 4 (4), 623−626.
(49) Kimura, J.; Nakamichi, S.; Ogawa, S.; Obora, Y. Iridium-
Catalyzed Vinylation of Carbazole Derivatives with Vinyl Acetate.
Synlett 2017, 28 (06), 719−723.
(50) Lam, P. Y. S.; Deudon, S.; Averill, K. M.; Li, R.; He, M. Y.;
DeShong, P.; Clark, C. G. Copper-Promoted C−N Bond Cross-
Coupling with Hypervalent Aryl Siloxanes and Room-Temperature
N-Arylation with Aryl Iodide. J. Am. Chem. Soc. 2000, 122 (31),
7600−7601.
(51) Arsenyan, P.; Petrenko, A.; Paegle, E.; Belyakov, S. Direct N-
and C-vinylation with trimethoxyvinylsilane. Mendeleev Commun.
2011, 21 (6), 326−328.
(52) Utsunomiya, M.; Kuwano, R.; Kawatsura, M.; Hartwig, J. F.
Rhodium-Catalyzed Anti-Markovnikov Hydroamination of Vinyl-
arenes. J. Am. Chem. Soc. 2003, 125 (19), 5608−5609.
(53) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. Rh(III)-
Catalyzed Directed C−H Olefination Using an Oxidizing Directing
Group: Mild, Efficient, and Versatile. J. Am. Chem. Soc. 2011, 133 (8),
2350−2353.
12997
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998

Journal of the American Chemical Society
pubs.acs.org/JACS
Communication
(54) Tomita, R.; Yasu, Y.; Koike, T.; Akita, M. Combining
Photoredox-Catalyzed Trifluoromethylation and Oxidation with
DMSO: Facile Synthesis of α-Trifluoromethylated Ketones from
Aromatic Alkenes. Angew. Chem., Int. Ed. 2014, 53 (28), 7144−7148.
(55) Wang, D.; Wu, L.; Wang, F.; Wan, X.; Chen, P.; Lin, Z.; Liu, G.
Asymmetric Copper-Catalyzed Intermolecular Aminoarylation of
Styrenes: Efficient Access to Optical 2,2-Diarylethylamines. J. Am.
Chem. Soc. 2017, 139 (20), 6811−6814.
(56) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N.
Enantioselective epoxidation of unfunctionalized olefins catalyzed by
salen manganese complexes. J. Am. Chem. Soc. 1990, 112 (7), 2801−
2803.
(57) Dewkar, G. K.; Narina, S. V.; Sudalai, A. NaIO4-Mediated
Selective Oxidative Halogenation of Alkenes and Aromatics Using
Alkali Metal Halides. Org. Lett. 2003, 5 (23), 4501−4504.
(58) Ye, Y.; Zhu, J.; Huang, Y. Diverse C−P Cross-Couplings of
Arylsulfonium Salts with Diarylphosphines via Selective C−S Bond
Cleavage. Org. Lett. 2021, 23 (6), 2386−2391.
(59) Berger, F.; Plutschack, M. B.; Riegger, J.; Yu, W.; Speicher, S.;
Ho, M.; Frank, N.; Ritter, T. Site-selective and versatile aromatic C−
H functionalization by thianthrenation. Nature 2019, 567 (7747),
223−228.
(60) Engl, P. S.; Häring, A. P.; Berger, F.; Berger, G.; Pérez-Bitrián,
A.; Ritter, T. C−N Cross-Couplings for Site-Selective Late-Stage
Diversification via Aryl Sulfonium Salts. J. Am. Chem. Soc. 2019, 141
(34), 13346−13351.
(61) Alvarez, E. M.; Plutschack, M. B.; Berger, F.; Ritter, T. Site-
Selective C−H Functionalization−Sulfination Sequence to Access
Aryl Sulfonamides. Org. Lett. 2020, 22 (12), 4593−4596.
(62) Selmani, A.; Gevondian, A. G.; Schoenebeck, F. Germylation of
Arenes via Pd(I) Dimer Enabled Sulfonium Salt Functionalization.
Org. Lett. 2020, 22 (12), 4802−4805.
(63) Lansbergen, B.; Granatino, P.; Ritter, T. Site-Selective C−H
alkylation of Complex Arenes by a Two-Step Aryl Thianthrenation-
Reductive Alkylation Sequence. J. Am. Chem. Soc. 2021, 143 (21),
7909−7914.
(64) Tobisu, M.; Masuya, Y.; Baba, K.; Chatani, N. Palladium(ii)-
catalyzed synthesis of dibenzothiophene derivatives via the cleavage of
carbon−sulfur and carbon−hydrogen bonds. Chem. Sci. 2016, 7 (4),
2587−2591.
(65) Spencer, J.; Pfeffer, M.; DeCian, A.; Fischer, J. Palladium-
Mediated Intramolecular Formation of a C-S Bond: Application to
the Selective Syntheses of Six- and Seven-Membered Sulfur-
Containing Heterocycles. J. Org. Chem. 1995, 60 (4), 1005−1012.
(66) Broos, R.; Anteunis, M. A Simplified Wittig Synthesis of
Substituted Styrenes. Synth. Commun. 1976, 6 (1), 53−57.
12998
https://doi.org/10.1021/jacs.1c06632
J. Am. Chem. Soc. 2021, 143, 12992−12998