5-(Cyano)dibenzothiophenium Triflate: A Sulfur-Based Reagent for Electrophilic Cyanation and Cyanocyclizations

Article abstract of DOI:10.1002/anie.201904557

The synthesis of 5-(cyano)dibenzothiophenium triflate 9, prepared by activation of dibenzo[b,d]thiophene-5-oxide with Tf₂O and subsequent reaction with TMSCN is reported, and its reactivity as electrophilic cyanation reagent evaluated. The scalable preparation, easy handling and broad substrate scope of the electrophilic cyanation promoted by 9, which includes amines, thiols, silyl enol ethers, alkenes, electron rich (hetero)arenes and polyaromatic hydrocarbons, illustrate the synthetic potential of this reagent. Importantly, Lewis acid activation of the reagent is not required for the transfer process. We additionally report herein biomimetic cyanocyclization cascade reactions, which are not promoted by typical electrophilic cyanation reagents, demonstrating the superior ability of 9 to trigger challenging transformations.

Full text of DOI:10.1002/anie.201904557

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: 5-(Cyano)dibenzothiophenium Triflate: A Sulfur–Based Reagent
for Electrophilic Cyanation and Cyanocyclizations
Authors: Manuel Alcarazo, Xiangdong Li, and Christopher Golz
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.201904557
Angew. Chem. 10.1002/ange.201904557
Link to VoR: http://dx.doi.org/10.1002/anie.201904557
http://dx.doi.org/10.1002/ange.201904557

10.1002/anie.201904557
Angewandte Chemie International Edition
COMMUNICATION
5-(Cyano)dibenzothiophenium Triflate: A Sulfur–Based Reagent
for Electrophilic Cyanation and Cyanocyclizations
Xiangdong Li, Christopher Golz and Manuel Alcarazo*[a]
Dedicated to Prof. Armin de Meijere on the occasion of his 80th birthday
Abstract: The synthesis of 5-(cyano)dibenzothiophenium triflate 9,
prepared by activation of dibenzo[b,d]thiophene-5-oxide with Tf2O
and subsequent reaction with TMSCN is reported, and its reactivity
as electrophilic cyanation reagent evaluated. The scalable
preparation, easy handling and broad substrate scope of the
electrophilic cyanation promoted by 9, which includes amines, thiols,
silyl enol ethers, alkenes, electron rich (hetero)arenes and
polyaromatic hydrocarbons, illustrate the synthetic potential of this
reagent. Importantly, Lewis acid activation of the reagent is not
required for the transfer process. We additionally report herein
biomimetic cyanocyclization cascade reactions, which are not
promoted by typical electrophilic cyanation reagents, demonstrating
the superior ability of 9 to trigger challenging transformations.
unstable hypervalent I(III) platforms.[18]
Electrophilic cyanating reagents
N-based reagents
pseudohalogenides
N
N
X
CN
Ph
CN
X
N
1
2
3
; X = Cl
; X = Br
; X = CN
Ts
4
CN
5
6
; X = N
; X = CH
S-based reagents
I(III)-based reagents
SbF6
CN
S
S
I
CN
O
CN
iPr
iPr
N
N
O
TfO
This work
9
Me
Me
8
7
The synthetic versatility of the cyano group, which is a privileged
precursor of amines, amides, aldehydes, carboxylic acids and N-
containing heterocycles;[1] as well as the prevalence of nitriles in
natural products,[2] pharmaceuticals,[3] agrochemicals,[4] dyes[5]
and high performance materials and polymers[6] has stimulated
the development of efficient methodologies for the selective
incorporation of –CN substituents at specific positions of
elaborated organic scaffolds.[ 7 ] Despite of the sophistication
achieved in this area,[8] most of the protocols described still use
the inherent nucleophilicity of the cyanide anion to promote the
C-CN bond forming event and hence, they are reminiscent to the
classical Sandmeyer[9] and Rosenmund–von Braun reactions for
the preparation of aromatic nitriles,[ 10 ] or the Kolbe nitrile
synthesis for aliphatic ones.[11] Disconnection strategies based
on the umpolung of the CN moiety are comparatively scarce and
their synthetic potential has still not been fully exploited mainly
due to the disadvantages associated with the use of the
available electrophilic cyanide sources.[12] Namely, the extreme
Figure 1. Representative electrophilic cyanation reagents.
Nature often uses carbocationic cascade cyclisations to
produce complex molecular architectures from simple
precursors, and chemists have been quite successful
transferring this strategy into routine synthesis planning.[ 19 ]
Initiation of such cyclisations is often triggered by elimination of
a leaving group, the activation of olefins by π-acid catalysts, or
the reaction of carbon-carbon double bonds with
electrophiles.[20] However, we are not aware of the use of neither
7 nor 8 as promoters for the metal-free cyanofunctionalization of
olefins, presumably due to the moderate electrophilic character
of the cyano moieties in these two [CN]+ synthons.[21]
Given the synthetic potential that such cyano-
functionalization may have, we were encouraged to develop a
new electrophilic cyanation reagent able to trigger these
transformations. At that stage we envisioned that the
dibenzothiophenium unit, which has been previously used for
the preparation of electrophilic trifluoromethylation and
alkynylation reagents might be an adequate platform to achieve
a more efficient umpolung of the CN-group. [22] Herein, we report
the synthesis of 5-(cyano)dibenzothiophenium triflate 9, and
preliminarily evaluate its reactivity on the cyanation of typical
organic nucleophiles, and the cyanofunctionalization of a variety
of indole derivatives.
The desired 5-(cyano)dibenzothiophenium salt 9 has been
obtained in a one pot synthesis from sulfoxide 10 by activation
with one equivalent of triflic acid anhydride at -50 °C and
quenching of the in situ generated bistriflate with TMSCN.
Compound 9 precipitates from the reaction mixture and is
isolated as a beige solid. This synthetic route has been scaled
up to ten grams with a reproducible 60% yield (Scheme 1).
Diagnostic spectroscopic features of compound 9 are the 13C-
NMR signal for the carbon atom of the cyano moiety (δ = 103.8
ppm.), which is upfield shifted if compared with that of
13
]
toxicity and volatility of pseudo halogens 1-3,[
or the
considerably lower reactivity of N-cyano sulfonamides 4, N-
cyanobenzotriazole 5 and N-cyanobenzoimidazole 6, which
require the use of strong C-nucleophiles such as organometallic
reagents or enolates to transfer the formal [CN]+ unit.[14] It was
not until the introduction of cyanobenziodoxone
Zhdankin,[15] and its intensive use by Waser[16] and others[17] that
metal-free electrophilic cyanation at unfunctionalized C-H
7 by
positions of electron rich organic substrates could be efficiently
achieved (Figure 1). We recently contributed to this area with the
introduction of imidazolium thiocyanate 8; it depicts a reactivity
profile similar to the one of 7, but is not based on thermally
[a]
Dr. X. Li, Dr. C. Golz and Prof. Dr. M. Alcarazo
Institut für Organische und Biomolekulare Chemie
Georg-August- Universität Göttingen
Tammannstr 2, 37077-Göttingen, Germany
e-mail: malcara@gwdg.de
arylsulfonyl cyanides (δ = 110-119 ppm.), and the stretching
Supporting information for this article is given via a link at the end of
the document
~
frequency of the C≡N moiety at (CN )= 2191.7 cm-1.
ν
This article is protected by copyright. All rights reserved.

10.1002/anie.201904557
Angewandte Chemie International Edition
COMMUNICATION
olefins, as well as electron rich homo-, hetero-, and polycyclic
aromatics were also transformed into the desired nitriles 29-38
under similar conditions.[ 25 ] While the profile of 8 and 9
regarding substrate scope is quite similar, all cyano transfer
reactions shown in Scheme 2 took place at relatively low
temperatures (-50°C→50°C), and without activation of the
transfer reagent with BF3·OEt2. This suggests inherently higher
electrophilicity at the CN moiety of 9.
TfO
O
OTf
S
S
S
CN
TfO
a)
b)
9
10
Scheme 1. Synthesis of 5-(cyano)dibenzothiophenium triflate. Reagents and
conditions: a) Tf2O (1 equiv.), -50°C, 1h, (not isolated); c) TMSCN (1 equiv.),
CH2Cl2, -50°C, 8h, 60%.
9
Method A:
Cs or K
(1.5 equiv.),
(1.5 equiv.)
3PO4
2CO3
H
1
R-CN
R-
X-ray diffraction analysis of monocrystals of 9 confirmed
the expected connectivity (Figure 2). In the cationic part the
sulfur atom remains at the plane defined by the
dibenzothiophene skeleton; however, the C-S bond distances
within the aromatic moiety, 1.7911(8) Å for S1-C2 and 1.7991(8)
Å for S1-C13 are significantly longer than in dibenzothiophene
(1.740 Å). This probably results from the reduction of aromaticity
at the thiophene platform after coordination of the cyano moiety.
In addition, the central sulfur atom adopts a trigonal-pyramidal
coordination environment, being the sum of the bond angles
around S1 286.6°(4); thus, there is a stereochemically relevant
electron pair at this atom. Also of particular relevance is the
short contact S1-O3 (2.6085(7) Å), which is significantly shorter
than the sum of the van der Waals radii of the corresponding
elements (3.32 Å). This interaction evidences some Lewis
acidity at S1 and suggests that the initial step of the cyano
transfer using 9 might imply the approach of the incoming
nucleophile to the electron poor sulfur atom, followed by a
reductive elimination type process. An analogous mechanism
has been proposed for cyanation reactions promoted by reagent
7.[23]
9
Method B:
(1.5 equiv.),
no base
tBu
CN
CN
Ph
N
N
R
CN
CN
N
H
N
H
a
a
a
a
11
13
, 98%
14
15
12
, 72%
, R = Me, 90%
, 97%
a
, R = Bn, 91%
CN
NC
N
n
N
N
X
a
CN
a
18
19
20
21
, X = CH2, 88%
16
17
, n = 1, 95%
a
a
a
22
, 68%
, X = O, 71%
, n = 2, 92%
, X = (CH2 2, 94%a
22
X-ray structure of
)
a
, X = (CH=CH), 99%
CN
CN
S
CN
CN
S
N
S
Me
Me
Br
N
Ph
Me
b
a
b
b
24
, 68%
25
, 61%
26
, 84%
23
, 42%
CN
O
OMe
S
O
CN
CN
S
CN
Ph
29
OMe
b
MeO
b
a
b,c
30
, 94%
, 92%
CN
Ph
28
, 71%
27
, 61%
R
Ph
CN
CN
N
Ph
N
Ph
N
Me
CN
a
a
b
33
34
32
, 99%
, R = H, 70%
31
, 74%
b
35
, R = H, 53%
a
, R = OMe, 79%
Figure 2. Molecular structure of compound 9 in the solid state. Anisotropic
displacement shown at 50% probability level and hydrogen atoms omitted for
clarity. Selected bond lengths [Å] and angles [deg]: S1-C1, 1.7404(9); S1-C2,
1.7911(8); S1-C13, 1.7991(8); S1-O3, 2.6085(7); O3-S1-C1, 176.07(3); C2-
S1-C1, 96.06(4); C13-S1-C1, 98.92(4).[24]
CN
OMe
NC
CN
Ph2N
MeO
a
b
b,d
37
,33%
36
, 80%
OMe
38
, 27%
Once compound 9 was completely characterized, we started
our investigation by subjecting benchmark N-, S- and C-based
nucleophiles to its action. Optimization of the reaction conditions
using anilines revealed Cs2CO3 as the optimal base (Scheme 2,
Method A). Under these conditions cyanamides 11-23 can be
obtained in moderate to excellent yields. Aromatic thiols do not
require the addition of base to afford thiocyanates 24-27
(Method B), while for aliphatic ones Cs2CO3 is again necessary
to obtain acceptable results, 28. Silyl enol ethers and terminal
Scheme 2. Substrate scope of the electrophilic cyanation using 5-(cyano)
dibenzothiophenium triflate 9. All yields are isolated unless otherwise stated.
aMethod A was applied. bMethod B was applied. cNMR yield. The identity of 30
was confirmed by its derivatization with TsNH-NH2 and isolation of the
corresponding 3-aminopyrazole. dTwo equivalents of 9 were employed.
In an attempt to further evaluate the utility of 9 in more
complex transformations, we tested its reactivity towards indole
39, in which the most reactive position 3 is blocked with a methyl
This article is protected by copyright. All rights reserved.

10.1002/anie.201904557
Angewandte Chemie International Edition
COMMUNICATION
substituent. A mixture of two products 40 and 41 was obtained
under these conditions. The connectivity of 40, which could be
assessed by X-ray analysis, corresponds to a dimeric structure
originated from the initial attack of the [CN]+ moiety at position 3
of indole 39 and subsequent trapping of the in situ generated
iminium salt with a second equivalent of 39. Compound 41 is the
product of additional cyanation at the most nucleophilic amino
group of 40 (Scheme 3a). Only the diasteromer coming from the
syn-attack of both groups to the carbon-carbon double bond was
detected. Simultaneous decoration of the indole substrate with
two alkyl-substituents in positions 2- and 3-, as is the case of 42
and 44, quenches the dimerization pathway. In these cases,
after the initial electrophilic cyanation step deprotonation of the
N-atom takes place affording indolenines 43 and 45 (See the SI
for the X-ray structure of 43).
unprecedented, and renders cyano-pyrroloindolines of potential
synthetic and/or pharmacological interest.
The superiority of 9 as [CN]+ synthon when compared with
7 or 8 can be inferred from these cyanoaminations; under
identical reaction conditions neither 7 nor 8 are capable to
promote the cyanoamination of the simplest substrate of the
series, N-tosyl tryptamine, to afford 46 (See the Supporting
Information). Moreover, the scope of this reaction can be
likewise extended to indole substrates tethered with O- or even
C-nucleophiles. Exception made of compound 62, where an
additional chiral center is formed; in all other cases only one
diasteromer is observed (Scheme 4).
n
NC
NuH
R1
n
a)
Nu
R1
R2
N
N
R2
rac-(
46-62
n = 1, 2
NC
)
a)
Me
Me
HN
CN
Me
HN
CN
Me
Me
a)
N
R1
Ts
N
N
NH
N
H
R2
CN
2 = H; 69 %
41
39
40
1
46
47
48
; R , R
1 = Me, R2 = H; 85%
1 = H, R2 = Me; 61%
; R
; R
48
X-ray structre of
NC
NC
NC
N
R1
N
N
R1
Et
CO2
Ms
Bn
CO2
Me
N
N
H
N
R2
R2
2 = H; 56%
1 = Me, R2 = H; 81%
1 = Me, R2 = Bn; 93%
2 = H; 68 %
1 = Me, R2 = Bn; 89%
1 = Me, R2 = H; 71%
1
1
55
; 68%
52
53
54
49
50
51
; R , R
; R , R
b)
; R
; R
Me
Me
; R
; R
NC
NC
a)
a)
Me
Me
NC
N
N
N
NC
N
H
H
O
R1
44
43
45
42
O
N
N
H
H
H
1 = H; 55%
56
57
58
; R
Scheme 3. a)Reaction of 9 with 3-methylindole 39. Reagents, conditions and
isolated yields: a) 9 (1.5 equiv.), Cs2CO3 (1.0 equiv.) 0°C, DCM, 2h, 40 (50%),
41 (30 %). Molecular structures of compounds 40 and 41 in the solid state.
Anisotropic displacement shown at 30% probability level. Only selected
hydrogen atoms are shown.[24] b) Reaction of 9 with 42 and 44. Reagents,
conditions and isolated yields: a) 9 (1.5 equiv.), CH3CN, r.t., 15 min., 43 (76%),
44 (86 %).
1 = Me; 66%
1 = Ph; 89%
59
; 64%
; R
59
X-ray structre of
EtO2C
; R
Et
CO2
O
NC
NC
NC
Et
CO2
O
*
Et
CO2
H
N
Me
N
N
H
Me
Me
H
H
a
60
; 19%
62
; 96%
61
; 86%
(*d.r.= 4.7:1)
In order to explore the generality and synthetic relevance
of these cyanation reactions, we first decided to equip a series
of indoles with an internal nucleophilic group and explore
intramolecular cyanofunctionalizations. Hence, a series of N-
protected tryptamine derivatives were initially subjected to the
action of 9. All substrates tested, regardless of the nature of the
N-protecting group, smoothly delivered the corresponding
tricyclic pyrroloindolines in good chemical yields 46-55 (Scheme
4). The length of the tether connecting the olefin and amino
functionalities explains that only the diasteromer derived from
the anti-cyanoamination is observed. The pyrroloindoline core is
found in a number of alkaloids,[ 26 ] and has classically been
synthesized by treatment of N-protected tryptophan esters with
electrophilic reagents such as halonium, selenonium or even
sulfonium ions.[ 27 ] Promotion of this kind of cyclization by
electrophilic cyano moieties is to the best of our knowledge
Scheme 4. Reaction scope of the cyano-cyclisation of triptamine and
triptophol derivatives. Reagents, conditions: a) 9 (1.5 equiv.), r.t., CH3CN, 2h,
unless otherwise stated. aCH2Cl2 was used as solvent. Molecular structures of
compounds 47 and 59 in the solid state. Anisotropic displacement shown at
50% probability level. Only selected hydrogen atoms are shown.[24]
Finally, having established conditions for the effective
cyanation of 2,3-disubstituted indoles towards cyano-substituted
indolenines 43 and 45, we evaluated the possible involvement of
these substrates into
a
subsequent [4+2] Povarov-type
cyclization. Such cascade process is not easy because it
requires the consecutive dearomatization of both rings of the
original indole; however, a couple single precedents found in the
literature for cousin structures indicated that the transformation
This article is protected by copyright. All rights reserved.

10.1002/anie.201904557
Angewandte Chemie International Edition
COMMUNICATION
might be possible.[ 28 ] Hence, allyl substituted indoles were
prepared and submitted to reaction with 9. To our delight, the
desired products 63-68 containing a pentacyclic skeleton were
smoothly delivered with excellent diasteroselectivities (Scheme
5a). Note that despite four consecutive chiral centres being
formed, three of them on quaternary carbon atoms, only the
diasteromer shown is formed. The slightly lower chemical yield
obtained for 64 is explained by the concurrent direct cyanation at
position 2- of the indole core. The depicted transformation also
takes place intermolecularly; in that case, liberated from the
constrains exerted by the malonate tether, the incoming olefin
preferentially attacks the azadiene intermediate from its less
sterically hindered face, that is the one occupied by the cyano
substituent (Scheme 5b). This explains the reverse facial
selectivity observed in 69 and 70.
Experimental Section
Synthesis of 5-(cyano)dibenzothiophenium triflate (9): Tf2O (25 mmol,
1 equiv, 4.205 mL) was added dropwise within 5 minutes to a solution of
dibenzo[b,d]thiophene 5-oxide (1.00 equiv., 25 mmol, 5.007 g) in dry
dichloromethane (350 mL) at -50°C. After stirring the resulting mixture for
1 hour, TMSCN (25 mmol, 1 equiv, 3.353 mL) was added dropwise and
the mixture was further stirred at -50°C for 8 additional hours. Then, the
cooling system was removed, and the formed suspension allowed
reaching room temperature. Filtration of the solvents afforded 9 as a
white/beige solid, which was further washed with dichloromethane (2 x
50 mL), and finally dried under vacuum (5.39 g.; 60%).
Acknowledgements
Support from the European Research Council (ERC CoG
771295), the Deutsche Forschungsgemeinschaft (INST
186/1237-1) and the University of Göttingen is gratefully
acknowledged. We also thank B. Waldecker and F. Kraft for
preliminary experimental contributions towards the synthesis of
9 and Dr. M. John for assistance with NMR analysis.
a)
R2
R2
O2C
R2
CO2
CO2
CO2
CN
R2
H
R'
R'
a)
R
N
R
N
H
rac-(
63-68
)
Et
CO2
Et
CO2
Conflict of interest
Et
CO2
H
Et
H
CO2
MeO
CN
CN
A patent regarding reagent 9 and its synthetic applications has
been filed by the University of Göttingen (application number
DE102018211606.7).
H
N
Me
Et
N
64
, 67%
63
, 80%
X-ray structure of 64
R2
CO2
CO2
Et
CO2
CO2
CN
Me
, 81%
CO2
R2
H
Keywords: electrophilic cyanation • transfer reagents •
Et
H
Et
CO2
H
Me
sulfonium salts • metal-free functionalizations • umpolung
CN
CN
Ph
Me
N
N
2 = Me; 76%
2 = Et; 85%
N
66
67
, R
, R
68
65
, 78%
[1]
A. J. Fatiadi, Preparation and Synthetic Applications of Cyano
Compounds; 1983, Eds.: S. Patai, Z. Rappoport, Wiley-VCH, New York.
F. F. Fleming, Nat. Prod. Rep. 1999, 16, 597–606.
Ph
n
*
b)
[2]
[3]
NC
b)
Ph
F. F. Fleming, L. Yao, P. C. Ravikumar, L. Funk, B. C. Shook, J. Med.
Chem. 2010, 53, 7902-7917.
44
n
Me
N
Me
[4]
[5]
P. Pollack, Fine Chemicals: The industry and the Buisness; 2007, John
Wiley & Sons, Hoboken, New Jersey.
69
70
; n = 0; 89%
; n = 1; 87% (*d.r.= 8:1)
70
X-ray structure of
S. T. Huang, Y. C. Hsu, Y. S. Yen, H. H. Chou, J. T. Lin, C. W. Chang,
C. P. Hsu, C. T., D. J. Yin, J. Phys. Chem. C, 2008, 112, 19739–19747.
E. N. Zil'berman, Russ. Chem. Rev. 1986, 55, 39-48.
Scheme 5. Reaction scope of the electrophilic cyanation-Povarov cascade.
Reagents, conditions: a) 9 (1.0-1.5 equiv.), r.t., CH2Cl2, 3-36h; b) 9 (1.5 equiv.),
r.t., CH2Cl2, 11-36h. aDiasteromeric mixture (8:1 ratio); the second diasteromer
only differs in the configuration of the carbon marked (*). Molecular structures
of compounds 64 and 70 in the solid state. Anisotropic displacement shown at
50% probability level. Only selected hydrogen atoms are shown.[24]
[6]
[7]
For recent reviews see: a) G. Yan, Y. Zhang, J. Wang, Adv. Synth.
Catal. 2017, 357, 4068-4105; b)
[8]
a) J. Zanon, A. Klapars, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125,
2890–2891; b) J. Ramnauth, N. Bhardwaj, P. Renton, S. Rakhit, S. P.
Maddaford, Synlett 2003, 14, 2237–2239; a) M. Sundermeier, A. Zapf,
M. Beller, Angew .Chem. Int. Ed. 2003, 42, 1661–1664; c) M.
Sundermeier, S. Mutyala, A. Zapf, A. Spannenberg, M. Beller, J.
Organomet. Chem. 2003, 684, 50–55; d) R. Chidambaram,
Tetrahedron Lett. 2004, 45, 1441–1444; e) T. Schareina, A. Zapf, M.
Beller, Chem. Commun. 2004,1388–1389; f) S. A. Weissman, D.
Zewge, C. Chen, J. Org. Chem. 2005, 70, 1508–1510; g) T. Schareina,
A. Zapf, M. Beller, Tetrahedron Lett. 2005, 46, 2585-2588; h) H.-J.
Cristau, A. Ouali, J.-F. Spindler, M. Taillefer, Chem. Eur. J. 2005, 11,
2483–2492; i) J. M. Veauthier, C. N. Carlson, G. E. Collis, J. L.
Kiplinger, K. D. John, Synthesis 2005, 16, 2683–2686; j) R. S. Jensen,
A. S. Gajare, K. Toyota, M. Yoshifuj, F. Ozawa, Tetrahedron Lett. 2005,
46, 8645–8647; k) O. Grossman, D. Gelman, Org. Lett. 2006, 8,1189–
In summary, in 5-(cyano)dibenzothiophenium triflate 9,
whose synthesis is described along this paper, the umpolung of
the cyano moiety is so efficient that this moiety can not only be
transferred to typical organic nucleophiles, but also is capable to
promote electrophilic cyanocyclization cascades in appropriately
designed substrates. The development of asymmetric versions
of the reaction sequences herein described, and the applications
of structurally related sulfonium salts in other chemical
transformations are currently under investigation in our
laboratory.
This article is protected by copyright. All rights reserved.

10.1002/anie.201904557
Angewandte Chemie International Edition
COMMUNICATION
1191; l) T. Schareina, A. Zapf, W. Mägerlein, N. Müller, M. Beller,
Tetrahedron Lett. 2007, 48, 1087–1090; m) Y.-Z. Zhu, C. Cai, Eur. J.
Org. Chem. 2007, 2401–2404; n) F. G. Buono, R. Chidambaram, R. H.
Mueller, R. E. Waltermire, Org. Lett. 2008, 10, 5325–5328; o) X. Jia, D.
Yang, S. Zhang, J. Cheng, Org. Lett. 2009, 11, 4716–4719; p) G.Yan,
C. Kuang, Y. Zhang, J. Wang, Org. Lett. 2010, 12, 1052-1055; q) A. V.
Ushkov ,V. V. Grushin, J. Am. Chem. Soc. 2011, 133, 10999–11005; r)
T. Schareina, A. Zapf, A. Cotté, M. Gotta, M. Beller, Adv. Synth. Catal.
2011, 353, 777–780; s) P. Y. Yeung, C. M. So, C. P. Lau, F. Y. Kwong,
Org. Lett. 2011, 13, 648–651; t) J. Chen, Y. Sun, B. Liu, D. Liu, J.
Cheng, Chem. Commun. 2012, 48, 449–451;.
8, 1790-1800; c) N. Declas, F. Le Vaillant, J. Waser, Org. Lett. 2019, 21,
524-528.
[17] X. Wang, A. Studer, Angew. Chem. Int. Ed. 2018, 57, 11792-11796.
[18] a) G. Talavera, J. Peña, M. Alcarazo, J. Am. Chem. Soc. 2015, 137,
8704-8707; b) A. G. Barrado, A. Zieliński, R. Goddard, M. Alcarazo,
Angew. Chem. Int. Ed. 2017, 56, 13401-13405.
[19] D. J. Tantillo, Chem. Soc. Rev., 2010, 39, 2847–2854.
[20] C. N. Ungarean, E. H. Southgate, D. Sarlah, Org. Biomol. Chem.
2016,14, 5454-5467.
[21] The electrophilic C-H cyanation of alkenes employing an in situ
generated polyfluorinated I(III) reagent has been recently reported, see
ref. 17.
[9]
a) T. Sandmeyer, Ber. Dtsch. Chem. Ges. 1884, 17,1633-1635; b) T.
Sandmeyer, Ber. Dtsch. Chem. Ges. 1884, 17, 2650–2653; c) T.
Sandmeyer, Ber. Dtsch. Chem. Ges. 1885, 18,1492–1496; d) T.
Sandmeyer, Ber. Dtsch. Chem. Ges. 1885, 18, 1946–1948.
[22] For other transfer reagents based on the dibenzothiophene unit: a) T.
Umemoto, S. Ishihara, J. Am. Chem. Soc. 1993, 115, 2156-2164; b) B.
Waldecker, F. Kraft, C. Golz, M. Alcarazo, Angew. Chem. Int. Ed. 2018,
57, 12538-12542.
[10] K. W. Rosenmund, E. Struck, Ber. Dtsch. Chem. Ges. 1919, 52, 1749-
1756.
[23] R. Frei, T. Courant, M. D. Wodrich, J. Waser, Chem. Eur. J. 2015, 21,
2662-2668.
[11] Z. Wang, Comprehensive Organic Name Reactions and Reagents;
2010, John Wiley & Sons Inc. pp 1661-1663.
[24] CCDC 1904769-1904778 and 1907655-1907657 contain the
supplementary crystallographic data for this paper. These data are
provided free of charge by The Cambridge Crystallographic Data
Centre.
[12] a) J. Kim, J. H. Kim, S. Chang, Angew. Chem., Int. Ed., 2012, 51,
11948-11959; b) J. Schörgenhumer, M. Waser, Org. Chem. Front. 2016,
3, 1535-1540; c) A. M. Nauth, T. Opatz, Org. Biomol. Chem. 2018, 17,
11-23.
[25] Noteworthy, the nitrile formation takes place for these more challenging
substrates without the necessity of activation of the cyanation reagent
with a Lewis acid catalyst.
[13] C. R. Noller, Lehrbuch der Organischen Chemie, 2013 Springer-Verlag.
[14] a) T. V. Hughes, S. D. Hammond, and M. P. Cava, J. Org. Chem. 1998,
63, 401-402; b) Y. Q. Wu, D. C. Limburg, D. E. Wilkinson, G. S.
Hamilton, Org. Lett. 2000, 2, 795-797; c) P. Anbarasan, H. Neumann,
M. Beller, Chem. Eur. J. 2010, 16, 4725-4728; d) P. Anbarasan, H.
Neumann, M. Beller, Chem. Eur. J. 2011, 17, 4217-4222; e) R. Akula, Y.
Xiong, H. Ibrahim, RSC Adv. 2013, 3, 10731-10735; f) J. Cui, J. Song,
Q. Liu, H. Liu, Y. Dong, Chem. Asian J. 2018, 13, 482-495.
[26] D. Crich, A. Banerjee, Acc. Chem. Res. 2007, 40, 151-161.
[27] Selected references: a) S. P. Marsden, K. M. Depew, S. J. Danishefsky,
J. Am. Chem. Soc. 1994, 116, 11143-11144; b) C. Silva-López, C.
Pérez-Balado, P. Rodríguez-Graña, A. R. de Lera, Org. Lett. 2008, 10,
77-80; c) M. Tayu, Y. Hui, S. Takeda, K. Higuchi, N. Saito, T. Kawasaki,
Org. Lett. 2017, 19, 76582-6585; d) X. Jiang, W. Zhu, L. Yang, Z.
Zheng, C. Yu, Eur. J. Org. Chem. 2019, 2268-2274.
[15] V. V. Zhdankin, C. J. Kuehl, A. P. Krasutsky, J. T. Bolz, B. Mismash, J.
K. Woodward, A. J. Simonsen, Tetrahedron Lett. 1995, 36, 7975-7978.
[16] a) R. Frei, T. Courant, M. D. Wodrich, J. Waser, Chem. Eur. J. 2005, 21,
2662-2668; b) F. Le Vaillant, M. D. Wodrich, J. Waser, Chem. Sci. 2017,
[28] a) J. Hájíček, J. Trojánek, Tetrahedron Lett. 1981, 22, 1823-1826; b) M.
Šoral, J. Markus, J. Doháňošová, S. Šoralová, D. Dvoranová, A. Chyba,
J. Moncol, D. Berkeš, T. Liptaj, J. Mol. Struct. 2017, 1128, 230-238.
This article is protected by copyright. All rights reserved.

10.1002/anie.201904557
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
NC
Xiangdong Li, Christopher Golz, Manuel
Alcarazo*
Nu
R'
5-(Cyano)dibenzothiophenium
Triflate: A Sulfur–Based Reagent for
Electrophilic Cyanation and
Cyanocyclizations
N
R'
N
R
S
CN
R
Nu:
16 examples
Nu CN
Et
CO2
CO2
CN
27 examples
TfO
Et
H
R'
R
N
8 examples
Perfidious to its nature: The synthesis of 5-(cyano)dibenzothiophenium triflate is reported. In this compound the umpolung of the
cyano moiety is so efficient that this group can not only be transferred to typical organic nucleophiles, but it is also capable to initiate
cationic cyanocyclization cascades in appropriately designed substrates.
This article is protected by copyright. All rights reserved.