Regio- and Stereoselective Chlorocyanation of Alkynes

Article abstract of DOI:10.1002/anie.201705851

A variety of terminal and internal alkynes were converted regio- and stereoselectively into (Z)-3-chloroacrylonitriles by treatment with BCl₃ in the presence of stoichiometric amounts of imidazolium thiocyanates. These products could be readily functionalized to provide useful building blocks, thus demonstrating the synthetic value of the method. Preliminary mechanistic studies suggest initial activation of the cationic thiocyanate by the Lewis acid, followed by electrophilic attack of the alkyne. The syn addition of a chloride to the vinyl cation intermediate and final elimination of the thiourea unit afford the desired chloroacrylonitriles.

Full text of DOI:10.1002/anie.201705851

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: Regio- and Stereoselective Chlorocyanation of Alkynes
Authors: Manuel Alcarazo, Alejandro G Barrado, Richard Goddard,
and Adam Zielinski
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.201705851
Angew. Chem. 10.1002/ange.201705851
Link to VoR: http://dx.doi.org/10.1002/anie.201705851
http://dx.doi.org/10.1002/ange.201705851

Angewandte Chemie International Edition
10.1002/anie.201705851
COMMUNICATION
Regio- and Stereoselective Chlorocyanation of Alkynes
[a]
[a]
[b]
[a],
Alejandro G. Barrado, Adam Zieliński, Richard Goddard and Manuel Alcarazo *
Abstract: The regio- and stereoselective conversion of alkynes into
Z)-3-chloroacrylonitriles was achieved by treatment of a variety of
terminal as well as internal alkynes with BCl in the presence of
been achieved in moderate to good yields. Note however, that
(
the number of electrophilic reagents able to perform this
transformation, as well as their substrate scope, remains quite
limited. In fact, to proceed satisfactorily these routes require the
3
stoichiometric amounts of imidazolium thiocyanates. These products
can be easily functionalized into useful building blocks,
demonstrating the synthetic value of the method. Preliminary
mechanistic studies suggest initial activation of the cationic
thiocyanate by the Lewis acid followed by electrophilic attack of the
alkyne. syn-Addition of a chloride to the vinyl cation intermediate and
final elimination of the thiourea unit afford the desired
chloroacrylonitriles.
+
[13]
use of unpleasant cyanogen halides as CN precursors.
Late transition metal catalysed
a)
cyanofunctionalization
X
R1
CN
R2
X
CN
CN
CN
1
R
X = Ar,
SiMe3, SR,
SnR , BR
M
M
X
M
X
M
R2
R2
R1
A
C
3
2
B
NC
R2
Acrylonitrile is a key monomer for the manufacture of plastics,
rubbers and fibres, and substituted acrylonitriles are highly
valuable precursors for the synthesis of fine chemicals in
b) Direct cyanofunctionalization
X
R1
1
R2
LA
[
1]
X
CN
R
X
E
pharmaceutical and agrochemical industry. This justifies the
enormous attention that has been paid to reactions involved in
the preparation, functionalization and transformation of
X = Br
δ
+
δ
−
CN
R1
LA
X
CN LA
R2
D
[
2]
acrylonitrile and its derivatives. Among the methods known to
gain acrylonitrile derivatives depicting well-defined substitution
patterns, those based on the stereoselective cyano-
functionalization of alkynes using X-CN type reagents are
especially useful since two functionalities, the cyano and a
This work
S
1
CN
iPr
NC
BCl3
R
2
R1
R2
iPr
N
N
Cl
R1 = Ar
R2 = H, Ar, Alkyl, SR
SbF6
Me
R1
regio- and
stereoselective
Me
second
group
X
(which may be amenable to further
transformation) are simultaneously installed in vicinal positions
with ideal atom efficiency. This approach can be materialized in
two different ways. In the majority of the cases an electron-rich
late transition metal catalyst cleaves the X-CN bond forming
intermediate A (Scheme 1a). This is followed by migratory
insertion of the alkyne into the M-X bond B→C, and reductive
elimination of the desired acrylonitrile from C. Transformations
that are reported to follow this general mechanistic scheme
Scheme 1. Synthesis of substituted acrylonitriles from alkynes.
In the course of our investigation aimed at the development
of new electrophilic reagents of synthetic interest, we recently
demonstrated that imidazolium thiocyanates such as 1 act as
+
efficient and easy to handle [CN] synthons for the metal-free
[
3]
[4,5]
[6]
cyanation of non-prefunctionalized (hetero)aromatics, activated
include hydrocyanations, carbocyanation,
cyanosilylation,
[
14, 15]
[
7]
[8]
[9]
methylenes, thiols and amines.
Hence, we reasoned that if
thiocyanation, cyanostannations and cyanoborations. Most
of the products thus obtained can be subsequently modified
employing, for example, well-established coupling chemistry.
Much less attention has been paid to a complementary
route: the synthesis of substituted acrylonitriles exploiting the
inherent nucleophilicity of alkynes. In analogy to the well-
this inherent electrophilicity could be further enhanced, for
example by Lewis acid activation, then the scope of 1 as
electrophilic cyanating reagent might be further extended to
intrinsically less reactive substrates such as alkynes. Note, that
to materialize this hypothesis a nucleophile compatible with the
Lewis acid needs to be present in the reaction mixture in order
to trap the transient vinyl cation E formed after attack of the
electrophilic cyanating reagent. For this reason, we envisioned
that metal halides would be appropriate promoters for such
reaction: they possess well-known Lewis acid character and
simultaneously could behave as latent source of halogenides.
Herein, we report the realization of such a transformation using
[
10 ]
documented addition of acids,
derivatives,
halogens or halogen
[
11,12]
+
reaction of alkynes with suitable CN synthons
D generates highly electrophilic vinyl species E, which after
trapping by an appropriate nucleophile, renders the desired
functionalized acrylonitriles (Scheme 1b). Making use of this
approach, the halocyanation of (mainly terminal) alkynes has
3
BCl as an efficient promoter. The new chlorocyanation protocol
is operationally simple, works with a variety of terminal as well
as internal alkynes, and offers an exquisite route to fully
substituted (Z)-3-chloroacrylonitriles in good yields and excellent
regio- and stereoselectivities.
[
a]
b]
A. G. Barrado, A. Zieliński, Prof. Dr. M. Alcarazo
Institut für Organische und Biomolekulare Chemie
Georg-August-Universität Göttingen
Tammannstr 2, 37077-Göttingen, Germany
E-mail: malcara@gwdg.de
[
Dr. R. Goddard
Initially, we tested the reaction of alkyne 2a with
thioimidazolium salt 1 in the presence of a range of Lewis acids
Max-Planck-Institut für Kohlenforschung
Kaiser Wilhelm Platz 1, 45470-Mülheim an der Ruhr, Germany
such as FeCl
observed in any case with exception of TiCl
provide the desired product 4a, albeit with a poor 14% yield
3
, TiCl
4
, AlCl
3
and BF
3
·OEt
2
. No reaction was
Supporting information for this article is given via a link at the end of
the document.
4
, which was able to
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705851
COMMUNICATION
(
Table 1, Entries 1-4). Interestingly, when B(C
5
F
6
)
3
was
S
CN
iPr
R1
employed to activate 1, the product of thiocyanation 5 was
obtained in high yield as a 80:20 Z-, E-mixture (Table 1, Entry 5).
This superior performance of B(C
Cl
CN
iPr
BCl3
N
N
(2 equiv.)
R2
SbF6
1,2-DCE, 1h.
R
1
R
2
5
F
6
)
3
made us speculate that
Me
Me
BCl or BBr might promote the desired cynation event and avoid
3
3
2a-x
Cl
1
4a-x
the undesired incorporation of the thiourea moiety to the product
by providing nucleophilic halogenides to the medium. The
product of bromocyanation 6 was unfortunately obtained in very
low yield (Table 1, Entry 6); however, the chlorocyanation
reaction was much more efficient and to our delight it proceeded
with complete stereo- and regioselectivities (Table 1, Entry 7).
CN
Cl
CN
MeO
MeO
R
4
4
4
4
a; R = H, 98%
b; R = Me, 82%
c; R = F, 76% (99:1)
d; R = Cl, 98%
4e; R = Br, 79%
f; R = I, 67% (93:7)
4g; R = NO , 46%
b
Further optimization of the conditions (BCl
3
, 2 equiv., r.t.)
4i; 92%
X-ray of
Cl
4
e
(98:2)
a
allowed the complete conversion of 2a into 4a and the isolation
of this product with excellent yield (Table 1, Entry 9).
(94:6a)
CN
Cl
CN
a
a
(
98:2)
Table 1. Reaction optimization.
(
98:2)
a
4
MeO
a,c
S
CN
iPr
Cl
CN
2
(96:4)
Me
Et
Me
a,c
4j
; 50% (91:9)b
b
4
h; R = CO Et, 36%
4k; 70%
2
(95:5)
(50:50)
iPr
Lewis Acid
N
N
Cl
CN
SbF6
Me
1,2-DCE, 3h.
Cl
CN
Me
2
a
1
MeO
Temp. °C
4a
S
Ph
Lewis Acid
[
a]
Entry
Equiv.
1.0
Yield
N
4
l; 56%
X-ray of 4l
Me
m; 15%
[
b]
1
2
3
4
5
6
7
8
9
FeCl
TiCl
BF ·OEt
AlCl
B(C
BBr
3
50
50
50
50
50
50
50
r.t.
r.t.
n.r.
a
4
(93:7)
Cl CN
Cl
CN
Cl
CN
1.0
14%
n.r.
Cl
CN
4
R
3
2
1.0
4n; R = Et, 65%c
Cl
3
1.0
traces
90% of 5
9% of 6
37%
o; R = Pr, 71%c
4q; 76%
4r; 80%
4s; 62%
4
[
c]
6
F
5
)
3
1.0
=
4
p; R
Bn, 63%
Cl CN
Cl
CN
Cl
CN
Cl
CN
3
1.0
Bu
H
H
S
BCl
BCl
BCl
3
1.0
3
1.5
65%
Me Si
4t; 57%
4u; 82%
CN
4v; 59%
Cl
4w; 46%
3
3
2.0
97%
Cl
iPr
iPr
Me
Me
N
N
[a] Yields are of isolated
products; [b] no
reaction; [c] Obtained as
a 80:20 mixture of the
Me
S
S
CN
Br
CN
4
x; 62%
X-ray of
4x
SbF6
MeO
Z:E
respectively.
isomers
5
MeO
6
Figure 1. Substrate Scope of Alkyne Chlorocyanation. Reaction conditions: 2
0.5 mmol, 1.0 equiv.), 1 (0.6 mmol, 1.3 equiv.), BCl (1.0 M in DCM; 1.0 mmol,
equiv.), 1,2-DCE (1 mL), rt, 1h.; yields are of isolated products; [a] Z:E ratios
determined by H-NMR; only the Z-alkene is detected in all other cases; [b]
Obtained as mixtures of regioisomers, but only Z-isomers; [c] Reaction
conducted at 60 °C during 3h.
(
2
3
Having identified the optimal conditions, the scope and
1
limitations of the transformation were explored. Terminal as well
as internal alkynes are suitable substrates and afford the desired
chloroacrylonitriles in moderate to excellent yields (Figure 1).
This includes 1,2-diaryl alkynes, which are reluctant to
participate in similar transformations.
different steric demand (4n-u), halogens (4c-f,s), silyl groups
4t), heterocycles (4l,m,u), as well as thioether substituents (4x)
were also tolerated. The practicability of the reaction is also
demonstrated through the gram scale synthesis of 4a.
Unfortunately, 1,2-dialkyl alkynes did not react under the
[
12]
Aliphatic groups of
The stereo- and regioselectivity observed are remarkable.
The cyanide group is exclusively incorporated at the
unsubstituted carbon in terminal alkynes, or at the alkyl-
substituted one in 1-aryl-2-alkyl alkynes (4n-w), following a
regioselectivity that is typical for an electrophilic mechanism. In
both cases only the Z-isomer is formed, suggesting a syn-
(
conditions developed; this still remains a limitation of the method. addition pathway for the reaction. When 1,2-bisarylalkynes are
employed as substrates, again excellent Z-stereoselectivities are
observed (4a-i); however, mixtures of regioisomers appear in
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705851
COMMUNICATION
detectable amounts when both aromatic rings are electronically
very similar (4j,k). It worth noting that slow isomerization of all
original Z-products to the E-isomers takes place in solution until
alkyne 2a-x and concomitant generation of vinyl cation B. syn-
Transfer of one chloride from boron to the carbocationic center
affords iminoborane C, which generates the desired
chlorocyanated products 4a-x by elimination of the imidazolium-
[
16,17]
the thermodynamic equilibrium is achieved.
[
21]
thioborane fragment D.
into disulfide 10.
Finally, a redox process transforms D
To learn more about the mechanism governing the
chlorocyanation reaction, a series of control experiments were
performed (Scheme 2). We first turned our attention to the
recently reported cyclization of 2i to the borylated benzofuran 7
[22]
A
Cl
CN
BCl (2 equiv.)
MeO
no reaction
3
[
18]
(
Scheme 2A).
The authors propose that alkyne activation by
is followed by nucleophilic attack of the oxygen atom and
is added to
1
(
1.2 equiv.)
BCl
3
1 (1.2 equiv.)
no borane
1
,2-DCE, rt, 1h.
formation of chloromethane. Interestingly, when BCl
3
4i; 92%
OMe
Ph
a mixture of 1 and 2i, the only product detected is the one of
chlorocyanation 4i. Moreover, if 1 is added to solutions of 7
generated in situ, no cyanation is observed. Hence, 4i is not
O
1
BCl (1 equiv.)
(1.2 equiv.)
1 h.
3
no
reaction
Ph
likely to be formed by addition of Cl
BCl /CN displacement. We also conclude from this experiment
that BCl preferentially activates 1 (and not the alkyne). This is
2
B-Cl to 2a, followed by
1,2-DCE, rt, 1h.
2i
BCl2
ref. 18
7
2
3
B
iPr
additionally supported by the isolation of the Lewis adduct 8 in
crystalline form by cooling to -80 °C an equimolar solution of 1
S
N
6F5
3
equiv.)
B(C
)
(1
Me
N
[
19]
6F5
8
1
N
B(C
)
3
6 5 3
and B(C F ) (Scheme 2B and the Supporting Information).
CH Cl2
iPr
2
Me
SbF6
Also very informative is the formation of cyanated
phenanthrene 9 when the biphenyl decorated substrate 2y is
made react with a solution of in situ prepared 8 (Scheme 2C). In
this case, the electrophilic cyanation and subsequent cyclisation
takes place without the participation of any chloride, excluding
cyanogen chloride as the actual cyanating reagent. Product 9 is
also obtained when BCl is used as promotor, indicating that
3
intramolecular trapping of the vinyl cation intermediate by the
hanging phenyl ring is faster than the attack of the chloride.
(X-ray)
C
6F5
equiv.)
B(C
)
3
(1
OMe
55%
OMe
1
(1.2
equiv.)
1,2-DCE, rt, 1h.
CN
BCl3
(1 equiv.)
3%
2y
5
9
iPr
S
(
X-ray)
Me
Me
D
iPr
We also analyzed the very insoluble orange powder that is
N
+
1
13
(2
BCl3 equiv.)
N
S
formed during the chlorocyanation reaction,10. H and C NMR
spectra pointed to the formation of a bis(imidazolium)disulphide,
presumably formed by oxidation of the thiourea byproduct.
However, the key information could only be obtained from X-ray
diffraction (See Scheme 2D and the Supporting Information).
Me
Me
2a
4a
N
1
(1.3 equiv.)
N
iPr
SbCl4
SbF6
1
,2-DCE, rt, 1h.
iPr
10
(
X-ray)
E
This analysis indicated that one of the two counteranions of 10
iPr
BF
3
2
SbCl6
-
S
N
N
corresponds to a tetrachloroantimonate [SbCl
4
] unit. Hence, the
N
H
BCl3 (1 equiv.)
Me
iPr
hexafluoroantimonate anions from 1 do not remain innocent;
they participate in fluoride/chloride exchange with BCl and act
as oxidants transforming the urea side-product into disulphide
1
Cl
S
N
N
CH Cl2
iPr
2
Me
Me
3
Me
N
iPr
11
(
X-ray)
10. This additionally hinders the adventitious formation of 5.
Cl
X
Cl/F
B
Intrigued by this result we cooled to -80 °C the complex
F
R1
1
BCl3
N
4a-x
D
mixture formed after mixing
1
and BCl
3
obtaining some
C
Cl/F
colourless plates, which were analysed by X-ray diffraction (See
Scheme 2E and the Supporting Information). Although by no
mean representative of the reaction bulk, the dimeric structure of
R2
+
SIm
C
+
SIm
B
syn-addition
−
δ
+
δ
F/Cl
Cl/F
F/Cl
1
1 well serves to illustrate the different processes involved in the
+
CN BCl3-n
F
n
=
R1
Cl/F
ImS
S
A
Cl
B
SbCl6-n
F
n
chlorocyanation reaction; namely, halogen exchange between
-
iPr
iPr
N
N
N
BCl
3
and [SbF
6
] , activation of 1 by Lewis acids, and addition of
C
X
R2
SIm
+
10
chloride to electrophilic carbon centres.
Me
Me
B
R1
R2
X
[
20 ]
On the basis of literature precedents
and our own
2a-x
Regioselective
investigation, we preliminarily propose the following mechanism
for the chlorocyanation reaction (Scheme 2F). First, activation of
the cyanating reagent 1 takes place by formation of Lewis
adduct A, which could be already partially fluorinated at boron.
This is followed by regioselective attack of the corresponding
Scheme 2. Control experiments and proposed mechanism.
Willing to underscore the synthetic utility of the method, we
tested the expedite conversion of the chloroacrylonitriles
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705851
COMMUNICATION
prepared into more complex products using 4a as model
substrate. Suzuki coupling with aryl boronic acids affords the
corresponding triaryl substituted acrylonitriles 12 and 13 with
Encyclopedia of Polymer Science and Technology, H. F. Mark, John
rd
Wiley & Sons, Inc. 2007, 3 Ed.
[
23]
high stereocontrol.
Not less interesting is the reaction of 4a
[2]
(a)Three Carbon-Heteroatom Bonds: Nitriles, Isocyanides, and
Derivatives, Murahashi, S., Ed.; Science of Synthesis; Georg Thieme
Verlag, Sttutgart, 2004; Vol 19; (b) Industrial Organic Chemistry, H. J.
with hydrazine to produce pyrazole 14, which could be further
transformed into the corresponding pyrazolo[1,5-a]pyrimidine
th
Arpe, Wiley-VCH, Weinheim. 2010, 5 Ed.
1
5 by condensation with acetylacetone. A similar synthetic
[3]
Hydrocyanation of alkynes and alkenes, T. V. Rajanbabu, Organic
Reactions, Inc. 2011, Vol. 75.
[
24]
procedure renders thiophene 16 in only two steps.
H N
Ph
[4]
For selected references see: (a) Y. Nakao, S. Oda, T. Hiyama, J. Am.
Chem. Soc. 2004, 126, 13904-13905; (b) Y. Nakao, T. Yukawa, Y.
Hirata, S. Oda, J. Satoh, T. Hiyama, J. Am. Chem. Soc. 2006, 128,
7116-7117; (c) Y. Nakao, A. Yada, S. Ebata, T. Hiyama, J. Am. Chem.
Soc. 2007, 129, 2428-2429; (d) S. Arai, T. Sato, Y. Koike, M. Hayashi,
A. Nishida, Angew. Chem. Int. Ed. 2009, 48, 4528-4531; (e) Y. Hirata,;
A.Yada, E. Morita, Y. Nakao, T. Hiyama, M. Ohashi, S. Ogoshi, J. Am.
Chem. Soc. 2010, 132, 10070-10077.
2
MeO
F
N
N
H
OMe
a)
c)
Ph
CN
12
14
d)
Me
N
Ph
4a
[5]
For reviews in carbocyanation see: (a) Y. Nakao, T. Hiyama, Pure Appl.
Chem. 2008, 80, 1097-1107; (b) M. Tobisu, N. Chatani, Chem. Soc.
Rev. 2008, 37, 300-307; (c) C. Nájera, J. Sansano, Angew. Chem. Int.
Ed. 2009, 48, 2452-2456; (d) S. M. Bonesi, M. Fagnoni, Chem. Eur. J.
N
N
Me
OMe
15
of 12)
b)
e)
(
X-ray
2010, 16, 13572-13589; (e) M. Murakami, T. Matsuda, Chem. Commun.
MeO
O
2011, 47, 1100-1105; (f) L. Souillart, N. Cramer, Chem. Rev. 2015, 115,
9410-9464.
CN
S
MeO
[6]
(a) N. Chatani, T. Hanafusa, J. Chem. Soc. Chem. Commun. 1985,
838-839; (b) N. Chatani, N. Horiuchi, T. Hanafusa, J. Org. Chem. 1990,
Ph
CN
NH2
13
16
Ph
55, 3393-3395; (c) M. Suginome, H. Kinugasa, Y. Ito, Tetrahedron Lett.
1
994, 35, 8635-8638.
Scheme 3. Further transformations of 4a. Reaction conditions: a) p-(F)C
B(OH) (1.0 equiv.), Pd (dba) (5 mol%), (tBu) P (20 mol%), THF:H O (9:1),
0 °C, 92%, Z:E = 30:1; b) 2-furylboronic acid (1.0 equiv.), Pd (dba) (5
mol%), (tBu) P (20 mol%), THF:H O (9:1), 60 °C, 68%, Z:E = 12:1); c) NH
NH , EtOH reflux, 12h, 90%; d) acetylacetone (3.0 equiv.), piperidine (2
equiv), EtOH, 85°C, 80 min., 81%; e) Na S·9H O, DMF, 50 min. and then,
ClCH CN (1 equiv.), NaOEt (1 equiv.) 23%.
6 4
H
[
7]
8]
(a) I. Kamiya, J. Kawakami, S. Yano, A. Nomoto, A. Ogawa,
Organometallics 2006, 25, 3562-3564; (b) Y. T. Lee, S. Y. Choi, Y. K.
Chung, Tetrahedron Lett. 2007, 48, 5673-5677.
2
2
3
3
2
6
2
3
3
2
2
-
[
Y. Obora, A. S. Baleta, M. Tokunaga, Y. Tsuji, J. Organomet. Chem.
2
2
002, 660, 173-177.
(a) M. Suginome, A. Yamamoto, M. Murakami, J. Am. Chem. Soc. 2003,
25, 6358-6359; (b) M. Suginome, A. Yamamoto, M. Murakami, Angew.
2
2
[9]
2
1
Chem. Int. Ed. 2005, 44, 2380-2382; (c) A. Yamamoto, Y. Ikeda, M.
Suginome , Tetrahedron Lett. 2009, 50, 3168-3170.
In conclusion, we disclose here the use of 1/BCl
for the chlorocyanation of alkynes, thereby providing
straightforward access to synthetically useful
chloroacrylonitriles of very different substitution patterns.
Reactions proceed at room temperature, are scalable and
occur with excellent regio- and stereoselectivities. The
extension of the newly developed method to other substrates is
currently under investigation in our research group.
3
mixtures
[
[
[
10] (a) March’s Advanced Organic Chemistry; M. B. Smith, J. March, Wiley
a
3-
Interscience, 2001; (b) Vinyl cations; P. J. Stang, Z. Rappoport, M.
Hanack, L. R. Subramanian, Academic Press: NY, 1979.
11] (a) T. M. Kasumov, N. S. Pirguliyev, V. K. Brel, Y. K. Grishin, N. S.
Zefirov, P. J. Stang, Tetrahedron, 1997, 53, 13139-13148; (b) G. F.
Koser, L. Rebrovic, R. H. Wettach, J. Org. Chem. 1981, 46, 4324-4326.
12] The cyanotriflation of akynes has been recently reported employing a
I(III)-based electrophilic cyanating reagent. The authors proposed the
formation of a vinyl cation intermediate generated after two consecutive
Fe-catalyzed SET steps, see: X. Wang, A. Studer, J. Am. Chem. Soc.
2016, 138, 2977-2980.
[
13] (a) N. Sakata, K. Sasakura, G. Matsushita, K. Okamoto, K. Ohe, Org.
Lett. 2017, 19, 3422-3425; (b) M. Murai, R. Hatano, S. Kitabata, K .Ohe,
Chem. Commun. 2011, 47, 2375-2377; (c) N. V. Lukashev, A. V.
Kazantsev, A. A. Borisenko, I. P. Beletskaya, Tetrahedron, 2001, 57,
10309-10317; (d) P. Moreau, A. Commeyras, J. Chem. Soc. Chem.
Commun. 1985, 817-818.
Acknowledgements
Support from the DFG (AL 1348/7-1 and INST 186/1237-1) and
the DAAD (fellowship to A. Z.) is gratefully acknowledged. We
also thank M. Böhm and Dr. C. Golz for assistance in the
determination of the X-ray structures, N. Ostermann for the
preparation of compounds 2t, 4t and 4m and our NMR
department for support.
[
[
[
14] (a) G. Talavera, J. Peña, M. Alcarazo, J. Am. Chem. Soc. 2015, 137,
8704-8707; (b) A. J. Arduengo, E. M. Burgess, J. Am. Chem. Soc. 1977,
99, 2376-2378.
15] For the use of similar reagents as electrophilic thiocyanating reagents
see: J. Peña, G. Talavera, B. Waldecker, M. Alcarazo, Chem. Eur. J.
2017, 23, 75-78.
Keywords: Electrophilic cyanation • alkynes • nitriles •
16] The Z:E isomerization is faster for 4f-h. We assume that the
chlorocyanation takes place, as in the other cases, with excellent
stereoselectivity, but the Z:E ratios decrease because 4f-h already start
to isomerize during the reaction time.
chlorocyanation • stereoselectivity
[1]
(a) Ullmann’s Encyclopedia of Industrial Chemistry: Acrylonitrile, P.W.
Langvardt, vol 1, JohnWiley Sons Ltd, 2011, 365-372; (b)
&
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705851
COMMUNICATION
[
17] Comparison of the NMR spectra of both isomers after the isomerization
process additionally helped to establish the Z-configuration of the
primarily obtained products (See the supplementary Information).
18] A. J. Warner, A. Churn, J. S. McGough, M. J. Ingleson, Angew. Chem.
Int. Ed. 2017, 56, 354-358.
63897-63900; (e) M. Al-Talib, M. Zaki, S. Hehl, R. Stumpf, H. Fischer, J.
C. Jochims, Synthesis 1996, 1115-1121.
[21] The involvement of Sb species acting as Lewis acids and not only as
oxidants cannot be discard at this moment.
[
[
[22] For related oxidations see: a) R. H. Cragg, J. P. N. Husband, A. F.
Weston, Chem. Commun. 1970, 1701 b) T. Imamoto, E. Hirakawa, Y.
Yamanoi, T. Inoue, K. Yamaguchi, H. Seki, J. Org. Chem. 1995, 60,
7697-7700.
19] CCDC 1545693-1545697, 1567971 and 1567989 contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic data
centre via www.ccdc.cam.ac.uk/data_request/cif.
[23] J. Gilbert, J. F. Miquel, G. Precigoux, M. Hospital, J. P. Raynaud, F.
Michel, M. C. de Paulet, J. Med. Chem. 1983, 26, 693-699.
[24] (a) A. V. Bogolubsky, S. V. Ryabukhin, A. S. Plaskon, S. Stetsenko, D.
M. Volochnyuk, A. A. Tolmachev, J. Comb. Chem., 2008, 10, 858-862;
(b) Z. Brzozowski, J.Sławiński, F. Saczewski, T.Sánchez, N. Neamati,
Eur. J. Med. Chem. 2008, 43, 1188-1197; (c) P. K. Sharma, S. Ram, N.
Chandak, Adv. Synth. Cat. 2016, 358, 894-899.
[20] For selected examples of nucleophilic additions to activated nitriles see:
(a) A. Saito, Y. Kambara, T. Yagyu, K. Noguchi, A. Yoshimura, V. V.
Zhdankin, Adv. Synth. Cat. 2015, 357, 667-671; (b) B. Zhou, Y. Hu, C.
Wang, Angew. Chem. Int. Ed. 2015, 54, 13659-13663; (c) D. S. Bolotin,
M. Y. Demakova, A, S. Novikov, M. S. Avdontceva, M. L. Kuznetsov, N.
A. Bokach, V. Y. Kukushkin, Inorg. Chem. 2015, 54, 4039-4046; (d) X.
Cheng, S. Pei, C. Xue, K. Cao, L. Hai, Y. Wu, RSC Adv. 2014, 4,
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.201705851
COMMUNICATION
COMMUNICATION
The conversion of alkynes into Z-
A. G. Barrado, A. Zieliński, R.
(
3)-chloroacrylonitriles has been
Goddard and M. Alcarazo*
achieved employing imidazolium
thiocyanates as electrophilic
cyanating reagents.
Page No. – Page No.
Regio- and Stereoselective
Chlorocyanation of Alkynes
((Insert TOC Graphic here))
This article is protected by copyright. All rights reserved.