From 1,2-difunctionalisation to cyanide-transfer cascades-Pd-catalysed cyanosulfenylation of internal (oligo)alkynes

Article abstract of DOI:10.1039/c9sc04569d

Internal alkynes substituted by aliphatic or aromatic moieties or by heteroatoms were converted into sulphur-substituted acrylonitrile derivatives. Key is the use of Pd catalysis, which allows the addition of aromatic and aliphatic thiocyanates in an intra- A nd intermolecular manner. Substrates with several alkyne units underwent further carbopalladation steps after the initial thiopalladation step, thus generating in a cascade-like fashion an oligoene unit with sulphur at one terminus and the cyano group at the other.

Full text of DOI:10.1039/c9sc04569d

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DOI: 10.1039/C9SC04569D
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From 1,2-difunctionalisation to cyanide-transfer cascades –
Pd-catalysed cyanosulfenylation of internal (oligo)alkynes
a
a
b
a
Marcel Bürger, Maximilian N. Loch, Peter G. Jones and Daniel B. Werz*
Received 00th January 20xx,
Accepted 00th January 20xx
Internal alkynes substituted by aliphatic or aromatic moieties or by heteroatoms were converted into sulphur-substituted
acrylonitrile derivatives. Key is the use of Pd catalysis, which allows the addition of aromatic and aliphatic thiocyanates in an
intra- and intermolecular manner. Substrates with several alkyne units underwent further carbopalladation steps after the
initial thiopalladation step, thus generating in a cascade-like fashion an oligoene unit with sulphur at one terminus and the
cyano group at the other.
DOI: 10.1039/x0xx00000x
www.rsc.org/
these transformations the S-CN bond is broken and added
across the C-C triple bond, which is comparable to reactions
where O-CN or N-CN-bonds are activated to react with
Introduction
An important method of accessing tetrasubstituted double
1
6
alkenes. Later, we found that a similar Pd-catalysed process
allows the reaction with arynes, which contain highly reactive
formal triple bonds, leading to o-thiobenzonitriles (Scheme 1A,
1
bonds is the dual functionalisation of internal alkynes. In its
ideal and atom-economic way a substrate X-Y is attached to the
C-C triple bond in a completely regio- and diastereoselective
fashion. Depending on the type of substituents, either specially
designed reagents are required or transition-metal catalysts are
employed.2 As prime example for the first scenario a syn-
chlorocyanation using imidazolium thiocyanate in combination
1
7
right).
A) Previous work
-4
terminal alkynes
arynes
R'
[Pd], base
S
R
CN
2
a
3
with BCl was recently reported by Alcarazo et al. Morandi
[
Pd]
developed a Pd-catalysed intermolecular syn-aryliodination of
internal alkynes while Lautens and co-workers disclosed a
CN
CN
5
S
S
R
series of intramolecular reactions leading to syn- and anti-
R'
Ogawa (2006)
Werz (2015)
6
carbohalogenations of triple bonds. The key step of the latter
B) This work
internal alkynes
reaction is a carbopalladation of the C-C triple bond followed by
reductive elimination of the Pd to generate the carbon-halogen
bond. Such a step is rare and can only be triggered by specific
ligands.5 The more common scenario is further reaction in a
CN
R'
[Pd]
S
R
CN
R
R'
,6
S
XantPhos
R'
R'
7
carbopalladation cascade when other alkyne or alkene units
8
CN
CN
are present. In most cases a final elimination or cross-coupling
S
R
S
X
[
Pd]
reaction is employed to terminate the process. By such
X
R
Y
XantPhos or
SPhos
Y
9
protocols, structures of astonishing complexity such as
fenestranes,10 cyclooctatetraenes, helicenes, and several
natural products13 have been prepared from appropriately
designed starting materials in just one synthetic step. The
groups of Lautens, Cook and others have precisely designed
11
12
internal oligoynes
cascade of thiopalladation, carbopalladation, cyanide-transfer
R
CN
S
[Pd]
NC
S
X
1
4
X
intramolecular iodine-transfer reactions along these lines.
SPhos
X
0
,1
1,2
With other moieties such transfer reactions over several carbon
atoms have only rarely been investigated.
R
0,1
1
,2
X
X = O, CH2
Cyanosulfenylation reactions of terminal alkynes have been
developed to access sulphur-substituted acrylonitrile
derivatives starting from thiocyanates (Scheme 1A, left). In
Scheme 1 Inter- and intramolecular cyanosulfenylation reactions.
1
5
Thus, we were first interested in seeking conditions to
transform internal non-activated triple bonds to generate
tetrasubstituted alkenes with sulphur and cyano in 1,2-position
(Scheme 1B), and to determine whether this reaction might be
also the starting point for a longer cascade involving – besides
a. Technische Universität Braunschweig
Institute of Organic Chemistry
Hagenring 30, 38106 Braunschweig (Germany)
Technische Universität Braunschweig
b.
Institute of Inorganic and Analytical Chemistry
Hagenring 30, 38106 Braunschweig (Germany)
†
Electronic Supplementary Information (ESI) available: Experimental details and
This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2019, 00, 1-3 | 1
characterisation data. CCDC 1948156‒1948162 and 1969696-1969698. See
DOI: 10.1039/x0xx00000x
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the thiopalladation step – carbopalladation steps of additional tetrasubstituted olefin moiety. In these cases, the
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DOI: 10.1039/C9SC04569D
C-C triple bonds. The termination of the cascade was envisioned thioacrylonitrile moiety, as a strong push-pull-system, easily
1
9
as a reductive elimination of the Pd catalyst to form the C-CN stabilizes a zwitterionic structure. The positive charge is well
bond. Such an approach would lead to formal 1,4- and 1,6- stabilized at the sulphur and the negative charge next to the aryl
cyanosulfenylation reactions (Scheme 1B).
substituent. This formal single bond character allows rotation
leading to isomeric mixtures.
2
0
Results and Discussions
Furthermore, 2l (10%) and 2m (34%) were synthesised from two
alkenes as starting materials to demonstrate that also other
π-systems can be employed in our protocol. To address smaller
ring sizes the tether between the aromatic ring system and the
C-C triple bond was shortened to afford substituted
benzothiophene 2o as the result of a subsequent isomerisation
to the more stabilized aromatic system. A further shortening led
not to an isolable four-membered ring benzothiete, but to a 3-
cyano-substituted benzothiophene, as proved by X-ray
Optimisation of the reaction conditions
Initially, we explored the Pd-catalysed reaction of the aromatic
thiocyanate unit across the C-C triple bond in 1a. PdCl (PhCN) ,
2 2
1
8
tris(t-butyl)phosphine as ligand (derived from Fu’ s salt ) and
triethylamine in DMF at 100 °C generated the benzoxathiin 2a
in 4 h with 35% yield. Various other ligands gave no better
results. A breakthrough was achieved using XantPhos, which led
to an excellent yield of 93% (for full optimisation details, see
Supporting Information).
21
crystallography.
Seven- to nine-membered ring systems
Scope of aromatic thiocyanates
We varied the ring size also in the opposite direction by
increasing the tether length. In moderate to excellent yields the
seven-membered ring 2p (59%), the eight-membered
oxathiocin 2q (96%) and even the nine-membered oxathionin
derivative 2r (92%) were obtained. The structures of the latter
two compounds were proved by X-ray crystallography
With these conditions in hand, we explored the scope and
limitations of this transformation (Scheme 2).
CN
PdCl2(PhCN)2
XantPhos, NEt3
CN
S
R
S
X
R
Y
DMF, 100 °C
Y
7-12 h
X
(
Scheme 3). The formation of a ten- and a twelve-membered
1
2
2
2
ring system was unsuccessful.
CN
CN
S
S
R
Me
NC
Me
O
O
Pd2(dba)3
XantPhos
R = Me 93%a
S
2
2
a
X-ray of 2a
2c 71%
S
CN
b R = t-Bu 94%
O
n
PhMe, 160 °C, 6-12 h
n = 0,1,2
CN
S
CN
O
n
S
1
2
Me
Me
O
O
Me
NC
Me
CN
2e 90% (E/Z 2:1)b
2
d 46%
X-ray of 2e (E-isomer)
Me
S
S
CN
CN
S
CN
S
S
O
O
X-ray
R
2p 59%
2q 96%
of 2q
O
O
R
O
2g R = F 77% (E/Z 1.5:1)b
2
R = 2-Me 86% (E/Z 1:2)
2i
2
f 75% (E/Z 2:1)b
h R = Cl 91% (E/Z 2:1)b
Me
S
2j R = 3-Me 84% (E/Z 1:1)
b
2
k R = 4-Me 72% (E/Z 1.7:1)
NC
1CN
CN
R
S
S
S
CN
Me
R2
Me
O
R1 = Me, R = H 10%c
O
2
2n 86% d
2o 75% d
2
2
l
2r 92%
X-ray of 2r
m R = H, R = Ph 27%c
1
2
Scheme
3
Intramolecular cyanosulfenylation for large ring synthesis. Reaction
(dba) (10 mol%), XantPhos (20 mol%), PhMe (20 mM),
Scheme 2 Intramolecular cyanosulfenylation with aromatic thiocyanates. Reaction
conditions: 1 (1.00 equiv.), PdCl (PhCN) (10 mol%), XantPhos (20 mol%), NEt (5.00
(5 mol%),
conditions: 1 (1.00 equiv.), Pd
60 °C, 6-12 h.
2
3
2
2
3
1
equiv.), DMF (20 mM), 100 °C, 7 h. a Large scale (1.5 mmol, 93%), Pd(PPh
)
3 4
SPhos (20 mol%), 160 °C, 3 h, PhMe (20 mM). b Z-isomer is shown also in case it is the
Scope of aliphatic thiocyanates
minor isolated product because that is consistent with the plausible mechanism;
E-isomer arises as result of a strong push-pull-system.19 c Pd(PPh
)
(5 mol%), SPhos
(5 mol%), SPhos (20 mol%), 110 °C, 3 h,
2 n
) ; m, n = 0,1,2.
3
4
Next, we focused on the scope with respect to aliphatic
thiocyanates (Scheme 4). We realized that higher temperatures
are required to enable the transformation. This observation
might be traced back to a stronger S-CN bond (because of its
non-conjugated nature) and/or the lack of preorganisation.
Hence, a complete reoptimisation of the reaction conditions
(
20 mol%), 160 °C, 6 h, DMF (20 mM). d Pd(PPh
3 4
)
DMF (20 mM). X = O, (CH ; Y = (CH
2
)
m
Substrates with aliphatic termini were smoothly transformed
and yielded products 2a-2c in 71-94% yield. A 1,3-diyne unit
reacted to enyne 2d (46%). Differently substituted aromatic
termini were tolerated and furnished products 2e-2k in up to
1% yield. However, mixtures of E/Z-isomers were found
because of the highly polarized character of the emerging
was necessary (see Supporting Information). Finally, Pd
2 3
(dba)
or Pd(PPh and the use of toluene as solvent and a reaction
3 4
)
9
temperature of 160 °C proved to be the optimal choice. Under
2
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these conditions 4a was obtained in 89% yield. The successful This allowed a diastereoselective access to the coVirerweAsrpticolenOdnilninge
synthesis of products 4b-4d shows that the reaction tolerates doubly or triply heterosubstituted olefinDmOIo: i1e0t.1ie0s39i/nC9mSCo0d4e5r6a9tDe
aliphatic termini, as well as a conjugated triple bond as to good yields. TBS-substituted triple bonds (e.g. 6a, 6d), and
exemplified in isothiochromene 4d. The motif of a molecular also the very electron-rich mono- or bis-substituted triple bonds
switch was achieved with the synthesis of 4e (64%). The with sulphur (6b, 6c, 6e) and selenium (6d, 6f) were successfully
generation of five-membered exocyclic thioenol ethers also transformed. An ynamide furnished the sulphur/nitrogen-
proceeded smoothly. Electron-poor (4g), electron-rich (4h), substituted (E)-alkene 6g in 81%.
sterically encumbered (4i), aromatic and heteroaromatic (4j)
termini also permit the transformation. Compound 4f’ was
Intermolecular cyanosulfenylation
prepared to investigate whether an acceleration of the reaction All the transformations described so far proceeded in an intra-
2
3
by a Thorpe-Ingold effect is be observed; the effect was small.
molecular manner. With an excess of alkyne (2.0 equiv.) and the
catalytic system of Pd (dba) and Xantphos in toluene at 160 °C
2
3
we were able to realize an intermolecular variant (Scheme 6).
3-Hexyne was converted in yields of 44-90% into the
tetrasubstituted alkenes 8a-8c. The attack to methylphenyl
acetylene afforded in 88% a regioisomeric mixture (3:1); the
steric and electronic differentiation of the two acetylenic
carbons seems not high enough to lead to a clear preference of
the thiopalladation step. In contrast, with phenyl trimethylsilyl
acetylene only one regioisomeric product 8e was formed
CN
CN
S
R
S
R
Pd2(dba)3, XantPhos
PhMe, 160 °C, 3-14 h
0,1
0,1
3
4
CN
CN
CN
CN
S
S
S
S
R
Me
4b R = t-Bu 99%a
4c R = Pr
4
(
a 89%
E/Z 1:8)
47%
4d 71%
4e 64%
CN
(compare also X-ray crystal structure); however, as the major
S
CN
S
CN
S
CN
S
product desilylated trisubstituted olefin 8e’ was found.
Me
R
R
Me
N
Pd2(dba)3
XantPhos
CN
R3
R3
R
Me
R1 CN
S
S
4
4
f
R = H
91% 4g R = CHO 57%
f' R = Me 96% 4h R = OMe 76%
4i 68%
4j 97%
R1
R2
PhMe, 160 °C, 24 h
R2
Scheme 4 Intramolecular cyanosulfenylation with aliphatic thiocyanates. Reaction
7a
7b
8
conditions: 3 (1.00 equiv.), Pd
2
(dba) (10 mol%), XantPhos (20 mol%), PhMe (20 mM),
3
Me
a
CN
CN
S
CN
1
60 °C, 3-14 h. Pd(PPh
3
)
4
(5 mol%), SPhos (20 mol%), 160 °C, 3 h, PhMe (20 mM).
S
Me
Me
S
Me
Me
Me
Me
Multiple heteroatom-substitution
8
a 80% (E/Z 1:1.2)
8b 44%
8c 90%
Because we have a special interest in multiply hetero-
substituted C-C double bonds, we subjected several α- and α,α’-
CN
CN

S

S
Me
R
(
(
di)substituted triple bonds to the reaction conditions
Scheme 5).
8d 88% (Ph / 3:1)
8e R = TMS 18%
X-ray of
8e
CN
S
R
CN
8e' R = H
80% (by-product)
Conditionsa
S
X
X
Y
R
Scheme 6 Intermolecular cyanosulfenylation with different thiocyanates. Reaction
Y
conditions: 7a (1.00 equiv.), 7b (2.00 equiv.), Pd
PhMe (20 mM), 160 °C, 24 h.
2
(dba) (10 mol%), XantPhos (20 mol%),
3
5
6
Me
CN
CN
S
Me
Me
S
S
S
CN
Me
Si
Me Me
Thiopalladation-carbopalladation cascade with cyanide transfer
S
O
S
a 54%b
6b 81%c
6c 62%c
Our ultimate goal was to extend the sequence that starts with
the thiopalladation by further carbopalladation steps. The
reductive elimination of the Pd should then occur as the final
step, generating a C-CN bond. Such an approach using
oligoalkynes would lead to a formal 1,4- or 1,6-cyano-
sulfenylation with a conjugated double bond system in between
(Scheme 7). To successfully perform such a cascade, the carbo-
palladation step must be faster than the reductive elimination
of Pd forming the C-CN bond. Initial experiments using model
6
CN Me
Me
Me
S
Si
Se Me Me
6
d 67%c
X-ray of 6d
S
CN
S
S
CN
S
CN
N
O
Se
O
6
e 71%d
6f 43%d
6g 81%d
Scheme 5 Cyanosulfenylation of heterosubstituted triple bonds. a Reaction conditions: compound 9a and trimethylphosphine as ligand for Pd showed
5
PdCl
3
(1.00 equiv.). b Pd(PPh
3
)
4
(5 mol%), SPhos (20 mol%), 110 °C, 3 h, DMF (20 mM).
(10 mol%), XantPhos (20 mol%), NEt (5.00 equiv.), DMF (20 mM), 100 °C,
(dba) (10 mol%), XantPhos (20 mol%), 160 °C, 3 h, PhMe (20 mM).
that a thiopalladation-carbopalladation sequence is possible.
However, as final step a protodepalladation occurred and thus
the cyano moiety was not found in the product (for X-
c
2
(PhCN)
2
3
-7 h. d Pd
2
3
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R
Me
CN
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DOI: 10.1039/C9SC04569D
Pd(PPh3)4
SPhos
CN
S
1,2
1,2
NC
S
Me
X
DMF or PhMe,
10 - 160 °C, 3-6.5 h
X
X
CN
S
CN
1
0,1
S
0
,1
S
Me
R
X
9
10
(
Z,E,Z)-10d
(Z,Z,Z)-10d
Pd-L2
9d
Me
L
reductive
elimination
oxidative
addition
NC
S
NC
S
Me
NC
S
L
Pd
S
Me
NC
CN
L
Pd
Me
L
10a 70%
10b 66%
X-ray of 10b
10c 15%
S
Me
CN
D
syn-thio-
palladation
CN
Me
A
Me
2
nd syn-carbo-
O
palladation
S
S
CN
L
L
Pd
L
S
CN
O
S
Pd
1
0d 51%
X-ray of 10d
11 23%
Scheme 7 Thiopalladation/carbopalladation/(carbopalladation)/cyanide transfer cas-
cades with translocation of the CN group over four or six atoms. Product 9 uses an enyne
C
B
Me
1st syn-carbopalladation
as starting material. Conditions: 7 (1.00 eqiuv.), Pd(PPh
3 4
) (5 mol%), SPhos (20 mol%),
Scheme
8 Proposed mechanism of the thiopalladation/carbopalladation/carbo-
1
10 - 160 °C, 3-7 h, DMF or PhMe (20 mM).
palladation/cyanide transfer cascade.
ray analysis of this undesired product 10a’, see Supporting
Information). Reoptimisation studies revealed that the best
Follow-up chemistry
To demonstrate the versatility of the thioacrylonitrile moiety,
some postsynthetic functionalisations with 2a were performed
results are obtained with SPhos and Pd(PPh
3 4
) as Pd source. The
1
,4-cyanosulfenylation products 10a and 10b were obtained in
(Scheme 9). Depending on the amount of mCPBA, we were able
yields of 66-70%. Because the conditions had been optimised
for aryl thiocyanates, we expected a much lower yield for
cascades starting with alkyl thiocyanates. Indeed, compound
to prepare either sulfoxide 12a or sulfone 12b in good to
excellent yields, thus transforming the strongly polarized olefin
into very electron-poor olefins. A Michael addition with
ethanethiol led to a diastereomeric mixture of 12c in 83% yield.
Furthermore, the hydrolysis of the nitrile with aqueous KOH
gave access to the carboxylic acids exo-12d and endo-12d. The
partial reduction of the Michael system trapped by methyl
chloroformate lead to carbamate 12e in a good yield of 75%.
Reaction of 2a with DIBAL-H furnished the aldehyde 12f in a
moderate yield.
1
0c was obtained in only 15% yield. The thiopalladation-
carbopalladation-carbopalladation cascade, generating one C-S
and three C-C bonds in one step, yielded push-pull-substituted
triene 10d in 51% yield. X-ray crystallography unequivocally
showed the translocation of the cyano group; the central
2
4
double bond has isomerized to avoid a helical arrangement.
First unoptimised experiments with an alkyne-alkene system,
furnishing 11, demonstrated that, after formation of the
tetrasubstituted double bond, the subsequent carbopalladation
O
S
CN
Me
O
S
O
CN
Me
3
25
also allows the generation of an C(sp )-CN bond.
Proposed mechanism
O
O
1
2a 62%
12b 94%
A plausible mechanism of the thiopalladation/carbopalla-
mCPBA (1 equiv.)
mCPBA (3 equiv.)
dation/carbopalladation/cyanide transfer cascade to 10d,
based on our additional experimental results (such as proto-
DCM, 25 °C, 24 h
DCM, 25 °C, 24 h
2
6
O
CN
Me
NC Me
depalladation) and previously reported carbopalladation
S
DIBAL-H
PhMe
S
EtSH, piperidine
DMSO
S
H
Me
cascades,1
0-12
SEt
is depicted in Scheme 8. After the oxidative
25 °C, 1 h
O
-78 °C, 0.5 h
O
O
addition of the Pd catalyst into the S-CN bond of 9d, a
thiopalladation occurs (A → B). Instead of delivering the CN
group via reductive elimination of the Pd to the emerging
double bond, the sequence continues by a first syn-
carbopalladation to yield C. A repetition with another triple
1
2f 44%
12c 83%
d.r. 1:1
2a
1
2
. AlCl3, LiAlH4, Et2O, 0-25 °C
. NaHCO3 (aq.), 0 °C
ClCOOMe, 25 °C
H
KOH (aq., 34 wt%)
EtOH, 25 °C, 12 h
N
O
O
OH
Me
O
S
OH
Me
Me
2
bond affords D. As terminating step, the C(sp )-CN bond is
S
O
S
Me
formed by reductive elimination of the Pd to furnish E. Because
a strongly push-pull-substituted oligoene is formed, the double
bonds are much weaker than in non-push-pull-substituted
oligoenes; thus, isomerisation from (Z,Z,Z)-10d to (Z,E,Z)-10d
might happen relatively easily.
O
O
O
12e 75%
exo
-12d
61%
:3 mixture
endo-
12d
1
Scheme 9 Follow-up chemistry.
4
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5
6
Y. H. Lee and B. Morandi, Angew. Chem. Int. EVdie.w, A2r0tic1le9O, n5lin8e,
Conclusions
6
444.
DOI: 10.1039/C9SC04569D
In conclusion, we have developed a Pd-catalysed syn-1,2-
cyanosulfenylation of internal alkynes to access tetra-
substituted double bonds with sulphur and cyano in adjacent
positions. Both aromatic and aliphatic thiocyanates undergo the
reaction. Various substitution patterns of the C-C triple bond
are tolerated, such as aliphatic and aromatic residues, but also
heteroatoms such as sulphur, selenium, silicon and nitrogen.
Our methodology facilitates access to tetrasubstituted olefins
with four different elements as substituents of the double bond.
The reaction works in an intramolecular manner paving the way
to five-, six-, seven-, eight, and nine-membered ring systems,
but also in an intermolecular way leading to acyclic compounds.
By offering further alkyne moieties the transformation was
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There are no conflicts to declare.
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Acknowledgements
We are grateful to the TU Braunschweig for funding. Marcel
Bürger thanks Anna Lehmann, Theresa Schitter and Adrian
Bauschke for their support.
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This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2019, 00, 1-3 | 5
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PleaseC dh oe mn oi ct a al dS cj ui es nt cme argins
Page 6 of 7
ARTICLE
Chemical Science
M. Kobayashi, D. B. Werz and Y. Nakao, J. Am. Chem. Soc.,
012, 134, 6544.
7 M. Pawliczek, L. K. B. Garve and D. B. Werz, Org. Lett., 2015,
View Article Online
DOI: 10.1039/C9SC04569D
2
1
1
7, 1716.
1
1
8 M. R. Netherton and G. C. Fu, Org. Lett., 2001, 3, 4295.
9
R
S
CN
R
S
CN
R
S
R

R
R
CN
R
R
R
2
0 The configurational stability of E- and Z-isomers of 2e was
investigated in additional experiments under the reaction
conditions. The E-configured starting material shows the
generation of the Z-configured counterpart and vice versa. For
more information, see Supporting Information.
2
2
1 CCDC 1948156 (2a), 1948157 (2e), 1969697 (2q), 1969698 (2r)
1
1
948158 (6d), 1996969 (8e)1948159 (10b), 1948160 (10d),
948161 (2s, SI) and 1948162 (10a’, SI) contain the
supplementary crystallographic data for this paper.
2 For the synthesis of the starting material for larger rings, see
Supporting Information.
2
2
3 For respective GC experiments, see Supporting Information.
4 An HPLC experiment directly after the reaction showed the
existence of (Z,Z,Z)-8d, which slowly isomerizes to (Z,E,Z)-8d.
For results of thermal and photochemical experiments, see
Supporting Information.
2
2
5 The formation of a product from an alkene-alkene system was
observed only in traces in GC-MS. For the synthesis of starting
material, see Supporting information.
6 Experiments in the presence of TEMPO did not significantly
decrease the yield (77% of 2a); thus, we rule out the
involvement of any radical intermediates.
6
| Chem. Sci., 2019, 00, 1-3
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Page 7 of 7
Chemical Science
View Article Online
Pd
DOI: 10.1039/C9SC04569D
Drop
Drag
R
and
NC
S
CN
S
Z
Z
X
XantPhos or SPhos
PhMe or DMF
Y
0,1,2
Y
R
,1,2
X
0





45 examples, yields of up to 99%
intra- and intermolecular version
broad functional group tolerance
up to four new bonds in one step
multi-substituted double bonds with
up to four different elements
The intra- and intermoleculart Pd-catalysed cyanosulfenylation of internal alkynes enables the formation of tetrasubstituted
thioacrylonitriles with up to four different elements as substituents and is extended to oligoyne systems leading to conjugated
oligoenes and a cyanide transfer over four or six atoms.