Free-Radical Carbocyanation of Olefins

Article abstract of DOI:10.1002/chem.201605946

The free-radical three-component carbocyanation of electron-rich olefins was investigated with p-tosyl cyanide as cyanide source. The scope and limitations of the process were established by varying the nature of the alkene and radical precursor. Carbocyanation of chiral allylsilanes was shown to occur with high diastereocontrol, leading to syn β-silyl nitriles. The origin of the stereocontrol was rationalized by a Felkin–Anh-type transition-state model. Finally, a tin-free carbocyanation process was also devised, based on the use of a new alkylsulfonyl cyanide incorporating both carbon fragments to be added across the olefinic π system.

Full text of DOI:10.1002/chem.201605946

A Journal of
Accepted Article
Title: Free-radical Carbo-cyanation of Olefins
Authors: Yannick Landais, Vincent Pirenne, Haitham Hassan, Frédéric
Robert, Maren Wissing, Chahinaz Khiar, and Ashique
Hussain
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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
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To be cited as: Chem. Eur. J. 10.1002/chem.201605946
Link to VoR: http://dx.doi.org/10.1002/chem.201605946
Supported by

Chemistry - A European Journal
10.1002/chem.201605946
FULL PAPER
Free-radical Carbo-cyanation of Olefins.
Haitham Hassan,‡[a] Vincent Pirenne,‡[a] Maren Wissing, Chahinaz Khiar,
[a]
[a],[b]
Ashique Hussain,[a]
[
a]
[a]
Frédéric Robert, and Yannick Landais*
Abstract: The free-radical 3-component carbo-cyanation of electron-
rich olefins has been investigated using p-tosyl cyanide as a cyanide
source. Scope and limitation of the process was established varying
the nature of the alkene and that of the radical precursor.
Carbocyanation of chiral allylsilanes was shown to occur with high
diastereocontrol, leading to syn -silyl nitriles. The origin of the
stereocontrol was rationalized through a Felkin-Anh type transition
state model. Finally, a tin-free carbocyanation process was also
a better formyl or aminomethyl surrogate, it was envisioned that a
cyano group might be particularly well suited as it may be
selectively reduced into an aldehyde (with DIBAL-H) or fully
hydrogenated into an amine using H
2
and Raney-Nickel under
4
mild conditions. Moreover, the small size of the CN substituent
should allow the elaboration of acyclic systems bearing
quaternary centers with a nitrile function, ready for further
transformation.5 While organometallic intra- and intermolecular
carbo-cyanation of alkenes and alkynes have been well
devised, based on the use of
incorporating both carbon fragments to be added across the olefinic
-system.
a new alkylsulfonyl cyanide
developed
using
Ni
and
Pd-catalysis,6
free-radical

carbocyanation of olefins has been more scarcely studied. 1,2-
Cyanocarbofunctionalization of alkenes has thus been limited to
copper-catalyzed cyano-trifluoromethylation.7 Recently, Inoue8
disclosed an interesting intramolecular cyanide transfer process
Introduction
3
during the addition of Cl CCN onto an olefin catalyzed by a copper
complex. Zhu9a and Liu9b also developed an elegant cyano-
functionalization of olefins relying on an intramolecular cyano
migration strategy. However, in all these cases, the scope is
restricted to olefins bearing specific functional groups or
The regioselective addition of two carbon fragments onto olefins
gives rise to useful intermediates for organic synthesis starting
from readily available starting materials. Organometallic but also
free-radical additions of carbon moieties across the olefinic π-
system have thus been thoroughly studied and applied to a broad
range of electron-rich and electron-deficient olefins.1 In this
context, this laboratory has recently developed several radical
processes relying on such additions, providing original substrates
bearing two new C-C bonds along with two additional functional
groups.2 Amongst these reactions, one-pot 3-component carbo-
oximation of olefins proved to be particularly efficient,2a,2e allowing
the incorporation on the carbon backbone of an oxime functional
group which was later hydrolyzed into an aldehyde or reduced into
an aminomethyl substituent, as illustrated recently in the total
10
substituents. Fang et al described earlier the addition of p-
TolSO CN across olefins -bonds to afford the corresponding -
2
sulfonyl cyanides. Various reports have also described the use of
sulfonyl cyanides as efficient cyanating agents in radical
11
processes, but none of them have reported on the consecutive
incorporation of a carbon fragment and a cyano substituent on an
olefinic backbone.
3
synthesis of Eucophylline alkaloid. However, further use of this
carbo-oximation as a formal carbo-formylation process with more
hindered substrates (i.e. 2a, Figure 1) led to less satisfactory
3
yields, underlining the limitation of the process. In the search for
[
a]
Dr. H. Hassan, V. Pirenne, C. Khiar, M. Wissing, Dr. F. Robert, Prof.
Dr. Y. Landais
Institute of Molecular Sciences, UMR-CNRS 5255
University of Bordeaux
351, Cours de la libération
33405 Talence cedex, France
E-mail: y.landais@ism.u-bordeaux1.fr
Figure 1. Free-radical carbo-oximation and carbo-cyanation of olefins.
[b]
C. Khiar
Laboratoire de Chimie Appliquée et du Génie Chimique (LCAGC)
Université Mouloud Mammerie de Tizi-Ouzou
Based upon previous work on carbo-azidation,12 carbo-
15000, Tizi-Ouzou, Algeria
2b,c
2a,e
alkenylation
and carbo-oximation,
we describe here an
efficient 3-component free-radical carbo-cyanation of electron-
rich olefins.13 Optimization of the process also led us developing
a tin-free (two-component) version of this carbo-cyanation using
‡
These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of
the document
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Chemistry - A European Journal
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a readily available sulfonyl cyanide incorporating both functional
groups which will be added onto the olefin.
6i or enol ether 6j. In contrast with carbo-oximation reaction,
which led to moderate yields with sterically hindered substrates,
carbo-cyanation allowed the incorporation of the cyano group on
tertiary center and thus the generation of all-carbon quaternary
centers as in 6a-f. The reaction conditions were also compatible
with functional groups as exemplified with esters (6d-f), nitrile (6l),
phosphonate (6m) and substituted olefins (6o). Finally, the nature
of the radical precursor was varied including -iodoimides and
amides 1d-f. 3-component adducts 6q-v were thus obtained in
moderate to good yields. Interestingly, useful O-protecting groups
such as OPiv, but also OTs as in 6r-s and 6v were also tolerated
in these reactions. Finally, we also tested the efficiency of the
photochemical initiation. For instance, 3-component adducts 6r-
Results and Discussion
3-component carbo-cyanation of olefins
Preliminary studies were carried out using iodide 1a and olefin 2b
respectively as radical precursor and olefin, and p-TolSO CN as
2
a commercially available cyanating agent, using first optimal
conditions set up for the carbo-oximation process2e (Table 1, entry
3 2
1). (Bu Sn) (1.5 equiv.) was used as a chain carrier and di-tbutyl
6v were prepared under similar conditions, but using a sunlamp
hyponitrite (DTBHN) as an initiator. Pleasingly, under these
conditions, the carbocyanation product 6a was formed in an
excellent 79% yield. Lowering both the amount of olefin and that
instead of DTBHN. Moderate to good yields were obtained,
suggesting that this protocol may be suitable for reactions on a
larger scale as to avoid the use of costly DTBHN.
of
5 slightly lowered the yield, which however remained
satisfactory (Table 1, entry 2). A further decreased of the quantity
of olefin to 1.1 equiv. led to only 50% yield of 6a. Finally, the
scaling up of the reaction using conditions in entry 2 led to an
acceptable yield and showed that such multicomponent process
could be used for further synthetic purposes.
Table 1. Optimization of the carbocyanation conditions.
Entry
Olefin 2b (eq.)
p-TsCN 5 (eq.)
Yield [%][a]
1
2
4
2
1.1
2
2
79
68
50
60
1.2
1.2
1.2
3
4[
b]
[
a] Yield of isolated products. [b] Scaling up experiment starting from 20 mmol
of 2b.
These preliminary studies showed that tin-mediated carbo-
cyanation of olefin is efficient even with substrates for which the
carbo-oximation led to poor yield. Best conditions (Table 1, entry
1) were then applied to the carbocyanation of a series of olefins
as summarized in Scheme 1. It is worth noticing that for large
scale synthesis and for costly olefins, the use of 2 equivalents of
olefin (Table 1, entry 2 and 4) gave generally suitable yields. As
already observed before,2b-c electron-rich olefins (enol ethers,
enamides, allylsilanes, …..) being more reactive, 2 equivalents is
usually sufficient to attain reasonable yields. -Iodoesters 1b-c
were also tested and led to the expected 3-component adducts
6b-c, 6e-f and 6h-6i with yields similar to those obtained from
thioester 1a (Scheme 1). The latter generally led to faster and
cleaner reactions. Moreover, the presence of the reactive
orthogonal thioester group allows for further manipulation in the
3
presence of esters as in 6d. As observed in carbo-alkenylation
and oximation reactions,2b,c,e electron-richer olefins reacted faster
and led to higher yields as illustrated with the formation of silane
Scheme 1. Carbo-cyanation of olefins using p-tosyl cyanide 5.
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Other radical precursors than -iodoesters 1a-c were tested,
including -bromosulfone 7, which proved to be less reactive than
its ester counterpart, however providing the desired compounds
With reactive electron-rich olefins, we observed along with the
expected carbo-cyanation product, various amount of sulfonyl-
cyanation product.10 For instance, addition of sulfone 7 onto
allylsilane 2d led to the desired adduct 13a, along with the sulfonyl
cyanide by-product 13a’, resulting from the facile addition of the
electrophilic p-tosyl radical onto the double bond.17 Similarly,
addition to the strained norbornene 14a (4 equiv) led to compound
15a as 2:1 mixture of separable diastereomers, along with a high
percentage of sulfonylated cyanide 15a’. Repeating the reaction
with only 1.1 equivalent of norbornene however led to a reduced
amount of 15a’. The same behavior was observed during the
carbo-cyanation of vinyl pivalate 2n. Sulfonyl-cyanation10 is thus
observed when excess of both 5 and olefins are present in the
medium, and thus occurs after the limiting iodide substrate has
been consumed. This side-reaction is observed on these
particular cases, as 2d and 14a-b are electron-rich and thus
particularly reactive. This was not observed with less reactive
alkenes. Limiting the quantity of olefin disfavors the addition of the
electrophilic tosyl radical.18 The fast reaction of the tosyl radical
with ditin then allows an efficient propagation of the radical chain
and prevents the formation of side products 13a’, 15a’, 15b’ and
8
in moderate yield (Scheme 2). Fluorinated alkyl iodide chains
are also competent radical precursors in these reactions, as
shown by the addition of 9a-b onto olefins 2f and 2o, which led to
1
0a-c in reasonable yields.14 Pyramidal C-centered fluorinated
1
5
radicals are known to add efficiently onto double bonds.
1
5c’.19
Scheme 2. Carbo-cyanation of olefin 2a, 2f and 2o with -sulfonyl bromide and
fluorinated alkyl chains.
In these multi-component processes, dienes were shown to
behave differently than normal olefins,16 leading to higher
amounts of sulfonyl addition products (vide infra).10 In order to
suppress these side-reactions, the radical process is carried out
using only 1 equivalent of olefin. These conditions were used here
to access carbo-cyanation products in modest yields (Scheme 3).
In the reaction of diene 11c, the expected product 12c was thus
obtained in 30% yield along with a large amount of the iodide
transfer product 12c’.
Scheme 4. Carbo-cyanation and competing sulfonyl-cyanation of electron-rich
olefins.
The carbo-cyanation reaction was also applied to chiral olefins in
order to study the level of 1,2-stereocontrol in these reactions.
Previous studies have shown that carbo-azidation of chiral
allylsilanes could be highly stereoselective with d.r. ranging
between 80:20 and 100:0.20 Extension of this study to carbo-
oximation was plagued by the low reactivity of the -silyl radical
species with the sulfonyloxime due to steric hindrance.21 It was
anticipated that the small size of the cyano group would allow the
reaction of the -silyl radical intermediate with the p-tosyl cyanide
Scheme 3. Carbo-cyanation of dienes 11a-c.
5
and provide the carbo-cyanation product. The reaction was thus
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Scheme 5. Carbocyanation of chiral allylsilanes 16a-d and ester 18.
performed with a series of chiral allylsilanes 16a-d prepared
following reported procedures.20 The 3-component carbo-
cyanation was found to be highly diastereoselective when
sufficient steric bulk was present on the -carbon, as in
allylsilanes 16a-b affording 17a-b in good yield (Scheme 5). The
sole presence of a phenyl group as in 16c (leading to 17c) on the
stereogenic center was surprisingly not sufficient to induce the
stereocontrol, in contrast with our previous observations in carbo-
azidation on the same substrate. With sterically hindered
allylsilane 16d having a t-Bu substituent on the -center, no
reaction was observed. Finally, we extended the study to the
carbo-cyanation of a chiral allylic ester 18, which led to the desired
compound 19, albeit in low yield and no stereocontrol, in good
“
Tin-free” carbo-cyanation of olefins
Examples above thus showed that three-component carbo-
cyanation of olefins using commercially available p-tosyl cyanide
has a rather broad scope, providing polyfunctional substrates in
satisfying to excellent yields. However, such a process would be
really useful for synthetic purposes, if a “tin-free” version was
made available, as in certain cases, complete removal of tin
residues may be tedious. Based on literature precedents,22 it was
intended to develop an access to a sulfone such as 20 having
both an ester functional group as in radical precursors 1a-c and a
cyano substituent (Scheme 6). An initiation step should generate
electrophilic radical I, the addition of which onto the olefin would
afford a new nucleophilic radical II. Reaction of the latter with 20
would give the product along with an alkylsulfonyl residue
agreement with precedent in carbo-azidation and carbo-
alkenylation processes.16,20 The relative configuration of the major
diastereomer was determined through X-ray diffraction studies of
the crystalline nitrile 17b, which was shown to possess the syn-
configuration, similarly to azidosilanes prepared through carbo-
azidation.20 The origin of the diastereocontrol was thus
rationalized invoking a similar transition state model as depicted
in Scheme 5. In this Felkin-Anh-type model, the p-tosyl-cyanide is
believed to approach the nucleophilic radical anti relative to the
bulky silicon group on the side of the small hydrogen substituent,
(EtO CCH SO ), which -scission (and loss of SO ) would
2
2
2
2
regenerate I and thus sustain the radical chain.23 Although Kim
and co-workers have developed a general procedure to access
alkylsulfonyl cyanides from alkylsulfinyl salts and ClCN,24 the use
of volatile and highly toxic ClCN prompted us to test the
alternative oxidation of a thiocyanate such as 21.25 This approach
is usually limited to arylthiocyanate26 and only one report
mentioned a good yield for an oxidation of an alkylthiocyanate
using m-CPBA.27
2 2 2
with the bulkiest substituents (SiMe Ph and CH CH COSPh)
orthogonal to each other. When the size of the substituents on the
stereogenic center was decreased as in 16c (R = Ph), the
diastereocontrol decreased dramatically. This may be explained
by the now alternative approach of the cyanide group from the
side of the medium-sized phenyl group (R = Ph).
Scheme 6. Synthesis of sulfonyl cyanide 20 and radical chain in the 2-
component process.
®
Preliminary attempts at oxidizing 21 using oxone, but also MnO
2
or KMnO
sulfonyl cyanide 20, leading instead to the formation of the
corresponding carbamothioate (EtO CCH S(C=O)NH ), through
4 2
/MnO failed to afford satisfying yields of the desired
2
2
2
hydrolysis of 21 (see supporting information). With m-CPBA,
formation of 20 was observed, but excess peracid was difficult to
remove, which prompted us to use a more soluble oxidizing agent.
More encouraging results were thus obtained using CF
prepared from (CF CO) O and H O .
3 2 2 2
3
CO
Optimization of this
oxidation process is summarized in Table 2.
3
H
28
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Chemistry - A European Journal
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FULL PAPER
encouraging yield, which could not be increased using additional
amount of initiator (entry 6). The cheaper AIBN also led to full
conversion of 20 and moderate to good yields of 6i depending on
the amount of initiator which was added (entries 7-9). Although
good yields of 6i were obtained using AIBN (entry 8), large
amount of initiator was required. Moreover, when less reactive
olefins such as 1-octene was used under these conditions, the
carbocyanation product was formed in low yield (47%). We thus
turned our attention to V-40 (1,1’-azobis(cyclohexane-1-
carbonitrile)), known to decompose at a higher temperature,
Table 2. Optimization of the oxidation conditions of 21.
[
a]
20/20’ (%)[b]
Entry
H
O
2 2
3 2
(CF CO) O
T(°C)
Time
(h)
Yield
[%][
which should also facilitates the fragmentation (-scission) of
c]
(equiv)
(equiv)
24
2
0. At this temperature (120°C), and using a low amount (2 x
1
2
3
4
5
6
5
5
7.5
13
10
2
5
5
7.5
20
10
2
20
40
35
20
40
40
15
16
18
7
16
3
44:56
80:20
70:30
100:0
>95:<5
5:95
-
-
-
0
.05 mol%) of V-40 in chlorobenzene, satisfying yield of 6i was
obtained (entry 10). Reversing the ratio of 2d and 20 (entry 11),
we finally observed that although the conversion was still
complete, the yield of 6i slightly decreased. These conditions are
however useful when the starting olefins are less reactive than
allylsilane and their preparation requires several steps.
32
75
[
d]
-
[
a] H
2
O
2
50%wt in water was used. [b] 20/20’ ratio was estimated through 1
H
O
NMR of the reaction mixture. [c] Crude yield of 20-20’ after washing with H
2
and evaporation of the solvent (> 95:5 purity). [d] 20’ was isolated with 20%
unreacted 21.
Table 3. Optimization of the reaction conditions for the carbo-cyanation of
2d with 20.
The use of a 5-fold excess of both reagents to ensure the
formation of CF CO H and the complete oxidation of 21 led to a
3 3
mixture of the sulfone 20 and sulfinyl cyanide 20’ (Table 2, entry
1
1
). 20’ could be easily detected through H NMR, showing two
sets of peaks at 4.5 and 4.7 ppm for diastereotopic CH
2
protons.29
A higher conversion into 20 was obtained using 5- then 7.5-fold
excess of reagents and increasing the temperature (entries 2-3).
A still higher amount of reagent led to a complete conversion into
Conv. (%)[f] Yield [%][g]
Entry
Init.
Init.
(equiv.)
T(°C)
Time
(h)
2
0, but afforded a low yield after work-up (entry 4). Finally, a good
compromise was found by using 10 equiv. of both reagents at
0°C. A simple washing of the reaction mixture with H O and
evaporation of the solvent led to good and reproducible yields of
0 (68-75%) with > 95:5 purity. This procedure was repeated and
scaled up to 30 mmol of 21 (affording ~ 4g of 20). Sulfinyl cyanide
0’ (vide infra) could also be isolated using only 2 equiv. of
[a]
1
2
3
4
5
6
7
8
9
-
-
65
65
80
120
20
80
80
65
80
120
120
14
4.5
6
6
5
6
6
14
6
2
0
nd
nd
< 15
100
100
nd
-
[
[
[
[
a]
a]
a]
a]
4
2
DTBHN
DLP
3 x 0.1
3 x 0.1
3 x 0.1
2
0.5
3 x 0.1
2
3 x 0.25
2 x 0.05
0.1
49
32
-
50
58
47
74
75
83
72
[c]
DTBP
2
Et
3
B[d]
[a]
[a]
[e]
DTBD
2
AIBN
AIBN
AIBN
[
[
a]
a]
peracid (along with 20% unreacted 21) (entry 6). This method was
also found suitable to prepare other volatile alkylsulfonyl cyanides
100
100
100
100[h]
1
1
0[
a]
b]
V-40
V-40
[c]
23a-b in good yields.
[
[c]
1
2
[
a] 2d (2 equiv) and 20 (1 equiv). [b] 2d (1 equiv) and 20 (2 equiv). [c] PhCl was
used as a solvent. [d] Et B 1.0 M in hexane. [e] h (sunlamp) and benzene were
3
used. [f] Conversion of 20. [g] Isolated yield of 6i after chromatography. [h]
Conversion of 2d.
These optimized conditions (entry 11) were then applied to a
series of olefins as summarized in Scheme 8. The “tin-free” carbo-
cyanation reaction proved to be efficient with a broad range of
olefins, leading to the final nitriles in moderate to excellent yields.
Functional groups such as esters, ketones, olefins and
substituents such as halides, silanes, were found compatible with
the reaction conditions. Modest yields were in turn obtained with
Scheme 7. Synthesis of sulfonyl cyanides 23a-b.
With 20 in hands, the radical carbo-cyanation was then studied
with allylsilane 2d as a model compound. The reaction was
studied using first an excess of olefin 2d (2 equiv.). Thermal
initiation at 65°C led to no reaction (Table 3, entry 1). Several
initiation protocols were thus tried, which are summarized in Table
acid-sensitive olefins (i.e. 24g), likely due to the presence of SO
in the reaction medium. Attempts at using a base to trap the acid
resulting from the reaction of SO with traces of moisture failed to
2
3. DTBHN and dilauroyl peroxide (DLP) led to modest yields of 6i
2
with three consecutive additions (3 x 0.1 eq.) (entries 2-3). Di-t-
butyl peroxide (DTBP) under thermal conditions led to no
conversion (entry 4). Reaction using Et B and oxygen at room
3
improve yields. Methallyl chloride was found to be a competent
partner, providing nitrile 24h albeit in modest yield. Interestingly,
this olefin is also an allylating agent30 under these conditions,
providing a new olefin (not shown) which reacted further with 20
to give compound 24i. The same reaction carried out with
methallyl bromide led to no product. This carbo-cyanation also
temperature was effective, leading to full conversion of 20, but to
isolation of 6i in only moderate yield (entry 5). Di-t-butyldiazene
(
DTBD) under photochemical conditions22f afforded an
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Chemistry - A European Journal
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FULL PAPER
opens a straightforward access to 24j a precursor of Kuehne’s
aldehyde, a key synthon in the synthesis of important mono-
terpene indole alkaloids.31 Finally, the carbo-cyanation of
allylsilane 2d and 1-octene was also attempted with the sulfinyl
cyanide 20’ (~70-80% pure), using respectively AIBN at 80°C and
V-40 at 120°C. In both cases, only traces of the nitriles 6i and 24e
were observed, showing that 20’ is not an efficient cyanide
transfer agent.
from tin residues than in carbo-oximation. Carbo-cyanation was
also found to be more efficient than carbo-oximation for the
incorporation of a CN substituent on a quaternary center. Finally,
on a broader context, this work also complements recent studies
reported on the use of sulfone and sulfinate derivatives as radical
traps.32
Experimental Section
General procedure for the 3-component carbo-cyanation process
To a solution of the bromide or iodide (1.0 equiv) in dry benzene (1.0 M),
olefin (2.0 or 4.0 equiv), p-toluenesulfonyl cyanide
5 (2.0 equiv),
bis(tributyltin) (1.5 equiv) were added. The reaction mixture was degassed
for 20 min with argon and the process was initiated by adding DTBHN (20
mol%). The mixture was then stirred for 1.5 h at 65°C. The reaction
progress was monitored by TLC and another addition of DTBHN (20 mol%)
was performed when necessary, then the reaction mixture was stirred for
another 1.5 h at 65 °C. After 3 h, the reaction mixture was concentrated
under reduced pressure and the residue purified by flash chromatography
on silica gel.
General procedure for the “tin-free“ carbo-cyanation process using
sulfonyl cyanide 20.
In a sealed tube, sulfonyl cyanide 20 (2 equiv) and alkene (1 equiv) were
diluted in distilled chlorobenzene. The mixture was degassed for 15
minutes with argon and 1,1’-Azobis(cyclohexanecarbonitrile) (0.1 equiv)
was added in one portion. The flask was tightly closed and the reaction
mixture was stirred at 120°C for 2 h. The chlorobenzene was then partially
evaporated under reduced pressure and the crude reaction mixture was
directly purified by flash chromatography on silica gel.
Acknowledgements
H.H., V.P. and A.H. thank respectively the Erasmus-Mundus Green IT
program (3772227-1-2012-ES-ERA MUNDUS-EMA21), the “Fondation
pour le développement de la Chimie des substances Naturelles et ses
applications“ and the Shaheed Benazir Bhutto University for PhD grants.
The Erasmus+ and Algerian PNE programs are also acknowledged for
financial support respectively to M.W. and C.K. The CNRS and the
University of Bordeaux are thanked for financial help. M. Stephane Massip
Scheme 8. “Tin-free” carbocyanation reaction.
Conclusions
(IECB, University of Bordeaux) is acknowledged for X-ray diffraction
studies.
In summary, we reported a comprehensive study on the free-
radical carbo-cyanation of olefins. This process can be applied to
a broad range of electron-rich olefins, leading to functionalized
nitriles. The process is compatible with many functional groups
including ketones, esters, double bonds, amides, nitriles,
phosphonates and sulfonates. With very reactive olefins (strained
olefins, enol ethers,…), sulfonyl-cyanation products may be
formed, a problem which can be solved by decreasing the amount
of olefin in the medium. An efficient “tin-free” version was also
devised, relying on a new sulfonyl cyanide incorporating the
radical precursor, and easily available through oxidation of the
corresponding thiocyanate. Overall, the 3-component carbo-
Keywords: Radical • carbo-cyanation • multicomponent • -scission •
sulfones
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[
3
3
3
(
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Chemistry - A European Journal
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Entry for the Table of Contents
FULL PAPER
H. Hassan,[ V. Pirenne, W. Missing,
a]
[a]
[a]
C. Khiar,[
a],[b]
A.Hussain, F. Robert,
[a]
[a]
and Y. Landais*[
a]
Page No. – Page No.
Free-radical Carbo-cyanation of
Olefins.
The free-radical 3-component carbo-cyanation of electron-rich olefins has been
investigated using p-tosylcyanide as a cyanide source. Scope and limitation of the
process was established varying the nature of the alkene and that of the radical
precursor. A “tin-free” carbo-cyanation process was also devised, relying on the use
of a new alkylsulfonyl cyanide incorporating both carbon fragments which will be
added across the olefinic -system.
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