Boronic Acid Mediated Carbocyanation of Olefins and Vinylation of Alkyl Iodides

Article abstract of DOI:10.1002/ejoc.201800444

Phenylboronic acid was shown to mediate the multicomponent free-radical carbocyanation of olefins and the addition of alkyl iodides to vinylsulfones. The reaction of the boronic acid with di-tert-butyl hyponitrite generates an aryl radical, which can sele

Full text of DOI:10.1002/ejoc.201800444

A Journal of
Accepted Article
Title: Boronic-acid Mediated Carbo-cyanation of Olefins and Vinylation
of Alkyl Iodides
Authors: Reina HARA, Chahinaz KHIAR, Nitin S. DANGE, Pierre
BOUILLAC, Frederic ROBERT, and Yannick Landais
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: Eur. J. Org. Chem. 10.1002/ejoc.201800444
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800444
Supported by

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
Boronic-acid Mediated Carbo-cyanation of Olefins and Vinylation
of Alkyl Iodides
Reina Hara,[a] Chahinaz Khiar,[a][b] Nitin S. Dange,[a] Pierre Bouillac,[a] Frédéric Robert,[a] and Yannick
Landais*[a]
Abstract: Phenylboronic acid was shown to mediate the free-radical
multicomponent carbo-cyanation of olefins and the addition of alkyl
iodides onto vinylsulfones. Reaction of the boronic acid with di-tert-
butyl hyponitrite generates an aryl radical, which was able to
selectively abstract the iodine atom from alkyl iodide precursors to
form the key C-centered radical precursor. Arylboronic acids may thus
be considered as efficient tin surrogates in these free-radical
processes.
medium to sustain the radical chain (Figure 1, (3)). The
concomitant need for tin reagents, having perceived toxicity, still
hamper the development of C-C bond forming processes using
arylsulfonyl derivatives. While several solutions to this problem
have been reported in recent time,[8] including the use of
alkylsulfonyl analogues,[5a,d][9] there is still
a
need for
environmentally benign alternative methods to promote radical
processes using arylsulfonyl derivatives. Moreover, the synthesis
of the latter has been recently studied extensively, making them
readily available reagents.[10]
Introduction
In
R
X
R
While transition-metal catalyzed processes[1] constitute
a
(1)
R
SO2Ar
+
powerful method to build C-C bonds, free-radical strategies offer
an attractive alternative, allowing consecutive C-C bond
formations through cascade and multicomponent reactions.[2] The
addition of alkyl radicals onto C=C bonds provides an effective
mean to construct C-C bonds as it is energetically favorable.[3]
This addition generates a new radical species, which may then
react further with a radical trap, or be oxidized or reduced
respectively into carbocation or carbanion species.[4] Unsaturated
sulfone derivatives (vinyl-, alkynyl, cyano,…) are well-known
efficient radical traps for alkyl radicals, affording, through an
addition-elimination process, a new unsaturated system, along
with a sulfonyl residue (Figure 1, eq. 1).[5] The power of this
strategy has been illustrated earlier with simple addition of alkyl
halides to vinylsulfones,[6] and more recently in three-component
olefin carbo-alkynylation, alkenylation and cyanation, using the
corresponding arylsulfonyl precursors (Figure 1, eq. 2).[5b,7]
Depending on the nature of the substituent on the sulfonyl group,
the reaction however requires that a tin reagent is present in the
+ ArSO2
R'
R'
R
O
PhO2S
(Bu3Sn)2
PhO
DTBHN
OTBDMS (2)
PhO2C
I
SO2Ph
1,2-DCE
65°C
SO2Ph
64%
OTBDMS
R1
R2
EWG
(Bu3Sn)2
X
PhSO2
PhSO2-SnBu3
SO2Ph
(3)
X
t-BuO
R1
R2
Bu3Sn
(Bu3Sn)2
EWG
II
EWG
Y
Y=Br, I, SC(=S)
EWG
R1
I
Bu3SnY
[a]
R. Hara, C. Khiar, Dr. N. S. Dange, M. P. Bouillac, Dr. F. Robert,
Prof. Dr. Y. Landais
R2
Institute of Molecular Sciences, UMR-CNRS 5255
University of Bordeaux
Figure 1. Tin-mediated C-C bond formation using addition of alkyl halides to
351, Cours de la libération
33405 Talence cedex, France
unsaturated sulfonyl derivatives.
E-mail: yannick.landais@u-bordeaux.fr
http://ylandais-chemistry.info/
We report here on the development of a “tin-free” strategy, using
phenylboronic acids to mediate the three-component carbo-
cyanation of olefins and the vinylation of alkyl halides under
radical conditions. It is shown that alkyl radicals may be
selectively generated through the fast abstraction (k ~ 109 M-1 s-
[b]
C. Khiar
Laboratoire de Chimie Appliquée et du Génie Chimique (LCAGC)
Université Mouloud Mammerie de Tizi-Ouzou
15000, Tizi-Ouzou, Algeria
)
1 [11] of iodine atom from alkyl iodides by aryl radicals, issued from
the fragmentation of arylboronic acids under oxidative
conditions.[12] This fast abstraction outperforms all other
competitive processes which might occur in the medium,
Supporting information for this article is given via a link at the end of
the document
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
including the addition to sulfonyl derivatives or the olefin
partners.[13] Arylboronic acids are thus stable aryl radical
precursors, which may be regarded as useful tin surrogates in
above radical processes.
Table 1. Phenylboronic acid-mediated carbo-cyanation of olefin. Search for
an oxidant.
O
1
PhB(OH)2
Results and Discussion
I
PhS
2a
3a
p-TsCN (2 eq.)
+
Oxidant
Our studies started with the search for an oxidant able to initiate
the formation of the desired aryl radical.Preliminary studies were
thus carried out using -iodothioester 2a as a radical precursor,
2-ethylbutene 3a as model olefin and p-TsCN as a cyanide source
in the presence of PhB(OH)2 1 in benzene as a solvent. Several
oxidants were tested as summarized in Table 1. We first
investigated the use of di-tert-butyl hyponitrite (DTBHN), as
recent studies by Hayashi and co-workers showed that boronic
acids reacted cleanly with DTBHN to produce the corresponding
aryl radical.[14] Using conditions for the 3-component carbo-
cyanation of olefins reported earlier, we were pleased to observe
that using DTBHN and replacing (Bu3Sn)2 with 1 eq. of PhB(OH)2
1 led to the expected 4a in 44% yield (Table 1, entry 1). The
absence of 1 led to no reaction showing the importance of the
boronic acid in the transformation (entry 2). Increasing the amount
of 1 furnished 4a in 60% yield (entry 3), while a further increase
led to little improvement (entry 4). The amount of DTBHN was
also varied and surprisingly, an increase of the hyponitrite did not
raise the yield (entries 5-6), while decreasing the quantity to 0.6
eq. had a dramatic effect on the isolated yield of 4a (entry 7). It is
important noticing that in contrast with previous work using
(Bu3Sn)2 reagent[7] (see Figure 1, (3)), the PhSO2 radical does not
react with the boronic acid.[15] The process is therefore not a chain
and requires at least a stoichiometric amount of DTBHN. Although
conditions described in entry 3 seemed optimal, a rapid screening
of other peroxides was performed as DTBHN is quite expensive.
Results summarized in entries 8-12 (Table 1) indicate that only
PhCO3t-Bu in the presence of a catalytic amount of Cu(II)[16] was
able to afford acceptable yields of 4a (entry 11), albeit inferior to
those observed with DTBHN. Surprisingly, a poor yield was
obtained with t-BuOOt-Bu, while as in DTBHN a t-BuO radical is
generated upon heating at 130°C. Mn(OAc)3 in 1,2-
dichloroethane (DCE) was also tested (not shown), as it is known
to react efficiently with boronic acids,[17] but it failed to afford traces
of 4a. Using DTBHN as an oxidant, we also varied the amount of
2a (entry 13), p-TsCN (entry 14) and 3a (entry 15), showing that
the olefin and the cyanide source must be used in excess. Finally,
variation of the nature of the solvent was also looked at, using for
instance DCE or t-BuOH, which afforded respectively 28% and
3% of 4a, while CH3CN and acetone did not afford the required
compound. The nature of the boron derivative was also varied.
For instance, using the phenylpinacolborate instead of 1 led to 4a
in only 19% yield. Modifying the nature of the aryl radical using 4-
MeOPhB(OH)2 instead of 1, led to 50% yield. Amongst the by-
products that were formed, we were able to isolate a small
quantity of i (Table 1), which results from the carbo-cyanation of
isobutene, itself likely issued from the decomposition of t-
BuOB(OH)2.
PhSOC
CN
4a
Entry 2a (eq.) 3a (eq.) 1 (eq.) Oxidant (eq.)
Time (h) Yield [%][a]
DTBHN[b] (1.2)
DTBHN (1.2)
DTBHN (1.2)
DTBHN (1.2)
DTBHN (2)
DTBHN (2)
DTBHN (0.6)
t-BuOOt-Bu (2)
(PhCO2)2 (2) /
Cu(acac)
PhCO3t-Bu (2)
PhCO3t-Bu (2) /
Cu(acac)
K2S2O8 (2),
AgNO3
DTBHN (1.2)
DTBHN (1.2)
1
1
2
1
2
44
0
2
3
4
5
6
7
1
1
1
1
1
1
1
2
2
2
2
2
2
2
0
2
3
2
2
2
2
2
2
2
2
2
2
6
60
62
59
59
13
6
8[c]
9
1
2
2
24
10
10
11
1
1
2
2
2
2
48
48
-
40
12
1
2
2
15
-
13[d]
14[f]
15
11[e]
16
57
50
2
1
1
1
1
2
3
2
1
1
2
2
2
2
2
DTBHN (1.2)
DTBHN (1.2)
2[g]
16
[a] Yield of isolated products. [b] DTBHN: t-BuON=NOt-Bu. [c] 130°C. [d] 1:1
CH2Cl2/water was used as a solvent. [e] Trace amount of compound i below was
also isolated. [f] 1.2 eq. of p-TsCN was used. [g] 4-MeOPhB(OH)2 was used
instead of 1.
With the optimal conditions set up in entry 3 in hands, we then
studied the scope of the reaction, varying first the nature of the
olefin (Scheme 1). The process proved to be compatible with a
range of functional groups, including ketones, nitrile,
phosphonates, but also bromides and carbamates. Yields range
from moderate to good. The radical nature of the process is
indicated by the formation of nitrile 4j, generated from carbo-
cyanation of -pinene.[18] Surprisingly, the reaction of 2-
methoxypropene under optimized conditions led to a complex
mixture in which the expected nitrile 4e was absent.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
O
addition of the sulfonyl and cyanide fragments across the double
bond was not observed in the other cases, and may be attributed
to the combined effect of (1) the documented slow -
fragmentation of the sulfonyl radical in this case;[7b,22] (2) the lower
reactivity of radicals - to nitriles as compared to those - to
esters (i.e. 5a). A relatively low reactivity was also observed in
these reactions with radicals - to sulfones.[7f]
PhB(OH)2 1 (2 eq.)
I
PhS
p-TsCN (2 eq.)
R1
2a
(1.0 eq.)
DTBHN (1.2 eq.)
Benzene, 65 °C
R2
R1
+
PhSOC
PhSOC
CN
R2
4b-m
3b-m (2.0 eq.)
O
NHBoc
R
I
1
PhSOC
4b
CN
PhSOC
CN
4c
PhB(OH)2 (2 eq.)
CN
5a
, R = EtO2CCH2
p-TsCN (2 eq.)
R1
5b, R = EtO2CCF2
4d
57%
57%
74%
R2
CN
6a-g
DTBHN (1.2 eq.)
5c
5d
, R = NCCH2
R
, R = PhSO2CH2
Benzene, 65 °C
Br
+
OMe
R1
PhSOC
4e
CN
ND
PhSOC
PhSOC
CN
4f
PhSOC
CN
R2
3b-l
4g
60%
59%
F
OPiv
OPiv
F
OPiv
CN
EtO2C
CN
EtO2C
CN
EtO2C
CN
PhSOC
4h 30%
PO(OEt)2
CN
PhSOC
CN
6a 87%
6b 57%
6c 62%
4i 58%
4j 43%
F
F
OPiv
CN
EtO2C
CN
NC
6e 55%
OPiv
CN
6g-a
CN
PhO2S
CN
COSPh
PhSOC
CN
6d 55%
6f 47%
PhSOC
CN
CN
4k 68%
4l 65%
4m 63% (d.r. 1:1)
OPiv
CN
6g-b 44%
p-Ts
NC
Scheme 1. PhB(OH)2-mediated carbo-cyanation of olefins. Variation of the
55%
nature of the olefin.
Scheme 2. PhB(OH)2-mediated carbo-cyanation of olefins. Variation of the
nature of the radical precursor.
These preliminary studies were then extended to radical addition
varying the nature of the radical precursor 5a-d (Scheme 2).
Several iodides bearing an ester (5a), -difluoroester (5b),
nitrile (5c) or sulfone groups (5d) were reactive under the above
conditions, affording the desired nitriles 6a-g in moderate to
excellent yields. Difference of reactivity between iodides 5a and
5b is worth noticing,[19] the former generally leading to higher
yields. This observation had already been made previously in
carbo-alkenylation reactions.[7e] Several contrasting reports have
appeared recently concerning the role of fluorine substituents in
C-centered radicals.[20] While the strong electronegativity of the
fluorine atom should increase the electrophilicity of radical
intermediate I (Figure 1 (3)) and thus lead to improved reactivity
toward electron-rich olefins, this is not reflected in terms of yield
of 3-component adducts (compare 6b, 6d with non-fluorinated
analogues 6a, 6c). A recent report by Dolbier and co-workers[21]
The reaction was also applied to dienes 7, 9 and 11, leading to
the desired 3-component adducts albeit in moderate yields, but
generally good diastereoselectivity (Scheme 3). The
stereochemistry of 8, 10 and 12 were assigned based on X-ray
diffraction studies of related carbo-alkenylation products (i.e.
10),[7e] and relying on literature precedent for the 5-exo-trig radical
cyclizations (i.e. 12).[23]
.
showed that difluoroalkyl radicals (RCF2 ) reacted faster with the
most electron-deficient olefins, as a result of a polarized transition
state. Charge transfer from RCF2. to acrylonitrile for instance was
shown through computational studies to lead to the development
of a positive charge at the RCF2 carbon center stabilized by the
electron-donation of fluorine atoms. Although 5b also bears an
additional ester group, the resulting radical species may not be so
electrophilic, explaining its moderate reactivity toward electron-
rich olefins. Similar observations were done during previous
studies with related polyfluoroalkyl radicals.[7e,f] Finally, reaction
with electron-rich olefins such as vinyl pivalate led to the desired
nitrile 6g-a, along with the sulfonylcyanation product 6g-b. Such
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
R1
I
PhB(OH)2 (2 eq.)
O
1
1
PhB(OH)2 (2 eq.)
I
13a-g
DTBHN (1.2 eq.)
PhS
p-TsCN (2 eq.)
SO2Ph
15a-g
+
R1
PhSOC
2a
CN
DTBHN (1.2 eq.)
Benzene, 65 °C
SO2Ph
PhO2S
AcO
Benzene, 65 °C
14
8
, 31%, d.r. 8 : 2
SO2Ph
SO2Ph
7
AcO
15a
15b
52%
40%
O
PhB(OH)2 1 (2 eq.)
I
PhS
PhSOC
p-TsCN (2 eq.)
H
SO2Ph
SO2Ph
2a
SO2Ph
DTBHN (1.2 eq.)
Benzene, 65 °C
H
15c 74%
15e 67%
15d 71%
CN
10 35% (d.r. 95:5)
9
O
SO2Ph
PhB(OH)2 1 (2 eq.)
p-TsCN (2 eq.)
I
COSPh
PhS
2a
15f
EtO2C
EtO2C
57% d.r. > 95:5
DTBHN (1.2 eq.)
EtO2C
EtO2C
CN
Benzene, 65 °C
SO2Ph
51%
12, 42% (d.r. 95:5)
15g
11
Scheme 3. PhB(OH)2-mediated carbo-cyanation of dienes.
Scheme 4. PhB(OH)2-mediated vinylation of alkyl iodides.
Our efforts to extend the above vinylation to a three-component
carbo-alkenylation process[7e] unfortunately met with little success,
affording moderate yields of products, as exemplified below with
the carbo-alkenylation of vinyl pivalate 3i, which led to the 3-
component adduct 16 in 36% yield (Scheme 5).
The cyanation using sulfonylcyanide being efficient, we also
extended our investigation to the development of a carbo-
alkenylation and vinylation of alkyl halide.[6,8] We first studied the
addition of simple alkyl iodides to vinyl disulfone 14, an efficient
radical trap.[6n,7e] Under the same conditions than above, the
expected vinylated products were formed in satisfying yields
(Scheme 4). Primary, secondary and tertiary alkyl radicals added
efficiently onto 14. Interestingly, formation of vinylsulfone 15f
occurred with high stereocontrol and inversion of configuration of
the neomenthyl iodide precursor 13f. Finally, other vinylation
agents, including diethyl-2-(chloromethylene)malonate),[7e] 1,1,2-
1
EtO2C
5a
I
PhB(OH)2 (2 eq.)
OPiv
OPiv
DTBHN (1.2 eq.)
EtO2C
Benzene
3i
65 °C, 4 h
SO2Ph
PhO2S
SO2Ph
16 36%
14
trichloroethylene,[24]
or
(E)-ethyl-3-chloro-2-
(phenylsulfonyl)acrylate were also tested but led to disappointing
results with yields not exceeding 20%.
Scheme 5. PhB(OH)2-mediated carbo-alkenylation of olefins.
A final experiment was carried out in order to identify the presence
of an aryl iodide and thus the formation of an aryl radical as the
initiator of the radical process. Carbo-cyanation of n-octene 3f
was thus carried out as described above, using functionalized
boronic acid 17 instead of 1 to allow for the isolation of the
corresponding aryl iodide (Scheme 6). Under these conditions,
the carbo-cyanation product 4f was formed as the major
compound, along with the sulfonyl-cyanation product 18 and the
expected aryl iodide 19.[25] As mentioned above, this radical
process is not a chain reaction, and the electrophilic sulfonyl
radical, formed upon fragmentation of p-TsCN, may thus react
with excess olefin to generate 18.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
Experimental Section
EtO2C
B(OH)2
O
17 (2 eq.)
I
General Information: All reactions were carried out under an argon
atmosphere with dry solvents under anhydrous conditions. Yields refer to
chromatographically and spectroscopically (1H NMR) homogeneous
materials. Commercial reagents were used without purification, unless
otherwise stated. Silica gel 60M (230-400 mesh ASTM) was used for flash
chromatography. In some cases, silica gel was preliminary deactivated by
mixing with 5% (v/v) of triethylamine. CH2Cl2 was dried over activated
alumina columns on MBraun Solvent Purification System (SPS-800). DCE
and MeCN were distilled from CaH2 and benzene was distilled from
Na/Benzophenone. 1H-NMR and 13C-NMR were recorded on a Brüker
Avance-300 FT (1H: 300 MHz, 13C: 75.5 MHz), a Brüker DPX-400 FT (1H:
400 MHz, 13C: 100.2 MHz) and a Brüker Avance 600 (1H: 600 MHz, 13C:
150.9 MHz) apparatus using CDCl3 as internal reference unless otherwise
indicated. The chemical shifts (δ) and coupling constants (J) are expressed
in ppm and Hz respectively. FT-IR spectra were recorded on a Perkin-
Elmer Spectrum 100 using a diamond ATR accessory. HRMS were
recorded with a Waters Q-TOF 2 spectrometer in the electrospray
ionization (ESI) mode.
PhSOC
CN
PhS
p-TsCN (2 eq.)
4f 45%
2a
DTBHN (1.2 eq.)
Benzene
65°C, 2 h
EtO2C
I
p-Ts
CN
18 (22%)
3f
19 (10%)
Scheme 6. Boronic acid 17- mediated carbo-cyanation of n-octene.
Based on these experimental evidences, the mechanism of the
above radical processes may be summarized as in Figure 2.
Addition of the alkoxy radical (resulting from the thermal
decomposition of DTBHN) onto boronic acid 1, generates the
phenyl radical (eq. 1).[14] The latter then abstracts the iodine atom
from the alkyl iodide (eq. 2), to form radical I, which then reacts
with the electron-rich olefin to generate a new nucleophilic radical
II (eq. 3), being finally trapped by the sulfonyl derivative, leading
to the addition product, along with the sulfonyl radical (eq. 4).
PhSO2 radical does not react with 1 and thus is not able to
propagate the radical chain.[15] This has two consequences: (1)
equimolar amount of oxidant is required; (2) the sulfonyl radical
accumulates in the medium during the reaction and may, with
electron-richer olefins, provides sulfonyl-cyanation products such
as 18.[7f] Fortunately, addition of sulfonyl radicals onto olefins is a
reversible process,[22,26] so that sulfonyl-cyanation generally does
not impede the desired carbo-cyanation pathway.
Boronic-acid mediated carbo-cyanation - General procedure. To a
solution of iodide precursor 2a (1 eq.) in dry benzene (1 M), were added
olefin 3a-m (2 eq.), p-toluenesulfonyl cyanide (2 eq.) and phenyl boronic
acid 1 (2 eq.), and the reaction mixture was degassed for 10 min. Then,
the process was initiated by adding slowly DTBHN (1.2 eq) at room
temperature. The mixture was then stirred at 65°C and the reaction
progress monitored by TLC. After the reaction was completed, the mixture
was concentrated under reduced pressure and the residue purified by
chromatography on silica gel.
Boronic-acid mediated vinylation of alkyl iodides
– General
procedure. To a solution of alkyl iodide 13a-g (1 eq.) in dry benzene (1.0
M), was added (E)-1,2-bis(phenyl-sulfonyl)ethene 14 (2 eq.) and phenyl
boronic acid 1 (2 eq.). The reaction mixture was then degassed for 10 min
under argon, and the process initiated by adding DTBHN (1.2 eq.). The
mixture was stirred at 65°C and the reaction progress monitored by TLC.
After the reaction was complete, the solvent was concentrated under
reduced pressure and the residue purified by chromatography on silica gel.
t-BuO
Ph B(OH)2
(1)
(2)
Ph
EWG
+
+ PhI
Ph
EWG
I
I
R1
R2
R1
EWG
+
(3)
R2
EWG
II
I
R1
A
Acknowledgements
R1
R2
R2
+
PhSO2 (4)
+
A
SO2Ph
EWG
EWG
RH and CK thanks respectively the Yamaguchi University Faculty
of Engineering (YUFE) and the Algerian PNE program for
financial support. NSD thanks EU for a postdoctoral grant through
H2020 Marie-Curie IF program (N°655527). We also thank M.
Jonathan Lusseau for additional experiments. The CNRS and the
University of Bordeaux are thanked for financial help.
II
A = vinyl, alkynyl, CN, CH=NOR
(5)
Ph B(OH)2
+
PhSO2
PhSO2-Ph
X
Figure 2. Phenylboronic acid mediated three-component carbo-
functionalization of olefins.
Keywords: Radicals • C-C coupling • boronic acids • tin-free
Conclusions
methodology • sulfones
As a summary, we have described a “tin-free” carbo-cyanation of
olefins and vinylation of alkyl iodides using phenyl boronic acids
as radical mediators. The reaction of the t-BuO radical, resulting
from the decomposition of DTBHN, with the boronic acid
generates an aryl radical, which then abstracts the iodine atom
from alkyl iodides to form a C-centered radical, finally adding onto
the olefin to form a new C-C bond. Moderate to excellent yields of
2- and 3-component adducts are finally obtained, through a
methodology, which is operationally simple, using readily
available PhB(OH)2.
[1]
(a) A. Ding, H. Guo, Carbometalation and heterometalation reactions of
alkenes, alkynes and allenes in Comprehensive Organic Synthesis II,
Eds P. Knochel, G. A. Molander, Elsevier, 2014, Vol. 4, 891; (b) J. Choi,
G. C. Fu, Science 2017, 356, 152; (c) H. Yang, X. Yang, W. Tang,
Tetrahedron 2016, 72, 6143; (d) A. H. Cherney, N. T. Kadunce, S. E.
Reisman, Chem. Rev. 2015, 115, 9587; (e) M. Garcia-Melchor, X.
Solans-Monfort, G. Ujaque, C-C bond formation in Comprehensive
Organic Synthesis II, Eds J. Reedijk, K. Poeppelmeier, 2013, Vol. 9, 767.
(a) G. J. Rowlands, Tetrahedron 2009, 65, 8603 and references cited
therein; (b) G. S. C. Srikanth, S. L. Castle, Tetrahedron 2005, 61, 10377;
(c) I. Ryu, Multicomponent radical reactions. In Multicomponent Radical
[2]
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
Reactions; J. Zhu, H. Bienayme, Eds.; Wiley-VCH: Weinheim, 2005, pp
169-198; (d) V. Liautard, Y. Landais, in Multicomponent Reactions, Eds.
J. Zhu, Q. Wang, M. X. Wang, Wiley, 2nd Edition. 2014, pp 401-438.
[12] (a) I. B. Seiple, S. Su, R. A. Rodriguez, R. Gianatassio, Y. Fujiwara, A. L.
Sobel, P. S. Baran, J. Am. Chem. Soc. 2010, 132, 13194; (b) Y. Fujiwara,
V. Domingo, I. B. Seiple, R. Gianatassio, M. D. Bel, P. S. Baran, J. Am.
Chem. Soc. 2011, 133, 3292; (c) P. P. Singh, S. K. Aithagani, M. Yadav,
V. P. Singh, R. A. Vishwakarma, J. Org. Chem. 2013, 78, 2639; (d) J.
Wang, S. Wang, G. Wang, J. Zhang, X.-Q. Yu, Chem. Commun. 2012,
48, 11769; (e) M. Yan, J. C. Lo, J. T. Edwards, P. S. Baran, J. Am. Chem.
Soc. 2016, 138, 12692.
[3]
H. Subramanian, Y. Landais, M. P. Sibi in Comprehensive Organic
synthesis, Eds. G. A. Molander, P. Knochel, 2nd ed., Vol. 4, Oxford:
Elsevier, 2014, pp. 699-741.
[4]
[5]
Radicals in Organic Synthesis, ed. Renaud, P.; Sibi, M. P. Wiley-VCH,
Weinheim, Germany, 2001, vol. 1.
(a) F. Bertrand, F. Leguyader, L. Liguori, G. Ouvry, B. Quiclet-Sire, S.
Seguin, S. Z. Zard, C. R. Acad. Sci. Paris, 2001, 4, 547; (b) B. Ovadia,
F. Robert, Y. Landais, Chimia 2016, 70, 34; (c) I. J.Rosenstein in
Radicals in Organic Synthesis, ed. Renaud, P.; Sibi, M. P. Wiley-VCH,
Weinheim, Germany, 2001, vol. 1, pp. 50–71; (d) B. Quiclet-Sire, S. Zard,
Beilstein J. Org. Chem. 2013, 9, 557.
[13] Model reactions involving phenylboronic acids and DTBHN in the
presence of p-TsCN, vinylsulfones or olefins did not provide addition
products.
[14] N. Uchiyama, E. Shirakawa, R. Nishikawa, T. Hayashi, Chem. Commun.
2011, 47, 11671.
[15] V. Darmency, P. Renaud, Top. Curr. Chem. 2006, 263, 71.
[16] (a) J. Lalevée, J.-P. Fouassier, Overview of radical Initiation in
Encyclopedia of Radicals in Chemistry, Biology and Materials, 2012 J.
Wiley & Sons, Ltd; (b) Z. Xu, Z. Hang, L. Chai, Z.-Q. Liu, Org. Lett. 2016,
18, 4662.
[6]
For selected examples, see : (a) J. Gong, P. L. Fuchs, J. Am. Chem. Soc.
1996, 118, 4486; (b) J. Xiang, P. L. Fuchs, J. Am. Chem. Soc. 1996, 118,
11986; (c) J. Xiang, W. Jiang, J. Gong, P. L. Fuchs, J. Am. Chem. Soc.
1997, 119, 4123; (d) J. Xiang, P. L. Fuchs, Tetrahedron Lett. 1996, 37,
5269; (e) J. Xiang, W. Jiang, P. L. Fuchs, Tetrahedron Lett. 1997, 38,
6635; (f) J. Xiang, P. L. Fuchs, Tetrahedron Lett. 1998, 39, 8597; (g) X.
Liu, Z. Wang, X. Cheng, C. Li, J. Am. Chem. Soc. 2012, 134, 14330; (h)
G. Rouquet, F. Robert, R. Méreau, F. Castet, Y. Landais, Chem. Eur. J.
2011, 17, 13904; (i) J. Lei, X. Wu, Q. Zhu, Org. Lett. 2015, 17, 2322. (j)
J. L. García Ruano, J. Alemán, A. Parra, L. Marzo, Eur J. Org. Chem.
2014, 8, 1577 and references cited therein; (k) G. A. Russell, P.
Ngoviwatchai, H. I. Tastoush, Organometallics, 1988, 7, 696; (l) G. A.
Russell, H. I. Tashtoush, P. Ngoviwatchai, J. Am. Chem. Soc. 1984,106,
4622; (m) G. A. Russell, P. Ngoviwatchai, H. I. Tashtoush, A. Pla-
Dalmau, R. K. Khanna, J. Am. Chem. Soc. 1988,110, 3530; (n) N.
Miyamoto, D. Fukuoka, K. Utimoto, H. Nozaki, Bull. Chem. Soc. Jpn 1974,
47, 503; (o) Y. Amaoka, M. Nagatomo, M. Watanabe, K. Tao, S. Kamijo,
M. Inoue, Chem. Sci. 2014, 5, 4339; (p) T. Hoshikawa, S. Kamijo, M.
Inoue, Org. Biomol. Chem. 2013, 11, 164; (q) G. Rouquet, F. Robert, R.
Méreau, F. Castet, P. Renaud, Y. Landais, Chem. Eur. J. 2012, 18, 940.
(a) E. Godineau, Y. Landais, J. Am. Chem. Soc. 2007, 129, 12662; (b)
V. Liautard, F. Robert, Y. Landais, Org. Lett. 2011, 13, 2658; (c) Y.
Landais, F. Robert, E. Godineau, L. Huet, N. Likhite, Tetrahedron 2013,
69, 10073; (d) C. Poittevin, V. Liautard, R. Beniazza, F. Robert, Y.
Landais, Org. Lett. 2013, 15, 2814; (e) R. Beniazza, V. Liautard, C.
Poittevin, B. Ovadia, S. Mohammed, F. Robert, Y. Landais, Chem. Eur.
J. 2017, 23, 2439; (f) H. Hassan, V. Pirenne, M. Wissing, C. Khiar, A.
Hussain, F. Robert, Y. Landais, Chem. Eur. J. 2017, 23, 4651.
[17] (a) A. S. Demir, O. Reis, M. Emrullahoglu, J. Org. Chem. 2003, 68, 578;
(b) M. Tobisu, K. Koh, T. Furukawa, N. Chatani, Angew. Chem. Int. Ed.
2012, 51, 11363. Angew. Chem. 2012, 124, 11525; (c) A. Dickschat, A.
Studer Org. Lett. 2010, 12, 3972.
[18] D. M. Oldroyd, G. S. Fisher, L. A. Goldblatt, J. Am. Chem. Soc. 1950, 72,
2407.
[19] (a) E. Godineau, C. Schäfer, Y. Landais, Org. Lett. 2006, 8, 4871; (b) B.
Moreno, C. Quehen, M. Rose-Hélène, E. Leclerc, J. C. Quirion, Org. Lett.
2007, 9, 2477.
[20] (a) A. Studer, Angew. Chem. Int. Ed. 2012, 51, 8950. Angew. Chem.,
2012, 124, 9082; (b) D. Leifert, A. Studer, Angew. Chem., Int. Ed. 2016,
55, 11660. Angew. Chem. 2016, 128, 11832.
[21] X.-J. Tang, Z. Zhang, W. R. Dolbier, Jr., Chem. Eur. J. 2015, 21, 18961.
[22] The rate constant for the β-fragmentation of the β-tosyl benzoyl radical
was determined to be 2.7 x 105 s -1 M-1 . See: V. L. Timokhin, S. Gastaldi,
M. P. Bertrand, C. Chatgilialoglu, J. Org. Chem. 2003, 68, 3532.
[23] (a) J. C. Tripp, C. H. Schiesser, D. P. Curran, J. Am. Chem. Soc. 2005,
127, 5518 ; (b) E. Godineau, K. Schenk, Y. Landais, J. Org. Chem. 2008,
73, 6983.
[7]
[24] G. Kraus, B. Andersh, Q. Su, J. Shi, Tetrahedron Lett. 1993, 34, 1741.
[25] The low yield of iodide 19, as compared to the carbo-cyanation product
4f, is attributed to the difficulty in isolating pure 19 from a complex mixture.
[26] Rate constant for sulfonyl radical addition, see: C. Chatgilialoglu, O.
Mozziconacci, M. Tamba, K. Bobrowski, G. Kciuk, M. P. Bertrand, S.
Gastaldi, V. I. Timokhin, J. Phys. Chem. A 2012, 116, 7623. Rate
constant for sulfonyl radical -elimination, see: (a) P. J. Wagner, J. H.
Sedon, M. J. Lindstrom, J. Am. Chem. Soc. 1978, 100, 2579.
[8]
[9]
(a) A.-P. Schaffner, V. Darmency, P. Renaud, Angew. Chem., Int. Ed.
2006, 45, 5847. Angew. Chem., 2006, 118, 5979; (b) A. Schaffner, K.
Sarkunam, P. Renaud, Helv. Chim. Acta 2006, 89, 2450; (c) S. Kim, S.
Kim, Bull. Chem. Soc. Jpn. 2007, 80, 809; (d) S. Sumino, M. Uno, H.-J.
Huang, Y. K. Wu, I. Ryu, Org. Lett. 2018, 20, 1078.
(a) F. Le Guyader, B. Quiclet-Sire, S. Seguin, S. Z. Zard, J. Am. Chem.
Soc. 1997, 119, 7410; (b) F. Bertrand, B. Quiclet-Sire, S. Z. Zard, Angew.
Chem., Int. Ed. 1999, 38, 1943. Angew. Chem., 1999, 111, 2135; (c) S.
Kim, C. J. Lim, Bull. Korean. Chem. Soc. 2003, 24, 1219; (d) K. Weidner,
A. Giroult, P. Panchaud, P. Renaud, J. Am. Chem. Soc. 2010, 132,
17511; (e) B. Ovadia, F. Robert, Y. Landais, Org. Lett. 2015, 17, 1958;
(f) J. Lei, X. Wu, Q. Zhu, Org. Lett. 2015, 17, 2322.
[10] For selected recent examples, see: (a) S. Tang, Y. Wu, W. Liao, R. Bai,
C. Liu, A. Lei, Chem. Commun. 2014, 50, 4496; (b) Z. Huang, Q. Lu, Y.
Liu, D. Liu, J. Zhang, A. Lei, Org. Lett. 2016, 18, 3940; (c) Y. Sun, A.
Abdukader, D. Lu, H. Zhang, C. Liu, Green Chem. 2017, 19, 1255; (d) S.
Shaaban, S. Liang, N.-W. Liu, G. Manolikakes, Org. Biomol. Chem.
2017,15, 1947; (e) A. Rodríguez, W. J. Moran, J. Org. Chem. 2016, 81,
2543; (f) A. Garcia-Dominguez, S. Müller, C. Nevado, Angew. Chem. Int.
Ed. 2017, 56, 9949; (g) C. Simon Gloor, F. Denes, P. Renaud, Angew.
Chem. Int. Ed. 2017, 56, 13329; (h) A. S. Deeming, E. J. Emmett, C. S.
Richards-Taylor, M. Willis, Synthesis 2014, 46, 2701; (i) J. Zhang, Y. An,
J. Wu, Chem. Eur. J. 2017, 23, 9477.
[11] (a) M. R. Heinrich, Chem. Eur. J. 2009, 15, 820 and references cited
therein; (b) S. K. Fehler, M. R. Heinrich, Synlett 2015, 580.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800444
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Radical Addition
Reina Hara, Chahinaz Khiar, Nitin S.
Dange, Pierre Bouillac, Frédéric Robert,
and Yannick Landais*
Page No. – Page No.
Boronic-acid Mediated Carbo-cyanation
of Olefins and Vinylation of Alkyl Iodides
”Tin-free” carbo-cyanation of olefins and addition of alkyl iodides onto vinylsulfones was developed using phenylboronic acid as an
aryl radical precursor and tin surrogate. It was shown that the aryl radical was able to abstract selectively the iodine atom from alkyl
iodide precursors to generate alkyl radicals that were then used in C-C bond forming processes.
This article is protected by copyright. All rights reserved.