Radical Metal-Free Borylation of Aryl Iodides

Article abstract of DOI:10.1055/s-0036-1588431

A simple metal-free borylation of aryl iodides mediated by a fluoride sp ² -sp ³ diboron adduct is described. The reaction conditions are compatible with various functional groups. Electronic effects of substituents do not affect the borylation while steric hindrance does. The reaction proceeds via a radical mechanism in which pyridine serves to stabilize the boryl radicals, generated in situ.

Full text of DOI:10.1055/s-0036-1588431

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
special topic
A
en
S. Pinet et al.
Special Topic
Synthesis
Radical Metal-Free Borylation of Aryl Iodides
Sandra Pinet*
F
O
O
O
O
Virginie Liautard
B
B
O
Mégane Debiais
I
B
O
Mathieu Pucheault*
0
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0
0-
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2
7-
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1
2-
8
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3
R
R
SET
Institut des Sciences Moléculaires, UMR 5255 CNRS -
Université de Bordeaux, Bordeaux-INP, 351 cours de la
libération, 33405 Talence cedex, France
sandra.pinet@u-bordeaux.fr
44 examples
up to 88% yield
R = Br, Cl, F, CF3, CN, COR, COOR,
OR, NH2, alkyl, heteroaryl
mathieu.pucheault@u-bordeaux.fr
Published as part of the Special Topic Modern Strategies
for Borylation in Synthesis
Received: 21.03.2017
Accepted after revision: 02.05.2017
Published online: 29.05.2017
bonate was also able to mediate the borylation of aryl io-
dides with diboron in methanol.13 In this case, the authors
ruled out a radical mechanism, only mentioning a possible
C–I bond cleavage by cesium.
DOI: 10.1055/s-0036-1588431; Art ID: ss-2017-c0180-st
Abstract A simple metal-free borylation of aryl iodides mediated by a
fluoride sp2–sp3 diboron adduct is described. The reaction conditions
are compatible with various functional groups. Electronic effects of
substituents do not affect the borylation while steric hindrance does.
The reaction proceeds via a radical mechanism in which pyridine serves
to stabilize the boryl radicals, generated in situ.
In 2009, Marder’s group published a copper-catalyzed
borylation of aryl iodides in the presence of dialkoxydibo-
ron and potassium tert-butoxide.14 According to the au-
thors, in such conditions, a borylcopper species is formed,
promoting the borylation. If one considers examples of
base-mediated aryl halide borylations, the necessity for the
formation of a copper-boryl complex can be questioned. In
other words, can borylation of aryl halides be promoted by
tert-butoxide alone, or by other nucleophiles known to
form with dialkoxydiboron sp2–sp3 diboron adducts? In this
context, we present here a metal-free borylation of aryl io-
dides triggered by fluoride salts in the presence of pyridine
operating via a radical mechanism. During the preparation
of this paper, Zhang et al. reported a very similar borylation
method with potassium methoxide, in the presence of 4-
phenylpyridine.15
Key words metal-free borylation, radical process, cesium fluoride,
pyridine
Arylboronic acids and their derivatives are known to be
very important compounds in organic chemistry, as both
chemical intermediates and building blocks.1 Traditional
methods of preparation include a metal–halogen exchange
with lithium or magnesium on an aryl halide, followed by
reaction with trialkoxyboranes.1 Very recently, such reac-
tions have been extended to encompass aminoboranes2 and
bench-stable amine borane complexes.3 In parallel, metal-
catalyzed Miyaura’s borylation of aryl halides, sulfonates,
and diazonium salts with either alkoxyboron and dialkoxy-
diboron,4 or aminoboranes,5 and amine-borane complexes6
have been largely developed. Very recently, thermal7 and
photochemical8 metal-free borylation of isolated diazoni-
um salts or those generated in situ from anilines and tri-
azenes, have been studied. One example of metal-free bory-
lation of diaryliodonium salts has also been reported.9 In
contrast, metal-free borylation of aryl halides has been less
investigated (Scheme 1). In 2016, metal-free borylation of
aryl halides under irradiation was described by Mfuh et
al.10 and Chen et al.10c,d In 2012, Ito et al. reported an
alkoxy-mediated borylation of aryl bromides with silylbo-
rane,11 leading to the proposal of a carbanion-mediated
mechanism.12 In 2013, Zhang et al. showed that cesium car-
B(OR)2
X
RO
RO
OR
OR
R
+
B
B
R
X = I, Br, Cl, F
TMDAM, hν or TMEDA, TBAF, hν
L. Pengfei15a,b
MeCN/H2O/acetone
hν, MeOH
O.V. Larionov15c,d
X = I, Br
H. Ito16,17
L. Jiao20
PhSi(Me)2-Bpin, MeOK, DME
MeOK, 4-Ph-Py, MTBE, 85 °C, 12 h
X = I
J. Zhang18
Cs2CO3, MeOH, Δ
CsF, Py, DMSO, 105 °C, 2 h
this work
Scheme 1 Metal-free borylation of aryl halides
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

B
S. Pinet et al.
Special Topic
Synthesis
Using an excess of bispinacolatodiboron as the borylat-
ing agent and 3 equivalents of potassium tert-butoxide,
known to form sp2–sp3 diboron adduct,16 as starting condi-
tions the reaction mixture was heated to 100 °C in DMF for
24 hours leading to the desired borylated product 2a in 9%
yield (Table 1, entry 1). Despite the low yield, this clearly in-
dicates that copper is not compulsory, providing that the
mixture is sufficiently heated. This in turn, prompted us to
investigate the use of additives. Ethanol, likely to generate a
more nucleophilic ethoxide in situ, slightly improved the
yield (entry 2) whilst increasing the temperature to 140 °C
had a negative impact on the reaction (entry 3). Use of
phenanthroline led to better results. Indeed, at 80 °C 2a was
obtained in 49% yield, which was increased to a decent 78%
at 105 °C (entries 4 and 5). Yields were similar in NMP or
DMAC but improved in DMSO, 2a reaching 87% (entries 6 to
8). Using sodium instead of potassium as the counter ion
did not significantly affect the course of the reaction (entry
9). On the other hand, replacing the tert-butoxide by either
phenoxide or methoxide affected the product’s yield drasti-
cally (entries 9 and 11). Replacing potassium tert-butoxide
by cesium fluoride improved the yield of 2a to 94%. Keeping
cesium fluoride as the nucleophile, this reaction was con-
ducted at 105 °C in other solvents such as toluene, DMF, N-
methylpyrrolidinone, pyridine, dichloroethane, nitrometh-
ane, ethylene glycol diacetate, and isoamyl acetate. This,
however, mostly led to poor conversion (inferior to 20%) of
the aryl iodide.
Table 1 Metal-Free Borylation of 4-Iodoanisole Using Bispinacolatodi-
boron as the Borylating Agent
O
B2pin2 (5.2 equiv), base (3 equiv)
I
B
additive (0.4 equiv)
O
solvent, temp, time
O
O
2a
1a
Entry
Base
Additive
Solventa
Temp
(°C)
Time
(h)
Yield
(%)b
1
2
t-BuOK
none
EtOH
EtOH
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
Phen
none
DMF
100
100
140
80
24
24
24
18
18
18
18
18
18
18
18
18
18
9
25
8
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuONa
PhONa
MeONa
CsF
DMF
3
DMF
4
DMF
49
78
64
76
87
74
30
23
94
14
5
DMF
105
105
105
105
105
105
105
105
105
6
NMP
DMAC
DMSO
DMF
7
8
9
10
11
12
13
DMF
DMF
DMSO
DMSO
CsF
a A 0.5 M solution 4-iodoanisole was used.
b Yields were determined by GC/MS using decalin as internal reference.
Results obtained in the presence of sodium methoxide
were surprisingly not in agreement with the mechanism
proposed by Marder to explain Zhang’s aryl iodide boryla-
tion.13 Following the proposed mechanism, methanol
would be deprotonated by cesium carbonate. The resulting
nucleophilic methoxide would then attack one boron atom
of the diboron to form the sp2–sp3 diboron adduct
[B2pin2OMe]–, nucleophilic enough to facilitate the synthe-
sis of the pinacolboranate ester.16 As methylate is more nu-
cleophilic than tert-butoxide, one would expect a better re-
sult with methoxide. Nevertheless, the opposite was ob-
served. In the absence of phenanthroline, the reaction
became sluggish (Table 1, entries 1 and 13). One can there-
fore wonder if an ionic mechanism is really implied in this
arylborylation or a radical process occurs. tert-Butoxide is
known to be a reducing agent by itself,17 or as adduct with
ligands18 such as phenantholine,19 phenylhydrazine,20 dial-
kylamines,21 and diols.22 Furthermore, fluoride has also
been used as a reductant in single-electron-transfer pro-
cesses.23
cies between reaction conditions (Tables 2 and 3). Various
experiments were conducted varying the bispinacolatodi-
boron:CsF ratio (Table 2, entries 1 to 14). In the absence of
cesium fluoride, no reaction occurred, indicating that this
reagent is mandatory to the reaction (entry 1). Moreover, it
seems that three equivalents of cesium fluoride are re-
quired to reach a complete conversion of 1b (entries 4, 5, 8,
12, and 13). A minimum of 2 equivalents of bispinacolato-
diboron is essential to attain an acceptable yield of 3a (en-
tries 8, 9 12, and 13 vs entries 4 and 5). Using higher
amounts of diboron does not improve 3a formation (entries
10 to13) and increasing the cesium fluoride quantity favors
the formation the by-product 4 (entry 4 vs 5, and entry 8 vs
9).
As a result, a 2:3 B2pin2/CsF ratio was kept. Varying the
halide source, we clearly demonstrated that the softer the
fluoride counter ion is, the better the results are (Table 2,
entries 8, 14 to 16). Interestingly, tetramethylammonium
fluoride (entry 16) led to complete conversion and 3a is ob-
tained in 30% yield and 4 in 29% yield. The high amount of 4
is most likely due to the water present in the hygroscopic
ammonium salt. This attempt with tetrametylammonium
fluoride proves that the cesium ion is not implicated in the
cleavage of the C–I bound. This is confirmed by the experi-
ment carried out with cesium chloride in which almost no
conversion of 1b was observed (entry 17).
During this preliminary study, the formation of anisole
was noticed. This by-product may result from either a pro-
todeborylation phenomenon or the direct protonation of an
intermediate. Reaction optimization was continued using
1-iodonaphthalene, which had usually led to mitigate re-
sults and can therefore be used to increase the discrepan-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

C
S. Pinet et al.
Special Topic
Synthesis
O
B
I
B2pin2 (2 equiv), CsF (3 equiv), Py (1 equiv)
DMSO (1.1 M), 105 °C, Ar, 2 h
R
O
R
2a–m; 3a,b
5a–k; 6a–i; 7–18
Bpin
H2N
NC
O
Bpin
MeO2C
H2N
Bpin
Bpin
Bpin
O
Bpin
Bpin
O
Bpin
H2N
O
NH2
6b: 32% (17%)
2a: 94% (85%)c
5a: 96% (83%)
6a: 40% (31%)d
8: 62% (43%)
7: 28% (22%)
2b: 33%
5b: 61%
[80%]
[85%]
Bpin
Bpin
Bpin
Bpin
Bpin
Cl
Cl
Bpin
F3C
Bpin
Cl
Bpin
10: 89% (73%)
Bpin
F3C
2d: 85% (73%) [51%] 5d: 94% (81%)
CF3
6d: 16%d
2c: 94% (83%)a
5c: 98% (86%)a
6c: 75% (67%)a
[83%]
9: 80% (62%)
[94%]
[84%]
Bpin
Bpin
Bpin
Bpin
F
Bpin
Br
Bpin
Cl
Bpin
NC
F
F
Br
Br
F
F
6f: 37% (28%)b
12: 32%
2e: 91% (79%) [75%]
5e: 78%
6e: 36%
11: 83% (71%)
2f: 97% (88%)
5f: 77% (69%)
F
Bpin
Bpin
Cl
Bpin
Cl
Bpin
Bpin NC
Bpin
NC
Bpin
13: 54% [79%]
F
Bpin
Cl
CN
F
14: 53%
2g: 96% (82%)
5g: 91% (76%)
[68%]
6g: 42% (32%)
5h: 55%
5i: 71%
6i: 26%
[67%]
Bpin
Bpin
Bpin
Bpin
MeOC
Bpin
Bpin
EtO2C
Bpin
Bpin
EtO2C
MeOC
N
2j: 80%b [67%]
3a: 71% (65%)c
2k: 66%b
16: 55%
5j: 78%
15: 91% (79%)
5k: 56%
3b: 66% (59%)
[50%]
Bpin
O
Bpin
Bpin
Bpin
S
2l: 65%
Bpin
18: 54% (32%)
Bpin
17: 19% [51%]
2m: 81% (72%)
Scheme 2 Aryl iodide borylation: scope and limitations. Reagents and conditions: ArI (0.5 mmol, 1 equiv), bispinacolatodiboron (2 equiv), CsF (3 equiv),
pyridine (1 equiv) in distilled DMSO (0.4 mL), argon, 105 °C for 2 h. The reaction was conducted with (a) 0.8 equiv, (b) 0.5 equiv, and (c) 0.4 equiv of
pyridine; (d) 2 to 3% of the regioisomer 5 was detected by GC/MS analysis. Yields were determined by GC/MS using decalin as internal reference. Yields
of isolated products are given in parenthesis. For comparison, yield of isolated products from ref. 20 are shown in square brackets.
The influence of the additive was then studied (Table 3).
In the absence of nitrogen heteroaromatics, 3a was ob-
tained in 15% yield besides a significant amount of naph-
thalene (4; 20%); in these conditions, the conversion of 1b
reached only 56% (Table 3, entry 1). With phenylhydrazine,
2,2′-bipyridine, pyrrole, 2-aminopyrimidine, 1,2,3,4-tetra-
hydroquinoline, imidazole or piperazine derivatives, and di-
methylfuran, conversions of 1b were deceiving (entries 3, 5,
6, 10, 18 to 20, and 22 to 24), the best yield in 3a being ob-
tained in the presence of N-methylimidazole (41%, entry
18). Thiophene derivatives and sulfides favor the formation
of naphthalene (entries 7–9) although with 2,2′-bithio-
phene, the desired borylated product 3a was obtained in a
yield comparable to phenanthroline (entries 8 and 2).
2,4,6-Tris(2-pyridyl)-s-triazine and 4-methylquinoline
(lepidine) seem to be as efficient as phenanthroline (Table
3, entries 21 and 25). Pyridine appeared to be the best addi-
tive with 100% conversion and 71% yield (entry 4). Use of
various substituted pyridines did not allow for an increase
in the yield (entries 11 to 16). 1H NMR experiments carried
out in order to determine the optimal temperature show
that the aryl iodide is consumed only at temperatures high-
er than 80 °C (Figure 1S, Supporting Information). With
these optimized conditions in hand, the scope and limita-
tions of this reaction were investigated (Scheme 2). The
concentration of aryl iodide was fixed at 1 M. In such condi-
tions, 1-iodonaphthalene was consumed completely in 1.5
hours. Reactions were carried out at 105 °C for 2 hours be-
fore GC/MS analysis. Overall, yields positively correlated to
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

D
S. Pinet et al.
Special Topic
Synthesis
Table 2 Influence of the Diboron/Fluoride Ratio and the Halide Source
spectively. The reaction conditions are compatible with flu-
orides and chlorides but also bromides, esters, ketones ni-
triles, or methoxy groups. Although less efficient, the bory-
lation is also possible in the presence of free amines. For
instance, anilines 2b and 5b were synthesized in 33% and
61% yield, respectively. 1-Iodo- and 2-iodonaphthalene led
to comparable results. Finally, heteroaromatic iodides such
as quinoline and dibenzofuran also react, leading to 16 and
18 in 55% and 54% yield, respectively. In contrast, thiophene
does not react well (compound 17 obtained in 19% yield on-
O
O
I
B
B2pin2 (x equiv), halide (y equiv)
Phen (0.4 equiv)
+
DMSO, 105 °C, 18 h
1b
3a
4
Entrya
B2pin2
(equiv)
Halide
Conv. (%)b Yield (%)b
3a
4
1
2
2
1
1
1
1
2
2
2
2
3
3
3
3
2
2
2
2
2
none
0
43
0
20
27
28
24
25
45
58
55
28
51
60
57
46
1
0
12
18
18
24
5
Table 3 Lewis Base Additive Effect
CsF (1 equiv)
CsF (2 equiv)
CsF (3 equiv)
CsF (4 equiv)
CsF (1 equiv)
CsF (2 equiv)
CsF (3 equiv)
CsF (4 equiv)
CsF (1 equiv)
CsF (2 equiv)
CsF (3 equiv)
CsF (4 equiv)
KF (3 equiv)
NaF (3 equiv)
NMe4F (3 equiv)
CsCl (3 equiv)
KI (3 equiv)
3
73
4
100
100
49
O
O
I
B
B2pin2 (2 equiv), CsF (3 equiv)
5
additive (0.4 equiv)
4
+
6
DMSO, 105 °C, 18 h
7
84
6
3a
1b
8
100
100
55
11
21
6
Entrya
Additive
Conv. (%)b Yields (%)b
9
3a
4
10
11
12
13
14
15
16
17
18
85
8
1
2
none
56
100
78
15
58
37
71
29
23
17
55
35
21
42
41
27
27
46
47
44
41
30
35
56
19
17
16
56
20
11
21
6
100
100
86
12
10
16
1
1,10-phenanthroline
phenylhydrazine
pyridine
3
4
100
62
11
5
2,2′-bipyridine
2
100
4
30
1
29
2
6
pyrrole
84
8
7
thiophene
67
20
42
41
19
28
6
6
1
0
8
2,2′-bithiophene
diphenyl sulfide
2,5-dimethylfuran
N,N-dimethylaminopyridine
4-aminopyridine
3-aminopyridine
2-amino-4-methylpyridine
2-phenylpyridine
2-methylpyridine
3,5-dimethylpyrazole
N-methylimidazole
imidazole
100
81
a A 0.5 M solution 1-iodonaphthalene was used.
9
b Conversions and yields were determined by 1H NMR analysis after workup
and filtration though silica gel.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
79
100
87
the amount of pyridine added, maximizing at 0.8 equiva-
lent. The amount of pyridine was therefore stated to 1
equivalent. In some cases, it was possible to diminish the
pyridine quantity without hampering yields. For instance,
with 4-iodoanisole 2a is obtained in an excellent yield of
94%, using only 0.5 equivalent of additive. Likewise, 4-
methylphenyl and 3-methylphenyl boronates (2c and 5c)
were obtained with 0.8 equivalent of pyridine in 94% and
98% yield, respectively.
As shown in Scheme 2, the reaction works well on sub-
strates with substituents in para or meta positions to the
iodine atom (compounds 2 and 5). This is efficient for both
electron-donating and -withdrawing groups in yields vary-
ing from 55 to 98%. Substrates with two substituents in the
either meta and para positions (compounds 7 to 12) or in
meta and meta′ positions (compounds 13 to 15) were ob-
tained in comparable or slightly lower yields. Diiodoarenes
can be bisborylated in good yields as shown in the case of
compounds 2l and 2m, obtained in 65% and 81% yield, re-
58
3
70
13
31
21
20
9
100
93
100
91
73
11
13
17
48
4
2-aminopyrimidine
2,4,6-tris(2-pyridyl)-s-triazine
1-methylpiperazine
1,2,3,4-tetrahydroquinoline
piperazine
87
100
85
60
61
7
4-methylquinoline
100
20
a A 0.5 M solution 1-iodonaphthalene was used.
b Conversions and yields were determined by 1H NMR analysis after workup
and filtration though silica gel.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

E
S. Pinet et al.
Special Topic
Synthesis
ly). The borylation is also very sensitive to steric hindrance
as shown in the case of ortho-substituted compounds 6, for
which the yields drop drastically; they are between 25%
and 40% except in the case of 6c (R = Me: 75%). These re-
sults differ slightly from those described by Jiao15 (yields
given between square brackets for comparison). Compara-
ble yields are obtained for methoxy and methyl substitu-
ents in para- and meta-positions (compounds 2a, 5a, 2c,
and 5c), higher yields in the case of the ortho-substituted
compound 6c. Under Jiao’s conditions, the thiophene 17
was borylated in 51% yield. On the other hand, with elec-
tron-withdrawing groups such as trifluoromethyl, chloride,
and fluoride (compounds 2d, 2e, and 2g), our system leads
to better results. Moreover, in the present case, the boryla-
tion is possible in the presence of bromides, which react us-
ing the previously described system. These results clearly
show that both methods are complementary. By GC/MS
analysis, we noticed that 2 to 3% of regioisomers 5a and 5d
were formed during the syntheses of 6a and 6d, respective-
ly. The presence of such by-products indicates that a 1,2-
migration of hydrogen atom occurs during the reaction,
probably to compensate for the steric hindrance. Such mi-
gration, added to the fact that conversion in the borylated
product could not be correlated to the solvent’s ionic con-
stant, favors the radical mechanism. To check this hypothe-
sis, complementary experiments were conducted on com-
pound 19 known to give the cyclic product 20 via radical in-
termediate (Table 4). In the absence of either cesium
fluoride or bispinacolatodiboron, with or without pyridine
(Table 4, entries 1 to 3), only starting material 19 was recov-
ered.
F
O
O
O
O
O
O
O
O
CsF
B
B
B
B
Cs
A
Reducing agent
A
Ar-I
F
O
O
F
SET
B
D
O
O
F
N
B
O
B
B
O
C
Boryl radical stabilized by pyridine
[Ar-I]
Ar
Cs
CsI
B
O
or
Ar
B
O
B2pin2
B
Scheme 3 Proposed reaction mechanism
dine shows that pyridine has an impact on the starting ma-
terial/cyclic product ratio (entries 4 and 5). In the absence
of pyridine, cyclization remained limited, with 84% of re-
maining 19. In the presence of pyridine, the 19:20 ratio was
reversed in favor of the cyclic compound 20 that now rep-
resents 83% of the mixture. Thus, the pyridine would stabi-
lize radical intermediates. Such stabilization of boryl radi-
cals has been already proposed in literature.24 From these
results, we propose the possible mechanism described in
Scheme 3. The fluoride ion reacts with bispinacolatodibo-
ron to form adduct A. This negatively charged intermediate
A would be reductive enough to reduce the aryl iodide via a
single-electron-transfer process and generate the radical
anion, precursor to the aryl radical. Simultaneously, boryl
radical pyridine adduct B and fluoropinacolborane C would
be formed. Intermediate C can react with A to drive out D
and regenerate the starting diboron. The formation of A, C,
and D has been confirmed by 19F and 11B NMR spectroscopy
(Figures S2 and S3, Supporting Information). The final prod-
uct is then obtained by reaction of the aryl radical with ei-
ther B or B2pin2. In this last case, the boryl radical interme-
diate B would be formed again. The mechanism proposed
by Zhang et al. is slightly different. In their case the ‘ate’
complex resulting from the addition of methylate to the di-
boron reacts with pyridine to form a Bsp3–Bsp3 adduct.
Homolytic cleavage of the intermediate generates a pyr-
idine stabilized boryl radical and an alkoxyboronate radical
anion responsible for the SET process. In our case, as the re-
action is possible in the absence of pyridine, we think that
the species undergoing the SET process is the ‘ate’ complex
A. Pyridine is, however, useful for stabilization of boryl rad-
ical B reacting subsequently with aryl radicals in the down-
stream process.
The introduction of CsF to diboron leads to the forma-
tion of cyclic compound 20, indicating that a radical inter-
mediate is generated (Table 4, entry 4). Moreover, this radi-
cal cannot be generated from only a fluoride ion, although
it is known to be a possible reducing agent. Comparison of
experiments carried out in the presence or absence of pyri-
Table 4 Complementary Experiments
I
B2pin2 and/or CsF and/or Py
DMSO, 105 °C, 2 h
OBn
O
20
19
Entry
Experimental conditions
Obtainedproducts
(ratio)
CsF
B2pin2
(equiv)
Pyridine
(equiv)
(equiv)
1
2
3
4
5
0
3
3
3
3
2
0
0
2
2
0.4
0
19
To conclude, a metal-free borylation method has been
developed showing that fluoride can promote single-elec-
tron transfer to the aryl iodide by forming a sp2–sp3 diboron
adduct. The absence of strong base such as t-BuOK rules out
an entirely ionic mechanism and may widen the scope of
this reaction.
19
0.4
0
19
19/20 (84:16)
19/20 (13:87)
0.4
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

F
S. Pinet et al.
Special Topic
Synthesis
DMSO and pyridine were purchased from Sigma Aldrich, dried over
CaH2, and freshly distilled before use. All commercially available re-
agents were used directly as received, unless otherwise specified. CsF
was purchased from Aldrich, dried, and maintained anhydrous at 35
°C under vacuum. Aryl iodides were purchased from various commer-
cial sources (TCI, Aldrich, Fluorochem). Bispinacolatodiboron and bor-
ylated products used as references for GC calibration curves were pur-
chased from Fluorochem. Analytical TLC was carried out using 0.25
mm silica gel plates purchased from Merck. Eluted plates were visual-
ized using KMnO4 solution. Purification of products was accom-
plished by flash column chromatography on silica gel (Sigma Aldrich
silica gel, 230–400 mesh particle size). Melting points were measured
using a Kofler Heizbank melting point bench (model 7841). NMR
spectra were recorded on a Bruker Avance 300 or Avance 400 spec-
trometers relative to TMS (external standard). All coupling constants
are reported in Hz. Standard abbreviations were used for the NMR
spectral splitting patterns. GC/MS analyses were performed on an Ag-
ilent 7890A instrument equipped with a J & W Scientific DB-1701
capillary column and an Agilent 5975C VL MSD with triple axis detec-
tor (EI). The following methods were used. Method 1: 70 °C for 1 min,
then 20 °C/min until 230 °C. Method 2: 20 °C/min from 100 to 280 °C.
Response coefficients of both aryl iodides and borylated products
were determined using decalin as internal reference and commercial-
ly available pure chemicals or purified borylated products. Benzyl 2-
iodophenyl ether (19) was synthesized according to published proce-
dure.25
2-(4-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(2a)
[CAS Reg. No. 171364-79-7]
Compound 2a was synthesized according to General Procedure A
from 4-iodoanisole (117 mg) and pyridine (16 μL, 0.4 equiv). Purifica-
tion by column chromatography (elution gradient: 100:0 to 95:5 pen-
tane/EtOAc) gave 2a (110 mg, 0.47 mmol, 85%) as a colorless oil; Rf =
0.32 (pentane/EtOAc 95:5).
1H NMR (CDCl3, 300 MHz): δ = 7.66 (d, J = 8.7 Hz, 2 H, ArH), 6.79 (d, J =
8.7 Hz, 2 H, ArH), 3.70 (s, 3 H, OCH3), 1.23 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 161.1, 135.4, 112.2, 82.5, 54.0, 23.8.
11B NMR (CDCl3, 96 MHz): δ = 30.9 (s, Bpin).
GC/MS (EI, Method 1): tR = 8.88 min; m/z (%) = 234.1 (M+., 64), 219.1
(42), 148.1 (47), 134.0 (100).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)toluene (2c)
[CAS Reg. No. 195062-57-8]
Compound 2c was synthesized according to General Procedure from
4-iodotoluene (109 mg) and pyridine (32 μL, 0.8 equiv). Purification
by column chromatography (eluent: pentane/EtOAc 98:5) gave 2c (91
mg, 0.42 mmol, 83%) as a pale yellow oil; Rf = 0.20 (pentane/EtOAc
98:2).
1H NMR (CDCl3, 300 MHz): δ = 7.62 (d, J = 7.9 Hz, 2 H, ArH), 7.09 (d, J =
7.9 Hz, 2 H, ArH), 2.28 (s, 3 H, CH3), 1.25 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 141.3, 134.8, 128.5, 83.6, 24.8, 21.7.
11B NMR (CDCl3, 96 MHz): δ = 30.9 (s, Bpin).
Metal-Free Borylation of Aryl Iodides
GC/MS (EI, Method 1): tR = 7.78 min; m/z (%) = 219.1 (M+., 38), 203.1
For Solid Aryl Iodides; General Procedure A
An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir
bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv), bispinacolato-
diboron (254 mg, 1 mmol, 2 equiv), and the appropriate aryl iodide
(0.5 mmol). Under an argon atmosphere, freshly distilled DMSO (0.4
mL) and pyridine (0.4 to 1 equiv) were added successively using a sy-
ringe. The reaction mixture was heated to 105 °C and stirred and
stirred for 2 h under argon.
(53), 130.1 (66), 119.0 (100).
4,4,5,5-Tetramethyl-2-(4-trifluoromethylphenyl)-1,3,2-dioxaboro-
lane (2d)
[CAS Reg. No. 214360-65-3]
Compound 2d was synthesized according to General Procedure B
from 4-iodobenzotrifluoride (136 mg) and pyridine (40 μL, 1 equiv).
Purification by column chromatography (eluent: pentane/EtOAc
98:2) gave 2d (99 mg, 0.36 mmol, 73%) as a white solid; mp 71 °C
(Lit.4g mp 68–69 °C); Rf = 0.15 (pentane/EtOAc 98:2).
1H NMR (CDCl3, 300 MHz): δ = 7.83 (d, J = 7.7 Hz, 2 H, ArH), 7.52 (d, J =
7.7 Hz, 2 H, ArH), 1.27 (s, 12 H, 4 × CH3).
For Liquid Aryl Iodides; General Procedure B
An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir
bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv) and bispinaco-
latodiboron (254 mg, 1 mmol, 2 equiv). Under an argon atmosphere,
freshly distilled DMSO (0.4 mL), the appropriate aryl iodide (0.5
mmol), and pyridine (0.4 to 1 equiv) were added successively. The re-
action mixture was heated to 105 °C and stirred for 2 h under argon.
13C NMR (CDCl3, 75 MHz): δ = 135.0, 132.8 (q, JC,F = 32.1 Hz), 124.3 (q,
JC,F = 3.8 Hz), 124.0 (q, JC,F = 272.3 Hz), 84.2, 24.8.
11B NMR (CDCl3, 96 MHz): δ = 30.5 (s, Bpin).
Analysis (A or B)
GC/MS (EI, Method 1): tR = 6.85 min; m/z (%) = 272.1 (M+., 9), 257.1
For analysis purpose by GS/MS only, DMF (2 to 4 mL) was added to the
mixture in order to dissolve the solid residue and a precisely weighed
amount of decalin (internal standard) was added (40 μL).
(100), 229 (9), 186 (73), 173.0 (76).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)fluorobenzene
(2e)
Workup and Purification (A or B)
[CAS Reg. No. 214360-58-4]
Et2O (100 mL) and aq 0.1 N HCl (10 mL) were added to the crude mix-
ture. The aqueous phase was extracted with Et2O (2 × 10 mL). The
combined organic layers were dried (anhyd Na2SO4), concentrated
under reduced pressure, and the residue was purified by silica gel
flash column chromatography to yield the pure aryl pinacolboronate.
Compound 2e was synthesized according to General Procedure B
from 1-fluoro-4-iodobenzene (58 μL, 111 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient:
100:0 to 7:3 PE/EtOAc) gave 2e (88 mg, 0.44 mmol, 79%) as a colorless
oil; Rf = 0.15 (PE/EtOAc 98:2).
1H NMR (CDCl3, 300 MHz): δ = 7.71 (dd, J = 8.7 Hz, JH,F = 6.2 Hz, 2 H,
ArH), 6.96 (dd, JH,F = 8.8 Hz and J = 8.7 Hz, 2 H, ArH), 1.26 (s, 12 H, 4 ×
CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

G
S. Pinet et al.
Special Topic
Synthesis
13C NMR (CDCl3, 75 MHz): δ = 165.1 (d, JC,F = 250.3 Hz), 137.0 (d, JC,F
8.2 Hz), 114.8 (d, JC,F = 20.2 Hz), 83.9, 24.8.
11B NMR (CDCl3, 96 MHz): δ = 30.6 (s, Bpin).
=
100:0 to 95:5 pentane/EtOAc) gave 3a (83 mg, 0.33 mmol, 65%) as a
pale yellow solid; mp 57–58 °C (Lit.4g mp 54–55 °C); Rf = 0.36 (pen-
tane/EtOAc 95:5).
1H NMR (CDCl3, 300 MHz): δ = 8.68 (d, J = 8.6 Hz, 1 H, ArH), 8.00 (dd,
J = 6.8, 1.2 Hz, 1 H, ArH), 7.85 (d, J = 8.2 Hz, 1 H, ArH), 7.75 (dd, J = 7.7,
1.4 Hz, 1 H, ArH), 7.45 (td, J = 7.1, 1.4 Hz, 1 H, ArH), 7.44–7.34 (m, 2 H,
Ar), 1.34 (s, 12 H, 4 × CH3).
19F NMR (CDCl3, 282 MHz): δ = –108.4 (tt, JH,F = 8.8, 6.2 Hz, Ar–F).
GC/MS (EI, Method 1): tR = 6.85 min; m/z (%) = 222.1 (M+., 17), 207.1
(79), 136.0 (38), 123.0 (100), 85.0 (14).
13C NMR (CDCl3, 75 MHz): δ = 136.9, 135.6, 133.1, 131.6, 128.4, 128.3,
126.3, 125.4, 124.9, 83.7, 24.9.
11B NMR (CDCl3, 96 MHz): δ = 30.5 (s, Bpin).
2-(4-Bromophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2f)
[CAS Reg. No. 68716-49-4]
Compound 2f was synthesized according to General Procedure A from
1-bromo-4-iodobenzene (142 mg) and pyridine (40 μL, 1 equiv). Puri-
fication by column chromatography (elution gradient: 100:0 to 7:3
PE/EtOAc) gave 2f (124 mg, 0.44 mmol, 88%) as a white solid; mp 68–
70 °C ; Rf = 0.21 (PE/EtOAc, 98:2).
1H NMR (CDCl3, 300 MHz): δ = 7.58 (d, J = 8.4 Hz, 2 H, ArH), 7.42 (d, J =
8.4 Hz, 2 H, ArH), 1.26 (s, 12 H, 4 × CH3).
GC/MS (EI, Method 1): tR = 10.91 min; m/z (%) = 254.1 (M+., 61), 239.1
(11), 210.1 (11), 181.1 (16), 168.1 (23), 154.1 (100), 128.0 (8), 77.0 (5),
59.0 (3).
4,4,5,5-Tetramethyl-2-(naphthalen-2-yl)-1,3,2-dioxaborolane (3b)
[CAS Reg. No. 256652-04-7]
Compound 3b was synthesized according to General Procedure A
from 2-iodonaphthalene (127 mg) and pyridine (40 μL, 1 equiv). Puri-
fication by column chromatography (elution gradient: 98:2 to 95:5
pentane/EtOAc) gave 3b (38 mg, 0.30 mmol, 59%) as a white solid; mp
62–63 °C (Lit.26 mp 62–65 °C); Rf = 0.40 (PE/EtOAc, 95:5).
13C NMR (CDCl3, 75 MHz): δ = 135.3, 129.9, 125.2, 83.0, 23.8.
11B NMR (CDCl3, 96 MHz): δ = 30.7 (s, Bpin).
GC/MS (EI, Method 1): tR = 8.77 min; m/z (%) = 282.0 (M+., 41), 267.0
(100), 196.9 (71), 182.3 (100), 103.0 (32), 85.0 (22), 77 (19), 59 (13).
1H NMR (CDCl3, 300 MHz): δ = 8.38 (s, 1 H, ArH), 7.93–7.79 (m, 4 H,
ArH), 7.56–7.43 (m, 2 H, ArH), 1.40 (s, 12 H, 4 × CH3).
2-(4-Chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2g)
[CAS Reg. No. 195062-61-4]
13C NMR (CDCl3, 75 MHz): δ = 136.2, 135.0, 132.8, 130.4, 128.6, 127.7,
Compound 2g was synthesized according to General Procedure A
from 1-chloro-4-iodobenzene (119 mg) and pyridine (40 μL, 1 equiv).
Purification by column chromatography (eluent: cyclohexane/CH2Cl2
95:5) gave 2g (98 mg, 0.41 mmol, 82%) as a white solid; mp 48–50 °C;
Rf = 0.54 (cyclohexane/CH2Cl2 95:51H NMR (CDCl3, 300 MHz): δ = 7.65
(d, J = 8.4 Hz, 2 H, ArH), 7.25 (d, J = 8.4 Hz, 2 H, ArH), 1.26 (s, 12 H, 4 ×
CH3).
126.9, 125.8, 83.9, 24.9.
11B NMR (CDCl3, 96 MHz): δ = 31.1 (s, Bpin).
GC/MS (EI, Method 1): tR = 10.93 min; m/z (%) = 254.1 (M+., 47), 239.1
(11), 168.1 (66), 154.0 (100), 128.0 (9), 77.0 (5), 59.0 (3).
2-(3-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(5a)
13C NMR (CDCl3, 75 MHz): δ = 137.3, 135.9, 127.8, 83.8, 24.7.
11B NMR (CDCl3, 96 MHz): δ = 30.7 (s, Bpin).
[CAS Reg. No. 325142-84-5]
Compound 5a was synthesized according to General Procedure B
from 3-iodoanisole (66 μL, 117 mg) and pyridine (40 μL, 1 equiv). Pu-
rification by column chromatography (elution gradient: 98:2 to 95:5
PE/EtOAc) gave 5a (97 mg, 0.41 mmol, 83%) as a pale yellow oil; Rf =
0.35 (PE/EtOAc 95:5).
GC/MS (EI, Method 1): tR = 8.16 min; m/z (%) = 238.0 (M+., 35), 223.0
(100), 154 (20), 139 (89), 103.0 (9), 85.0 (13), 77 (10), 59 (8).
1,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene (2m)
[CAS Reg. No. 99770-93-1]
1H NMR (CDCl3, 300 MHz): δ = 7.40–7.15 (m, 3 H, ArH), 6.93 (ddd, J =
Compound 2m was synthesized according to General Procedure A
from 1,4-diiodobenzene (165 mg) and pyridine (40 μL, 1 equiv). Puri-
fication by column chromatography (elution gradient: 98:2 to 9:1
PE/EtOAc) gave 2m (119 mg, 0.36 mmol, 72%) as a white solid; mp
230–232 °C; Rf = 0.23 (PE/EtOAc, 95:5).
1H NMR (CDCl3, 300 MHz): δ = 7.73 (s, 4 H, ArH), 1.28 (s, 24 H, 8 ×
CH3).
8.7, 2.8, 1.8 Hz, 1 H, ArH), 3.75 (s, 3 H, OCH3), 1.26 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 159.0, 128.9, 127.9, 118.7, 117.9, 83.8,
55.2, 24.8.
11B NMR (CDCl3, 96 MHz): δ = 31.0 (s, Bpin).
GC/MS (EI, Method 1): tR = 8.67 min; m/z (%) = 234.1 (M+., 81), 219.1
(36), 177.0 (8), 161.0 (6), 148.0 (92), 134.0 (100), 104.0 (13), 91.0 (12),
77.0 (10), 59.0 (5).
13C NMR (CDCl3, 75 MHz): δ = 133.9, 83.8, 24.9.
11B NMR (CDCl3, 96 MHz): δ = 30.9 (s, Bpin).
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)toluene (5c)
GC/MS (Method 1): tR = 12.54 min; m/z (%) = 330.2 (M+., 23), 315.2
(43), 273.1 (21), 244.2 (76), 231.1 (100), 215.0 (20), 188.1 (10), 158.1
(15), 131.0 (38), 85.0 (21), 59.0 (18).
[CAS Reg. No. 253342-48-2]
Compound 5c was synthesized according to General Procedure B
from 3-iodotoluene (64 μL, 109 mg) and pyridine (32 μL, 0.8 equiv).
Purification by column chromatography (elution gradient: 98:2 to
95:5 PE/EtOAc) gave 5c (94 mg, 0.43 mmol, 86%) as a pale yellow oil;
Rf = 0.61 (PE/EtOAc 95:5).
2-(1-Naphthyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3a)
[CAS Reg. No. 68716-52-9]
Compound 3a was synthesized according to General Procedure B
from 1-iodonaphthalene (73 μL, 127 mg) and pyridine (16 μL, 0.4
equiv). Purification by column chromatography (elution gradient:
1H NMR (CDCl3, 300 MHz): δ = 7.70–7.55 (m, 2 H, ArH), 7.35–7.20 (m,
2 H, Ar), 2.36 (s, 3 H, CH3), 1.35 (s, 12 H, 4 × CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

H
S. Pinet et al.
Special Topic
Synthesis
13C NMR (CDCl3, 75 MHz): δ = 137.1, 135.3, 132.0, 131.7, 127.7, 83.7,
11B NMR (CDCl3, 96 MHz): δ = 30.6 (s, Bpin).
24.8, 21.2.
GC/MS (EI, Method 1): tR = 8.27 min; m/z (%) = 238.0 (M+., 38), 223.0
(80), 151.9 (100), 138.9 (92), 117.0 (11), 102.9 (11), 85.0 (18), 76.9
(14), 59.0 (12).
11B NMR (CDCl3, 96 MHz): δ = 31.0 (s, Bpin).
GC/MS (EI, Method 1): tR = 7.68 min; m/z (%) = 218.0 (M+., 25), 203.0
(37), 160.9 (9), 132.0 (76), 119.0 (100), 90.0 (16), 85.0 (13), 77 (5),
59.0 (9).
2-(2-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(6a)
[CAS Reg. No. 190788-60-4]
4,4,5,5-Tetramethyl-2-(3-trifluoromethylphenyl)-1,3,2-dioxaboro-
lane (5d)
Compound 6a was synthesized according to General Procedure B
from 2-iodoanisole (65 μL, 117 mg) and pyridine (40 μL, 1 equiv). Pu-
rification by column chromatography (eluent: toluene/EtOAc 95:5)
gave 6a (36 mg, 0.15 mmol, 31%) as a pale yellow oil; Rf = 0.33 (tolu-
ene/EtOAc 95:5).
1H NMR (CDCl3, 300 MHz): δ = 7.60 (dd, J = 7.3, 1.8 Hz, 1 H, ArH), 7.32
(ddd, J = 7.4, 7.3, 1.8 Hz, 1 H, ArH), 6.86 (td, J = 7.3, 0.7 Hz, 1 H, ArH),
7.78 (dd, J = 7.4, 0.7 Hz, 1 H, ArH), 3.75 (s, 3 H, OCH3), 1.28 (s, 12 H, 4 ×
CH3).
[CAS Reg. No. 325142-82-3]
Compound 5d was synthesized according to General Procedure B
from 3-iodobenzotrifluoride (72 μL, 136 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient:
98:2 to 95:5 toluene/EtOAc) gave 5d (110 mg, 0.40 mmol, 81%) as a
white solid; mp 40–42 °C; Rf = 0.81 (toluene/EtOAc 95:5).
1H NMR (CDCl3, 300 MHz): δ = 7.99 (d, J = 0.6 Hz, 1 H, ArH), 7.90 (d, J =
7.4 Hz, 1 H, Ar), 7.62 (dd, J = 7.8, 0.6 Hz, 1 H, ArH), 7.40 (dd, J = 7.8, 7.4
Hz, 1 H, ArH), 1.28 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 163.0, 135.5, 131.3, 119.0, 109.3, 82.3,
54.6.
13C NMR (CDCl3, 75 MHz): δ = 138.0 (q, J = 1.2 Hz), 131.3 (q, J = 3.7 Hz),
130.0 (q, JC,F = 32.1 Hz), 128.0, 127.8 (q, JC,F = 3.8 Hz), 124.2 (q, JC,F
=
11B NMR (CDCl3, 96 MHz): δ = 31.0 (s, Bpin).
272.2 Hz), 84.3, 24.0.
GC/MS (EI, Method 1): tR = 8.55 min; m/z (%) = 234.1 (M+., 68), 219.1
(28), 203.0 (12), 176.0 (10), 161.0 (32), 148.0 (6) 134.0 (100), 118.0
(17), 105.0 (44), 91.0 (58), 77.0 (12), 59.0 (6).
11B NMR (CDCl3, 96 MHz): δ = 30.3 (s, Bpin).
19F NMR (CDCl3, 282 MHz): δ = –62.6 (s, Bpin).
GC/MS (EI, Method 1): tR = 6.83 min; m/z (%) = 272.0 (M+., 7) 257.0
(100), 229 (6), 215 (5), 185.9 (46), 172.9 (70), 152.9 (6), 85.0 (7), 58.0
(7).
2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (6b)
[CAS Reg. No. 191171-55-8]
Compound 6b was synthesized according to General Procedure A
from 2-iodoaniline (110 mg) and pyridine (40 μL, 1 equiv). Purifica-
tion by column chromatography (elution gradient: 100:0 to 8:2
PE/EtOAc) gave 6b (19 mg, 0.09 mmol, 17%) as a yellow solid; mp 68–
69 °C (Lit.27 mp 67–68 °C); Rf = 0.46 (PE/EtOAc 8:2).
1H NMR (CDCl3, 300 MHz): δ = 7.54 (dd, J = 7.4, 1.6 Hz, 1 H, ArH), 7.14
(ddd, J = 7.4 , 7.3, 1.6 Hz, 1 H, ArH), 6.60 (td, J = 7.3, 1.1 Hz, 1 H, ArH),
6.52 (dd, J = 7.4, 1.1 Hz, 1 H, ArH), 4.52 (br s, 2 H, NH2), 1.26 (s, 12 H, 4
× CH3).
13C NMR (CDCl3, 75 MHz): δ = 153.6, 136.8, 132.7, 116.9, 114.7, 83.5,
24.9.
11B NMR (CDCl3, 96 MHz): δ = 31.0 (s, Bpin).
GC/MS (EI, Method 1): tR = 9.18 min; m/z (%) = 219.1 (M+., 69), 162.1
2-(3-Bromophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5f)
[CAS Reg. No. 594823-67-3]
Compound 5f was synthesized according to General Procedure B from
1-bromo-3-iodobenzene (64 μL, 141 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient:
98:2 to 95:5 PE/EtOAc) gave 5f (98 mg, 0.35 mmol, 69%) as a pale yel-
low oil; Rf = 0.53 (PE/EtOAc 95:5).
1H NMR (CDCl3, 300 MHz): δ = 7.86 (d, J = 1.2 Hz, 1 H, ArH), 7.64 (ddd,
J = 7.3, 2.1, 1.2 Hz, 1 H, ArH), 7.50 (ddd, J = 8.0, 2.1, 1.2 Hz, 1 H, ArH),
7.16 (dd, J = 7.6, 8.0 Hz, 1 H, ArH), 1.27 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 137.9, 134.6, 133.5, 129.9, 122.8, 84.5,
25.3.
(83), 141.0 (53), 119.0 (100), 91.0 (14), 77.0 (15).
11B NMR (CDCl3, 96 MHz): δ = 30.4 (s, Bpin).
GC/MS (EI, Method 1): tR = 8.86 min; m/z (%) = 281.9 (M+., 83), 266.9
(79), 238.9 (6), 224.9 (7), 195.9 (100), 182.8 (83), 160.9 (7), 117.0 (20),
102.9 (34), 85.0 (24), 76.9 (21), 59.0 (17).
2-(2-Chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6g)
[CAS Reg. No. 870195-94-1]
Compound 6g was synthesized according to General Procedure B
from 1-chloro-2-iodobenzene (61 μL, 119 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient:
100:0 to 9:1 PE/EtOAc) gave 6g (38 mg, 0.16 mmol, 32%) as a pale yel-
low oil; Rf = 0.22 (PE/EtOAc 98:2).
1H NMR (CDCl3, 300 MHz): δ = 7.61 (dd, J = 6.9, 1.0 Hz, 1 H, ArH),
7.30–7.24 (m, 2 H, ArH), 7.21–7.11 (m, 1 H, ArH), 1.30 (s, 12 H, 4 ×
CH3).
13C NMR (CDCl3, 75 MHz): δ = 138.8, 135.7, 131.1, 128.7, 125.1, 83.4,
24.1.
11B NMR (CDCl3, 96 MHz): δ = 30.7 (s, Bpin).
2-(3-Chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5g)
[CAS Reg. No. 635305-47-4]
Compound 5g was synthesized according to General Procedure B
from 1-chloro-3-iodobenzene (62 μL, 119 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient:
98:2 to 95:5 PE/EtOAc) gave 5g (91 mg, 0.38 mmol, 76%) as a pale yel-
low oil; Rf = 0.42 (PE/EtOAc, 95:5).
1H NMR (CDCl3, 300 MHz): δ = 7.70 (d, J = 2.1 Hz, 1 H, ArH), 7.59 (dt,
J = 7.4, 1.1 Hz, 1 H, ArH), 7.34 (ddd, J = 8.0, 2.1, 1.2 Hz, 1 H, ArH), 7.22
(dd, J = 8.0, 7.4 Hz, 1 H, ArH), 1.27 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 134.5, 134.0, 132.6, 131.2, 129.2, 84.1,
24.8.
GC/MS (EI, Method 1): tR = 8.33 min; m/z (%) = 238.1 (M+., 9), 223.0
(20), 203 (100), 161 (45), 139.0 (100), 117.0 (7), 103.0 (23), 85.0 (23),
77 (13), 59.0 (12).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

I
S. Pinet et al.
Special Topic
Synthesis
Methyl 2-Amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)benzoate (7)
Compound 10 was synthesized according to General Procedure B
from 2-chloro-4-iodotoluene (71 μL, 126 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient:
100:0 to 7:3 PE/EtOAc) gave 10 (93 mg, 0.37 mmol, 73%) as a white
solid; mp 46–48 °C; Rf = 0.24 (PE/EtOAc 9 :1).
1H NMR (CDCl3, 300 MHz): δ = 7.59 (d, J = 0.9 Hz, 1 H, ArH), 7.49 (dd,
J = 7.5, 0.9 Hz, 2 H, ArH), 7.16 (d, J = 7.5 Hz, 1 H, ArH), 2.32 (s, 3 H,
CH3), 1.26 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 139.2, 135.1, 134.2, 132.8, 130.5, 84.0,
24.8, 20.3.
11B NMR (CDCl3, 96 MHz): δ = 30.5 (s, Bpin).
[CAS Reg. No. 363185-87-9]
Compound 7 was synthesized according to General Procedure A from
methyl 2-amino-5-iodobenzoate (139 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient: 1:1
cyclohexane/CH2Cl2 to pure CH2Cl2) gave 7 (31 mg, 0.11 mmol, 22%)
as a pale beige solid; mp 108–110 °C; Rf = 0.31 (CH2Cl2).
1H NMR (CDCl3, 300 MHz): δ = 8.27 (d, J = 1.5 Hz, 1 H, ArH), 7.61 (dd,
J = 8.2, 1.5 Hz, 2 H, ArH), 6.57 (d, J = 8.2 Hz, 1 H, ArH), 5.90 (br s, 2 H,
NH2), 3.80 (s, 3 H, OCH3), 1.27 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 168.6, 152.5, 140.0, 138.8, 115.8, 110.1,
83.4, 51.3, 24.1.
11B NMR (CDCl3, 96 MHz): δ = 30.9 (s, Bpin).
GC/MS (EI, Method 1): tR = 8.89 min; m/z (%) = 252.1 (M+., 52), 237.1
(78), 217.1 (8), 195.1 (8), 166.0 (93), 153.0 (100), 131.1 (9), 117.0 (38),
85.0 (13), 59.0 (7).
GC/MS (EI, Method 1): tR = 13.13 min; m/z (%) = 277.1 (M+., 100), 262.1
(15), 245.1 (25), 234.0 (9), 220.1 (15), 204.0 (10), 191.0 (9), 177.0 (68),
145.0 (39), 118.0 (21), 91 (10).
2-(3-Chloro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (11)
[CAS Reg. No. 445303-10-6]
2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo-
nitrile (8)
Compound 11 was synthesized according to General Procedure B
from 3-chloro-4-fluoroiodobenzene (64 μL, 128 mg) and pyridine (40
μL, 1 equiv). Purification by column chromatography (elution gradi-
ent: 100:0 to 7:3 PE/EtOAc) gave 11 (91 mg, 0.35 mmol, 71%) as an oil;
Rf = 0.40 (PE/EtOAc 9:1).
1H NMR (CDCl3, 300 MHz): δ = 8.37 (br s, 1 H, ArH), 7.89 (dm, 1 H,
ArH), 7.86 (dd, J = 8.3, 1.3 Hz, 1 H, ArH), 7.52–7.45 (2 superimposed
dm, 2 H, ArH), 7.37 (ddd, J = 7.3, 6.9, 1.4 Hz, 1 H, ArH), 7.27 (ddd, J =
7.5, 7.3, 1.0 Hz, 1 H, ArH), 1.32 (s, 12 H, 4 × CH3).
[CAS Reg. No. 1220219-22-6]
Compound 8 was synthesized according to General Procedure A from
5-iodo-2-methoxybenzonitrile (130 mg) and pyridine (40 μL, 1
equiv). Purification by column chromatography (elution gradient: 1:1
cyclohexane/CH2Cl2 to pure CH2Cl2) gave 8 (56 mg, 0.22 mmol, 43%)
as a colorless oil; Rf = 0.45 (CH2Cl2).
1H NMR (CDCl3, 300 MHz): δ = 7.94 (d, J = 1.6 Hz, 1 H, ArH), 7.88 (dd,
J = 8.5, 1.6 Hz, 2 H, ArH), 6.89 (d, J = 8.5 Hz, 1 H, ArH), 3.88 (s, 3 H,
OCH3), 1.27 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 158.4, 156.2, 133.8, 127.8, 127.1, 124.1,
123.9, 122.9, 121.8, 83.9, 24.9.
11B NMR (CDCl3, 96 MHz): δ = 31.0 (s, Bpin).
13C NMR (CDCl3, 75 MHz): δ = 163.2, 140.9, 140.6, 116.4, 110.5, 101.7,
GC/MS (EI, Method 1): tR = 8.15 min; m/z (%) = 256.0 (M+., 31), 241.0
(100), 213.0 (7), 199.0 (6), 170.0 (66), 157.0 (78), 85.0 (13), 75.0 (9),
59.0 (12).
84.2, 56.0, 24.8.
11B NMR (CDCl3, 96 MHz): δ = 30.2 (s, Bpin).
GC/MS (EI, Method 1): tR = 12.36 min; m/z (%) = 259.1 (M+., 57), 244.1
(100), 216.0 (11), 202.0 (9), 173.0 (83), 160.0 (80), 130.0 (17), 85 (8).
2-(3-Fluoro-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (15)
2-(3,4-Dichlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(9)
[CAS Reg. No. 1583286-47-8]
Compound 15 was synthesized according to General Procedure A
from 3-fluoro-5-iodotoluene (118 mg) and pyridine (40 μL, 1 equiv).
Purification by column chromatography (elution gradient: 100:0 to
7:3 PE/EtOAc) gave 15 (93 mg, 0.39 mmol, 79%) as a colorless oil; Rf =
0.53 (PE/EtOAc 9:1).
1H NMR (CDCl3, 300 MHz): δ = 7.32 (br d, J = 0.6 Hz, 1 H, ArH), 7.20
(dd, JH,F = 8.9, 2.5 Hz, 1 H, ArH), 6.88 (dm, JH,F = 9.8 Hz, 1 H, ArH), 2.27
(q, J = 0.6 Hz, 3 H, CH3), 1.27 (s, 12 H, 4 × CH3).
[CAS Reg. No. 401797-02-2]
Compound 9 was synthesized according to General Procedure A from
1,2-dichloro-4-iodobenzene (136 mg) and pyridine (40 μL, 1 equiv).
Purification by column chromatography (elution gradient: 100:0 to
7:3 PE/EtOAc) gave 9 (85 mg, 0.31 mmol, 62%) as a colorless oil; Rf =
0.37 (PE/EtOAc 9:1).
1H NMR (CDCl3, 300 MHz): δ = 7.79 (d, J = 1.4 Hz, 1 H, ArH), 7.52 (dd,
J = 7.9, 1.4 Hz, 2 H, ArH), 7.36 (d, J = 7.9 Hz, 1 H, ArH), 1.27 (s, 12 H, 4 ×
CH3).
13C NMR (CDCl3, 75 MHz): δ = 136.5, 135.5, 133.7, 132.2, 130.0, 84.3,
24.8, 20.3.
11B NMR (CDCl3, 96 MHz): δ = 30.1 (s, Bpin).
13C NMR (CDCl3, 75 MHz): δ = 161.5 (d, JC,F = 245.9 Hz), 138.8 (d, JC,F
7.3 Hz), 129.9 (d, JC,F = 2.6 Hz), 117.8 (d, JC,F = 21.0 Hz), 116.8 (d, JC,F
19.5 Hz), 83.0, 23.8, 20.0 (d, JC,F = 1.7 Hz).
=
=
11B NMR (CDCl3, 96 MHz): δ = 30.6 (s, Bpin).
19F NMR (CDCl3, 282 MHz): δ = –115.4 (dd, JF,H = 9.8, 8.9 Hz, Ar–F).
GC/MS (EI, Method 1): tR = 7.67 min; m/z (%) = 236.2 (M+., 42), 221.1
(62), 193.0 (6), 179.0 (10), 150.0 (100), 137.0 (98), 109.0 (9), 85.0 (11),
59.0 (8).
GC/MS (EI, Method 1): tR = 9.34 min; m/z (%) = 272.0 (M+., 43), 257.0
(100), 229.0 (7), 186.0 (95), 174.0 (79), 136.9 (6), 109.9 (6), 85.0 (18),
77.0 (10), 58 (13).
2-(3-Chloro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (10)
2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-dibenzofuran
(18)
[CAS Reg. No. 445303-10-6]
[CAS Reg. No. 947770-80-1]
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

J
S. Pinet et al.
Special Topic
Synthesis
Compound 18 was synthesized according to General Procedure B
from 2-iododibenzofuran (147 mg) and pyridine (40 μL, 1 equiv). Pu-
rification by column chromatography (elution gradient: 98:2 to 7:3
PE/EtOAc) gave 18 (47 mg, 0.16 mmol, 32%) as a white solid; mp 74–
76 °C; Rf = 0.37 (PE/EtOAc 95:5).
1H NMR (CDCl3, 300 MHz): δ = 8.48 (br s, 1 H, ArH), 8.0 (ddd, J = 7.6,
1.4, 0.7 Hz, 1 H, ArH), 7.96 (dd, J = 7.3, 1.4 Hz, 1 H, ArH), 7.62–6.56 (2
dm, 2 H, ArH), 6.48 (ddd, J = 7.6, 7.3, 1.4 Hz, 1 H, ArH), 6.38 (td, J = 7.6,
1.1 Hz, 1 H, ArH), 1.43 (s, 12 H, 4 × CH3).
13C NMR (CDCl3, 75 MHz): δ = 158.4, 156.1, 133.8, 127.8, 127.1, 124.1,
123.9, 122.9, 120.8, 111.6, 111.1, 83.9, 24.9.
11B NMR (CDCl3, 96 MHz): δ = 31.0 (s, Bpin).
GC/MS (EI, Method 2): tR = 9.68 min; m/z (%) = 294.1 (M+., 53), 279.1
(6) (a) Guerrand, H. D. S.; Marciasini, L. D.; Gendrineau, T.; Pascu,
O.; Marre, S.; Pinet, S.; Vaultier, M.; Aymonier, C.; Pucheault, M.
Tetrahedron 2014, 70, 6156. (b) Guerrand, H. D. S.; Vaultier, M.;
Pinet, S.; Pucheault, M. Adv. Synth. Catal. 2015, 357, 1167.
(7) (a) Erb, W.; Albini, M.; Rouden, J.; Blanchet, J. J. Org. Chem. 2014,
79, 10568. (b) Erb, W.; Hellal, A.; Albini, M.; Rouden, J.; Blanchet,
J. Chem. Eur. J. 2014, 20, 6608. (c) Qiu, D.; Jin, L.; Zheng, Z.; Meng,
H.; Mo, F.; Wang, X.; Zhang, Y.; Wang, J. J. Org. Chem. 2013, 78,
1923. (d) Mo, F.; Jiang, Y.; Qiu, D.; Zhang, Y.; Wang, J. Angew.
Chem. Int. Ed. 2010, 49, 1846. (e) Qiu, D.; Zhang, Y.; Wang, J. Org.
Chem. Front. 2014, 1, 422. (f) Qiu, D.; Wang, S.; Tang, S.; Meng,
H.; Jin, L.; Mo, F.; Zhang, Y.; Wang, J. J. Org. Chem. 2014, 79, 1979.
(g) Iakobson, G.; Du, J.; Slawin, A. M. Z.; Beier, P. Beilstein J. Org.
Chem. 2015, 11, 1494. (h) Qiu, D.; Meng, H.; Jin, L.; Tang, S.;
Wang, S.; Mo, F.; Zhang, Y.; Wang, J. Org. Synth. 2014, 91, 106.
(i) Pucheault, M. J. D.; Marciasini, L. D. A.; Vaultier, M. Patent
WO2014009169, 2014. (j) Zhao, C.-J.; Xue, D.; Jia, Z.-H.; Wang,
C.; Xiao, J. Synlett 2014, 25, 1577. (k) Zhu, C.; Yamane, M. Org.
Lett. 2012, 14, 4560.
(13), 217.1 (8), 204.0 (51), 165.0 (20), 139.0 (11), 85.0 (5), 59.0 (4).
Acknowledgment
(8) (a) Yu, J.; Zhang, L.; Yan, G. Adv. Synth. Catal. 2012, 354, 2625.
(b) Ahammed, S.; Nandi, S.; Kundu, D.; Ranu, B. C. Tetrahedron
Lett. 2016, 57, 1551.
This work was funded by the University of Bordeaux and the CNRS.
(9) Miralles, N.; Romero, R. M.; Fernandez, E.; Muniz, K. Chem.
Commun. 2015, 51, 14068.
Supporting Information
Supporting information for this article is available online at
(10) (a) Mfuh, A. M.; Doyle, J. D.; Chhetri, B.; Arman, H. D.; Larionov,
O. V. J. Am. Chem. Soc. 2016, 138, 2985. (b) Mfuh, A. M.; Nguyen,
V. T.; Chhetri, B.; Burch, J. E.; Doyle, J. D.; Nesterov, V. N.; Arman,
H. D.; Larionov, O. V. J. Am. Chem. Soc. 2016, 138, 8408. (c) Chen,
K.; Cheung, M. S.; Lin, Z.; Li, P. Org. Chem. Front. 2016, 3, 875.
(d) Chen, K.; Zhang, S.; He, P.; Li, P. Chem. Sci. 2016, 7, 3676.
(11) Yamamoto, E.; Izumi, K.; Horita, Y.; Ito, H. J. Am. Chem. Soc.
2012, 134, 19997.
(12) Yamamoto, E.; Ukigai, S.; Ito, H. Chem. Sci. 2015, 6, 2943.
(13) Zhang, J.; Wu, H.-H.; Zhang, J. Eur. J. Org. Chem. 2013, 6263.
(14) Kleeberg, C.; Dang, L.; Lin, Z.; Marder, T. B. Angew. Chem. Int. Ed.
2009, 48, 5350.
(15) Zhang, L.; Jiao, L. J. Am. Chem. Soc. 2017, 139, 607.
(16) Pietsch, S.; Neeve, E. C.; Apperley, D. C.; Bertermann, R.; Mo, F.;
Qiu, D.; Cheung, M. S.; Dang, L.; Wang, J.; Radius, U.; Lin, Z.;
Kleeberg, C.; Marder, T. B. Chem. Eur. J. 2015, 21, 7082.
(17) Cuthbertson, J.; Gray, V. J.; Wilden, J. D. Chem. Commun. 2014,
50, 2575.
(18) Zhou, S.; Anderson, G. M.; Mondal, B.; Doni, E.; Ironmonger, V.;
Kranz, M.; Tuttle, T.; Murphy, J. A. Chem. Sci. 2014, 5, 476.
(19) (a) Roman, D. S.; Takahashi, Y.; Charette, A. B. Org. Lett. 2011, 13,
3242. (b) Shirakawa, E.; Itoh, K.-i.; Higashino, T.; Hayashi, T.
J. Am. Chem. Soc. 2010, 132, 15537.
https://doi.org/10.1055/s-0036-1588431.
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References
(1) Hall, D. G. Structure, Properties, and Preparation of Boronic Acid
Derivatives. Overview of Their Reactions and Applications, In
Boronic Acids: Preparation and Applications in Organic Synthesis
and Medicine;
1
V
o.
l
Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2005, 1–
99.
(2) (a) Pucheault, M.; Vaultier, M.; Marciasini, L. D.; Guerrand, H.
Patent WO2015082592 (A2), 2015. (b) Marciasini, L.;
Cacciuttolo, B.; Vaultier, M.; Pucheault, M. Org. Lett. 2015, 17,
3532.
(3) Richard, J.; Birepinte, M.; Charbonnier, J. B.; Liautard, V.; Pinet,
S.; Pucheault, M. Synthesis 2017, 49, 736.
(4) (a) Ratniyom, J.; Dechnarong, N.; Yotphan, S.; Kiatisevi, S. Eur. J.
Org. Chem. 2014, 1381. (b) Labre, F.; Gimbert, Y.; Bannwarth, P.;
Olivero, S.; Duñach, E.; Chavant, P. Y. Org. Lett. 2014, 16, 2366.
(c) Chow, W. K.; Yuen, O. Y.; Choy, P. Y.; So, C. M.; Lau, C. P.;
Wong, W. T.; Kwong, F. Y. RSC Adv. 2013, 3, 12518.
(d) Nagashima, Y.; Takita, R.; Yoshida, K.; Hirano, K.; Uchiyama,
M. J Am. Chem. Soc. 2013, 135, 18730. (e) Molander, G. A.;
Cavalcanti, L. N.; García-García, C. J. Org. Chem. 2013, 78, 6427.
(f) Li, P.; Fu, C.; Ma, S. Org. Biomol. Chem. 2014, 12, 3604.
(g) Wang, L.; Li, J.; Cui, X.; Wu, Y.; Zhu, Z. Adv. Synth. Catal. 2010,
352, 2002. (h) Fürstner, A.; Seidel, G. Org. Lett. 2002, 4, 541.
(i) Ma, Y.; Song, C.; Jiang, W.; Xue, G.; Cannon, J. F.; Wang, X.;
Andrus, M. B. Org. Lett. 2003, 5, 4635. (j) Willis, D. M.; Strongin,
R. M. Tetrahedron Lett. 2000, 41, 8683.
(5) (a) Guerrand, H. D. S.; Marciasini, L. D.; Jousseaume, M.;
Vaultier, M.; Pucheault, M. Chem. Eur. J. 2014, 20, 5573.
(b) Marciasini, L.; Richy, N.; Vaultier, M.; Pucheault, M. Chem.
Commun. 2012, 48, 1553. (c) Marciasini, L. D.; Richy, N.;
Vaultier, M.; Pucheault, M. Adv. Synth. Catal. 2013, 355, 1083.
(d) Marciasini, L. D.; Vaultier, M.; Pucheault, M. Tetrahedron Lett.
2014, 55, 1702. (e) Euzenat, L.; Horhant, D.; Ribourdouille, Y.;
Duriez, C.; Alcaraz, G.; Vaultier, M. Chem. Commun. 2003, 2280.
(20) Dewanji, A.; Murarka, S.; Curran, D. P.; Studer, A. Org. Lett. 2013,
15, 6102.
(21) Zhang, L.; Yang, H.; Jiao, L. J. Am. Chem. Soc. 2016, 138, 7151.
(22) Yanagisawa, S.; Itami, K. ChemCatChem 2011, 3, 827.
(23) (a) Ajayakumar, M. R.; Hundal, G.; Mukhopadhyay, P. Chem.
Commun. 2013, 49, 7684. (b) Maity, K.; Panda, D. K.; Lochner, E.;
Saha, S. J. Am. Chem. Soc. 2015, 137, 2812.
(24) Lu, D.; Wu, C.; Li, P. Chem. Eur. J. 2014, 20, 1630.
(25) Dahlen, A.; Petersson, A.; Hilmersson, G. Org. Biomol. Chem.
2003, 1, 2423.
(26) Morandi, S.; Caselli, E.; Forni, A.; Bucciarelli, M.; Torre, G.; Prati,
F. Tetrahedron: Asymmetry 2005, 16, 2918.
(27) Yamamoto, T.; Morita, T.; Takagi, J.; Yamakawa, T. Org. Lett.
2011, 13, 5766.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J