Synthesis of pinacol arylboronates from aromatic amines: A metal-free transformation

Article abstract of DOI:10.1021/jo3018878

A metal-free borylation process based on Sandmeyer-type transformation using arylamines derivatives as the substrates has been developed. Through optimization of the reaction conditions, this novel conversion can be successfully applied to a wide range of aromatic amines, affording borylation products in moderate to good yields. Various functionalized arylboronates, which are difficult to access by other methods, can be easily obtained with this metal-free transformation. Moreover, this transformation can be followed by Suzuki-Miyaura cross-coupling without purification of the borylation products, which enhances the practical usefulness of this method. A possible reaction mechanism involving radical species has been proposed.

Full text of DOI:10.1021/jo3018878

Article
pubs.acs.org/joc
Synthesis of Pinacol Arylboronates from Aromatic Amines: A Metal-
Free Transformation
Di Qiu, Liang Jin, Zhitong Zheng, He Meng, Fanyang Mo,* Xi Wang, Yan Zhang, and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of
Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
S
* Supporting Information
ABSTRACT: A metal-free borylation process based on Sandmeyer-type transformation
using arylamines derivatives as the substrates has been developed. Through optimization of
the reaction conditions, this novel conversion can be successfully applied to a wide range of
aromatic amines, affording borylation products in moderate to good yields. Various
functionalized arylboronates, which are difficult to access by other methods, can be easily
obtained with this metal-free transformation. Moreover, this transformation can be followed by Suzuki−Miyaura cross-coupling
without purification of the borylation products, which enhances the practical usefulness of this method. A possible reaction
mechanism involving radical species has been proposed.
activation has been extensively explored in the groups of Smith
III, Miyaura, Hartwig, Marder, and others (Scheme 1, path c).8
Recently, Lewis acid catalyzed electrophilic borylation of
electron-rich arenes has been explored (Scheme 1, path
d).9,10 These borylation methods have the advantage of being
transition-metal-free processes and thus avoiding heavy metal
contamination in the final products.
We have recently communicated an entirely different
approach toward arylboronates synthesis by direct conversion
of the amino group of aniline derivatives to the boronate group
(Scheme 1, path e).11 This transformation is under Sandmeyer-
type reaction conditions by using tert-butyl nitrite (t-BuONO)
as diazotization agent.12,13 This borylation method has the
following features: (1) the reaction is under metal-free
conditions, (2) arylamines are cheap and abundant starting
materials, (3) the borylation tolerates various functional groups,
and (4) the reaction is under very mild conditions. As a result,
this novel borylation will not only find wide application in
organic synthesis but also shed light on the unique reactivity of
aryldiazonium ion and diboron compounds.14
INTRODUCTION
■
Arylboronic acids and arylboronates have shown great
importance due to their widespread applications in organic
synthesis and other fields.1,2 In particular, functionalized
arylboronic acids and arylboronates are highly valuable because
consecutive cross-coupling is possible from these compounds,
which can rapidly construct the complex structure of target
molecules.3 Consequently, the syntheses of various function-
alized arylboronic compounds have attracted significant
attentions in recent years.
The reaction of aryl Grignard reagents or aryllithium species
with trialkyl boronates remains the most general synthetic
method to prepare aromatic boronic compounds (Scheme 1,
Scheme 1. Different Routes to Arylboronic Acids or
Arylboronates
In this article, we report the further optimization of the
reaction conditions and the expansion of the substrate scope to
various aniline derivatives. Compared to the results reported in
the preliminary communication, the newly optimized reaction
conditions offered improved yields and have wider substrate
scope. Moreover, this borylation has also been extended to
heterocyclic amines, although with limited success.
RESULTS AND DISCUSSION
■
To further optimize the reaction that was reported in our
preliminary communication,11 we have chosen 2-amino-
benzonitrile as the substrate, with which only a low yield of
path a).4 In 1995, Miyaura et al. developed the palladium-
catalyzed borylation of arylhalides using bis(pinacolato)diboron
as the boron source.5 Subsequently, Masuda et al. reported the
palladium-catalyzed borylation from arylhalides using pinacol-
borane.6 The groups of Ma and Marder then reported the
copper-catalyzed borylation reaction (Scheme 1, path b).7 In
the past decade, direct borylation via aromatic C−H bond
Special Issue: Howard Zimmerman Memorial Issue
Received: September 2, 2012
© XXXX American Chemical Society
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22% was obtained under the previous reaction conditions [t-
BuONO, benzoyl peroxide (BPO, 2 mol %), MeCN, rt] (Table
1, entry 1). Thus, a number of experiments were conducted to
Scheme 2. Comparison of Yields with Those Reported
Previously
a
Table 1. Optimization of Reaction Conditions for 2-
a
Aminobenzonitrile
a
Current reaction conditions: arylamine (1 mmol), B2pin2 (1.1
b
mmol), t-BuONO (1.5 mmol), MeCN (3 mL), 80 °C, 2 h. Isolated
yield. The figure in brackets refers to the yields reported under the
previous reaction conditions; see ref 11. The previous reaction
conditions: arylamine (1 mmol), B2pin2 (1.1 mmol), t-BuONO (1.5
mmol), BPO (2 mol %), MeCN (3 mL), room temperature, 2 h.
a
Scheme 3. Scope of para-Substitued Aniline Derivatives
a
Reaction conditions: arylamine (1 mmol), B2pin2 (1.1 mmol),
b
RONO (1.5 mmol), 1 h. GC yield measured with GC−MS,
mesitylene was used as internal standard. See ref 11. B2pin2:
c
bis(pinacolato)diboron. Bpin: 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl.
improve the yield, and these experiments provide further
insight into the factors that affect this transformation. First, it
was observed that the reaction is significantly affected by
temperature (entries 2−4). The yield of 4aa could be improved
when the reaction was carried at elevated temperature. At 80
°C, 4aa could be obtained in 77% GC yield and 66% isolated
yield. Addition of radical initiator BPO slightly affects the
reaction at this temperature (entries 5−7). Use of other
solvents, such as toluene, DCE, and dioxane, proved to be
ineffective. Finally, alkyl nitrites 2b and 2c were found to be
compatible with this reaction, albeit less efficient than 2a
(entries 11,12).
a
Reaction conditions: arylamine (1 mmol), B2pin2 (1.1 mmol), t-
b
c
BuONO (1.5 mmol), MeCN (3 mL), 2 h. Isolated yield. t-BuONO
(1.1 mmol). B2pin2 (2.2 mmol), t-BuONO (3 mmol).
d
The optimization experiments demonstrate that by simply
raising reaction temperature, the yield of the borylation product
could be markedly improved. With this in hand, the aniline
substrates that afforded the low yields of the corresponding
borylation products under the previous conditions were
examined, and the yields were compared (Scheme 2). The
results show that in general the yields are improved when the
reactions are carried out at high temperature, especially for
those with halogen substituents (4ab, 4ac, 4af, 4ah).
Encouraged by the results, we proceeded to apply this metal-
free borylation to a series of new substrates. First, para-
substituted aniline derivatives were investigated (Scheme 3).
Moderate to good yields were obtained for most of the para-
substituted aniline substrates. The borylation showed good
tolerance to various functional groups, including methylthio
(4ba), hydroxyl (4bb), formyl (4bc), carboxyl (4bd), sulfonyl
(4be), azo (4bf), amino (4bh), iodo (4bk), and alkynyl (4bj)
groups. In the cases of 4bc, 4bg, and 4bl, the low yields are due
to their low stability on column chromatography or TLC.
When 4-aminostryne was employed as the substrate, the
corresponding boronate 4bg was isolated in very low yield. In
this case, a large quantity of precipitate was observed. We
speculate that polymerization occurs in this reaction, which
may be initiated by a radical intermediate (vide infra).
Interestingly, with p-aminoaniline as the substrate, selective
B
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a
mono- or diborylation could be realized by simply controlling
the amount of t-BuONO and B2pin2 used in the reaction (4bh
and 4bi).
Scheme 5. Scope of Other Aromatic Derivatives
Furthermore, we expanded the scope of substrates to meta-,
ortho-, or multi-substituted arylamine substrates (Scheme 4).
Scheme 4. Reaction with meta, ortho, or multi-Substitued
a
Arylamines
a
Reaction conditions: arylamine (1 mmol), B2pin2 (1.1 mmol), t-
b
c
BuONO (1.5 mmol), 2 h, MeCN (3 mL). Isolated yield. The
isolated yield of 5da in brackets refer to the reaction in water: a
mixture of arylamine (1 mmol), NaNO2 (1.1 mmol), HCl (0.41 mL,
12 mol/L), and H2O (1 mL) was stirred at 0 °C for 15 min, then to
the mixture was added B2pin2 (1.1 mmol) in MeCN (1 mL), and
stirring was continued at 80 °C for 2 h. Arylamine (0.5 mmol), B2pin2
(1.1 equiv), t-BuONO (1.5 equiv), MeCN (1.5 mL), 2 h. Isolated by
recrystallization. Yields in brackets refer to GC yield measured with a
d
e
f
GC−MS instrument (mesitylene as internal standard).
of t-BuONO, resulting in low yields of borylation products
(5de and 5df).
It is noteworthy that most of the heterocyclic boronates are
not stable on silica gel column chromatography. To simplify the
synthetic procedure and in particular to avoid the problem of
product decomposition during the purification process, a
sequential borylation and Pd-catalyzed cross-coupling reaction
has been demonstrated in our preliminary communication.11
Such a sequential process avoids the troublesome purification
process and significantly strengthens the usefulness of this new
borylation method. Herein we further expand the scope of this
sequential process, especially for the heterocyclic substrates
(Scheme 6). Thus, upon completion of the borylation, MeCN
is removed under reduced pressure to give crude borylation
product, which is then subjected next to Pd-catalyzed Suzuki−
Miyaura cross-coupling reaction without further purification to
afford coupling products in moderately high yields in general.
However, in some cases the yields are less satisfactory (6d, 6h,
6r, and 6s).
a
Reaction conditions: arylamine (1 mmol), B2pin2 (1.1 mmol), t-
b
BuONO (1.5 mmol), MeCN (3 mL), 2 h. Isolated yield.
The borylation in general affords relatively low to moderate
yields. Compared with electron-rich aniline derivatives,
electron-deficient ones usually give higher yields when the
corresponding borylation products are stable toward column
chromatography (for example, 4cj, 4ck, and 4cn). Moreover,
the steric bulkiness of the ortho substitution seems to affect the
borylation reaction. The substrates with ortho substitution
generally afforded diminished yields. For example, reaction with
2,6-dimethylaniline gave only 23% yield (4cd).
Subsequently, we proceeded to extend the reaction to some
complicated aromatic amines and heterocyclic amines. These
results are shown in Scheme 5. The reaction with 2-
aminonaphthalene afforded 5da with low yield, and large
amount of B2pin2 was recovered. This is likely due to the facile
oxidation of 2-aminonaphthalene under the reaction conditions.
In the case of 5db and 5dc, the low yields are attributed to the
instability of these products.
Heterocyclic boronic acids or boronates have found wide
applications in organic synthesis, especially for pharmaceuticals.
However, these boron compounds are usually not easy to
synthesize as a result of the limitations of other methodologies
that have been discussed in the Introduction. Thus, we
investigated the application of this new borylation method to
access heterocyclic boronates. We found that electron-deficient
heterocyclic amines demonstrate high reactivity with nearly
complete conversion of B2pin2. However, electron-rich
heterocyclic amines are prone to be oxidized in the presence
Finally, to demonstrate the practical usefulness of this
borylation method, the reaction has been carried out in gram-
scale for selected substrates. As shown in Scheme 7, the
reaction provided the desired boronates in good yields. The
sequential borylation and Pd-catalyzed cross-coupling has also
been scaled up (eq 1).
Since it is well documented that Sandmeyer reaction
proceeds through a radical mechanism,13b,15 a possible reaction
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Scheme 6. Sequential Borylation and Pd-Catalyzed Cross-
Coupling Reaction
Scheme 8. Possible Reaction Mechanism
a
complex A. Single electron transfer (SET) between ate complex
A and aryldiazonium ion is then followed to afford aryl radical
D through N2 extrusion from radical B. Finally, reaction of aryl
radical D with intermediate C gives the borylation product.
This reaction mechanism is substantiated by the following
experimental observations: (1) When the borylation was
carried out in the presence of 1.5 equiv of the radical scavenger
TEMPO, the reaction became sluggish and phenylboronate was
formed in only 8% yield after 4 h, while a control experiment
has demonstrated that TEMPO does not react directly with
B2pin2 under these conditions (eq 2). (2) Heating a 1:1 mixture
of BPO and B2pin2 in MeCN at 100 °C for 4 h affords the
phenylboronate in 37% yield (eq 3). It is known that BPO
cleaves under thermolytic conditions to benzoic acid radical
upon heating, which generates phenyl radical by further
decomposition. Thus, the desired product is likely formed by
the reaction of benzoic acid radical and/or phenyl radical with
B2pin2. (3) EPR experiments provide supportive evidence for a
radical process.16
a
Reaction condition for the first step: arylamine (1 mmol), B2pin2 (1.1
mmol), t-BuONO (1.5 mmol), 2 h; second step: DMF (1.5 mL).
b
c
Isolated yield. Reaction conditions for the second step: Pd(PPh3)4
However, when B2pin2 was set to react with phenyl radical,
which was generated by an alternative process (PhI, n-Bu3SnH,
and AIBN),17 the product Ph-Bpin was formed only in 7% yield
(eq 4). Consequently, even though most of the experimental
(5 mmol %), 10% aq Na2CO3 (2 mL), toluene (4 mL), EtOH (2 mL),
12 h.
a
Scheme 7. Gram-Scale Experiments
observations are consistent with the mechanism shown in
Scheme 8, alternative mechanisms involving an ionic process,
such as nucleophilic aromatic substitution of the aryldiazonium
salt by the boron ate complex, cannot be completely ruled out.
Further rigorous investigation is required to unambiguously
establish the reaction mechanism.
a
Reaction conditions: arylamine (20 mmol), B2pin2 (1.05 equiv), t-
b
CONCLUSION
BuONO (1.5 equiv), 12 h, MeCN (60 mL). Isolated yield.
■
c
Arylamine (10 mmol).
In this report we have further optimized the metal-free
deaminoborylation reaction. The yields are improved, and the
substrate scope has been significantly expanded, especially to
heterocyclic amine derivatives, for which the corresponding
boronate products are highly important both in academic
pathway involving radical species is proposed for this borylation
reaction as shown in Scheme 8. First, the tert-butoxide anion
interacts with B2pin2 to form a tetra-coordinated boron
D
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2-(4-Bromophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4af).11 Flash chromatography (silica gel, petroleum ether, then
petroleum ether/EtOAc = 500:1) afforded 4af (147 mg, 52%); pale
yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.1 Hz, 2H),
7.50 (d, J = 8.1 Hz, 2H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3)
δ 136.3, 130.9, 126.2, 84.0, 24.8; IR (film) 2978 (w), 1589 (m), 1389
(m), 1359 (s), 1166 (m), 1144 (m), 1089 (s), 1012 (m), 821 (m)
cm−1; EI-MS (m/z, relative intensity) 284 (51), 282 (M+, 50), 269
(100), 267 (100), 198 (71), 196 (72), 185 (89), 183 (96), 103 (36).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile
(4ag).11 Flash chromatography (silica gel, petroleum ether/EtOAc =
30:1 then 0:1) afforded 4ag (153 mg, 67%); pale yellow solid; mp 93−
95 °C. 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 7.8 Hz, 2H), 7.64
(d, J = 7.8 Hz, 2H), 1.35 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
135.1, 131.1, 118.8, 114.5, 84.4, 24.8; IR (film) 2980 (w), 2229 (w),
1398 (m), 1360 (s), 1168 (m), 1143 (s), 1125 (m), 1088 (s), 668 (m)
cm−1; EI-MS (m/z, relative intensity) 229 (M+, 14), 214 (100), 213
(20), 186 (12), 143 (81), 130 (50), 58 (16).
research and in the pharmaceutical industry. A radical
mechanism involving SET between aryldiazonium ion and
tetra-coordinated boron complex has been proposed. Since
arylamines are inexpensive and ubiquitous starting materials,
this borylation method is expected to find wide applications in
organic synthesis.
EXPERIMENTAL SECTION
■
The solvents were all distilled prior to use. MeCN and DMF were
distilled from calcium hydride. Silica gel, 200−300 mesh, was used for
the chromatography. 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded in ppm using tetramethylsilane (TMS) as the
internal standard; IR spectra are reported in wave numbers, cm−1. For
HRMS measurements, the mass analyzer is FT-ICR. Melting points
are reported as uncorrected.
Typical Procedure of Borylation Reaction. B2pin2 (279 mg, 1.1
mmol) and 2-aminobenzonitrile (1aa, 118 mg, 1.0 mmol) were
weighed in a 25 mL round-bottom flask. MeCN (3 mL) and t-BuONO
(2a, 155 mg, 1.5 mmol) were then added in succession. The resulting
reaction solution was stirred for 2 h at 80 °C (N2 evolution completed
within 5 to 15 min). The solution was then concentrated under
reduced pressure, and the crude residue was purified by flash
chromatography (silica gel, petroleum ether/EtOAc = 200:1). 2-
(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (4aa)11 was
obtained (152 mg, 66%) as pale yellow solid; mp 80−82 °C; 1H NMR
(400 MHz, CDCl3) δ 7.89 (dd, J = 1.2, 7.3 Hz, 1H), 7.70 (dd, J = 1.2,
7.5 Hz, 1H), 7.55 (m, 2H), 1.39 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 135.8, 133.4, 131.5, 131.0, 118.9, 117.3, 84.8, 24.8; IR (film)
2981 (w), 2228 (w), 1488 (w), 1441 (m), 1382 (s), 1356 (s), 1143
(m), 1119 (m), 857 (m), 731 (m), 654 (m) cm−1; EI-MS (m/z,
relative intensity) 229 (M+, 24), 214 (46), 188 (50), 186 (61), 171
(45), 130 (100), 129 (29), 103 (24), 85 (17).
2-(4-Fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ab).11 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4ab (169 mg, 76%); pale yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.80 (t, J = 7.2 Hz, 2H), 7.04 (t, J = 8.8 Hz, 2H), 1.33
(s, 12H); 13C NMR (100 MHz, CDCl3) δ 165.1 (d, J = 250.3 Hz),
137.0 (d, J = 8.2 Hz), 114.8 (d, J = 20.3 Hz), 83.8, 24.8; IR (film) 2980
(w), 1603 (m), 1399 (m), 1361 (s), 1143 (m), 1088 (m), 860 (w),
668 (w) cm−1; EI-MS (m/z, relative intensity) 222 (M+, 21), 207 (87),
136 (41), 123 (100), 122 (31), 85 (14).
2-(3,4-Dichlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ah).11 Flash chromatography (silica gel, petroleum ether) afforded
1
4ah (194 mg, 71%); pale yellow liquid. H NMR (400 MHz, CDCl3)
δ 7.86 (s, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 1.33
(s, 12H); 13C NMR (100 MHz, CDCl3) δ 136.5, 135.5, 133.7, 132.2,
130.0, 84.3, 24.8; IR (film) 2978 (w), 1590 (w), 1381 (m), 1354 (s),
1143 (m), 1094 (m), 1032 (w), 867 (m) cm−1; EI-MS (m/z, relative
intensity) 274 (31), 272 (M+, 46), 259 (69), 257 (100), 188 (65), 186
(95), 175 (48), 173 (84), 85 (23).
4,4,5,5-Tetramethyl-2-(4-(methylthio)phenyl)-1,3,2-dioxaboro-
lane (4ba).18 Flash chromatography (silica gel, petroleum ether/
1
EtOAc = 500:1) afforded 4ba (160 mg, 64%); pale yellow liquid. H
NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.8 Hz, 2H), 7.22 (d, J = 7.8
Hz, 2H), 2.47 (s, 3H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
142.5, 135.0, 125.0, 83.6, 24.8, 15.0; IR (film) 2978 (w), 1597 (m),
1395 (m), 1359 (s), 1327 (m), 1103 (s), 859 (m), 668 (m) cm−1; EI-
MS (m/z, relative intensity) 250 (M+, 100), 249 (28), 235 (29), 164
(30), 151 (63), 150 (95).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (4bb).19
Flash chromatography (silica gel, petroleum ether/EtOAc = 10:1)
1
afforded 4bb (145 mg, 66%); pale yellow solid; mp 113−114 °C. H
NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0 Hz, 2H), 6.81 (d, J = 8.0
Hz, 2H), 6.68 (s, 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
158.7, 136.7, 115.0, 83.9, 24.7; IR (film) 3364 (w), 2979 (w), 1607 (s),
1397 (m), 1358 (s), 1170 (m), 1141 (s), 1084 (m), 670 (m) cm−1; EI-
MS (m/z, relative intensity) 220 (M+, 48), 205 (58), 134 (40), 121
(100), 120 (97).
2-(4-Chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ac).11 Flash chromatography (silica gel, petroleum ether, then
petroleum ether/EtOAc = 200:1) afforded 4ac (160 mg, 67%); pale
yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.8 Hz, 2H),
7.33 (d, J = 7.8 Hz, 2H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3)
δ 137.5, 136.1, 127.9, 83.9, 24.8; IR (film) 2979 (w), 1597 (m), 1393
(m), 1360 (s), 1144 (m), 1094 (s), 1017 (m), 858 (m) cm−1; EI-MS
(m/z, relative intensity) 240 (13), 238 (M+, 38), 225 (34), 223 (100),
152 (63), 141 (33), 139 (95).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde
(4bc).20 Flash chromatography (silica gel, petroleum ether/EtOAc =
50:1 then 20:1) afforded 4bc (121 mg, 52%); pale yellow solid; mp
55−58 °C. 1H NMR (400 MHz, CDCl3) δ 10.05 (s, 1H), 7.97 (d, J =
7.9 Hz, 2H), 7.86 (d, J = 7.9 Hz, 2H), 1.36 (s, 12H); 13C NMR (100
MHz, CDCl3) δ 192.5, 138.0, 135.2, 128.6, 84.2, 24.8; IR (film) 2979
(w), 1707 (s), 1508 (m), 1358 (s), 1169 (m), 1086 (s), 857 (m), 825
(m), 800 (m) cm−1; EI-MS (m/z, relative intensity) 232 (M+, 21), 217
(78), 146 (90), 133 (100), 85 (25).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic Acid
(4bd).21 Flash chromatography (silica gel, petroleum ether/EtOAc =
50:1) afforded 4bd (150 mg, 60%); yellow solid; mp 228−231 °C. 1H
NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.0 Hz, 2H), 7.91 (d, J = 8.0
Hz, 2H), 1.37 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 172.2, 134.7,
133.8, 129.2, 84.3, 24.8; IR (film) 2981 (w), 1686 (m), 1360 (s), 1167
(w), 1143 (m), 1126 (m), 856 (m), 739 (w) cm−1; EI-MS (m/z,
relative intensity) 248 (M+, 23), 233 (90), 162 (84), 149 (100), 148
(20), 85 (16).
4,4,5,5-Tetramethyl-2-o-tolyl-1,3,2-dioxaborolane (4ad).11 Flash
chromatography (silica gel, then petroleum ether/EtOAc = 500:1)
1
afforded 4ad (126 mg, 58%); white solid; mp 32−34 °C. H NMR
(400 MHz, CDCl3) δ 7.78−7.74 (m, 1H), 7.30 (m, 1H), 7.16 (m,
2H), 2.53 (s, 3H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
144.8, 135.8, 130.7, 129.7, 124.7, 83.4, 24.9, 22.2; IR (film) 2978 (w),
2926 (w), 1380 (m), 1346 (s), 1146 (m), 1073 (m), 862 (m), 730
(m), 659 (m) cm−1; EI-MS (m/z, relative intensity) 218 (M+, 25), 203
(35), 161 (85), 119 (100), 118 (84), 91 (20).
4,4,5,5-Tetramethyl-2-p-tolyl-1,3,2-dioxaborolane (4ae).11 Flash
chromatography (silica gel, petroleum ether, then petroleum ether/
EtOAc = 250:1) afforded 4ae (163 mg, 75%); white solid; mp 53−54
°C. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.7 Hz, 2H), 7.17 (d, J
= 7.7 Hz, 2H), 2.35 (s, 3H), 1.33 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 141.3, 134.8, 128.4, 83.5, 24.8, 21.6; IR (film) 2978 (w),
1613 (w), 1517 (w), 1398 (m), 1360 (s), 1318 (m), 1304 (w), 1144
(m), 860 (m) cm−1; EI-MS (m/z, relative intensity) 218 (M+, 44), 203
(61), 132 (67), 119 (100), 118 (50), 91 (17).
Ethyl 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
benzenesulfonate (4be). Flash column chromatography (silica gel,
petroleum ether/EtOAc = 30:1 then 10:1) afforded 4be (240 mg,
1
77%); yellow solid; mp 82−84 °C. H NMR (400 MHz, CDCl3) δ
7.98 (d, J = 8.3 Hz, 2H), 7.89 (d, J = 8.3 Hz, 2H), 4.12 (q, J = 7.1 Hz,
2H), 1.36 (s, 12H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 138.4, 135.3, 126.7, 84.5, 67.1, 24.8, 14.7; IR (film) 2981
E
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(w), 1393 (m), 1358 (s), 1188 (m), 1143 (m), 1099 (w), 962 (w), 668
(m) cm−1; EI-MS (m/z, relative intensity) 312 (M+, 7), 297 (52), 226
(100), 213 (27), 185 (18), 104 (18); HRMS (ESI) calcd for
C14H22BO5S [M + H]+ 313.1278, found 313.1272.
(E)-1-Phenyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenyl)diazene (4bf).22 Flash chromatography (silica gel, petroleum
ether/EtOAc = 200:1) afforded 4bf (184 mg, 60%); red solid; mp 87−
89 °C. 1H NMR (400 MHz, CDCl3) δ 7.98−7.89 (m, 6H), 7.50−7.43
(m, 3H), 1.35 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 154.3, 152.6,
135.6, 131.1, 129.0, 122.9, 121.9, 84.0, 24.8; IR (film) 2978 (w), 1603
(w), 1397 (m), 1358 (s), 1142 (s), 1087 (s), 858 (m), 688 (m), 667
(w) cm−1; EI-MS (m/z, relative intensity) 308 (M+, 55), 203 (100),
202 (24), 105 (32), 77 (84).
2-(Biphenyl-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4bm).26 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1 then 100:1) afforded 4bm (165 mg, 59%); yellow solid; mp
104−106 °C. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 7.3 Hz, 2H),
7.61 (d, J = 7.1 Hz, 4H), 7.43 (t, J = 7.3 Hz, 2H), 7.35 (t, J = 7.1 Hz,
1H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 143.8, 141.0,
135.2, 128.7, 127.5, 127.2, 126.4, 83.8, 24.8; IR (film) 2978 (w), 1609
(w), 1398 (m), 1360 (s), 1144 (m), 1092 (m), 766 (m), 697 (m)
cm−1; EI-MS (m/z, relative intensity) 280 (M+, 67), 265 (21), 194
(60), 181 (74), 180 (100), 152 (18).
2-(2-Isopropylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ca).27 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4ca (118 mg, 48%); pale yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.74 (d, J = 7.3 Hz, 1H), 7.39−7.35 (m, 1H), 7.30 (d,
J = 7.8 Hz, 1H), 7.15 (m, 1H), 3.68 (m, 1H), 1.33 (s, 12H), 1.23 (d, J
= 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 155.4, 135.7, 130.9,
124.8, 124.4, 83.3, 31.5, 24.8, 24.4; IR (film) 2976 (w), 1599 (w), 1380
(m), 1346 (s), 1310 (m), 1144 (s), 1060 (m), 861 (m), 766 (m)
cm−1; EI-MS (m/z, relative intensity) 246 (M+, 20), 231 (15), 189
(50), 146 (56), 145 (60), 131 (74), 101 (62), 84 (100).
2-(2-Fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4cb).7a Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4cb (108 mg, 48%); pale yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.76−7.72 (m, 1H), 7.42 (m, 1H), 7.13 (m, 1H), 7.02
(m, 1H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 167.2 (d, J =
250.8 Hz), 136.8 (d, J = 8.0 Hz), 133.2 (d, J = 8.8 Hz), 123.5 (d, J =
3.2 Hz), 115.2 (d, J = 23.8 Hz), 83.8, 24.8; IR (film) 2980 (w), 1615
(m), 1389 (m), 1356 (s), 1324 (m), 1144 (m), 1074 (m), 790 (w)
cm−1; EI-MS (m/z, relative intensity) 222 (M+, 23), 207 (38), 160
(19), 123 (100), 122 (33), 85 (18).
4,4,5,5-Tetramethyl-2-(4-vinylphenyl)-1,3,2-dioxaborolane
(4bg).23 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
500:1 then 100:1) afforded 4bg (37 mg, 16%); pale yellow liquid. H
NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 7.8
Hz, 2H), 6.72 (dd, J = 10.9, 17.6 Hz, 1H), 5.81 (d, J = 17.6 Hz, 1H),
5.29 (d, J = 10.9 Hz, 1H), 1.35 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 140.2, 136.9, 135.0, 125.5, 114.8, 83.8, 24.8; IR (film) 2979
(w), 1610 (w), 1398 (m), 1360 (s), 1144 (m), 1108 (w), 963 (w), 859
(m), 668 (m) cm−1; EI-MS (m/z, relative intensity) 230 (M+, 52), 215
(40), 144 (82), 131 (90), 130 (100).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (4bh).20
Flash chromatography (silica gel, petroleum ether/EtOAc = 25:1)
afforded 4bh (135 mg, 62%); yellow solid; mp 148−150 °C. 1H NMR
(400 MHz, CDCl3) δ 7.62 (d, J = 7.8 Hz, 2H), 6.65 (d, J = 7.8 Hz,
2H), 1.32 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 149.3, 136.4,
114.0, 83.2, 24.8; IR (film) 3450 (w), 3358 (w), 2927 (w), 1628 (w),
1359 (s), 1182 (w), 1143 (s), 860 (m), 738 (s) cm−1; EI-MS (m/z,
relative intensity) 219 (M+, 65), 204 (16), 161 (13), 133 (22), 120
(77), 119 (100).
2-(2-Chlorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4cc).28 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
500:1) afforded 4cc (102 mg, 43%); yellow liquid. H NMR (400
1,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene
(4bi).5a Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1 then 100:1) afforded 4bi (172 mg, 52%); pale yellow solid; mp
MHz, CDCl3) δ 7.68 (d, J = 7.2 Hz, 1H), 7.35−7.32 (m, 2H), 7.24−
7.20 (m, 1H), 1.37 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 139.5,
136.4, 131.8, 129.3, 125.8, 84.1, 24.7; IR (film) 2979 (w), 1593 (w),
1380 (m), 1352 (s), 1144 (s), 1039 (m), 758 (m), 670 (m) cm−1; EI-
MS (m/z, relative intensity) 240 (6), 238 (M+, 18), 223 (21), 203
(100), 161 (44), 139 (90), 103 (20).
2-(2,6-Dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4cd).19 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4 cd (53 mg, 23%); pale yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.11 (t, J = 7.6 Hz, 1H), 6.93 (d, J = 7.6 Hz, 2H), 2.39
(s, 6H), 1.38 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 141.7, 129.1,
126.4, 83.6, 24.9, 22.2; IR (film) 2978 (w), 1597 (w), 1371 (m), 1332
(s), 1302 (s), 1144 (s), 1060 (s), 859 (m), 770 (m) cm−1; EI-MS (m/
z, relative intensity) 232 (M+, 32), 175 (100), 174 (35), 133 (53), 132
(66).
1
232−233 °C. H NMR (400 MHz, CDCl3) δ 7.81 (s, 4H), 1.34 (s,
24H); 13C NMR (100 MHz, CDCl3) δ 133.8, 83.8, 24.8; IR (film)
2977 (w), 1439 (w), 1394 (m), 1371 (m), 1354 (s), 1142 (s), 1101
(s), 858 (s), 701 (w) cm−1; EI-MS (m/z, relative intensity) 330 (M+,
35), 315 (52), 273 (27), 244 (88), 231 (100), 230 (50), 131 (30).
Triisopropyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenyl)ethynyl)silane (4bj.24 Flash chromatography (silica gel,
petroleum ether/EtOAc = 500:1) afforded 4bj (238 mg, 62%);
orange solid; mp 80−82 °C. 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J
= 8.1 Hz, 2H), 7.46 (d, J = 8.1 Hz, 2H), 1.33 (s, 12H), 1.13 (s, 21H);
13C NMR (100 MHz, CDCl3) δ 134.4, 131.1, 126.2, 107.2, 92.0, 83.9,
24.8, 18.6, 11.3; IR (film) 2943 (w), 2866 (w), 1606 (m), 1398 (m),
1358 (s), 1143 (m), 1019 (m), 860 (m), 675 (s) cm−1; EI-MS (m/z,
relative intensity) 384 (M+, 4), 342 (21), 341 (100), 313 (18), 299
(30), 285 (35), 271 (54), 185 (16), 171 (22).
2-(2-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ce).29 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
100:1 then 50:1) afforded 4ce (61 mg, 26%); colorless liquid. H
2-(4-Iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4bk).7a Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4bk (132 mg, 40%); pale yellow solid; mp 89−91 °C.
1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.51 (d, J =
NMR (400 MHz, CDCl3) δ 7.69−7.65 (m, 1H), 7.39 (m, 1H), 6.94
(m, 1H), 6.85 (d, J = 8.3 Hz, 1H), 3.83 (s, 3H), 1.35 (s, 12H); 13C
NMR (100 MHz, CDCl3) δ 164.2, 136.7, 132.4, 120.2, 110.5, 83.4,
55.8, 24.8; IR (film) 2979 (w), 1600 (m), 1461 (m), 1386 (m), 1353
(s), 1273 (m), 1145 (m), 1073 (m), 760 (m) cm−1; EI-MS (m/z,
relative intensity) 234 (M+, 67), 219 (28), 203 (11), 161 (33), 134
(100), 133 (60), 105 (47), 91 (69).
8.0 Hz, 2H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 136.9,
136.2, 98.8, 84.0, 24.8; IR (film) 2976 (w), 1587 (m), 1387 (m), 1359
(s), 1325 (m), 1088 (s), 1007 (m), 857 (m) cm−1; EI-MS (m/z,
relative intensity) 330 (M+, 100), 315 (52), 244 (82), 230 (71), 229
(76), 104 (35), 103 (30).
2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (4cf).30
Flash chromatography (silica gel, petroleum ether/EtOAc = 100:1)
(E)-Ethyl 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenyl)acrylate (4bl).25 Flash chromatography (silica gel, petroleum
ether/EtOAc = 50:1 then 10:1) afforded 4bl (124 mg, 41%); Colorless
oil. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 2H), 7.69 (d, J
= 16.0 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 6.49 (d, J = 16.0 Hz, 1H),
4.26 (q, J = 7.1 Hz, 2H), 1.36−1.34 (m, 15H); 13C NMR (100 MHz,
CDCl3) δ 166.8, 144.4, 136.9, 135.2, 127.2, 119.1, 84.0, 60.5, 24.8,
14.3; IR (film) 2979 (w), 1714 (m), 1398 (m), 1359 (s), 1143 (s),
1089 (s), 858 (m), 706 (m) cm−1; EI-MS (m/z, relative intensity) 302
(M+, 100), 287 (72), 257 (22), 216 (60), 203 (92), 157 (64), 129
(58), 77 (38).
1
afforded 4cf (44 mg, 20%); pale yellow liquid. H NMR (400 MHz,
CDCl3) δ 7.80 (s, 1H), 7.61 (dd, J = 1.6, 7.5 Hz, 1H), 7.37 (m, 1H),
6.90−6.86 (m, 2H), 1.37 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
163.6, 135.7, 133.8, 119.5, 115.4, 84.4, 24.8; IR (film) 3448 (w), 2980
(w), 1620 (s), 1486 (m), 1390 (s), 1167 (m), 1140 (s), 860 (m), 671
(m) cm−1; EI-MS (m/z, relative intensity) 220 (M+, 18), 163 (100),
162 (25), 121 (20), 120 (47).
2-(3-Fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4cg).31 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4cg (104 mg, 47%); pale yellow liquid. 1H NMR (400
F
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MHz, CDCl3) δ 7.57 (d, J = 7.2 Hz, 1H), 7.48 (m, 1H), 7.33 (m, 1H),
7.13 (m, 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 162.5
(d, J = 246.4 Hz), 130.3 (d, J = 2.9 Hz), 129.4 (d, J = 7.0 Hz), 120.9
(d, J = 19.3 Hz), 118.1 (d, J = 21.0 Hz), 84.1, 24.8; IR (film) 2980 (w),
1431 (m), 1381 (m), 1355 (s), 1144 (m), 1091 (w), 901 (m), 716
(m) cm−1; EI-MS (m/z, relative intensity) 222 (M+, 39), 207 (85),
136 (98), 123 (100), 122 (37), 85 (18), 58 (18).
2981 (w), 1614 (m), 1519 (m), 1390 (s), 1360 (s), 1272 (s), 1167
(m), 1144 (s), 890 (w), 689 (m) cm−1; EI-MS (m/z, relative intensity)
240 (M+, 21), 225 (84), 154 (80), 141 (100), 131 (18), 79 (38), 58
(56).
2-(Benzo[d][1,3]dioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (4co).37 Flash chromatography (silica gel, petroleum ether/
1
EtOAc = 500:1) afforded 4co (35 mg, 14%); yellow liquid. H NMR
(400 MHz, CDCl3) δ 7.36 (d, J = 7.7 Hz, 1H), 7.24 (s, 1H), 6.83 (d, J
= 7.7 Hz, 1H), 5.95 (s, 2H), 1.33 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 150.2, 147.2, 129.7, 113.9, 108.3, 100.7, 83.7, 24.8; EI-MS
(m/z, relative intensity) 248 (M+, 76), 233 (20), 162 (43), 149 (67),
148 (100), 147 (50).
Dimethyl 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-
isophthalate (4cp).38 Flash chromatography (silica gel, petroleum
ether/EtOAc = 50:1) afforded 4 cP (109 mg, 34%); yellow solid; mp
125−127 °C. 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.64 (d, J =
1.4 Hz, 2H), 3.95 (s, 6H), 1.37 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 166.2, 139.8, 133.2, 130.0, 84.3, 52.2, 24.8; IR (film) 1726
(s), 1381 (m), 1334 (m), 1287 (m), 1262 (s), 1244 (s), 1008 (m), 736
(s) cm−1; EI-MS (m/z, relative intensity) 320 (M+, 11), 305 (28), 289
(25), 277 (100), 221 (55), 189 (24), 161 (22).
2-(3-Bromophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ch).32 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4ch (153 mg, 54%); pale yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.93 (s, 1H), 7.71−7.56 (m, 2H), 7.22 (t, J = 7.7 Hz,
1H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 137.4, 134.1,
133.0, 129.4, 122.4, 84.1, 24.8; IR (film) 2979 (w), 1407 (m), 1372
(m), 1351 (s), 1321 (m), 1143 (s), 1101 (w), 700 (s) cm−1; EI-MS
(m/z, relative intensity) 284 (43), 282 (M+, 51), 269 (78), 267 (81),
198 (98), 196 (100), 185 (71), 183 (76), 103 (36), 85 (33).
2-(3-Iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4ci).33 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
500:1) afforded 4ci (132 mg, 40%); yellow solid; mp 64−66 °C. H
NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.77−7.73 (m, 2H), 7.10 (t,
J = 7.6 Hz, 1H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 143.4,
140.0, 133.6, 129.6, 94.5, 84.1, 24.8; IR (film) 2978 (w), 1402 (m),
1372 (m), 1349 (s), 1320 (m), 1143 (s), 1097 (w), 701 (m) cm−1; EI-
MS (m/z, relative intensity) 330 (M+, 98), 315 (67), 244 (100), 231
(67), 230 (64), 104 (30), 103 (28).
2-(4-Chloro-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (4cq).39 Flash column chromatography (silica gel, petroleum
ether/EtOAc = 200:1) afforded 4cq (88 mg, 31%); yellow solid; mp
1
39−41 °C; H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 7.89 (d, J =
8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 1.35 (s, 12H); 13C NMR (100
MHz, CDCl3) δ 147.8, 138.9, 131.3, 131.2, 129.5, 84.8, 24.8; IR (film)
2981 (w), 1604 (m), 1537 (m), 1390 (m), 1348 (s), 1143 (s), 1097
(m), 851 (m) cm−1; EI-MS (m/z, relative intensity) 285 (2), 283 (M+,
7), 270 (30), 268 (90), 223 (26), 197 (40), 181 (80), 155 (100), 85
(42), 58 (51); HRMS (ESI) calcd for C12H15B35ClNNaO4 [M + Na]+
306.0677, found 306.0668.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile
(4cj).29 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
30:1) afforded 4cj (147 mg, 64%); colorless liquid. H NMR (400
MHz, CDCl3) δ 8.09 (s, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.72−7.47 (m,
2H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 138.6, 138.2,
134.2, 128.3, 118.7, 111.9, 84.4, 24.7; IR (film) 2980 (w), 2230 (w),
1603 (w), 1358 (s), 1167 (w), 1143 (s), 880 (m), 700 (s), 672 (m)
cm−1; EI-MS (m/z, relative intensity) 229 (M+, 23), 214 (96), 186
(17), 143 (100), 130 (65), 58 (31).
4,4,5,5-Tetramethyl-2-(naphthalen-2-yl)-1,3,2-dioxaborolane
(5da).40 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
500:1) afforded 5da (58 mg, 23%); white solid; mp 64−66 °C. H
Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
(4ck).18 Flash chromatography (silica gel, petroleum ether/EtOAc =
NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 7.89−7.82 (m, 4H), 7.49−
7.47 (m, 2H), 1.39 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 136.2,
135.0, 132.8, 130.4, 128.6, 127.7, 126.9, 125.8, 83.9, 24.9; IR (film)
2978 (w), 1476 (m), 1383 (s), 1351 (s), 1144 (s), 1080 (m), 877 (m),
747 (s), 687 (m) cm−1; EI-MS (m/z, relative intensity) 254 (M+, 45),
239 (10), 168 (64), 154 (100), 128 (10).
1
50:1 then 30;1) afforded 4ck (192 mg, 70%); pale yellow liquid. H
NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 8.14 (d, J = 7.8 Hz, 1H),
7.99−7.44 (m, 2H), 4.39 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H),
1.35 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 166.5, 139.0, 135.6,
132.2, 129.8, 127.6, 83.9, 60.8, 24.7, 14.3; IR (film) 2980 (w), 1720
(s), 1390 (m), 1358 (s), 1280 (m), 1252 (s), 1167 (m), 1144 (s), 734
(w), 659 (m) cm−1; EI-MS (m/z, relative intensity) 276 (M+, 25), 261
(40), 233 (100), 205 (64), 177 (86), 149 (28), 131 (33), 103 (35).
4,4,5,5-Tetramethyl-2-m-tolyl-1,3,2-dioxaborolane (4cl).34 Flash
chromatography (silica gel, petroleum ether/EtOAc = 500:1) afforded
4cl (42 mg, 19%); colorless solid; mp 33−34 °C. 1H NMR (400 MHz,
CDCl3) δ 7.64−7.61 (m, 2H), 7.27 (s, 2H), 2.35 (s, 3H), 1.33 (s,
12H); 13C NMR (100 MHz, CDCl3) δ 137.0, 135.3, 132.0, 131.8,
127.6, 83.6, 24.8, 21.2; IR (film) 2978 (w), 1379 (m), 1356 (s), 1145
(s), 1103 (w), 852 (m), 708 (s), 665 (m) cm−1; EI-MS (m/z, relative
intensity) 218 (M+, 38), 203 (43), 132 (77), 119 (100), 118 (57), 91
(20).
2-Phenyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4H-
chromen-4-one (5db).41 Flash chromatography (silica gel, petroleum
ether/EtOAc = 15:1 then 10:1) afforded 5db (56 mg, 32%); yellow
1
solid; mp 88−90 °C. H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 1.2
Hz, 1H), 8.10 (dd, J = 1.4, 8.4 Hz, 1H), 7.94−7.92 (m, 2H), 7.56−
7.52 (m, 4H), 6.85 (s, 1H), 1.37 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 178.4, 163.3, 158.2, 139.6, 133.3, 131.7, 131.6, 129.0, 126.3,
123.2, 117.3, 107.9, 84.2, 24.9; IR (film) 2978 (w), 2924 (w), 1644 (s),
1608 (m), 1351 (s), 1306 (m), 1143 (m), 712 (m) cm−1; EI-MS (m/z,
relative intensity) 348 (M+, 73), 333 (44), 305 (39), 262 (20), 249
(100), 248 (71), 220 (19), 102 (54).
6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-chromen-2-
one (5dc). Flash column chromatography (silica gel, petroleum ether/
EtOAc = 20:1 then 10:1) afforded 5dc (78 mg, 57%); white solid; mp
2-(3,5-Difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4cm).35 Flash chromatography (silica gel, petroleum ether/EtOAc =
500:1) afforded 4 cm (151 mg, 63%); colorless solid; yellow solid; mp
1
105−107 °C; H NMR (400 MHz, CDCl3) δ 7.96−7.94 (m, 2H),
1
7.72 (d, J = 9.5 Hz, 1H), 7.32 (d, J = 8.6 Hz, 1H), 6.42 (d, J = 9.5 Hz,
1H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 160.6, 156.1,
143.6, 138.1, 135.0, 118.3, 116.5, 116.2, 84.2, 24.8; IR (film) 2984 (w),
1753 (m), 1730 (s), 1393 (m), 1382 (s), 1371 (s), 1180 (m), 1131
(m) cm−1; EI-MS (m/z, relative intensity) 272 (M+, 71), 257 (69),
186 (100), 173 (96), 144 (58), 116 (20), 85 (15); HRMS (ESI) calcd
for C15H18BO4 [M + H]+ 273.1295, found 273.1291.
36−38 °C. H NMR (400 MHz, CDCl3) δ 7.28 (dd, J = 1.9, 7.8 Hz,
2H), 6.87 (tt, J = 2.4, 9.1 Hz, 1H), 1.34 (s, 12H); 13C NMR (100
MHz, CDCl3) δ 162.7 (dd, J = 11.0, 249.7 Hz), 116.8 (dd, J = 5.7, 17.1
Hz), 106.5 (t, J = 25.1 Hz), 84.4, 24.8; IR (film); 2981 (w), 1587 (m),
1427 (s), 1368 (s), 1144 (m), 980 (m), 872 (m), 717 (w) cm−1; EI-
MS (m/z, relative intensity) 240 (M+, 27), 225 (81), 197 (10), 154
(100), 141 (61), 85 (15), 58 (31).
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (5dd).19
Recrystallization from cyclohexane afforded 5dd (123 mg, 60%);
2-(3,4-Difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
4cn).36 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
1
500:1 then 100:1) afforded 4cn (156 mg, 65%); yellow liquid. H
white solid; mp 99−101 °C. H NMR (400 MHz, CDCl3) δ 8.95 (s,
NMR (400 MHz, CDCl3) δ 7.60−7.51 (m, 2H), 7.17−7.10 (m, 1H),
1.34 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 152.6 (dd, J = 12.7,
252.2 Hz), 150.2 (dd, J = 12.0, 248.6 Hz), 131.4 (dd, J = 3.8, 6.7 Hz),
123.3 (d, J = 15.1 Hz), 116.9 (d, J = 16.3 Hz), 84.2, 24.8; IR (film)
1H), 8.69−8.65 (m, 1H), 8.06 (d, J = 7.5 Hz, 1H), 7.30−7.27 (m,
1H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 155.3, 151.8,
142.2, 123.0, 84.2, 24.8; IR (film) 2976 (w), 1474 (m), 1413 (m),
1363 (m), 1156 (s), 1048 (s), 1024 (m), 876 (m), 734 (m) cm−1; EI-
G
dx.doi.org/10.1021/jo3018878 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
MS (m/z, relative intensity) 205 (M+, 36), 190 (100), 148 (44), 120
(15), 106 (87), 105 (33).
IR (film) 3031 (w), 1582 (w), 1473 (m), 1407 (m), 1024 (w), 1006
(w), 754 (s), 697 (s) cm−1; EI-MS (m/z, relative intensity) 155 (M+,
100), 154 (50), 127 (14), 102 (10), 63 (8), 51 (13).
5-Methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
thiophene-3-carbonitrile (5de). Flash column chromatography (silica
gel, petroleum ether/EtOAc = 20:1) afforded 5de (37 mg, 15%);
4-Fluorobiphenyl (6a).46 Flash chromatography (silica gel,
petroleum ether) afforded 6a (122 mg, 71%); white solid; mp 75−
77 °C. 1H NMR (400 MHz, CDCl3) δ 7.53−7.51 (m, 4H), 7.41 (t, J =
7.2 Hz, 2H), 7.32 (t, J = 7.2 Hz, 1H), 7.12−7.08 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 162.4 (d, J = 246.1 Hz), 140.2, 137.3 (d, J = 3.1
Hz), 128.8, 128.6 (d, J = 8.0 Hz), 127.2, 127.0, 115.6 (d, J = 21.4 Hz);
IR (film) 1517 (m), 1485 (m), 1235 (m), 1196 (w), 907 (s), 837 (m),
760 (m), 732 (s) cm−1; EI-MS (m/z, relative intensity) 172 (M+, 100),
171 (41), 170 (27), 142 (18), 100 (9), 85 (9).
1
yellow liquid. H NMR (400 MHz, CDCl3) δ 7.05 (s, 1H), 2.52 (s,
3H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 147.9, 129.4,
117.9, 84.9, 24.7, 15.2; IR (film) 2926 (w), 2228 (w), 1726 (w), 1463
(s), 1364 (s), 1167 (m), 1140 (s), 1048 (s), 851 (s) cm−1; EI-MS (m/
z, relative intensity) 249 (M+, 62), 234 (31), 219 (15), 207 (54), 191
(54), 163 (28), 150 (100), 59 (30); HRMS (ESI) calcd for
C12H17BNO2S [M + H]+ 250.1070, found 250.1066.
Biphenyl-4-carbonitrile (6b).47 Flash chromatography (silica gel,
petroleum ether/EtOAc = 100:1) afforded 6b (88 mg, 49%); white
6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole
(5df).42 Flash chromatography (silica gel, petroleum ether/EtOAc =
20:1 then 10:1) afforded 5df (53 pmg, 22%); orange solid; mp 181−
1
solid; mp 83−85 °C. H NMR (400 MHz, CDCl3) δ 7.70 (m, 4H),
1
7.59−7.42 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 145.6, 139.1,
132.5, 129.1, 128.6, 127.7, 127.2, 118.9, 110.8; IR (film) 2227 (m),
1606 (m), 1485 (m), 1265 (w), 1008 (w), 844 (m), 766 (s), 698
cm−1; EI-MS (m/z, relative intensity) 179 (M+, 100), 178 (25), 151
(14), 76 (10), 63 (5).
183 °C. H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.90 (s, 1H),
7.65 (d, J = 7.9 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.24 (d, J = 1.5 Hz,
1H), 6.55 (s, 1H), 1.36 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
135.5, 130.4, 125.6, 125.5, 120.0, 118.0, 102.7, 83.5, 24.9; IR (film)
3320 (w), 2925 (w), 1514 (m), 1392 (m), 1358 (s), 1166 (w), 1142
(s), 894 (w) cm−1; EI-MS (m/z, relative intensity) 243 (M+, 79), 228
(25), 170 (17), 157 (26), 144 (54), 143 (100), 116 (17).
5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinoline
(5dg).43 Flash chromatography (silica gel, petroleum ether/EtOAc =
10:1) afforded 5dg (143 mg, 56%); yellow liquid. 1H NMR (400
MHz, CDCl3) δ 9.23 (s, 1H), 8.57 (s, 2H), 8.27 (d, J = 6.8 Hz, 1H),
8.02 (d, J = 8.1 Hz, 1H), 7.57 (m, 1H), 1.41 (s, 12H); 13C NMR (100
MHz, CDCl3) δ 152.8, 143.5, 139.7, 139.4, 130.9, 128.3, 126.2, 121.0,
83.9, 24.8; IR (film) 2978 (w), 1612 (w), 1488 (w), 1371 (m), 1344
(s), 1136 (s), 1111 (w), 868 (m) cm−1; EI-MS (m/z, relative
intensity) 255 (M+, 63), 240 (20), 182 (18), 169 (40), 156 (55), 155
(100), 128 (19).
Ethyl Biphenyl-3-carboxylate (6c).48 Flash chromatography (silica
gel, petroleum ether, then petroleum ether/EtOAc = 100:1) afforded
6c (131 mg, 58%); pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ
8.28 (s, 1H), 8.02 (d, J = 7.9 Hz, 1H), 7.75−7.61 (m, 3H), 7.50−7.42
(m, 3H), 7.35 (t, J = 7.3 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 1.40 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.4, 141.3, 140.1,
131.3, 131.0, 128.8, 128.7, 128.2, 128.1, 127.6, 127.1, 61.0, 14.3; IR
(film) 1717 (s), 1305 (m), 1272 (w), 1239 (s), 1108 (m), 1084 (w),
742 (s), 697 (m) cm−1; EI-MS (m/z, relative intensity) 226 (M+, 73),
198 (30), 181 (100), 153 (55), 152 (75), 76 (21).
(E)-Ethyl 3-(Biphenyl-4-yl)acrylate (6d).49 Flash chromatography
(silica gel, petroleum ether/EtOAc = 200:1 then 100:1) afforded 6d
(81 mg, 32%); white solid; mp 77−79 °C. 1H NMR (400 MHz,
CDCl3) δ 7.73 (d, J = 16.0 Hz, 1H), 7.63−7.58 (m, 6H), 7.45−7.37
(m, 3H), 6.47 (d, J = 16.0 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.35 (t, J
= 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.0, 144.1, 143.0,
140.2, 133.4, 128.9, 128.5, 127.8, 127.5, 127.0, 118.1, 60.5, 14.3; EI-MS
(m/z, relative intensity) 252 (M+, 100), 224 (19), 207 (100), 180
(46), 178 (78), 165 (32), 76 (20).
2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
pyridine (5di).44 Flash chromatography (silica gel, petroleum ether/
1
EtOAc = 20:1) afforded 5di (117 mg, 50%); yellow liquid. H NMR
(400 MHz, CDCl3) δ 8.56 (s, 1H), 7.92 (d, J = 8.3 Hz, 1H), 6.71 (d, J
= 8.3 Hz, 1H), 3.95 (s, 3H), 1.33 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 166.0, 154.1, 144.3, 110.1, 83.6, 53.2, 24.7; IR (film) 2979
(w), 1600 (s), 1500 (w), 1372 (m), 1354 (s), 1145 (m), 859 (m), 687
(w) cm−1; EI-MS (m/z, relative intensity) 235 (M+, 80), 234 (100),
220 (19), 206 (15), 136 (88), 135 (63), 105 (28).
Borylation of 2-Naphthylamine (1da) in Water. 2-Naphthyl-
amine (1da, 1 mmol, 143 mg), aqueous HCl (0.41 mL, 12 mol/L),
and H2O (0.5 mL) were stirred with ice bath. Then, NaNO2 (1.1
mmol, 76 mg) in H2O (0.5 mL) was added by dropping funnel. The
reaction system was stirred for 15 min. B2pin2 (1.1 mmol, 279 mg) and
MeCN (1 mL) solution were then added in succession. The resulting
solution was stirred at 80 °C for 2 h. The reaction mixture was then
concentrated under reduced pressure, and the crude residue was
purified by silica gel flash chromatography (petroleum ether). 4,4,5,5-
Tetramethyl-2-(naphthalen-2-yl)-1,3,2-dioxaborolane (5da) was ob-
tained (95 mg, 38%).
Typical Procedure of Consecutive Suzuki−Miyaura Cross-
Coupling Reactions. B2pin2 (279 mg, 1.1 mmol) and 3-amino-
pyridine (94 mg, 1.0 mmol) were weighed in a 25 mL round-bottom
flask. MeCN (3 mL) and t-BuONO (2a, 155 mg, 1.5 mmol) were then
added in succession. The resulting reaction solution was stirred for 2 h
at 80 °C (N2 evolution completed within 5−15 min). After the MeCN
was removed by evaporation under reduced pressure, the system was
degassed 3 times and was set under nitrogen atmosphere. Then
Pd(PPh3)4 (58 mg, 5 mmol %), K2CO3 (276 mg, 2 mmol), DMF (1.5
mL), and PhI (245 mg, 1.2 mmol) were added, and the solution was
stirred at 100 °C for 12 h. The solution was then concentrated by
rotovap under reduced pressure to leave a crude residue, which was
purified by silica gel column chromatography (petroleum ether/EtOAc
= 50:1, then 5:1) to give 3-phenylpyridine 6f45 in 63% isolated yield as
pale yellow liquid.1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.59
(d, J = 4.1 Hz, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 7.5 Hz, 2H),
7.47 (t, J = 7.5 Hz, 2H), 7.42−7.33 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 148.4, 148.3, 137.7, 136.5, 134.2, 129.0, 128.0, 127.0, 123.4;
2,6-Diphenyl-4H-chromen-4-one (6e).50 Flash column chromatog-
raphy (silica gel, petroleum ether/EtOAc = 100:1, then 20:1) afforded
6e (122 mg, 41%); white solid; mp 152−155 °C; 1H NMR (400 MHz,
CDCl3) δ 8.45 (d, J = 2.3 Hz, 1H), 7.96−7.93 (m, 3H), 7.69−7.63 (m,
3H), 7.55−7.53 (m, 3H), 7.47 (t, J = 7.4 Hz, 2H), 7.39 (t, J = 7.4 Hz,
1H), 6.87 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 178.5, 163.4,
155.6, 139.2, 138.4, 132.6, 131.7, 131.6, 129.0, 128.9, 127.8, 127.1,
126.3, 124.0, 123.5, 118.6, 107.5; IR (film) 1634 (s), 1616 (s), 1496
(w), 1473 (m), 1359 (s), 1049 (w), 772 (m), 687 (m) cm−1; HRMS
(ESI) calcd for C21H15O2 [M + H]+ 299.1067, found 299.1063.
2-Methyl-5-phenylpyridine (6g).51 Flash chromatography (silica
gel, petroleum ether/EtOAc = 20:1 then 5:1) afforded 6g (91 mg,
54%); pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.73 (s, 1H),
7.75 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 7.6 Hz, 2H), 7.45−7.20 (m, 4H),
2.59 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.1, 147.4, 137.8,
134.6, 133.6, 128.9, 127.7, 126.8, 123.0, 24.0; IR (film) 1604 (w), 1479
(m), 1445 (w), 1374 (w), 1030 (w), 759 (s), 731 (w), 697 (s) cm−1;
EI-MS (m/z, relative intensity) 169 (M+, 100), 168 (24), 141 (23),
115 (18), 102 (10), 51 (8).
3-Methyl-5-phenylpyridine (6h).52 Flash chromatography (silica
gel, petroleum ether/EtOAc = 50:1 then 5:1) afforded 6h (59 mg,
35%); pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H),
8.42 (s, 1H), 7.66 (s, 1H), 7.56−7.38 (m, 5H), 2.38 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 148.8, 145.4, 137.8, 136.0, 134.8, 132.9, 128.9,
127.8, 127.0, 18.3; IR (film) 3033 (w), 1453 (w), 1414 (m), 1150 (w),
1028 (w), 875 (m), 760 (s), 697 (s) cm−1; EI-MS (m/z, relative
intensity) 169 (M+, 100), 168 (35), 141 (15), 115 (16), 102 (6).
4-Methyl-3-phenylpyridine (6i).52 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 5:1) afforded 6i (88 mg, 52%);
yellow liquid. 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 2H), 7.45−7.31
(m, 5H), 7.18 (d, J = 2.6 Hz, 1H), 2.28 (s, 3H); 13C NMR (100 MHz,
H
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CDCl3) δ 149.9, 148.2, 144.4, 137.8, 137.6, 129.2, 128.3, 127.5, 125.1,
19.7; IR (film) 1590 (m), 1444 (m), 1401 (m), 1007 (m), 995 (w),
766 (s), 732 (w), 702 (s) cm−1; EI-MS (m/z, relative intensity) 169
(M+, 95), 168 (100), 167 (49), 154 (20), 115 (18), 91 (18).
Methyl 5-Phenylnicotinate (6j).53 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 5:1) afforded 6j (106 mg, 50%);
4-Phenylisoquinoline (6q).60 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 5:1) afforded 6q (88 mg, 43%);
yellow liquid. H NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 8.49 (s,
1H), 8.01 (d, J = 7.7 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.64−7.59 (m,
2H), 7.50−7.46 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 151.8,
142.7, 136.9, 134.1, 133.2, 130.4, 130.0, 128.5, 128.3, 127.8, 127.8,
127.0, 124.7; IR (film) 3030 (w), 1620 (w), 1504 (w), 1390 (m), 1219
(w), 1073 (w), 828 (w), 760 (s), 703 (s) cm−1; EI-MS (m/z, relative
intensity) 205 (M+, 100), 204 (73), 178 (15), 176 (22), 151 (8), 102
(15), 88 (12), 76 (11).
1
1
yellow liquid. H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 9.00 (s,
1H), 8.48 (s, 1H), 7.61−7.43 (m, 5H), 3.98 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 165.6, 151.7, 149.2, 136.5, 136.3, 135.1, 129.1, 128.5,
127.1, 125.9, 52.4; IR (film) 1726 (s), 1440 (m), 1310 (s), 1251 (s),
1111 (m), 1026 (w), 754 (s), 700 (m) cm−1; EI-MS (m/z, relative
intensity) 213 (M+, 100), 182 (67), 154 (68), 127 (48), 77 (30), 63
(9).
3-Phenyl-1H-indazole (6r).61 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 10:1) afforded 6r (58 mg, 30%);
yellow solid; mp 92−94 °C. 1H NMR (400 MHz, CDCl3) δ 10.4 (br,
1H), 7.98 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 7.4 Hz, 2H), 7.46 (t, J = 7.4
Hz, 2H), 7.38−7.34 (m, 3H), 7.18 (d, J = 6.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 145.9, 141.7, 133.5, 128.8, 128.1, 127.6, 126.8, 121.4,
121.2, 121.0, 110.0; EI-MS (m/z, relative intensity) 194 (M+, 100),
193 (22), 167 (14), 165 (12), 77 (16), 51 (12).
5-Phenyl-2-(trifluoromethyl)pyridine (6k).54 Flash chromatography
(silica gel, petroleum ether/EtOAc = 100:1) afforded 6k (134 mg,
60%); white solid; mp 90−92 °C. 1H NMR (400 MHz, CDCl3) δ 8.80
(s, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.46 (d, J =
7.4 Hz, 2H), 7.40−7.33 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
148.3, 146.6 (q, J = 34.7 Hz), 139.4, 136.2, 135.4, 129.2, 128.9, 127.2,
121.8 (q, J = 272 Hz), 120.3; IR (film) 1376 (w), 1339 (s), 1245 (m),
1174 (m), 1121 (s), 1093 (s), 1042 (w), 754 (m) cm−1; EI-MS (m/z,
relative intensity) 223 (M+, 100), 222 (21), 154 (25), 127 (20), 102
(10), 77 (10).
3-Phenyl-1H-pyrazole (6s).61 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 10:1) afforded 6s (29 mg, 20%);
1
colorless liquid. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 1.3 Hz,
1H), 7.74 (s, 1H), 7.61 (d, J = 2.0 Hz, 1H), 7.41 (t, J = 7.4 Hz, 2H),
7.33 (t, J = 7.4 Hz, 1H), 6.61 (d, J = 2.0 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 148.8, 133.2, 131.9, 128.8, 128.1, 125.8, 102.7; IR
(film) 3213 (m), 2978 (w), 1370 (m), 1353 (w), 1155 (m), 1113 (m),
757 (s), 693 (s) cm−1; EI-MS (m/z, relative intensity) 144 (M+, 100),
143 (14), 117 (14), 115 (31), 89 (15), 77 (15), 51 (13).
Typical Procedure of Gram-Scale Borylation. 4-Nitroaniline
(1ai, 20 mmol, 2.76 g) and B2pin2 (5.334 g, 21 mmol) were weighed
in a 250 mL round-bottom flask. MeCN (60 mL), and t-BuONO (3.09
g, 30 mmol) were then added in succession. The resulting reaction
solution was allowed to stir for 12 h at 80 °C (nitrogen gas evolution
completed within 1 h). The solution was then concentrated under
reduced pressure and the crude residue was purified by silica gel flash
chromatography (petroleum ether/EtOAc = 500:1) to give 4,4,5,5-
tetramethyl-2-(4-nitrophenyl)-1,3,2-dioxaborolane (4ai)11 (3.88 g,
78%).
2-Methoxy-5-phenylpyridine (6l).55 Flash chromatography (silica
gel, petroleum ether/EtOAc = 50:1) afforded 6l (92 mg, 50%); yellow
1
liquid. H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 7.77 (d, J = 8.5
Hz, 1H), 7.51 (d, J = 7.6 Hz, 2H), 7.43−7.34 (m, 3H), 6.81 (d, J = 8.5
Hz, 1H), 3.98 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.6, 144.9,
137.9, 137.4, 130.0, 128.9, 127.2, 126.6, 110.8, 53.5; IR (film) 1606
(m), 1508 (m), 1480 (s), 1286 (s), 1046 (w), 1019 (m), 830 (m), 769
(s) cm−1; EI-MS (m/z, relative intensity) 185 (M+, 98), 184 (100),
156 (42), 154 (46), 128 (12), 115 (31).
3-Bromo-5-phenylpyridine (6m).56 Flash chromatography (silica
gel, petroleum ether/EtOAc = 50:1 then 5:1) afforded 6m (105 mg,
45%); white solid. mp 43−45 °C. 1H NMR (400 MHz, CDCl3) δ 8.74
(s, 1H), 8.64 (s, 1H), 8.00 (s, 1H), 7.54−7.42 (m, 5H); 13C NMR
(100 MHz, CDCl3) δ 149.3, 146.3, 138.2, 136.8, 136.2, 129.1, 128.6,
127.1, 120.8; IR (film) 1580 (w), 1428 (m), 1405 (m), 1045 (w),
1011 (m), 798 (m), 760 (s), 698 (s) cm−1; EI-MS (m/z, relative
intensity) 235 (98), 233 (M+, 100), 154 (32), 127 (71), 77 (28), 63
(22), 51 (18).
2-(4-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(4aj).11 Flash chromatography (silica gel, petroleum ether/EtOAc =
1
500:1 then 100:1) afforded 4aj (3.302 g, 71%). Colorless liquid. H
NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.7 Hz, 2H), 6.89 (d, J = 8.7
Hz, 2H), 3.82 (s, 3H), 1.33 (s, 12H); 13C NMR (100 MHz, CDCl3) δ
162.1, 136.4, 113.2, 83.5, 55.0, 24.8; IR (film) 2978 (w), 1605 (s),
1396 (m), 1360 (s), 1318 (m), 1277 (m), 1247 (s), 1175 (w), 1143
(s), 1091 (m), 1031 (m), 962 (w), 860 (m), 831 (m), 736 (w) cm−1;
EI-MS (m/z, relative intensity) 234 (M+, 62), 219 (27), 148 (39), 135
(86), 134 (100), 133 (22), 43 (30), 41 (33).
2-Chloro-4-phenylpyridine (6n).57 Flash chromatography (silica
gel, petroleum ether/EtOAc = 50:1 then 10:1) afforded 6n (30 mg,
16%); pale yellow solid; mp 64−66 °C. 1H NMR (400 MHz, CDCl3)
δ 8.34 (d, J = 3.8 Hz, 1H), 7.52 (d, J = 6.1 Hz, 2H), 7.45 (s, 1H),
7.43−7.37 (m, 3H), 7.34 (d, J = 2.1 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 152.2, 151.5, 149.9, 136.8, 129.6, 129.2, 127.0, 122.0, 120.4;
IR (film) 1604 (w), 1588 (s), 1535 (s), 1375 (m), 1130 (m), 878 (w),
760 (s), 730 (w) cm−1; EI-MS (m/z, relative intensity) 191 (35), 189
(M+, 100), 154 (57), 127 (36), 77 (14), 51 (10).
ASSOCIATED CONTENT
■
S
* Supporting Information
3-Phenylquinoline (6o).58 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 10:1) afforded 6o (111 mg,
54%); pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ 9.16 (s, 1H),
8.20 (s, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.68−
7.64 (m, 3H), 7.52−7.45 (m, 3H), 7.38 (t, J = 7.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 149.7, 147.1, 137.6, 133.6, 132.9, 129.2, 129.0,
129.0, 127.9, 127.8, 127.2, 126.8; IR (film) 3058 (w), 1597 (w), 1493
(m), 1362 (w), 1141 (w), 1025 (w), 786 (s), 761 (s), 696 (s) cm−1;
EI-MS (m/z, relative intensity) 205 (M+, 100), 204 (58), 176 (14),
102 (9), 88 (8), 76 (11).
EPR experiments, copies of 1H and 13C spectra for all products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: mofanyang@gmail.com; wangjb@pku.edu.cn.
■
Notes
5-Phenylisoquinoline (6p).59 Flash chromatography (silica gel,
petroleum ether/EtOAc = 50:1 then 5:1) afforded 6p (113 mg, 55%);
yellow liquid. 1H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 8.48 (d, J =
5.7 Hz, 1H), 7.96 (s, 1H), 7.71 (d, J = 5.7 Hz, 1H), 7.63 (d, J = 4.1 Hz,
2H), 7.52−7.43 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 152.8,
143.3, 139.1, 138.9, 134.0, 130.8, 129.8, 128.9, 128.4, 127.7, 127.0,
126.7, 118.4; IR (film) 3055 (w), 1618 (m), 1485 (m), 1058 (w), 829
(s), 799 (w), 758 (s), 701 (s) cm−1; EI-MS (m/z, relative intensity)
205 (M+, 100), 204 (76), 178 (19), 176 (30), 151 (13), 102 (18),
88(18).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The project is supported by National Basic Research Program
(973 Program, No. 2012CB821600), Natural Science Founda-
tion of China.
DEDICATION
Dedicated to the memory of Prof. Howard E. Zimmerman.
■
I
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