Iridium-Catalyzed Site-Selective C-H Borylation of 2-Pyridones

Article abstract of DOI:10.1055/s-0036-1588735

An iridium-catalyzed site-selective C-H borylation of 2-pyridones has been developed. The site selectivity is predominantly controlled by steric factors, and we can access C4, C5, and C6 C-H on the 2-pyridone ring by the judicious choice of ligand and sol

Full text of DOI:10.1055/s-0036-1588735

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–H
A
special topic
W. Miura et al.
Special Topic
Synthesis
Iridium-Catalyzed Site-Selective C–H Borylation of 2-Pyridones
Wataru Miura
Koji Hirano*
Bpin
Br
C–H Borylation of
Boc-protected (–)-cytisine
O
N
Masahiro Miura*
Bpin
pinB Bpin
Me
NBoc
O
N
61%, >99% C5
Department of Applied Chemistry, Graduate School of
Engineering, Osaka University, Suita, Osaka 565-0871,
Japan
k_hirano@chem.eng.osaka-u.ac.jp
miura@chem.eng.osaka-u.ac.jp
[Ir(OMe)(cod)]2/L
(4 mol%)
R
Me
O
N
CO2Me
O
N
L = dtbpy or bpy
Me
Me
Bpin
43%, >99% C4
O
N
Bpin
77%, >99% selectivity
Me
75%, 93% C6
Received: 24.01.2017
Accepted after revision: 07.02.2017
Published online: 02.03.2017
the C6 position. Given the rich and versatile chemistry of
the organoboron compounds, further development of C–H
borylation catalysis that accesses more diverse C–H on the
pyridone ring is strongly appealing. Herein, we report an
iridium-catalyzed site selective C–H borylation of 2-pyri-
dones with a diboron reagent: the site selectivity is mainly
controlled by the steric nature of substrate, and the judi-
cious choice of catalyst and solvent allows C–H borylation
at the otherwise challenging C4 as well as C5 and C6 posi-
tions without any directing groups. The borylated products
can be readily converted into arylated pyridones via
Suzuki–Miyaura reaction with aryl halides. Additionally,
the iridium catalysis can be applicable to the C–H boryl-
ation of a biologically active (–)-cytisine derivative.
DOI: 10.1055/s-0036-1588735; Art ID: ss-2017-c0044-st
Abstract An iridium-catalyzed site-selective C–H borylation of 2-pyri-
dones has been developed. The site selectivity is predominantly con-
trolled by steric factors, and we can access C4, C5, and C6 C–H on the
2-pyridone ring by the judicious choice of ligand and solvent. Subse-
quent Suzuki–Miyaura cross-coupling of the borylated products also
proceeds to form the corresponding arylated pyridones in good overall
yields.
Key words borylation, C–H functionalization, iridium, 2-pyridones,
site selectivity
2-Pyridones are frequently occurring heterocyclic sub-
structures in bioactive molecules, natural products, and
pharmaceutical agents, including ciclopirox, milrinone,
camptothecin, fredericamycin, perampanel, and cytisine.1
Many synthetic chemists thus have developed synthetic
methodologies to construct and functionalize the 2-pyri-
done ring, particularly by transition-metal catalysts. While
traditional strategies largely rely on prefunctionalization,
such as halogenation, of the parent 2-pyridone, recent ad-
vances in metal-promoted C–H activation2 can skip the pre-
activation step and provide a more straightforward ap-
proach to densely functionalized 2-pyridone cores. To date,
site-selective C–H alkylation,3 arylation,4 alkenylation,5
alkynylation,6 and thiolation7 have been reported.
Meanwhile, our research group recently developed the
rhodium-catalyzed, pyridine-directed C6-selective C–H bo-
rylation of 2-pyridones.8 The resulting boryl group under-
went the Suzuki–Miyaura cross-coupling reaction to form
C6-arylated 2-pyridones selectively. Although this is the
first successful example of the C–H borylation of 2-pyri-
done, the tedious installation/removal steps of the directing
group are inevitable and the reaction site is also limited to
Inspired by the recent rapid progress of iridium-cata-
lyzed aromatic C–H borylation,9,10 we selected N-methyl-2-
pyridone (1a) and bis(pinacolato)diboron (pinB–Bpin) as
model substrates and began optimization studies, in con-
junction with [Ir(OMe)(cod)]2 catalyst, by screening ancil-
lary ligands (Table 1, Figure 1). In an initial attempt, treat-
ment of 1a (0.25 mmol) with pinB–Bpin (0.38 mmol) in the
presence of 4 mol% Ir/phen catalyst in THF at 80 °C afforded
a 92:8 mixture of the C5-borylated pyridone 2a and dibory-
lated compounds 2a′ in 39% combined yield (entry 1). The
structures of diborylated products 2a′ were not completely
determined, but the major isomer was found to be a 3,5-di-
borylated pyridone. While some related bipyridine-type li-
gands also promoted the reaction with moderate efficiency
and selectivity (entries 3–7, 11), the introduction of sub-
stituents at the position α to nitrogen largely suppressed
the substrate conversion (entries 2, 8–10). On the other
hand, bisphosphine ligands showed remarkably high C5 site
selectivity, but the yield of 2a was lower even at higher
temperatures (135–150 °C; entries 12–14). Using pinB-H as
the boron reagent also worked to some extent, but the reac-
tivity was somewhat lower (entry 15). In contrast to our
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

B
W. Miura et al.
Special Topic
Synthesis
previous work, [Rh(OMe)(cod)]2 instead of [Ir(OMe)(cod)]2
did not catalyze the reaction of 1a at all, as far as we tested
(data not shown).
R1
R1
R1
R1
R2
R2
N
N
N
N
R3
R1 = R2 = R3 = H: phen
1 = R2 = H, R3 = Me: Me2-phen
R1 = R2 = Me, R3 = H: Me4-phen
1 = Ph, R2 = R3 = H: bathophen
R3
R2
R2
Table 1 Optimization Studies for Iridium-Catalyzed Site-Selective C–H
Borylation of N-Methyl-2-pyridone (1a) with pinB–Bpina
R
1 = R2 = H: bpy
R
R1 = t-Bu, R2 = H: dtbpy
R1 = OMe, R2 = H: MeO-bpy
pinB Bpin (1.5 equiv)
R
R
1 = H, R2 = Me: Me2-bpy
4
Bpin
5
6
3
O
[Ir(OMe)(cod)]2 (4 mol% Ir)
ligand (4 mol%)
O
(Bpin)2
+
O
N
O
N
O
N
THF, 80 °C, 4 h
N
N
Me
Me
Me
2a'
N
O
N
N
N
1a
2a
N1
N2
N3
Entry
Ligand
Yieldb (%) of 2a + 2a′ Ratioc 2a/2a′
t-Bu
OMe
t-Bu
PPh2
PPh2
O
O
1
2
phen
39
4
92:8
>99:1
85:15
42:58
83:17
44:56
75:25
–
PPh2
PPh2
PAr2
PAr2
Fe
Ar =
Me2-phen
Me4-phen
bathophen
bpy
3
9
O
dppf
4
24
35
49
51
0
rac-Binap
(R)-DTBM-Segphos
5
Figure 1
6
dtbpy
7
MeO-bpy
Me2-bpy
N1
Unfortunately, we could not obtain a satisfactory yield
and selectivity with the parent 1a, but 3-, 4-, 5-, and 6-
methyl-2-pyridones 3a, 4a, 5a, and 6a were then tested un-
der conditions identical to entry 6 in Table 1 (Scheme 1). To
our delight, remarkable increase in the yield and/or selec-
tivity was observed for 3a, 4a, and 6a to afford C5- (7a), C6-
(8a), and C4-borylated (10a) products with >90:10 site se-
lectivity. Exceptionally, the reaction of 5-methyl-2-pyri-
done (5a) was sluggish and gave 9a in 8% yield albeit with
>99% C3 selectivity. Additional fine tuning of ligand, sol-
vent, temperature, and stoichiometry identified optimal
conditions for each substitution pattern. Representative re-
sults are shown in Scheme 2. Various C3-substituted 2-pyr-
idones 3 underwent C–H borylation smoothly under the
Ir/bpy or dtbpy catalyst system at 40 °C to deliver the corre-
sponding C5-borylated compounds 7a–d in good yields
with >97:3 site selectivity [Scheme 2 (a)]. Notably, haloge-
nated substrates 3b and 3c necessitated the preactivation of
iridium catalyst for satisfactory conversion (see the experi-
mental section for details): without the preactivation, the
reaction stopped at an early stage of reaction, although we
did not observe any borylation products at the C–halogen
bond. Similar trends were observed for other halogen-sub-
stituted pyridones (vide infra). The combination of
[Ir(OMe)(cod)]2 and dtbpy efficiently catalyzed the reaction
of C4-substituted pyridones 4 [Scheme 2 (b)]. While meth-
yl- and trifluoromethyl-substituted 4a and 4c formed the
C6-borylated products 8a and 8c with 93% and >99% C6 se-
lectivity, respectively, chloro and methoxy substituents de-
creased the site selectivity for 8b and 8b. It is noteworthy
that the C6-substituted pyridones 6 were borylated in the
presence of the Ir/bpy catalyst11 selectively at the more
electron-deficient C4 position [Scheme 2 (c); 10a–c], which
is otherwise difficult to access by other C–H activation
8
9
0
–
10
11
12d
13e
14e
15f
N2
0
–
N3
36
7
89:11
>99:1
>99:1
>99:1
88:12
dppf
rac-Binap
(R)-DTBM-Segphos
dtbpy
5
14
24
a Reaction conditions: 1a (0.25 mmol), pinB–Bpin (0.38 mmol),
[Ir(OMe)(cod)]2 (0.0050 mmol), ligand (0.010 mmol), THF (1.5 mL), 80 °C, 4
h, N2.
b Determined by 1H NMR with dibenzyl ether as an internal standard.
c Determined by 1H NMR of the crude mixture.
d In CPME at 150 °C.
e In octane at 135 °C.
f With pinB-H (0.75 mmol) instead of pinB–Bpin.
Me
Me
O
Bpin
N
O
N
Bpin
4
Me
Me
5
3
Me
7a, 77%, C5/C6 = 96:4 8a, 58%, C6/C5 = 90:10
6
O
N
conditions of
entry 6 in Table 1
Bpin
Me
pinB
O
Me
3a–6a
N
O
N
Me
Me
Me
9a, 8%, >99% C3
10a, 26%, >99% C4
Scheme 1 Initial attempts of Ir/dtbpy-catalyzed C–H borylation of 3-,
4-, 5-, and 6-methyl-2-pyridones 3a–6a; 1H NMR yields are given
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

C
W. Miura et al.
Special Topic
Synthesis
group12 and the higher acidity of C–H ortho to the methoxy
group13 as well as higher electron density at the C5 position.
However, detailed reasons are not clear at this stage. On the
other hand, we could not optimize conditions for the bory-
lation of C5-substituted pyridones such as 5a. Further ef-
forts are essential.
a) C–H Borylation of C3-substituted pyridones 3
R
O
Bpin
R
[Ir(OMe)(cod)]2 (4 mol% Ir)
dtbpy (4 mol%)
+
pinB Bpin
(1.5 equiv)
N
THF, 40 °C, 4 h
O
N
Me
Me
7
3
The obtained borylated pyridones easily participated in
the Suzuki–Miyaura cross-coupling reaction with aryl ha-
lides (Scheme 3). The C5- and C4-borylated pyridones 7a
and 10a coupled with bromobenzene under Pd/XPhos
(XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbi-
phenyl) catalysis14 to furnish the corresponding arylpyri-
dones 7a-Ph and 10a-Ph in 87% and 95% yields, respective-
ly. For C6-borylated 8a, a Pd/P(t-Bu)3 catalyst15 and iodo-
benzene were more suitable, and the desired 8a-Ph was
obtained in 55% yield.
Finally, we applied this protocol to conceivably more
challenging pyridone derivatives (Scheme 4). While less site
selective, the Ir/bpy-catalyzed C–H borylation of 1,3-di-
methyluracil (11) proceeded to form the boryluracil 12 in a
good combined yield (60%). Under slightly modified condi-
tions, the NH-pyridone 13 could also be employed, and de-
sired C5-borylated 14 was obtained in 38% yield with >99%
C5 selectivity, probably via in situ N- or O-borylation of the
CONH moiety.10g Moreover, Boc-protected (–)-cytisine 15
was effectively borylated to give 16 in 77% yield and with
>99% site selectivity. The boryl group can be a good handle
for further modification of biological activity of the parent
cytisine.16
Me
Bpin
Br
Bpin
Cl
Bpin
F3C
O
Bpin
O
N
O
N
O
N
N
Me
Me
Me
Me
7a,a 83% (81%)
7c,b 67% (61%)
7b,b 65% (51%)
7d,c 41% (39%)
C5/C6 = 97:3
>99% C5
>99% C5
>99% C5
b) C–H Borylation of C4-substituted pyridones 4
R
R
[Ir(OMe)(cod)]2 (4 mol% Ir)
dtbpy (4 mol%)
+
pinB Bpin
(2.0 equiv)
O
N
Bpin
O
N
Me
4
THF, 80 °C, 8 h
Me
8
Cl
CF3
Me
OMe
Bpin
O
N
Bpin
O
N
Bpin
O
N
Bpin
O
N
Me
Me
Me
Me
8c,d 66% (39%)
>99% C6
8d, 66% (39%)f
C6/C5 = 35:65
8b,b,d 38% (32%)
C6/C5 = 80:20e
8a, 76% (75%)
C6/C5 = 93:7
c) C–H Borylation of C6-substituted pyridones 6
Bpin
[Ir(OMe)(cod)]2 (4 mol% Ir)
bpy (4 mol%)
+
pinB Bpin
(2.0 equiv)
O
N
R
O
N
Me
6
R
1,4-dioxane, 40 °C, 4 h
Me
10
Bpin
Bpin
Bpin
Pd2(dba)3•CHCl3 (2.5 mol%)
XPhos (5.0 mol%)
K3PO4 (2.0 equiv)
Me
O
Bpin
+
Me
O
Br
(1.0 equiv)
N
N
1,4-dioxane/H2O (4:1)
O
N
CO2Me
O
N
Me
O
N
Cl
reflux, 4 h
Me
Me
Me
Me
Me
7a
7a-Ph, 87%
>99% C5
10bb, 58% (58%)g
C4/C5 = 94:6
10c, 50% (43%)
>99% C4
10a, 71% (64%)
>99% C4
C5/C6 = 97:3
Bpin
Scheme 2 Iridium-catalyzed site-selective C–H borylation of C3-, C4-,
and C6-substituted 2-pyridones; 1H NMR yields are shown, combined
isolated yields are given in parenthesis. The site selectivity was deter-
mined by 1H NMR analysis of the crude mixture. a With 2.0 equiv of
pinB–Bpin and bpy in 1,4-dioxane. b Preactivation of the catalyst was
performed. See the experimental section for details. c 24 h. d 40 °C, 4 h.
e The C6/C5 ratio of the isolated product was 77:23. f Isolated yield of
the pure C5-borylated isomer. g Isolated yield of the pure C4-borylated
isomer.
Pd2(dba)3•CHCl3 (2.5 mol%)
XPhos (5.0 mol%)
K3PO4 (2.0 equiv)
+ Br
O
N
Me
O
N
Me
1,4-dioxane/H2O (4:1)
reflux, 4 h
Me
10a
Me
(1.0 equiv)
10a-Ph, 95%
Me
Me
Pd2(dba)3 (5.0 mol%)
P(t-Bu)3 (20 mol%)
KOH (3.0 equiv)
+
strategies;3–8 just a single example under Ni/Al cooperative
catalysis has been reported.3a In general, the site selectivity
was controlled by the innate steric nature of the pyridone
substrates. However, exceptionally lower selectivity was
observed in the C6-selective borylation of 4-chloro-, and
methoxy-substituted pyridones [Scheme 2 (b), 8b and 8d].
This is probably because of the directing effect of the chloro
I
THF/H2O (10:1)
O
N
O
N
Bpin
rt, 12 h
(1.1 equiv)
Me
Me
8a
8a-Ph, 55%
C6/C5 = 92:8
C6/C5 = 92:8
Scheme 3 Suzuki–Miyaura cross-coupling of borylated 2-pyridones;
isolated yields are given
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

D
W. Miura et al.
Special Topic
Synthesis
Iridium-Catalyzed C–H Borylation of 2-Pyridones; General Proce-
dure A (GPA)
O
O
Me
[Ir(OMe)(cod)]2 (4 mol% Ir)
bpy (4 mol%)
Me
O
5
N
N
Bpin
+
pinB Bpin
(2.0 equiv)
Ligand (0.010 mmol) and [Ir(OMe)(cod)]2 (3.3 mg, 0.0050 mmol) were
placed in a 20-mL two-necked reaction flask, which was filled with
N2 by using the standard Schlenk technique. Solvent (0.50 mL) was in-
jected via a syringe, and the mixture was stirred for 5 min at r.t. A
solution of 2-pyridone (0.25 mmol) and bis(pinacolato)diboron
(0.38–0.75 mmol) in solvent (1.0 mL) was then added, and the sus-
pension was stirred under the indicated conditions. The resulting
mixture was allowed to cool to r.t., diluted with EtOAc, and filtered
through a short pad of neutral alumina and anhyd Na2SO4. After con-
centration under reduced pressure, purification by GPC (EtOAc) af-
forded the corresponding borylated 2-pyridone.
6
1,4-dioxane, 80 °C, 4 h
O
N
N
Me
11
Me
12, 60%
C5/C6 = 50:50
Me
O
[Ir(OMe)(cod)]2 (4 mol% Ir)
dtbpy (4 mol%)
Me
Bpin
+
pinB Bpin
(3.0 equiv)
THF, 80 °C, 4 h
N
O
N
H
H
14, 38%
>99% C5
13
NBoc
N
NBoc
N
O
[Ir(OMe)(cod)]2 (4 mol% Ir)
bpy (4 mol%)
O
Iridium-Catalyzed C–H Borylation of Halogenated 2-Pyridones;
General Procedure B (GPB, Preactivation Method)
+
pinB Bpin
(2.0 equiv)
1,4-dioxane, 40 °C, 6 h
Ligand (0.010 mmol) and [Ir(OMe)(cod)]2 (3.3 mg, 0.0050 mmol) were
placed in a 20-mL two-necked reaction flask, which was filled with
N2 by using the standard Schlenk technique. Solvent (0.50 mL) was in-
jected via a syringe, and the mixture was stirred for 5 min at r.t. A
solution of bis(pinacolato)diboron (0.38–0.50 mmol) in solvent (0.50
mL) was then added, and the suspension was stirred for an additional
5 min at r.t. A solution of halogenated 2-pyridone (0.25 mmol) in sol-
vent (0.50 mL) was subsequently added, and the solution was stirred
under the indicated conditions. The resulting mixture was allowed to
cool to r.t., diluted with EtOAc, and filtered through a short pad of
neutral alumina and anhyd Na2SO4. After concentration under re-
duced pressure, purification by GPC (EtOAc) afforded the correspond-
ing halogen-containing borylated 2-pyridone.
Bpin
16, 77%
>99% site selectivity
15
Boc-protected
(–)-cytisine
Scheme 4 Iridium-catalyzed C–H borylation of uracil, NH-pyridone,
and Boc-protected (–)-cytisine; isolated yields are given
In conclusion, we have developed an iridium-catalyzed
site-selective C–H borylation of 2-pyridones. The site selec-
tivity is mainly controlled by steric factors of substrates.
This catalysis can provide a more straightforward approach
to C4-, C5-, and C6-borylated pyridones; some of which are
traditionally prepared by two-step procedures, i.e., haloge-
nation and Pd-catalyzed Miyaura borylation. Additionally,
subsequent Suzuki–Miyaura coupling readily converts the
borylated pyridones into the corresponding aryl-substitut-
ed pyridones of great potential in medicinal chemistry. Re-
lated metal-catalyzed site-selective C–H functionalizations
of 2-pyridones are currently underway and will be reported
in due course.
1,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyri-
din-2(1H)-one (7a) and 1,3-Dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)pyridin-2(1H)-one (7a′)
According to GPA, purification by GPC (EtOAc) gave the product (51
mg, 0.20 mmol, 81%) as a white solid; ratio 7a/7a′ 97:3; mp 140.3–
142.3 °C.
1H NMR (400 MHz, CDCl3): δ = 1.31 (s, 0.97 × 12 H for 7a), 1.34 (s, 0.03
× 12 H for 7a′), 2.13 (d, J = 1.0 Hz, 0.97 × 3 H for 7a), 2.17 (s, 0.03 × 3 H
for 7a′), 3.56 (s, 0.97 × 3 H for 7a), 3.73 (s, 0.03 × 3 H for 7a′), 6.70 (d,
J = 6.7 Hz, 0.03 × 1 H for 7a′), 7.15 (d, J = 6.7 Hz, 0.03 × 1 H for 7a′),
7.48 (d, J = 1.0 Hz, 0.97 × 1 H for 7a), 7.66 (s, 0.97 × 1 H for 7a).
13C{1H} NMR (100 MHz, CDCl3): for 7a δ = 17.03, 24.93, 37.93, 84.04,
128.5, 140.8, 144.2, 164.2. The carbon signal bound to the boron was
not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3): δ = 30.47.
HRMS (APCI): m/z [M + H]+ calcd for C13H21BNO3: 250.1611; found:
1H, 13C{1H}, 19F{1H}, and 11B NMR spectra were recorded at 400, 100,
376, and 128 MHz, respectively, for CDCl3 solutions. HRMS data were
obtained by APCI using TOF. Silica gel (Wakosil C-200) was used for
column chromatography. Gel permeation chromatography (GPC) was
performed by LC-20AR (pump, Shimadzu, 7.5 mL/min) and RID-20A
(RI detector, Shimadzu) with two in-line YMC-GPC T2000 (20 × 600
mm, particle size: 10 μm) (preparative columns, YMC, EtOAc eluent)
or two in-line GPC H-2001 (20 × 500 mm, particle size: 15 μm) and H-
2002 columns (20 × 500 mm, particle size: 15 μm) (preparative col-
umns, Shodex, CHCl3 eluent). Unless otherwise noted, materials ob-
tained from commercial suppliers were used as received. Anhyd THF
was purchased and used out of the bottle without further purifica-
tion. 1,4-Dioxane was dried on a Glass Contour Solvent dispensing
system (Nikko Hansen & Co., Ltd.) prior to use. [Ir(OMe)(cod)]2 was
prepared according to the literature procedure.17 Pyridone 1a is com-
mercially available, and others were synthesized from the corre-
sponding NH-pyridones by reported methods.5b,18
250.1602.
3-Chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)pyridin-2(1H)-one (7b)
According to GPB, purification by GPC (EtOAc) gave the product (34
mg, 0.13 mmol, 51%) as a white solid; mp 174.9–176.9 °C.
1H NMR (400 MHz, CDCl3): δ = 1.31 (s, 12 H), 3.61 (s, 3 H), 7.70 (d, J =
1.8 Hz, 1 H), 7.80 (d, J = 1.8 Hz, 1 H).
13C{1H} NMR (100 MHz, CDCl3): δ = 24.9, 38.7, 84.5, 125.5, 141.7,
144.8, 159.9. The carbon signal bound to the boron was not observed
due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3): δ = 29.65.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

E
W. Miura et al.
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HRMS (APCI): m/z [M + H]+ calcd for C12H18BClNO3: 270.1065; found:
270.1077.
1H NMR (400 MHz, CDCl3): δ = 1.33 (s, 0.23 × 12 H for 8b′), 1.36 (s,
0.77 × 12 H for 8b), 3.53 (s, 0.23 × 3 H for 8b′), 3.68 (s, 0.77 × 3 H for
8b), 6.60 (s, 0.23 × 1 H for 8b′), 6.71 (d, J = 2.4 Hz, 0.77 × 1 H for 8b),
6.76 (d, J = 2.4 Hz, 0.77 × 1 H for 8b), 7.75 (s, 0.23 × 1 H for 8b′).
3-Bromo-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
13C{1H} NMR (100 MHz, CDCl3): for 8b δ = 24.8, 35.3, 85.6, 117.9,
121.8, 145.3, 163.1; for 8b′ δ = 24.9, 37.5, 84.3, 119.5, 147.5, 151.0,
162.3. The carbon signal bound to the boron was not observed due to
quadrupolar relaxation.
yl)pyridin-2(1H)-one (7c)
According to GPB, purification by GPC (EtOAc) gave the product (48
mg, 0.15 mmol, 61%) as a white solid; mp 172.4–174.4 °C.
1H NMR (400 MHz, CDCl3): δ = 1.31 (s, 12 H), 3.61 (s, 3 H), 7.74 (d, J =
1.8 Hz, 1 H), 8.00 (d, J = 1.7 Hz, 1 H).
11B NMR (128 MHz, CDCl3): δ = 28.45.
HRMS (APCI): m/z [M + H]+ calcd for C12H18BClNO3: 270.1065; found:
270.1073.
13C{1H} NMR (100 MHz, CDCl3): δ = 24.9, 39.0, 84.5, 115.6, 145.7 (2 C),
159.9. The carbon signal bound to the boron was not observed due to
quadrupolar relaxation.
11B NMR (128 MHz, CDCl3): δ = 30.12.
HRMS (APCI): m/z [M + H]+ calcd for C12H18BBrNO3: 314.0560; found:
1-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(tri-
fluoromethyl)pyridin-2(1H)-one (8c)
According to GPA, purification by GPC (EtOAc) gave the product (30
mg, 0.10 mmol, 39%) as a yellow solid; mp 131.9–133.9 °C.
314.0567.
1H NMR (400 MHz, CDCl3): δ = 1.37 (s, 12 H), 3.75 (s, 3 H), 6.87 (d, J =
2.0 Hz, 1 H), 6.93 (dd, J = 1.0, 2.0 Hz, 1 H).
1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(tri-
fluoromethyl)pyridin-2(1H)-one (7d)
13C{1H} NMR (100 MHz, CDCl3): δ = 24.8, 35.7, 85.7, 111.2 (q, J = 2.6
Hz), 120.6 (q, J = 4.2 Hz), 122.3 (q, J = 272.4 Hz), 139.8 (q, J = 33.5 Hz),
162.8. The carbon signal bound to the boron was not observed due to
quadrupolar relaxation.
19F{1H} NMR (376 MHz, CDCl3): δ = –66.59.
11B NMR (128 MHz, CDCl3): δ = 28.52.
According to GPA, purification by GPC (EtOAc) gave the product (30
mg, 0.10 mmol, 39%) as a white solid; mp 142.3–144.3 °C.
1H NMR (400 MHz, CDCl3): δ = 1.32 (s, 12 H), 3.60 (s, 3 H), 7.94 (d, J =
1.7 Hz, 1 H), 8.02 (d, J = 1.7 Hz, 1 H).
13C{1H} NMR (100 MHz, CDCl3): δ = 24.9, 38.0, 84.6, 119.6 (q, J = 30.4
Hz), 122.9 (q, J = 270.0 Hz), 143.1 (q, J = 4.8 Hz), 149.8, 159.4. The car-
bon signal bound to the boron was not observed due to quadrupolar
relaxation.
HRMS (APCI): m/z [M + H]+ calcd for C13H18BF3NO3: 304.1329; found:
304.1321.
19F{1H} NMR (376 MHz, CDCl3): δ = –65.85.
11B NMR (128 MHz, CDCl3): δ = 29.87.
HRMS (APCI): m/z [M + H]+ calcd for C13H18BF3NO3: 304.1329; found:
4-Methoxy-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)pyridin-2(1H)-one (8d)
According to GPA, purification by GPC (EtOAc) gave the product (26
mg, 0.10 mmol, 39%) as an orange solid; mp 162.2–164.2 °C.
304.1323.
1H NMR (400 MHz, CDCl3): δ = 1.32 (s, 12 H), 3.49 (s, 3 H), 3.79 (s, 3
H), 5.86 (s, 1 H), 7.66 (s, 1 H).
13C{1H} NMR (100 MHz, CDCl3): δ = 24.8, 36.9, 55.9, 83.7, 96.2, 147.6,
165.1, 171.2. The carbon signal bound to the boron was not observed
due to quadrupolar relaxation.
1,4-Dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyri-
din-2(1H)-one (8a) and 1,4-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)pyridin-2(1H)-one (8a′)
According to GPA, purification by GPC (EtOAc) gave the product (46
mg, 0.19 mmol, 75%) as a brown solid; ratio 8a/8a′ 97:3; mp 70.5–
72.5 °C.
11B NMR (128 MHz, CDCl3): δ = 29.80.
1H NMR (400 MHz, CDCl3): δ = 1.30 (s, 0.070 × 12 H for 8a′), 1.35 (s,
0.93 × 12 H for 8a), 2.15 (d, J = 1.0 Hz, 0.93 × 3 H for 8a), 2.31 (s, 0.070
× 3 H for 8a′), 3.52 (s, 0.070 × 3 H for 8a′), 3.68 (s, 0.93 × 3 H for 8a),
6.33 (s, 0.070 × 1 H for 8a′), 6.48 (dd, J = 1.0, 2.0 Hz, 0.93 × 1 H for 8a),
6.60 (d, J = 2.0 Hz, 0.93 × 1 H for 8a), 7.71 (s, 0.070 × 1 H for 8a′).
13C{1H} NMR (100 MHz, CDCl3): for 8a δ = 24.7, 34.9, 68.0, 85.0, 119.3,
122.0, 149.0, 163.9; for 8a′ δ = 25.6, 37.1, 60.4, 83.5, 118.9, 146.8,
156.0, 163.3. The carbon signal bound to the boron was not observed
due to quadrupolar relaxation.
HRMS (APCI): m/z [M + H]+ calcd for C13H21BNO4: 266.1561; found:
266.1565.
1,6-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyri-
din-2(1H)-one (10a)
According to GPA, purification by GPC (EtOAc) gave the product (40
mg, 0.16 mmol, 64%) as a white solid; mp 133.1–135.1 °C.
1H NMR (400 MHz, CDCl3): δ = 1.32 (s, 12 H), 2.33 (s, 3 H), 3.52 (s, 3
H), 6.29 (s, 1 H), 6.89 (s, 1 H).
11B NMR (128 MHz, CDCl3): δ = 28.60.
HRMS (APCI): m/z [M + H]+ calcd for C13H21BNO3: 250.1611; found:
13C{1H} NMR (100 MHz, CDCl3): δ = 20.9, 25.0, 31.3, 84.6, 109.9, 124.8,
145.2, 163.5. The carbon signal bound to the boron was not observed
due to quadrupolar relaxation.
250.1600.
11B NMR (128 MHz, CDCl3): δ = 30.13.
HRMS (APCI): m/z [M + H]+ calcd for C13H21BNO3: 250.1611; found:
4-Chloro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)pyridin-2(1H)-one (8b) and 4-Chloro-1-methyl-5-(4,4,5,5-te-
tramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (8b′)
250.1600.
According to GPB, purification by GPC (EtOAc) gave the product (21
mg, 0.080 mmol, 32%) as a yellow solid; ratio 8b/8b′ 77:23; mp 95.8–
97.8 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

F
W. Miura et al.
Special Topic
Synthesis
6-Chloro-1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
HRMS (APCI): m/z [M + H]+ calcd for C12H19BNO3: 236.1455; found:
yl)pyridin-2(1H)-one (10b)
236.1442.
According to GPB, purification by GPC (EtOAc) gave the product (39
mg, 0.15 mmol, 58%) as a white solid; mp 116.2–118.2 °C.
1H NMR (400 MHz, CDCl3): δ = 1.32 (s, 12 H), 3.67 (s, 3 H), 6.56 (d, J =
1.1 Hz, 1 H), 6.92 (d, J = 1.1 Hz, 1 H).
tert-Butyl (1R,5R)-8-Oxo-10-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]di-
azocine-3(4H)-carboxylate (16)
According to GPA, purification by GPC (EtOAc) gave the product (71
mg, 0.19 mmol, 77%) as a brown solid; mp 108.5–110.5 °C.
1H and 13C NMR spectra of compound 16 are complicated by the pres-
13C{1H} NMR (100 MHz, CDCl3): δ = 24.8, 33.2, 84.8, 109.9, 125.4,
137.2, 162.9. The carbon signal bound to the boron was not observed
due to quadrupolar relaxation.
ence of rotamers, and all observed signals are thus described.
11B NMR (128 MHz, CDCl3): δ = 30.22.
HRMS (APCI): m/z [M + H]+ calcd for C12H18BClNO3: 270.1065; found:
1H NMR (400 MHz, CDCl3): δ = 1.18 (s, 3 H), 1.32 (s, 17 H), 1.90–1.97
(m, 2.5 H), 2.42 (s, 1 H), 3.02–3.06 (m, 3 H), 3.83 (dd, J = 6.0, 15.6 Hz. 1
H), 4.15–4.18 (m, 3 H), 4.36–4.39 (m, 0.5 H), 6.33 (s, 1 H), 6.87 (s, 1 H).
270.1052.
13C{1H} NMR (100 MHz, CDCl3): δ = 24.6, 24.8, 26.1, 27.5, 28.1, 34.6,
48.9, 49.2, 50.2, 50.6, 51.7, 67.0, 80.2, 82.2, 84.4, 108.8, 109.3, 124.4,
147.5, 147.9, 154.6, 162.9.
11B NMR (128 MHz, CDCl3): δ = 30.14.
HRMS (APCI): m/z [M + H]+ calcd for C22H34BN2O5: 417.2559; found:
Methyl 1-Methyl-6-oxo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)-1,6-dihydropyridine-2-carboxylate (10c)
According to GPA, purification by GPC (EtOAc) gave the product (31
mg, 0.11 mmol, 43%) as a white solid; mp 109.8.1–111.8 °C.
1H NMR (400 MHz, CDCl3): δ = 1.33 (s, 12 H), 3.68 (s, 3 H), 3.91 (s, 3
H), 7.02 (d, J = 1.3 Hz, 1 H), 7.18 (d, J = 1.3 Hz, 1 H).
417.2547.
13C{1H} NMR (100 MHz, CDCl3): δ = 25.0, 33.7, 53.1, 85.0, 114.1, 132.4,
137.5, 162.6, 163.1. The carbon signal bound to the boron was not ob-
served due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3): δ = 30.26.
HRMS (APCI): m/z [M + H]+ calcd for C14H21BNO5: 294.1510; found:
Suzuki–Miyaura Cross-Coupling of 7a and 10a; General Procedure
Pd2(dba)3·CHCl3 (2.6 mg, 0.0025 mmol), XPhos (2.4 mg, 0.0050
mmol), and K3PO4 (42 mg, 0.20 mmol) were placed in a 20-mL two-
necked reaction flask, which was filled with N2 by using the standard
Schlenk technique. 1,4-Dioxane (0.20 mL) was injected via a syringe,
and the mixture was stirred for 5 min at r.t. A solution of 7a or 10a
(0.10 mmol) in 1,4-dioxane (1.0 mL), bromobenzene (10 μL, 0.10
mmol), and water (0.30 mL) were sequentially added, and the mix-
ture was stirred for 4 h at 110 °C. The resulting mixture was allowed
to cool to r.t. and then quenched with water. The mixture was extract-
ed with EtOAc (3 ×). The combined organic layers were dried (anhyd
Na2SO4). After concentration under reduced pressure, column purifi-
cation (silica gel, CH2Cl2/EtOAc/Et3N 1:1:0.02) afforded 7a-Ph or 10a-
Ph.
294.1499.
1,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)py-
rimidine-2,4(1H,3H)-dione (12) and 1,3-Dimethyl-6-(4,4,5,5-te-
tramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2,4(1H,3H)-dione
(12′)
According to GPA, purification by GPC (EtOAc) gave the product (40
mg, 0.15 mmol, 60%) as an orange solid; ratio 12/12′ 50:50; mp
150.6–152.6 °C.
1H NMR (400 MHz, CDCl3): for 12 and 12′ δ = 1.32 (s, 0.50 × 12 H),
1.34 (s, 0.50 × 12 H), 3.34 (s, 0.50 × 3 H), 3.35 (s, 0.50 × 3 H), 3.42 (s,
0.50 × 3 H), 3.53 (s, 0.50 × 3 H), 6.23 (s, 0.50 × 1 H), 7.66 (s, 0.50 × 1 H).
1,3-Dimethyl-5-phenylpyridin-2(1H)-one (7a-Ph)
Purification by column chromatography (Rf = 0.33) gave the product
(17 mg, 0.087 mmol, 87%) as a pale yellow solid; mp 159.2–161.2 °C.
13C{1H} NMR (100 MHz, CDCl3): for 12 and 12′ δ = 24.7, 24.8, 27.7,
27.9, 35.5, 37.2, 83.9, 85.7, 111.0, 152.0, 152.1, 152.8, 162.7, 164.0.
The carbon signal bound to the boron was not observed due to quad-
rupolar relaxation.
1H NMR (400 MHz, CDCl3): δ = 2.23 (d, J = 1.0 Hz, 3 H), 3.63 (s, 3 H),
7.29–7.35 (m, 1 H), 7.39 (d, J = 2.6 Hz, 1 H), 7.40–7.42 (m, 4 H), 7.52
(dd, J = 1.0, 2.6 Hz, 1 H).
11B NMR (128 MHz, CDCl3): δ = 28.80.
13C{1H} NMR (100 MHz, CDCl3): δ = 17.6, 38.2, 119.8, 126.0, 127.3,
129.1, 129.8, 133.1, 136.8, 137.0, 162.9.
HRMS (APCI): m/z [M + H]+ calcd for C13H14NO: 200.1070; found:
HRMS (APCI): m/z [M + H]+ calcd for C12H20BN2O4: 267.1513; found:
267.1503.
200.1063.
3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-
2(1H)-one (14)
1,6-Dimethyl-4-phenylpyridin-2(1H)-one (10a-Ph)
According to GPA, purification by GPC (EtOAc) gave the product (22
mg, 0.10 mmol, 38%) as an orange solid; mp 216.6–218.6 °C.
Purification by column chromatography (Rf = 0.20) gave the product
(19 mg, 0.095 mmol, 95%) as a white solid; mp 103.6–105.6 °C.
1H NMR (400 MHz, CDCl3): δ = 1.30 (s, 12 H), 2.14 (s, 3 H), 7.59 (s, 1
H), 7.73 (s, 1 H), 12.21 (br, 1 H).
13C{1H} NMR (100 MHz, CDCl3): δ = 16.5, 24.9, 84.0, 128.2, 140.6,
143.1, 166.0. The carbon signal bound to the boron was not observed
due to quadrupolar relaxation.
1H NMR (400 MHz, CDCl3): δ = 2.42 (d, J = 1.0 Hz, 3 H), 3.58 (s, 3 H),
6.33 (dd, J = 1.0, 1.9 Hz, 1 H), 6.70 (d, J = 1.9 Hz, 1 H), 7.41–7.47 (m, 3
H), 7.55–7.58 (m, 2 H).
13C{1H} NMR (100 MHz, CDCl3): δ = 21.4, 31.2, 106.2, 114.0, 126.8,
129.0, 129.4, 138.0, 146.2, 150.9, 164.2.
11B NMR (128 MHz, CDCl3): δ = 29.55.
HRMS (APCI): m/z [M + H]+ calcd for C13H14NO: 200.1070; found:
200.1089.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

G
W. Miura et al.
Special Topic
Synthesis
1,4-Dimethyl-6-phenylpyridin-2(1H)-one (8a-Ph) and 1,4-Dimeth-
yl-5-phenylpyridin-2(1H)-one (8a′-Ph) by Suzuki–Miyaura Cross-
Coupling of 8a
2009, 48, 5094. (j) Ackermann, L.; Vicente, R.; Kapdi, A. R.
Angew. Chem. Int. Ed. 2009, 48, 9792. (k) Sun, C.-L.; Li, B.-J.; Shi,
Z.-J. Chem. Commun. 2010, 46, 677. (l) Lyons, T. W.; Sanford, M.
S. Chem. Rev. 2010, 110, 1147. (m) Dudnik, A. S.; Gevorgyan, V.
Angew. Chem. Int. Ed. 2010, 49, 2096. (n) Satoh, T.; Miura, M.
Chem. Eur. J. 2010, 16, 11212. (o) Ackermann, L. Chem. Commun.
2010, 46, 4866. (p) Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev.
2011, 111, 1780. (q) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K.
Angew. Chem. Int. Ed. 2012, 51, 8960. (r) Guo, X.-X.; Gu, D.-W.;
Wu, Z.; Zhang, W. Chem. Rev. 2015, 115, 1622. (s) Hirano, K.;
Miura, M. Chem. Lett. 2015, 44, 868.
In a glovebox filled with N2, Pd2(dba)3 (4.6 mg, 0.0050 mmol), P(t-Bu)3
(4.0 mg, 0.020 mmol), and KOH (17 mg, 0.30 mmol) were placed in a
20-mL two-necked reaction flask and dissolved in THF (0.50 mL). The
reaction flask was sealed with a septum and then taken out of the
glovebox. The mixture was stirred for 5 min at r.t. A solution of 8a/8a′
(93:7; 25 mg, 0.10 mmol) in THF (1.0 mL), iodobenzene (12 μL, 0.11
mmol), and water (0.15 mL) were sequentially added, and the mix-
ture was stirred for 12 h at r.t. The resulting mixture was quenched
with sat. aq NH4Cl and extracted with EtOAc (3 ×). The combined or-
ganic layers were dried (anhyd Na2SO4). After concentration under re-
duced pressure, column purification (silica gel, CH2Cl2/EtOAc/Et3N
1:1:0.02) followed by GPC (CHCl3) afforded a mixture of 1,4-dimethyl-
6-phenylpyridin-2(1H)-one (8a-Ph) and 1,4-dimethyl-5-phenylpyri-
din-2(1H)-one (8a′-Ph) (11 mg, 0.055 mmol, 55%) as a yellow oil; ra-
tio 8a-Ph/8a′-Ph 92:8.
1H NMR (400 MHz, CDCl3): δ = 2.09 (s, 0.080 × 3 H for 8a′-Ph), 2.19 (d,
J = 1.0 Hz, 0.92 × 3 H for 8a-Ph), 3.34 (s, 0.92 × 3 H for 8a-Ph), 3.56 (s,
0.080 × 3 H for 8a′-Ph), 5.96 (d, J = 2.0 Hz, 0.92 × 1 H for 8a-Ph), 6.41
(dd, J = 1.0, 2.0 Hz, 0.92 × 1 H for 8a-Ph), 6.49 (s, 0.080 × 1 H for 8a′-
Ph), 7.13 (s, 0.080 × 1 H for 8a′-Ph), 7.22–7.24 (m, 0.080 × 3 H for 8a′-
Ph), 7.32–7.34 (m, 0.92 × 2 H for 8a-Ph), 7.39–7.40 (m, 0.080 × 2 H for
8a′-Ph), 7.45–7.47 (m, 0.92 × 3 H for 8a-Ph).
(3) (a) Tamura, R.; Yamada, Y.; Nakao, Y.; Hiyama, T. Angew. Chem.
Int. Ed. 2012, 51, 5679. (b) Nakatani, A.; Hirano, K.; Satoh, T.;
Miura, M. Chem. Eur. J. 2013, 19, 7691. (c) Nakatani, A.; Hirano,
K.; Satoh, T.; Miura, M. J. Org. Chem. 2014, 79, 1377. (d) Najib, A.;
Tabuchi, S.; Hirano, K.; Miura, M. Heterocycles 2016, 92, 1187.
(e) Donets, P. A.; Cramer, N. Angew. Chem. Int. Ed. 2015, 54, 633.
(f) Das, D.; Biswas, A.; Karmakar, U.; Chand, S.; Samanta, R.
J. Org. Chem. 2016, 81, 842. (g) Peng, P.; Wang, J.; Jiang, H.; Liu,
H. Org. Lett. 2016, 18, 5376.
(4) See refs. 3c,d,g and: (a) Chen, Y.; Wang, F.; Jia, A.; Li, X. Chem.
Sci. 2012, 3, 3231. (b) Odani, R.; Hirano, K.; Satoh, T.; Miura, M.
Angew. Chem. Int. Ed. 2014, 53, 10784. (c) Anagnostaki, E. A.;
Fotiadou, A. D.; Demertzidou, V.; Zografos, A. L. Chem. Commun.
2014, 50, 6879. (d) Modak, A.; Rana, S.; Maiti, D. J. Org. Chem.
2015, 80, 296. (e) Chauhan, P.; Ravi, M.; Singh, S.; Prajapati, P.;
Yadav, P. P. RSC Adv. 2016, 6, 109.
13C{1H} NMR (100 MHz, CDCl3): for 8a-Ph δ = 21.3, 34.1, 110.5, 117.6,
128.5, 128.8, 129.3, 135.8, 149.0, 150.1, 163.9.
HRMS (APCI): m/z [M + H]+ calcd for C13H14NO: 200.1070; found:
200.1074.
(5) See ref. 4a and: (a) Itahara, T.; Ouseto, F. Synthesis 1984, 488.
(b) Nakao, Y.; Idei, H.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc.
2009, 131, 15996.
(6) (a) Li, Y.; Xie, F.; Li, X. J. Org. Chem. 2016, 81, 715. (b) Li, T.;
Wang, Z.; Xu, K.; Liu, W.; Zhang, X.; Mao, W.; Guo, Y.; Ge, X.;
Pan, F. Org. Lett. 2016, 18, 1064.
(7) Peng, P.; Wang, J.; Li, C.; Zhu, W.; Jiang, H.; Liu, H. RSC Adv. 2016,
6, 57441.
(8) Miura, W.; Hirano, K.; Miura, M. Org. Lett. 2016, 18, 3742.
(9) Selected seminal works and reviews: (a) Ishiyama, T.; Takagi, J.;
Hartwig, J. F.; Miyaura, N. Angew. Chem. Int. Ed. 2002, 41, 3056.
(b) Chotana, G. A.; Rak, M. A.; Smith, M. R. III J. Am. Chem. Soc.
2005, 127, 10539. (c) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T.
B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890.
(d) Hartwig, J. F. Chem. Soc. Rev. 2011, 40, 1992.
Acknowledgment
This work was supported by JSPS KAKENHI Grant Nos. JP 15K13696
(Grant-in-Aid for Exploratory Research) and JP 15H05485 [Grant-in-
Aid for Young Scientists (A)] to K.H. and JP 24225002 [Grant-in-Aid for
Scientific Research (S)] to M.M.
Supporting Information
Supporting information for this article is available online at
(10) To the best of our knowledge, the nondirected catalytic C–H
borylation of 2-pyridones has not been reported while the reac-
tivity and selectivity of several nitrogen-containing heterocy-
cles has been extensively investigated; see: (a) Ishiyama, T.;
Takagi, J.; Yonekawa, Y.; Hartwig, J. F.; Miyaura, N. Adv. Synth.
Catal. 2003, 345, 1103. (b) Ishiyama, T.; Nobuta, Y.; Hartwig, J.
F.; Miyaura, N. Chem. Commun. 2003, 2924. (c) Mkhalid, I. A. I.;
Coventry, D. N.; Albesa-Jove, D.; Batsanov, A. S.; Howard, J. A. K.;
Perutz, R. N.; Marder, T. B. Angew. Chem. Int. Ed. 2006, 45, 866.
(d) Kallepalli, V. A.; Shi, F.; Paul, S.; Onyeozili, E. N.; Maleczka, R.
E.; Smith, M. R. J. Org. Chem. 2009, 74, 9199. (e) Klecka, M.; Pohl,
R.; Klepetarova, B.; Hocek, M. Org. Biomol. Chem. 2009, 7, 866.
(f) Preshlock, S. M.; Plattner, D. L.; Maligres, P. E.; Krska, S. W.;
Maleczka, R. E.; Smith, M. R. Angew. Chem. Int. Ed. 2013, 52,
12915. (g) Larsen, M. A.; Hartwig, J. F. J. Am. Chem. Soc. 2014,
136, 4287.
http://dx.doi.org/10.1055/s-0036-1588735.
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ortiInfogrmoaitn
References
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Special Topic
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H