Facile and economical Miyaura borylation and one-pot Suzuki–Miyaura cross-coupling reaction

Article abstract of DOI:10.1016/j.ica.2020.119538

Facile and economical method for Miyaura borylation reaction between B₂pin₂ and aryl bromides is reported. The catalytic system containing 2 mol% PdCl₂(PPh₃)₂ and KOAc serves to enable borylations to occur under solvent-free and atmospheric conditions. The developed protocol can be applied to synthesize symmetrical and unsymmetrical biaryls via one-pot two-step Suzuki–Miyaura cross-coupling reaction and also offers the up-scalability.

Full text of DOI:10.1016/j.ica.2020.119538

Journal Pre-proofs
Research paper
Facile and economical Miyaura borylation and one-pot Suzuki–Miyaura cross-
coupling reaction
Phongsakorn Boontiem, Supavadee Kiatisevi
PII:
S0020-1693(19)31881-X
https://doi.org/10.1016/j.ica.2020.119538
ICA 119538
DOI:
Reference:
Inorganica Chimica Acta
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Revised Date:
Accepted Date:
2 December 2019
16 February 2020
16 February 2020
Please cite this article as: P. Boontiem, S. Kiatisevi, Facile and economical Miyaura borylation and one-pot
Suzuki–Miyaura cross-coupling reaction, Inorganica Chimica Acta (2020), doi: https://doi.org/10.1016/j.ica.
2020.119538
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Facile and economical Miyaura borylation and one-pot Suzuki–
Miyaura cross-coupling reaction
Phongsakorn Boontiem1, Supavadee Kiatisevi*1,2
1. Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-
CIC), Faculty of Science, Rama VI Rd, Ratchathewi, Bangkok 10400, Thailand;
2. Center of Sustainable Energy and Green Materials, Faculty of Science, Mahidol
University, 999 Phuttamonthon Sai 4 Road, Salaya, Nakhon Pathom 73170, Thailand
*Corresponding author E-mail address: supavadee.mon@mahidol.edu
1. Introduction
Aryl boronic acids and their derivatives have great potential in many applications such
as organic synthesis for the formation of C–C and C–X (X = heteroatom) bonds, organic
electronics, bioimaging and pharmaceutical applications.1-4 The traditional method for their
synthesis is the reaction of trialkyl borates with organolithium or organomagnesium.5
However, this method is difficult to handle and incompatible with functional groups sensitive
to base, air and moisture. Transition metal-catalyzed Miyaura reaction of boron nucleophiles
is an alternative and convenient route to such boronic ester and their derivatives. Although
numerous palladium-catalyzed methods have emerged for the conversion of aryl halides to
the corresponding aryl pinacol boronated esters,6-14 the system requires an air-sensitive
technique, expensive bulky ligands, and purification of solvent and substrates. Therefore,
preparations of aryl boronic ester from aryl halides (bromide, chloride) via a mild and
environmentally friendly protocol are challenging.
A list of Miyaura borylation protocols under mild conditions reported in literature is
shown in Table 1. A few reports involve expensive ligands (conditions A and B)15 and
harmful solvent (condition F).18 Some of them still face the difficulties of phosphorus ligands
(conditions C and D).16 A more environmentally friendly approach using PEG-600 allows
cross-coupling of aryl bromides, however, under an inert atmosphere (condition E).17

Table 1 Literature reports on palladium-catalyzed Miyaura borylation of aryl
halide under mild conditionsa
Conditionsa
Ar in ArX
X in ArX
Temperature
(°C)
Time
(h)
12
Yield
(%)
99
A
A
B
p-OMeC6H4
p-NO2C6H4
p-NO2C6H4
Br
Br
Cl
110
110
12
99
110
12
99
C
D
p-OMeC6H4
Br
Br
rt
rt
3
3
86
87
p-CO2MeC6H4
E
E
p-NO2C6H4
p-NO2C6H4
Br
Cl
90
90
6
78
72
10
F
p-OMeC6H4
p-NO2C6H4
Br
Br
110
110
8
5
80
92
a A: Pd(dba)2/ DPEPhos/ NaOAc / neat/ air,15 B: Pd(dba)2/ XPhos/ NaOAc/ neat/ air,15 C:
Pd(PtBu3)2/ KOAc/ Cremophore/ H2O/ Ar,16 D: Pd(PtBu3)2/ KOAc/ TPGS-750-M/ H2O/ Ar,16
E: PdCl2(PPh3)2/ NaOAc/ PEG-600/ N2,17 and F: PdII-TpTP/ KOAc/ dioxane/ air.18
In continuation on the development of Pd catalytic systems, we reported a straightforward,
environmentally friendly and economical method for the synthesis of aryl boronate ester from
aryl bromides and B2pin2 using simple and moisture-insensitive palladium complexes under
solvent-free and atmospheric conditions. In addition, we performed one-pot two-step
preparation of symmetrical and unsymmetrical biaryls from aryl bromides by Miyaura
borylation, followed by Suzuki–Miyaura cross-coupling reaction.
2. Material and methods
All reagents were purchased from commercial sources (Aldrich, Merck and TCI Chemicals)
and used without further purification. 1,4-Dioxane and tetrahydrofuran (THF) were distilled

from sodium and sodium benzophenone ketyl under argon. Thin-layer chromatography
(TLC) was performed with aluminum-backed silica gel 60 F254 analytical plates from Merck.
Column chromatography was performed using Merck silica gel 60 (70–230 mesh). NMR
spectra were recorded on Bruker Ascend 400 spectrometer. Chemical shifts (δ) for 1H, 13C,
and 11B NMR were reported in ppm relative to CDCl3. Chemical shifts for 11B were reported
relative to external BF3.OEt2 (δ = 0 ppm). Coupling constants (J) were reported in Hz. Gas
chromatography analysis was performed on Agilent technologies 6890A equipped with a
flame ionized detector and HP-1 capillary column (Stationary phase: 100%
dimethylpolysiloxane, 30 m  0.32 mm  3.00 m film thickness) using helium as a carrier
gas.
3. Experimental
Miyaura borylation
Under atmospheric conditions, a 10-mL screwcap vial equipped with a magnetic stir bar was
charged with Pd source (0.01 mmol, 0.02 equiv), base (0.6 mmol, 1.2 equiv),
bis(pinacolato)diboron (0.525 mmol, 1.05 equiv) and aryl halide (0.5 mmol, 1 equiv). The
reaction vial was transferred to a preheated oil bath. The reaction was stirred at 110 °C for the
desired time to give a grey mixture. The reaction mixture was extracted with 10 mL of ethyl
acetate, washed with water (2 15 mL), brine (10 mL), and dried over Na2SO4. The solvent
was evaporated in vacuo to afford the crude product. The product yield was determined by
GC-FID based on integration relative to hexamethylbenzene as an internal standard. The
residue was purified by column chromatography on silica gel (eluting with 5:95 ethyl acetate
in hexane) to give pure aryl boronic ester.
4,4,5,5-Tetramethyl-2-phenyl-1,3,2-dioxaborolane (3a)
Eluent: Hexane/EtOAc (95:5); Colorless liquid; yield: 81 mg (79%).
1H NMR (400 MHz, CDCl3).  = 7.85 (d, J = 7.4 Hz, 2 H), 7.48 (m, 1 H), 7.40 (m, 2 H), 1.37
(s, 12 H).
13C NMR (100 MHz, CDCl3):  = 134.8, 131.3, 127.8, 83.8, 25.0. The carbon attached to
boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 31.2.

HRMS (ESI): m/z [M + Na]+ calcd for C13H19BNaO2: 241.1370; found: 241.1375.
4,4,5,5-Tetramethyl-2-(p-tolyl)-1,3,2-dioxaborolane (4a)
Eluent: Hexane/EtOAc (95:5); Colorless liquid; yield: 71 mg (65%).
1H NMR (400 MHz, CDCl3):  = 7.73 (d, J = 7.9 Hz, 2 H), 7.20 (d, J = 7.6 Hz, 2 H), 2.38 (s,
3 H), 1.36 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 141.5, 134.9, 128.6, 83.7, 25.0, 21.8. The carbon attached
to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.3.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19BNaO2: 241.1370; found: 241.1378.
4,4,5,5-Tetramethyl-2-(o-tolyl)-1,3,2-dioxaborolane (5a)
Eluent: Hexane/EtOAc (95:5); Colorless liquid; yield: 68.5 mg (63%).
1H NMR (400 MHz, CDCl3):  = 7.77 (dd, J = 7.4 Hz, 1.3 Hz, 1 H), 7.30–7.35 (td, J = 7.4
Hz, 1.2 Hz, 1 H), 7.15–7.18 (m, 2 H), 2.55 (s, 3 H), 1.35 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 145.0, 136.0, 130.9, 129.8, 124.8, 83.5, 25.0, 22.4. The
carbon attached to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.8.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19BNaO2: 241.1370; found: 241.1375.
2-Mesityl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6a)
Eluent: Hexane/EtOAc (95:5); Colorless liquid; yield: 86 mg (71%).
1H NMR (400 MHz, CDCl3):  = 6.78 (s, 2 H), 2.37 (s, 6 H), 2.25 (s, 3 H), 1.38 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 142.3, 139.1, 127.6, 83.6, 25.1, 22.3, 21.4. The carbon
attached to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 33.7.
HRMS (ESI): m/z [M + Na]+ calcd for C15H23BNaO2: 269.1683; found: 269.1693.
2-(4-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7a)

Eluent: Hexane/EtOAc (95:5); Pale yellow liquid; yield: 70 mg (70%).
1H NMR (400 MHz, CDCl3):  = 7.76 (d, J = 8.6 Hz, 2 H), 6.90 (d, J = 8.6 Hz, 2 H), 3.83 (s,
3 H), 1.34 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 162.3, 136.6, 113.4, 83.7, 55.2, 25.0. The carbon attached
to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.0.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19BNaO3: 257.1319; found: 257.1327.
4,4,5,5-Tetramethyl-2-(4-nitrophenyl)-1,3,2-dioxaborolane (8a)
Eluent: Hexane/EtOAc (90:10); White solid; yield: 102 mg (82%).
1H NMR (400 MHz, CDCl3):  = 8.19 (d, J = 8.6 Hz, 2 H), 7.96 (d, J = 8.6 Hz, 2 H), 1.36 (s,
12 H).
13C NMR (100 MHz, CDCl3):  = 150.0, 135.8, 122.6, 84.8, 25.0. The carbon attached to
boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 31.7.
HRMS (ESI): m/z [M + Na]+ calcd for C13H16BNNaO2: 272.1065; found: 272.1071.
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl) benzonitrile (9a)
Eluent: Hexane/EtOAc (90:10); White solid; yield: 82 mg (72%).
1H NMR (400 MHz, CDCl3):  = 7.88 (d, J = 8.0 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 2 H, ArH),
1.35 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 135.2, 131.3, 119.0, 114.7, 84.6, 25.0. The carbon attached
to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.0.
HRMS (ESI): m/z [M + Na]+ calcd for C13H16BNNaO2: 252.1166; found: 252.1167.
1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl)ethanone (10a)
Eluent: Hexane/EtOAc (90:10); White solid; yield: 89 mg (72%).
1H NMR (400 MHz, CDCl3):  = 7.90 (m, 4 H), 2.61 (s, 3 H), 1.35 (s, 12 H).

13C NMR (100 MHz, CDCl3):  = 198.6, 139.1, 135.0, 127.4, 84.3, 26.9, 25.0. The carbon
attached to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.0.
HRMS (ESI): m/z [M + Na]+ calcd for C14H19BNaO3: 269.1319; found: 269.1330.
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl) benzaldehyde (11a)
Eluent: Hexane/EtOAc (90:10); White solid; yield: 73 mg (65%).
1H NMR (400 MHz, CDCl3):  = 10.0 (s, 1 H), 7.96 (d, J = 8.0 Hz, 2 H), 7.86 (d, J = 8.0 Hz,
2 H), 1.36 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 192.9, 138.2, 135.4, 128.9, 84.5, 25.0. The carbon attached
to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.9
HRMS (ESI): m/z [M + Na]+ calcd for C13H17BNaO3: 272.1163; found: 272.1168.
Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzoate (12a)
Eluent: Hexane/EtOAc (90:10); White solid; yield: 86.5 mg (66%).
1H NMR (400 MHz, CDCl3):  = 8.01 (d, J = 8.1 Hz, 2 H), 7.86 (d, J = 8.2 Hz, 2 H), 3.92 (s,
3 H), 1.35 (s, 12 H).
13C NMR (100 MHz, CDCl3):  = 167.3, 134.8, 132.4, 128.7, 84.3, 52.3, 25.0. The carbon
attached to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.2
HRMS (ESI): m/z [M + Na]+ calcd for C14H19BNaO4: 275.1269; found: 275.1277.
4,4,5,5-Tetramethyl-2-(4-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane (13a)
Eluent: Hexane/EtOAc (75:25); White solid; yield: 72% (NMR yield).
1H NMR (400 MHz, CDCl3):  = 7.91 (d, J = 7.9 Hz, 2 H), 7.61 (d, J = 8.0 Hz, 2 H), 1.36 (s,
12 H).

13C NMR (100 MHz, CDCl3):  = 135.1, 133.0 (q, J = 32 Hz, 1 C), 124.5 (d, J = 3.6 Hz, 1 C),
124.3 (q, J = 270 Hz, 1 C), 84.4, 25.0. The carbon attached to boron was not observed due to
quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.4
EI-MS (m/z): 272 (M+), 257, 256, 186, 173, 172, 85, 58.
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl) phenol (14a)
Eluent: Hexane/EtOAc (90:10); Brown solid; yield: 63 mg (57%).
1H NMR (400 MHz, CDCl3):  = 7.71 (d, J = 8.4 Hz, 2 H), 6.82 (d, J = 8.4 Hz, 2 H), 1.33 (s,
12 H).
13C NMR (100 MHz, CDCl3):  = 158.4, 136.9, 114.9, 83.8, 25.0. The carbon attached to
boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.2.
HRMS (ESI): m/z [M + Na]+ calcd for C12H17BNaO3: 243.1163; found: 243.1169.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (15a)
Eluent: Hexane/EtOAc (90:10); Brown solid; yield: 82 mg (52%).
1H NMR (400 MHz, DMSO):  = 11.43 (s, 1 H), 8.45 (s, 1 H), 8.18 (d, J = 7.7 Hz, 1 H), 7.69
(d, J = 8.1 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 1 H), 7.39 (t, J = 7.7 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1
H), 1.33 (s, 12 H)
13C NMR (100 MHz, CDCl3):  = 141.8, 139.5, 132.4, 127.9, 126.0, 123.6, 123.2, 120.7,
119.9, 110.7, 110.1, 83.8, 25.1. The carbon attached to boron was not observed due to
quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 33.1.
HRMS (ESI): m/z [M + Na]+ calcd for C18H20BNNaO2: 316.1479; found: 316.1484.
2-(4-Fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (16a)
Eluent: Hexane/EtOAc (90:10); White solid; yield: 66% (NMR yield).

1H NMR (400 MHz, CDCl3):  = 7.80 (dd, J = 8.2 Hz, 6.3 Hz, 2 H), 7.05 (m, 2 H), 1.34 (s, 12
H)
13C NMR (100 MHz, CDCl3):  = 165.3 (d, J = 249 Hz, 1 C), 137.2 (d, J = 8.1 Hz, 2 C),
115.0 (d, J = 20.1 Hz, 2 C), 84.0, 25.0. The carbon attached to boron was not observed due to
quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.8.
EI-MS (m/z): 222 (M+), 207, 206, 136, 123, 122, 85.
2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl) benzonitrile (17a)
Eluent: Hexane/EtOAc (90:10); Colorless liquid; yield: 56 mg (49%).
1H NMR (400 MHz, CDCl3):  = 7.88 (d, J = 7.6 Hz, 1 H), 7.70 (d, J = 7.2 Hz, 1 H), 7.50 –
7.59 (m, 2 H), 1.39 (s, 12 H)
13C NMR (100 MHz, CDCl3):  = 136.0, 133.5, 131.7, 131.2, 119.1, 117.4, 84.9, 24.9. The
carbon attached to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 31.6.
HRMS (ESI): m/z [M + Na]+ calcd for C13H16BNNaO2: 252.1166; found: 252.1167.
2-(3-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (18a)
Eluent: Hexane/EtOAc (95:5); Colorless liquid; yield: 66 mg (58%).
1H NMR (400 MHz, CDCl3):  = 7.40 (d, J = 7.2 Hz, 1 H), 7.32 (d, J = 2.5 Hz, 1 H), 7.29 (t,
J = 7.6 Hz, 1 H), 7.01 (dd, J = 8.2 Hz, 2.7 Hz, 1 H), 3.83 (s, 3 H), 1.34 (s, 12 H)
13C NMR (100 MHz, CDCl3):  = 159.2, 129.1, 127.3, 118.8, 118.1, 84.0, 55.4, 25.0. The
carbon signal bound to the boron atom was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.4.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19BNaO3: 257.1319; found: 257.1314.
2-(3,5-Dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (19a)
Eluent: Hexane/EtOAc (95:5); White solid; yield: 50 mg (43%).
1H NMR (400 MHz, CDCl3):  = 7.44 (s, 2 H), 7.10 (s, 1 H), 2.32 (s, 6 H), 1.34 (s, 12 H)

13C NMR (100 MHz, CDCl3):  = 137.3, 133.1, 132.5, 83.8, 25.0, 21.3. The carbon attached
to boron was not observed due to quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 32.5.
HRMS (ESI): m/z [M + Na]+ calcd for C14H21BNaO2: 255.1527; found: 255.1522.
2-(3,5-Bis(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (20a)
Eluent: Hexane/EtOAc (95:5); White solid; yield: 65 mg (38%).
1H NMR (400 MHz, CDCl3):  = 8.23 (s, 2 H), 7.94 (s, 1 H), 1.37 (s, 12 H)
13C NMR (100 MHz, CDCl3):  = 134.8, 131.1 (q, J = 30 Hz, 2 C), 124.9 (t, J = 3.7 Hz, 2 C),
123.6 (q, J = 260 Hz, 2 C), 85.8, 25.0. The carbon attached to boron was not observed due to
quadrupolar relaxation.
11B NMR (128 MHz, CDCl3):  = 31.9.
HRMS (ESI): m/z [M + Na]+ calcd for C14H18BF3O2: 339.1106; found: 339.1598.
Suzuki-Miyaura Cross-coupling reaction
Under atmospheric conditions, a 10-mL screwcap vial equipped with a magnetic stir bar was
charged with PdCl2(PPh3)2 (0.01 mmol, 0.02 equiv), KOAc (0.6 mmol, 1.2 equiv),
bis(pinacolato)diboron (0.525 mmol, 1.05 equiv) and aryl halide (0.5 mmol, 1 equiv). The
reaction vial was transferred to a preheated oil bath. The reaction was stirred at 110 °C for 4 h
to give the grey mixture. An aryl halide (0.5 mmol, 1.0 equiv), KOtBu (1.25 mmol, 2.5
equiv), and EtOH (1 mL) were added into the reaction vial and stirred at 110 °C for 24 h. The
reaction mixture was extracted with 10 mL of ethyl acetate, washed with water (2 15 mL),
brine (10 mL), and dried over Na2SO4. The solvent was evaporated in vacuo to afford the
crude product. The residue was purified by column chromatography on silica gel (eluting
with 5:95 ethyl acetate in hexane).
4-Methoxy-1,1'-biphenyl
Eluent: Hexane/EtOAc (95:5); White solid; yield: 77 mg (64%).

1H NMR (400 MHz, CDCl3):  = 7.54 (t, 4 H), 7.41 (t, 2 H), 7.30 (t, 2 H), 6.97 (d, J = 8.8 Hz,
2 H), 3.85 (s, 3 H)
13C NMR (100 MHz, CDCl3):  = 159.2, 140.8, 134.7, 128.7, 128.1, 126.7, 126.6, 114.2,
55.3.
HRMS (ESI): m/z [M + Na]+ calcd for C13H13O: 184.0888 ; found: 184.0890.
4-Nitro-1,1'-biphenyl
Eluent: Hexane/EtOAc (95:5); Yellow solid; yield: 64 mg (58%).
1H NMR (400 MHz, CDCl3):  = 8.30 (d, J = 8.8 Hz, 2 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.43–
7.52 (m, 3 H), 3.87 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 160.5, 147.2, 146.5, 131.1, 128.6, 127.1, 124.1, 114.6,
55.4.
HRMS (ESI): m/z [M + H]+ calcd for C13H13O: 222.0527; found: 252.0525.
4-Methoxy-4'-nitro-1,1'-biphenyl
Eluent: Hexane/EtOAc (95:5); Yellow solid: yield: 64 mg (56%).
1H NMR (400 MHz, CDCl3):  = 8.25 (d, J = 8.8 Hz, 2 H), 7.68 (d, J = 8.8 Hz, 2 H), 7.57 (d,
J = 8.8 Hz, 2 H), 7.01 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H)
13C NMR (100 MHz, CDCl3):  = 160.5, 147.2, 146.6, 131.1, 128.6, 127.1, 124.1, 114.6, 55.4
HRMS (ESI): m/z [M + Na]+ calcd for C13H11NNaO3: 252.0633; found: 252.0631.
Gram-scale synthesis of 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (3a)
Under atmospheric conditions, a 25-mL round-bottom flask equipped with a magnetic stir bar
was charged with PdCl2(PPh3)2 (0.13 mmol, 0.02 equiv), KOAc (7.46 mmol, 1.2 equiv),
bis(pinacolato)diboron (6.69 mmol, 1.05 equiv) and bromobenzene (6.37 mmol, 1 equiv).
The reaction vial was transferred to a preheated oil bath. The reaction was stirred at 110 °C
for the desired time to give a grey mixture. The reaction mixture was extracted with 10 mL of
ethyl acetate, washed with water (2 20 mL), brine (20 mL), and dried over Na2SO4. The
solvent was evaporated in vacuo to afford the crude product. The residue was purified by

column chromatography on silica gel (eluting with 1:99 ethyl acetate in hexane) to give 3a in
76%.
Gram-scale synthesis of 4,4,5,5-tetramethyl-2-(4-nitrophenyl)-1,3,2-dioxaborolane (8a)
Under atmospheric conditions, a 25-mL round-bottom flask equipped with a magnetic stir bar
was charged with PdCl2(PPh3)2 (0.099 mmol, 0.02 equiv), KOAc (5.94 mmol, 1.2 equiv),
bis(pinacolato)diboron (5.20 mmol, 1.05 equiv) and 1-bromo-4-nitrobenzene (4.95 mmol, 1
equiv). The reaction vial was transferred to a preheated oil bath. The reaction was stirred at
110 °C for the desired time to give a grey mixture. The reaction mixture was extracted with
10 mL of ethyl acetate, washed with water (2 15 mL), brine (10 mL), and dried over
Na2SO4. The solvent was evaporated in vacuo to afford the crude product. The residue was
purified by column chromatography on silica gel (eluting with 5:95 ethyl acetate in hexane)
to give 8a in 79%.
Gram-scale synthesis of 1,1'-biphenyl
Under atmospheric conditions, a 25-mL round-bottom flask equipped with a magnetic stir bar
was charged with PdCl2(PPh3)2 (0.13 mmol, 0.02 equiv), KOAc (7.46 mmol, 1.2 equiv),
bis(pinacolato)diboron (6.69 mmol, 1.05 equiv) and bromobenzene (6.37 mmol, 1 equiv).
The reaction vial was transferred to a preheated oil bath. The reaction was stirred at 110 °C
for 4 h to give the grey mixture. Bromobenzene (6.37 mmol, 1.0 equiv), KOtBu (15.93 mmol,
2.5 equiv), and EtOH (13 mL) were added into the reaction vial and stirred at 110 °C for 24 h.
The reaction mixture was extracted with 10 mL of ethyl acetate, washed with water (2  20
mL), brine (20 mL), and dried over Na2SO4. The solvent was evaporated in vacuo to afford
the crude product. The residue was purified by column chromatography on silica gel (eluting
with 5:95 ethyl acetate in hexane) to give the desired product in 68%.
Gram-scale synthesis of 4-nitro-1,1'-biphenyl.
Under atmospheric conditions, a 25-mL round-bottom flask equipped with a magnetic stir bar
was charged with PdCl2(PPh3)2 (0.099 mmol, 0.02 equiv), KOAc (5.94 mmol, 1.2 equiv),
bis(pinacolato)diboron (5.20 mmol, 1.05 equiv) and 1-bromo-4-nitrobenzene (4.95 mmol, 1
equiv). The reaction vial was transferred to a preheated oil bath. The reaction was stirred at
110 °C for 4 h to give the grey mixture. Bromobenzene (6.37 mmol, 1.0 equiv), KOtBu

(15.93 mmol, 2.5 equiv), and EtOH (10 mL) were added into the reaction vial and stirred at
110 °C for 24 h. The reaction mixture was extracted with 10 mL of ethyl acetate, washed
with water (2  20 mL), brine (20 mL), and dried over Na2SO4. The solvent was evaporated
in vacuo to afford the crude product. The residue was purified by column chromatography on
silica gel (eluting with 5:95 ethyl acetate in hexane) to give the desired product in 75%.
4. Results and discussion
Initially, the screening of Pd-catalyzed Miyaura borylation of phenyl bromide (1a)
with bis(pinacolato)diboron (B2pin2) (2a) was performed by using 1 mol% of various
palladium sources in the presence of potassium acetate under solvent-free and atmospheric
conditions at 110 °C to afford phenyl boronic ester (3a). Results of the initial screening of
catalyst systems are summarized in Table 2. Pd(OAc)2 without phosphine ligand exhibited a
very low catalytic activity in the borylation reaction of phenyl bromide, whereas the addition
of triphenylphosphine in Pd(OAc)2, Pd2(dba)3 and PdCl2 systems under low catalyst loading
(1 mol%) increased the yields of 3a to 61–68% (entries 1–4). It was found that Pd(PPh3)4 and
PdCl2(PPh3)2 gave comparable yields of 3a at 75% and 72%, respectively (entries 5–6).
However, Pd(PPh3)4 was avoided due to the requirement of inert atmosphere and glovebox.
Upon varying the catalyst loading, 2 mol% of PdCl2(PPh3)2 gave the highest yield of 79%
(entry 8). With the purpose to improve the Miyaura borylation reaction, 2 mol% of
PdCl2(PPh3)2 and 1.2 equiv of KOAc were thus chosen for further screening.
Table 2 Screening of catalyst systems and catalyst loading for borylation of bromobenzenea
O
Br
O
O
O
O
Pd sources
B
+
O
B
B
KOAc (1.2 equiv)
neat, 110 oC, 24 h
atmospheric conditions
1a
2
3a
Entry
Catalyst
Ligand
Yield
(%)b

1
2
3
4
5
6
7
8
9
Pd(OAc)2 (1 mol%)
Pd(OAc)2 (1 mol%)
Pd2(dba)3 (1 mol%)
PdCl2 (1 mol%)
-
4
PPh3 (2 mol%)
61
65
68
75
72
63
79
77
PPh3 (4 mol%)
PPh3 (2 mol%)
Pd(PPh3)4 (1 mol%)
PdCl2(PPh3)2 (1 mol%)
PdCl2(PPh3)2 (0.5 mol%)
PdCl2(PPh3)2 (2 mol%)
PdCl2(PPh3)2 (5 mol%)
-
-
-
-
-
a Reaction conditions: Pd source, phenyl bromide (0.5 mmol), bis(pinacolato)diboron
(0.525 mmol), KOAc (0.6 mmol), 110 °C, 24 h.
b Product yield was determined by GC/FID using relative peak areas versus
hexamethylbenzene (0.005 mmol) as an internal standard.
We next screened bases for Miyaura borylation of phenyl bromide and
bis(pinacolato)diboron because the base plays an important role in the acceleration of
transmetallation step and the prevention of biaryl compound formation.6 In Table 3, the
presence of KOMe, KOtBu, KOH, K3PO4, and triethylamine gave moderate yields of the aryl
boronated product (entries 2–6, 8), whereas the use of K2CO3 resulted in a very low yield
(entry 1). Acetate bases were found to be the most effective base for the borylation reaction
(entries 7, 8). The use of NaOAc and KOAc led to significant increases in the yields, i.e. 70%
and 79%, respectively. A previous study showed that the size of cations affects the
coordination site of aryl boronated species.19 A large cation provides the larger coordination
site to bind with diboron compound than a small cation in the transition state. In this work,
the effect of cation size on the yield of Miyaura borylation seems to follow the same trend.
Table 3 Screening of bases for Miyaura borylation reactiona
O
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
B
+
O
B
B
Base (1.2 equiv)
neat, 110 oC, 24 h
atmospheric conditions
1a
2
3a

Entry
Bases
Yield (%)b
1
2
3
4
5
6
7
8
K2CO3
KOMe
KOtBu
KOH
6
47
34
53
53
34
79
70
K3PO4
NEt3
KOAc
NaOAc
a Reaction conditions: PdCl2(PPh3)2 (0.01 mmol), phenyl bromide (0.5 mmol),
bis(pinacolato)diboron (0.525 mmol), base (0.6 mmol), 110 °C, 24 h.
b Product yield was determined by GC/FID using relative peak areas versus
hexamethylbenzene (0.005 mmol) as an internal standard.
The reaction was further examined with various types of solvents (Table 4).
Acetonitrile (CH3CN), water, DMSO and DMF were not effective according to low yields
(entries 7–10), whereas the use of MeOH, 1,4-dioxane, THF and toluene gave moderate
yields (entries 3–6). The best yield (85 %) was obtained when the reaction was performed in
EtOH (entry 2), suggesting that the solvents play an important role in stabilizing the
unsaturated palladium center.20 Noteworthy, the solvent-free conditions also gave a relatively
high yield although the number is lower than that of EtOH (entry 1). Therefore, the solvent-
free condition was selected for further studies based on its environmental and economic
impacts.
Table 4 Screening of solvents for borylation of bromobenzenea
O
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
B
+
O
B
B
KOAc (1.2 equiv)
solvent (1 mL)
110 oC, 24 h
2
3a
1a
atmospheric conditions
Entry
Solvent (1 mL)
Yield (%)b

1
2
3
4
5
6
7
8
9
10
Neat
79
85
63
75
76
61
40
51
17
5
EtOH
MeOH
1,4-dioxane
THF
Toluene
DMSO
DMF
CH3CN
H2O
a Reaction conditions: PdCl2(PPh3)2 (0.01 mmol), phenyl bromide (0.5 mmol),
bis(pinacolato)diboron (0.525 mmol), KOAc (0.6 mmol), solvent (1 mL), 110
°C, 24 h.
b Product yield was determined by GC/FID using relative peak areas versus
hexamethylbenzene (0.005 mmol) as an internal standard.
Since concentrations of bases were reported to significantly affect the reaction pH
value and borylated product yield,19 the effect of base was studied by addition of 0.5–2.5
equiv of KOAc under the solvent-free conditions (Table 5). It was found that 1.2 equiv of
KOAc was sufficient to achieve the high yield of 3a (79%) (entry 3). Noteworthy, under the
same conditions, 3a could be isolated by column chromatography to give 75% yield and the
recovery of the starting material bromobenzene (7–20%) was observed (entry 3).
Furthermore, we also conducted the same experiments in EtOH (Table S1 in Supporting
Information). The results clearly indicated that most concentrations of KOAc in EtOH were
inferior to those under the solvent-free conditions in terms of yield, although the
concentration of 1.2 equiv KOAc in EtOH gave the highest yield up to 85%. Thus, the
optimal system for this reaction involved PdCl2(PPh3)2 (2 mol%) and KOAc (1.2 equiv)
under the solvent-free and atmospheric conditions.
Table 5 Effect of KOAc concentrations on the borylation of bromobenzenea

O
B
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
O
B
B
+
KOAc (n equiv)
neat, 110 oC, 24 h
atmospheric conditions
3a
2
1a
Entry
KOAc (equiv)
Yield (%)b
1
2
3
4
5
6
0.5
1
36
70
1.2
1.5
2
79 (75)c
76
75
2.5
74
a Reaction conditions: PdCl2(PPh3)2 (0.01 mmol), phenyl bromide (0.5 mmol),
bis(pinacolato)diboron (0.525 mmol), KOAc, 110 °C, 24 h.
b Product yield was determined by GC/FID using relative peak areas versus
hexamethylbenzene (0.005 mmol) as an internal standard.
c Product was isolated from column chromatography by using ethyl acetate
and hexane as an eluent.
Effects of reaction temperature and reaction time were also studied and the results are
summarized in Table 6. Temperature was shown to exert a significant influence on the
product formation. Lower temperature led to a decrease of the yield of phenyl boronic ester
3a from 79% at 110 °C down to 11% at room temperature (entries 1–4). In terms of reaction
times, the yields of ⩾ 75% were obtained after only 2 hours.
Table 6 Investigation of reaction temperature and time on borylation of bromobenzenea
O
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
B
+
O
B
B
KOAc (1.2 equiv)
reaction temperature (oC)
reaction time (h)
2
1a
3a
atmospheric conditions
Entry
Temperature (°C)
Reaction time (h)
Yield (%)b

1
2
3
4
5
6
7
8
Room temperature
24
24
24
24
8
11
45
71
79
78
76
75
74
60
80
110
110
110
110
110
4
2
1
a Reaction conditions: PdCl2(PPh3)2 (0.01 mmol), aryl bromide (0.5 mmol),
bis(pinacolato)diboron (0.525 mmol), KOAc (0.6 mmol), 110 °C, 24 h.
b Product yield was determined by GC/FID using relative peak areas versus
hexamethylbenzene (0.005 mmol) as an internal standard.
Substrate scope was subsequently investigated under the optimized conditions at 110
°C for 24 hours in order to complete product formation (Table 7). A variety of aryl bromides
bearing electron-donating or electron-withdrawing substituents could be successfully
borylated using PdCl2(PPh3)2 (2 mol%) and KOAc (1.2 equiv) under neat conditions to
provide the corresponding arylpinacol esters in moderate to high isolated yields. The highest
product yield of 82% was obtained when using 1-bromo-4-nitrobenzene (8a: entry 5).
Sterically demanding substrates gave the expected product in slightly lower yield of 71% (6a:
entry 3). Several functional groups, including ester, ketone, aldehyde, and cyanide, were
tolerated under these conditions. However, 1-bromo-3,5-dimethylbenzene and 1,3-
bis(trifluoromethyl)-5-bromobenzene afforded relatively low isolated yields of 43% and 38%,
respectively (19a, 20a: entries 16–17).
Table 7 Representative examples of borylationsa
O
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
B
+
O
B
B
R
KOAc (1.2 equiv)
neat, 110 oC, 24 h
R
atmospheric conditions
2
4a-20a

Entry
1
Product
Yield Entry
(%)b
Product
Yield
(%)b
O
O
O
O
65
10
72c
B
B
F3C
13a
4a
O
O
B
O
2
3
63
11
57
HO
B
O
14a
5a
O
O
O
O
H
71
70
12
13
52
B
B
N
15a
6a
O
O
O
4
5
66c
MeO
B
B
F
O
16a
7a
CN
O
O
82
14
49
O2N
B
O
B
O
8a
9a
17a
H3CO
O
O
O
O
6
7
8
72
72
65
15
16
17
58
43
38
NC
B
B
18a
O
O
O
O
B
O
B
10a
19a
F3
C
C
O
H
O
O
O
O
B
B
F3
11a
20a

O
O
O
9
66
B
H
3CO
12a
a Reaction conditions: PdCl2(PPh3)2 (0.01 mmol), aryl bromide (0.5 mmol),
bis(pinacolato)diboron (0.525 mmol), KOAc (0.6 mmol), 110 °C, 24 h.
b Product was isolated from column chromatography by using ethyl acetate and
hexane as eluents.
c NMR yield
Furthermore, we studied a one-pot two-step borylation (Step I)/Suzuki–Miyaura
cross-coupling (Step II). Homocoupling of bromobenzene was chosen as a model reaction for
the optimization of the one-pot protocol (Table 8). The base in Step II was firstly optimized.
The results indicated that the use of weak bases including K2CO3, K3PO4, and KOAc (1.5
equiv) led to low product yields (12–22%: entries 1–3) whereas introduction of a stronger
base, KOtBu, at the same concentration activated boron and led to subsequent coupling to
give 46% yield of the biaryl product (entry 4). It was assumed that the stronger base is
required in Step II than the one needed in Step I because of the formation of the more reactive
boronate that interacts with the palladium species and facilitates an intramolecular
transmetallation.23
Upon variation of KOtBu concentrations, the best concentration was 2.5 equiv in
terms of the product yield (51%: entry 8). At this concentration, we also varied the reaction
time of Step I and found a good yield (65%) of the homocoupling product in only four hours.
In contrast, the best reaction time of the Step II was 24 hours in terms of the product yield
(Table 9, entry 4). The optimized conditions are thus: 2 mol% of PdCl2(PPh3)2, 1.2 equiv of
KOAc and 4 hours for the borylation, followed by 2.5 equiv of KOtBu and 24 hours for the
Suzuki–Miyaura homocoupling. It is noteworthy that we also tried to carry out the Step II in
EtOH (entry 5) and found the product yield comparable with the neat condition.
Table 8 Optimization of reaction conditions of borylation/Suzuki–Miyaura
homocoupling reactiona

PdCl2(PPh3)2 2mol%
B2pin2, KOAc
Br
Phenyl bromide
Bpin
, neat, 110 oC, 24 h
atmospheric conditions
Step II
neat, 110 oC,
h
base
n
atmospheric conditions
Step I
Entry
Base in
Step II
Concentration of
Time of
Yield (%)b
Step I (h)
base in Step II (equiv)
1
K2CO3
K3PO4
KOAc
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
1.5
1.5
1.5
1.5
1
2
2
2
2
2
2
1
2
4
6
8
24
2
12
12
22
46
5
2
3
4
5
6
2
39
59
51
65
50
41
44
45
7
2.5
2.5
2.5
2.5
2.5
2.5
3
8
9
10
11
12
13
a Reaction conditions: (Step I) phenyl bromide (0.5 mmol), PdCl2(PPh3)2 (0.01 mmol),
bis(pinacolato)diboron (0.525 mmol), KOAc (0.60 mmol); (Step II) phenyl bromide (0.5
mmol), base, 110 °C, 24 h.
b NMR yield
Table 9 Optimization of the Step II reaction time of borylation/Suzuki–Miyaura cross-
coupling reaction
PdCl2(PPh3)2 2mol%
Br
B2pin2
Phenyl bromide
Bpin
KOtBu, neat, 110 o
C
KOAc, neat, 110 o
C
n
h
4
h
atmospheric conditions
atmospheric conditions
Entry
Time of Step II (h)
Yield (%)b

1
1
39
38
55
65
65
2
2
3
4
4
24
24
5c
a Reaction conditions: (Step I) phenyl bromide (0.5 mmol), PdCl2(PPh3)2 (0.01 mmol),
bis(pinacolato)diboron (0.525 mmol), KOAc (0.60 mmol); (Step II) phenyl bromide (0.5
mmol), KOtBu (1.25 mmol), 110 °C.
b NMR yield
c in 1 mL EtOH
The one-pot borylation/Suzuki–Miyaura cross-coupling reaction of unsymmetrically
coupled biaryl compounds was also studied. Results of the Suzuki–Miyaura cross-coupling
reaction of phenyl bromide with different aryl bromides were shown in Schemes 1–3. In the
case of the aryl bromide with electron-donating group, the formation of biaryl product was
obtained in a moderate yield (64%, Scheme 1) whereas the aryl bromide with the electron-
withdrawing group gave the corresponding biaryl product in the higher yield (78%, Scheme
2). We also performed the Suzuki–Miyaura cross-coupling reaction by using two different
functional groups, i.e. 1-bromo-4-nitrobenzene and 4-bromoanisole as substrates for Step I
and II, respectively, yielding the product in 56% (Scheme 3). Noteworthy, the yields of the
unsymmetrically coupled biaryl compounds reported here were obtained from the Suzuki–
Miyaura cross-coupling in EtOH, which were higher than those under neat conditions due to
homogeneity of the reagents.
Insert schemes 1, 2, and 3 here
Finally, we have successfully demonstrated gram-scale syntheses of boronate ester,
symmetrical and unsymmetrical biaryls. The results were reported in Schemes 4–7. The aryl
boronate esters were obtained under solvent-free conditions in 76–79%, whereas the yields of
the homocoupling and cross-coupling products were 63–75%. These results are similar to

those from the small-scale reactions suggesting the scalability and efficiency of our
procedure.
Insert schemes 4, 5, 6 and 7 here
Noteworthy, these environmentally friendly and safe conditions meet the demand of
green chemistry. The “greenness” is measured by E factor which is the ratio of the total mass
used in the process to the mass of the final product.21 The Miyaura borylation and one-pot
Miyaura/Suzuki-cross coupling reaction in this work exhibited low E factors, i.e. 1.94 and
5.66 respectively (see Supporting Information), when comparing with that of most fine
chemicals ranging from 5 to 50.22
5. Conclusion
In conclusion, an economical, operationally simple and environmentally friendly
protocol for Miyaura borylations of aryl bromides was developed in the presence of 2 mol%
of PdCl2(PPh3)2, 1.2 equiv of KOAc under atmospheric and solvent-free conditions. The
reaction system exhibits the wide scope of substrates, scalability and low E factors that meet
demands of green chemistry. The optimized one-pot two-step borylation/Suzuki–Miyaura
cross coupling was also developed to synthesize unsymmetrically biaryls compounds. The
products were obtained in moderate to good yields.
Funding information
This work was financially supported by Mahidol University and the Thailand
Research Fund (TRF) (Grant numbers: IRG5980007 and RSA6080065).
Acknowledgement
Financial support from the Center of Excellence for Innovation in Chemistry
(PERCH-CIC), Ministry of Higher Education, Research and Innovation is gratefully
acknowledged.
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Scheme captions:
Scheme 1: One-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide and 4-
bromoanisole
Scheme 2: One-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide and 1-
bromo-4-nitrobenzene

Scheme 3: One-pot Miyaura borylation/Suzuki cross-coupling of 1-bromo-4-nitrobenzene
and 4-bromoanisole
Scheme 4 Gram-scale Miyaura borylation of bromobenzene
Scheme 5 Gram-scale Miyaura borylation of 1-bromo-4-nitrobenzene
Scheme 6 Gram-scale one-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide
Scheme 7 Gram-scale one-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide
and 1-bromo-4-nitrobenzene

List of Schemes
OMe
OMe
PdCl2(PPh3)2 (2 mol%)
Br
Br
Bpin
B2pin2, KOAc (1.2 equiv)
KOtBu (2.5 equiv)
EtOH, 110 oC, 24 h
atmospheric conditions
neat, 110 oC, 4 h
atmosphreric conditions
64%
Scheme 1 One-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide and 4-
bromoanisole
NO2
PdCl2(PPh3)2 (2 mol%)
NO2
Br
B2pin2, KOAc (1.2 equiv)
Bpin
Br
neat, 110 oC, 4 h
atmospheric conditions
KOtBu (2.5 equiv)
EtOH, 110 oC, 24 h
atmospheric conditions
78%
Scheme 2 One-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide and 1-
bromo-4-nitrobenzene
OCH3
OCH3
PdCl2(PPh3)2 (2 mol%)
Br
Bpin
B2pin2, KOAc (1.2 equiv)
Br
neat, 110 oC, 4 h
atmospheric conditions
KOtBu (2.5 equiv)
EtOH, 110 oC, 24 h
atmospheric conditions
O2N
O2N
O2N
56%
Scheme 3 One-pot Miyaura borylation/Suzuki cross-coupling of 1-bromo-4-nitrobenzene and
4-bromoanisole
O
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
B
+
O
B
B
KOAc (1.2 equiv)
neat, 110 oC, 24 h
atmospheric conditions
1 g
982 mg
76%
Scheme 4 Gram-scale Miyaura borylation of bromobenzene
O
Br
O
O
O
O
PdCl2(PPh3)2 (2 mol%)
B
+
O
B
B
KOAc (1.2 equiv)
neat, 110 oC, 24 h
O2N
O2N
atmospheric conditions
1 g
978 mg
79%
Scheme 5 Gram-scale Miyaura borylation of 1-bromo-4-nitrobenzene

PdCl2(PPh3)2 (2 mol%)
Br
1 g
B
2pin2, KOAc (1.2 equiv)
Bpin
Br
neat, 110 oC, 4 h
KOtBu (2.5 equiv)
EtOH, 110 oC, 24 h
atmospheric conditions
atmospheric conditions
1 g
624 mg
63%
Scheme 6 Gram-scale one-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide
NO2
PdCl2(PPh3)2 (2 mol%)
NO2
Br
1.3 g
B
2pin2, KOAc (1.2 equiv)
Bpin
Br
neat, 110 oC, 4 h
KOtBu (2.5 equiv)
EtOH, 110 oC, 24 h
atmospheric conditions
atmospheric conditions
1 g
738 mg
75%
Scheme 7 Gram-scale one-pot Miyaura borylation/Suzuki cross-coupling of phenyl bromide
and 1-bromo-4-nitrobenzene

Graphical abstract
Br
R2
R1
B2pin2
R1
R1
Br
2 mol% PdCl2(PPh3)2
KOAc, neat
110 oC, 4 h
KOtBu, neat or EtOH
110 oC, 24 h
Bpin
R2
28-82%
18 examples
R
1 = H, Me, OMe, NO2
CN, aldehyde, ketone,
ester, CF3 etc.
56-79%
3 examples

Abstract
Facile and economical method for Miyaura borylation reaction between B2pin2 and
aryl bromides is reported. The catalytic system containing 2 mol% PdCl2(PPh3)2 and KOAc
serves to enable borylations to occur under solvent-free and atmospheric conditions. The
developed protocol can be applied to synthesize symmetrical and unsymmetrical biaryls via
one-pot two-step Suzuki–Miyaura cross-coupling reaction and also offers the up-scalability.
Keywords
aryl boronate ester, Miyaura borylation, Suzuki–Miyaura cross-coupling reaction,
one-pot reaction, palladium