A C-H borylation approach to suzuki-miyaura coupling of typically unstable 2-heteroaryl and polyfluorophenyl boronates

Article abstract of DOI:10.1021/ol301570t

A method for the synthesis of biaryls and heterobiaryls from arenes and haloarenes without the intermediacy of unstable boronic acids is described. Pinacol boronate esters that are analogous to unstable boronic acids are formed in high yield by iridium-catalyzed C-H borylation of heteroarenes and fluoroarenes. These boronates are stable in the solid state or in solution and can be generated and used in situ. They couple with aryl halides in the presence of simple palladium catalysts, providing a convenient route to biaryl and heteroaryl products that have been challenging to prepare via boronic acids.

Full text of DOI:10.1021/ol301570t

S1
A C-H Borylation Approach to Suzuki-Miyaura Coupling of Typically
Unstable 2-Heteroaryl and Polyfluorophenyl Boronates with Simple
Catalysts
Supporting Information
Daniel W. Robbins and John F. Hartwig*
University of Illinois, Department of Chemistry
6
00 South Matthews Avenue, Urbana, Illinois 61801
and
Department of Chemistry, University of California, Berkeley, Berkeley, CA,
4720
9

S2
Table of Contents
Experimental Information
Experimental Procedures
S3
S4

S3
Experimental Information
General Procedures. All reactions were conducted under a nitrogen atmosphere in
flame-dried glassware or in an inert atmosphere glovebox. Dry and degassed solvents
were used unless otherwise noted. The water used as co-solvent was deionized and
degassed by bubbling N
with a Teledyne Isco Combiflash® R
2
gas for 10 minutes. Column chromatography was performed
system with RediSep R columns. Analytical thin-
f
f
layer chromatography was performed on glass plates coated with silica gel (Silicycle, 60
A pore size, 40-64 um particle size) impregnated with a fluorescent indicator (254 nm).
TLC plates were visualized by ultraviolet light and staining solution of p-anisaldehyde or
KMnO4.
Materials.
butylphosphino)ferrocene) were obtained from Johnson Matthey and used as received.
,4’-Di-tert-butylbipyridine was obtained from Aldrich Chemicals and used as received.
Bis(pinacolato)diboron (B pin ) was obtained from Allychem and used as received.
[Ir(cod)OMe]
2
and
Q-phos
(1,2,3,4,5-Pentaphenyl-1'-(di-t-
4
2
2
Arenes, heteroarenes, aryl halides, tri-o-tolylphosphine, sodium carbonate, potassium
phosphate, and pinacolborane were obtained from Aldrich, Alfa Aesar, Acros,
Combiblocks, Oakwood Chemicals or TCI America and used as received. Heteroaryl
boronic acids and boronate esters were obtained from Combi-Blocks or Aldrich and used
1
as received. Pd(dba)
2
was synthesized according to published procedures. Pd-hydroxide
2
complexes were prepared according to published procedures.
1
Instruments. H NMR spectra were recorded on a 500 MHz Varian instrument (126
MHz for C). Chemical shifts are reported in parts per million relative to residual
protiated solvent (7.26 ppm for CDCl ). The carbon bonded to boron in the arene and
heteroarene borylation products were not observed via C NMR spectroscopy. This
observation is consistent with previous reports of borylated arenes and heteroarenes.
1
3
3
1
3
3
GC-MS data were obtained on an Agilient 6890-N GC system containing an Alltech EC-
1
capillary column and an Agilient 5973 mass selective detector. GC analyses were
obtained on an Agilent 6890 Gas Chromatograph equipped with an HP- 5 25 m x 0.20
mm ID x 0.33 µm capillary column (Agilent) and an FID detector.

S4
Experimental Procedures
General Procedure for the Borylation of Heteroarenes. Inside a glove box,
Ir(cod)OMe] (1.7 mg, 0.0025 mmol, 0.0025 equiv), dtbpy (1.4 mg, 0.0050 mmol,
.0050 equiv), B pin (127 mg, 0.500 mmol, 0.500 equiv) or HBpin (141 mg, 1.10 mmol,
.10 equiv), the heteroarene (1.00 mmol, 1.00 equiv), and THF (2 mL) were added
[
2
0
1
2
2
consecutively to a dry vial with a magnetic stir bar. The vial was sealed and heated at 80
C for 18 h. The reaction mixture was cooled to room temperature, concentrated and
°
purified by column chromatography to give the product.
Borylation of Indole. Prepared according to the general procedure with indole (117 mg,
1
.00 mmol, 1.00 equiv). The mixture was purified by flash column chromatography
1
(10% EtOAc:90% hexanes) to give the product (175 mg, 72%). H NMR (499 MHz,
CDCl ) δ 8.60 (s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.40 (m, 1H), 7.25 (m, 1H), 7.13 (m, 2H),
3
1
3
1
1
.38 (s, 12H). C NMR (126 MHz, CDCl
3
) δ 138.48, 128.55, 123.87, 121.85, 120.03,
: C, 68.17; H, 7.46; N, 5.76.
14.12, 111.51, 84.40, 25.07. Anal. Calcd for C14
H
17BNO
2
Found: C, 69.55; H, 7.42; N, 6.08.
Borylation of ethyl 3-furoate. Prepared according to the general procedure with ethyl 3-
furoate (140 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash column
1
chromatography (5% EtOAc:95% hexanes) to give the product (172 mg, 65%). H NMR
(
500 MHz, CDCl
3
) δ 8.12 (s, 1H), 7.31 (s, 1H), 4.22 (q, J = 6.9 Hz, 2H), 1.24 (m, 15H).
C NMR (126 MHz, CDCl ) δ 163.06, 151.99, 123.01, 120.45, 84.77, 60.65, 24.88,
4.43. Anal. Calcd for C13 : C, 58.68; H, 7.20. Found: C, 58.75; H, 7.12.
1
3
3
1
H19BO
5
Borylation of 2-Methylthiophene. Prepared according to the general procedure with 2-
methylthiophene (98 mg, 1.0 mmol, 1.0 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (166 mg, 74%).
1
H NMR (499 MHz, CDCl
3
) δ 7.48 (d, J = 3.4 Hz, 1H), 6.86 (d, J = 3.3 Hz, 1H), 2.55 (s,
H), 1.35 (s, 12H). C NMR (126 MHz, CDCl ) δ 147.73, 137.89, 127.24, 84.08, 24.99,
5.62. Anal. Calcd for C11 S: C, 58.95; H, 7.65. Found: C, 58.71; H, 7.40.
1
3
3
1
3
H
17BO
2

S5
General Procedure for the Borylation of Fluoroarenes. Inside a glove box,
[
0
1
Ir(cod)OMe]
2
(1.7 mg, 0.0025 mmol, 0.0025 equiv), dtbpy (1.4 mg, 0.0050 mmol,
.0050 equiv), B pin (153 mg, 0.600 mmol, 0.600 equiv) or HBpin (141 mg, 1.10 mmol,
.10 equiv), the arene (1.00 mmol, 1.00 equiv), and THF (2 mL) were added
2
2
consecutively to a dry vial with a magnetic stir bar. The vial was sealed and heated at 80
C for 18 h. The reaction mixture was cooled to room temperature and purified by
°
column chromatography to give the product.
Borylation of 2-chloro-4-fluorotoluene. Prepared according to the general procedure
with 2-chloro-4-fluorotoluene (144 mg, 1.00 mmol, 1.00 equiv). The mixture was
purified by flash column chromatography (10% EtOAc:90% hexanes) to give the product
1
(
223 mg, 83%). H NMR (499 MHz, CDCl
3
) δ 7.58 (d, J = 6.3 Hz, 1H), 7.07 (d, J = 8.9
) δ 165.46 (d, J = 252.9
Hz), 138.45 (d, J = 8.7 Hz), 131.57 (d, J = 3.7 Hz), 116.52 (d, J = 5.3 Hz), 116.30 (d, J =
1
3
Hz, 1H), 2.33 (s, 3H), 1.37 (s, 12H). C NMR (126 MHz, CDCl
3
1
9
5
.1 Hz), 84.25 (s), 25.01 (s), 19.18 (s). F NMR (376 MHz, CDCl
3
) δ -106.11 (s). Anal.
Calcd for C13 : C, 57.71; H, 6.33. Found: C, 58.04; H, 6.14.
H17BClFO
2
Borylation of Methyl 3,4-difluorobenzoate. Prepared according to the general
procedure with methyl 3,4-difluorobenzoate (172 mg, 1.0 mmol, 1.0 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (217 mg, 73%). H NMR (499 MHz, CDCl
7
3
) δ 8.16 (dd, J = 4.1, 2.0 Hz, 1H),
1
3
.88 (ddd, J = 10.2, 7.6, 2.2 Hz, 1H), 3.90 (s, 3H), 1.35 (s, 12H). C NMR (126 MHz,
3
CDCl ) δ 165.40 (d, J = 2.3 Hz), 157.71 (dd, J = 260.6, 12.0 Hz), 150.25 (dd, J = 250.5,
1
4.9 Hz), 133.244 (dd, J = 7.9 Hz, 3.7 Hz), 126.83 (t, J = 4.4Hz), 121.491 (dd, J = 18.8
1
9
Hz, 2.3 Hz), 84.73 (s), 52.58 (s), 24.99 (s). F NMR (376 MHz, CDCl
4.1, 21.3), -137.78 (dd, J = 10.5, 21.2). Anal. Calcd for C14 : C, 56.41; H, 5.75.
Found: C, 56.30; H, 5.68.
3
) δ -121.44 (dd, J
=
2 4
H17BF O

S6
Borylation of Methyl 3,5-difluorobenzoate. Prepared according to the general
procedure with methyl 3,5-difluorobenzoate (172 mg, 1.0 mmol, 1.0 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (202 mg, 68%). H NMR (499 MHz, CDCl
3
) δ 7.48 (m, 2H), 3.91 (s, 3H), 1.37
1
3
(
s, 12H). C NMR (126 MHz, CDCl
.4 Hz), 135.25 (t, J = 9.9 Hz), 112.35 (m), 84.88 (s), 52.82 (s), 24.91 (s). F NMR (376
MHz, CDCl ) δ -100.06 (d, J = 6.5). Anal. Calcd for C14 : C, 56.41; H, 5.75.
Found: C, 56.15; H, 6.01.
3
) δ 166.36 (dd, J = 251.3, 12.8 Hz), 165.03 (t, J =
1
9
3
3
2 4
H17BF O
Borylation of 3,5-difluoroanisole. Prepared according to the general procedure with
,5-difluoroanisole (144 mg, 1.0 mmol, 1.0 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (200 mg, 74%).
3
1
13
H NMR (499 MHz, CDCl
3
) δ 6.38 (d, J = 9.5 Hz, 2H), 3.78 (s, 3H), 1.35 (s, 12H). C
NMR (126 MHz, CDCl ) δ 168.19 (dd, J = 249.8, 16.6 Hz), 164.11 (t, J = 14.7 Hz),
3
1
9
9
8
7.92 (m), 83.94 (s), 55.94 (s), 24.94 (s). F NMR (376 MHz, CDCl
3
) δ -99.53 (d, J =
.2). Anal. Calcd for C13 : C, 57.81; H, 6.34. Found: C, 57.82; H, 6.24.
H
2 3
17BF O
General Procedure for one-pot C-H Borylation and Suzuki-Miyaura cross-coupling
of heteroarenes with aryl bromides. Inside a glove box, [Ir(cod)OMe]
2
(2.0 mg, 0.0030
2
(153 mg, 0.600
mmol, 0.0030 equiv), dtbpy (1.6 mg, 0.0060 mmol, 0.0060 equiv), B pin
2
mmol, 0.600 equiv), the heteroarene (1.20 mmol, 1.20 equiv), and THF (2 mL) were
added consecutively to a dry vial with a magnetic stir bar. The vial was sealed and
heated at 80 °C for 18 h. The reaction mixture was cooled to room temperature, and the
volatile materials were removed under vacuum. Pd(dba)
equiv), tri-o-tolylphosphine (6.1 mg, 0.020 mmol, 0.020 equiv), Na
mmol, 4.00 equiv), the aryl halide (1.00 mmol, 1.00 equiv), THF (3 mL) and degassed
O (0.3 mL) were added consecutively to the reaction mixture. The reaction mixture
2
(5.8 mg, 0.010 mmol, 0.010
2
CO (424 mg, 4.00
3
H
2
was sealed and stirred at room temperature for 18 h. The reaction mixture was filtered
through silica gel, washing with EtOAc, and concentrated under vacuum. The reaction
mixture was purified by column chromatography to give the product.
Arylation of indole with 4-bromotoluene. Prepared according to the general procedure
with indole (141 mg, 1.20 mmol, 1.20 equiv) and 4-bromotoluene (171 mg, 1.00 mmol,

S7
1
.00 equiv). The mixture was purified by flash column chromatography (10%
1
EtOAc:90% hexanes) to give the product (174 mg, 84%). H NMR (500 MHz, CDCl
3
) δ
8
7
.30 (s, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 8.1 Hz, 2H), 7.40 (d, J = 7.8 Hz, 1H),
.27 (d, J = 7.8 Hz, 2H), 7.22 (m, 1H), 7.16 (t, J = 7.5 Hz, 1H), 6.82 (s, 1H), 2.43 (s, 3H).
C NMR (126 MHz, CDCl ) δ 138.32, 137.89, 136.95, 129.96, 128.69, 125.32, 122.37,
3
1
3
1
6
20.77, 120.45, 111.10, 102.85, 99.64, 21.51. Anal. Calcd for C15
.32; N, 6.76. Found: C, 86.60; H, 6.29; N, 6.79.
H13N: C, 86.92; H,
Arylation of indole with ethyl 4-bromobenzoate. Prepared according to the general
procedure with indole (141 mg, 1.20 mmol, 1.20 equiv) and ethyl 4-bromobenzoate (229
mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash column chromatography
1
(
15% EtOAc:85% hexanes) to give the product (231 mg, 87%). H NMR (500 MHz,
CDCl
3
) δ 8.51 (s, 1H), 8.04 (s, 1H), 8.00 (s, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 8.4
Hz, 2H), 7.20 (t, J = 2.8 Hz, 1H), 6.92 (s, 1H), 6.58 (s, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.40
1
3
(
1
t, J = 7.1 Hz, 3H). C NMR (126 MHz, CDCl
28.26, 125.55, 122.36, 121.38, 119.07, 116.88, 111.76, 103.27, 102.79, 60.79, 14.61.
Anal. Calcd for C17 : C, 76.48; H, 5.21; N, 5.47. C, 76.10; H, 5.46; N, 5.29.
3
) δ 163.94, 157.04, 146.34, 135.95,
H
15NO
2
Arylation of indole with 2-bromotoluene. Prepared according to the general procedure
with indole (141 mg, 1.20 mmol, 1.20 equiv) and 2-bromotoluene (171 mg, 1.00 mmol,
1
.00 equiv). The mixture was purified by flash column chromatography (10%
1
EtOAc:90% hexanes) to give the product (151 mg, 73%). H NMR (499 MHz, CDCl
3
) δ
8
2
.07 (s, 1H), 7.79 (d, J = 7.7 Hz, 1H), 7.54 (m, 2H), 7.46 (d, J = 8.1 Hz, 1H), 7.41 (m,
H), 7.34 (m, 1H), 7.29 (m, 1H), 6.74 (s, 1H), 2.60 (s, 3H). C NMR (126 MHz, CDCl )
3
1
3
δ 137.79, 136.51, 136.42, 132.96, 131.40, 129.34, 129.20, 128.30, 126.41, 122.39, 120.88,
20.40, 111.16, 103.29, 21.43. Anal. Calcd for C15 13N: C, 86.92; H, 6.32; N, 6.76.
Found: C, 86.76; H, 6.16; N, 6.76.
1
H

S8
Arylation of indole with 3-bromothiophene. Prepared according to the general
procedure with indole (141 mg, 1.20 mmol, 1.20 equiv) and 3-bromothiophene (163 mg,
.00 mmol, 1.00 equiv). The mixture was purified by flash column chromatography
1
1
(
10% EtOAc:90% hexanes) to give the product (148 mg, 74%). H NMR (499 MHz,
CDCl ) δ 8.24 (s, 1H), 7.63 (dd, J = 7.9, 1.0 Hz, 1H), 7.43 (s, 3H), 7.39 (m, 1H), 7.21
ddd, J = 8.2, 7.1, 1.2 Hz, 1H), 7.14 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H), 6.73 (m, 1H). C
NMR (126 MHz, CDCl ) δ 136.65, 134.37, 134.18, 129.33, 126.88, 125.94, 122.51,
20.81, 120.51, 119.31, 110.97, 100.21. Anal. Calcd for C12 NS: C, 72.33; H, 4.55; N,
.03. Found: C, 72.39; H, 4.56; N, 7.03.
3
1
3
(
3
1
7
H
9
Arylation of benzofuran with 2,6-dimethylbromobenzene. Prepared according to the
general procedure with benzofuran (142 mg, 1.20 mmol, 1.20 equiv) and 2,6-
dimethylbromobenzene (185 mg, 1.00 mmol, 1.00 equiv) and the Suzuki coupling step at
5
0 °C. The mixture was purified by flash column chromatography (5% EtOAc:95%
1
3
hexanes) to give the product (159 mg, 72%). H NMR (500 MHz, CDCl ) δ 7.71 (m, 1H),
7
1
3
.61 (m, 1H), 7.36 (m, 3H), 7.23 (m, 2H), 6.75 (s, 1H), 2.36 (s, 6H). C NMR (126
MHz, CDCl
3
) δ 155.14, 155.06, 138.84, 130.91, 129.48, 129.08, 127.88, 124.11, 122.97,
14O: C, 86.45; H, 6.35. Found: C,
1
8
21.09, 111.51, 106.42, 20.93. Anal. Calcd for C16
6.41; H, 6.17.
H
Arylation of indole with 1-Bromo-3,4-(methylenedioxy)benzene. Prepared according
to the general procedure with indole (141 mg, 1.20 mmol, 1.20 equiv) and 1-Bromo-3,4-
(methylenedioxy)benzene (201 mg, 1.00 mmol, 1.00 equiv). The mixture was purified
by flash column chromatography (10% EtOAc:90% hexanes) to give the product (199 mg,

S9
1
8
6
6
1
1
4%). H NMR (499 MHz, Acetone-d6) δ 9.74 (s, 1H), 6.76 (dd, J = 7.8, 1.0 Hz, 1H),
.59 (m, 3H), 6.30 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 6.23 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H),
1
3
.15 (d, J = 8.5 Hz, 1H), 6.01 (m, 1H), 5.27 (s, 2H). C NMR (126 MHz, Acetone) δ
48.63, 147.50, 138.21, 137.55, 129.63, 127.33, 121.69, 120.20, 119.75, 118.99, 111.18,
08.78, 105.84, 101.59, 98.61. Anal. Calcd for C15H11NO : C, 75.94; H, 4.67; N, 5.90.
2
Found: C, 75.68; H, 4.37; N, 5.63.
Arylation of methyl 2-methyl-3-furancarboxylate with ethyl 4-bromobenzoate.
Prepared according to the general procedure with methyl 2-methyl-3-furancarboxylate
(168 mg, 1.20 mmol, 1.20 equiv) and ethyl 4-bromobenzoate (229 mg, 1.00 mmol, 1.00
equiv). The mixture was purified by flash column chromatography (15% EtOAc:85%
1
hexanes) to give the product (280 mg, 97%). H NMR (499 MHz, CDCl
3
) δ 7.97 (d, J =
8
2
1
1
.5 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H), 6.91 (s, 1H), 4.33 (q, J = 7.1 Hz, 2H), 3.79 (s, 3H),
1
3
.59 (s, 3H), 1.35 (t, J = 7.5 Hz 3H). C NMR (126 MHz, CDCl
59.80, 150.84, 133.91, 130.20, 129.31, 123.30, 115.64, 107.77, 61.15, 51.60, 14.52,
4.05. Anal. Calcd for C16 : C, 66.66; H, 5.59. Found: C, 66.28; H, 5.50.
3
) δ 166.26, 164.20,
16 5
H O
Arylation of ethyl 3-furoate with 5-bromoindole. Prepared according to the general
procedure with ethyl 3-furoate (168 mg, 1.20 mmol, 1.20 equiv) and 5-bromoindole (196
mg, 1.00 mmol, 1.00 equiv) and the Suzuki coupling step at 50 °C. The mixture was
purified by flash column chromatography (15% EtOAc:85% hexanes) to give the product
1
(
225 mg, 88%). H NMR (500 MHz, CDCl
3
) δ 8.51 (s, 1H), 8.04 (s, 1H), 7.52 (m, 1H),
7
4
1
1
7
.40 (s, 1H), 7.38 (s, 1H), 7.21 (t, J = 2.8 Hz, 1H), 6.93 (s, 1H), 6.59 (d, J = 3.0 Hz, 1H),
1
3
.36 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H). C NMR (126 MHz, CDCl
3
) δ 163.94,
57.04, 146.34, 135.95, 128.26, 125.55, 122.36, 121.38, 119.07, 116.88, 111.76, 103.27,
02.79, 60.79, 14.61. Anal. Calcd for C15
0.40; H, 5.13; N, 5.42.
3
H13NO : C, 70.58; H, 5.13; N, 5.49. Found: C,

S10
Arylation of ethyl 3-furoate with 4-bromochlorobenzene. Prepared according to the
general procedure with ethyl 3-furoate (168 mg, 1.20 mmol, 1.20 equiv) and 4-
bromochlorobenzene (192 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by
flash column chromatography (10% EtOAc:90% hexanes) to give the product (223 mg,
1
8
7
9%). H NMR (500 MHz, CDCl
3
) δ 8.00 (d, J = 0.8 Hz, 1H), 7.58 (d, J = 8.6 Hz, 2H),
.36 (d, J = 8.6 Hz, 2H), 6.95 (s, 1H), 4.32 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H).
C NMR (126 MHz, CDCl ) δ 163.15, 154.24, 147.10, 134.12, 129.24, 128.55, 125.46,
3
1
3
1
6
21.65, 105.18, 60.85, 14.56. Anal. Calcd for C13
1.94; H, 4.25.
3
H11ClO : C, 62.29; H, 4.42. Found: C,
Arylation of ethyl 3-furoate with 4-bromophenyl pivalate. Prepared according to the
general procedure with ethyl 3-furoate (168 mg, 1.20 mmol, 1.20 equiv) and 4-
bromophenyl pivalate (257 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by
flash column chromatography (10% EtOAc:90% hexanes) to give the product (253 mg,
1
8
8
0%). H NMR (499 MHz, CDCl
3
) δ 8.00 (s, 1H), 7.66 (d, J = 8.6 Hz, 2H), 7.10 (d, J =
1
3
.6 Hz, 2H), 6.94 (s, 1H), 4.32 (q, J = 7.1 Hz, 2H), 1.37 (m, 12H). C NMR (126 MHz,
) δ 177.10, 163.24, 154.68, 151.14, 146.95, 127.65, 125.31, 122.21, 121.58, 104.71,
0.77, 39.33, 27.34, 14.57. Anal. Calcd for C18 : C, 68.34; H, 6.37. Found: C,
7.96; H, 6.41.
CDCl
6
6
3
20 5
H O
Arylation of 2-methylthiophene with 4-bromotoluene. Prepared according to the
general procedure with 2-methylthiophene (118 mg, 1.20 mmol, 1.20 equiv) and 4-
bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (171 mg, 91%).
1
3
H NMR (499 MHz, CDCl ) δ 7.57 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 7.8 Hz, 2H), 7.17 (d,

S11
1
3
J = 3.5 Hz, 1H), 6.82 (s, 1H), 2.60 (s, 3H), 2.46 (s, 3H). C NMR (126 MHz, CDCl
42.50, 139.18, 137.08, 132.33, 129.81, 126.43, 125.75, 122.68, 21.46, 15.73. Anal.
Calcd for C12 12S: C, 76.55; H, 6.42. Found: C, 76.37; H, 6.47.
3
) δ
1
H
Arylation of 2-methylthiophene with 4-bromoanisole. Prepared according to the
general procedure with 2-methylthiophene (118 mg, 1.20 mmol, 1.20 equiv) and 4-
bromoanisole (187 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (172 mg, 84%).
1
3
H NMR (499 MHz, CDCl ) δ 7.54 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 3.5 Hz, 1H), 6.95 (d,
1
3
J = 8.7 Hz, 2H), 6.76 (m, 1H), 3.86 (s, 3H), 2.55 (s, 3H). C NMR (126 MHz, CDCl
59.15, 142.20, 138.69, 127.95, 127.03, 126.35, 122.11, 114.51, 55.57, 15.67. Anal.
Calcd for C12 12OS: C, 70.55; H, 5.92. Found: C, 70.36; H, 6.00.
3
) δ
1
H
Arylation of 2-methylthiophene with 4-bromoacetophenone. Prepared according to
the general procedure with 2-methylthiophene (118 mg, 1.20 mmol, 1.20 equiv) and 4-
bromoacetophenone (199 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (195 mg, 90%).
1
3
H NMR (499 MHz, CDCl ) δ 7.92 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.21 (d,
1
3
J = 3.6 Hz, 1H), 6.75 (d, J = 4.6 Hz, 1H), 2.58 (s, 3H), 2.51 (s, 3H). C NMR (126 MHz,
CDCl ) δ 197.48, 141.73, 140.67, 139.28, 135.46, 129.31, 126.94, 125.25, 124.86, 26.75,
5.79. Anal. Calcd for C13 12OS: C, 72.19; H, 5.59. Found: C, 72.50; H, 5.70.
3
1
H
Arylation of 2-methylthiophene with 1-bromo-4-(methoxymethoxy)benzene.
Prepared according to the general procedure with 2-methylthiophene (118 mg, 1.20 mmol,
1
.20 equiv) and 1-bromo-4-(methoxymethoxy)benzene (217 mg, 1.00 mmol, 1.00 equiv).

S12
The mixture was purified by flash column chromatography (5% EtOAc:95% hexanes) to
1
give the product (197 mg, 84%). H NMR (499 MHz, CDCl
3
) δ 7.59 (d, J = 8.3 Hz, 2H),
7
.39 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 3.5 Hz, 1H), 6.77 (d, J = 3.5, 1H), 4.77 (s, 2H), 4.64
1
3
(s, 2H), 3.47 (s, 3H), 2.55 (s, 3H).
C NMR (126 MHz, CDCl
36.91, 134.45, 128.69, 126.51, 125.75, 123.22, 95.92, 69.11, 55.62, 15.72. Anal. Calcd
S: C, 67.71; H, 6.49. Found: C, 68.01; H, 6.53.
3
) δ 141.95, 139.76,
1
16 2
for C14H O
Arylation of 2-chlorothiophene with 4-bromotoluene. Prepared according to the
general procedure with 2-chlorothiophene (143 mg, 1.20 mmol, 1.20 equiv) and 4-
bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (192 mg, 92%).
1
3
H NMR (500 MHz, CDCl ) δ 7.44 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.05 (d,
1
3
J = 3.9 Hz, 1H), 6.91 (d, J = 3.8 Hz, 1H), 2.41 (s, 3H). C NMR (126 MHz, CDCl
43.41, 138.04, 131.20, 129.95, 128.76, 127.31, 125.71, 121.96, 21.48. Anal. Calcd for
ClS: C, 63.30; H, 4.35. Found: C, 63.35; H, 4.44.
3
) δ
1
11 9
C H
Arylation of 2-chlorothiophene with 4-bromobenzonitrile. Prepared according to the
general procedure with 2-chlorothiophene (143 mg, 1.20 mmol, 1.20 equiv) and 4-
bromobenzonitrile (182 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (10% EtOAc:90% hexanes) to give the product (187 mg, 85%).
1
H NMR (499 MHz, CDCl
3
) δ 7.63 (m, 2H), 7.56 (m, 2H), 7.18 (d, J = 3.9 Hz, 1H), 6.93
d, J = 4.0 Hz, 1H). C NMR (126 MHz, CDCl ) δ 140.65, 137.95, 133.05, 131.97,
27.94, 125.84, 124.68, 118.89, 111.14. Anal. Calcd for C11 ClNS: C, 60.14; H, 2.75;
N, 6.38. Found: C, 59.97; H, 2.64; N, 6.14.
1
3
(
1
3
H
6

S13
Arylation of methyl thiophene-3-carboxylate with 4-bromobenzaldehyde. Prepared
according to the general procedure with methyl thiophene-3-carboxylate (171 mg, 1.20
mmol, 1.20 equiv) and 4-bromobenzaldehyde (185 mg, 1.00 mmol, 1.00 equiv). The
mixture was purified by flash column chromatography (10% EtOAc:90% hexanes) to
1
give the product (204 mg, 83%). H NMR (500 MHz, CDCl
1
3
) δ 9.94 (s, 1H), 8.04 (s,
1
3
H), 7.82 (d, J = 8.3 Hz, 2H), 7.76 (s, 1H), 7.67 (d, J = 8.2 Hz, 2H), 3.84 (s, 3H).
C
NMR (126 MHz, CDCl
3
) δ 191.49, 162.96, 143.41, 139.11, 135.74, 134.75, 133.46,
S: C, 63.40; H, 4.09. Found: C,
1
6
30.67, 126.20, 125.44, 52.22. Anal. Calcd for C13
3.11; H, 3.98.
10 3
H O
Arylation of methyl thiophene-3-carboxylate with 4-bromotoluene.
Prepared
according to the general procedure with methyl thiophene-3-carboxylate (171 mg, 1.20
mmol, 1.20 equiv) and 4-bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (221 mg, 95%). H NMR (499 MHz, CDCl
3
) δ 8.00 (s, 1H), 7.69 (s, 1H), 7.50 (d,
1
3
J = 8.1 Hz, 2H), 7.20 (d, J = 7.8 Hz, 2H), 3.90 (s, 3H), 2.38 (s, 3H). C NMR (126 MHz,
CDCl ) δ 163.41, 145.46, 138.30, 134.34, 131.46, 130.96, 129.91, 126.03, 123.03, 52.03,
1.42. Anal. Calcd for C13 S: C, 67.22; H, 5.21. Found: C, 67.53; H, 5.23.
3
2
12 2
H O
Arylation of 2-methylthiophene with 2-bromotoluene. Prepared according to the
general procedure with 2-methylthiophene (118 mg, 1.20 mmol, 1.20 equiv) and 2-
bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (181 mg, 96%).
1
H NMR (499 MHz, CDCl
d, J = 3.3 Hz, 1H), 2.63 (s, 3H), 2.56 (s, 3H). C NMR (126 MHz, CDCl
39.91, 136.21, 134.86, 131.06, 130.60, 127.80, 126.60, 126.21, 125.64, 21.57, 15.58.
Anal. Calcd for C12 12S: C, 76.55; H, 6.42. Found: C, 76.87; H, 6.43.
3
) δ 7.51 (m, 1H), 7.33 (m, 3H), 6.97 (d, J = 3.4 Hz, 1H), 6.85
1
3
(
1
3
) δ 141.18,
H

S14
Arylation of 2-acetylthiophene with 3-bromonitrobenzene. Prepared according to the
general procedure with 2-acetylthiophene (152 mg, 1.20 mmol, 1.20 equiv) and 3-
bromonitrobenzene (202 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (205 mg, 83%).
1
3
H NMR (499 MHz, CDCl ) δ 8.43 (s, 1H), 8.16 (m, 1H), 7.92 (m, 1H), 7.68 (d, J = 3.9
1
3
Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 3.9 Hz, 1H), 2.57 (s, 3H). C NMR (126
MHz, CDCl ) δ 190.81, 149.33, 148.91, 144.83, 135.17, 133.67, 132.12, 130.48, 125.75,
23.53, 121.00, 25.04. Anal. Calcd for C12 NO S: C, 58.29; H, 3.67; N, 5.66. Found:
C, 58.37; H, 3.83; N, 5.43.
3
1
H
9
3
Arylation of 2-methylthiophene with 5-bromopyrimidine. Prepared according to the
general procedure with 2-methylthiophene (118 mg, 1.20 mmol, 1.20 equiv) and 5-
bromopyrimidine (159 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (15% EtOAc:85% hexanes) to give the product (139 mg, 79%).
1
3
H NMR (500 MHz, CDCl ) δ 9.02 (s, 1H), 8.83 (d, J = 2.2 Hz, 2H), 7.17 (t, J = 2.7 Hz,
1
3
1
1
1
H), 6.76 (s, 1H), 2.50 (s, 3H). C NMR (126 MHz, CDCl
3
) δ 156.95, 153.11, 142.56,
9 8 2
33.91, 129.05, 127.03, 125.42, 15.69. Anal. Calcd for C H N S: C, 61.34; H, 4.58; N,
5.90. Found: C, 61.24; H, 4.55; N, 15.56.
Arylation of methyl pyrrole-2-carboxylate with 4-fluorobromobenzene. Prepared
according to the general procedure with methyl pyrrole-2-carboxylate (150 mg, 1.20
mmol, 1.20 equiv) and 4-fluorobromobenzene (175 mg, 1.00 mmol, 1.00 equiv). The
mixture was purified by flash column chromatography (15% EtOAc:85% hexanes) to
1
give the product (199 mg, 91%). H NMR (500 MHz, CDCl
3
) δ 9.87 (s, 1H), 7.59 (dd, J

S15
=
8.8, 5.2 Hz, 2H), 7.09 (t, J = 8.6 Hz, 2H), 6.96 (dd, J = 3.8, 2.4 Hz, 1H), 6.48 (dd, J =
1
3
3
1
.8, 2.7 Hz, 1H), 3.87 (s, 3H). C NMR (126 MHz, CDCl
62.14 (s), 136.56 (s), 128.01 (d, J = 3.3 Hz), 126.96 (d, J = 8.0 Hz), 123.25 (s), 117.26
3
) δ 162.58 (d, J = 248.5 Hz),
1
9
(s), 116.16 (d, J = 21.8 Hz), 108.17 (s), 51.88 (s). F NMR (376 MHz, CDCl
3
) δ -114.20
(
s). Anal. Calcd for C12 : C, 65.75; H, 4.60; N, 6.39. Found: C, 65.49; H, 4.40;
H
10FNO
2
N, 6.17.
Arylation of 2-acetylpyrrole with 4-fluorobromobenzene. Prepared according to the
general procedure with 2-acetylpyrrole (131 mg, 1.20 mmol, 1.20 equiv) and 4-
fluorobromobenzene (175 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by
flash column chromatography (15% EtOAc:85% hexanes) to give the product (152 mg,
1
7
2
1
1
5%). H NMR (500 MHz, CDCl
3
) δ 10.47 (s, 1H), 7.69 (d, J = 5.4 Hz, 2H), 7.10 (m,
1
3
H), 6.97 (d, J = 2.5 Hz, 1H), 6.50 (m, 1H), 2.46 (s, 3H). C NMR (126 MHz, CDCl
88.10 (s), 162.81 (d, J = 248.2 Hz), 138.33 (s), 132.94 (s), 127.40 (d, J = 8.1 Hz),
19.05 (s), 116.12 (d, J = 21.9 Hz), 110.82 (s), 108.41 (s), 25.56 (s). F NMR (376 MHz,
) δ -113.57 (s). Anal. Calcd for C12 10FNO: C, 70.93; H, 4.96; N, 6.89. Found: C,
0.58; H, 4.87; N, 6.83.
3
) δ
1
9
CDCl
7
3
H
Arylation of 2,3-dimethylfuran with 4-bromoacetophenone. Prepared according to
the general procedure with 2,3-dimethylfuran (116 mg, 1.20 mmol, 1.20 equiv) and 4-
bromoacetophenone (199 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (10% EtOAc:90% hexanes) to give the product (204 mg, 95%).
1
3
H NMR (499 MHz, CDCl ) δ 7.89 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H), 6.56 (s,
1
3
1
1
H), 2.55 (s, 3H), 2.26 (s, 3H), 1.96 (s, 3H). C NMR (126 MHz, CDCl
49.95, 149.28, 135.46, 134.95, 129.14, 122.96, 117.10, 111.37, 26.62, 11.79, 10.09.
: C, 78.48; H, 6.59. Found: C, 78.48; H, 6.63.
3
) δ 197.62,
14 2
Anal. Calcd for C14H O
General Procedure for one-pot C-H Borylation and Suzuki-Miyaura cross-coupling
of ortho-fluoroarenes with aryl bromides. Inside a glove box, [Ir(cod)OMe] (2.0 mg,
.0030 mmol, 0.0030 equiv), dtbpy (1.6 mg, 0.0060 mmol, 0.0060 equiv), B pin (183
2
0
2
2
mg, 0.720 mmol, 0.720 equiv), the heteroarene (1.20 mmol, 1.20 equiv), and THF (2 mL)
were added consecutively to a dry vial with a magnetic stir bar. The vial was sealed and

S16
heated at 80 °C for 18 h. The reaction mixture was cooled to room temperature, and the
volatile materials were removed under vacuum. Pd(dba)
equiv), tri-o-tolylphosphine (6.1 mg, 0.020 mmol, 0.02 equiv), Na
mmol, 4.00 equiv), the aryl halide (1.00 mmol, 1.00 equiv), THF (3 mL) and degassed
O (0.3 mL) were added consecutively to the reaction mixture. The reaction mixture
2
(5.8 mg, 0.01 mmol, 0.01
2
CO (424 mg, 4.00
3
H
2
was sealed and stirred at room temperature for 18 h. The reaction mixture was filtered
through silica gel, washing with EtOAc, and concentrated under vacuum. The reaction
mixture was purified by column chromatography to give the product.
Arylation of 2-chloro-4-fluorotoluene with 4-chlorobromobenzene.
according to the general procedure with 2-chloro-4-fluorotoluene (174 mg, 1.20 mmol,
.20 equiv) and 4-chlorobromobenzene (192 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (5% EtOAc:95% hexanes) to give the
Prepared
1
1
product (245 mg, 96%). H NMR (499 MHz, CDCl
1
3
) δ 7.44 (m, 4H), 7.27 (d, J = 8.2 Hz,
H), 7.20 (d, J = 10.1 Hz, 1H), 2.40 (s, 3H). C NMR (126 MHz, CDCl ) δ 157.77 (d, J
249.2 Hz), 134.22, 134.16, 133.59 (d, J = 1.7 Hz), 132.48 (d, J = 3.9 Hz), 132.17 (d, J
3.8 Hz), 130.35 (d, J = 3.0 Hz), 128.97, 126.50 (d, J = 13.2 Hz), 117.22 (d, J = 26.2
1
3
3
=
=
1
9
Hz), 19.57. F NMR (376 MHz, CDCl
H, 3.56. Found: C, 61.01; H, 3.54.
3 9 2
) δ -120.64. Anal. Calcd for C13H Cl F: C, 61.20;
Arylation of 2-chloro-4-fluorotoluene with 4-bromoacetophenone.
according to the general procedure with 2-chloro-4-fluorotoluene (174 mg, 1.20 mmol,
.20 equiv) and 4-bromoacetophenone (199 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
Prepared
1
1
product (222 mg, 85%). H NMR (500 MHz, CDCl
3
) δ 7.98 (d, J = 8.3 Hz, 2H), 7.57 (d,
J = 8.4 Hz, 2H), 7.27 (d, J = 8.1 Hz, 1H), 7.15 (d, J = 10.1 Hz, 1H), 2.60 (s, 3H), 2.35 (s,
1
3
3
H). C NMR (126 MHz, CDCl
3
) δ 197.74, 157.80 (d, J = 249.9 Hz), 139.79 (d, J = 1.7
Hz), 136.40, 134.76 (d, J = 10.2 Hz), 132.58 (d, J = 3.8 Hz), 132.22 (d, J = 3.6 Hz),
1
1
4
29.20 (d, J = 3.2 Hz), 128.72 , 126.45 (d, J = 13.1 Hz), 117.26 (d, J = 26.1 Hz), 26.85,
1
9
9.53. F NMR (376 MHz, CDCl
.60. Found: C, 68.61; H, 4.79.
3
) δ -120.24. Anal. Calcd for C15H12ClFO: C, 68.58; H,

S17
Arylation of 2-chloro-4-fluorotoluene with ethyl 4-bromobenzoate.
Prepared
according to the general procedure with 2-chloro-4-fluorotoluene (174 mg, 1.20 mmol,
.20 equiv) and ethyl 4-bromobenzoate (229 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
1
product (237 mg, 81%). H NMR (499 MHz, CDCl
3
) δ 8.10 (d, J = 8.4 Hz, 2H), 7.56 (dd,
J = 8.4, 1.7 Hz, 2H), 7.28 (d, J = 8.2 Hz, 1H), 7.17 (d, J = 10.1 Hz, 1H), 4.41 (q, J = 7.1
1
3
Hz, 2H), 2.37 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H). C NMR (126 MHz, CDCl
3
) δ 166.44,
57.84 (d, J = 249.8 Hz), 139.56 (d, J = 1.7 Hz), 134.65 (d, J = 10.2 Hz), 132.50 (d, J =
.9 Hz), 132.27 (d, J = 3.7 Hz), 130.02, 129.91, 128.97 (d, J = 3.1 Hz), 126.66 (d, J =
1
3
1
1
1
9
3.0 Hz), 117.24 (d, J = 26.1 Hz), 61.25, 19.49, 14.56. F NMR (376 MHz, CDCl
20.26. Anal. Calcd for C16 : C, 65.65; H, 4.82. Found: C, 65.51; H, 4.97.
3
) δ -
H
14ClFO
2
Arylation of 2-chloro-4-fluorotoluene with 4-bromoveratrole. Prepared according to
the general procedure with 2-chloro-4-fluorotoluene (174 mg, 1.20 mmol, 1.20 equiv)
and 4-bromoveratrole (217 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by
flash column chromatography (5% EtOAc:95% hexanes) to give the product (278 mg,
1
9
1
3
1
1
1
9%). H NMR (499 MHz, CDCl
3
) δ 7.26 (dd, J = 8.2, 0.8 Hz, 1H), 7.14 (d, J = 10.2 Hz,
H), 7.07 (t, J = 1.8 Hz, 1H), 7.05 (t, J = 1.5 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 3.92 (s,
H), 3.91 (s, 3H), 2.36 (s, 3H). C NMR (126 MHz, CDCl ) δ 157.79 (d, J = 247.9 Hz),
3
49.08 (d, J = 7.5 Hz), 133.22 (d, J = 10.1 Hz), 132.19 (d, J = 3.8 Hz), 132.15, 127.81,
27.50 (d, J = 13.2 Hz), 121.58 (d, J = 2.9 Hz), 117.14, 116.92, 112.33 (d, J = 3.2 Hz),
1
3
1
9
11.38, 56.16, 56.11, 19.52. F NMR (376 MHz, CDCl
: C, 64.18; H, 5.03. Found: C, 64.18; H, 5.16.
3
) δ -120.64. Anal. Calcd for
15 2
C H14ClFO

S18
Arylation of 2,4-dichlorofluorobenzene with ethyl 4-bromobenzoate. Prepared
according to the general procedure with 2,4-dichlorofluorobenzene (198 mg, 1.20 mmol,
1
.20 equiv) and 4-bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was
purified by flash column chromatography (5% EtOAc:95% hexanes) to give the product
1
(
243 mg, 95%). H NMR (499 MHz, CDCl
3
) δ 7.43 (dd, J = 8.1, 1.8 Hz, 2H), 7.39 (dd, J
=
5.9, 2.6 Hz, 1H), 7.34 (dd, J = 6.0, 2.7 Hz, 1H), 7.31 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H).
1
3
C NMR (126 MHz, CDCl
3
) δ 154.29 (d, J = 249.9 Hz), 138.95, 131.98 (d, J = 15.1 Hz),
1
1
31.10, 129.67, 129.52 (d, J = 4.5 Hz), 129.02 (d, J = 3.1 Hz), 128.97 (d, J = 3.2 Hz),
1
9
28.90, 122.95 (d, J = 20.5 Hz), 21.49. F NMR (376 MHz, CDCl
Cl F: C, 61.20; H, 3.56. Found: C, 60.80; H, 3.44.
3
) δ -122.63. Anal.
Calcd for C13
H
9
2
Arylation of indole with 4-bromotoluene on 5 mmol scale. Inside a glove box,
[
Ir(cod)OMe]
2
(0.9 mg, 0.001 mmol, 0.0003 equiv), dtbpy (0.8 mg, 0.002 mmol, 0.0005
2
(667 mg, 2.63 mmol, 0.525 equiv), indole (615 mg, 5.25 mmol, 1.05
equiv), B pin
2
equiv), and THF (10 mL) were added to a dry vial with a magnetic stir bar. The vial was
sealed and heated at 80 °C for 18 h. The reaction mixture was cooled to room
temperature and the volatile materials were removed under vacuum. Pd(dba)
.025 mmol, 0.0050 equiv), tri-o-tolylphosphine (15.2 mg, 0.050 mmol, 0.010 equiv), 4-
bromotoluene (855 mg, 5.00 mmol, 1.00 equiv), Na CO (2.12 mg, 20.0 mmol, 20.0
equiv), THF (15 mL) and degassed H O (1.5 mL) were added to the reaction mixture.
2
(14.4 mg,
0
2
3
2
The reaction mixture was sealed and stirred at room temperature for 18 h. The reaction
mixture was filtered through silica gel washing with EtOAc, and concentrated under
vacuum. The reaction mixture was purified by column chromatography (15%
EtOAc:85% hexanes) to give the product (859 mg, 83%). Spectral data matched that
obtained for the reaction conducted on 1 mmol scale.
General Procedure for one-pot C-H Borylation and Suzuki-Miyaura cross-coupling
of heteroarenes with aryl chlorides. Inside a glove box, [Ir(cod)OMe]
2
(2.0 mg, 0.003
2
(153 mg, 0.600
mmol, 0.003 equiv), dtbpy (1.6 mg, 0.0060 mmol, 0.0060 equiv), B pin
2
mmol, 0.600 equiv), the heteroarene (1.20 mmol, 1.20 equiv), and THF (2 mL) were
added to a dry vial with a magnetic stir bar. The vial was sealed and heated at 80 °C for

S19
1
8 h. The reaction mixture was cooled to room temperature and the volatile materials
were removed under vacuum. Pd(dba)
0
4
2
(5.8 mg, 0.01 mmol, 0.01 equiv), Q-phos (7.1 mg,
.010 mmol, 0.010 equiv), the aryl chloride (1.00 mmol, 1.00 equiv), K PO (849 mg,
.00 mmol, 4.00 equiv), 1,4-dioxane (3 mL) and degassed H O (0.3 mL) were added to
3
4
2
the reaction mixture. The reaction mixture was sealed and stirred at 40 °C for 18 h. The
reaction mixture was filtered through silica gel washing with EtOAc, and concentrated
under vacuum. The reaction mixture was purified by column chromatography to give the
product.
Arylation of 2-methylthiophene with 4-chloronitrobenzene. Prepared according to the
general procedure with 2-methylthiophene (152 mg, 1.20 mmol, 1.20 equiv) and 4-
chloronitrobenzene (158 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (10% EtOAc:90% hexanes) to give the product (178 mg, 79%).
1
3
H NMR (499 MHz, CDCl ) δ 8.17 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.27 (d,
1
3
J = 3.7 Hz, 1H), 6.79 (s, 1H), 2.54 (s, 3H). C NMR (126 MHz, CDCl
43.24, 141.07, 139.32, 127.29, 126.04, 125.53, 124.57, 15.81. Anal. Calcd for
NO S: C, 60.26; H, 4.14; N, 6.39. Found: C, 60.35; H, 4.07; N, 6.52.
3
) δ 146.39,
1
C
11
H
9
2
Arylation of methyl 2-furoate with 4-chlorobenzonitrile. Prepared according to the
general procedure with methyl 2-furoate (151 mg, 1.20 mmol, 1.20 equiv) and 4-
chlorobenzonitrile (138 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (15% EtOAc:85% hexanes) to give the product (218 mg, 96%).
1
3
H NMR (500 MHz, CDCl ) δ 7.85 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.26 (d,
1
3
J = 3.6 Hz, 1H), 6.88 (d, J = 3.7 Hz, 1H), 3.92 (s, 3H). C NMR (126 MHz, CDCl
59.07, 155.25, 145.08, 133.47, 132.89, 125.28, 120.08, 118.74, 112.23, 109.73, 52.34.
Anal. Calcd for C13 NO : C, 68.72; H, 3.99; N, 6.16. Found: C, 68.56; H, 3.87; N, 6.46.
3
) δ
1
H
9
3

S20
Arylation of 2-acetylthiophene with 4-chlorobenzaldehyde. Prepared according to the
general procedure with 2-acetylthiophene (152 mg, 1.20 mmol, 1.20 equiv) and 4-
chlorobenzaldehyde (141 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (10% EtOAc:90% hexanes) to give the product (210 mg, 91%).
1
H NMR (500 MHz, CDCl
H), 7.66 (d, J = 3.9 Hz, 1H), 7.42 (d, J = 3.8 Hz, 1H), 2.55 (s, 3H). C NMR (126 MHz,
CDCl ) δ 191.57, 190.84, 150.60, 144.90, 138.99, 136.34, 133.68, 130.71, 126.80, 125.88,
5.04. Anal. Calcd for C13 S: C, 67.80; H, 4.38. Found: C, 67.86; H, 4.38.
3
) δ 9.99 (s, 1H), 7.90 (d, J = 7.7 Hz, 2H), 7.76 (d, J = 7.8 Hz,
1
3
2
3
2
10 2
H O
Arylation of methyl 2-methyl-3-furancarboxylate with 4-chloroanisole. Prepared
according to the general procedure with methyl 2-methyl-3-furancarboxylate (168 mg,
1
.20 mmol, 1.20 equiv) and 4-chloroanisole (143 mg, 1.00 mmol, 1.00 equiv). The
mixture was purified by flash column chromatography (10% EtOAc:90% hexanes) to
1
give the product (133 mg, 54%). H NMR (499 MHz, CDCl
3
) δ 7.57 (s, 2H), 6.91 (s,
H), 6.74 (s, 2H), 3.85 (s, 3H), 3.82 (s, 3H), 2.64 (s, 3H). C NMR (126 MHz, CDCl ) δ
64.78, 159.49, 158.32, 152.08, 125.34, 123.29, 115.21, 114.39, 103.96, 55.51, 51.54,
4.04. Anal. Calcd for C14 : C, 68.28; H, 5.73. Found: C, 68.64; H, 5.80.
1
3
1
1
1
3
14 4
H O
Arylation of methyl 2-methyl-3-furancarboxylate with 3-chlorotoluene. Prepared
according to the general procedure with methyl 2-methyl-3-furancarboxylate (168 mg,
1
.20 mmol, 1.20 equiv) and 3-chlorotoluene (127 mg, 1.00 mmol, 1.00 equiv). The
mixture was purified by flash column chromatography (10% EtOAc:90% hexanes) to
1
give the product (133 mg, 58%). H NMR (500 MHz, CDCl
3
) δ 7.46 (s, 1H), 7.44 (d, J =
8
2
.1 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 7.5 Hz, 1H), 6.86 (s, 1H), 3.85 (s, 3H),
1
3
.65 (s, 3H), 2.38 (s, 3H).
3
C NMR (126 MHz, CDCl ) δ 164.71, 158.85, 152.15,

S21
1
38.56, 130.15, 128.85, 128.69, 124.47, 121.04, 115.28, 105.50, 51.58, 21.69, 14.09.
14 3
Anal. Calcd for C14H O : C, 73.03; H, 6.13. Found: C, 72.79; H, 6.13.
Arylation of methyl 2-methyl-3-furancarboxylate with 2-chlorobenzonitrile.
Prepared according to the general procedure with methyl 2-methyl-3-furancarboxylate
(168 mg, 1.20 mmol, 1.20 equiv) and 2-chlorobenzonitrile (138 mg, 1.00 mmol, 1.00
equiv). The mixture was purified by flash column chromatography (20% EtOAc:80%
1
hexanes) to give the product (193 mg, 80%). H NMR (500 MHz, CDCl
3
) δ 7.79 (d, J =
8
.1 Hz, 1H), 7.65 (m, 1H), 7.57 (td, J = 7.8, 1.4 Hz, 1H), 7.43 (s, 1H), 7.30 (m, 1H), 3.82
1
3
(
s, 3H), 2.64 (s, 3H). C NMR (126 MHz, CDCl
33.15, 132.45, 127.64, 125.92, 118.80, 115.85, 110.95, 106.95, 51.71, 14.01. Anal.
Calcd for C14 : C, 69.70; H, 4.60; N, 5.81. Found: C, 69.46; H, 4.47; N, 5.74.
3
) δ 164.08, 160.22, 147.70, 134.40,
1
H11NO
3
Arylation of indole with 2-fluorochlorobenzene. Prepared according to the general
procedure with indole (141 mg, 1.20 mmol, 1.20 equiv) and 2-fluorochlorobenzene (131
mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash column chromatography
1
(
15% EtOAc:85% hexanes) to give the product (127 mg, 60%). H NMR (499 MHz,
CDCl
3
8.1 Hz, 1H), 7.27 (m, 5H), 7.03 (d, J = 2.1 Hz, 1H). C NMR (126 MHz, CDCl ) δ
3
) δ 8.90 (s, 1H), 7.82 (dd, J = 8.8, 6.9 Hz, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.47 (d, J
1
3
=
1
8
1
59.60 (d, J = 246.4 Hz), 136.93 (d, J = 1.6 Hz), 132.89 (d, J = 2.4 Hz), 129.10 (d, J =
.9 Hz), 128.49 (s), 128.25 (d, J = 4.0 Hz), 125.09 (d, J = 3.1 Hz), 122.99 (s), 120.99 (s),
1
9
20.55 (s), 120.24 (s), 116.80 (d, J = 23.0 Hz), 111.36 (s), 101.97 (d, J = 3.2 Hz). F
) δ -117.86 (s). Anal. Calcd for C14 10FN: C, 79.60; H, 4.77; N,
.63. Found: C, 79.22; H, 4.72; N, 6.42.
NMR (376 MHz, CDCl
6
3
H

S22
Arylation of 2,3-dimethylfuran with methyl 4-chlorobenzoate. Prepared according to
the general procedure with 2,3-dimethylfuran (116 mg, 1.20 mmol, 1.20 equiv) and
methyl 4-chlorobenzoate (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by
flash column chromatography (10% EtOAc:90% hexanes) to give the product (184 mg,
1
8
6
1
1
0%). H NMR (500 MHz, CDCl
3
) δ 7.99 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H),
1
3
.55 (s, 1H), 3.89 (s, 3H), 2.27 (s, 3H), 1.97 (s, 3H). C NMR (126 MHz, CDCl
67.16, 150.04, 149.05, 135.35, 130.25, 127.83, 122.85, 116.98, 111.06, 52.20, 11.77,
0.10. Anal. Calcd for C14 : C, 73.03; H, 6.13. Found: C, 72.93; H, 6.28.
3
) δ
14 3
H O
General Procedure for one-pot C-H Borylation and Suzuki-Miyaura cross-coupling
of 3,5-difluoroarenes with aryl bromides. Inside a glove box, [Ir(cod)OMe]
2
(2.0 mg,
0
0
.003 mmol, 0.003 equiv), dtbpy (1.6 mg, 0.0060 mmol, 0.0060 equiv), B pin (183 mg,
.720 mmol, 0.720 equiv), the arene (1.20 mmol, 1.20 equiv), and THF (2 mL) were
2 2
added consecutively to a dry vial with a magnetic stir bar. The vial was sealed and
heated at 80 °C for 18 h. The reaction mixture was cooled to room temperature and the
volatile materials were removed under vacuum. Pd(dba)
equiv), Q-phos (7.1 mg, 0.010 mmol, 0.010 equiv), the aryl bromide (1.00 mmol, 1.00
equiv), K PO (849 mg, 4.00 mmol, 4.00 equiv), 1,4-dioxane (3 mL) and degassed H
0.3 mL) were added consecutively to the reaction mixture. The reaction mixture was
2
(5.8 mg, 0.010 mmol, 0.010
3
4
2
O
(
sealed and stirred at 50 °C for 18 h. The reaction mixture was filtered through silica gel
washing with EtOAc, and concentrated under vacuum. The reaction mixture was purified
by column chromatography to give the product.
Arylation of 3,5-difluoroanisole with 4-bromotoluene. Prepared according to the
general procedure with 3,5-difluoroanisole (173 mg, 1.20 mmol, 1.20 equiv) and 4-
bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (180 mg, 77%).
1
3
H NMR (500 MHz, CDCl ) δ 7.39 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 7.7 Hz, 2H), 6.59 (d,
1
3
J = 9.3 Hz, 2H), 3.84 (s, 3H), 2.45 (s, 3H). C NMR (126 MHz, CDCl
3
) δ 160.94 (dd, J
=
246.96 Hz, 10.46 Hz), 160.094 (t, J = 14.24 Hz), 137.85 (s), 130.45 (s), 129.24 (s),
1
9
1
26.57 (s), 111.21 (t, J = 19.6 Hz), 98.39 (m), 55.96 (s), 21.50 (s). F NMR (376 MHz,
CDCl ) δ -114.24 (s). Anal. Calcd for C14 O: C, 71.79; H, 5.16. Found: C, 71.87; H,
.24.
3
12 2
H F
5

S23
Arylation of 3,5-difluoroanisole with 4-bromoanisole. Prepared according to the
general procedure with 3,5-difluoroanisole (173 mg, 1.20 mmol, 1.20 equiv) and 4-
bromoanisole (187 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (185 mg, 74%).
1
3
H NMR (500 MHz, CDCl ) δ 7.40 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 6.56 (d,
1
3
J = 9.5 Hz, 2H), 3.86 (s, 3H), 3.82 (s, 3H). C NMR (126 MHz, CDCl
3
) δ 160.91 (dd, J
=
245.70 Hz, 10.46 Hz), 159.901 (t, J = 14.24 Hz), 159.42 (s), 131.70 (s), 121.71 (s),
1
9
1
14.00 (s), 110.88 (t, J = 19.4 Hz), 98.37 (m), 55.95 (s), 55.45 (s). F NMR (376 MHz,
CDCl ) δ -114.35 (s). Anal. Calcd for C14 : C, 67.20; H, 4.83. Found: C, 67.52; H,
.66.
3
12 2 2
H F O
4
Arylation of 3,5-difluoroanisole with 2-bromotoluene. Prepared according to the
general procedure with 3,5-difluoroanisole (173 mg, 1.20 mmol, 1.20 equiv) and 2-
bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (5% EtOAc:95% hexanes) to give the product (164 mg, 70%).
1
H NMR (500 MHz, CDCl3) δ 7.34 (s, 2H), 7.28 (m, 3H), 6.59 (d, J = 9.1 Hz, 1H), 3.85
1
3
(s, 3H), 2.23 (s, 3H). C NMR (126 MHz, CDCl
3
) δ 160.87 (dd, J = 245.83, 10.96),
1
60.55 (t, J = 13.8 Hz), 137.96 (s), 131.27 (s), 130.29 (s), 129.17 (s), 128.66 (s), 125.79
1
9
(s), 110.63 (t, J = 22.1 Hz), 98.13 (m), 56.00 (s), 20.03 (s). F NMR (376 MHz, CDCl
3
)
δ -112.03 (s). Anal. Calcd for C14 O: C, 71.78; H, 5.16. Found: C, 72.00; H, 5.00.
15 2
H F
Arylation of methyl 3,5-difluorobenzoate with ethyl 4-bromobenzoate. Prepared
according to the general procedure with methyl 3,5-difluorobenzoate (207 mg, 1.20 mmol,
1
.20 equiv) and ethyl 4-bromobenzoate (229 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
3
product (269 mg, 84%). H NMR (500 MHz, CDCl ) δ 8.11 (d, J = 8.3 Hz, 2H), 7.63 (d,

S24
J = 7.5 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 4.38 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 1.38 (t, J
1
3
=
7.1 Hz, 3H). C NMR (126 MHz, CDCl
3
) δ 166.21 (s), 164.81 (t, J = 3.2 Hz), 159.79
(
(
dd, J = 250.8, 6.8 Hz), 132.92 (s), 131.97 (t, J = 9.6 Hz), 130.95 (s), 130.41 (s), 129.68
1
9
s), 122.14 (t, J = 18.5 Hz), 113.26 (m), 61.36 (s), 52.91 (s), 14.51 (s). F NMR (376
) δ -113.08 (s). Anal. Calcd for C17 : C, 63.75; H, 4.41. Found: C,
3.86; H, 4.37.
MHz, CDCl
6
3
14 2 4
H F O
Arylation of 3,5-difluoropropiophenone with 3-bromoanisole. Prepared according to
the general procedure with 3,5-difluoropropiophenone (204 mg, 1.20 mmol, 1.20 equiv)
and 3-bromoanisole (187 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by flash
column chromatography (10% EtOAc:90% hexanes) to give the product (199 mg, 72%).
1
H NMR (500 MHz, CDCl
3
) δ 7.57 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 8.0 Hz, 1H), 7.06 (m,
1
H), 7.02 (d, J = 1.3 Hz, 1H), 6.98 (m, 1H), 3.83 (s, 3H), 2.97 (q, J = 7.2 Hz, 2H), 1.24 (t,
1
3
J = 7.2 Hz, 3H). C NMR (126 MHz, CDCl
3
) δ 198.07 (s), 160.23 (dd, J = 245.70 Hz,
6
1
.80 Hz), 159.68 (s), 137.80 (t, J = 7.8 Hz), 129.63 (s), 123.05 (s), 122.90 (s), 122.72 (s),
1
9
16.03 (s), 114.67 (s), 111.51 (m), 55.51 (s), 32.13 (s), 8.23 (s). F NMR (376 MHz,
) δ -112.67 (s). Anal. Calcd for C16 : C, 69.56; H, 5.11. Found: C, 69.59; H,
CDCl
.08.
3
14 2 2
H F O
5
Arylation of 3,5-difluoropropiophenone with 4-bromoveratrole. Prepared according
to the general procedure with 3,5-difluoropropiophenone (204 mg, 1.20 mmol, 1.20 equiv)
and 4-bromoveratrole (217 mg, 1.00 mmol, 1.00 equiv). The mixture was purified by
flash column chromatography (10% EtOAc:90% hexanes) to give the product (187 mg,
1
6
6
7
1
(
(
1%). H NMR (499 MHz, CDCl
3
) δ 7.53 (d, J = 7.7 Hz, 2H), 7.05 (d, J = 8.1 Hz, 1H),
.99 (s, 1H), 6.95 (d, J = 8.3 Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H), 2.94 (m, 2H), 1.22 (t, J =
.2 Hz, 3H). C NMR (126 MHz, CDCl
49.78 (s), 148.97 (s), 137.25 (t, J = 7.8 Hz), 123.31 (s), 122.84 (t, J = 18.6 Hz), 120.70
s), 113.54 (s), 111.50 (m), 111.21 (s), 56.18 (s), 56.08 (s), 32.06 (s), 8.23 (s). F NMR
376 MHz, CDCl ) δ -113.05 (s). Anal. Calcd for C20 : C, 69.35; H, 5.82. Found:
1
3
3
) δ 198.03 (s), 160.22 (dd, J = 249.8, 6.9 Hz),
1
9
3
20 2 3
H F O
C, 69.20; H, 5.62.

S25
Arylation of 3,5-difluoropropiophenone with 4-bromophenyl pivalate. Prepared
according to the general procedure with 3,5-difluoropropiophenone (204 mg, 1.20 mmol,
1
.20 equiv) and 4-bromophenyl pivalate (257 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (194 mg, 56%). H NMR (500 MHz, CDCl
3
) δ 7.57 (d, J = 8.1 Hz, 2H), 7.51 (d,
J = 8.7 Hz, 2H), 7.19 (d, J = 8.6 Hz, 2H), 3.00 (q, J = 7.2 Hz, 2H), 1.37 (s, 9H), 1.26 (t, J
1
3
=
7.2 Hz, 3H). C NMR (126 MHz, CDCl
3
) δ 198.05 (s), 177.02 (s), 160.22 (dd, J =
2
1
50.8, 6.8 Hz), 151.71 (s), 137.81 (t, J = 7.8 Hz), 132.57 (s), 131.53 (s), 125.72 (s),
1
9
21.80 (s), 111.55 (m), 39.38 (s), 32.14 (s), 27.33 (s), 8.25 (s). F NMR (376 MHz,
) δ -112.99 (s). Anal. Calcd for C17 : C, 66.66; H, 5.26. Found: C, 66.45; H,
CDCl
.07.
3
16 2 3
H F O
5
Arylation of 3,5-difluorochlorobenzene with 4-bromobenzonitrile.
according to the general procedure with 3,5-difluorochlorobenzene (179 mg, 1.20 mmol,
.20 equiv) and 4-bromobenzonitrile (182 mg, 1.00 mmol, 1.00 equiv). The mixture was
purified by flash column chromatography (10% EtOAc:90% hexanes) to give the product
Prepared
1
1
(
7
1
192 mg, 77%). H NMR (499 MHz, CDCl
3
) δ 7.75 (d, J = 8.4 Hz, 2H), 7.57 (m, 2H),
.07 (d, J = 7.4 Hz, 2H). C NMR (126 MHz, CDCl ) δ 159.85 (dd, J = 252.6, 7.9 Hz),
35.63 (t, J = 13.4 Hz), 133.28 (s), 132.30 (s), 131.19 (s), 118.58 (s), 115.82 (t, J = 18.6
1
3
3
1
9
Hz), 113.36 (m), 112.71 (s). F NMR (376 MHz, CDCl
3
) δ -112.95 (s). Anal. Calcd for
C
13
H
6
ClF N: C, 62.54; H, 2.42; N, 5.61. Found: C, 62.34; H, 2.36; N, 5.42.
2
Arylation of 3,5-difluorochlorobenzene with 3-bromobenzotrifluoride. Prepared
according to the general procedure with 3,5-difluorochlorobenzene (179 mg, 1.20 mmol,
1
.20 equiv) and 3-bromobenzotrifluoride (225 mg, 1.00 mmol, 1.00 equiv). The mixture

S26
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (196 mg, 67%). H NMR (499 MHz, CDCl
1
1
3
) δ 7.74 (s, 1H), 7.70 (d, J = 7.0 Hz,
1
3
H), 7.64 (m, 1H), 7.60 (m, 1H), 7.08 (d, J = 7.3 Hz, 2H). C NMR (126 MHz, CDCl
60.00 (dd, J = 252.1, 8.3 Hz), 135.03 (t, J = 13.4 Hz), 133.75 (s), 131.20 (q, J = 32.5
3
) δ
Hz), 129.29 (s), 129.14 (s), 127.24 (m), 125.56 (q, J = 3.7 Hz), 124.16 (q, J = 273 Hz),
1
9
1
16.19 (t, J = 18.6 Hz), 113.27 (m). F NMR (376 MHz, CDCl
3
) δ -63.20 (s), -113.16 (s).
Anal. Calcd for C13 ClF : C, 53.36; H, 2.07. Found: C, 53.09; H, 2.35.
H
6
5
Arylation of 3,5-difluoro-N,N-dimethylaniline with 2-bromotoluene.
Prepared
according to the general procedure with 3,5-difluoro-N,N-dimethylaniline (189 mg, 1.20
mmol, 1.20 equiv) and 2-bromotoluene (182 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (232 mg, 94%). H NMR (499 MHz, CDCl
(
3
) δ 7.38 (m, 3H), 7.34 (s, 1H), 6.37
) δ 161.28
dd, J = 242.3, 11.6 Hz), 151.34 (t, J = 13.4 Hz), 138.26 (s), 131.63 (s), 130.26 (s),
30.06 (s), 128.29 (s), 125.73 (s), 105.53 (t, J = 22.4 Hz), 95.20 (m), 40.44 (s), 20.21 (s).
1
3
d, J = 10.9 Hz, 2H), 3.03 (s, 6H), 2.31 (s, 3H). C NMR (126 MHz, CDCl
3
(
1
1
9
F NMR (376 MHz, CDCl
3 15 2
) δ -113.47 (s). Anal. Calcd for C15H F N: C, 72.86; H, 6.11;
N, 5.66. Found: C, 73.06; H, 6.20; N, 5.66.
Arylation of methyl 3,5-difluorobenzoate with 2-bromo-5-fluorotoluene. Prepared
according to the general procedure with methyl 3,5-difluorobenzoate (207 mg, 1.20 mmol,
1
.20 equiv) and 2-bromo-5-fluorotoluene (189 mg, 1.00 mmol, 1.00 equiv). The mixture
was purified by flash column chromatography (10% EtOAc:90% hexanes) to give the
1
product (163 mg, 58%). H NMR (499 MHz, CDCl
3
) δ 7.68 (d, J = 7.4 Hz, 2H), 7.28 (m,
1
3
1
H), 7.07 (td, J = 8.4, 2.8 Hz, 1H), 6.96 (dd, J = 9.0, 2.7 Hz, 1H), 3.97 (s, 3H), 2.13 (s,
1
3
H). C NMR (126 MHz, CDCl
3
) δ 165.01 (t, J = 3.4 Hz), 160.89 (d, J = 245.32 Hz),
59.92 (dd, J = 250.74 Hz, 7.2 Hz), 133.04 (d, J = 3.4 Hz), 132.29 (t, J = 9.5 Hz), 131.78
(
1
1
d, J = 7.9 Hz), 129.65 (d, J = 8.2 Hz), 121.91 (t, J = 21.4 Hz), 117.28 (d, J = 22.3 Hz),
1
9
16.14 (d, J = 20.6 Hz), 113.03 (m), 52.94 (s), 19.10 (s). F NMR (376 MHz, CDCl
3
) δ -
11.12 (s), -118.26 (s). Anal. Calcd for C15 : C, 64.29; H, 3.96. Found: C, 64.30;
11 3 2
H F O
H, 3.82.

S27
Arylation of 3,5-difluoro-N,N-dimethylaniline with 4-bromobenzaldehyde. Prepared
according to the general procedure with 3,5-difluoro-N,N-dimethylaniline (189 mg, 1.20
mmol, 1.20 equiv) and 4-bromobenzaldehyde (185 mg, 1.00 mmol, 1.00 equiv). The
mixture was purified by flash column chromatography (10% EtOAc:90% hexanes) to
1
give the product (186 mg, 71%). H NMR (499 MHz, CDCl
2
1
3
) δ 10.03 (s, 1H), 7.90 (s,
) δ 192.11 (s),
61.17 (dd, J = 244.9, 10.8 Hz), 151.60 (t, J = 13.8 Hz), 137.23 (s), 134.97 (s), 131.05 (t,
1
3
H), 7.63 (s, 2H), 6.27 (s, 2H), 2.99 (s, 6H). C NMR (126 MHz, CDCl
3
1
9
J = 2.6 Hz), 129.62 (s), 104.47 (t, J = 18.7 Hz), 95.45 (m), 40.26 (s). F NMR (376 MHz,
CDCl ) δ -115.20 (s). Anal. Calcd for C15 NO: C, 68.96; H, 5.02; N, 5.36. Found: C,
8.65; H, 4.89; N, 5.09.
3
13 2
H F
6
Arylation of methyl 3,4-difluorobenzoate with 4-bromotoluene. Prepared according
to the general procedure with methyl 3,4-difluorobenzoate (207 mg, 1.20 mmol, 1.20
equiv) and 4-bromotoluene (171 mg, 1.00 mmol, 1.00 equiv). The mixture was purified
by flash column chromatography (10% EtOAc:90% hexanes) to give the product (231 mg,
1
8
8%). H NMR (500 MHz, CDCl
3
) δ 7.95 (m, 1H), 7.80 (m, 1H), 7.46 (dd, J = 8.1, 1.6
1
3
Hz, 2H), 7.28 (m, 2H), 3.93 (s, 3H), 2.42 (s, 3H). C NMR (126 MHz, CDCl ) δ 165.49
d, J = 2.6 Hz), 151.20 (dd, J = 250.74, 6.43 Hz), 150.93 (dd, J = 248.72, 12.85 Hz),
3
(
1
1
38.88, 131.50 (d, J = 11.0 Hz), 131.00 (d, J = 2.6 Hz), 129.66 , 128.97 (d, J = 3.1 Hz),
1
9
27.26 (t, J = 3.2 Hz), 126.63 (dd, J = 6.6, 4.2 Hz), 117.15 (m), 52.72, 21.45. F NMR
) δ -136.27 (d, J = 20.0 Hz), -136.70 (dd, J = 20.6, 10.4 Hz). Anal.
: C, 68.70; H, 4.61. Found: C, 68.73; H, 4.56.
(376 MHz, CDCl
3
12 2 2
Calcd for C15H F O
General Procedure for (hetero)aryl Bpin stability studies. Into a vial with a magnetic
stir bar were added the (hetero)aryl Bpin (0.1 mmol), THF (0.3 mL), 2M aqueous
2 3
Na CO and 1,3,5-trimethoxybenzene (10 mg). The vial was sealed and was allowed to
stir at room temperature for 5 hours. At this time, a sample was removed and analyzed

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using gas chromatography. The conversion of the (hetero)aryl Bpin was determined by
comparison to the internal standard.
General Procedure for competition experiments between heteroaryl pinacol
boronate esters and phenyl pinacol boronate. Inside a glove box, Pd complex 1 (9.6
mg, 0.010 mmol, 1.0 equiv), heteroaryl Bpin (0.100 mmol, 10.0 equiv), PhBpin (20.4 mg,
0
3
.100 mmol, 10.0 equiv), PPh (15.9 mg, 0.0600 mmol, 6.00 equiv), THF (0.25 mL),
H
2
O (0.025 mL), and 1,3,5-trimethoxybenzene (10 mg) were added to a dry vial
equipped with a magnetic stir bar. The reaction mixture was sealed and stirred at room
temperature for 5 h. At this time, a sample was removed and the yields of the 2-aryl-
heteroarene and 4-fluorobiphenyl were determined using gas chromatography by
comparison to the internal standard.
General Procedure for competition experiments between 2,6-difluoroaryl pinacol
boronate esters and phenyl pinacol boronate. Inside a glove box, Pd(dba)
.0040 mmol, 0.10 equiv), Q-phos (2.9 mg, 0.0040, 0.10 equiv), 2,6-difluoroaryl Bpin
0.200 mmol, 5.00 equiv), PhBpin (40.8 mg, 0.200 mmol, 5.00 equiv), 1-bromo-4-
fluorobenzene (7.0 mg, 0.040 mmol, 1.0 equiv), K PO (170 mg, 0.80 mmol, 20 equiv),
,4-dioxane (0.5 mL), H O (0.05 mL), and 1,3,5-trimethoxybenzene (10 mg) were added
2
(2.3 mg,
0
(
3
4
1
2
to a dry vial equipped with a magnetic stir bar. The reaction mixture was sealed and
stirred at 50 °C for 2 h. At this time, a sample was removed and the yields of the 2,6-
difluorobiaryl and 4-fluorobiphenyl were determined using gas chromatography by
comparison to the internal standard.

S29
References
(
1
(
1)
974, 65, 253.
2) a) Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 2116;
Driver, M. S.; Hartwig, J. F. Organometallics 1997, 16, 5706.
3) a) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F.
Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A. J. Organomet. Chem.
b)
(
J. Am. Chem. Soc. 2001, 124, 390; b) Robbins, D. W.; Boebel, T. A.; Hartwig, J. F. J.
Am. Chem. Soc. 2010, 132, 4068.

S30
NMR Spectra