New catalysts for Suzuki-Miyaura coupling reactions of heteroatom- substituted heteroaryl chlorides

Article abstract of DOI:10.1021/jo070341w

(Chemical Equation Presented) The new air-stable PdCl₂{PR ₂(Ph-R′)}₂ complexes, readily prepared from commercial reagents, exhibit unique efficiency as catalysts for the Suzuki-Miyaura coupling reactions of a variety of he

Full text of DOI:10.1021/jo070341w

1
Supporting Information
New Catalysts for Suzuki-Miyaura Coupling Reactions of Heteroatom-Substituted
Heteroaryl Chlorides
Anil S. Guram,* Xiang Wang, Emilio E. Bunel, Margaret M. Faul,
Robert D. Larsen, and Michael J. Martinelli
Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California
9
1320
aguram@amgen.com
Experimental Section
General. All experiments were performed under nitrogen atmosphere in screw-cap vials. All reagents
including di-tert-butylphosphine, dicylclohexylphosphine, Pd dba , PdCl (COD), aryl- and heteroaryl
2
3
2
halides, aryl- and heteroaryl boronic acids/esters, and organic/inorganic bases were purchased from
commercial sources and used as received. Anhydrous, sure-seal grade organic solvents including toluene,
3
tetrahydrofuran (THF), acetonitrile (CH CN), dioxane, 1-butanol (1-BuOH), dimethoxyethane (DME),
dimethylacetamide (DMAC), and pentane were used as purchased. Distilled water purged with nitrogen
was used. Stock solutions of catalysts were generally used particularly for high TON experiments.
Commercially available pre-packed silica gel plugs and hexanes/ethyl acetate solvents were used for
column chromatographic purification of oragnic products. The syntheses of PdCl
complexes were typically performed on 4.0 – 5.0 mmol scale of the aryl halide. Few of the PdCl
R’)} complexes are now commercially available. The Suzuki coupling reactions were typically performed
2
{PR
2
(Ph-R’)}
2
2
{PR (Ph-
2
2
on 1.0 mmol scale of the aryl halide. The yields correspond to isolated products of > 95 % purity as
determined by NMR, GCMS and/or HPLC. The conversions were determined by GCMS area% in the
presence of a standard (BHT). The catalyst turnover numbers (TON) were determined in some cases using
calibrated LC area% (calibrated using purified product). NMR spectra were recorded on 400 MHz
1
13
31
19
instrument and all NMR ( H, C, P, and F) chemical shifts are reported in parts per million (ppm) and
all coupling constants are reported in Hertz (Hz).
t
t
Syntheses of PdCl
2
{PR
2
(Ph-R’)}
2
complexes (A: R = Bu, R’ = p-CF
3
; B: R = Bu, R’ = H; B’: R = Cy,
t
t
t
R’ = H; C: R = Bu, R’ = 3,4,5-tri-OMe; D: R = Bu, R’ = p-OMe; E: R = Bu, R’ = p-NMe ; E’: R = Cy,
2

2
R’ = p-NMe
2
). The syntheses were typically performed on a 4.0 – 5.0 mmol scale of the aryl halide. A
t
toluene or xylene solution of di-alkylphosphine (1.0 equiv), aryl bromide (1.0 equiv), NaO Bu (1.5 equiv)
o
and Pd
2
dba
3
(1 mol %) was stirred at 90 – 130 C for 12 h. The reaction was cooled to ambient
temperature and filtered through a short silica gel plug. The silica gel plug was rinsed with toluene or
dioxane. The combined filtrate was concentrated under vacuum and the residue was dissolved in THF.
Alternatively, the combined filtrate was used as such. The PdCl
added as a solid and the reaction mixture was stirred at ambient temperature for 12 h. For complex B’, a
:1 reaction mixture of commercially available PCy Ph and PdCl (COD) in THF was stirred at ambient
2
(COD) (0.35 – 0.40 equiv) complex was
2
2
2
temperature for 12 h. The reaction mixture was filtered, and the yellow solid was washed with pentane and
dried under vacuum. The desired complexes were typically obtained in about 85% isolated yields.
t
1
PdCl
2
{P Bu
2
(Ph-p-CF
3
)}
2
(A): H NMR (CDCl
3
): δ 8.00 (br. s, 4H), 7.59 (br. d, J = 7.9, 4H), 1.62 (br. t,
3
1
19
J
PH = 7.0, 36H).
P NMR (CDCl ): δ 55.7.
3
3
F NMR (CDCl ): δ - 63.4. Elemental Analysis:
-1
Calculated: C 47.54, H 5.85; Found: C 47.57, H 6.05. Raman: cm 297.9 (Pd-Cl).
t
1
PdCl
2
{P Bu
2
(Ph)}
2
(B): H NMR (CD
2
Cl
2
): δ 7.9 – 7.8 (m, 4H), 7.36 – 7.30 (m, 6H), 1.56 (br. t, JPH
=
3
1
-1
6
.9, 36H). P NMR (CD Cl
2
2
): δ 54.4. Raman: cm 300.9 (Pd-Cl).
1
31
PdCl
2
{PCy
2
(Ph)}
2
(B’): H NMR (C
6
D
6
): δ 7.90 (m, 4H), 7.29 – 7.18 (m, 6H), 2.93 – 1.16 (m, 44H).
P
NMR (C
6
D
6
): δ 41.9. Elemental Analysis: Calculated: C 59.55, H 7.50; Found: C 59.38, H 7.01.
t
1
PdCl
2
{P Bu
2
(Ph-3,4,5-tri-OMe)}
2
(C): H NMR (C
6
D
6
): δ 7.41 (t, JPH = 4.7, 4H), 3.93 (s, 6H) , 3.71 (s,
3
1
1
7
2H), 1.76 (br. t, JPH = 6.8, 36 H). P NMR (C
D
6 6
): δ 69.4. Elemental Analysis: Calculated: C 50.91, H
.29; Found: C 50.74, H 7.03.
t
1
PdCl
2
{P Bu
2
(Ph-p-OMe)}
2
(D): Isolated material contained 1,4-dioxane (0.25 mol equiv). H NMR
(
C D ): δ 8.06 – 8.02 (p, J = 4.3, 4H), 6.85 (d, J = 8.6, 4H), 3.32 (s, 6H). 1.77 (br. t, J = 6.8, 36H).
6
6
Elemental Analysis: Calculated: C 53.28, H 7.45; Found: C 53.36, H 7.03.

3
t
1
PdCl
2
{P Bu
2
(Ph-p-NMe
2
)}
2
(E): H NMR (CDCl
3
): δ 7.5 (br. s, 4H), 6.42 (d, J = 8.3, 4H), 2.75 (s, 12H),
3
1
1
.38 (t, JPH = 6.6, 36H). P NMR (CDCl ): δ 52.1. Elemental Analysis: Calculated: C 54.28, H 7.97;
3
-1
Found: C 53.17, H 7.58. Raman: cm 295.8 (Pd-Cl).
1
PdCl
4H), 2.52 (s, 12H). P NMR (C
C 58.85, H 7.63.
2
{PCy
2
(Ph-p-NMe
2
)}
2
(E’): H NMR (C
6
D
6
): δ 7.91 (m, 4H), 6.64 (d, J = 8.8, 4H), 3.03 – 1.28 (m,
3
1
4
6
D
6
): δ 39.2. Elemental Analysis: Calculated: C 59.15, H 7.94; Found:
General procedure for the Suzuki-Miyaura coupling reactions. All Suzuki-Miyaura coupling reactions
Tables 1 – 9, equations 1 and 2) were typically performed on a 1.0 mmol scale of the aryl halide. A
(
mixture of aryl halide (1.0 equiv), aryl boronic acid/ester (1.2 – 1.5 equiv), base (2.0 – 3.0 equiv.) and
catalyst (0.01 – 2.0 mol %) in aqueous solvent (~ 3-4 mL for 1.0 mmol starting substrate, ~ 10 % water)
o
was stirred at 80 – 100 C in screw-capped glass vials for 5 h – 20 h. The reaction was cooled to ambient
temperature and extracted in organic solvent (ether or dichloromethane). The organic extract was
subjected to an aqueous work-up (when product stability permitted, 1N NaOH was used to facilitate
2 4
removal of excess boronic acid), dried over anhydrous Na SO , and concentrated under vacuum. The
crude material was purified by column chromatography on silica gel using hexanes and hexanes/ethyl
o
acetate or 5 % methanol in ethyl acetate as eluents. High TON experiments were stirred at 80 – 100 C for
2
4 h. Additional details are provided in the schematics and text.
2
-(o-Tolyl)-3-pyridinamine (Table 5, entry 1). This compound was isolated as a white solid (93 % yield)
1
from the reaction of 2-chloropyridin-3-amine and o-tolylboronic acid using the general procedure.
H
NMR (CDCl ): δ 8.08 (d, J = 4.5, 1H), 7.29-7.26 (m, 4H), 7.08-7.00 (m, 2H), 3.59 (s br, 2H), 2.17 (s, 3H).
3
1
3
C NMR (CDCl ): δ 146.0, 140.3, 139.2, 137.4, 136.7, 130.7, 129.1, 128.5, 126.3, 123.2, 121.9, 19.3.
3
2
-(p-Tolyl)-3-pyridinamine (Table 5, entry 2). This compound was isolated as a white solid (95 % yield)
1
from the reaction of 2-chloropyridin-3-amine and p-tolylboronic acid using the general procedure.
NMR (CDCl
H
3
): δ 8.1 (d/d, J = 4.1/1.8, 1H), 7.55 (d, J = 8.2, 2H), 7.26 (d, J = 7.8, 2H), 7.04 – 6.98 (m,

4
1
3
2
H), 3.84 (s br, 2H), 2.39 (s, 3H). C NMR (CDCl ): δ 145.1, 140.0, 139.9, 138.0, 135.7, 129.4, 128.3,
3
1
22.8, 122.6, 21.3.
2
-{4-(Trifluoromethyl)phenyl}-3-pyridinamine (Table 5, entry 3). This compound was isolated as a
white solid (92
%
yield) from the reaction of 2-chloropyridin-3-amine and 4-
1
(
trifluoromethyl)phenylboronic acid using the general procedure. H NMR (CDCl
3
): δ 8.12 (d/d, J =
1
3
4
.5/1.6, 1H), 7.81 (d, J = 8.0, 2H), 7.71 (d, J = 8.3, 2H), 7.10 – 7.02 (m, 2H), 3.85 (s br). C NMR
2
3
(
CDCl ): δ 143.1, 142.3, 140.2, 140.2, 130.1 (q, J = 32.5), 128.9, 125.7 (q, J = 3.5), 123.8, 123.2,
3
CF
CF
1
1
24.2 (q, JCF = 272).
2
-(4-Methoxyphenyl)-3-pyridinamine (Table 5, entry 4). This compound was isolated as a white solid
(
93 % yield) from the reaction of 2-chloropyridin-3-amine and 4-methoxyphenylboronic acid using the
1
general procedure. H NMR (CDCl
3
): δ 8.08 (d/d, J = 3.7/1.1, 1H), 7.60 (d, J = 8.4, 2H), 7.01 – 6.96 (m,
1
3
4
H), 3.85 (s br, 2H, partially overlapped), 3.82 (s, 3H). C NMR (CDCl ): δ 159.5, 144.8, 140.1, 139.8,
3
1
31.1, 129.8, 122.7, 122.6, 114.2, 55.4.
2
-{4-(Trifluoromethyl)phenyl}-4-pyridinamine (Table 5, entry 5). This compound was isolated as a
white solid (90
%
yield) from the reaction of 2-chloropyridin-4-amine and 4-
1
(
trifluoromethyl)phenylboronic acid using the general procedure. H NMR (CDCl
3
): δ 8.31 (d, J = 5.4,
1
3
1
H), 8.0 (d, J = 8.2, 2H), 7.67 (d, J = 8.2, 2H), 6.93 (s, 1H), 6.51 (br d, J = 5.5, 1H), 4.39 (br s, 2H).
C
2
3
NMR (CDCl ): δ 156.8, 153.7, 150.3, 143.2, 130.5 (q, J = 32.2), 127.2, 125.5 (q, J = 3.5), 124.3 (q,
3
CF
CF
1
JCF = 272), 109.0, 106.9.
2
-(4-Fluorophenyl)-4-pyridinamine (Table 5, entry 6). This compound was isolated as a white solid (93
%
yield) from the reaction of 2-chloropyridin-4-amine and 4-fluorophenylboronic acid using the general
1
procedure. H NMR (CDCl ): δ 7.46 – 7.42 (m, 2H), 7.14 – 7.10 (m, 2H), 6.97 – 6.92 (m, 3H), signal for
3
1
3
1
3
NH
2
protons not observed. C NMR (CDCl
3
): δ 161.3 (d, JCF = 246.0), 142.3, 129.6 (d, JCF = 3.4),
3
2
1
27.0, 126.58, 126.54 (d, J = 7.8), 123.73, 122.1, 114.76 (d, J = 21.5).
CF
CF

5
2-Mesityl-4-pyridinamine (Table 5, entry 7). This compound was isolated as a white solid (98 % yield)
1
from the reaction of 2-chloropyridin-4-amine and mesitylboronic acid using the general procedure.
H
NMR (CDCl ): δ 8.02 (d, J = 5.5, 1H), 6.75 (s, 2H), 6.23 (d, J = 5.4, 1H), 6.20 (s, 1H), 4.57 (s br, 2H),
3
1
3
2
.17 (s, 3H), 1.90 (s, 6H). C NMR (CDCl
06.8, 20.0, 18.9.
3
): δ 159.0, 152.7, 148.4, 137.1, 135.9, 134.5, 127.0, 109.1,
1
2-Mesityl-3-pyridinamine (Table 5, entry 8). This compound was isolated as a white solid (92 % yield)
1
from the reaction of 2-chloropyrdin-3-amine and mesitylboronic acid using the general procedure.
H
NMR (CDCl ): δ 7.98 (d, J = 4.5, 1H), 6.92 (d/d, J = 8.0/5.0, 1H), 6.84 (d, J = 8.0, 1H), 6.82 (s, 2H), 3.45
3
1
3
(
s br, 2H), 2.20 (s, 3H), 1.88 (s, 6H). C NMR (CDCl ): δ 145.8, 140.5, 139.4, 137.6, 136.5, 133.8, 128.6,
3
1
22.8, 121.3, 21.2, 19.4.
3
-Methoxy-6-(4-methoxyphenyl)pyridazine (Table 6, entry 1). This compound was isolated as a white
solid (97 % yield) from the reaction of 3-chloro-6-methoxypyridazine and 4-methoxyphenylboronic acid
1
using the general procedure. H NMR (CDCl
3
): δ 7.96 (d, J = 8.8, 2H), 7.72 (d, J = 9.2, 1H), 7.27 – 6.99
): δ 164.0, 160.8, 154.9, 128.8, 127.8, 126.6, 117.7,
1
3
(
m, 3H), 4.17 (s, 3H), 3.86 (s, 3H). C NMR (CDCl
3
1
14.4, 55.4, 54.8.
4
-(4-Methoxyphenyl)-2-methylthiopyrimidine (Table 6, entry 2). This compound was isolated as a
white solid (95 % yield) from the reaction of 4-chloro-2-(methylthio)pyrimidine and 4-
1
methoxyphenylboronic acid using the general procedure. H NMR (CDCl
3
): δ 8.45 (d, J = 5.3, 1H), 8.05
1
3
(
d, J = 9.0, 2H), 7.26 (d, J = 5.8, 1H), 6.97 (d, J = 9.0, 2H), 3.85 (s, 3H), 2.62 (s, 3H). C NMR (CDCl3):
δ 172.5, 163.3, 162.2, 157.4, 128.8, 128.7, 114.3, 111.0, 55.5, 14.2.
4
-{2-(Methylthio)pyrimidin-4-yl}benzonitrile (Table 6, entry 3). This compound was isolated as an off-
white solid (94 % yield) from the reaction of 4-chloro-2-(methylthio)pyrimidine and 4-cyanophenylboronic
1
acid using the general procedure. H NMR (CDCl ): δ 8.64 (d, J = 5.3, 1H), 8.20 (d, J = 8.6, 2H), 7.79 (d,
3
1
3
J = 8.4, 2H), 7.40 (d, J = 5.3, 1H), 2.65 (s, 3H). C NMR (CDCl
27.8, 118.4, 114.5, 112.2, 14.3.
3
): δ 173.5, 161.8, 158.3, 140.5, 132.7,
1

6
Methyl 2-(4-Methoxyphenyl)-6-methylpyrimidine-4-carboxylate (Table 6, entry 4). This compound
was isolated as an off-white solid (89 % yield) from the reaction of methyl 2-chloro-6-methylpyrimidine-4-
carboxylate and 4-methoxyphenylboronic acid using the general procedure except (i) anhydrous toluene
1
was used as solvent and (ii) 0.01 mol% catalyst was used. H NMR (CDCl
3
): δ 8.47 (d, J = 8.8, 2H), 7.63
): δ 169.5, 165.5,
1
3
(
s, 1H), 6.98 (d, J = 8.6, 2H), 4.02 (s, 3H), 3.86 (s, 3H), 2.63 (s, 3H). C NMR (CDCl
3
1
64.8, 162.1, 154.9, 130.2, 129.8, 117.3, 113.9, 55.4, 53.1, 24.6.
4
-(2,6-Dimethylphenyl)-2-(methylthio)pyrimidine (Table 6, entry 5). This compound was isolated as a
colorless oil (99 % yield) from the reaction of 4-chloro-2-(methylthio)pyrimidine and 2,6-
1
dimethylphenylboronic acid using the general procedure except 0.1 mol% catalyst was used. H NMR
3
(CDCl ): δ 8.47 (d, J = 4.9, 1H), 7.12 (t, J = 7.6, 1H), 7.01 (d, J = 7.5, 2H), 6.80 (d, J = 5.0, 1H), 2.47 (s,
1
3
3
3
H), 2.01 (s, 6H). C NMR (CDCl ): δ 171.9, 166.8, 156.1, 136.9, 134.2, 127.6, 126.8, 116.1, 19.2, 13.1.
2
,4-Dimethoxy-6-(4-methoxyphenyl)pyrimidine (Table 6, entry 6). This compound was isolated as an
off-white solid (98 % yield) from the reaction of 6-chloro-2,4-dimethoxypyrimidine and 4-
1
methoxyphenylboronic acid using the general procedure except 0.1 mol% catalyst was used. H NMR
(
CDCl
3
): δ 8.02 (d, J = 8.6, 2H), 6.97 (d, J = 8.6, 2H), 6.7 (s, 1H), 4.07 (s, 3H), 3.99 (s, 3H), 3.86 (s, 3H).
): δ 172.5, 165.6, 165.4, 161.7, 129.3, 128.6, 114.0, 95.9, 55.4, 54.7, 53.9.
1
3
C NMR (CDCl
3
5
-(6-Methoxypyridin-3-yl)pyridin-2-amine (Table 7, entry 1). This compound was isolated as a white
solid (97 % yield) from the reaction of 5-chloropyridin-2-amine and 6-methoxypyridin-3-ylboronic acid
1
using the general procedure. H NMR (CDCl ): δ 8.27 (d/d, J = 8/2.3, 2H), 7.70 (d/d, J = 8.6/2.6, 1H),
3
1
3
7
.59 (d/d, J = 8.6/2.5, 1H), 6.80 (d, J = 8.6, 1H), 6.58 (d, J = 8.4, 1H), 4.53 (br s, 2H), 3.97 (s, 3H). C
NMR (CDCl ): δ 163.4, 157.7, 146.1, 144.2, 136.8, 136.2, 127.4, 124.2, 110.9, 108.6, 53.5.
3
4
-(Pyridin-3-yl)pyridin-2-amine (Table 7, entry 2). This compound was isolated as an off-white solid (95
yield) from the reaction of 4-chloropyridin-2-amine and pyridin-3-ylboronic acid using the general
%

7
1
procedure. H NMR (CDCl ): δ 8.84 (s, 1H), 8.65 (d, J = 3.5 Hz, 1H), 8.17 (d, J = 5.0, 1H), 7.87 (d, J =
3
1
3
7
.5, 1H), 7.34 - 7.45 (m, 1H), 6.86 (d, J = 5.0, 1H), 6.69 (s, 1H), 4.68 (br. s, 2H). C NMR (CDCl
58.3, 149.1, 148.2, 147.3, 146.3, 133.6, 133.4, 122.9, 111.6, 105.4.
3
): δ
1
2
-(Pyridin-3-yl)pyridin-3-amine (Table 7, entry 3). This compound was isolated as a white solid (88 %
yield) from the reaction of chloropyridin-3-amine and pyridin-3-ylboronic acid using the general
1
procedure. H NMR (CDCl
3
): δ 8.96 (s, 1H), 8.63 (d, J = 4.0, 1H), 8.15 (d, J = 3.5, 1H), 8.03 (d, J = 7.5,
1
3
1
H), 7.40-7.42 (m, 1H), 7.05 - 7.17 (m, 2H), 3.79 (s, br, 2H). C NMR (CDCl
38.1, 138.1, 133.9, 132.2, 121.4, 121.3, 120.8.
3
): δ 147.2, 146.9, 139.0,
1
4
-(2-Fluoropyridin-3-yl)-2,6-dimethoxypyrimidine (Table 7, entry 4). This compound was isolated as
an off-white solid (97 % yield) from the reaction of Cl-chloro-2,4-dimethoxypyrimidine and 2-
1
fluoropyridin-3-ylboronic acid using the general procedure. H NMR (CDCl
3
): δ 8.92-8.99 (m, 1H), 8.53
1
3
(
d, J = 5.0, 1H), 7.60-7.57 (m, 1H), 7.02 (s, 1H), 4.31 (s, 3H), 4.26 (s, 3H). C NMR (CDCl ): δ 172.7,
3
1
65.2, 161.2 (d, JCF = 244), 159.1 (d, JCF = 7.8), 148.8 (d, JCF = 15.6), 141.2, 121.9 (d, JCF = 4.3), 119.8 (d,
J
CF = 25.2), 101.7 (d, JCF = 13.9), 54.8, 54.1.
4
-(2-Fluoropyridin-3-yl)-2-(methylthio)pyrimidine (Table 7, entry 5). This compound was isolated as a
white solid (92 % yield) from the reaction of 4-chloro-2-(methylthio)pyrimidine and 2-fluoropyridin-3-
1
ylboronic acid using the general procedure. H NMR (CDCl
3
): δ 8.71 (t, J = 8.8, 1H), 8.61 (d, J = 5.5, 1H),
1
3
8
.33 (s, 1H), 7.56 (d, J = 3.5, 1H), 7.33-7.42 (m, 1H), 2.62 (s, 3H). C NMR (CDCl
JCF = 243), 158.1, 158.0 (d, JCF = 7.8), 149.5 (d, JCF = 15.6), 141.2, 122.1, 119.4 (d, JCF = 26.0), 115.5 (d,
CF = 13.0), 14.2.
3
): δ 172.3, 161.2 (d,
J
3
-(2-Fluoropyridin-3-yl)-6-methoxypyridazine (Table 7, entry 6). This compound was isolated as a
white solid (99 % yield) from the reaction of 3-chloro-6-methoxypyridazine and 2-fluoropyridin-3-
1
ylboronic acid using the general procedure. H NMR (CDCl
3
): δ 8.60 - 8.70 (m, 1H), 8.31 (d, J = 4.5, 1H),
1
3
7
3
.97 (d/d, J = 9.5/2.0, 1H), 7.35 - 7.45 (m, 1H), 7.10 (d, J = 9.0, 1H), 4.21 (s, 3H). C NMR (CDCl ):

8
δ 164.4, 160.5 (d, JCF = 240), 150.4 (d, JCF = 6.1), 148.4 (d, JCF = 15.6), 140.9, 130.0 (d, JCF = 11.3),
1
22.3, 119.4 (d, JCF = 26.8), 117.3, 55.0.
2
-(p-Tolyl)thiophene (Table 8, entry 1). This compound was isolated as a white solid (96 % yield) from
1
the reaction of 2-chlorothiophene and p-tolylboronic acid using the general procedure. H NMR (CDCl
3
):
δ 7.48 (d, J = 8.2, 2H), 7.24 (d, J = 3.5, 1H), 7.2 (d, J = 5, 1H), 7.15 (d, J = 7.9, 2H), 7.03 (d/d, J = 5.1/3.6,
1
3
1
3
H), 2.33 (s, 3H). C NMR (CDCl ): δ 144.6, 137.3, 131.6, 129.5, 127.9, 125.8, 124.2, 122.6, 21.2.
4
-(4-Methoxyphenyl)-1,3,5-trimethyl-1H-pyrazole (Table 8, entry 2). This compound was isolated as a
white solid (93 % yield) from the reaction of 4-bromo-1,3,5-trimethylpyrazole and 4-
1
methoxyphenylboronic acid using the general procedure. H NMR (CDCl
3
): δ 7.15 (d, J = 8.6, 2H), 6.94
1
3
(
J = 8.6, 2H), 3.82 (s, 3H), 3.76 (s, 3H), 2.22 (s, 3H), 2.20 (s, 3H). C NMR (CDCl ): δ 158.1, 145.0,
3
1
36.0, 130.5, 126.6, 118.8, 113.9, 55.3, 36.0, 12.4, 10.2.
4
-(4-Fluorophenyl)-1,3,5-trimethyl-1H-pyrazole (Table 8, entry 3). This compound was isolated as a
white solid (95 % yield) from the reaction of 4-bromo-1,3,5-trimethylpyrazole and 4-fluorophenylboronic
1
acid using the general procedure. H NMR (CDCl
3
): δ 7.10 (d/d. J = 8.8/5.7, 2H), 6.99 (t, J = 8.8, 2H),
): δ 160.5 (d, J = 244), 143.9, 135.1, 129.9 (d, J
1
3
3
.69 (s, 3H), 2.13 (s, 3H), 2.12 (s, 3H). C NMR (CDCl
3
1
9
=
7.7), 129.2 (d, J = 2.6), 117.3, 114.2 (d, J = 20.7), 35.0, 11.3, 9.1. F NMR (CDCl ): δ -116.
3
3
-(1,3,5-Trimethyl-1H-pyrazol-4-yl)pyridine (Table 8, entry 4). This compound was isolated as an off-
white solid (95% yield) from the reaction of 4-bromo-1,3,5-trimethylpyrazole and pyridine-3-ylboronic
1
acid using the general procedure. H NMR (CDCl ): δ 8.50-8.52 (m, 2H), 7.57 (d, J = 8.0, 1H), 7.33 (d/d, J
3
1
3
=
7.5, 5.0, 1H), 3.80 (s, 3H), 2.25 (s, 6 H). C NMR (CDCl
3
): δ 150.3, 147.3, 145.2, 136.7, 136.5, 130.2,
1
23.4, 115.6, 36.1, 12.4, 10.2.
2
-(6-Methoxypyridin-3-yl)benzo[d]oxazole (Table 8, entry 5). This compound was isolated as an off-
white solid (88 % yield) from the reaction of 2-chlorobenzoxazole and 6-methoxypyridin-3-ylboronic acid

9
using the general synthetic procedure with a modified work-up procedure where the product was
precipitated by adding water to the reaction mixture in dioxane. The precipitated product was washed with
1
water (5 mL), cold pentane (1 mL), and dired under vacuum. H NMR (CDCl
3
): δ 9.04 (br. s, 1H), 8.36
1
3
(
br. d, J = 11.0, 1H), 7.75 (br. s, 1H), 7.56 (br. s, 1H), 7.34 (m, 2H), 6.88 (d, J = 8.8, 1H), 4.03 (s, 3H).
C
NMR (CDCl ): δ 166.0, 161.4, 150.6, 147.2, 142.0, 137.5, 125.0, 124.7, 119.8, 117.1, 111.4, 110.5, 54.0.
3
2
-(Thiophen-2-yl)benzo[d]oxazole (Table 8, entry 6). This compound was isolated as a white solid (95 %
yield) from the reaction of 2-chlorobenzooxazole and 2-thiopheneboronic acid using the general procedure.
1
H NMR (CDCl ): δ 7.89 (d, J = 4.0, 1H), 7.67 - 7.78 (m, 1 H), 7.49 - 7.58 (m, 2H), 7.28 - 7.37 (m, 2H),
3
1
3
7
1
.11 - 7.21 (m, 1H). C NMR (CDCl ): δ 159.1, 150.4, 142.0, 130.3, 130.0, 129.7, 128.3, 125.1, 124.8,
3
19.8, 110.5.
2
-(p-Tolyl)-3-pyridinamine (Equation 1). This compound was isolated as a white solid (96 % yield) from
the reaction of 2-chloro-3-pyridinamine and 4,4,5,5-tetramethyl-2-p-tolyl-1,3,2-dioxaborolane using the
1
13
general procedure. Isolated material contained some 2,3-dimethylbutane-2,3-diol. The H and C NMR
data matched entry 2, Table 5.
2
-(Quinolin-6-yl)pyridine-4-amine (Equation 2). This compound was isolated as a white solid (92 %
yield) from the reaction of 2-chloro-4-pyridinamine and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
1
yl)quinoline using the general procedure. H NMR (CD
3
OD): δ 8.88 (d, J = 4.0, 1H), 8.45 (d, J = 8.0,
1H), 8.35 (s, 1 H), 8.19 (d, 8.6, 1H), 8.12 (d, 6.1, 2H), 7.60 - 7.57 (dd, J = 8.2, 4.2, 1H), 7.14 (s, 1H), 6.66
13
(
d, J = 5.5, 1H), -NH
2
protons not observed. C NMR (CDCl
3
): δ 157.1, 155.5, 150.6, 147.5, 147.2,
1
37.6, 136.9, 128.5, 128.4, 128.3, 126.4, 121.8, 108.0, 107.0.

1
0

1
1

1
2

1
3

1
4

15

1
6

1
7

1
8

1
9

2
0

2
1

2
2

2
3

24

2
5

26

2
7

28

29

30