Easily accessible and highly tunable Lndolyl phosphine ligands for suzuki-miyaura coupling of aryl chlorides

Article abstract of DOI:10.1021/ol070898y

This study describes a new class of easily accessible indolyl phosphine ligands, prepared via an efficient protocol involving Fischer indolization from readily available Phenylhydrazine and substituted acetophenones. This versatile ligand scaffold provides beneficial features, including high potential of steric and electronic tunability. The air-stable indolyl phosphines in combination with a palladium metal precursor provide highly effective catalysts for Suzuki-Miyaura coupling of unactivated aryl chlorides, and the catalyst loading down to 0.02 mol % can be achieved.

Full text of DOI:10.1021/ol070898y

Supporting Information
Suppporting Information
Easily Accessible and Highly Tunable Indolyl Phosphine Ligands for Suzuki-
Miyaura Coupling of Aryl Chlorides
Chau Ming So, Chak Po Lau and Fuk Yee Kwong*
Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and
Synthesis, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Hung Hom, Hong Kong.
E-mail: bcfyk@inet.polyu.edu.hk
Table of Contents
1
2
3
4
5
6
7
8
. General considerations…………………………………………………………………….…
S2
. Preparation of new indolyl phosphine ligands 2a-2g……………...……………………… S3
. Procedures for preparation arylboronic acid substrates ……………………………..… S9
. General procedures/data for intial ligand and reaction conditions screening………… S10
. General procedures for Suzuki-Miyaura couplings of aryl chlorides….………………
S11
. Characterization data for coupling products………………………………………………. S12
1
13
31
. H, C, P NMR and MS spectra…………………………………………………………… S18
. References………………………………………………………………………………………. S114
S1

Supporting Information
1
. General considerations.
Unless otherwise noted, all reagents were purchased from commercial suppliers and used
®
without purification. All Suzuki-Miyaura reactions were performed in Rotaflo (England)
resealable screw cap Schlenk flask (approx. 20 mL volume) in the presence of Teflon coated
magnetic stirrer bar (2 mm × 7 mm). Toluene and tetrahydrofuran (THF) were distilled from
1
sodium
and
sodium
benzophenone
ketyl
under
nitrogen,
respectively.
Chlorodiphenylphosphine (Tech grade from Aldrich) was distilled under vacuum prior to use.
Commercial aryl chlorides (liquid form only) were purified by passed through a short plug (0.5
cm width × 4 cm height) of neutral alumina or distillation. Commercially available arylboronic
acids were used as received except naphthylboronic acid was recrystallized under diethyl
1
ether/hexane solvent mixture in freezer. New bottle of n-butyllithium was used (Note: since the
concentration of n-BuLi from old bottle may vary, we recommend to perform a titration prior to
3 4
use). K PO was purchased from Fluka. Thin layer chromatography was performed on Merck
precoated silica gel 60 F254 plates. Silica gel (Merck, 70-230 and 230-400 mesh) was used for
column chromatography. Melting points were recorded on an uncorrected Büchi Melting Point
1
B-545 instrument. H NMR spectra were recorded on a Bruker (400 MHz) or Varian (500 MHz)
spectrometer. Spectra were referenced internally to the residual proton resonance in CDCl
3
(δ
7
.26 ppm), or with tetramethylsilane (TMS, δ 0.00 ppm) as the internal standard. Chemical
1
3
shifts (δ) were reported as part per million (ppm) in δ scale downfield from TMS. C NMR
3
1
spectra were referenced to CDCl (δ 77.0 ppm, the middle peak).
P NMR spectra were
3
referenced to 85% H PO externally. Coupling constants (J) were reported in Hertz (Hz). Mass
3 4
spectra (EI-MS and ES-MS) were recorded on a HP 5989B Mass Spectrometer. High-resolution
mass spectra (HRMS) were obtained on a Brüker APEX 47e FT-ICR mass spectrometer
(
(
ESIMS). GC-MS analysis was conducted on a HP 5973 GCD system using a HP5MS column
30 m × 0.25 mm). The products described in GC yield were accorded to the authentic
samples/dodecane calibration standard from HP 6890 GC-FID system.
S2

Supporting Information
2
. Preparation of new indolyl phosphine ligands 2a-2g
N-(Diphenylphosphino)-2-phenylindole (2a)
H
PPh
2
N
ClPPh2
N
1a
2a
General procedure for direct ligand synthesis: Commercially available 2-phenylindole (1a)
1.93 g, 10.0 mmol) was dissolved in freshly distilled THF (50 mL) at room temperature under
(
nitrogen atmosphere. The solution was cooled to -78 °C in dry ice/acetone bath. Titrated n-
BuLi (11.0 mmol) was added dropwise by syringe. After the reaction mixture was stirred for 15
min at -78 °C, distilled chlorodiphenylphosphine (1.97 mL, 11.0 mmol) in THF (20 mL) was
added. The reaction was allowed to warm to room temperature and stirred overnight. Solvent
was removed under reduced pressure. Toluene (10 mL × 4) was added and the solution was
filtered over Celite. The combined solvent was removed in vacuo. The crude product was
recyrstallized in hot ethanol under nitrogen. White crystals of N-(diphenylphosphino)-2-
phenylindole (2a) (2.95 g, 78%) were obtained after standing overnight at room temperature.
1
Melting point. 160.3-162.3 °C; H NMR (400 MHz, CDCl ) δ 6.93 (d, J = 2.9 Hz, 1H), 6.97-
3
7
.05 (m, 2H), 7.21-7.25 (m, 1H), 7.44-7.46 (m, 6H), 7.51-7.57 (m, 7H), 7.69-7.72 (m, 2H), 7.76
1
3
(
d, J = 7.7 Hz, 1H); C NMR (100 MHz, CDCl
3
) δ 106.55, 106.58, 115.33, 120.60, 121.11,
1
1
21.59, 127.90, 127.98, 128.42, 128.48, 128.92, 130.11, 130.16, 130.83, 131.03, 131.47, 133.63,
3
1
33.69, 134.78, 134.95, 139.92, 140.01, 146.92, 147.41; P NMR (202 MHz, CDCl ) δ 38.09;
3
-1
IR (cm ) 3052.63, 3006.54, 1603.41, 1480.51, 1444.67, 1429.30, 1321.76, 1265.43, 1122.05,
1
075.96, 994.03, 768.71, 743.10, 691.89, 589.47, 512.66, 461.45; MS (EI): m/z (relative
+
intensity) 376 (M -1, 80), 300 (5), 222 (10), 193 (10), 183 (100), 165 (15), 152 (10) ; HRMS:
+
calcd. for C26
H
20NPH : 378.1412, found 378.1410.
N-(Dicyclohexylphosphino)-2-phenylindole (2b)
S3

Supporting Information
H
PCy
2
N
ClPCy2
N
1a
2b
General procedures for the synthesis of ligand 2a were followed. 2-phenylindole (1a) (386 mg,
.0 mmol), n-BuLi (2.4 mmol), chlorodicyclohexylphosphine (486 μL, 2.2 mmol) were used to
2
afford N-(dicyclohexylphosphino)-2-phenylindole (2b) (660 mg, 85%) as white crystal. Melting
1
point. 143.8-145.2 °C; H NMR (400 MHz, CDCl ) δ 1.1-1.8 (m, 20H), 2.72 (m, 2H), 6.57(d, J
3
1
3
=
1.9 Hz, 1H), 7.19-7.27 (m, 2H), 7.4-7.5 (m, 5H), 7.65-7.69 (m, 2H); C NMR (100 MHz,
CDCl ) δ 25.82, 26.02, 26.27, 26.41, 26.46, 26.54, 28.73, 28.82, 30.35, 30.62, 36.67, 36.84,
3
1
1
2
8
05.18, 113.67, 120.70, 120.81, 121.53, 127.49, 130.88, 130.92, 131.06, 134.36, 134.41, 140.44,
3
1
-1
40.55, 148.02, 148.25; P NMR (162 MHz, CDCl
3
) δ 58.04; IR (cm ) 3078.24, 3057.75,
929.73, 2909.25, 2842.67, 1485.63, 1444.67, 1321.76, 1260.31, 1070.84, 994.03, 850.64,
+
25.04, 758.46, 732.86, 691.89; MS (EI): m/z (relative intensity) 388 (M -1, 100), 334 (2), 307
+
(
15), 224 (90), 193 (60), 165 (10), 145 (5); HRMS: calcd. for C26
H
32NPH : 390.2351, found
3
90.2361.
N-(Diisopropylphosphino)-2-phenylindole (2c)
H
PiPr
2
N
ClPiPr2
N
1a
2c
General procedures for the synthesis of ligand 2a were followed. 2-phenylindole (1a) (772 mg,
.0 mmol), n-BuLi (4.8 mmol), chlorodiisopropylphosphine (710 μL, 4.4 mmol) were used to
4
afford N-(dicyclohexylphosphino)-2-phenylindole (2b) (880 mg, 71%) as white crystal. Melting
1
point. 74.9-76.2 °C; H NMR (400 MHz, CDCl ) δ 1.02 (dd, J = 6.9 Hz and 12.8 Hz, 6H) 1.33
3
(
dd, J = 6.8 Hz and J = 18.2 Hz, 6H), 3.09 (m, 2H), 6.76 (d, J = 1.9 Hz, 1H), 7.37-7.40 (m, 2H),
1
3
7
2
1
.54-7.83 (m, 7H); C NMR (100 MHz, CDCl
3
) δ 19.66, 19.82, 19.93, 19.99, 20.30, 20.48,
6.59, 26.75, 105.47, 113.78, 113.79 (overlapped), 120.88, 120.98 (overlapped), 121.59, 127.63,
3
1
-1
30.97; P NMR (162 MHz, CDCl ) δ 68.35; IR (cm ) 3042.39, 2970.70, 2939.97, 2909.25,
3
S4

Supporting Information
2
7
852.92, 1444.67, 1321.76, 1265.43, 1224.47, 1173.26, 1122.05, 1075.96, 983.78, 922.33,
+
53.34, 691.89, 650.92, 579.23, 492.18; MS (EI): m/z (relative intensity) 308 (M -1, 95), 266
+
(20), 224 (100), 193 (30), 165 (20), 146 (15); HRMS: calcd. for C20
H
24NPH : 310.1725, found
3
10.1736.
N-(Dicyclohexylphosphino)-2-(2’-tolyl)indole (2d)
H N
2
Me
Me
O
Fischer-Indole
Synthesis
H
PCy
2
NH
N
ClPCy2
N
Me
Me
1b
2d
General procedure for Fischer-indole synthesis: 2’-Methylacetophenone (1.31 mL, 10 mmol)
was mixed with phenylhydrazine (0.99 mL, 10 mmol) in ethanol (5 mL) with a few drops of
glacial acetic acid. The reaction was heated to 80 °C and stirred for 1 hour. Solvent was
evaporated to yield the phenylhydrazone intermediate, which was added to polyphosphoric acid
(20 g). Exothermic reaction was observed and the reaction mixture was slowly heated to 120 °C
(
keep for 1 hour). The mixtures were poured into crashed ice cube and then neutralized with 2
M NaOH and extracted with CH
2
C1
2
. The combined organic extracts were washed with water,
dried over anhydrous Na SO , and concentrated to give to give the desired 2-(2’-tolyl)-1H-
2 4
2
indole (1b) (1.48 g, 71%) as a light brown solid, which was then dried under reduced pressure.
1
Melting point. 93.0-94.3 °C, lit. 92-93 °C; H NMR (400 MHz, CDCl
3
) δ 2.55 (s, 3H), 6.67 (d, J
1
3
=
1.9 Hz, 1H), 7.19-7.51 (m, 7H), 7.72 (d, J = 7.7 Hz, 1H), 8.10 (bs, 1H); C NMR (100 MHz,
CDCl ) δ 21.03, 102.86, 110.73, 119.87, 120.45, 121.96, 126.00, 127.88, 128.75, 128.90, 130.99,
3
-
1
1
1
7
32.51, 135.97, 136.08, 137.34; IR (cm ) 3395.73, 3052.63, 3016.79, 2960.46, 1603.41,
485.63, 1454.91, 1398.58, 1347.37, 1301.28, 1224.47, 1116.93, 1040.11, 799.43, 743.10,
+
12.38, 671.41, 533.14; MS (EI): m/z (relative intensity) 207 (M , 100), 191 (5), 178 (20), 165
(
5), 152 (5).
General procedures for the synthesis of ligand 2a were followed. 2-(2’-Tolyl)-1H-indole (1b)
414 mg, 2.0 mmol), n-BuLi (2.4 mmol), chlorodicyclohexylphosphine (486 μL, 2.2 mmol) were
(
used to afford N-(dicyclohexylphosphino)-2-(2’-tolyl)indole (2d) (600 mg, 74%) as white crystal.
1
Melting point. 147.4-148.6 ºC; H NMR (400 MHz, CDCl
S5
3
) δ 1.09-1.77 (m, 20H), 2.25 (s, 3H),

Supporting Information
1
3
2
.63 (m, 2H), 6.45 (d, J = 2.3 Hz, 1H), 7.16-7.36 (m, 6H), 7.61-7.66 (m, 2H); C NMR (100
MHz, CDCl ) δ 20.67, 26.06, 26.25, 26.45, 26.59, 26.64, 26.72, 29.09, 29.16, 30.54, 30.81,
3
37.08, 37.13, 105.41, 113.56, 120.51, 120.64, 121.34, 121.53, 124.56, 128.22, 129.52, 131.13,
3
1
1
32.43, 132.59, 134.24, 134.30, 137.60, 139.85, 139.96, 146.49, 146.75; P NMR (162 MHz,
-1
CDCl ) δ 57.79; IR (cm )3073.12, 3057.75, 3011.66, 2924.61, 2837.55, 1444.67, 1311.52,
3
1
255.19, 1122.05, 1065.72, 994.03, 804.55, 758.46, 737.98, 589.47; MS (EI): m/z (relative
+
intensity) 402 (M -1, 100), 388 (100), 320 (15), 306 (15), 238 (95), 222 (50), 207 (80), 191 (5),
+
1
78 (10); HRMS: calcd. for C H NPH : 404.2507, found 404.2515.
2
7
34
N-(Dicyclohexylphosphino)-2-(2’-methoxyphenyl)indole (2e)
H N
2
Me
MeO
O
Fischer-Indole
Synthesis
H
PCy
2
NH
N
ClPCy2
N
MeO
MeO
1c
2e
General procedures for the synthesis of 2-arylindole 1b were used. 2’-Methoxylacetophenone
(
1.38 mL, 10 mmol), phenylhydrazine (0.99 mL, 10 mmol), ethanol (5 mL), glacial acetic acid (a
3
few drops) and PPA (20 g) were used to afford 2-(2’-methoxyphenyl)-1H-indole (1c) (1.58 g,
1
7
1%) as off-white solid. Melting point. 78.5-81.0 °C, lit. 75-77 °C ; H NMR (400 MHz, CDCl
3
)
δ 4.00 (s, 3H), 7.00 (d, J = 1.5 Hz), 7.05 (d, J = 8.2 Hz), 7.10-7.34 (m, 4H), 7.50 (d, J = 8.0 Hz),
1
3
7
.74 (d, J = 7.7 Hz), 7.91 (dd, J = 1.6 Hz and 7.7 Hz), 9.72 (bs, NH, 1H); C NMR (100 MHz,
CDCl ) δ 55.68, 99.76, 110.87, 111.83, 119.70, 120.18, 120.50, 121.41, 121.73, 128.03, 128.17,
3
-
1
1
1
9
28.46, 135.89, 136.03, 155.66; IR (cm ) 3446.94, 3042.93, 3001.42, 2939.97, 2837.55,
598.29, 1577.81, 1541.96, 1460.03, 1434.42, 1311.52, 1234.71, 1173.26, 1122.05, 1019.63,
+
22.33, 789.19, 732.86, 661.17, 558.75; MS (EI): m/z (relative intensity) 223 (M , 100), 208
(35), 193 (20), 180 (35), 165 (20), 152 (25).
General procedures for the synthesis of ligand 2a were followed. 2-(2’-Methoxyphenyl)-1H-
indole (1c) (446 mg, 2.0 mmol), n-BuLi (2.4 mmol), chlorodicyclohexylphosphine (486 μL, 2.2
mmol) were used to afford N-(dicyclohexylphosphino)-2-(2’-methoxyphenyl)indole (2e) (670
1
mg, 80%) as white crystal. Melting point. 131.1-132.5 °C; H NMR (400 MHz, CDCl ) δ 1.12-
3
1
.81 (m, 20H), 2.65 (m, 2H), 6.52 (d, J = 1.6 Hz, 1H), 6.99 (d, J = 8.2 Hz, 1H), 7.05 (t, J = 7.3
S6

Supporting Information
1
3
Hz, 1H), 7.16-7.30 (m, 3H), 7.44-7.48 (m, 1H), 7.63-7.67 (m, 2H) C NMR (100 MHz, CDCl
3
)
δ 26.03, 26.18, 26.43, 26.58, 26.63, 28.45, 28.53, 30.39, 30.59, 30.87, 36.72, 36.88, 54.87,
1
1
3
1
04.91, 110.04, 113.43, 119.83, 120.17, 120.78, 121.25, 123.83, 123.88, 129.83, 131.22, 132.84,
3
1
-1
40.02, 140.13, 144.87, 145.14, 157.27;
P NMR (162 MHz, CDCl ) δ 59.90; IR (cm )
3
078.24, 3006.54, 2919.49, 2842.67, 1582.93, 1541.96, 1490.75, 1444.67, 1326.88, 1244.95,
122.05, 1024.75, 999.15, 778.95, 743.10, 661.17, 471.69; MS (EI): m/z (relative intensity) 418
+
(
M -1, 2), 388 (100), 306 (4), 254 (10), 239 (13), 222 (10), 209 (3), 192 (2); HRMS: calcd. for
+
C H NOPH : 420.2456, found 420.2469.
2
7
34
N-(Dicyclohexylphosphino)-2-(4’-tolyl)indole (2f)
Me
O
H N
2
Fischer-Indole
Synthesis
H
PCy
2
NH
N
ClPCy2
N
Me
1d
2f
Me
Me
General procedures for the synthesis of 2-arylindole 1b were used. 4’-Methylacetophenone
(
1.34 mL, 10 mmol), phenylhydrazine (0.99 mL, 10 mmol), ethanol (5 mL), glacial acetic acid (a
4
few drops) and PPA (20 g) were used to afford 2-(4’-tolyl)-1H-indole (1d) (1.64 g, 79%) as off-
1
white solid. Melting point. 218.0-219.9 °C, lit. 220 °C; H NMR (400 MHz, CDCl
3
) δ 2.41 (s,
3
H), 6.81 (s, 1H), 7.13-7.27 (m, 4H), 7.39 (d, J = 7.7 Hz, 1H), 7.56 (d, J = 7.7 Hz, 2H), 7.65 (d, J
1
3
=
3
7.5 Hz, 1H); C NMR (100 MHz, CDCl ) δ 21.19, 99.35, 110.79, 120.15, 120.48, 122.07,
-
1
1
2
7
25.02, 129.29, 129.51, 129.66, 136.65, 137.60, 138.02; IR (cm ) 3431.58, 3047.51, 3021.91,
909.25, 1501.00, 1454.91, 1424.18, 1347.37, 1296.16, 1229.59, 1122.05, 825.04, 789.19,
+
32.86, 656.05, 512.66; MS (EI): m/z (relative intensity) 207 (M , 100), 191 (4), 178 (7), 165
(
4), 152 (2).
General procedures for the synthesis of ligand 2a were followed. 2-(4’-Tolyl)-1H-indole (1d)
414 mg, 2.0 mmol), n-BuLi (2.4 mmol), chlorodicyclohexylphosphine (486 μL, 2.2 mmol) were
(
used to afford N-(dicyclohexylphosphino)-2-(4’-tolyl)indole (2f) (620 mg, 77%) as white crystal.
1
Melting point. 168.8-169.2 °C; H NMR (400 MHz, CDCl
3
) δ 1.14-1.83 (m, 20H), 2.46 (s, 3H),
2
.73 (m, 2H), 7.56 (d, J = 1.0 Hz, 1H), 7.20-7.29 (m, 4H), 7.40 (d, J = 7.5 Hz, 2H), 7.65-7.69 (m,
S7

Supporting Information
1
3
2
3
1
5
1
H); C NMR (100 MHz, CDCl ) δ 21.32, 26.02, 26.29, 26.44, 26.47, 26.56, 28.73, 28.82,
3
0.35, 30.63, 36.67, 36.84, 104.4, 113.63, 120.63, 120.70, 121.37, 128.33, 130.70, 130.74,
3
1
31.12, 131.45, 131.50, 137.25, 140.38, 140.49, 148.10, 148.34; P NMR (162 MHz, CDCl ) δ
3
-1
7.71; IR (cm ) 3083.36, 3042.39, 3016.79, 2914.37, 2842.67, 1495.87, 1439.54, 1321.76,
260.31, 1183.50, 1116.93, 1070.84, 994.03, 819.91, 784.07, 748.22, 727.74, 686.77, 574.11;
+
MS (EI): m/z (relative intensity) 403 (M , 100), 321 (20), 238 (95), 222 (30), 207 (70), 191 (3),
+
1
78 (5), 165 (2); HRMS: calcd. for C27
H
34NPH : 404.2507, found 404.2513.
N-(Dicyclohexylphosphino)indole (2g)
ClPCy2
H
N PCy
2
N
H
H
2g
General procedures for the synthesis of ligand 2a were followed. Indole (469 mg, 4.0 mmol), n-
BuLi (4.4 mmol), chlorodicyclohexylphosphine (972 μL, 4.4 mmol) were used to afford N-
(
dicyclohexylphosphino)indole (2g) (921 mg, 73%) as white crystal. Melting point. 65.0-66.9
1
°
C; H NMR (400 MHz, C
6
D
6
) δ 1.05-1.22 (m, 11H), 1.47-1.82 (m, 11H), 1.99 (s, 2H), 6.74 (d,
J = 2.6 Hz, 1H), 7.10 (s, 1H), 7.24-7.39 (m, 2H), 7.77 (d, J = 7.7 Hz, 1H), 8.14 (d, J = 6.0 Hz,
1
3
1
H); C NMR (100 MHz, C
6 6
D ) δ 26.88, 27.03, 27.36, 27.42, 27.44, 27.55, 28.82, 28.89, 30.07,
3
1
3
0.28, 37.12, 37.27, 106.77, 113.42, 113.58, 121.36, 121.63, 123.06, 130.98; P NMR (162
-1
MHz, C
6
D
6
) δ 47.82; IR (cm ) 3042.93, 2914.37, 2847.80, 1444.67, 1291.04, 1270.55, 1132.29,
+
1
2
3
004.27, 881.37, 763.58, 737.98, 640.68, 492.18; MS (EI): m/z (relative intensity) 313 (M , 40),
+
58 (3), 231 (40), 197 (4), 148 (100), 117 (30); HRMS: calcd. for C H NPH : 314.2038, found
2
0
28
14.2043.
S8

Supporting Information
3
. Procedures for preparation arylboronic acid substrates
5
1-Naphthylboronic acid
HO
OH
B
Anhydrous THF (20 mL) was added to 1-bromonaphthalene (5.56 mL, 40 mmol) under nitrogen
o
at room temperature. n-Butylithium (44 mmol) was added dropwise to the solution at -78 C and
i
stirred for 30min. The reaction mixture was transferred to a solution of B(O Pr)
3
(18.6 mL, 80
mmol) in THF (10 mL) at -78 °C via cannular under nitrogen. The solution was warm to room
temperature and stirred overnight. Diluted HCl (10%, 20 mL) was added to the mixture and
stirred for 30min. The organic layer was separated and the aqueous phase was extracted by
diethyl ether (50 mL × 3). The combined organic extracts were washed with brine and dried
4
over MgSO . The solvent was removed and the residue was crystallized under ether/hexane to
give colorless crystals (5.0 g, 72%). The product was used without further characterization.
S9

Supporting Information
4
. General procedures/data for intial ligand and reaction conditions screening
2 3
General procedure for base screening: A stock solution of Pd (dba) (15 mg) with ligand 2b (51
mg) (Pd:L = 1:4) in freshly distilled toluene (10.0 mL) was initially prepared with continuously
stirring at room temperature. 4-Chlorotoluene (82.9 mg), phenylboronic acid (120 mg), base (3.0
equiv.) and magnetic stirrer bar (2 mm × 7 mm) were charged to an array of Schlenk tubes. Each
tube was carefully evacuated and backfilled with nitrogen (3 cycles). Stock solution of
palladium complex (2.0 mL, 1 mol% Pd) were added by syringe. This batch of Schlenk tube was
resealed and magnetically stirred in a preheated oil bath. The reactions were allowed to reach
room temperature. Diethylether (~5 mL), dodecane (149 μL, internal standard) water (~5 mL)
were added. The organic layer was subjected to GC analysis. The GC yield was previously
calibrated by authentic sample/dodecane calibration curve.
1
% Pd-2b
Me
Me
PCy2
N
base
toluene
Cl
(HO) B
2
o
100 C
2b
entry
base
PO
CO
CsF
Na CO
GC yield (%)
1
2
3
4
5
K
3
4
93
58
41
14
5
Cs
2
3
2
3
KOt-Bu
S10

Supporting Information
5
. General procedures for Suzuki-Miyaura couplings of aryl chlorides
General procedure for Suzuki-Miyaura coupling of aryl chlorides: A stock solution of Pd
3 mg) with ligand (Pd:L = 1:4) in freshly distilled toluene (2 mL, 1.0 mol% Pd) was initially
prepared with continuously stirring at room temperature. Aryl chloride (0.65 mmol), arylboronic
acid (1.5 equiv.), K PO (3.0 equiv.) and magnetic stirrer bar (2 mm × 7 mm) were charged to an
2 3
(dba)
(
3
4
array of Schlenk tubes. Each tube was carefully evacuated and backfilled with nitrogen (3
cycles). The stock solution was further diluted to give different concentrations of palladium
complex (final solution volume: 2.0 mL). The diluted solutions were then transferred to Schlenk
tubes via syringes. This batch of Schlenk tube was resealed and magnetically stirred in a
preheated oil bath. After the completion of reaction as judged by GC or TLC analysis, the
reactions were allowed to reach room temperature. Water (~3 mL) and diethylether (~10 mL × 3)
were added. The organic layers were combined and concentrated. The crude products were
purified by column chromatography on silica gel (230-400 mesh).
S11

Supporting Information
6
. Characterization data for coupling products
6
4
-Methylbiphenyl (Table 2, entry 1).
Me
1
R
f
= 0.5 (hexane); H NMR (400 MHz, CDCl
3
)

1
3
7
.50 (m, 1H), 7.36 (t, J = 7.4 Hz, 2H), 7.66 (d, J = 8.12, 2H), 7.74-7.76 (m, 2H); C NMR (100
MHz, CDCl
3
) δ 21.02, 126.89, 126.92, 128.65, 129.42, 136.89, 138.28, 141.08; MS (EI): m/z
+
(
relative intensity) 168 (M , 100), 152 (30), 128 (10).
6
2
-Methylbiphenyl (Table 2, entry 2).
Me
1
R
f
= 0.5 (hexane); H NMR (400 MHz, CDCl
3
) δ 2.43 (s, 3H), 7.39-7.42 (m, 4H), 7.47-7.49 (m,
1
3
3
1
1
H), 7.53-7.57 (m, 2H); C NMR (100 MHz, CDCl ) δ 20.41, 125.71, 126.70, 127.19, 128.00,
3
+
29.13, 129.74, 130.25, 135.24, 141.88, 141.91; MS (EI): m/z (relative intensity) 168 (M , 100),
53 (40), 128 (10).
6
2
-Methyl-4’-methylbiphenyl (Table 2, entry 3).
Me
Me
1
R
f
= 0.65 (hexane); H NMR (400 MHz, CDCl
3
) δ 2.45 (s, 3H), 2.56 (s, 3H), 7.38-7.41 (m, 8H);
1
3
C NMR (100 MHz, CDCl
3
) δ 20.44, 21.09, 125.69, 127.01, 128.72, 129.01, 129.79, 130.22,
+
1
35.28, 136.25, 139.00, 141.83; MS (EI): m/z (relative intensity) 182 (M , 95), 167 (100), 152
(25), 141 (10), 128 (10).
7
2
,6-Dimethylbiphenyl (Table 2, entry 4).
S12

Supporting Information
Me
Me
1
13
R
f
= 0.5 (hexane); H NMR (400 MHz, CDCl
3
) δ 2.22 (s, 6H), 7.2-7.6 (m, 8H); C NMR (100
MHz, CDCl ) δ 20.77, 126.54, 126.97, 127.23, 128.35, 128.94, 135.92, 141.05, 141.80; MS (EI):
3
+
m/z (relative intensity) 182 (M , 95), 167 (100), 152 (30), 139 (10), 128 (10).
8
4
-(2’-Tolyl)benzophenone (Table 2, entry 5).
Me
O
Ph
1
R
f
= 0.2 (hexane:DCM = 8:2); H NMR (400 MHz, CDCl
3
) δ 2.34 (s, 3H,), 7.33-7.28 (m, 4H),
1
3
7
1
.62-7.5 (m, 5H), 7.89 (m, 4H); C NMR (100 MHz, CDCl ) δ 20.34, 125.84, 127.77, 128.18,
3
29.05, 129.45, 129.90, 130.43, 132.25, 135.06, 135.83, 137.59, 140.67, 146.21, 196.25; MS
+
(
EI): m/z (relative intensity) 272 (M , 70), 195 (100), 164 (40), 152 (40), 105 (40).
9
3
-(2’-Tolyl)aniline (Table 2, entry 6).
Me
H N
2
1
R
f
= 0.4 (hexane:DCM = 4:6); H NMR (400 MHz, CDCl
3
) δ 2.34 (s, 3H), 3.72 (bs, 2H, NH),
) δ 20.34,
1
3
6
.67-6.71 (m, 2H), 6.76-6.78 (m, 1H), 7.2-7.32 (m, 5H); C NMR (100 MHz, CDCl
3
1
13.46, 115.88, 119.56, 125.52, 127.01, 128.83, 129.47, 130.10, 135.21, 142.04, 143.01, 146.02;
+
MS (EI): m/z (relative intensity) 183 (M , 100), 165(45), 152(20).
1
0
4
-(1-Naphthyl)acetophenone (Table 2, entry 7).
O
Me
S13

Supporting Information
1
R = 0.2 (hexane:DCM = 6:4); H NMR (400 MHz, CDCl ) δ 2.68 (s, 3H), 7.42-7.56 (m, 4H),
f
3
1
3
7
.60 (d, J = 8.4 Hz, 2H), 7.88-7.95 (m, 3H), 8.10 (d, J = 8.4 Hz, 2H); C NMR (100 MHz,
CDCl
3
) δ 26.47, 125.15, 125.35, 125.81, 126.20, 126.75, 128.17, 128.25, 130.08, 130.98, 133.61,
+
1
35.76, 138.78 ,145.51, 197.55; MS (EI): m/z (relative intensity) 246 (M , 90), 231 (100), 202
(
95), 176 (10).
6
Methyl 4-(4’-tolyl)benzoate (Table 2, entry 8).
MeOOC
Me
1
R
f
= 0.25 (hexane:DCM = 8:2); H NMR (400 MHz, CDCl
3
) δ 2.42 (s, 3H), 3.95 (s, 3H), 7.27 (d,
1
3
J = 8.0Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.3 Hz), 8.11 (d, J = 8.3 Hz, 2H).;
C
NMR (100 MHz, CDCl
3
) δ 21.00, 51.89, 126.60, 126.93, 128.44, 129.51, 129.94, 136.89, 137.92,
+
1
1
45.38, 166.85; MS (EI): m/z (relative intensity) 226 (M , 85), 195 (100), 165 (40), 152 (50),
39 (10).
1
1
Methyl 3-(3’,5’-dimethylphenyl)benzoate (Table 2, entry 9).
MeO
Me
O
Me
1
R
f
= 0.25 (hexane:DCM = 7:3); H NMR (400 MHz, CDCl
3
) δ 2.43 (s, 3H), 3.98 (s, 3H), 7.05 (s,
1
H), 7.28 (s, 1H), 7.50 (t, J = 7.76 Hz, 1H), 7.78-7.80 (m, 1H), 8.03-8.06 (m, 1H), 8.33 (m, 1H);
1
3
C NMR (100 MHz, CDCl
3
) δ 21.17, 51.90, 124.86, 127.98, 128.04, 128.53, 129.20, 130.39,
+
1
31.33, 138.18, 139.85, 141.50, 166.89; MS (EI): m/z (relative intensity) 240 (M , 100), 209
(80), 181 (25), 165 (60), 152 (10).
1
2
4
-Phenylanisole (Table 2, entry 10).
S14

Supporting Information
MeO
1
R
f
= 0.5 (hexane:DCM = 7:3); H NMR (400 MHz, CDCl
3
) δ 3.92 (s, 3H), 7.09 (dt, 2H, J = 8.7
1
3
3
Hz and J = 2.4 Hz), 7.42 (m, 1H), 7.53 (m, 2H), 7.64-7.68 (m, 4H); C NMR (100 MHz, CDCl )
δ 55.15, 114.13, 126.56, 126.62, 128.039, 128.649, 133.63, 140.71, 159.08; MS (EI): m/z
+
(
relative intensity) 184 (M , 100), 169 (55), 152 (10), 141 (50), 115 (40).
1
3
4
-(1-Naphthyl)benzonitrile (Table 2, entry 11).
NC
1
13
R
f
= 0.25 (hexane:DCM = 8:2); H NMR (400 MHz, CDCl
3
) δ 7.38-7.96 (m, 11H); C NMR
(
100 MHz, CDCl ) δ 110.88, 118.72, 124.95, 125.15, 125.98, 126.45, 126.84, 128.35, 128.57,
3
+
1
2
30.54, 130.69, 131.88, 133.57, 137.95, 145.33; MS (EI): m/z (relative intensity) 229 (M , 100),
01 (15), 189 (5).
1
2
2
-(2’-Tolyl)pyridine (Table 3, entry 1).
Me
N
1
R
f
= 0.2 (hexane:EA = 9:3); H NMR (400 MHz, CDCl
3
) δ 2.38 (s, 3H), 7.18-7.45 (m, 6H), 7.72
1
3
(
dt, J = 7.7 Hz and 1.8 Hz, 1H), 8.69-8.71 (m, 1H); C NMR (100 MHz, CDCl ) δ 20.12,
3
1
21.45, 123.91, 125.70, 128.10, 129.45, 130.57, 135.57, 135.93, 140.28, 149.02, 159.88; MS
+
(
EI): m/z (relative intensity) 168 (M , 100), 141 (5), 128 (2), 115 (5).
2
-(3’,5’-Dimethylphenyl)-6-methylpyridine (Table 3, entry 2).
Me
Me
N
Me
S15

Supporting Information
1
R = 0.25 (hexane:DCM = 7:3); light yellow viscous liquid; H NMR (400 MHz, CDCl ) δ 2.40
f
3
1
3
(
(
s, 6H), 2.64 (s, 3H), 7.05-7.08 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H); 7.58-7.62 (m, 3H) C NMR
100 MHz, CDCl
3
) δ 21.35, 24.67, 117.72, 121.37, 1247.83, 130.33, 136.72, 138.07, 139.65,
+
1
57.28, 158.12; MS (EI): m/z (relative intensity) 197 (M , 100), 181 (25), 167 (10), 152 (5), 139
+
(
3); HRMS: calcd. for C14H15NH : 198.1283, found 198.1282.
3
-(3’,5’-Dimethylphenyl)pyridine (Table 3, entry 3).
Me
N
Me
1
R = 0.15 (DCM); light yellow viscous liquid; H NMR (400 MHz, CDCl ) δ 2.39 (s, 6H), 7.04
f
3
(
m, 1H), 7.19 (s, 2H), 7.32 (dd, J = 7.8 Hz and J = 4.8 Hz, 1H), 7.84 (dt, J = 7.9 Hz and 1.9 Hz),
1
3
8
1
1
.57 (m, 1H), 8.84 (bs, 1H); C NMR (100 MHz, CDCl
3
) δ 21.23, 123.40, 124.90, 129.64,
+
34.39, 136.84, 137.88, 138.53, 147.89, 147.98; MS (EI): m/z (relative intensity) 183 (M , 100),
+
68 (60), 152 (7), 139 (8), 128 (5); HRMS: calcd. for C13
H13NH : 184.1126, found 184.1121.
2
-(1-Naphthyl)-6-methylpyridine (Table 3, entry 4).
Me
N
1
R
f
= 0.15 (hexane:DCM = 1:1); colorless viscous liquid; H NMR (400 MHz, CDCl
3
) δ 2.71 (s,
3
8
1
H), 7.18 (d, J = 7.7 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.42-7.70 (m, 5H), 7.91-7.93 (m, 2H),
1
3
.11-8.14 (m, 1H);
3
C NMR (100 MHz, CDCl ) δ 24.56, 121.32, 121.81, 125.12, 125.55,
25.58, 126.11, 127.12, 128.07, 128.46, 131.08, 133.76, 136.32, 138.59, 157.95, 158.38; MS
+
(
EI): m/z (relative intnsity) 218 (M -1, 100), 204 (10), 189 (5), 176 (5), 163 (2), 151 (4); HRMS:
+
calcd. for C16
H
13NH : 220.1126, found 220.1133.
1
4
1
-Phenylcyclopentene (Table 3, entry 5).
S16

Supporting Information
1
R
f
= 0.8 (hexane); H NMR (400 MHz, CDCl
3
) δ 2.04-2.12 (m, 2H), 2.57-2.62 (m, 2H), 2.75-
1
3
2
.80 (m, 2H), 6.24-6.26 (m, 1H), 7.25-7.39 (m, 3H), 7.51 (d, J = 7.8 Hz, 2H); C NMR (100
MHz, CDCl ) δ 23.31, 33.12, 33.31, 125.49, 126.01, 126.03, 126.76, 128.20, 136.75, 142.38;
3
+
MS (EI): m/z (relative intensity) 144 (M , 100), 129 (15), 115 (40), 102 (10), 91 (12), 77 (10).
1
5
4
-(n-Butyl)acetophenone (Table 3, entry 6).
O
Me
n-Bu
1
R
f
= 0.25 (hexane:DCM = 8:2); H NMR (400 MHz, CDCl
3
) δ 0.91 (t, J = 7.3 Hz, 3H), 1.35 (m,
2
H), 1.59 (m, 2H), 2.55 (s 3H), 2.64 (t, J = 7.7 Hz, 2 H), 7.24 (d, J = 8.2 Hz, 2H), 7.86 (d, J = 8.2
1
3
Hz, 2 H); C NMR (100 MHz, CDCl
3
) δ13.78, 22.20, 26.40, 33.13, 35.56, 128.34, 128.49,
+
1
34.80, 148.66, 197.69; MS (EI): m/z (relative intensity) 176 (M , 20), 161 (100), 133 (10), 118
(5), 105 (15).
S17

Supporting Information
1
13
31
7
. H, C, P NMR and MS spectra
NH
Me
1
H NMR of 1b
S18

Supporting Information
NH
Me
1
3
C NMR of 1b
S19

Supporting Information
NH
Me
MS spectrum of 1b
S20

Supporting Information
NH
MeO
1
H NMR of 1c
S21

Supporting Information
NH
MeO
1
3
C NMR of 1c
S22

Supporting Information
NH
MeO
MS spectrum of 1c
S23

Supporting Information
NH
Me
1
H NMR of 1d
S24

Supporting Information
NH
Me
1
3
C NMR of 1d
S25

Supporting Information
NH
Me
MS spectrum of 1d
S26

Supporting Information
PPh2
N
3
1
P NMR of 2a
S27

Supporting Information
PPh2
N
1
H NMR of 2a
S28

Supporting Information
PPh2
N
1
3
C NMR of 2a
S29

Supporting Information
PPh2
N
MS spectrum of 2a
S30