A bulky biaryl phosphine ligand allows for palladium-catalyzed amidation of five-membered heterocycles as electrophiles

Article abstract of DOI:10.1002/anie.201201244

The incredible bulk: The first palladium-catalyzed amidation of five-membered heterocyclic bromides with multiple heteroatoms was achieved using the Pd/1 catalyst system. N-Arylated imidazoles, pyrazoles, thiazoles, pyrroles, and thiophenes were synthesized in moderate to excellent yield. Experimental results and DFT calculations point to the need for an electron-rich and sterically demanding biaryl phosphine ligand to promote these difficult reactions. Copyright

Full text of DOI:10.1002/anie.201201244

Supporting Information
ꢀ
Wiley-VCH 2012
69451 Weinheim, Germany
A Bulky Biaryl Phosphine Ligand Allows for Palladium-Catalyzed
Amidation of Five-Membered Heterocycles as Electrophiles**
Mingjuan Su and Stephen L. Buchwald*
anie_201201244_sm_miscellaneous_information.pdf

Supporting Information
General Procedures
All reactions were carried out under an argon atmosphere. Anhydrous 2-Methyl-2-Butanol was purchased
TM
2
from Aldrich Chemical Co. in Sure/Seal bottles and was used as received. [(allyl)PdCl] and L1 were
purchased from Strem Chemicals Inc. and heterocycles, heteroaryl halides and amides were purchased
from Aldrich Chemical Co., Alfa Aesar, TCI America or Combi-Blocks and were used without further
purification. Anhydrous cesium carbonate was purchased from Alfa Aesar, and stored in a glovebox.
Small portions were removed and stored in a desiccator for up to 2 weeks (All reactions were set-up in the
[
1]
[2]
[3]
air outside of the glovebox). L2, L3 and L4 were prepared by literature procedure.
Reactions were monitored by GC and thin-layer chromatography (TLC) carried out on 0.25 mm E. Merck
silica gel plates (60F-254) using UV light. Flash silica gel chromatography was performed using Silicycle
1
13
31
SiliaFlashP60 (230-400 mesh) silica gel. All compounds were characterized by H NMR, C NMR, P
1
9
1
13
31
19
NMR, F NMR, and IR spectroscopy. Copies of the H NMR, C NMR, P NMR and F NMR spectra
can be found at the end of the Supporting Information. Nuclear Magnetic Resonance spectra were
1
recorded on a Varian 300 and Bruker 400 MHz instrument. All H NMR experiments are reported in δ
units, parts per million (ppm), and were measured relative to the signals for residual chloroform (7.26
ppm), methylene chloride (5.32 ppm) or dimethylsulfoxide-d6 (2.50 ppm) in the deuterated solvent. All
1
3
C NMR spectra are reported in ppm relative to deuterochloroform (77.16 ppm), deuterated methylene
chloride (53.84 ppm) or dimethylsulfoxide-d6 (39.52 ppm) and all were obtained with 1H decoupling. All
IR spectra were taken on a Perkin – Elmer 2000 FTIR. All GC analyses were performed on a Agilent
6
890 gas chromatograph with an FID detector using a J & W DB-1 column (10m, 0.1 mm I.D.). Melting
points were obtained on a Mel-Temp II capillary melting point apparatus. Elemental analyses were
performed by Atlantic Microlabs Inc., Norcross, GA. The pure compounds are estimated to be ≥ 95%
1
pure as determined by H NMR and GC analysis.
Computational Methods
[
4]
All calculations were carried out with Q-Chem suite of computational programs. Ground state geometry
optimizations were evaluated using B3LYP density functional method. For C, H, O, N, P, and Br atoms,
the 6-31G(d) basis set was used; while LANL2DZ effective core potentials of Hay and Wadt with
double-ζ basis sets were used for Pd atom. Frequency calculations were performed on all optimized
structures to verify that they have no negative frequencies. The Gibbs free energies were calculated at
[
5]
[
6]
2
98.15 K and 1 atm.
Ligand Synthesis
tert-butyl-adamantyl(2’,4’,6’-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (L5)
OMe
An oven-dried three-neck 250 mL round-bottom flask was charged with magnesium
shavings (7.70 g, 0.32 mol) and 1-bromoadamantane (4.50 g, 0.02 mol). The necks
were fitted with a reflux condenser, glass stopper, and rubber septum. The flask was
then evacuated and backfilled with argon (this process was repeated a total of three
tBu
MeO
i-Pr
P
Ad
i-Pr
times). To the reaction vessel was added Et
heated to a gentle reflux for 15 h in an oil bath. Upon completion, the resulting
2
O (26 mL) via syringe, and the mixture was
i-Pr
Grignard reagent was taken up in a syringe, and added dropwise to a second oven-dried three-neck 250
mL round-bottom flask fitted with a reflux condenser, glass stopper and rubber septum and containing
tBuPCl
2 2
(0.60 g, 3.77 mmol) and 6 mL Et O at -40 °C. The resulting mixture was stirred for 30 min at -
4
0°C. The reaction mixture was allowed to slowly warm to room temperature where it was stirred for an
additional 30 min. The reaction vessel was placed into a preheated oil bath and was warmed to a gentle
reflux for 3 h. The mixture was cooled to room temperature, layered with anhydrous pentane (20 mL) and
S1

filtered using a cannula filter. The volatiles were removed in vacuo, taking care to not expose the product
to air, to afford crude tert-butyl-1-adamantylchlorophosphine.
An oven-dried resealable Schlenk tube equipped with a magnetic stir bar was charged with 2-iodo-
[
7]
2
’,4’,6’-triisopropyl-3,6-dimethoxybiphenyl (1.10 g, 2.35 mmol). The flask was evacuated and
backfilled with argon (this process was repeated a total of three times). Toluene (18 mL) was added via
syringe and the reaction mixture was cooled to -78°C. tBuLi (1.7M in pentane, 2.8 mL, 4.7 mmol) was
added in a dropwise fashion over a 10 min period via syringe. The resulting solution was stirred for 30
min at -78°C and CuCl (233 mg, 2.35 mmol) was added rapidly by removing the septum of the Schlenk
tube under a positive pressure of argon. The septum was refitted and a solution of tert-butyl-1-
adamantylchlorophosphine (in 8 mL toluene and 0.5 mL THF) was added via cannula in a dropwise
fashion. The reaction mixture was then allowed to warm to rt. The Schlenk tube was sealed with a Teflon
screw cap once the reaction mixture turned dark grey and was then heated to 140 °C for 24 h. The
reaction mixture was cooled to rt, diluted with EtOAc, washed with 30% NH
with brine, dried over MgSO , filtered and concentrated in vacuo. The resulting solid was recrystallized
from dichloromethane to give white crystals (0.50 g, 38%), mp 208-210 °C; H NMR (400 MHz, CDCl
4
OH (three times), washed
4
1
3
)
δ 6.95 (s, 2H), 6.85 (q, J = 8.8 Hz, 2H), 3.79 (s, 3H), 3.55 (s, 3H), 2.94 (m, 1H), 2.49 (m, 2H), 1.84 (s, 10
H), 1.63 (s, 7H), 1.31 (d, J = 7.2 Hz, 6H), 1.21 (dd, J = 6.6, 2.4 Hz, 6H), 1.13 (d, J = 12.0 Hz, 8H), 0.92
1
3
(
1
3
dd, J = 6.8, 2.8 Hz, 6H) ; C NMR (100 MHz, CDCl
3
) δ 155.8, 155.7, 152.5, 152.4, 147.1, 146.7, 146.5,
40.6, 140.2, 133.0, 132.9, 126.7, 126.2, 120.0, 110.8, 108.0, 107.8, 54.3, 54.0, 41.8, 41.7, 38.4, 38.1,
7.2, 34.4, 34.1, 34.0, 32.3, 32.2, 31.2, 31.1, 29.4, 29.3, 29.2, 25.7, 25.6, 24.3, 24.1, 23.6, 23.6, 23.5
3
1
(
observed complexity due to P–C splitting); P NMR (161 MHz, CDCl
3
) δ 37.2, 35.4; IR (film) νmax
2
9
903, 2362, 2337, 1653, 1606, 1580, 1457, 1421, 1382, 1359, 1301, 1252, 1172, 1127, 1088, 1046, 1020,
08, 873, 797, 735, 651 cm .
-
1
di-adamantyl(2’,4’,6’-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (L6)
OMe An oven-dried three-neck 250 mL round-bottom flask, charged with magnesium
shavings (15.3 g, 0.63 mol) and 1-bromoadamantane (9.0 g, 0.04 mol). The necks were
MeO
i-Pr
PAd2
i-Pr
fitted with a reflux condenser, glass stopper, and rubber septum. The flask was
evacuated and backfilled with argon (this process was repeated a total of three times).
2
To the reaction vessel, Et O (55 mL) was added via syringe, and the mixture was
heated to a gentle reflux for 15 h in an oil bath. Upon completion, the resulting
Grignard reagent was taken up in a syringe, and added dropwise to a second oven-dried
i-Pr
three-neck 250 mL round-bottom flask fitted with a reflux condenser, glass stopper and rubber septum,
and containing PCl (0.63 mL, 7.2 mmol) and 14 mL Et O at -40°C. The resulting mixture was stirred for
0 min at -40°C. The reaction mixture was allowed to slowly warm to room temperature where it was
3
2
3
stirred for an additional 30 min. The reaction vessel was placed into a heated oil bath and was warmed to
a gentle reflux for 3 h. The mixture was cooled to room temperature, layered with anhydrous pentane (30
mL) and filtered using a cannula filter. The volatiles were removed in vacuo, taking care to not expose the
product to air, to afford crude crude di-1-adamantylchlorophosphine.
An oven-dried resealable Schlenk tube, which was equipped with a magnetic stir bar and charged with 2-
[
7]
iodo-2’,4’,6’-triisopropyl-3,6-dimethoxybiphenyl (2.2 g, 4.7 mmol). The flask was evacuated and
backfilled with argon (this process was repeated a total of three times). Toluene (30 mL) was added via
syringe and the reaction mixture was cooled to -78°C. tBuLi (1.7M in pentane, 5.5 mL, 9.4 mmol) was
added in a dropwise fashion over 10 min period via syringe. The resulting solution was stirred for 30 min
at -78°C and CuCl (465 mg, 4.7 mmol) was added rapidly by removing the septum of the Schlenk tube
under a positive pressure of argon. The septum was refitted and a solution of di-1-
adamantylchlorophosphine in 15 mL toluene was added. The reaction mixture was then allowed to warm
to rt. The Schlenk tube was sealed with a Teflon screw cap once the reaction mixture turned dark grey and
was heated to 140°C for 24 h. The reaction mixture was cooled to rt, diluted with EtOAc, washed with
S2

3
0% NH
4 4
OH (three times), washed with brine, dried over MgSO , filtered and concentrated in vacuo. The
resulting solid was recrystallized from hot methanol to give white crystals (1.5 g, 50%), mp 226-228 °C;
1
H NMR (400 MHz, CDCl
3
) δ 6.94 (s, 2H), 6.85 (q, J = 8.0 Hz, 2H), 3.81 (s, 3H), 3.54 (s, 3H), 2.93 (m,
1
H), 2.49 (m, 2H), 1.85 (m, 18 H), 1.63 (s, 12H), 1.31 (d, J = 4.0 Hz, 6H), 1.21 (d, J = 8.0 Hz, 6H), 0.91
1
3
(
d, J = 8.0 Hz, 6H); C NMR (100 MHz, CDCl
3
) δ 155.7, 152.5, 152.4, 147.0, 146.6, 140.9, 140.6, 133.0,
1
2
32.9, 126.0, 125.6, 120.0, 110.7, 107.8, 60.6, 54.3, 54.0, 42.2, 42.1, 39.0, 38.7, 37.2, 34.0, 31.2, 29.4,
3
1
9.3, 25.7, 24.2, 23.7, 21.2, 14.4 (observed complexity due to P–C splitting); P NMR (161 MHz,
) δ 37.3; IR (film) νmax 2903, 2361, 2338, 1576, 1457, 1417, 1341, 1247, 1084, 1038, 1015, 971,
CDCl
10, 871, 797, 757, 733, 720, 668, 642, 479 cm .
3
-
1
9
Optimization Table
Table S1. Optimization of reaction conditions for the amidation of 4-bromo-1-methylimidazole
Me
Me
O
1
.0 mol% Pd
N
O
N
5.0 mol% AdBrettPhos
+
H N
2
Base (1.4 equiv)
Solvent, 21 h
N
N
H
N
Br
Entry
Palladium
Pd(OAc) /H
Base
Solvent
Conc. Temp. Conv. GC Yield
[
M]
(°C)
130
130
130
130
130
130
130
130
130
130
130
130
130
130
120
110
100
90
[%]
40
40
80
8
<5
78
<5
77
82
37
[%]
32
36
62
6
[
a]
1
2
2
O
Cs
Cs
Cs
Cs
2
2
2
2
CO
CO
CO
CO
3
3
3
3
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Toluene
Toluene
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.25
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
3
[Pd(π-cinnamyl)Cl]
2
[(allyl)PdCl]
Pd dba
2
[
b]
4
2
3
5
6
7
8
9
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
[(allyl)PdCl]
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
K
K
2
CO
PO
3
<5
77
<5
13
80
36
68
85
90
90
90
88
92
90
90
3
4
NaOtBu
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
2
2
2
2
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
2-Methyl-2-butanol
1
1
0
1
81
90
[
c]
1
2
[
[
[
[
[
[
[
d,e]
d,e]
d,e]
d,e]
d,e]
d,e]
d,e]
1
3
4
5
6
7
8
9
100
100
100
100
100
100
98
1
1
1
1
1
1
80
[
a] Pd(OAc)
2 2 2 3
, ligand and H O were premixed in dioxane at 130 °C for 3 min. [b] Pd dba and ligand were
premixed in dioxane at 130 °C for 3 min. [c] 1.5 equiv of benzamide was used. [d] 2.0 equiv of
benzamide and 2.0 equiv of base were used. [e] [(allyl)PdCl] (0.75 mol%), AdBrettPhos (3.0 mol%).
2
Substrate Synthesis
General Procedure A: Pd-Catalyzed Amidation of Heterocyclic Bromides
An oven-dried re-sealable screw cap test tube, equipped with a magnetic stir bar, was added [(allyl)PdCl]
2
(
2 3
0.75 mol%), L6 (3.0 mol %, Pd:L = 1:2), Cs CO (650 mg, 2.0 mmol, 2.0 equiv), amide (2.0 mmol, 2.0
equiv) and the heteroaryl halide (if it is a solid) (1.0 mmol, 1.0 equiv). The vial was evacuated and
backfilled with argon (this process was repeated a total of 3 times). Under argon, 2-methyl-2-butanol (2
S3

mL) was added followed by the aryl halide (if it is a liquid) (1.0 mmol, 1.0 equiv). The argon source was
removed and the sealed test tube was placed into a pre-heated 90°C oil bath with vigorous stirring. After
stirring for 21 h at 90°C, the vessel was cooled to room temperature, diluted with EtOAc, washed with
saturated aqueous NaHCO
chromatography.
3 2 4
, dried over Na SO , concentrated in vacuo and purified via flash
N-(1-methyl-1H-imidazol-4-yl)-2-thiophenecarboxamide
Following general procedure A, a mixture of 4-bromo-1-methylimidazole (161 mg,
.0 mmol), 2-thiophenecarboxamide (254 mg, 2.0 mmol), Cs CO (650 mg, 2.0
mmol), [(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-
Me
1
2
3
N
O
2
S
N
o
N
H
butanol (2.0 mL) was heated to 90 C for 21 h. The crude product was purified via
flash chromatography (100% EtOAc) to provide the title compound as white powder
1
(
145 mg, 70%), mp 166-167 °C. H NMR (400 MHz, CDCl
3
) δ 11.28 (s, 1H), 7.74 (d, J = 2.8 Hz, 1H),
1
3
7
1
1
.48 (d, J = 4.8, 0.8 Hz, 1H), 7.42 (s, 1H), 7.0 (m, 2H), 3.61 (s, 3H); C NMR (100 MHz, CDCl
59.5, 139.7, 138.3, 133.5, 130.4, 128.5, 127.5, 109.0, 33.9; IR (film) νmax 3181, 3083, 1645, 1560, 1514,
422, 1384, 1355, 1318, 1266, 1169, 1099, 1079, 1042, 999, 877, 856, 816, 762, 715, 624 cm ; Anal.
OS: C, 52.16; H, 4.38. Found: C, 52.02; H, 4.47.
3
) δ
-
1
9 9 3
Calcd. For C H N
N-(1-benzyl-1H-imidazol-4-yl)-benzamide
Following general procedure A, a mixture of 4-bromo-1-benzylimidazole (237 mg,
.0 mmol), 2-pyridineactamide (272 mg, 2.0 mmol), Cs CO (650 mg, 2.0 mmol),
(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol
2.0 mL) was heated to 90 C for 21 h. The crude product was purified via flash
Cl , 1:49) to provide the title compound as white powder
180 mg, 62%), mp 213-214 °C H NMR (400 MHz, DMSO-d ) δ 10.79 (s, 1H), 7.98-7.96 (m, 2H), 7.68
d, J = 1.6 Hz, 1H), 7.53-7.31 (m, 9H), 5.19 (s, 2H); C NMR (100 MHz, DMSO-d ) δ 163.4, 138.4,
37.7, 134.0, 133.5, 131.3, 128.7, 128.3, 127.8, 127.7, 127.6, 107.3, 49.9; IR (film) νmax 3171, 2987,
Bn
1
[
(
2
3
N
O
2
o
N
N
H
chromatography (MeOH/CH
2
2
1
(
(
6
1
3
6
1
2
-
1
361, 2339, 1650, 1562, 1514, 1464, 1418, 1347, 1272, 1121, 997, 760, 709, 668, 652, 598 cm ; Anal.
O: C, 73.63; H, 5,45. Found: C, 73.45; H, 5.41.
14 4
Calcd. For C17H N
N-(1-trityl-1H-imidazol-4-yl)-nicotinamide
Following general procedure A, a mixture of 4-bromo-1-tritylimidazole (389 mg, 1.0
mmol), nicotinamide (244 mg, 2.0 mmol), Cs CO (650 mg, 2.0 mmol), [(allyl)PdCl]
2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol (2.0 mL) was
Tr
2
3
2
N
N
O
(
o
N
H
heated to 90 C for 21 h. The crude product was purified via flash chromatography
MeOH/CH Cl , 1:24) to provide the title compound as white powder (387 mg, 90%),
mp 228-229 °C. H NMR (400 MHz, CDCl
.6Hz, 1H), 8.07 (d, J =8.0 Hz, 1H), 7.47 (s, 1H), 7.34-7.30 (m, 9H), 7.16-7.09 (m, 7H), 6.84 (s, 1H); C
NMR (100 MHz, CDCl ) δ 163.6, 152.0, 149.3, 142.0, 137.7, 135.2, 135.1, 130.8, 129.9, 128.3, 128.2,
22.9, 110.7, 75.9; IR (film) νmax 3207, 3057, 1669, 1559, 1492, 1473, 1445, 1417, 1340, 1261, 1158,
(
2
2
N
1
3
) δ 11.90 (s, 1H), 9.06 (s, 1H), 8.49 (d, J =
1
3
1
3
1
1
5
-
1
117, 1025, 1006, 896, 870, 824, 743, 701, 658, 639 cm ; Anal. Calcd. For C28
.15. Found: C, 78.02; H, 5.24.
22 4
H N O: C, 78.12; H,
N-(1-trityl-1H-imidazol-4-yl)-benzamide
Following general procedure A, a mixture of 4-bromo-1-tritylimidazole (389 mg, 1.0
mmol), benzamide (242 mg, 2.0 mmol), Cs CO (650 mg, 2.0 mmol), [(allyl)PdCl]
2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol (2.0 mL) was
Tr
N
N
2
3
2
O
(
N
H
o
heated to 90 C for 21 h. The crude product was purified via flash chromatography
MeOH/CH Cl , 1:24) to provide the title compound as white powder (387 mg, 90%),
mp 246-247°C. H NMR (400 MHz, CDCl ) δ 11.42 (s, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.51 (s, 1H), 7.34-
.28 (m, 10H), 7.19-7.14 (m, 8H), 6.87 (s, 1H); C NMR (100 MHz, CDCl
(
2
2
1
3
1
3
7
3
) δ 165.5, 142.2, 138.0,
S4

1
2
8
5
35.3, 135.0, 131.3, 129.9, 128.2, 128.1, 127.7, 110.3, 75.8; IR (film) νmax 3199, 3060, 3031, 2362, 2338,
247, 1663, 1559, 1494, 1476, 1446, 1340, 1259, 1226, 1186, 1158, 1114, 1087, 1028, 1007, 909, 871,
-
1
25, 801, 733, 701, 657, 491 cm ; Anal. Calcd. For C29
.38.
23 3
H N O: C, 81.09; H, 5.40. Found: C, 80.14; H,
N-imidazo[1,2-a]pyridin-3-yl-benzamide (CAS: 860257-98-3)
Following general procedure A, a mixture of 3-bromo-imidazo[1,2-a]pyridine (198
mg, 1.0 mmol), benzamide (242 mg, 2.0 mmol), Cs CO (650 mg, 2.0 mmol),
(2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol
N
O
2
3
N
N
H
[
(
(allyl)PdCl]
2.0 mL) was heated to 90 C for 21 h. The crude product was purified via flash
2
o
chromatography (100% EtOAc) to provide the title compound as pale yellow powder (200 mg, 84%), mp
1
1
1
7
1
1
70-171 °C. H NMR (400 MHz, CDCl
3
) δ 10.55 (s, 1H), 8.16 (d, J = 7.6 Hz, 1H), 7.86 (d, J = 6.8 Hz,
H), 7.60 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.33 (d, J = 9.2 Hz, 1H), 7.26 (s, 1H), 7.13 (t, J =
.6 Hz, 1H), 6.78 (t, J = 6.4 Hz, 1H); C NMR (100 MHz, CDCl ) δ 143.1, 132.9, 132.4, 128.6, 128.1,
3
27.1, 124.5, 123.6, 120.3, 117.0, 112.1; IR (film) νmax 3067, 2362, 2338, 1670, 1636, 1601, 1575, 1500,
479, 1360, 1310, 1280, 1142, 1120, 1027, 1006, 909, 847, 803, 752, 733, 709, 669, 646, 608, 516, 425
1
3
-
1
11 3
cm ; Anal. Calcd. For C14H N O: C, 70.87; H, 4.67. Found: C, 70.65; H, 4.56.
4
-fluoro-N-imidazo[1,2-b]pyridazin-3-yl-benzamide
Following general procedure A, a mixture of 3-bromo-imidazo[1,2-b]pyridazine
198 mg, 1.0 mmol), 4-fluorobenzamide (167 mg, 1.2 mmol), Cs CO (456 mg,
.4 mmol), [(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-
N
O
(
1
2
3
N
N
H
2
N
o
F
methyl-2-butanol (2.0 mL) was heated to 90 C for 21 h. The crude product was
purified via flash chromatography (100% EtOAc) to provide the title compound
1
as pale yellow powder (225 mg, 88%), mp 175-176 °C. H NMR (400 MHz, CDCl
3
) δ 8.86 (s, 1H), 8.34
(
dd, J = 1.6, 1.6 Hz, 1H), 8.30 (s, 1H), 8.04-8.00 (m, 2H), 7.95 (dd, J = 1.2, 1.2 Hz, 1H), 7.23-7.18 (m,
1
3
2
1
1
1
H), 7.01 (dd, J = 4.4, 4.4 Hz, 1H); C NMR (100 MHz, CDCl
30.0, 129.9, 129.3, 129.2, 126.1, 124.8, 123.5, 116.2, 116.0, 115.4; F NMR (282 MHz, CDCl
06.4; IR (film) νmax 3245, 2362, 1675, 1604, 1564, 1540, 1522, 1504, 1397, 1350, 1295, 1274, 1236,
3
) δ 166.6, 164.0, 162.7, 142.8, 134.7,
1
9
3
) δ -
-
1
160, 1121, 1069, 1015, 917, 850, 819, 788, 757, 730, 686, 648, 626, 602, 572, 511, 419 cm ; Anal.
FN O: C, 60.94; H, 3.54. Found: C, 61.08; H, 3.50.
Calcd. For C13
H
9
4
4
-trifluoromethyl-N-imidazo[1,2-a]pyrazin-3-yl-benzamide
Following general procedure A, a mixture of 3-bromo-imidazo[1,2-b]pyrizine
198 mg, 1.0 mmol), 4-trifluorobenzamide (378 mg, 2.0 mmol), Cs CO (650
mg, 2.0 mmol), [(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in
-methyl-2-butanol (2.0 mL) was heated to 90 C for 21 h. The crude product
was purified via flash chromatography (MeOH/CH Cl , 1:49) to provide the
title compound as pale green powder (256 mg, 84%), mp 209-210 °C. H NMR (400 MHz, DMSO-d ) δ
1.08 (s, 1H), 9.09 (s, 1H), 8.38 (d, J = 4.4 Hz, 1H), 8.28-8.26 (m, 2H), 7.99-7.90 (m, 4H); C NMR
100 MHz, DMSO-d ) δ 164.8, 143.2, 137.6, 136.8, 132.5, 132.2, 131.9, 131.6, 129.3, 129.1, 128.7,
N
O
(
2
3
N
N
H
2
N
o
2
CF3
2
2
1
6
1
3
1
(
1
6
1
9
3
28.0, 125.6, 125.5, 125.4, 125.3, 122.5, 121.7, 119.8, 117.7; F NMR (282 MHz, CDCl ) δ -64.3; IR
(
4
film) ν -m ax 3210, 2361, 2341, 1700, 1636, 1559, 1507, 1457, 1330, 1167, 1132, 1066, 857, 780, 668, 593,
1
9 3 4
33 cm ; Anal. Calcd. For C14H F N O: C, 54.91; H, 2.96. Found: C, 54.99; H, 2.91.
N-(thiazol-4-yl)-cinnamamide
Following general procedure A, a mixture of 4-bromothiazole (164 mg, 1.0 mmol),
cinnamamide (177 mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol), [(allyl)PdCl] (2.8
S
O
2
3
2
N
N
H
mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol (2.0 mL) was
heated to 90 C for 21 h. The crude product was purified via flash chromatography
o
(
Hexanes/EtOAc, 2:3) to provide the title compound as pale yellow powder (216 mg, 94%), mp 129-130
S5

1
°
C. H NMR (400 MHz, CDCl
3
) δ 9.33 (s, 1H), 8.66 (d, J = 2.0 Hz, 1H), 7.90 (d, 1H), 7.81 (d, J = 15.6
1
3
Hz, 1H), 7.54-7.52 (m, 2H), 7.40-7.38 (m, 3H), 6.61 (d, J = 15.6 Hz, 1H); C NMR (100 MHz, CDCl
3
) δ
63.8, 150.6, 148.8, 142.8, 134.6, 130.1, 129.0, 128.0, 120.0, 102.5; IR (film) νmax 3269, 3151, 3054,
677, 1631, 1579, 1555, 1525, 1449, 1404, 1339, 1297, 1281, 1205, 1189, 1131, 1071, 998, 972, 874,
1
1
8
6
-
1
52, 811, 761, 705, 667, 606, 562, 484 cm ; Anal. Calcd. For C12
2.66; H, 4.44.
10 2
H N OS: C, 62.59; H, 4.38. Found: C,
N-(2-phenoxy-thiazol-4-yl)-nicotinamide
Following general procedure A, a mixture of 4-bromo-2-phenoxythiazole (256
mg, 1.0 mmol), nicotinamide (147 mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol),
[(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-
S
O
2
3
PhO
N
N
H
2
o
butanol (2.0 mL) was heated to 90 C for 21 h. The crude product was purified via
N
flash chromatography (Hexanes/EtOAc, 2:3) to provide the title compound as pale
1
orange powder (210 mg, 71%), mp 172-173 °C. H NMR (400 MHz, DMSO-d
1
6
) δ 11.4 (s, 1H), 9.10 (s,
1
3
H), 8.72 (d, J = 4.8 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H), 7.52-7.48 (m, 3H), 7.40-7.32 (m, 4H); C NMR
100 MHz, DMSO-d ) δ 171.2, 163.7, 154.9, 152.2, 148.9, 142.0, 135.6, 130.3, 129.3, 126.4, 123.4,
20.5, 96.6; IR (film) νmax 3163, 2360, 2342, 1663, 1594, 1528, 1504, 1486, 1242, 1194, 1162, 1119,
(
6
1
1
-
1
11 3 2
028, 914, 743, 668 cm ; Anal. Calcd. For C15H N O S: C, 60.59; H, 3.73. Found: C, 60.94; H, 3.84.
N-(2-methoxycarbonyl-pyrrol-4-yl)-cyclohexanecarboxamide
Following general procedure
methoxycarbonylpyrrole (109 mg, 0.5 mmol), cyclohexanecarboxamide (76
mg, 0.6 mmol), Cs CO (228 mg, 0.7 mmol), [(allyl)PdCl] (1.4 mg, 0.75
mol%), L6 (9.6 mg, 3.0 mol%) in 2-methyl-2-butanol (2.0 mL) was heated to
Me
A,
a
mixture
of
4-bromo-2-
N
O
MeO C
2
2
3
2
N
H
o
9
0 C for 21 h. The crude product was purified via flash chromatography
(
1
3
(
3
1
Hexanes/EtOAc, 7:3) to provide the title compound as pale yellow-green powder (121 mg, 91%), mp
1
65-167 °C. H NMR (400 MHz, CDCl
H), 2.20 (tt, J = 4.0, 12.0 Hz, 1H), 1.90-1.66 (m, 5H), 1.49 (q, J = 12, 2H), 1.29-1.18 (m, 3H); C NMR
) δ 173.8, 161.6, 122.0, 121.3, 119.6, 108.1, 51.2, 45.7, 36.8, 29.8, 25.7; IR (film) νmax
283, 3118, 2931, 2855, 2362, 2338, 1711, 1653, 1577, 1450, 1407, 1374, 1354, 1250, 1209, 1148, 1128,
3
) δ 7.61 (s, 1H), 7.38 (s, 1H), 6.66 (s, 1H), 3.83 (s, 3H), 3.76 (s,
1
3
100 MHz, CDCl
3
-
1
20 2 3
100, 1063, 1005, 952, 914, 895, 822, 783, 756, 733, 668, 645, 630 cm ; Anal. Calcd. For C14H N O :
C, 63.62; H, 7.63. Found: C, 63.09; H, 7.43.
N-(5-((pyrolidin-1-yl)sulfonyl)-thiophen-2-yl)-benzamide
Following general procedure A, a mixture of 2-bromo-5-((pyrolidin-1-
yl)sulfonyl)thiophene (221 mg, 1.0 mmol), benzamide (145 mg, 1.2 mmol),
N
O
O
S
Cs
.0 mol%) in 2-methyl-2-butanol (2.0 mL) was heated to 90 C for 21 h. The
crude product was purified via flash chromatography (Hexanes/EtOAc, 1:1) to
2 3 2
CO (456 mg, 1.4 mmol), [(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg,
S
N
H
O
o
3
1
provide the title compound as pale orange powder (272 mg, 81%), mp 223-224 °C. H NMR (400 MHz,
DMSO-d ) δ 12.1 (s, 1H), 8.03 (d, J = 4.0 Hz, 2H), 7.66 (t, J = 8.0 Hz, 1H), 7.59 (t, J = 8.0 Hz, 2H), 7.52
d, J = 4.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 1H), 3.18 (t, J = 8.0 Hz, 4H), 1.69-1.66 (m, 4H); C NMR (100
MHz, DMSO-d ) δ 164.2, 145.8, 132.6, 132.1, 130.7, 128.8, 127.9, 125.0, 112.3, 48.0, 24.8; IR (film)
νmax 3309, 2090, 2976, 2361, 2340, 1700, 1663, 1602, 1554, 1507, 1485, 1441, 1385, 1332, 1292, 1198,
6
1
3
(
6
-
1
1
5
150, 1091, 1062, 1012, 890, 800, 753, 704, 646, 599, 568 cm ; Anal. Calcd. For C15
3.55; H, 4.79. Found: C, 53.47; H, 4.64.
16 2 3 2
H N O S : C,
S6

N-(5-methoxycarbonyl-thiophen-2-yl)-cyclohexanecarboxamide
Following general procedure A,
methoxycarbonylthiophene (221 mg, 1.0 mmol), cyclohexanecarboxamide (153
mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol), [(allyl)PdCl] (3.7 mg, 1.0 mol%),
L6 (25.6 mg, 4.0 mol%) in 2-methyl-2-butanol (2.0 mL) was heated to 90 C for
1 h. The crude product was purified via flash chromatography (Hexanes/EtOAc, 3:1) to provide the title
O
a
mixture
of
2-bromo-5-
MeO C
2
S
N
H
2
3
2
o
2
1
compound as pale orange powder (200 mg, 75%), mp 128-129 °C. H NMR (400 MHz, CDCl
3
) δ 8.52 (s,
1
1
1
3
8
H), 7.59 (d, J = 4.0 Hz, 1H), 6.60 (d, J = 4.0 Hz, 1H), 3.84 (s, 3H), 2.34 (tt, J = 3.2, 11.6 Hz, 1H), 1.97-
.70 (m, 5H), 1.54 (q, J = 12, 24 Hz, 2H) 1.34-1.22 (m, 3H); C NMR (100 MHz, CDCl ) δ 174.1,
3
74.0, 164.0, 146.3, 146.2, 132.0, 123.4, 123.3, 112.1, 112.0, 52.0, 45.1, 29.5, 25.6, 25.5; IR (film) νmax
1
3
280, 2932, 2855, 1706, 1684, 1560, 1507, 1452, 1386, 1344, 1297, 1259, 1188, 1171, 1099, 954, 894,
-
1
3
05, 750 cm ; Anal. Calcd. For C13H17NO S: C, 58.4; H, 6.41. Found: C, 58.53; H, 6.47.
4
-fluoro-N-(1-benzyl-1H-pyrazol-4-yl)-benzamide
Following general procedure A, a mixture of 4-bromo-1-benzylpyrazole (237 mg,
.0 mmol), 4-fluorobenzamide (167 mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol),
(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol
Bn
1
[
2
3
N
N
O
2
o
N
(2.0 mL) was heated to 90 C for 21 h. The crude product was purified via flash
H
chromatography (Hexanes/EtOAc, 1:1) to provide the title compound as white
F
1
powder (257 mg, 87%), mp 162-163 °C H NMR (400 MHz, CDCl
3
) δ 8.20 (s,
1
5
1
1
H), 8.05 (s, 1H), 7.83 (dd, J = 8.8, 5.2 Hz, 2H), 7.53 (s, 1H), 7.33-7.20 (m, 5H), 7.09 (t, J = 8.8 Hz, 2H),
1
3
.24 (s, 2H); C NMR (100 MHz, CDCl
3
) δ 166.2, 163.8, 136.3, 129.5, 129.0, 128.3, 127.9, 121.8, 121.5,
16.1, 115.8, 56.6; F NMR (282 MHz, CDCl ) δ -107.8; IR (film) νmax 3270, 3067, 1645, 1602, 1506,
3
385, 1278, 1234, 1159, 1020, 845, 705, 628, 594 cm ; Anal. Calcd. For C17 14FN O: C, 69.14; H, 4.78.
1
9
3
-
1
H
Found: C, 69.36; H, 4.75.
N-(1-benzyl-1H-pyrazol-4-yl)- 2-thiophenecarboxamide
Following general procedure A, a mixture of 4-bromo-1-benzylpyrazole (237 mg, 1.0
mmol), 2-thiophenecarboxamide (153 mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol),
[(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol
2.0 mL) was heated to 90 C for 21 h. The crude product was purified via flash
chromatography (Et O/CH Cl , 1:3) to provide the title compound as off-white crystalline powder (230
mg, 81%), mp 145-146 °C. H NMR (400 MHz, CDCl ) δ 8.68 (s, 1H), 7.97 (s, 1H), 7.60 (d, J = 3.2 Hz,
H), 7.47 (s, 1H), 7.45 (q, J = 0.8, 5.2 Hz, 1H), 7.26-7.23 (m, 3H), 7.16-7.14 (m, 2H), 6.99 (d, J = 4.8 Hz,
Bn
N
O
2
3
N
S
N
H
2
o
(
2
2
2
1
3
1
1
1
1
1
3
H), 5.17 (s, 2H); C NMR (100 MHz, CDCl
3
) δ 159.5, 138.7, 136.2, 130.8, 128.9, 128.6, 128.2, 128.0,
27.9, 121.9, 121.4, 56.5; IR (film) νmax 3279, 3089, 1633, 1586, 1560, 1496, 1423, 1393, 1423, 1393,
351, 1285, 1159, 1096, 1075, 1016, 993, 858, 788, 730, 700, 651, 628 cm ; Anal. Calcd. For
OS: C, 63.58; H, 4.62. Found: C, 63.51; H, 4.55.
-
1
15 13 3
C H N
N-(1-benzyl-1H-pyrazol-4-yl)-cinnamamide
Following general procedure A, a mixture of 4-bromo-1-benzylpyrazole (237 mg,
1.0 mmol), cinnamamide (177 mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol),
(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-
Bn
N
2
3
O
N
[
2
N
H
o
butanol (2.0 mL) was heated to 120 C for 21 h. The crude product was purified
via flash chromatography (Hexanes/EtOAc, 1:1) to provide the title compound as
1
pale yellow powder (260 mg, 86%), mp 141-142 °C. H NMR (400 MHz, CDCl
3
) δ 9.32 (s, 1H), 8.09 (s,
1
H), 7.69 (d, J =15.6 Hz, 1H), 7.53 (s, 1H), 7.34-7.15 (m, 10H), 6.61 (d, J = 15.6 Hz, 1H), 5.14 (s, 2H);
1
3
C NMR (100 MHz, CDCl
3
) δ 163.6, 141.7, 136.1, 134.6, 130.8, 129.9, 128.9, 128.8, 128.1, 127.9,
1
1
27.7, 121.9, 121.7, 120.2, 56.4; IR (film) νmax 3267, 3085, 1657, 1623, 1588, 1496, 1394, 1342, 1211,
150, 1023, 992, 836, 762, 728, 700, 629, 562, 491 cm ; Anal. Calcd. For C19H N O: C, 75.23; H, 5.65.
17 3
-
1
Found: C, 75.36; H, 5.71.
S7

N-(1-methyl-1H-pyrazol-4-yl)- 2-furancarboxamide
Following general procedure A, a mixture of 4-bromo-1-methylpyrazole (161 mg, 1.0
mmol), cinnamamide (134 mg, 1.2 mmol), Cs CO (456 mg, 1.4 mmol),
[(allyl)PdCl] (2.8 mg, 0.75 mol%), L6 (19.2 mg, 3.0 mol%) in 2-methyl-2-butanol
(2.0 mL) was heated to 120 C for 21 h. The crude product was purified via flash
chromatography (CH Cl /Et O, 1:4) to provide the title compound as pale yellow
powder (170 mg, 89%), mp 119-120 °C. H NMR (400 MHz, CDCl ) δ 8.31 (s, 1H), 7.98 (s, 1H), 7.49 (s,
Me
N
2
3
O
N
O
2
N
H
o
2
1
2
2
3
1
3
1
H), 7.45 (s, 1H), 7.17 (d, J = 3.6 Hz, 1H), 6.51 (dd, J = 1.6, 3.6 Hz, 1H), 3.86 (s, 3H); C NMR (100
3
MHz, CDCl ) δ 155.4, 147.6, 144.3, 130.4, 122.4, 120.5, 115.0, 112.6, 39.4; IR (film) νmax 3269, 3124,
2
8
4
937, 1654, 1594, 1539, 1476, 1444, 1406, 1348, 1288, 1228, 1183, 1159, 1122, 1075, 1011, 984, 938,
-
1
84, 867, 836, 761, 653, 608 cm ; Anal. Calcd. For C
.81.
9 9 3 2
H N O : C, 56.54; H, 4.74. Found: C, 55.72; H,
Synthesis of Complexes 2a and 2b
Complex 2a
CN In a nitrogen-filled glovebox, to an oven-dried 20 mL vial was added tBuBrettPhos
(L3) (137 mg, 0.28 mmol, 1.1 equiv.) and 4-bromobenzonitrile (140 mg, 0.77
mmol, 3 equiv.). With rapid stirring, cyclohexane was added dropwise until all
tBu tBu
Me
Me
O
P
Pd
iPr
Br
reagents had completely dissolved (10 mL total). (COD)Pd(CH
2 2
TMS) (100 mg,
0
.26 mmol, 1 equiv.) was added rapidly in one portion and the mixture was
i
O Pr
vigorously stirred at room temperature for 12 h, during which period a precipitate
formed. The mixture was filtrered through a sintered glass frit, washed with pentane
iPr
(
3 X 3 mL), and dried under reduced pressure to afford 2a as a yellow solid (130 mg, 66 %). To obtain X-
ray quality crystals, a small sample (10 mg) was dissolved in a minimal quantity of CH Cl , layered with
) δ 7.30 (d, J = 7.2 Hz, 2H), 7.05-
.00 (m, 4H), 6.96-6.87 (m, 2H), 3.79 (s, 3H), 3.32 (s, 3H), 3.06-3.01 (m, 1H), 2.62-2.55 (m, 2H), 1.57
2
2
1
2 2
pentane, and placed in a -20 °C freezer. H NMR (400 MHz, CD Cl
7
(
1
1
2
7
1
3
d, J = 6.4 Hz, 6H), 1.40-1.34 (m, 25H), 0.82 (d, J = 6.8 Hz, 6H); C NMR (100 MHz, CD
2
Cl
55.0, 154.0, 153.9, 151.8, 151.7, 147.1, 147.0, 140.9, 137.8, 137.6, 127.2, 127.1, 127.0, 124.9, 119.9,
15.5, 115.4, 113.6, 110.7, 110.6, 105.1, 54.4, 53.9, 53.8, 41.3, 41.2, 34.5, 32.4, 32.3, 31.4, 30.1, 30.0,
2
) δ 158.4,
3
1
2 2
6.9, 25.5, 24.5, 24.2 (observed complexity is due to C–P splitting); P NMR (121 MHz, CD Cl ) δ 82.7,
[
8]
2.4.
Complex 2b
In a nitrogen-filled glovebox, to an oven-dried 20 mL vial was added AdBrettPhos
L6) (91 mg, 0.14 mmol, 1.1 equiv.) and 4-bromobenzonitrile (70 mg, 0.39 mmol, 3
equiv.). With rapid stirring, cyclohexane was added dropwise until all reagents had
completely dissolved (10 mL total). (COD)Pd(CH TMS) (50 mg, 0.13 mmol, 1
equiv.) was added rapidly in one portion and the mixture was vigorously stirred at
room temperature for 12 h, during which period a precipitate formed. The mixture
was filtrered through a sintered glass frit, washed with pentane (3 X 3 mL), and dried
CN
(
Ad
Me Ad
O
P
Pd
iPr
2
2
Br
i
O Pr
Me
iPr
under reduced pressure to afford 2b as a yellow solid (52 mg, 46 %). To obtain X-ray quality crystals, a
small sample (10 mg) was dissolved in a minimal quantity of CH Cl , layered with pentane, and placed in
) δ 7.40 (d, J = 8.0 Hz, 2H), 7.04-7.02 (m, 4H), 6.97-6.86
m, 2H), 3.84 (s, 3H), 3.32 (s, 3H), 3.02 (m, 1H), 2.57 (m, 2H), 2.23-1.93 (m, 20H), 1.69-1.59 (m, 20H),
2
2
1
2 2
a -20 °C freezer. H NMR (400 MHz, CD Cl
(
1
3
1
1
1
2
2 2
.43 (s, 2H), 1.35 (d, J = 4.0 Hz, 6H), 0.82 (d, J = 8.0 Hz, 6H); C NMR (100 MHz, CD Cl ) δ 158.3,
55.6, 154.3, 154.3, 152.2, 152.8, 147.4, 147.3, 141.4, 138.9, 138.7, 127.5, 126.3, 126.1, 125.3, 120.3,
16.3, 116.2, 113.7, 110.9, 110.8, 105.3, 54.7, 47.7, 47.6, 41.7, 36.6, 34.8, 31.6, 29.9, 29.8, 27.3, 26.2,
4.8, 24.7 (observed complexity is due to C–P splitting); P NMR (121 MHz, THF-d8) δ 67.91.
3
1
S8

Cartesian Coordinates for all Calculated Complexes:
C
1.465975 2.760738 3.566852
2.031158 3.416257 2.906461
0.621844 3.329773 3.963975
0.176906 0.586283 3.775542
tBu
tBu
N
H
H
C
Me
Me
N
O
P
O
Pd
iPr
N
H
H -0.671898 1.118928 4.211234
H -0.202865 -0.301343 3.270130
Pd -0.343286 -0.714238 0.167065
i
O Pr
iPr
Complex A
H
1.263976 3.500438 -3.790667
H -0.097701 1.350422 -4.262294
P
1.985280 -1.356501 -0.226987
2.908696 0.330364 -0.274607
4.282083 0.424246 -0.605464
4.895419 -0.739907 -1.070423
6.321311 -0.737934 -1.340488
6.571057 -0.044500 -2.145858
6.553181 -1.751554 -1.651055
6.894155 -0.489640 -0.444549
4.975635 1.625899 -0.518865
6.027057 1.679704 -0.754016
4.303409 2.786952 -0.141280
4.850418 3.714803 -0.075638
2.939357 2.736804 0.110657
2.207579 1.518437 0.041102
0.710432 1.696475 0.243343
H
H
0.815747 0.261670 4.600700
2.102708 2.474963 4.407939
C
C
O
C
H
H
H
C
H
C
H
C
C
C
H -5.143462 3.949495 0.118535
H -3.790836 5.691551 1.430851
O
C
H
H
H
C
C
C
C
H
H
H
H
H
H
C
C
C
C
H
H
H
H
2.194369 3.875220 0.431192
2.858292 5.164114 0.497735
3.302152 5.432673 -0.463700
2.072938 5.869266 0.746903
3.624903 5.177288 1.276068
2.850355 -2.490284 1.179135
2.228252 -3.898952 1.077388
4.382982 -2.595609 1.116647
2.449040 -1.863104 2.526330
2.546277 -4.431101 0.183245
1.144191 -3.861078 1.104319
4.862773 -1.629440 1.258990
4.740957 -3.023550 0.185226
1.368785 -1.822044 2.641572
2.873174 -0.865578 2.645237
2.126178 -2.222737 -2.034156
2.154339 -1.100464 -3.085075
3.352490 -3.131076 -2.230020
0.836985 -3.049736 -2.219733
3.042796 -0.477430 -2.994154
1.266992 -0.476387 -3.020697
3.351823 -3.987593 -1.559489
4.278227 -2.581721 -2.105353
C -0.069279 2.155411 -0.864761
C
H
C -0.563541 1.488081 -3.283020
H -1.434548 2.131333 -3.427782
H -0.930661 0.524162 -2.927917
C
H
H -0.045533 4.196590 -2.829572
C -1.318284 2.746549 -0.633483
H -1.890576 3.081380 -1.485978
C -1.832573 2.927882 0.647861
C -3.142573 3.667729 0.913048
H -3.562764 3.249443 1.835015
C -4.199380 3.498073 -0.193898
H -3.893753 3.991346 -1.119562
H -4.383974 2.447227 -0.415290
C -2.865759 5.168678 1.176065
H -2.158839 5.303783 1.996444
H -2.441807 5.639980 0.285979
C -1.073387 2.457337 1.725911
H -1.464078 2.583605 2.728278
0.447161 2.129609 -2.304824
1.356786 1.531036 -2.321968
0.833061 3.548765 -2.787487
1.558440 4.011457 -2.119312
H -0.057416 -2.430902 -2.159123
0.747654 -3.844231 -1.480501
H
C -0.980407 -2.493656 0.821089
N -2.045561 -4.417559 1.151929
C -2.821181 -5.633629 0.937447
H -2.301489 -6.312112 0.260130
H -2.965903 -6.137550 1.891401
H -3.798687 -5.395820 0.517812
C -1.705784 -3.472590 0.178116
H -2.045549 -3.542348 -0.837152
N -2.339651 -0.277318 0.118131
C -3.095620 -0.661322 -0.922434
H -2.801783 0.118609 0.925825
C
C
H
0.180453 1.866137 1.563872
0.974882 1.498536 2.817658
1.859406 0.949698 2.496668
S9

O -2.601646 -1.157772 -1.991188
C -4.590643 -0.473957 -0.841706
C -5.306381 -0.304703 -2.036782
C -5.297198 -0.501291 0.371364
C -6.691068 -0.135937 -2.019042
H -4.753783 -0.321561 -2.965064
C -6.685591 -0.342116 0.389485
H -4.769537 -0.673252 1.300601
C -7.385817 -0.151627 -0.804705
H -7.228831 0.002150 -2.948288
H -7.218372 -0.374630 1.331288
H -8.460769 -0.025982 -0.790344
N -0.878180 -2.811350 2.179119
C -1.522910 -3.969857 2.341769
H -1.631559 -4.506330 3.266965
H
0.917512 3.904192 -2.795530
H -0.593908 3.593165 -3.660317
C -1.927177 2.519692 -1.318317
H -2.405744 2.500071 -2.292288
C -2.664951 2.925560 -0.208825
C -4.101359 3.418403 -0.330217
H -4.520716 3.439863 0.685462
C -4.995662 2.501542 -1.181731
H -4.681096 2.493197 -2.231927
H -4.974174 1.469153 -0.821089
C -4.128964 4.864320 -0.868805
H -3.536293 5.535771 -0.237366
H -3.716670 4.908622 -1.884182
C -2.018918 2.935706 1.029946
H -2.579870 3.255256 1.905038
C -0.674297 2.593236 1.183171
C -0.044328 2.768033 2.563004
H
H
H
H
H
H
0.866081 -3.512383 -3.211820
3.317912 -3.523702 -3.251921
2.161287 -1.556690 -4.079915
2.562691 -4.480004 1.942526
2.847738 -2.488256 3.332193
4.701367 -3.249713 1.935840
H
C
H
0.959990 2.340277 2.523107
0.104413 4.261039 2.927225
0.681182 4.803171 2.173673
H -0.877270 4.743172 3.008469
C -0.823339 2.032968 3.671785
H -1.803485 2.494748 3.843109
H -0.982114 0.976654 3.435452
Pd -0.501075 -0.299463 0.601338
N
tBu Ad
Me
N
O
P
O
Pd
iPr
N
H
H
H
0.927396 2.929874 -4.281549
0.058502 0.498373 -4.238415
i
O Pr
Me
iPr
H -0.269533 2.093453 4.616851
0.608725 4.366017 3.895736
H -6.033534 2.854505 -1.155120
H -5.156747 5.245855 -0.905106
Complex B
H
P
1.883402 -0.537154 0.641684
2.515351 1.176842 0.174903
3.894257 1.447700 -0.041058
4.733980 0.370643 -0.086923
6.130390 0.589054 -0.195968
6.388881 1.082668 -1.141624
6.590150 -0.400703 -0.171154
6.511542 1.186536 0.642304
4.359033 2.744357 -0.235093
5.415105 2.942894 -0.369970
3.461483 3.807553 -0.282103
3.841050 4.810257 -0.437539
2.097958 3.565452 -0.167935
1.596857 2.250703 0.052599
0.077812 2.178368 0.036863
C
C
O
C
H
H
H
C
H
C
H
C
C
C
O
C
H
H
H
C
C
C
C
H
H
H
H
H
H
C
C
C
C
H
1.159730 4.559560 -0.271657
1.598132 5.884202 -0.520693
2.141069 5.958453 -1.472549
0.692084 6.490083 -0.574370
2.236957 6.259644 0.290122
2.685738 -1.012449 2.347420
2.316489 -2.477501 2.672658
4.212618 -0.853967 2.478409
2.032834 -0.107439 3.409761
2.849612 -3.193874 2.043016
1.246152 -2.661561 2.585833
4.526040 0.188661 2.381323
4.770130 -1.453360 1.757811
0.948850 -0.230667 3.441621
2.280415 0.946078 3.245392
2.396133 -1.810560 -0.742534
2.376940 -1.071429 -2.104765
3.771425 -2.512166 -0.584052
1.292407 -2.907101 -0.789124
3.140199 -0.285210 -2.122826
C -0.578571 2.158123 -1.234831
C
H
0.150796 1.862058 -2.544853
1.141308 1.472494 -2.299061
C -0.578026 0.803287 -3.398089
H -1.503004 1.206073 -3.828057
H -0.851129 -0.084043 -2.816994
C
0.365545 3.151602 -3.365806
S10

N
H
C
H
H
C
H
H
C
H
C
C
H
C
H
H
H
H
H
H
H
1.403614 -0.594313 -2.245181
2.626563 -2.056244 -3.269718
3.813611 -3.074855 0.353401
4.571724 -1.772694 -0.558201
4.018980 -3.493132 -1.755134
0.309365 -2.444882 -0.928881
1.255654 -3.450367 0.161455
1.553851 -3.898023 -1.946149
2.606905 -1.491955 -4.212073
4.002455 -2.724696 -3.090439
1.525532 -3.134569 -3.283601
5.002873 -3.960988 -1.610017
2.924164 -4.575879 -1.765791
0.757792 -4.654160 -1.937488
4.797878 -1.965656 -3.099657
4.204163 -3.410633 -3.925128
0.541079 -2.672174 -3.427626
1.686354 -3.827129 -4.122033
3.106671 -5.292853 -2.578798
2.947582 -5.144985 -0.825506
Me Ad Ad
N
O
P
1
O
Pd
iPr
N
H
i
O Pr
Me
iPr
Complex C
P -1.670496 -0.097031 0.170730
C -1.845135 1.767273 0.411814
C -3.057414 2.361206 0.859649
O -4.036525 1.511838 1.294163
C -5.295388 2.044566 1.669265
H -5.207295 2.719104 2.530606
H -5.911238 1.187114 1.946922
H -5.771743 2.578161 0.836537
C -3.223407 3.741956 0.890567
H -4.160856 4.183365 1.205782
C -2.169309 4.579514 0.536507
H -2.315266 5.652458 0.570473
C -0.941629 4.032538 0.184427
C -0.750970 2.622436 0.122522
C -0.949157 -1.876395 1.751395
N -1.695615 -3.774984 2.599493
C -2.193628 -5.128616 2.751574
H -1.458309 -5.857768 2.394067
H -2.389832 -5.319809 3.809715
H -3.125183 -5.264324 2.191517
C -1.342425 -3.151198 1.411528
H -1.451707 -3.637893 0.455011
N -2.518618 -0.337748 0.186941
C -2.955614 -1.205084 -0.737697
H -3.208266 0.001567 0.846878
O -2.203723 -1.775067 -1.557706
C -4.446090 -1.483271 -0.821354
C -4.969686 -1.895525 -2.055295
C -5.312490 -1.389809 0.277917
C -6.326958 -2.178523 -2.195919
H -4.284244 -1.993276 -2.890757
C -6.670866 -1.685544 0.142833
H -4.924393 -1.110319 1.254274
C -7.183653 -2.073765 -1.096179
H -6.718441 -2.486378 -3.162553
H -7.326647 -1.617174 1.007442
H -8.241651 -2.300099 -1.202799
N -1.066431 -1.702480 3.114468
C -1.510567 -2.854501 3.587501
H -1.704434 -3.081351 4.628603
C
C
C
H
C
H
H
C
H
H
C
H
C
C
H
C
H
H
C
H
H
C
H
C
C
0.689048 2.228536 -0.170051
1.624156 2.260402 0.912865
1.198198 2.320329 2.378949
0.121398 2.141799 2.425511
1.897990 1.244097 3.234530
2.959495 1.479196 3.378041
1.848008 0.250690 2.775989
1.446074 3.721817 2.976895
0.927929 4.499581 2.408252
2.515205 3.965287 2.978612
2.993857 2.334956 0.639139
3.684132 2.362219 1.476188
3.496624 2.400901 -0.658178
4.979691 2.599811 -0.944526
5.137279 2.352379 -2.003683
5.898676 1.688765 -0.113738
5.849296 1.931294 0.954275
5.631754 0.634215 -0.228024
5.364478 4.082652 -0.757787
4.750198 4.735601 -1.387990
5.221427 4.392465 0.284573
2.578187 2.356705 -1.709999
2.952902 2.411576 -2.729359
1.198796 2.292734 -1.506560
0.292612 2.390622 -2.731033
H
H
H
2.608027 -2.678416 3.712100
2.430375 -0.384305 4.395907
4.496457 -1.189081 3.485675
H -0.730822 2.201349 -2.400137
C
H
H
0.323868 3.808259 -3.341434
0.052030 4.568721 -2.604927
1.324647 4.050721 -3.718996
S11

C
H
H
0.636887 1.345689 -3.811293
1.607602 1.556785 -4.276477
0.669386 0.329230 -3.407689
C -1.742075 -0.781874 4.383277
H -3.882411 -2.090416 1.338119
H -4.178742 -0.530874 2.099006
C -3.665971 -2.119677 3.486299
H -0.124019 -2.011435 1.754765
H -1.455324 -2.953223 1.098459
C -1.326439 -2.990668 3.269574
H -1.412449 -0.092329 5.172488
C -3.214469 -1.170831 4.612992
C -0.864244 -2.047756 4.396660
H -4.721223 -2.390557 3.631271
C -2.795774 -3.389660 3.498805
H -0.692659 -3.887316 3.256866
H -3.847560 -0.272052 4.628207
H -3.330111 -1.660227 5.590302
Pd 0.657129 -0.390671 -0.324243
H
H
H -0.115137 1.374921 -4.609551
H -0.375258 3.873189 -4.184405
H
H
O
C
1.093331 3.758958 4.014950
1.441306 1.202936 4.231543
6.941293 1.816163 -0.428482
6.417507 4.246317 -1.017558
0.154112 4.803074 -0.106717
0.032789 6.213219 -0.031335
H -0.238322 6.543059 0.980643
1.017300 6.608426 -0.287128
H
H -0.707798 6.596055 -0.746528
C -2.931075 -0.620320 -1.212239
C -2.912885 -2.171100 -1.339420
C -4.402345 -0.154610 -1.054538
C -2.394659 -0.020563 -2.539218
H -3.313480 -2.637577 -0.433630
H -1.888348 -2.525630 -1.461264
C -3.765617 -2.625341 -2.547033
H -4.443365 0.937755 -1.007062
H -4.838205 -0.535598 -0.127425
C -5.256103 -0.629961 -2.255684
H -1.356891 -0.325475 -2.693411
H -2.424084 1.074545 -2.480592
C -3.247175 -0.481516 -3.743194
H -3.725547 -3.721737 -2.603458
C -5.222573 -2.166579 -2.350838
C -3.198232 -2.017491 -3.844027
H -6.289741 -0.291620 -2.097116
C -4.703757 -0.019901 -3.557301
H -2.826643 -0.036869 -4.655208
H -5.641741 -2.612305 -1.437395
H -5.846742 -2.507498 -3.188844
H -2.163057 -2.347236 -3.990962
H -3.782629 -2.360090 -4.710099
H -5.317182 -0.332614 -4.414159
H -4.753108 1.077429 -3.511535
C -2.058648 -0.990789 1.861630
C -1.603522 -0.065542 3.020338
C -3.531812 -1.407883 2.118095
C -1.176553 -2.271947 1.909898
H -2.198337 0.854584 3.030567
H -0.557670 0.216734 2.874390
References
H
0.190219 -1.781165 4.251533
H -0.942480 -2.550707 5.370964
H -2.904559 -3.915329 4.458071
H -3.129314 -4.083447 2.713997
C
N
C
H
H
H
C
H
N
C
H
O
C
C
C
C
H
C
H
C
H
H
H
N
C
H
0.549903 -2.193417 -1.189627
0.784505 -4.321760 -1.733740
1.017988 -5.752198 -1.680148
0.260439 -6.249316 -1.064344
0.969262 -6.160336 -2.692938
2.007757 -5.966026 -1.262741
0.804918 -3.439506 -0.663613
1.056959 -3.755443 0.336428
2.677713 -0.776957 -0.352139
3.199669 -1.554246 0.607371
3.227252 -0.672427 -1.196556
2.601988 -1.837399 1.668078
4.606246 -2.092250 0.412420
5.365805 -2.379451 1.555628
5.163996 -2.354850 -0.847818
6.658846 -2.887099 1.443970
4.912423 -2.201554 2.525287
6.454715 -2.876284 -0.962134
4.580681 -2.177579 -1.747987
7.208986 -3.136818 0.183266
7.238586 -3.093879 2.340391
6.867961 -3.083252 -1.946351
8.215480 -3.538212 0.094876
0.387711 -2.290190 -2.556032
0.531194 -3.573692 -2.844197
0.452231 -4.015442 -3.829820
(
(
1) A. V. Vorogushin, X. Huang, S. L. Buchwald, J. Am. Chem. Soc. 2005, 127, 8146-8149.
2) B. P. Fors, K. Dooleweerdt, Q. Zeng, S. L. Buchwald, Tetrahedron, 2009, 65, 6576-6583.
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(
(
3) J. D. Hicks, A. M. Hyde, A. M. Cuezva, S. L. Buchwald, J. Am. Chem. Soc. 2009, 131, 16720-16734.
4) Y. Shao, L. Fusti-Molnar, Y. Jung, J. Kussmann, C. Ochsenfeld, S. T. Brown, A. T. B. Gilbert, L. V.
Slipchenko,S. V. Levchenko, D. P. O'Neill, R. A. DiStasio Jr., R. C. Lochan, T. Wang, G. J. O.
Beran, N. A. Besley, J. M. Herbert, C. Y. Lin, T. Van Voorhis, S. H. Chien, A. Sodt, R. P. Steele, V.
A. Rassolov, P. E. Maslen, P. P. Korambath, R. D. Adamson, B. Austin, J. Baker, E. F. C. Byrd, H.
Dachsel, R. J. Doerksen, A. Dreuw, B. D. Dunietz, A. D. Dutoi, T. R. Furlani, S. R. Gwaltney, A.
Heyden, S. Hirata, C.-P. Hsu, G. Kedziora, R. Z. Khaliullin, P. Klunzinger, A. M. Lee, M. S. Lee, W.
Liang, I. Lotan, N. Nair, B. Peters, E. I. Proynov, P. A. Pieniazek, Y. M. Rhee, J. Ritchie, E. Rosta, C.
D. Sherrill, A. C. Simmonett, J. E. Subotnik, H. L. Woodcock III, W. Zhang, A. T. Bell, A. K.
Chakraborty, D. M. Chipman, F. J. Keil, A. Warshel, W. J. Hehre, H. F. Schaefer III, J. Kong, A. I.
Krylov, P. M. W. Gill, M. Head-Gordon, Z. Gan, Y. Zhao, N. E. Schultz, D. Truhlar, E. Epifanovsky
and M. Oana, Q-Chem, Version 3.1, Q-Chem, Inc., Pittsburgh, PA (2007).
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5) a) A. D. Becke, J. Chem. Phys. 1993, 98, 1372-1377; b) A. D. Becke, J. Chem. Phys. 1993, 98, 5648-
5
652 (c) C. T. Lee, W. T. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785-789.
(
(
(
6) P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 299-310.
7) B. P. Fors, D. A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am. Chem. Soc. 2008, 130, 13552-13554.
8) T. J. Maimone, P. J. Milner, T. Kinzel, M. K. Takase, S. L. Buchwald, J. Am. Chem. Soc. 2011, 133,
1
8106-18109.
S13

ꢐ ꢀ ꢐ ꢏ ꢀ
ꢆ ꢁ ꢐ ꢏ ꢀ
ꢆ ꢂ ꢐ ꢏ ꢀ
ꢃ ꢃ ꢐ ꢏ ꢀ
ꢃ ꢁ ꢁ ꢏ ꢁ
ꢃ ꢄ ꢁ ꢏ ꢁ
ꢈ ꢐ ꢁ ꢏ ꢁ
ꢃ ꢀ ꢂ ꢏ ꢁ
ꢄ ꢁ ꢂ ꢏ ꢁ
ꢁ ꢃ ꢏ ꢆ
ꢈ ꢆ ꢏ ꢈ
ꢅ ꢄ ꢏ ꢆ
ꢈ ꢅ ꢏ ꢆ
ꢀ
ꢀ
ꢂ ꢂ ꢏ ꢁ
ꢀ ꢃ ꢏ ꢁ
ꢈ ꢁ ꢃ ꢏ ꢁ
ꢄ ꢃ ꢆ ꢏ ꢁ
ꢁ ꢈ ꢏ ꢆ
ꢃ ꢐ ꢏ ꢐ
ꢅ ꢄ ꢈ ꢏ ꢁ
ꢐ ꢂ ꢄ ꢏ ꢂ
ꢅ ꢄ ꢄ ꢏ ꢂ
ꢂ ꢆ ꢄ ꢏ ꢂ
ꢐ ꢇ ꢄ ꢏ ꢂ
ꢀ
ꢀ ꢅ ꢏ ꢂ
ꢇ ꢁ ꢅ ꢏ ꢂ
ꢃ ꢃ ꢅ ꢏ ꢂ
ꢅ ꢀ ꢏ ꢂ
ꢀ
ꢅ ꢅ ꢏ ꢂ
ꢅ ꢀ ꢐ ꢏ ꢂ
ꢂ ꢂ ꢐ ꢏ ꢂ
ꢐ ꢃ ꢐ ꢏ ꢂ
ꢆ ꢅ ꢐ ꢏ ꢂ
ꢄ ꢇ ꢐ ꢏ ꢂ
ꢀ ꢀ ꢏ ꢁ
ꢈ ꢄ ꢅ ꢏ ꢃ
ꢄ ꢐ ꢇ ꢏ ꢃ
ꢀ ꢁ ꢏ ꢃ
ꢐ ꢀ ꢏ ꢃ
ꢅ ꢁ ꢈ ꢏ ꢆ
ꢇ ꢃ ꢈ ꢏ ꢆ
ꢆ ꢅ ꢈ ꢏ ꢆ
ꢈ ꢇ ꢈ ꢏ ꢆ
ꢄ ꢀ ꢏ ꢂ
ꢃ ꢀ ꢏ ꢂ
ꢁ
ꢅ ꢐ ꢏ ꢆ
ꢀ
ꢆ ꢂ ꢏ ꢇ
S14

2 3 . 5 1
2 3 . 5 9
2 4 . 1 3
2 4 . 2 6
2 5 . 5 5
2 5 . 6 8
2 9 . 2 4
2 9 . 3 3
2 9 . 4 3
3 1 . 1 3
3 1 . 1 8
3 1 . 2 1
3 2 . 1 8
3 2 . 3 4
3 3 . 9 9
3 4 . 1 3
3 4 . 4 2
3 7 . 2 0
3 8 . 1 1
3 8 . 4 0
4 1 . 6 7
4 1 . 8 0
5
5
3 . 9 7
4 . 2 9
7 6 . 8 4
7 7 . 1 6
7 7 . 4 8
1 0 7 . 8 0
1 0 7 . 9 7
1 1 0 . 7 5
1
1
2 0 . 0 1
2 0 . 0 3
1
1
2 6 . 2 4
2 6 . 7 0
1
1
3 2 . 9 0
3 2 . 9 7
1 4 0 . 2 2
1
4 0 . 6 0
1
4 6 . 5 3
1
1
4 6 . 7 4
4 7 . 0 8
1 5 2 . 3 9
1 5 2 . 5 0
1 5 5 . 7 7
1 5 5 . 7 9
S15

S16

S17

S18

S19

ꢀ ꢀ ꢅ ꢐ ꢂ
ꢂ ꢀ ꢐ ꢂ
ꢅ ꢁ ꢉ ꢐ ꢆ
ꢇ ꢁ ꢉ ꢐ ꢆ
ꢄ ꢂ ꢉ ꢐ ꢆ
ꢄ ꢃ ꢉ ꢐ ꢆ
ꢆ ꢃ ꢉ ꢐ ꢆ
ꢆ ꢄ ꢉ ꢐ ꢆ
ꢅ ꢀ ꢃ ꢐ ꢆ
ꢈ ꢀ ꢃ ꢐ ꢆ
ꢄ ꢉ ꢐ ꢁ
ꢀ
ꢁ
ꢉ ꢐ ꢀ
ꢉ ꢐ ꢀ
ꢀ ꢆ ꢃ ꢐ ꢆ
ꢃ ꢉ ꢐ ꢀ
ꢂ ꢆ ꢃ ꢐ ꢆ
ꢂ ꢇ ꢃ ꢐ ꢆ
ꢄ ꢇ ꢃ ꢐ ꢆ
ꢂ ꢂ ꢆ ꢐ ꢆ
ꢄ ꢂ ꢆ ꢐ ꢆ
ꢁ ꢃ ꢆ ꢐ ꢆ
ꢂ ꢇ ꢁ ꢐ ꢀ ꢀ
ꢉ ꢉ ꢐ ꢀ
S20

ꢆ ꢈ ꢐ ꢃ ꢃ
ꢄ ꢈ ꢐ ꢆ ꢇ
ꢆ ꢁ ꢐ ꢇ ꢇ
ꢈ ꢄ ꢐ ꢇ ꢇ
ꢂ ꢀ ꢐ ꢉ ꢀ ꢁ
ꢅ ꢄ ꢐ ꢇ ꢂ ꢁ
ꢈ ꢄ ꢐ ꢈ ꢂ ꢁ
ꢄ ꢄ ꢐ ꢀ ꢃ ꢁ
ꢆ ꢄ ꢐ ꢃ ꢃ ꢁ
ꢁ ꢃ ꢐ ꢈ ꢃ ꢁ
ꢅ ꢆ ꢐ ꢉ ꢃ ꢁ
ꢅ ꢄ ꢐ ꢉ ꢅ ꢁ
S21

ꢉ ꢉ ꢄ ꢐ ꢁ
ꢈ ꢃ ꢂ ꢐ ꢂ
ꢁ ꢈ ꢀ ꢐ ꢄ
ꢅ ꢉ ꢐ ꢁ
ꢆ ꢉ ꢂ ꢐ ꢆ
ꢂ ꢀ ꢂ ꢐ ꢆ
ꢈ ꢀ ꢂ ꢐ ꢆ
ꢅ ꢁ ꢂ ꢐ ꢆ
ꢉ ꢂ ꢂ ꢐ ꢆ
ꢂ ꢅ ꢂ ꢐ ꢆ
ꢇ ꢆ ꢂ ꢐ ꢆ
ꢉ ꢇ ꢂ ꢐ ꢆ
ꢈ ꢈ ꢂ ꢐ ꢆ
ꢃ ꢀ ꢃ ꢐ ꢆ
ꢆ ꢀ ꢃ ꢐ ꢆ
ꢆ ꢂ ꢃ ꢐ ꢆ
ꢉ ꢃ ꢃ ꢐ ꢆ
ꢇ ꢄ ꢃ ꢐ ꢆ
ꢈ ꢈ ꢐ ꢇ
ꢉ ꢉ ꢐ ꢀ
ꢂ ꢉ ꢐ ꢁ
ꢀ ꢅ ꢃ ꢐ ꢆ
ꢆ ꢆ ꢃ ꢐ ꢆ
ꢆ ꢉ ꢄ ꢐ ꢆ
ꢉ ꢀ ꢄ ꢐ ꢆ
ꢃ ꢀ ꢄ ꢐ ꢆ
ꢈ ꢁ ꢄ ꢐ ꢆ
ꢄ ꢆ ꢅ ꢐ ꢆ
ꢈ ꢆ ꢅ ꢐ ꢆ
ꢀ ꢅ ꢈ ꢐ ꢆ
ꢄ ꢅ ꢈ ꢐ ꢆ
ꢂ ꢇ ꢈ ꢐ ꢆ
ꢈ ꢇ ꢆ ꢐ ꢉ ꢀ
ꢄ ꢈ ꢐ ꢉ
S22

ꢈ ꢉ ꢑ ꢊ ꢅ
ꢄ ꢄ ꢑ ꢈ ꢂ ꢁ
ꢃ ꢇ ꢑ ꢈ ꢃ ꢁ
ꢇ ꢇ ꢑ ꢈ ꢃ ꢁ
ꢊ ꢈ ꢑ ꢈ ꢃ ꢁ
ꢇ ꢃ ꢑ ꢉ ꢃ ꢁ
ꢃ ꢈ ꢑ ꢉ ꢃ ꢁ
ꢂ ꢄ ꢑ ꢁ ꢄ ꢁ
ꢈ ꢅ ꢑ ꢄ ꢄ ꢁ
ꢆ ꢊ ꢑ ꢄ ꢄ ꢁ
ꢉ ꢇ ꢑ ꢈ ꢄ ꢁ
ꢊ ꢄ ꢑ ꢉ ꢄ ꢁ
ꢊ ꢄ ꢑ ꢄ ꢇ ꢁ
S23

ꢈ ꢄ ꢆ ꢐ ꢅ
ꢈ ꢁ ꢉ ꢐ ꢆ
ꢀ ꢃ ꢉ ꢐ ꢆ
ꢆ ꢃ ꢉ ꢐ ꢆ
ꢉ ꢅ ꢉ ꢐ ꢆ
ꢄ ꢈ ꢉ ꢐ ꢆ
ꢄ ꢉ ꢀ ꢐ ꢆ
ꢃ ꢀ ꢀ ꢐ ꢆ
ꢇ ꢀ ꢀ ꢐ ꢆ
ꢈ ꢁ ꢁ ꢐ ꢆ
ꢅ ꢅ ꢁ ꢐ ꢆ
ꢉ ꢈ ꢁ ꢐ ꢆ
ꢈ ꢈ ꢁ ꢐ ꢆ
ꢄ ꢉ ꢂ ꢐ ꢆ
ꢄ ꢉ ꢐ ꢀ
ꢆ ꢈ ꢐ ꢉ
ꢈ ꢂ ꢐ ꢅ
ꢀ ꢅ ꢐ ꢈ
ꢈ ꢉ ꢐ ꢀ
ꢃ ꢄ ꢃ ꢐ ꢆ
ꢆ ꢄ ꢉ ꢐ ꢇ
ꢆ ꢆ ꢉ ꢐ ꢇ
ꢂ ꢇ ꢃ ꢐ ꢇ
ꢁ ꢉ ꢐ ꢀ
ꢀ
ꢈ ꢃ ꢐ ꢇ
ꢉ ꢉ ꢐ ꢀ
ꢉ ꢉ ꢐ ꢀ
ꢄ ꢈ ꢃ ꢐ ꢇ
ꢇ ꢄ ꢉ ꢐ ꢈ
ꢀ ꢅ ꢉ ꢐ ꢈ
ꢄ ꢆ ꢇ ꢐ ꢀ ꢀ
ꢆ ꢈ ꢐ ꢉ
S24

ꢁ ꢉ ꢐ ꢅ ꢇ
ꢄ ꢈ ꢐ ꢆ ꢇ
ꢆ ꢁ ꢐ ꢇ ꢇ
ꢈ ꢄ ꢐ ꢇ ꢇ
ꢄ ꢇ ꢐ ꢀ ꢁ ꢁ
ꢀ ꢉ ꢐ ꢂ ꢂ ꢁ
ꢉ ꢁ ꢐ ꢈ ꢂ ꢁ
ꢂ ꢂ ꢐ ꢈ ꢂ ꢁ
ꢇ ꢈ ꢐ ꢉ ꢂ ꢁ
ꢀ
ꢁ
ꢈ ꢐ ꢀ ꢃ ꢁ
ꢁ ꢐ ꢅ ꢃ ꢁ
ꢃ ꢂ ꢐ ꢅ ꢃ ꢁ
ꢆ ꢆ ꢐ ꢇ ꢃ ꢁ
ꢁ ꢀ ꢐ ꢂ ꢄ ꢁ
ꢉ ꢂ ꢐ ꢉ ꢄ ꢁ
ꢂ ꢀ ꢐ ꢂ ꢅ ꢁ
ꢈ ꢅ ꢐ ꢃ ꢆ ꢁ
S25

ꢆ ꢇ ꢐ ꢅ
ꢃ ꢀ ꢐ ꢆ
ꢄ ꢀ ꢐ ꢆ
ꢅ ꢀ ꢐ ꢆ
ꢅ ꢀ ꢐ ꢆ
ꢆ ꢀ ꢐ ꢆ
ꢈ ꢀ ꢐ ꢆ
ꢅ ꢁ ꢐ ꢆ
ꢇ ꢁ ꢐ ꢆ
ꢉ ꢂ ꢐ ꢆ
ꢉ ꢉ ꢐ ꢀ
ꢆ ꢁ ꢐ ꢇ
ꢉ ꢆ ꢐ ꢉ ꢀ
ꢉ ꢀ ꢐ ꢀ
ꢄ ꢉ ꢐ ꢁ
ꢁ ꢂ ꢐ ꢆ
ꢂ ꢂ ꢐ ꢆ
ꢃ ꢂ ꢐ ꢆ
ꢀ ꢄ ꢐ ꢆ
ꢂ ꢇ ꢐ ꢆ
ꢄ ꢇ ꢐ ꢆ
ꢁ ꢃ ꢐ ꢀ ꢀ
ꢅ ꢈ ꢐ ꢉ
S26

ꢆ ꢇ ꢐ ꢅ ꢇ
ꢄ ꢈ ꢐ ꢆ ꢇ
ꢆ ꢁ ꢐ ꢇ ꢇ
ꢈ ꢄ ꢐ ꢇ ꢇ
ꢁ
ꢃ ꢐ ꢀ ꢁ ꢁ
ꢇ ꢐ ꢇ ꢂ ꢁ
ꢀ
ꢂ ꢁ ꢐ ꢈ ꢂ ꢁ
ꢈ ꢁ ꢐ ꢈ ꢂ ꢁ
ꢂ ꢉ ꢐ ꢉ ꢂ ꢁ
ꢂ ꢃ ꢐ ꢁ ꢃ ꢁ
ꢃ ꢀ ꢐ ꢅ ꢃ ꢁ
ꢇ ꢂ ꢐ ꢅ ꢃ ꢁ
ꢀ ꢀ ꢐ ꢈ ꢃ ꢁ
ꢃ ꢂ ꢐ ꢂ ꢄ ꢁ
ꢆ ꢄ ꢐ ꢅ ꢆ ꢁ
S27

S28

ꢉ ꢄ ꢐ ꢂ ꢃ
ꢂ ꢆ ꢐ ꢃ ꢃ
ꢄ ꢉ ꢐ ꢃ ꢃ
ꢆ ꢆ ꢐ ꢇ ꢆ ꢆ
ꢆ ꢁ ꢐ ꢃ ꢆ ꢆ
ꢃ ꢇ ꢐ ꢁ ꢇ ꢆ
ꢆ ꢂ ꢐ ꢈ ꢇ ꢆ
ꢉ ꢀ ꢐ ꢉ ꢇ ꢆ
ꢈ ꢆ ꢐ ꢃ ꢇ ꢆ
ꢆ ꢆ ꢐ ꢄ ꢇ ꢆ
ꢃ ꢀ ꢐ ꢄ ꢇ ꢆ
ꢂ ꢈ ꢐ ꢇ ꢈ ꢆ
ꢅ ꢄ ꢐ ꢇ ꢈ ꢆ
ꢆ ꢆ ꢐ ꢈ ꢉ ꢆ
S29