A R T I C L E S
Marion et al.
Table 12. Buchwald-Hartwig Amination at Low Catalyst Loading
a
t
b
Reaction conditions: aryl halide (1 mmol), amine (1.1 mmol), (SIPr)Pd(cin)Cl (8) (1-0.001 mol %), KO Bu (1.1 mmol), DME (1 mL). GC yields
based on hexamethylbenzene as internal standard, average of two runs. c T ) 80 °C.
triturated with pentane and collected by filtration on a sintered frit in
air. The complex was then recrystallized from DCM/pentane.
of 3a or 6.5 mg of 7) was added to a vial equipped with a magnetic
bar and a screw cap fitted with a septum. Outside the glovebox,
technical grade 2-propanol (4.0 mL) was injected into the vial through
the septum and the mixture stirred at room temperature for 15 min
prior to the injection of the required amount of substrates.
(
IPr)Pd(crotyl)Cl (5). The general procedure yielded 1.09 g (92%)
1
of the complex. H NMR (CDCl
3
, 400 MHz): δ 7.42 (t, J ) 7.6 Hz,
H), 7.25 (d, J ) 1.6 Hz, 4H), 7.14 (s, 2H), 4.49 (dt, J ) 6.8, 4.8 Hz,
H), 3.46 (sextet, J ) 6.4 Hz, 1H), 3.06 (q, J ) 6.8 Hz, 2H), 2.89 (q,
2
1
Suzuki-Miyaura Cross-Coupling Reactions. General Procedure.
In a glovebox to a vial that closed with a screw cap fitted with a septum
and that was equipped with a magnetic stir bar were added in turn
potassium tert-butoxide (1.1 mmol, 124 mg), boronic acid (1.05 mmol),
and aryl halide (if solid, otherwise vide infra). Outside the glovebox,
the required amount of catalyst solution (catalyst loading 0.05 mol %,
J ) 6.8 Hz, 2H), 2.71 (d, J ) 6.4 Hz, 1H), 1.41 (d, J ) 8 Hz, 1H),
.35 (d, J ) 6.8 Hz, 12H), 1.15 (d, J ) 6.8 Hz, 6H), 1.11 (d, J ) 6.8
1
13
Hz, 6H). C NMR (CDCl
30.0, 124.2, 124.0, 113.3, 90.2, 44.9, 28.7, 26.5, 26.0, 23.1, 17.1. Anal.
Calcd for C31 Pd (MW 585.56): C, 63.59; H, 7.40; N, 4.78.
Found: C, 63.42; H, 7.53; N, 4.63.
IPr)Pd(prenyl)Cl (6). The general procedure yielded 1.13 g (95%)
3
, 100 MHz): δ 187.0, 146.3, 146.2, 136.24,
1
H43ClN
2
2
00 µL, catalyst loading 0.005 mol %, 20 µL) was injected through
(
the septum, followed by addition of technical grade 2-propanol (1 mL).
The mixture was then stirred at room temperature unless otherwise
indicated. After 15 min, the aryl halide (1 mmol) was injected (if liquid),
and the reaction was monitored by gas chromatography. When the
reaction reached completion, or no further conversion was observed
by gas chromatography, water was added to the reaction mixture, the
organic layer was extracted with tert-butylmethyl ether (MTBE), dried
over magnesium sulfate, and the solvent was evaporated in vacuo. When
necessary the product was purified by flash chromatography on silica
gel.
1
of the complex. H NMR (CDCl
3
, 400 MHz): δ 7.47 (t, J ) 8 Hz,
H), 7.32 (d, J ) 8 Hz, 4H), 7.20 (s, 2H), 4.42 (dd, J ) 12.4, 7.2 Hz,
H), 3.23 (q, J ) 6.8 Hz, 2H), 2.85 (q, J ) 6.8 Hz, 2H), 2.70 (dd, J
2
1
)
)
1
7.2, 1.6 Hz, 1H), 1.58 (d, J ) 8.4 Hz, 1H), 1.49 (s, 3H), 1.46 (d, J
6.8 Hz, 6H), 1.36 (d, J ) 6.8 Hz, 6H), 1.23 (d, J ) 6.8 Hz, 6H),
.11 (d, J ) 6.8 Hz, 6H), 0.78 (s, 3H). 1 C NMR (CDCl
3
, 100 MHz):
3
δ 187.1, 146.4, 146.1, 136.4, 130.0, 124.1, 124.0, 123.8, 106.6, 105.7,
1.6, 28.8, 28.6, 26.8, 26.0, 23.7, 20.0. Anal. Calcd for C32 Pd
MW 599.59): C, 64.10; H, 7.56; N, 4.67. Found: C, 64.36; H, 7.66;
N, 4.34.
IPr)Pd(cinnamyl)Cl (7). The general procedure yielded 1.10 g
4
H45ClN
2
(
Buchwald-Hartwig Cross-Coupling Reactions. General Proce-
dure. In a glovebox, to a vial that closed with a screw cap fitted with
a septum and that was equipped with a magnetic stir bar were added
in turn (SIPr)Pd(cinnamyl)Cl (1 mol %, 6.5 mg), potassium tert-
butoxide (1.1 mmol, 124 mg), and anhydrous DME (1 mL). Outside
the glovebox, the amine (1.1 mmol) and the aryl halide (1 mmol) were
injected in turn through the septum. If one of the two starting materials
was a solid, it was added to the vial inside the glovebox, and DME
and the second starting material were added outside the glovebox under
argon. The reaction mixture was then stirred at room temperature unless
otherwise indicated. When the reaction reached completion, or no
further conversion was observed by gas chromatography, water was
added to the reaction mixture, the organic layer was extracted with
tert-butylmethyl ether (MTBE), dried over magnesium sulfate, and the
solvent was evaporated in vacuo. When necessary the product was
purified by flash chromatography on silica gel. The reported yields
are the average of at least two runs.
(
1
(
85%) of the complex. H NMR (C
6 6
D , 400 MHz): δ 7.21-7.10 (m,
9
H), 6.98 (d, J ) 7.2 Hz, 2H), 6.64 (s, 2H), 5.07 (dd, J ) 18.8, 6.8
Hz, 1H), 4.30 (d, J ) 12.8 Hz, 1H), 3.31 (t, J ) 6.4 Hz, 2H), 3.13 (t,
J ) 6.4 Hz, 2H), 3.02 (d, J ) 6.4 Hz, 1H), 1.80 (d, J ) 11.6, 1H),
1
1
1
2
7
.46 (d, J ) 6.4 Hz, 6H), 1.39 (d, J ) 6.4 Hz, 6H), 1.03 (d, J ) 4 Hz,
1
3
2H). C NMR (CDCl
30.1, 128.4, 127.5, 126.8, 124.4, 124.0, 123.9, 109.0, 90.4, 28.8, 26.2,
3.1, 46.3. Anal. Calcd for C36 Pd (MW 647.63): C, 66.76; H,
.00; N, 4.33. Found: C, 67.03; H, 7.25; N, 4.03.
SIPr)Pd(cinnamyl)Cl (8). The general procedure yielded 1.06 mg
3
, 100 MHz): δ 185.2, 146.2, 138.1, 136.1,
H45ClN
2
(
1
(82%) of the title complex. H NMR (CDCl
3
, 400 MHz): δ 7.38 (t, J
)
7.6 Hz, 2H), 7.25 (d, J ) 8 Hz, 4H), 7.15-7.11 (m, 5H), 5.05 (dt,
J ) 12.4, 9.2, 1H), 4.34 (d, J ) 13.2 Hz, 1H), 4.03 (s, 4H), 3.44 (broad
s, 4H), 2.89 (broad s, 1H), 1.57 (broad s, 1H), 1.43 (d, J ) 2.8 Hz,
1
3
12H), 1.27 (d, J ) 6.8 Hz, 12H). C NMR (CDCl
212.3, 147.3, 137.8, 136.6, 129.3, 128.5, 127.5, 126.9, 125.3, 124.5,
2
109.3, 91.9, 54.2, 46.2, 28.7, 26.8, 24.0. Anal. Calcd for C36 47ClN -
3
, 100 MHz): δ
N-(4-Biphenylyl)piperidine58 (Table 9, entry 5). The general
procedure yielded, after flash chromatography on silica gel (pentane/
H
Pd (MW 649.64): C, 66.56; H, 7.29; N, 4.31. Found: C, 66.27; H,
7
.09; N, 4.13.
(
58) This compound had already been reported, but our spectroscopic data were
not in accordance with the literature. Louie, J.; Driver, M. S.; Hamann, B.
C.; Hartwig, J. F. J. Org. Chem. 1997, 62, 1268-1273.
Suzuki-Miyaura Cross-Coupling Reactions. Preparation of the
Precatalyst Solutions. In a glovebox, 0.01 mmol of complex (5.7 mg
4
110 J. AM. CHEM. SOC. VOL. 128, NO. 12, 2006
9