Palladium-Catalysed Amination of Aryl- and Heteroaryl Halides
organic phase was dried and evaporated to give tert-butyl tetraiso-
propylphosphorodiamidite (13; 0.984 g, 86%) as a white crystalline
solid. H NMR (300 MHz, CDCl3): δ = 3.64–3.47 (m, 4 H), 1.32
Experimental Section
1
General Remarks: Unless otherwise stated, the reactions were per-
formed under argon in a normal fume cupboard in 10 mL Schlenk
tubes sealed with PTFE septa, using an oil bath heated at 105 °C.
Reaction progress was monitored by GC, and compounds were
(m, 9 H), 1.23–1.08 (m, 24 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 74.86 [d, JP,C = 15.6 Hz, C(CH3)3], 44.88 [d, JP,C = 13.5 Hz, 4
C, CH(CH3)2], 30.97 [d, JP,C = 8.2 Hz, 3 C, C(CH3)3], 24.63 [d, JP,C
= 5.5 Hz, 4 C, CH(CH3)2], 24.23 [d, JP,C = 8.7 Hz, 4 C, CH(CH3)
2] ppm. 31P NMR (162 MHz, CDCl3): δ = 99.74 ppm. HRMS (EI):
calcd. for C16H37N2OP [M]+ 304.2644; found 304.2644.
1
identified by GC–MS or by H and 13C NMR spectroscopy using
authentic samples. Bis(diisopropylamino)chlorophosphine (11) was
bought from Sigma–Aldrich, and tert-butyl tetraisopropylphos-
phorodiamidite (13) was prepared as described below or was
bought from Sigma–Aldrich and used without further purification
(95%). Dry toluene was acquired from Sigma–Aldrich or TCI, and
was used without further drying. All other reagents were purchased
from Acros, Sigma–Aldrich, Alfa Aesar, and ABCR Chemicals,
and were used without further purification. NMR spectra were re-
corded with Bruker Avance 300 and DRX 400 (1H: 300 or
400 MHz, 13C: 75 or 101 MHz) spectrometers using tetramethylsil-
ane as internal standard (δ = 0 ppm). High-resolution EI mass
spectra were measured with a Finnigan MAT 95S spectrometer.
Conversions to the coupling product, based on aryl halide, were
determined by GC. Reported yields are an average of three or more
runs. Analytical thin-layer chromatography was carried out on
Merck silica gel 60 F254q plates, and column chromatography was
carried out using Merck silica gel 60 (230–400 mesh ASTM).
N-Phenyl-N-(pyrazin-2-yl)pyrazin-2-amine (67): Following the gene-
ral procedure, compound 67 was obtained as a white solid. Rf =
0.16 (EtOAc/petroleum ether, 1:1). 1H NMR (300 MHz, CDCl3): δ
= 8.41 (d, J = 1.3 Hz, 2 H), 8.27–8.17 (m, 4 H), 7.48 (t, J = 7.5 Hz,
2 H), 7.37 (t, J = 7.4 Hz, 1 H), 7.25 (d, J = 8.5 Hz, 2 H) ppm.
HRMS (EI): calcd. for C14H11N5 [M]+ 249.1014; found 249.1016.
N-Phenyl-N-(quinolin-2-yl)quinolin-2-amine (69): Following the ge-
neral procedure, compound 69 was obtained as colourless crystals.
Rf = 0.54 (EtOAc/petroleum ether, 1:4). 1H NMR (300 MHz,
3
CDCl3): δ = 8.00 (d, J = 8.8 Hz, 2 H), 7.82–7.69 (m, 4 H), 7.62–
7.56 (m, 2 H), 7.48–7.35 (m, 4 H), 7.35–7.23 (m, 5 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 156.72, 147.50, 144.65, 137.11,
129.61, 129.50, 128.28, 128.02, 127.32, 126.01, 125.80, 124.92,
117.92 ppm. HRMS (EI): calcd. for C24H17N3 [M]+ 347.1422;
found 347.1423.
Catalyst Preparation: A stock solution of catalyst was prepared as
follows: Pd(dba)2 (1 equiv.) was added to a heat-gun-dried Schlenk
tube under argon, and then tert-butyl tetraisopropylphosphorodi-
amidite (95%; 2 equiv.) was added. The tube was evacuated and
backfilled with argon three times, and then dry toluene was added
by syringe. The Schlenk tube was then capped with a PTFE sep-
tum, the solution was homogenised using an IKA MS2 mini shaker
for 30 s, and then an argon-filled balloon was attached to the tube.
The solution was stirred for at least 10 min before the catalyst was
added to the reaction mixture. The calculated amount of freshly
prepared catalyst was added using a 1 mL syringe. For each set of
reactions, a new batch of the catalyst solution was prepared.
N-(iso-Quinolin-1-yl)-N-phenylisoquinolin-1-amine (71): Following
the general procedure, compound 71 was obtained as a white solid.
Rf = 0.10 (EtOAc/petroleum ether, 1:4). 1H NMR (300 MHz,
3
CDCl3): δ = 8.23 (d, J = 5.7 Hz, 2 H), 7.92–7.76 (m, 4 H), 7.58
(dt, 3J = 7.6 Hz, 2 H), 7.50–7.43 (m, 2 H), 7.37–7.20 (m, 4 H), 7.10
(dt, 3J = 7.4 Hz, 1 H), 7.00–6.90 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 158.69, 148.63, 141.93, 138.81, 129.98,
129.47, 127.31, 125.93, 124.54, 124.08, 118.67 ppm. HRMS (EI):
calcd. for C24H17N3 [M]+ 347.1422; found 347.1414.
Supporting Information (see footnote on the first page of this arti-
cle): Selected spectroscopic characterization of known amination
General Procedure for the Amination Reaction: NaOtBu (2 mmol)
and aryl halide (1 mmol; when solid) were added to an oven-dried
Schlenk tube. The tube was evacuated and backfilled with argon
three times, and then dry toluene, catalyst (volume calculated based
on the desired concentration of catalyst), and amine (1.20 mmol)
were added to reach a total volume of 3 mL. When an liquid aryl
halide was used, this was added after the addition of the catalyst.
The tube was then sealed with a PTFE septum, the suspension
homogenized using an IKA MS2 mini shaker for 10–30 s, and the
mixture was stirred in a preheated oil bath at 105 °C. Reaction
progress was monitored by GC. After all the starting materials had
been consumed, or when the reaction did not progress any more,
the mixture was cooled down to room temperature, and then di-
ethyl ether (7 mL) and saturated aqueous NaCl solution (10 mL)
were added. The resulting suspension was transferred into a separa-
tory funnel, the layers were separated, and the organic phase was
washed with water (4ϫ 10 mL). The organic layer was dried with
anhydrous Na2SO4, and then concentrated under reduced pressure.
The crude residue was purified by column chromatography. The
spectroscopic data of all known amination products are in agree-
ment with literature values.
1
products; copies of the H and 13C NMR spectra; GC chromato-
grams.
Acknowledgments
Financial support by the Max Planck Society and the Arthur C.
Cope Foundation is gratefully acknowledged. The authors thank
Stephanie Dehn for help with GC analysis.
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tert-Butyl Tetraisopropylphosphorodiamidite (13): Bis(diisopropyl-
amino)chlorophosphine (11; 1.0 g, 3.75 mmol) and potassium tert-
butoxide (12; 0.504 g, 4.5 mmol) were placed in a Schlenk tube,
which was then degassed. Dry toluene (40 mL) was added under
an argon atmosphere. The reaction mixture was stirred at room
temperature for 24 h, then it was washed with water (4ϫ). The
10029.
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Eur. J. Org. Chem. 2014, 2070–2076
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