Journal of the American Chemical Society
ARTICLE
pyridone tautomer 2A and the other ligand occupying the
complementary hydroxypyridine form 2B. Dynamic proton
NMR allowed us to determine the barrier for interligand hydro-
gen bond breaking and, in combination with theory, led to an
estimate for the enthalpic stabilization through hydrogen bond-
ing of 15 kcal/mol. Hence, a theoretical understanding of the
ground-state structural features of this self-assembling ligand 2 is
now available and ready to be used to further explore its unique
properties as a ligand in homogeneous catalysis.
times with 150 mL portions of diethyl ether, and dried over Na2SO4.
Evaporation of the solvent in vacuo and recrystallization of the residual
oil from methanol yielded 31.0 g (92.4 mmol, 79%) of 2-tert-butoxy-6-
diphenylphosphanylpyridine (8) as a white solid.
Alternatively, 2-tert-butoxy-6-bromopyridine (7B, 100 mg, 0.43
mmol, 1.00 equiv) was dissolved in Et2O (3 mL) and cooled to 0 °C.
After addition of n-BuLi (0.28 mL, 0.43 mmol, 1.56 M in hexane), the
solution was stirred for 60 min at 0 °C. Chlorodiphenylphosphine was
added, and the reaction mixture was stirred at room temperature for an
additional 60 min. Water (1 mL) was added and the solvent removed
under reduced pressure. Purification of the residue by column chroma-
tography over silica gel (CH2Cl2) yielded 125 mg (0.34 mmol, 77%) of
2-tert-butoxy-6-diphenylphosphanylpyridine (8) as a white solid.
mp = 77 °C. 1H NMR (400.1 MHz, CDCl3, ppm) = 7.51-7.44 (m,
4H), 7.11-7.04 (m, 6H), 6.91 (ddd, J = 8.3, 7.3, 2.8 Hz, 1H), 6.75 (dd,
J = 7.3, 2.8 Hz, 1H), 6.45 (d, J = 8.3 Hz, 1H), 1.41 (s, 9H). 13C NMR
(100.6 MHz, CDCl3, ppm) = 164.1, 160.5, 138.0, 137.6, 134.7,
128.9, 128.7, 121.4, 112.2, 79.6, 28.5. 31P NMR (121.5 MHz, CDCl3,
ppm) = -1.7. CHN analysis calcd: C, 75.21; H, 6.61; N, 4.18. Found: C,
74.98; H, 6.57; N, 4.09.
Synthesis of 6-Diphenylphosphanyl-1H-pyridin-2-one (6-DPPon,
2). 2-tert-Butoxy-6-diphenylphosphanylpyridine (8, 9.7 g, 28.9 mmol)
was dissolved in concentrated formic acid (100 mL) saturated with
argon. After stirring for 30 min at room temperature, the solution was
diluted with water (distilled, 120 mL). The precipitate was collected by
filtration, washed with 30 mL of aqueous formic acid (2:1, v/v), and
dried. 6-Diphenylphosphanyl-1H-pyridin-2-one (2) was obtained as a
white solid (5.6 g, 20.05 mmol, 69%). The combined aqueous formic
acid solutions were concentrated in vacuo, and the residue was recrys-
tallized from acetone. This yielded another 1.8 g (6.45 mmol, 22%) of
6-diphenylphosphanyl-1H-pyridin-2-one (2).
’ METHODS
Experimental Methods. All reagents were obtained commer-
cially unless otherwise noted. Reactions were performed using oven-
dried glassware under an atmosphere of argon. Air- and moisture-
sensitive liquids and solutions were transferred via syringe. Organic
solutions were concentrated under reduced pressure (ca. 20 mbar) by
rotary evaporation. Toluene was distilled from sodium, dichlormethane
and MeOH were distilled from CaH2, THF was distilled from potas-
sium, and diethyl ether was refluxed over a potassium-sodium alloy
using benzophenone ketyl radical as indicator and distilled prior to use.
All solvents were stored under an argon atmosphere. Chromatographic
purification of products was accomplished using flash chromatography
on Macherey-Nagel silica gel 60 (230-400 mesh). Nuclear magnetic
resonance spectra were acquired on a Varian Mercury spectrometer
(300, 121.5, and 75.5 MHz for 1H, 31P, and 13C, respectively) and on a
Bruker AMX 400 (400.1 and 100.6 MHz for 1H and 13C, respectively)
and are referenced internally according to residual protio solvent signals.
1
Data for H and 31P NMR are recorded as follows: chemical shift (δ,
ppm), multiplicity (s, singlet; bs, broad singlet; d, doublet; t, triplet; pt,
pseudotriplet; q, quartet; quint, quintet; m, multiplet), coupling con-
stant (Hz), integration. Data for 13C NMR are reported in terms of
chemical shift (δ, ppm). 9 was prepared from commercially available 6B
according to the literature known procedure.23
Synthesis of 2-tert-Butoxy-6-chloropyridine (7A). To a solution of
2,6-dichloropyridine (6A) (10.0 g, 67.6 mmol, 1.00 equiv) in toluene
(150 mL) was added potassium tert-butoxide (9.10 g, 81.1 mmol, 1.20
equiv). After heating for 6 h to 80 °C, the suspension was filtered over
Celite and the solvent removed under reduced pressure. Distillation
(bp = 200 °C, 10-2 mbar) yielded 11.98 g (64.53 mmol, 96%) of 2-tert-
butoxy-6-chloropyridine (7A) as a colorless liquid.
mp = 187 °C. 1H NMR (400.1 MHz, CDCl3, ppm) = 9.29 (br s, 1H),
7.45-7.25 (m, 11H), 6.51 (d, J = 9.0 Hz, 1H), 6.20 (t, J = 6.3 Hz, 1H).
13C NMR (100.6 MHz, CDCl3, ppm) = 163.8, 146.6, 140.5, 133.9,
132.6, 130.2, 129.3, 120.7, 114.0. 31P NMR (121.5 MHz, CDCl3,
ppm) = -8.5. CHN analysis calcd: C, 73.11; H, 5.05; N, 5.02. Found:
C, 72.97; H, 5.18; N, 4.73.
Synthesis of 6-Diphenylphosphanyl-1-methylpyridin-2-one (6-
DPMePon, 10A). To a solution of 6-diphenylphosphanylpyridine-
2(1H)-one (2, 500 mg, 1.79 mmol, 1.00 equiv) in DMF (8 mL) was
added sodium hydride (46.0 mg, 1.91 mmol, 1.07 equiv) in one portion.
After gas evolution ceased, the solution was cooled to 0 °C. Methyl
iodide (255 mg, 1.80 mmol, 1.00 equiv) was added, and the reaction
mixture was stirred for 30 min at room temperature. After addition of
water (20 mL), the organic layer was separated and washed with Et2O.
After drying with MgSO4, the solvent was removed under reduced
pressure, and the residue was purified by column chromatography over
silica gel (CH2Cl2:PE 1:1 to CH2Cl2 to CH2Cl2:EE 1:1), yielding 300
mg (1.02 mmol, 57%) of the desired product as a colorless liquid.
mp = 159 °C. 1H NMR (400.1 MHz, CDCl3, ppm) = 7.37-7.46 (m,
6H), 7.29-7.35 (m, 4H), 7.14 (ddd, J = 8.8 Hz, J = 7.1 Hz, J = 1.5 Hz,
1H), 6.54 (d, J = 9.0 Hz, 1H), 5.62 (d, J = 6.9 Hz, 1H), 3.58 (s, 3H).
13C NMR (100.6 MHz, CDCl3, ppm) = 164.2, 150.6, 137.8, 134.3,
132.9, 130.2, 129.2, 119.8, 113.3, 33.8. 31P NMR (121.5 MHz, CDCl3,
ppm) = -11.1. CHN analysis calcd: C, 73.71; H, 5.50; N, 4.78. Found:
C, 73.42; H, 5.73; N, 4.75.
Synthesis of 2-Methoxy-6-diphenylphosphinopyridine (2-MeODPP,
10B). To a solution of 2-methoxy-6-bromopyridine (8, 855 mg,
4.55 mmol, 1.00 equiv) in Et2O (25 mL) was added n-BuLi (3.25 mL,
4.55 mmol, 1.40 M in hexane, 1.00 equiv) dropwise at 0 °C. The solution
was stirred for 1 h at 0 °C, and chlorodiphenylphosphane (0.82 mL,
1.00 g, 4.55 mmol, 1.00 equiv) was added at this temperature. The
reaction mixture was allowed to warm to room temperature and stirred
for 5 h. The reaction mixture was diluted with CH2Cl2 (50 mL) and
1H NMR (400.1 MHz, CDCl3, ppm) = 7.43 (t, J = 7.7 Hz, 1H), 6.81
(d, J = 7.3 Hz, 1H), 6.53 (d, J = 8.2 Hz, 1H), 1.58 (s, 9H). 13C NMR
(100.6 MHz, CDCl3, ppm) = 163.3, 147.7, 140.2, 115.7, 111.3, 80.9,
28.6. CHN analysis calcd: C, 58.23; H, 6.52; N, 7.54. Found: C, 58.27; H,
6.65; N, 7.48.
Synthesis of 2-tert-Butoxy-6-bromopyridine (7B). To a solution of
2,6-dibromopyridine (6B) (9.48 g, 40.0 mmol, 1.00 equiv) in toluene
(150 mL) was added potassium tert-butoxide, and the suspension was
stirred for 4 h at 80 °C. The reaction mixture was filtered over Celite and
the solvent removed under reduced pressure. Distillation (bp = 120 °C,
oil pump vacuum) yielded 8.50 g (36.7 mmol, 92%) of the desired
product as a colorless liquid.
1H NMR (400.1 MHz, CDCl3, ppm) = 7.34 (m, 1H), 6.98 (d, J =
7.3 Hz, 1H), 6.57 (d, J = 8.2 Hz, 1H), 1.59 (s, 9H). 13C NMR (100.6 MHz,
CDCl3, ppm) = 163.1, 140.1, 137.7, 119.5, 111.5, 80.9, 28.5.
Synthesis of 2-tert-Butoxy-6-diphenylphosphanylpyridine (8). To
liquid ammonia (ca. 500 mL) at -78 °C was added sodium (5.40 g,
235 mmol, 2.03 equiv) over 10 min. The dark blue solution was treated
portionwise first with triphenylphosphine (30.4 g, 116 mmol, 1.00 equiv)
and then, after stirring for 2 h at -78 °C, with 2-tert-butoxy-6-chloro-
pyridine (7A, 21.5 g, 116 mmol, 1.00 equiv). After addition of 175 mL of
tetrahydrofuran, the ammonia was allowed to evaporate overnight. The
residue was quenched with 200 mL of water (distilled), extracted three
973
dx.doi.org/10.1021/ja108639e |J. Am. Chem. Soc. 2011, 133, 964–975