Palladium-Catalyzed Synthesis of Aryl Ketones
FULL PAPER
(%) ϭ 212 (40) [Mϩ], 135 (100), 105 (12), 92 (10), 77 (30). HRMS (m, 2 H), 6.17 (brs, 1 H), 7.42Ϫ7.59 (m, 3 H), 7.93 (m, 2 H) ppm.
(EI): calcd. for C14H12O2 [Mϩ]: 212.083729; found 212.083698.
13C NMR (75 MHz, CDCl3): δ ϭ 23.3, 34.2, 38.2, 128.0, 128.7,
133.5, 136.4, 170.1, 199.6 ppm. MS (EI): m/z (%) ϭ 191 (24) [Mϩ],
176 (1), 148 (13), 132 (12), 120 (12), 105 (100). HRMS (EI): calcd.
for C11H13O2N [Mϩ]: 191.094628; found 191.094493.
12-Hydroxy-1-phenyldodecan-1-one (10t): The ketone was obtained
according to the general procedure from 12-hydroxydodecanoic
acid (5t) (216 mg, 1.00 mmol) and phenylboronic acid (2a) (146 mg,
1.20 mmol) using triphenylphosphane (18.4 mg, 0.07 mmol) as the
ligand. Purification by column chromatography (silica gel, ethyl
acetate/hexane, 60:40) afforded compound 10t (220 mg, 80%) as a
white solid. 1H NMR (300 MHz, CDCl3): δ ϭ 1.27Ϫ1.74 (m, 19
H), 2.94 (m, 2 H), 3.62 (m, 2 H), 7.41Ϫ7.53 (m, 3 H), 7.97 (m, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 24.3, 25.7, 29.3, 29.4,
29.5, 32.8, 38.6, 63.1, 128.0, 128.5, 132.8, 137.1, 200.6 ppm. MS
(EI): m/z (%) ϭ 276 (14) [Mϩ], 258 (1), 246 (1), 215 (1), 133 (12),
120 (100). HRMS (EI): calcd. for C18H28O2 [Mϩ]: 276.208929;
found 276.208987. C18H28O2 (276.4): calcd. C 78.21, H 10.21;
found C 78.13, H 10.16.
N-(3-Oxo-3-phenylpropyl)hexanamide (10y): The ketone was ob-
tained according to the general procedure from N-hexanoyl-β-alan-
ine (5y) (187 mg, 1.00 mmol) and phenylboronic acid (2a) (146 mg,
1.20 mmol) using DPPF (19.4 mg, 0.035 mmol) as the ligand. Puri-
fication by column chromatography (silica gel, ethyl acetate/hexane,
1
60:40) afforded compound 10y (150 mg, 60%) as a white solid. H
NMR (300 MHz, CDCl3): δ ϭ 0.82 (t, J ϭ 6.0 Hz, 3 H), 1.13Ϫ1.25
(m, 4 H), 1.55Ϫ1.59 (m, 2 H), 2.14 (m, 2 H), 3.22 (m, 2 H), 3.68
(m, 2 H), 6.17 (brs, 1 H), 7.42Ϫ7.58 (m, 3 H), 7.91 (m, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ ϭ 13.8, 22.3, 25.3, 31.4, 34.1, 36.8,
38.2, 128.0, 128.7, 133.5, 136.4, 173.6, 199.6 ppm. MS (EI): m/z
(%) ϭ 247 (22) [Mϩ], 218 (3), 204 (8), 191 (52), 148 (28), 105 (100).
HRMS (EI): calcd. for C15H21O2N [Mϩ]: 247.157228; found
247.157320.
Methyl 4-Benzoylbenzoate (10u): The ketone was obtained accord-
ing to the general procedure from 4-(methoxycarbonyl)benzoic acid
(5u) (180 mg, 1.00 mmol) and phenylboronic acid (2a) (146 mg,
1.20 mmol) using tris(p-methoxyphenyl)phosphane (24.7 mg,
0.07 mmol) as the ligand. Purification by column chromatography
(silica gel, ethyl acetate/hexane, 10:90) afforded compound 10u
9a,11a-Dimethyl-1-(1-methyl-4-oxo-4-phenylbutyl)-3a,3b,5,5a,6,8,9,
9a,9b,10,11a-dodecahydrocyclopenta[a]phenanthrene-4,7,11-trione
(10z): The ketone was obtained according to the general procedure
from dehydrocholic acid (5b) (402 mg, 1.00 mmol) and
phenylboronic acid (2a) (146 mg, 1.20 mmol) using tris(p-methoxy-
phenyl)phosphane (24.7 mg, 0.07 mmol) as the ligand. Purification
by column chromatography (silica gel, ethyl acetate/hexane, 40:60)
1
(122 mg, 51%) as a white solid. H NMR (300 MHz, CDCl3): δ ϭ
3.96 (s, 3 H), 7.45Ϫ7.62 (m, 3 H), 7.76Ϫ7.80 (m, 4 H), 8.13 (m, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 52.4, 128.4, 128.7,
129.4, 129.7, 132.9, 133.2, 136.9, 141.3, 166.2, 196.0 ppm. MS (EI):
m/z (%) ϭ 240 (52) [Mϩ], 209 (22), 181 (20), 163 (52), 105 (100).
HRMS (EI): calcd. for C15H12O3 [Mϩ]: 240.078644; found
240.078585.
1
afforded compound 10z (374 mg, 81%) as a white solid. H NMR
(300 MHz, CDCl3): δ ϭ 0.90Ϫ2.35 (m, 29 H), 2.86Ϫ2.95 (m, 4 H),
7.27Ϫ7.58 (m, 3 H), 7.93 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 11.8, 18.9, 21.9, 25.1, 27.6, 29.6, 29.7, 35.2, 36.0, 36.4,
38.6, 42.7, 44.9, 45.5, 45.6, 46.8, 48.9, 51.7, 56.9, 128.0, 128.5,
132.9, 137.0, 200.7, 208.6, 209.0, 212.0 ppm. MS (EI): m/z (%) ϭ
462 (15) [Mϩ], 444 (30), 384 (8), 343 (38), 329 (48), 120 (100).
HRMS (EI): calcd. for C30H38O4 [Mϩ]: 462.277008; found
462.277101. C30H38O4 (462.6): calcd. C 77.89, H 8.22; found C
78.07, H 8.34.
2-(2-Oxo-2-phenylethyl)isoindole-1,3-dione (10v): The ketone was
obtained according to the general procedure from N-phthaloylgly-
cine (5v) (205 mg, 1.00 mmol) and phenylboronic acid (2a) (146 mg,
1.20 mmol) using triphenylphosphane (18.4 mg, 0.07 mmol) as the
ligand. Purification by column chromatography (silica gel, ethyl
acetate/hexane, 60:40) afforded compound 10v (119 mg, 45%) as a
white solid. 1H NMR (300 MHz, CDCl3): δ ϭ 5.13 (s, 2 H),
7.52Ϫ7.64 (m, 3 H), 7.75 (m, 2 H), 7.91 (m, 2 H), 8.03 (m, 2 H)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 44.2, 123.5, 128.1, 132.2,
134.0, 134.1, 134.4, 167.9, 190.9 ppm. MS (EI): m/z (%) ϭ 265 (18)
[Mϩ], 237 (1), 208 (1), 180 (1), 160 (20), 133 (5), 105 (100). HRMS
(EI): calcd. for C16H11NO3 [Mϩ]: 265.073893; found 265.073997.
1-(4-Methoxyphenyl)-3-phenylpropan-1-one (12): The ketone was
obtained according to the general procedure from 3-phenylpropi-
onic acid (5b) (150 mg, 1.00 mmol) and (4-methoxyphenyl)boronic
acid (2b) (182 mg, 1.20 mmol) using tris(p-methoxyphenyl)phos-
phane (24.7 mg, 0.07 mmol) as the ligand. Purification by column
chromatography (Al2O3, ethyl acetate/hexane, 15:85) afforded com-
pound 12 (187 mg, 78%) as a white solid. 1H NMR (300 MHz,
CDCl3): δ ϭ 3.06 (t, J ϭ 7.0 Hz, 2 H), 3.24 (t, J ϭ 7.0 Hz, 2 H),
3.85 (s, 3 H), 6.92 (m, 2 H), 7.23Ϫ7.19 (m, 5 H), 7.95 (m, 2 H)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 30.3, 40.1, 55.5, 113.7,
126.1, 128.4, 128.5, 129.9, 130.3, 141.5, 163.5, 197.8 ppm. MS (EI):
m/z (%) ϭ 240 (33) [Mϩ], 135 (100), 121 (2), 107 (6), 92 (8), 77
(13). HRMS (EI): calcd. for C16H16O2 [Mϩ]: 240.115029; found
240.115054. C16H16O2 (240.3): calcd. C 79.97, H 6.71; found C
80.12, H 6.78.
Methyl 4-Oxo-4-phenylbutyrate (10w): The ketone was obtained ac-
cording to the general procedure from monomethyl succinate (5w)
(132 mg, 1.00 mmol) and phenylboronic acid (2a) (146 mg,
1.20 mmol) using tris(p-methoxyphenyl)phosphane (24.7 mg,
0.07 mmol) as the ligand. Purification by column chromatography
(silica gel, ethyl acetate/hexane, 20:80) afforded compound 10w
(134 mg, 70%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ ϭ
2.75 (t, J ϭ 7.0 Hz, 2 H), 3.30 (t, J ϭ 7.0 Hz, 2 H), 3.70 (s, 3 H),
7.42Ϫ7.58 (m, 3 H), 7.97 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 28.0, 33.3, 51.8, 128.0, 128.6, 133.2, 136.5, 173.3,
198.0 ppm. MS (EI): m/z (%) ϭ 192 (20) [Mϩ], 174 (1), 161 (22),
133 (2), 105 (100). HRMS (EI): calcd. for C11H12O3 [Mϩ]:
192.078644; found 192.078476.
1-(3-Chlorophenyl)-3-phenylpropan-1-one (13): The ketone was ob-
tained according to the general procedure from 3-phenylpropionic
acid (5b) (150 mg, 1.00 mmol) and (3-chlorophenyl)boronic acid
(2c) (187 mg, 1.20 mmol) using DPPF (19.4 mg, 0.035 mmol) as
the ligand. Purification by column chromatography (Al2O3, ethyl
acetate/hexane, 10:90) afforded compound 13 (134 mg, 55%) as a
white solid. 1H NMR (200 MHz, CDCl3): δ ϭ 7.94 (m, 1 H) ppm.
N-(3-Oxo-3-phenylpropyl)acetamide (10x): The ketone was ob-
tained according to the general procedure from N-acetyl-β-alanine
(5x) (131 mg, 1.00 mmol) and phenylboronic acid (2a) (146 mg,
1.20 mmol) using DPPF (19.4 mg, 0.035 mmol) as the ligand. Puri-
fication by column chromatography (silica gel, ethyl acetate/hexane, 13C NMR (50 MHz, CDCl3): δ ϭ 29.9, 40.5, 126.2, 128.1, 128.3,
1
60:40) afforded compound 10x (152 mg, 80%) as a white solid. H
NMR (300 MHz, CDCl3): δ ϭ 1.92 (s, 3 H), 3.23 (m, 2 H), 3.68
128.5, 129.9, 132.9, 134.9, 138.3, 140.9, 197.8 ppm. MS (EI): m/z
(%) ϭ 244 (52) [Mϩ], 209 (22), 191 (1), 165 (1), 139 (100). HRMS
Eur. J. Org. Chem. 2002, 3254Ϫ3267
3265