Job/Unit: O42224
/KAP1
Date: 26-05-14 11:22:48
Pages: 10
Gold-Catalyzed Synthesis of 2-Substituted 4-Quinolones
tert-Butyl [2-(1-Hydroxyhex-2-yn-1-yl)phenyl]carbamate (6e): Fol-
HRMS (EI+): calcd. for [C24H29NO4]+ m/z 395.2097; found
lowing general procedure B afforded 75.1 mg (62%) of the desired
product. H NMR (300 MHz, CDCl3): δ = 7.86 (d, J = 8.1 Hz, 1
395.2108.
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tert-Butyl
{2-[4-(Benzyloxy)-1-hydroxy-4-methylpent-2-yn-1-yl]-
H), 7.69 (s, 1 H), 7.47 (dd, J = 7.7, 1.4 Hz, 1 H), 7.33–7.25 (m, 1
H), 7.03 (td, J = 7.5, 1.2 Hz, 1 H), 5.46 (s, 1 H), 2.99 (s, 1 H), 2.25
(td, J = 7.1, 2.0 Hz, 2 H), 1.57 (dd, J = 14.5, 7.3 Hz, 2 H), 1.51 (s,
9 H), 1.00 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 153.45, 137.03, 129.48, 129.26, 127.79, 123.22, 121.81, 88.91,
80.47, 78.41, 63.52, 28.42, 22.03, 20.88, 13.61 ppm. HRMS (EI+):
calcd. for [C17H23NO3]+ m/z 289.1678; found 289.1680.
phenyl}carbamate (6k): Compound 4k reacted according to general
procedure B afforded 121.5 mg (76%) of the desired product. 1H
NMR (300 MHz, CDCl3): δ = 7.88 (d, J = 8.1 Hz, 1 H), 7.72 (s, 1
H), 7.44 (t, J = 6.2 Hz, 1 H), 7.33–7.25 (m, 1 H), 7.02 (t, J =
7.5 Hz, 1 H), 5.50 (s, 1 H), 4.36 (q, J = 6.6 Hz, 1 H), 3.33 (s, 1 H),
1.50 (s, 9 H), 1.41 (dd, J = 6.6, 3.9 Hz, 3 H), 1.24 (d, J = 5.9 Hz,
9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.35, 137.10, 129.29,
128.87, 127.81, 123.13, 121.66, 90.98, 81.31, 81.27, 80.44, 75.07,
63.30, 57.85, 28.44, 28.21, 24.29 ppm. HRMS (EI+): calcd. for
[C20H29NO4]+ m/z 347.2097; found 347.2103.
tert-Butyl {2-[1-Hydroxy-3-(trimethylsilyl)prop-2-yn-1-yl]phenyl}-
carbamate (6f): Following general procedure B afforded 58.0 mg
(54%) of the desired product. 1H NMR (300 MHz, CDCl3): δ =
7.86 (d, J = 8.2 Hz, 1 H), 7.60 (s, 1 H), 7.47 (dd, J = 7.6, 1.4 Hz,
1 H), 7.38–7.26 (m, 1 H), 7.05 (td, J = 7.6, 1.1 Hz, 1 H), 5.46 (s, 1
H), 3.03 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.47,
137.03, 129.51, 128.89, 128.01, 123.45, 122.02, 103.26, 93.12, 80.61,
63.66, 28.47, –0.11 ppm. HRMS (EI+): calcd. for [C17H25NO3Si]+
m/z 319.1604; found 319.1611.
General Procedure for the Boc-Deprotection Reaction Leading to
7a–7k: Compound 6 was dissolved in CH2Cl2 (10 mL). Trifluoro-
acetic acid (0.4 mL) was added dropwise to the solution. The solu-
tion was mixed at room temperature for 15 min. Water (15 mL) was
added and mixture was extracted with CH2Cl2. The product was
purified by flash chromatography with n-hexane and ethyl acetate
(3:1) as eluent.
tert-Butyl
{2-[4-(Benzyloxy)-1-hydroxybut-2-yn-1-yl]phenyl}carb-
amate (6g): Following general procedure B afforded 130.7 mg
(78%) of the desired product. 1H NMR (300 MHz, CDCl3): δ =
7.84 (d, J = 8.1 Hz, 1 H), 7.63 (s, 1 H), 7.48 (dd, J = 7.6, 1.5 Hz,
1 H), 7.40–7.18 (m, 6 H), 7.04 (td, J = 7.5, 1.2 Hz, 1 H), 5.52 (s, 1
H), 4.58 (s, 2 H), 4.23 (d, J = 1.8 Hz, 2 H), 3.37 (s, 1 H), 1.49 (s,
9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.54, 136.98, 129.49,
129.05, 128.52, 128.21, 128.02, 127.84, 126.66, 123.50, 122.19,
84.75, 83.80, 80.66, 71.80, 63.20, 57.40, 28.41 ppm. HRMS (EI+):
calcd. for [C22H25NO4]+ m/z 367.1784; found 367.1782.
1-(2-Aminophenyl)-3-phenylprop-2-yn-1-ol (7a): Following the gene-
ral procedure afforded 79.4 mg (91%) of the desired product. 1H
NMR (300 MHz, CDCl3): δ = 9.45 (s, 2 H), 7.52–7.45 (m, 2 H),
7.42–7.27 (m, 5 H), 7.11 (td, J = 7.6, 1.0 Hz, 1 H), 6.97 (d, J =
7.9 Hz, 1 H), 6.31 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
153.01, 135.09, 132.13, 130.07, 129.35, 128.47, 124.97, 123.82,
121.55, 119.00, 114.90, 89.27, 82.93, 69.91 ppm. HRMS (EI+):
calcd. for [C15H13NO]+ m/z 223.0997; found 223.0995.
1-(2-Aminophenyl)-3-(p-tolyl)prop-2-yn-1-ol (7b): Following the ge-
neral procedure afforded 68.2 mg (81%) of the desired product. 1H
NMR (300 MHz, DMSO): δ = 10.46 (s, 2 H), 7.45–7.29 (m, 4 H),
7.20 (d, J = 7.9 Hz, 2 H), 7.10 (t, J = 7.5 Hz, 1 H), 6.97 (d, J =
7.9 Hz, 1 H), 6.59 (s, 1 H), 2.31 (s, 3 H), 1.91 (s, 1 H) ppm. 13C
NMR (75 MHz, DMSO): δ = 150.57, 139.44, 135.77, 131.60,
129.67, 129.41, 124.69, 122.88, 119.14, 117.71, 114.31, 87.76, 83.77,
68.14, 21.03 ppm. HRMS (EI+): calcd. for [C16H15NO]+ m/z
237.1154; found 237.1147.
tert-Butyl {2-[5-(Benzyloxy)-1-hydroxypent-2-yn-1-yl]phenyl}carb-
amate (6h): Following general procedure B afforded 62.4 mg (38%)
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of the desired product. H NMR (300 MHz, CDCl3): δ = 7.85 (d,
J = 8.1 Hz, 1 H), 7.65 (s, 1 H), 7.54–7.45 (m, 1 H), 7.39–7.20 (m,
1 H), 7.01 (td, J = 7.5, 1.1 Hz, 1 H), 5.43 (d, J = 15.1 Hz, 1 H),
4.52 (s, 1 H), 3.67–3.53 (m, 1 H), 3.11 (s, 1 H), 2.57 (ddd, J = 11.6,
6.8, 1.6 Hz, 1 H), 1.50 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 153.49, 137.96, 137.07, 129.34, 128.53, 128.28, 127.80, 126.72,
123.36, 122.04, 85.61, 80.50, 79.49, 73.06, 68.26, 64.74, 63.34,
28.47, 20.36 ppm. HRMS (EI+): calcd. for [C23H27NO4]+ m/z
381.1940; found 381.1959.
1-(2-Aminophenyl)-3-(4-methoxyphenyl)prop-2-yn-1-ol (7c): Follow-
ing the general procedure afforded 66.6 mg (88%) of the desired
product. 1H NMR (300 MHz, DMSO): δ = 10.44 (s, 2 H), 7.47–
7.37 (m, 3 H), 7.33 (td, J = 7.7, 1.3 Hz, 1 H), 7.09 (td, J = 7.5,
1.0 Hz, 1 H), 7.02–6.89 (m, 3 H), 6.57 (s, 1 H), 3.77 (s, 3 H) ppm.
13C NMR (75 MHz, DMSO): δ = 160.06, 150.62, 135.76, 133.37,
129.62, 124.69, 122.85, 119.25, 114.42, 114.28, 112.58, 87.78, 83.00,
68.23, 55.29 ppm. HRMS (EI+): calcd. for [C16H15NO2]+ m/z
253.1103; found 253.1108.
tert-Butyl
{2-[4-(Benzyloxy)-1-hydroxyoct-2-yn-1-yl]phenyl}carb-
amate (6i): Following general procedure B afforded 68.2 mg (36%)
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of the desired product. H NMR (300 MHz, CDCl3): δ = 7.87 (d,
J = 8.0 Hz, 1 H), 7.64 (d, J = 3.2 Hz, 1 H), 7.58–7.44 (m, 1 H),
7.42–7.19 (m, 6 H), 7.04 (td, J = 7.5, 1.2 Hz, 1 H), 5.54 (s, 1 H),
4.77 (dd, J = 11.8, 3.3 Hz, 1 H), 4.50 (dd, J = 11.8, 2.4 Hz, 1 H),
4.22–4.12 (m, 1 H), 3.14 (s, 1 H), 1.89–1.69 (m, 2 H), 1.49 (s, 9 H),
1.47–1.19 (m, 4 H), 0.89 (t, J = 6.7 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 153.46, 137.93, 137.07, 129.50, 129.09,
128.66, 128.44, 128.08, 127.79, 126.71, 123.40, 122.00, 87.31, 83.92,
80.64, 70.79, 68.89, 63.23, 35.47, 28.43, 27.56, 22.44, 14.06 ppm.
HRMS (EI+): calcd. for [C26H33NO4]+ m/z 423.2410; found
423.2413.
1-(2-Aminophenyl)-3-(4-fluorophenyl)prop-2-yn-1-ol (7d): Following
the general procedure afforded 47.4 mg (87%) of the desired prod-
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uct. H NMR (300 MHz, DMSO): δ = 10.47 (s, 1 H), 7.56 (dd, J
= 8.2, 5.6 Hz, 2 H), 7.41 (d, J = 7.5 Hz, 1 H), 7.34 (t, J = 7.7 Hz,
1 H), 7.24 (t, J = 8.6 Hz, 2 H), 7.10 (t, J = 7.5 Hz, 1 H), 6.97 (d,
J = 7.9 Hz, 1 H), 6.61 (s, 1 H) ppm. 13C NMR (75 MHz, DMSO):
δ = 164.09, 160.79, 150.49, 135.76, 134.22, 134.11, 129.71, 124.71,
122.89, 118.95, 117.19, 116.23, 115.93, 114.31, 86.54, 84.16,
68.04 ppm. HRMS (EI+): calcd. for [C15H12FNO]+ m/z 241.0903;
found 241.0897.
tert-Butyl {2-[4-(tert-Butoxy)-1-hydroxypent-2-yn-1-yl]phenyl}carb-
amate (6j): Following general procedure B afforded 94.6 mg (57%)
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of the desired product. H NMR (300 MHz, CDCl3): δ = 7.88 (d,
J = 8.1 Hz, 1 H), 7.60 (s, 1 H), 7.44 (dd, J = 7.7, 1.4 Hz, 1 H),
7.36–7.17 (m, 6 H), 7.02 (td, J = 7.5, 1.1 Hz, 1 H), 5.49 (s, 1 H), 1-(2-Aminophenyl)hex-2-yn-1-ol (7e): Following the general pro-
4.62 (s, 2 H), 2.92 (s, 1 H), 1.57 (d, J = 1.8 Hz, 6 H), 1.49 (s, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.40, 138.95, 137.07,
129.56, 129.00, 128.41, 127.87, 127.78, 127.51, 123.41, 121.97,
90.34, 82.48, 80.66, 70.85, 66.80, 63.30, 29.01, 28.94, 28.46 ppm.
cedure afforded 41.3 mg (84%) of the desired product. 1H NMR
(300 MHz, CDCl3): δ = 9.52 (s, 1 H), 7.36–7.24 (m, 2 H), 7.08 (t,
J = 7.5 Hz, 1 H), 6.93 (d, J = 7.7 Hz, 1 H), 6.06 (s, 1 H), 2.26 (td,
J = 7.0, 2.1 Hz, 2 H), 1.64–1.50 (m, 2 H), 0.99 (t, J = 7.4 Hz, 3
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