828
Chem. Pharm. Bull.
Vol. 64, No. 7 (2016)
oil; Rf=0.60 (Silica gel, hexanes:AcOEt=8:2); IR (neat) 3375, at room temperature. The mixture was allowed to warm
1
2938, 1734, 1594, 1531, 1455, 757cm−1; H-NMR (400MHz, to 110°C and the suspension was stirred until TLC (hex-
CDCl3) δ: 8.16–8.08 (m, 2H), 7.45–7.32 (m, 7H), 7.03 (dd, anes : AcOEt=8:2) indicated a complete consumption of 7c.
J=8.0, 8.0Hz, 1H), 5.32 (s, 1H), 5.20 (s, 2H), 3.33 (s, 6H); The reaction mixture was filtered through a pad of Celite and
13C-NMR (100MHz, CDCl3, a mixture of rotamers) δ: 153.5, concentrated under reduced pressure. The residue was puri-
136.3, 132.4, 129.6, 129.3, 128.5, 128.3, 128.2, 128.1, 127.9, fied by preparative TLC on silica gel (hexanes:AcOEt=8:2,
125.2, 124.1, 122.6, 120.2, 103.1, 99.9, 66.8, 54.6, 53.2; ESI- then toluene; hexanes=3:1) to afford quinoline 8a (24.8mg,
MS m/z Calcd for C17H19NNaO4 324.1212 (M++Na). Found 0.105mmol, 66%). 1H-NMR spectra data was completely
1
324.1207.
identical with that reported32); H-NMR (400MHz, CDCl3) δ:
N-(2-(Hydroxymethyl)phenyl)-4-methylbenzenesulfon- 8.21–8.11 (m, 4H), 7.84 (d, J=8.8Hz, 1H), 7.80 (d, J=8.4Hz,
amide To a solution of (2-aminophenyl)methanol (616mg, 1H), 7.71 (dd, J=8.8, 8.4Hz, 1H), 7.50 (dd, J=8.4, 8.4Hz, 1H),
5.00mmol) and pyridine (0.485mL, 6.00mmol) in CH2Cl2 7.05 (d, J=9.2Hz, 2H), 3.89 (s, 3H).
(25mL) was added a solution of p-toluenesulfonyl chloride
(906mg, 4.75mmol) in CH2Cl2 (10mL) at 0°C. After stirring
for 6h, the reaction was quenched with saturated aqueous
Sub-gram Scale Reaction
2-(4-Methoxyphenyl)quinoline (8a)
A 30mL two-necked round-bottom flask with a mag-
NH4Cl and the mixture was extracted with CH2Cl2 three netic stirring bar and Liebig condenser was charged with
times. The combined organic extracts were washed with AgOTf (40.0mg, 0.156mmol, 10mol%), PPh3AuCl (77.0mg,
brine, dried over Na2SO4, filtered, and concentrated under 0.156mmol, 10mol%) and toluene (6.5mL, 0.25M). To the so-
reduced pressure to give sulfonamide as a white solid; Its lution were added alkyne 12a (900 µL, 7.78mmol, 5.0 equiv),
1H-NMR spectra data was completely identical with that DTBP (140µL, 0.622mmol, 40mol%), i-PrOH (2.40mL, 20
1
reported31); H-NMR (400MHz, CDCl3) δ: 7.86 (brs, 1H), 7.65 equiv) and amide 7c (500mg, 1.56mmol) at room temperature.
(d, J=8.4Hz, 2H), 7.43 (d, J=7.6Hz, 1H), 7.30–7.19 (m, 3H), The mixture was allowed to warm to 110°C and the suspen-
7.13–7.05 (m, 2H), 4.40 (s, 2H), 2.38 (s, 3H), 2.13 (brs, 1H).
sion was stirred until TLC (hexanes:AcOEt=8:2) indicated a
N-(2-(Dimethoxymethyl)phenyl)-4-methylbenzenesul- complete consumption of 7c. The reaction mixture was filtered
fonamide (7c) To the solution of N-(2-(hydroxymethyl)- through a pad of Celite and concentrated under reduced pres-
phenyl)-4-methylbenzenesulfonamide (777mg, 2.80mmol), sure. The residue was purified by flash column chromatogra-
N-methylmorphine N-oxide (NMO) (492mg, 4.20mmol), 4Å phy on silica gel (hexanes:AcOEt=92:8) to afford quinoline
moleculer sieves (powdered, 1.4mg), CH2Cl2 (14mL), and 8a (225mg, 0.956mmol, 62%).
MeCN (1.5mL) was added tetrapropylammonium perruthenate
(TPAP) (49.2mg, 0.140mmol). After stirring for 11h, the reac-
2-Phenylquinoline (8b)
According to the general procedure described for 8a,
tion mixture was passed through a silica gel pad. The filtrate quinoline 8b was obtained from 7c with phenylacetylene
was concentrated under reduced pressure to give the crude 12b in 32.0µmol scale (3.7mg, 18µmol, 56%); a white solid;
1
aldehyde. The crude aldehyde was directly subjected to the Its H-NMR spectra data was completely identical with that
1
next reaction without further purification. To a mixture of the reported32); H-NMR (400MHz, CDCl3) δ: 8.22 (d, J=8.8Hz,
above crude aldehyde and trimethyl orthoformate (0.530mL, 1H), 8.20–8.13 (m, 3H), 7.88 (d, J=8.4Hz, 1H), 7.83 (d,
4.80mmol) in MeOH (10mL) was added p-TsOH·H2O J=8.0Hz, 1H), 7.73 (d, J=8.4, 8.4Hz, 1H), 7.59–7.42 (m, 4H).
(60.3mg, 0.240mmol). After stirring for 2h at 70°C, the reac-
2-(p-Tolyl)quinoline (8c)
tion was quenched with saturated aqueous NaHCO3 and the
According to the general procedure described for 8a, quino-
resulting mixture was extracted with CH2Cl2 three times. line 8c was obtained from 7c with (4-methylphenyl)acetylene
The combined organic extracts were washed with brine, dried 12c in 32.0µmol scale (4.8mg, 22µmol, 68%); a yellow solid;
1
over Na2SO4, and concentrated under reduced pressure. The Its H-NMR spectra data was completely identical with that
1
residue was purified by flash column chromatography on reported32); H-NMR (400MHz, CDCl3) δ: 8.20 (d, J=8.8Hz,
silica gel (hexanes:AcOEt=8:2) to afford acetal 7c (557mg, 1H), 8.16 (d, J=8.4Hz, 1H), 8.07 (d, J=8.0Hz, 2H), 7.87 (d,
1.73mmol, 62%) as a white solid; Rf=0.30 (Silica gel, hex- J=8.4Hz, 1H), 7.81 (d, J=8.8Hz, 1H), 7.72 (d, J=8.4, 7.6Hz,
anes : AcOEt=8:2); mp 63–66°C (hexanes/CH2Cl2); IR (neat) 1H), 7.51 (dd, J=8.4, 7.6Hz, 1H), 7.33 (d, J=8.0Hz, 2H), 2.44
1
3310, 2941, 1495, 1338, 1154, 1060, 768, 665cm−1; H-NMR (s, 3H).
(400MHz, CDCl3) δ: 8.13 (brs, 1H), 7.67 (d, J=8.4Hz, 2H),
7.64 (d, J=8.4Hz, 1H), 7.35–7.18 (m, 4H), 7.06 (dd, J=8.0,
2-(4-Bromophenyl)quinoline (8d)
According to the general procedure described for 8a, quino-
7.7Hz, 1H), 4.89 (s, 1H), 3.19 (s, 6H), 2.36 (s, 3H); 13C-NMR line 8d was obtained from 7c with alkyne 12d in 32.0µmol
(100MHz, CDCl3) δ: 143.6, 136.9, 135.5, 129.7, 129.4, 128.4, scale (6.1mg, 22µmol, 67%); a yellow solid; Its 1H-NMR
127.2, 127.1, 124.0, 121.4, 103.5, 53.3, 21.4; ESI-MS m/z Calcd spectra data was completely identical with that reported32)
;
for C16H19NNaO4S 344.0927 (M++H). Found 344.0927.
1H-NMR (400MHz, CDCl3) δ: 8.23 (d, J=8.8Hz, 1H), 8.15 (d,
General Procedure for Gold-Catalyzed Quinoline J=8.8Hz, 1H), 8.06 (d, J=8.4Hz, 2H), 7.84 (d, J=8.8Hz, 1H),
Synthesis
2-(4-Methoxyphenyl)quinoline (8a)
A 10mL test tube equipped with a magnetic stirring bar
was charged with AgOTf (4.1mg, 0.016mmol, 10mol%),
7.83 (d, J=8.8Hz, 1H), 7.74 (dd, J=8.8, 7.6Hz, 1H), 7.65 (d,
J=8.4Hz, 2H), 7.54 (dd, J=8.8, 7.6Hz, 1H).
2-(3,4-Dimethoxyphenyl)quinoline (8e)
According to the general procedure described for 8a, quino-
PPh3AuCl (7.9mg, 0.016mmol, 10mol%) and toluene (0.74mL, line 8e was obtained from 7c with alkyne 12e in 32.0µmol
0.25M). To the solution were added alkyne 12a (93 µL, scale (4.9mg, 19µmol, 58%); a white solid; Its 1H-NMR
0.80mmol, 5.0 equiv), DTBP (14µL, 0.064mmol, 40mol%), spectra data was completely identical with that reported34)
;
i-PrOH (245µL, 20 equiv) and amide 7c (51.5mg, 0.160mmol) 1H-NMR (400MHz, CDCl3) δ: 8.18 (d, J=8.8Hz, 1H), 8.15