The Journal of Organic Chemistry
Note
135.0 (−C−), 133.6 (two peaks, −C− and −CH−), 131.1 (−CH−), 130.0
(−CH−), 129.9 (2 × −CH−), 129.2 (−CH−), 129.1 (−CH−), 128.9
(−C−), 128.5 (2 × −CH−), 127.5 (−CH−), 126.6 (−C−), 123.9
(−CH−), 122.3 (−CH−), 110.4 (−CH−), 80.2 (−C−), 42.1 (−CH2−);
HRMS (ESI) m/z 378.0899 (M + H+), calc. for C22H17ClNO3 378.0897.
The ee was determined by HPLC analysis. CHIRALPAK IC (4.6 mm i.d. ×
250 mm); hexane/2-propanol = 65/35; flow rate 0.8 mL/min; 25 °C;
254 nm; retention time: 6.7 min (major) and 19.2 min (minor).
(petroleum ether/ethyl acetate = 3/1); yellow solid; 138.4−140.1 °C;
25.9 mg (0.1 mmol); 74% yield; 90% ee; [α]2D6 + 64.71 (c 2.63, CHCl3);
1H NMR (300 MHz, CDCl3) δ 8.13−8.10 (m, 2H), 7.79 (s, 1H), 7.62−
7.56 (m, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.28−7.24 (m, 1H), 7.22−7.20
(m, 1H), 6.96−6.90 (m, 2H), 6.85−6.82 (m, 2H), 6.77 (d, J = 3.2 Hz, 1H),
3.78 (d, J = 14.5 Hz, 1H), 3.42 (d, J = 14.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ 175.9 (two peaks, −CONH−), 164.5 (−COO−), 141.0 (−C−),
134.5 (−C−), 133.5 (−CH−), 130.1 (2 × −CH−), 130.0 (−CH−), 128.8
(−C−), 128.7 (−CH−),128.4 (2 × −CH−), 126.6 (−C−), 126.4
(−CH−), 125.6 (−CH−), 123.9 (−CH−), 122.4 (−CH−), 110.3
(−CH−), 79.9 (−C−), 36.9 (−CH2−); HRMS (ESI) m/z 350.0847
(M + H+), calc. for C20H16NO3S 350.0851. The ee was determined
by HPLC analysis. CHIRALPAK IC (4.6 mm i.d. × 250 mm); hexane/
2-propanol = 65/15; flow rate 1.0 mL/min; 25 °C; 254 nm; retention time:
7.3 (major) and 30.1 (minor).
(S)-3-(3-Methoxybenzyl)-2-oxoindolin-3-yl Benzoate (6k). Reagents:
3-(3-methoxybenzyl)-3-bromooxindole 1j (33.1 mg, 0.1 mmol), benzoic
acid 5e (18.3 mg, 0.15 mmol), catalyst II (4.4 mg, 0.01 mmol), K2HPO4
(26.1 mg, 0.15 mmol), toluene (1.0 mL); Rf = 0.3 (petroleum ether/ethyl
acetate = 3/1); yellow solid; mp 142.9−143.3 °C; 32.9 mg (0.1 mmol);
88% yield; 91% ee; [α]2D6 + 88.53 (c 3.07, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 8.05 (d, J = 7.3 Hz, 2H), 7.72 (s, 1H), 7.58 (t, J = 7.4 Hz, 1H),
7.44 (t, J = 7.6 Hz, 2H), 7.24−7.17 (m, 1H), 7.14 (t, J = 7.9 Hz, 1H), 6.97−
6.90 (m, 2H), 6.80−6.76 (m, 2H), 6.71 (d, J = 7.6 Hz, 1H), 6.60 (s, 1H),
3.69 (s, 3H), 3.57 (d, J = 13.1 Hz, 1H), 3.19 (d, J = 13.1 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 176.2 (−CONH−), 164.5 (−COO−), 158.9 (−C−),
140.9 (−C−), 134.4 (−C−), 133.4 (−CH−), 129.9 (2 × −CH−), 129.8
(−CH−), 129.0 (−C−), 128.8 (−CH−), 128.4 (2 × −CH−), 126.9
(−C−), 124.0 (−CH−), 123.4 (−CH−), 122.1 (−CH−), 116.0 (−CH−),
113.3 (−CH−), 110.3 (−CH−), 80.6 (−C−), 55.0 (−OCH3), 42.5
(−CH2−); HRMS (ESI) m/z 374.1393 (M + H+), calc. for C23H20NO4
374.1392. The ee was determined by HPLC analysis. CHIRALPAK IC
(4.6 mm i.d. × 250 mm); hexane/2-propanol = 65/35; flow rate 1.0 mL/
min; 25 °C; 254 nm; retention time: 8.8 min (major) and 27.9 min (minor).
(S)-3-(2-Methylbenzyl)-2-oxoindolin-3-yl Benzoate (6l). Reagents:
3-(2-methylbenzyl)-3-bromooxindole 1h (31.5 mg, 0.1 mmol), benzoic
acid 5e (18.3 mg, 0.15 mmol), catalyst II (4.4 mg, 0.01 mmol), K2HPO4
(26.1 mg, 0.15 mmol), toluene (1.0 mL); Rf = 0.3 (petroleum ether/
ethyl acetate = 3/1); yellow oil; 22.9 mg (0.1 mmol); 64% yield; 90% ee;
(S)-3-Benzyl-7-fluoro-2-oxoindolin-3-yl Benzoate (6o). Reagents:
3-benzyl-7-fluoro-3-bromooxindole 1p (31.9 mg, 0.1 mmol), benzoic
acid 5e (18.3 mg, 0.15 mmol), catalyst II (4.4 mg, 0.01 mmol), K2HPO4
(26.1 mg, 0.15 mmol), toluene (1.0 mL); Rf = 0.3 (petroleum ether/ethyl
acetate = 3/1); yellow solid; 118.7−120.2 °C; 28.2 mg (0.1 mmol); 78%
yield; 92% ee; [α]2D6 + 119.62 (c 2.81, CHCl3); H NMR (300 MHz,
1
CDCl3) δ 8.05−8.02 (m, 2H), 7.62−7.57 (m, 2H), 7.45 (t, J = 7.6 Hz, 2H),
7.25−7.20 (m, 3H), 7.10−7.07 (m, 2H), 7.04−6.97 (m, 1H), 6.92−6.86
(m, 1H), 6.67 (d, J = 7.4 Hz, 1H), 3.59 (d, J = 13.2 Hz, 1H), 3.22 (d, J =
13.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 175.2 (−CONH−), 164.5
(−COO−), 148.5 (−CF−), 145.2 (−CF−), 133.6 (−CH−), 132.5
(−C−), 130.9 (2 × −CH−), 129.9 (2 × −CH−), 129.6 (two peaks, −C−),
128.7 (−C−), 128.4 (2 × −CH−), 128.2 (−C−), 128.0 (−C−), 127.9 (2 ×
−CH−), 127.4 (−CH−), 122.9 (−CH−), 122.8 (−CH−), 119.7 (−CH−),
119.6 (−CH−), 117.0 (−CH−), 116.8 (−CH−), 80.4 (two peaks, −C−),
42.4 (−CH2−); HRMS (ESI) m/z 362.1184 (M + H+), calc. for C22H17F-
NO3 362.1192. The ee was determined by HPLC analysis. CHIRALPAK IC
(4.6 mm i.d. × 250 mm); hexane/2-propanol = 65/35; flow rate 1.0 mL/
min; 25 °C; 254 nm; retention time: 7.3 (major) and 21.0 (minor).
(S)-3-Methyl-2-oxoindolin-3-yl Benzoate (6p). Reagents: 3-methyl-
3-bromooxindole 1w (22.5 mg, 0.1 mmol), benzoic acid 5e (18.3 mg,
0.15 mmol), catalyst II (4.4 mg, 0.01 mmol), K2HPO4 (26.1 mg,
0.15 mmol), toluene (1.0 mL); Rf = 0.3 (petroleum ether/ethyl acetate =
3/1); white solid; 73.1−74.5 °C; 21.6 mg (0.1 mmol); 81% yield; 90%
ee; [α]2D6 + 76.68 (c 1.91, CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.80
(s, 1H), 8.12−8.09 (m, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz,
2H), 7.30 (d, J = 7.5 Hz, 2H), 7.08−7.02 (m, 1H), 6.97 (d, J = 7.6 Hz,
1H), 1.85 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 177.2 (−CONH−),
164.6 (−COO−), 140.5 (−C−), 133.4 (−CH−), 129.9 (2 × −CH−),
129.7 (−CH−), 129.4 (−C−), 129.0 (−C−), 128.3 (2 × −CH−), 122.7
(−CH−), 122.4 (−CH−), 110.6 (−CH−), 77.9 (−C−), 23.3 (−CH3);
HRMS (ESI) m/z 268.0971 (M + H+), calc. for C16H14NO3 268.0974.
The ee was determined by HPLC analysis. CHIRALPAK IC (4.6 mm
i.d. × 250 mm); hexane/2-propanol = 65/35; flow rate 1.0 mL/min;
25 °C; 254 nm; retention time: 7.1 min (major) and 24.3 min (minor).
(S)-2-Oxo-3-phenylindolin-3-yl Benzoate (6q). Reagents: 3-phenyl-
3-bromooxindole 1s (28.7 mg, 0.1 mmol), benzoic acid 5e (18.3 mg,
0.15 mmol), catalyst II (4.4 mg, 0.01 mmol), K2HPO4 (26.1 mg, 0.15 mmol),
toluene (1.0 mL); Rf = 0.3 (petroleum ether/ethyl acetate = 3/1); white
solid; 63.4−65.1 °C; 28.0 mg (0.1 mmol); 85% yield; 89% ee; [α]2D6 + 91.15
(c 3.37, CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.32 (s, 1H), 8.13−8.08
(m, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.51−7.37 (m, 7H), 7.33 (td, J = 7.7,
1.2 Hz, 1H), 7.24 (s, 1H), 7.06 (td, J = 7.6, 0.8 Hz, 1H), 6.98 (d, J =
7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 175.5 (−CONH−), 164.8
(−COO−), 141.7 (−C−), 136.5 (−C−), 133.6 (−CH−), 130.2 (−CH−),
130.0 (2 × −CH−), 129.1 (−C−), 129.0 (−CH−), 128.7 (2 × −CH−),
128.5 (two peaks, −C− and 2 × −CH−), 126.3 (2 × −CH−), 124.6
(−CH−), 123.1 (−CH−), 110.5 (−CH−), 81.6 (−C−); HRMS (ESI)
m/z 330.1136 (M + H+), calc. for C21H16NO3 330.1130. The ee was
determined by HPLC analysis. CHIRALPAK IC (4.6 mm i.d. × 250 mm);
hexane/2-propanol = 65/35; flow rate 1.0 mL/min; 25 °C; 254 nm;
retention time: 7.4 (major) and 17.1 (minor).
1
[α]2D6 + 101.65 (c 1.66, CHCl3); H NMR (300 MHz, CDCl3) δ 8.14
(s, 1H), 7.98−7.95 (m, 2H), 7.50 (t, J = 7.4, 1H), 7.37 (t, J = 7.8 Hz, 2H),
7.33−7.30 (m, 1H), 7.16−7.10 (m, 3H), 7.07−7.02 (m, 1H), 6.82−6.72
(m, 2H), 6.44 (d, J = 7.4 Hz, 1H), 3.52 (d, J = 14.1 Hz, 1H), 3.10 (d, J =
14.1 Hz, 1H), 1.85 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 176.8
(−CONH−), 164.7 (−COO−), 140.7 (−C−), 138.1 (−C−), 133.5
(−CH−), 132.2 (−C−), 131.8 (−CH−), 130.3 (−CH−), 130.0 (2 ×
−CH−), 129.7 (−C−), 129.2 (−CH−), 128.5 (2 × −CH−), 127.5
(−CH−), 127.2 (−C−), 125.5 (−CH−), 124.1 (−CH−), 122.2
(−CH−), 110.2 (−CH−), 80.6 (−C−), 38.5 (−CH2−), 19.7 (−CH3);
HRMS (ESI) m/z 358.1445 (M + H+), calc. for C23H20NO3 358.1443.
The ee was determined by HPLC analysis. CHIRALPAK IC (4.6 mm
i.d. × 250 mm); hexane/2-propanol = 65/35; flow rate 1.0 mL/min;
25 °C; 254 nm; retention time: 7.6 (major) and 21.8 (minor).
(S)-3-(Naphthalen-1-ylmethyl)-2-oxoindolin-3-yl Benzoate (6m).
Reagents: 3-(naphthalen-1-ylmethyl)-3-bromooxindole 1l (35.1 mg,
0.1 mmol), benzoic acid 5e (18.3 mg, 0.15 mmol), catalyst II (4.4 mg,
0.01 mmol), K2HPO4 (26.1 mg, 0.15 mmol), toluene (1.0 mL); Rf = 0.3
(petroleum ether/ethyl acetate = 3/1); yellow solid, 75.8−77.0 °C;
27.5 mg (0.1 mmol); 70% yield; 90% ee; [α]2D6 + 105.61 (c 0.94, CHCl3);
1H NMR (300 MHz, CDCl3) δ 8.16−8.13 (m, 1H), 8.06 (s, 1H), 7.89−
7.80 (m, 4H), 7.54−7.39 (m, 4H), 7.35−7.28 (m, 3H), 7.18 (td, J = 7.8,
1.1 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H), 6.74 (td, J = 7.6, 0.7 Hz, 1H), 6.52
(d, J = 7.4 Hz, 1H), 4.15 (d, J = 14.2 Hz, 1H), 3.51 (d, J = 14.2 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 176.9 (−CONH−), 164.7 (−COO−),
140.6 (−C−), 133.7 (−C−), 133.4 (−CH−), 133.2 (−C−), 130.1
(−CH− and 2 × −CH−), 129.9 (−C−), 129.6 (−CH−), 128.8 (−C−),
128.5 (−CH−), 128.3 (−CH−), 128.2 (2 × −CH−), 127.1 (−C−),
125.7 (−CH−), 125.5 (−CH−), 125.0 (−CH−), 124.7 (−CH−),
124.6 (−CH−), 122.0 (−CH−), 110.3 (−CH−), 80.7 (−C−), 38.3
(−CH2−); HRMS (ESI) m/z 416.1267 (M + Na+), calc. for C26H19NO3
416.1263. The ee was determined by HPLC analysis. CHIRALPAK IC
(4.6 mm i.d. × 250 mm); hexane/2-propanol = 65/35 flow rate 1.0 mL/min;
25 °C; 254 nm; retention time: 8.0 (major) and 17.8 (minor).
(S)-2-Oxo-3-(thiophen-2-ylmethyl)indolin-3-yl Benzoate (6n). Re-
agents: 3-(thiophen-2-ylmethyl)-3-bromooxindole 1n (30.7 mg, 0.1 mmol),
benzoic acid 5e (18.3 mg, 0.15 mmol), catalyst II (4.4 mg, 0.01 mmol),
K2HPO4 (26.1 mg, 0.15 mmol), toluene (1.0 mL); Rf = 0.3
(S)-p-Tolyl 2-(3-Benzyl-2-oxoindolin-3-yl)ethanethioate (8). Reagents:
3-benzyl-3-bromooxindole (30.2 mg, 0.1 mmol), 3-oxo-3-(p-tolylthio)-
propanoic acid 7 (31.5 mg, 0.15 mmol), quinidine (3.2 mg, 0.01 mmol),
J
J. Org. Chem. XXXX, XXX, XXX−XXX