Typical Experimental Procedure for the Synthesis of Epoxides
To a solution of the catalyst 1 (38 mg, 0.15 mmol) and trans-α-ylideneoxindoles 11 (0.5 mmol) in nHexane for HPLC grade (2.7 mL) was added TBHP (5.5 M in decane solution, 0.6 mmol, 0.11 mL). The resultant heterogeneous mixture was maintained under stirring at room temperature (25 °C) until reaction completion (TLC nHexane/EtOAc). Afterwards, the crude reaction mixture was purified by flash chromatography on silica gel (nHexane/EtOAc) to furnish the expected epoxy oxindoles trans-12 and cis-13.
(2′R,3′R)-ethyl 1-methyl-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12a. Following the above general procedure, trans diastereoisomer 12a was obtained as a whitish solid in 61% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3), m.p. 132–134 °C. IR (CHCl3): = 3033, 3010, 2984, 1736, 1709, 1618, 1495, 1473, 1376, 1347 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.26 (t, J = 7.2 Hz, 3H, CH3CH2O), 3.25 (s, 3H, CH3N), 4.18 (s, 1H, OCH), 4.24 (dq, J = 10.9 Hz, 7.2 Hz, 1H, CH3CHHO), 4.29 (dq, J = 10.9 Hz, 7.2 Hz, 1H, CH3CHHO), 6.89 (ddd, J = 7.9 Hz, 0.9 Hz, 0.6 Hz, 1H, CHarom), 7.04 (dt, J = 7.7 Hz, 0.9 Hz,1H, CHarom), 7.39 (dt, J = 7.9 Hz, 1.3 Hz, 1H, CHarom), 7.45 (ddd, J = 7.7 Hz, 1.3 Hz, 0.6 Hz, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 27.0, 60.0, 60.3, 62.4, 109.1, 119.5, 123.3, 125.0, 131.3, 145.9, 165.9, 170.1. HRMS: exact mass calculated for (C13H13NNaO4) requires m/z 270.0742, found m/z 270.0741. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 7/3, flow rate 1.0 mL/min]: Tmajor = 11.91 min, Tminor = 14.97 min er = 91:9. [α]D = −93 (c = 1.6 g/cm3 inCH2Cl2).
(2′R,3′R)-ethyl 5-iodo-1-methyl-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12b. Following the above general procedure, trans diastereoisomer 12b was obtained as a pale yellow solid in 32% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3), m.p. 143–145 °C. IR (CHCl3): = 3028, 3017, 3008, 1736, 1727, 1611, 1535, 1486, 1358, 1340 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.33 (t, J = 7.1 Hz, 3H, CH3CH2O); 3.24 (s, 3H, NCH3); 3.94–4.41 (m, 3H, CH3CH2O, OCH); 6.69 (t, J = 8.2 Hz, 1H, CHarom); 6.68–6.78 (m, 2H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 27.0, 59.6, 60.0, 62.6, 85.6, 111.0, 121.7, 133.6, 140.0, 145.4, 165.5, 169.3. HRMS: exact mass calculated for (C13H12INNaO4) requires m/z 395.9709, found m/z 395.9712. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 70/30, flow rate 1.0 mL/min]: Tmajor = 13.04 min, Tminor = 10.19 min er = 80:20. [α]D = −9 (c = 0.0140 g/cm3 in CHCl3).
(2′R,3′R)-ethyl 5,7-dichloro-1-methyl-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12c. Following the above general procedure, trans diastereoisomer 12c was obtained as a pale yellow solid in 38% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 8/2), m.p. 98–100 °C. IR (CHCl3): = 3025, 3011, 2959, 1739, 1727, 1625, 1494, 1471, 1369, 1346 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.20 (d, J = 6.8 Hz, 6H, (CH3)2CHCarom); 1.29 (t, J = 7.1 Hz, 3H, CH3CH2O); 2.80–2.95 (m, 1H, (CH3)2CHCarom); 3.26 (s, 3H, NCH3); 4.18–4.41 (m, 3H, CH3CH2O, OCH); 6.84 (d, J = 7.9 Hz, 1H, CHarom); 7.24 (d, J = 7.9 Hz, 1H, CHarom); 7.33 (m, 2H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 24.2 (2 × C), 26.9, 34.0, 59.9, 60.3, 62.3, 108.9, 119.3, 123.0, 129.0, 143.6, 144.3, 165.9, 170.0. HRMS: exact mass calculated for (C16H19NNaO4) requires m/z 312.1212, found m/z 312.1215. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 70/30, flow rate 1.0 mL/min]: Tmajor = 14.85 min, Tminor = 8.42 min er = 89:11. [α]D = −79 (c = 0.0220 g/cm3 in CHCl3).
(2′R,3′R)-ethyl 5,7-dichloro-1-methyl-2-oxospiro[indoline-3,2′-oxirane]-3′- carboxylate 12d. Following the above general procedure, trans diastereoisomer 12d was obtained as a pale red solid in 29% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 8/2), m.p. 124–126 °C. IR (CHCl3): = 3031, 3006, 1740, 1729, 1578, 1463, 1337, 1309 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.31 (t, J = 7.1 Hz, 3H, CH3CH2O); 3.62 (s, 3H, NCH3); 4.18–4.40 (m, 3H, CH3CH2O, OCH); 7.34 (s, 1H, CHarom); 7.40 (s, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 30.5, 59.4, 60.6, 62.8, 117.0, 123.6, 124.0, 129.0, 132.9, 140.2, 165.1, 170.1. HRMS: exact mass calculated for (C13H11Cl2NNaO4) requires m/z 337.9963, found m/z 337.9961. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH=70/30, flow rate 1.0 mL/min]: Tmajor = 11.74 min, Tminor = 9.48 min er = 93:7. [α]D = −96 (c = 0.0160 g/cm3 in CHCl3).
(2′R,3′R)-ethyl 5-methoxy-1-methyl-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12e. Following the above general procedure, trans diastereoisomer 12e was obtained as a pale yellow solid in 50% yield after purification by flash chromatography on silica gel (nHexane /EtOAc = 8/2), m.p. 105–107 °C. IR (CHCl3): = 1735, 1734, 1614, 1492, 1467, 1358, 1260 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.28 (t, J = 7.1 Hz, 3H, CH3CH2O); 3.23 (s, 3H, NCH3); 3.75 (s, 3H, OCH3); 4.18 (s, 1H, OCH); 4.22–4.25 (m, 2H, CH3CH2O); 6.80 (d, J = 8.5 Hz, 1H, CHarom); 6.92 (d, J = 8.5 Hz, 1H, CHarom); 7.09 (s, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 26.9, 56.0, 59.9, 62.3, 66.1, 109.5, 112.3, 115.9, 120.5, 139.1, 156.3, 165.8, 169.8 ppm. HRMS: exact mass calculated for (C14H15NNaO4) requires m/z 300.0848, found m/z 300.0844. HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHeptane/EtOH = 70/30, flow rate 1.0 mL/min]: Tmajor = 16.33 min, Tminor = 11.45 min er = 90:10. [α]D = −10 (c = 0.0451 g/cm3 in CHCl3).
(2′R,3′R)-ethyl 1-methyl-5-nitro-2-oxospiro[indoline-3,2′-oxirane]-3′- carboxylate 12f. Following the above general procedure, trans diastereoisomer 12f was obtained as a pale yellow solid in 19% yield after purification by flash chromatography on silica gel (DCM 100%), m.p. 170–172 °C. IR (CHCl3): = 3031, 3017, 3009, 1754, 1743, 1617, 1533, 1494, 1340 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.34 (t, J = 7.1 Hz, 3H, CH3CH2O); 3.35 (s, 3H, NCH3); 4.23–4.42 (m, 3H, CH3CH2O, OCH); 7.03 (d, J = 8.9 Hz, 1H, CHarom); 8.37 (d, J = 7.4 Hz, 2H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.2, 27.4, 59.4, 60.1, 62.9, 108.9, 120.4, 121.1, 128.0, 143.8, 150.9, 165.1, 170.1. HRMS: exact mass calculated for (C13H12N2NaO6) requires m/z 315.0593, found m/z 315.0596. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 70/30, flow rate 1.0 mL/min]: Tmajor = 23.13 min, Tminor = 22.02 min er = 85:15. [α]D = −29 (c = 0.0180 g/cm3 in CDCl3).
(2′R,3′R)-ethyl 1-methyl-2-oxo-1,2-dihydrospiro[benzo[g]indole-3,2′-oxirane]-3′-carboxylate 12g. Following the above general procedure, trans diastereoisomer 12g was obtained as a pale red solid in 50% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 8/2), m.p. 185–187 °C. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.26–1.30 (m, 3H, CH3CH2O); 3.88 (s, 3H, NCH3); 4.21–4.31 (m, 3H, OCH, CH3CH2O), 7.50–7.55 (m, 4H, CHarom); 7.86–7.88 (m, 1H, CHarom), 8.40–8.43 (m, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 28.3, 59.2, 62.5, 63.6, 109.2, 118.5, 122.2, 123.7, 124.7, 126.6, 128.1, 129.2, 142.3, 149.3, 168.6, 170.1. HRMS: exact mass calculated for (C17H15NNaO4) requires m/z 320.0899, found m/z 320.0896. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 70/30, flow rate 1.0 mL/min]: Tmajor = 18.48 min, Tminor = 13.56 min er = 91:9. [α]D = −20.15 (c = 0.0059 g/cm3 in CHCl3).
(2′S,3′S)-diethyl 1-methyl-2-oxospiro[indoline-3,2′-oxiran]-3′-yl)phosphonate 12h. Following the above general procedure, trans diastereoisomer 12h was obtained as a pale yellow solid in 45% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 4/6), m.p. 166–168 °C. IR (CHCl3): = 1725, 1236 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.21 [t, J = 7.0 Hz, 3H, (CH3CH2O)2P], 1.41 [t, J = 7.1 Hz, 3H, (CH3CH2O)2P], 3.26 (s, 3H, NCH3), 3.73 (d, JHP = 27.6 Hz, 1H, OCH), 3.95–4.14 [m, 2H, (CH3CH2O)2P], 4.20–4.37 [m, 2H, (CH3CH2O)2P], 6.90 (d, J = 7.9 Hz, 1H, CHarom), 7.1 (dt, J = 7.7, 1.0 Hz, 1H, CHarom), 7.39 (dt, J = 7.9, 1.3 Hz, 1H, CHarom), 7.99 (d, J = 7.7 Hz, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 15.9 (d, JCCOP = 5.8 Hz), 16.0 (d, JCCOP = 5.7 Hz), 26.3, 55.5 (d, JCP = 203.5 Hz), 59.7, 62.7 (d, JCOP = 6.3 Hz), 63.1 (d, JCOP = 6.1 Hz), 108.4, 118.9, 122.6, 126.5, 130.6, 145.3, 170.2. HRMS: exact mass calculated for (C14H18NNaO5P) requires m/z 334.0820, found m/z 334.0824. Chiral-phase HPLC analysis: [Daicel Chiralpack IB 5μ, λ = 254 nm, nHexane/iPrOH = 9/1, flow rate 1.0 mL/min]: Tmajor = 42.20 min, Tminor = 23.60 min er = 80:20. [α]D = −2 (c = 0.0101 g/cm3 in CHCl3).
(2′S,3′S)-diethyl 1-phenyl-2-oxospiro[indoline-3,2′-oxiran]-3′-yl phosphonate 12i. Following the above general procedure, trans diastereoisomer 12i was obtained as a pale yellow solid in 57% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 1/1), m.p. 197–199 °C. IR (CHCl3): = 1716, 1265 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.18 [t, J = 7.1 Hz, 3H, (CH3CH2O)2P], 1.34 [t, J =7.1 Hz, 3H, (CH3CH2O)2P], 3.76 (d, JHP = 27.6 Hz, 1H, OCH), 4.00–4.08 [m, 2H, (CH3CH2O)2P], 4.18–4.33 [m, 2H, (CH3CH2O)2P], 6.77 (d, J = 7.6 Hz, 1H, CHarom), 7.05 (t, J = 7.6 Hz, 1H, CHarom), 7.22 (t, J = 7.6 Hz, 1H, CHarom), 7.35–7.46 (m, 5H, CHarom), 7.96 (d, J = 7.6 Hz, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 16.0 (d, JCCOP = 5.7 Hz), 16.2 (d, JCCOP = 5.8 Hz), 58.1 (d, JCP = 203.7 Hz), 60.1, 62.9 (d, JCOP = 6.2 Hz), 63.4 (d, JCOP = 6.1 Hz), 109.8, 118.8, 123.3, 126.1, 126.9, 128.3, 129.5, 130.6, 133.5, 145.5, 169.8 ppm. HRMS: exact mass calculated for (C19H20NNaO5P) requires m/z 396.0977, found m/z 396.0975. Chiral-phase HPLC analysis: [Daicel Chiralpack IB 5μ, λ = 254 nm, nHexane/iPrOH = 9/1, flow rate 1.0 mL/min]: Tmajor = 39.90 min, Tminor = 17.50 min er = 79:21. [α]D = −6.7 (c = 0.0122 g/cm3 in CHCl3).
(2′S,3′S)-diethyl 1-benzyl-2-oxospiro[indoline-3,2′-oxiran]-3′-yl phosphonate 12j. Following the above general procedure, trans diastereoisomer 12j was obtained as a yellow solid in 45% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 1/1), m.p. 205–207 °C. IR (CHCl3): = 1731, 1262 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.22 [t, J = 7.1 Hz, 3H, (CH3CH2O)2P], 1.43 [t, J = 7.1 Hz, 3H, (CH3CH2O)2P], 3.81 (d, JHP = 27.4 Hz, 1H, OCH), 4.02–4.14 [m, 2H, (CH3CH2O)2P], 4.24–4.39 [m, 2H, (CH3CH2O)2P], 4.96 (s, 2H, CH2N), 6.81 (d, J = 7.6 Hz, 1H, CHarom), 7.07 (t, J = 7.6 Hz, 1H, CHarom), 7.24–7.36 (m, 6H, CHarom), 8.00 (d, J = 7.6 Hz, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 16.2 (d, JCCOP = 5.7 Hz), 16.4 (d, JCCOP = 5.8 Hz), 44.4, 58.1 (d, JCP = 203.1 Hz), 60.2 (d, JCCP = 1.1 Hz), 62.9 (d, JCOP = 6.0 Hz), 63.3 (d, JCOP = 6.0 Hz), 109.3, 119.2, 122.1, 127.3, 127.5, 127.7, 128.7, 131.7, 135.2, 145.5, 170.7 ppm. HRMS: exact mass calculated for (C20H22NNaO5P) requires m/z 410.1133, found m/z 410.1130. Chiral-phase HPLC analysis: [Daicel Chiralpack IB 5μ, λ = 254 nm, nHexane/iPrOH = 9/1, flow rate 1.0 mL/min]: Tmajor = 39.90 min, Tminor = 17.50 min er = 74:26. [α]D = −6.7 (c = 0.0122 g/cm3 in CHCl3).
(2′S,3′S)-diethyl 1-(2,4-dichlorobenzyl)-2-oxospiro[indoline-3,2′-oxiran]-3′-yl)phosphonate 12k. Following the above general procedure, trans diastereoisomer 12k was obtained as a pale yellow solid in 54% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 1/1), m.p. 235–237 °C. IR (CHCl3): = 1733, 1253 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.23 [t, J = 7.1 Hz, 3H, (CH3CH2O)2P], 1.42 [t, J =7.1 Hz, 3H, (CH3CH2O)2P], 3.81 (d, JHP = 27.4 Hz, 1H, OCH), 3.97–4.19 [m, 2H, (CH3CH2O)2P], 4.22–4.39 [m, 2H, (CH3CH2O)2P], 5.03 (s, 2H, CH2N), 6.73 (d, J = 7.9 Hz, 1H, CHarom), 7.05–7.20 (m, 3H, CHarom), 7.30–7.34 (m, 3H, CHarom), 7.43 (d, J = 1.9 Hz, 1H, CHarom), 8.00 (d, J = 7.6 Hz, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 15.9 (d, JCCOP = 5.6 Hz), 16.0 (d, JCCOP = 5.5 Hz), 41.1, 57.9 (d, JCP = 203.0 Hz), 59.7 (d, JCCP = 1.1 Hz), 62.6 (d, JCOP = 6.2 Hz), 63.1 (d, JCOP = 6.2 Hz), 109.2, 118.9, 123.0, 126.8, 127.2, 128.8, 129.2, 130.6, 130.8, 133.2, 133.8, 144.0, 170.6 ppm. HRMS: exact mass calculated for (C20H20Cl2NNaO5P) requires m/z 478.0354, found m/z 478.0356. Chiral-phase HPLC analysis: [Daicel Chiralpack IB 5μ, λ = 254 nm, nHexane/iPrOH = 9/1, flow rate 1.0 mL/min]: Tmajor = 26.20 min, Tminor = 16.80 min er = 72:28. [α]D = −20.4 (c = 0.0091 g/cm3 in CHCl3).
(2′S,3′S)-diethyl 5-chloro-1-methyl-2-oxospiro[indoline-3,2′-oxiran]-3′-yl)phosphonate 12l. Following the above general procedure, trans diastereoisomer 12l was obtained as a white solid in 38% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 1/1), m.p. 211–215 °C. IR (CHCl3): = 1734, 1260 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.26 [t, J = 7.0 Hz, 3H, (CH3CH2O)2P], 1.42 [t, J =7.0 Hz, 3H, (CH3CH2O)2P], 3.26 (s, 3H, NCH3); 3.73 (d, JHP = 26.6 Hz, 1H, OCH), 4.05–4.18 [m, 2H, (CH3CH2O)2P], 4.25–4.34 [m, 2H, (CH3CH2O)2P], 6.83 (d, J = 8.3 Hz, 1H, CHarom), 7.38 (d, J = 8.3 Hz, 1H, CHarom), 8.02 (s, 2H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 16.4 (d, JCP = 5.9 Hz), 16.6 (d, JCP = 5.6 Hz), 27.1, 58.1 (d, JCP = 203.4 Hz), 59.9, 63.3 (d, JCP = 6.3 Hz), 63.8 (d, JCP = 6.1 Hz), 109.8, 121.2, 127.5, 128.8, 131.0, 144.3, 170.4. HRMS: exact mass calculated for (C14H17ClNNaO5P) requires m/z 368.0431, found m/z 368.0433. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 9/1, flow rate 1.0 mL/min]: Tmajor = 18.92 min, Tminor = 17.56 min er = 77:23. [α]D = +4 (c = 0.0170 g/cm3 in CHCl3).
(2′S,3′S)-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12m. Following the above general procedure, trans diastereoisomer 12m was obtained as a white solid in 62% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3433, 3035, 3009, 1751, 1726, 1622, 1474, 1340, 1318 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.29 (t, J = 7.1 Hz, 3H, CH3CH2O); 4.17–4.47 (m, 3H, CH3CH2O, OCH); 6.87–7.17 (m, 2H, CHarom); 7.27–7.51 (m, 2H, CHarom); 9.38 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 59.9, 60.5, 62.5, 111.4, 119.6, 123.3, 125.2, 131.3, 143.0, 165.7, 172.6. HRMS: exact mass calculated for (C12H11NNaO4) requires m/z 256.0586, found m/z 256.0582. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 90/10, flow rate 1.0 mL/min]: Tmajor = 6.28 min, Tminor = 5.51 min er = 75:25. [α]D = −84.22 (c = 0.0155 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 5-fluoro-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12n. Following the above general procedure, trans diastereoisomer 12n was obtained as a white solid in 32% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3429, 3207, 3031, 2979, 1715, 1767, 1752, 1630, 1481, 1319, 1231, 1204 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.32 (t, 3H, J = 7.1 Hz, CH3CH2O); 4.19 (s, 1H, OCH); 4.26–4.36 (m, 2H, CH3CH2O); 6.88 (m, 1H, CHarom); 7.06 (t, 1H, J = 8.4 Hz, CHarom); 7.24 (m, 1H, CHarom); 8.66 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 60.0, 60.5, 62.7, 111.9 (d, JCF = 7.9 Hz), 113.5 (d, JCF = 26.7 Hz), 117.9 (d, JCF = 23.9 Hz), 121.3 (d, JCF = 9.1 Hz), 138.8, 159.3 (d, JCF = 242.2 Hz), 165.4, 172.3. HRMS: exact mass calculated for (C12H10FNNaO4) requires m/z 274.0492, found m/z 274.0497. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 90/10, flow rate 1.0 mL/min]: Tmajor = 10.44 min, Tminor = 9.05 min er = 93:7. [α]D = −132 (c = 0.0155 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 5-chloro-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12o. Following the above general procedure, trans diastereoisomer 12o was obtained as a white solid in 33% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 1/1). IR (CHCl3): = 3433, 3213, 3021, 1764, 1755, 1602, 1441, 1240, 1228, 1213 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.32 (t, 3H, J = 7.1 Hz, CH3CH2O); 4.19 (s, 1H, OCH); 4.26–4.36 (m, 2H, CH3CH2O); 6.88 (m, 1H, CHarom); 7.06 (t, 1H, J = 8.4 Hz, CHarom); 7.24 (m, 1H, CHarom); 8.66 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 60.0, 60.5, 62.7, 112.1, 123.3, 125.9, 129.0, 131.3, 140.3, 165.4, 171.8. HRMS: exact mass calculated for (C12H10ClNNaO4) requires m/z 290.0196, found m/z 290.0198. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 70/30, flow rate 1.0mL/min]: Tmajor = 5.15 min, Tminor = 4.66 min er = 73:27. [α]D = −43 (c = 0.0108 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 5-iodo-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12p. Following the above general procedure, trans diastereoisomer 12p was obtained as a white solid in 71% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 1/1). IR (CHCl3): = 1765, 1760, 1602, 1441, 1240, 1228 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.34 (t, 3H, J = 7.0 Hz, CH3CH2O); 4.17–4.40 (m, 3H, CHO, CH3CH2O); 6.76 (d, 1H, J = 8.3 Hz, CHarom); 7.67 (d, 1H, J = 8.3 Hz, CHarom); 7.76 (s, 1H, CHarom), 8.73 (bs, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.4, 59.8, 60.1, 62.7, 85.6, 113.0, 122.0, 134.2, 140.1, 142.4, 165.4, 171.2. HRMS: exact mass calculated for (C12H10INNaO4) requires m/z 381.9552, found m/z 381.9555. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 90/10, flow rate 1.0 mL/min]: Tmajor = 11.56 min, Tminor = 9.81 min ee = 68:32. [α]D = −23 (c = 0.0120 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 2-oxo-5-(trifluoromethoxy)spiro[indoline-3,2′-oxirane]-3′-carboxylate 12q. Following the above general procedure, trans diastereoisomer 12q was obtained as a white solid in 29% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3433, 3210, 3028, 1764, 1724, 1630, 1478, 1371, 1234, 1197 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.31 (t, 3H, J = 7.0 Hz, CH3CH2O); 4.20 (s, 1H, OCH); 4.31 (q, 2H, J = 7.0 Hz, CH3CH2O); 6.97 (d, 1H, J = 8.4 Hz, CHarom); 7.22–7.26 (m, 1H, CHarom); 7.41 (s, 1H, CHarom); 8.41 (bs, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.2, 60.1, 60.0, 62.7, 111.6, 119.6, 120.6 (q, JCF = 256.0 Hz), 121.3, 124.6, 141.3, 145.1, 165.3, 171.7. HRMS: exact mass calculated for (C13H10F3NNaO5) requires m/z 340.0409, found m/z 340.0410. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 95/5, flow rate 1.0mL/min]: Tmajor = 12.04 min, Tminor = 9.15 min er = 87:13. [α]D = −56.53 (c = 0.0168 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 7-fluoro-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12r. Following the above general procedure, trans diastereoisomer 12r was obtained as a white solid in 21% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 8/2). IR (CHCl3): = 3433, 3031, 2976, 2930, 1752, 1737, 1639, 1493, 1234, 1228 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.30 (t, 3H, J = 7.0 Hz, CH3CH2O); 4.20 (s, 1H, OCH); 4.25–4.30 (m, 2H, CH3CH2O); 7.01–7.05 (m, 1H, CHarom); 7.14 (t, 1H, J = 9.2 Hz, CHarom); 7.28 (d, 1H, J = 9.2 Hz, CHarom); 7.84 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 60.0, 60.1, 62.5, 118.4 (d, JCF = 17 Hz), 121.1 (d, JCF = 3.6 Hz), 122.2, 124.0 (d, JCF = 5.9 Hz), 129.9, 147.4 (d, JCF = 244.7 Hz), 165.3, 170.5. HRMS: exact mass calculated for (C12H10FNNaO4) requires m/z 274.0492, found m/z 274.0493. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 8/2, flow rate 1.0 mL/min]: Tmajor = 7.88 min, Tminor = 8.60 min er = 92:8. [α]D = −63.2 (c = 0.0150 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 7-chloro-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12s. Following the above general procedure, trans diastereoisomer 12s was obtained as a white solid in 35% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3420, 3177, 3009, 1764, 1749, 1624, 1478, 1316, 1234, 1189 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.29 (t, 3H, J = 6.8 Hz, CH3CH2O); 4.20–4.31 (m, 2H, CH3CH2O, OCH); 7.01 (t, 1H, J = 8.1 Hz, CHarom); 7.36 (t, 2H, J = 8.1 Hz, CHarom); 8.14 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.2, 60.1, 60.7, 62.5, 116.3, 121.3, 123.6, 124.1, 131.1, 140.4, 165.3, 171.2. HRMS: exact mass calculated for (C12H10ClNNaO4) requires m/z 290.0196, found m/z 290.0197. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 8/2, flow rate 1.0 mL/min]: Tmajor = 7.72 min, Tminor = 10.00 min er = 88:12. [α]D = −186.6 (c = 0.0220 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 7-bromo-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12t. Following the above general procedure, trans diastereoisomer 12t was obtained as a white solid in 49% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3414, 3210, 3006, 1742, 1730, 1621, 1444, 1316, 1234 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.29 (t, 3H, J = 7.1 Hz, CH3CH2O); 4.20 (s, 1H, OCH); 4.23–4.37 (m, 2H, CH3CH2O); 6.96 (t, 1H, J = 7.9 Hz, CHarom); 7.42 (d, 1H, J = 7.9 Hz, CHarom); 7.48 (d, 1H, J = 7.9 Hz, CHarom); 8.06 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 60.1, 61.0, 62.6, 104.1, 121.4, 124.3, 124.5, 133.9, 141.9, 165.3, 170.5. HRMS: exact mass calculated for (C12H10BrNNaO4) requires m/z 333.9691, found m/z 333.9693. Chiralphase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 7/3, flow rate 1.0mL/min]: Tmajor = 6.14 min, Tminor = 7.18 min er = 92:8. [α]D = −15.85 (c = 0.0132 g/cm3 in CHCl3).
(2′S,3′S)-ethyl 5,7-dichloro-2-oxospiro[indoline-3,2′-oxirane]-3′-carboxylate 12u. Following the above general procedure, trans diastereoisomer 12u was obtained as a white solid in 27% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3423, 3031, 3009, 1757, 1743, 1463, 1323, 1290 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.32 (t, J = 7.0 Hz, 3H, CH3CH2O); 4.18–4.36 (m, 3H, CH3CH2O, OCH); 7.38 (s, 1H, CHarom); 7.42 (s, 1H, CHarom); 8.09 (s, 1H, NH). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.3, 60.1, 60.4, 62.9, 116.6, 122.4, 124.4, 129.3, 130.8, 138.9, 165.1, 170.1. HRMS: exact mass calculated for (C12H9Cl2NNaO4) requires m/z 323.9806, found m/z 323.9808. Chiral-phase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 7/3, flow rate 1.0 mL/min]: Tmajor = 5.52 min, Tminor = 6.34 min er = 83:17. [α]D = +137 (c = 0.0090 g/cm3 in CHCl3).
(2R,3′R)-1-(tert-butyl) 3′-ethyl-2-oxospiro[indoline-3,2′-oxirane]-1,3′-dicarboxylate 12v. Following the above general procedure, trans diastereoisomer 12v was obtained as a white solid in 60% yield after purification by flash chromatography on silica gel (nHexane/EtOAc = 7/3). IR (CHCl3): = 3035, 307, 2984, 1736, 1618, 1603, 1495, 1473, 1376, 1347 cm−1. 1H-NMR (CDCl3, 300 MHz, 25 °C): δ (ppm) 1.23 (t, J = 5.9 Hz, 3H, CH3CH2O), 1.48 (s, 9H), 4.22 (s, 2H, CH3CH2O), 4.59–4.45 (m, 1H), 7.22 (dtd, J = 26.3, 7.4, 2.0 Hz, 1H, CHarom), 7.38 (dd, J = 7.3, 2.2 Hz, 2H, CHarom), 7.89 (dd, J = 7.4, 2.1 Hz, 1H, CHarom). 13C-NMR (CDCl3, 75 MHz, 25 °C): δ (ppm) 14.0, 27.8, 60.5, 61.1, 69.2, 83.4, 114.4, 115.3, 125.2, 125.8, 129.3, 131.3, 150.5, 166.4, 170.8. HRMS: exact mass calculated for (C17H19NNaO6) requires m/z 356,1110, found m/z 356,1112. Chiralphase HPLC analysis: [Daicel Chiralpack IC 5μ, λ = 254 nm, nHexane/EtOH = 9/1, flow rate 1.0 mL/min]: Tmajor = 6.80 min, Tminor = 5.75 min er = 96:4. [α]D = +27 (c = 0.0103 g/cm3 in CHCl3).