, Hz, 1H), 2.77-2.64 (m, 1H), 2.19-2.09 (m, 1H), 2.06-1.92 (m, 1H); minor diastereomer: ? 7.75 (d, J = 8.7 Hz, 2H), 7.44-7.32 (m, 3H), 7.24-7.20 (m, 2H), vol.7
, 18 mmol, dr = 22:1, er = 55:1) reacted with DPHB (7 mg, 0.037 mmol) for 72 h to provide 4 d (54 mg, 75%, dr = 1.6:1, er = 43:1 and 21:1) as a white solid
, + = 407.1213, found = 407.1213. 1 H NMR (400 MHz, CDCl 3 ) major diastereomer: ? 7.75 (d, J = 8.7 Hz, 2H), 7.43-7.38 (m, 3H), 7.24-7.33 (m, 2H), 7.14 (d, J = 8.7 Hz, 2H), 5.23 (dd, J = 13.4, 7.3 Hz, 1H), 5.07 (dd, J = 13.4, 7.9 Hz, 1H)
,
, CDCl 3 ) major diastereomer: ? 62.7; minor diastereomer: ? 62.7. HPLC: Chiralpak IC eluted with 8:2 heptane/ ethanol at 1 mL/min at 25°C, UV detection at 235 nm, retention times: major diastereomer 11, Hz, 1H), 2.76-2.66 (m, 1H), 2.06-1.93 (m, 1H), 1.77 (ddd, J = 14.2, 9.6, 4.7 Hz, 1H). 13 C{ 1 H} NMR (100 MHz, vol.128
, 19 mmol, dr = 25:1, er = 58:1) reacted with DPHB (7 mg, 0.037 mmol) for 24 h to provide 4 e (77 mg, 85%, dr = 1.5:1, er = 44:1 and 38:1) as a colorless oil
, CDCl 3 ) major diastereomer: ? 7.92 (s, 1H), 7.53-7.35 (m, 5H), 7.26-7.19 (m, 2H), vol.5
, m, 1H
,
, CDCl 3 ) major diastereomer: ? 172.8 (C), 171.0 (C), 136.5 (C), 135.8 (C), vol.132
, , vol.122
, 129.3 (2CH), 128.7 (2CH), vol.128
, HPLC: Chiralpak IF eluted with 9:1 heptane/ethanol at 1 mL/min at 25°C, UV detection at 210 nm, retention times: major diastereomer 13.26 min (major enantiomer) and 6.20 min (minor enantiomer), minor diastereomer 7.38 min (major enantiomer), F{ 13 C} NMR (282 MHz, vol.9
, 16 mmol, dr = 26:1, er = 49:1) reacted with DPHB (6 mg, 0.032 mmol) for 48 h to provide 4 i (43 mg, 66%, dr = 1.7:1, er = 12:1 and 19:1) as a white solid. R f = 0.30 (petrol ether/ethyl acetate, HRMS (ESI +) m, vol.2
, 36 (s, 3H), 2.20-2.12 (m, 1H), 2.08-1.94 (m, 1H), + = 398.1347, found = 398.1345. 1 H NMR (400 MHz, CDCl 3 ) major diastereomer: ? 8.32 (d, J = 8.7 Hz, 2H), 7.25-7.09 (m, 6H), 5.20 (dd, J = 13.3, 7.6 Hz, 1H), 4.99 (dd, J = 13.3, 7.7 Hz, 1H), 4.00 (ddd, J = 7.7, 7.7, 3.6 Hz, 1H), 3.15 (ddd, J = 11.8, 5.2, 3.5 Hz, 1H), 2.82 (ddd, J = 17.5, 4.4, 4.4 Hz, 1H), 2.72-2.63 (m, 1H), vol.2
, er = 40:1 and 37:1) as a white solid. R f = 0.28 (petrol ether/ethyl acetate, 3:1). HRMS (ESI +) m/z calcd for C 20 H 20 N 3 O 7
, CDCl 3 ) major diastereomer: ? 8.31 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 5.18 (dd, J = 13.3, 7.5 Hz, 1H), 5.00 (dd, J = 13.3, 7.8 Hz, 1H), 3.97 (ddd, J = 7.7, 7.7, 3.6 Hz, 1H), vol.1296
, HPLC: Chiralpak IF eluted with 1:1 heptane/ethanol at 1 mL/min at 25°C, UV detection at 260 and 280 nm, Hz, 2H), 5.09 (dd, J = 13.3, 7.4 Hz, 1H), 4.73 (dd, J = 13.3, 7.5 Hz, 1H), 4.13 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H), vol.3, pp.147-155
, 0.12 mmol, dr > 20:1, er > 200:1) reacted with DPHB (5 mg, 0.026 mmol) for 15 h to provide 4 k (37 mg, 69%, dr = 1.8:1, er = 75:1 and 6.4:1) as a white solid
, Hz, 1H), 2.98-2.84 (m, 1H), 2.82-2.68 (m, 1H), 2.18-2.11 (m, 1H), 2.08-1.88 (m, 1H); minor diastereomer: ? 8.32 (d, Hz, 2H), 5.17 (dd, J = 13.5, 7.2 Hz, 1H), 5.04 (dd, J = 13.4, 8.0 Hz, 1H), vol.7
, HPLC: Chiralpak IC eluted with 7:3 heptane/ethanol at 1 mL/min at 25°C, UV detection at 280 nm, retention times: major diastereomer 12.64 min (major enantiomer) and 9.45 min (minor enantiomer), minor diastereomer 10, 134.5 (C), 132.5 (2CH), 131.5 (2CH), vol.130, pp.142-149
, 3 l (50 mg, 0.12 mmol, dr > 20:1, er = 39:1) reacted with DPHB (5 mg, 0.026 mmol) for 15 h to provide 4 l (22 mg, 44%, dr > 20:1, er = 50:1) as a white solid
, CHCl 3 ). HRMS (ESI +) m/z calcd for C 19 H 20 N 5 O 8 +
, CDCl 3 ): ? 8.33 (d, J = 8.8 Hz, 2H), MHz, vol.8, issue.400
,
,
, HPLC: Chiralpak IC eluted with 2:2:1 heptane/ethanol/chloroforme at 1 mL/min at 25°C, UV detection at 254 nm, 5 Hz, 1H). 13 C { 1 H} NMR (100 MHz, d6-acetone): ? 173.7 (C), 172.2 (C), 148.5 (C), 148.4 (C), 146.7 (C), 143.2 (C), 131.4 (2CH), 131.1 (2CH), 124.8 (2CH), 124.6 (2CH), vol.77
, dr = 28:1, er = 100:1) reacted with DPHB (6 mg, 0.032 mmol) for 15 h to provide 4 m (41 mg, 68%, dr = 2.4:1, er = 39:1 and 5.5:1) as a white solid. R f = 0.30 (petrol ether/ ethyl acetate, 3:1). HRMS (ESI +) m/z calcd for C 17 H 19 N 4 O 6 S +
,
, 20 (ddd, J = 12.4, 5.2, 3.3 Hz, 1H), 3.01-2.85 (m, 1H), 2.83-2.73 (m, 1H), 2.22-2.14 (m, 1H), 2.08-2.00 (m, 1H); minor diastereomer: ? 8.32 (d, CDCl 3 ) major diastereomer: ? 8.33 (d, J = 8.7 Hz, 2H), 7.33-7.30 (m, 1H), 7.24 (d, J = 8.7 Hz, 2H), 7.04-6.94 (m, 2H), 5.23 (dd, J = 13.5, 7.3 Hz, 1H), 4.99 (dd, J = 13.5, 7.4 Hz, 1H), 4.32 (ddd, J = 7.4, 7.4, 3.3 Hz, 1H), vol.3
, 19 mmol, dr = 15:1, er = 48:1) reacted with DPHB (7 mg, 0.037 mmol) for 15 h to provide 4 n (57 mg, 81%, dr = 2:1, er = 28:1 and 46:1) as a white solid. R f = 0.28 (petrol ether/ethyl acetate, HRMS (ESI +) m/z calcd for C 17 H 19 N 4 O 7, vol.3
, CDCl 3 ) major diastereomer: ? 8.31 (d, J = 8.8 Hz, 2H), 7.43 (br s, 1H), 7.37 (br s, 1H), 7.19 (d, J = 8.8 Hz, 2H), 6.30 (br s, 1H), 5.12 (dd, 1248.
, 2H); minor diastereomer: ? 8.30 (d, J = 8, m, 1H), 1.92-1.81 (m, 1H). 13 C{ 1 H} NMR (100 MHz, d8-tetrahydrofuran, vol.6
, HPLC: Chiralpak IC eluted with 4:1 heptane/ethanol at 1 mL/min at 25°C, UV detection at 254 nm, retention times: major diastereomer 24.80 min (major enantiomer) and 17.08 min (minor enantiomer), minor diastereomer 18.98 min (major enantiomer) and 43, vol.45
, 22 mmol, dr = 28:1, er = 24:1) reacted with DPHB (8 mg, 0.042 mmol) for 24 h to provide 4 o (59 mg, 66%, dr = 1.9:1, er = 19:1 and 15:1) as a white solid
, CDCl 3 ) major diastereomer: ? 8.30 (d, J = 9, Hz, 2H), vol.1769, pp.35-42
, HPLC: Chiralpak IE eluted with 1:1 heptane/ethanol at 1 mL/min at 25°C, UV detection at 260 nm, retention times: major diastereomer 9, C{ 1 H} NMR (100 MHz, d8-tetrahydrofuran) major diastereomer: ? 173.6 (C), 171.6 (C), 148.2 (C), 142.8 (C), 142.2 (C), 130.9 (2CH), 129.0 (2CH), 129.0 (2CH), vol.126, pp.130-139
, 74, 1531. (?)-Pomalidomide: marketed under the trade name Imnovid (Europe and Russia) or Pomalyst (USA) by Celgene. (?)-Lenalidomide: marketed under the trade name Revlimid (Europe) by Celgene. (?)-Aminoglutethimide: marketed under the trade name Cytraden by Novartis. For novel promising analogs of pomalidomide and lenalidomide: d), For more complex glutarimide-containing natural products: e), vol.101, p.6052, 1517.
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, Regrettably, the pKa and Lewis basicities of these catalyst in dichloromethane are essentially unknown, For the relative nucleophilicities of the catalysts depicted in Scheme, vol.3
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