tel-00559649, version 1 - 26 Jan 2011 Experimental section 180 PhSe F F 6 1 5 2 NHAc 4 3 BnO OBn 97 Rf = 0.42 (30% EtOAc in cyclohexane). 1 H NMR (CDCl3, 300 MHz): δ 7.65 (d, J = 7.9 Hz, 2H, Ph), 7.37-7.16 (m, 13H, Ph), 7.02 (d, J = 9.2 Hz, 1H, NH), 5.90 (ddd, J = 18.2 Hz, J = 10.1 Hz, J = 8.0 Hz, 1H, H5), 5.29-5.13 (m, 2H, H6), 5.10-4.91 (m, 1H, H2), 4.54 (d, J = 11.7 Hz, 1H, CH2Ph), 4.43 (d, J = 10.6 Hz, 1H, CH2Ph), 4.28 (d, J = 10.3 Hz, 1H, CH2Ph), 4.14 (d, J = 10.3 Hz, 2H, CH2Ph and H4), 3.65 (s, 1H, H3), 1.68 (s, 3H, C(CH3)3). 19 F NMR (CDCl3, 282.5 MHz): δ -77.0 (dd, J = 197.7 Hz, J = 7.2 Hz, 1F), -78.8 (dd, J = 197.7 Hz, J = 19.6 Hz, 1F). 13 C NMR (CDCl3, 75.5 MHz): δ 171.1 (C=O), 137.9 (Ph), 137.5, 137.0 (Ph), 135.4 (C5), 130.3, 129.7, 129.3, 128.9, 128.5 (Ph), 124.6 (t, J = 300.4 Hz, C1), 120.1 (C6), 83.7 (C4), 77.1 (C3), 72.9 (CH2Ph), 71.9 (CH2Ph), 55.0 (dd, J = 24.9 Hz, J = 20.7 Hz, H2), 23.6 (C(CH3)3). IR (neat) νmax 3397 (NH), 3031 (Ph), 2868 (CH2), 1686 (C=O) cm -1 . MS (ESI+) m/z = 562.8 ([M+H2O] + ), 546.0 ([M+H] + ). Anal. Calcd. for C28H29F2NO3Se: C, 61.76; H, 5.37; N, 2.57. Found: C, 61.74; H, 5.23; N, 2.53. 6.5.4 Radical <strong>cyclisation</strong> PhSe F O F S NH Bu 3SnH (1.5 equiv), AIBN (0.3 equiv) O F F S NH BnO OBn t-BuOH, 80°C, 1 h 72% BnO OBn 99 101 O F F S NH BnO OBn 101' To a <strong>de</strong>gassed solution of 99 (100 mg, 0.17 mmol) and AIBN (8.2 mg, 0.05 mmol, 0.3 equiv.) in 4 mL of t-BuOH was ad<strong>de</strong>d over 1 hour un<strong>de</strong>r reflux a <strong>de</strong>gassed solution of Bu3SnH (70 µL, 0.25 mmol, 1.5 equiv.) in 2 mL of t-BuOH. AIBN (8.2 mg, 0.05 mmol, 0.3 equiv) was ad<strong>de</strong>d each 30 minutes until total consumption of the starting material (followed by RMN 19 F). The solvent was then evaporated and the cru<strong>de</strong> residue obtained was purified by flash chromatography (cyclohexane/EtOAc 95:05 to 80:20) to afford an unse<strong>par</strong>able mixture of 101 and 101’ (46 mg, 72%) as a colorless oil.
tel-00559649, version 1 - 26 Jan 2011 Experimental section (R)-(+)-2-M<strong>et</strong>hyl-propane-2-sulfinic acid (3-(R),4-(R)-bis-benzyloxy-1,1-difluoro-5- m<strong>et</strong>hyl-cyclopentyl)-ami<strong>de</strong> (101): 6 BnO O F F S NH 5 4 1 2 3 OBn BnO O F F S NH 1 5 2 4 3 OBn 101 (Major) 101' (minor) Rf = 0.52 (30% EtOAc in cyclohexane). 1 H NMR (300 MHz, CDCl3) δ 7.43-7.23 (m, 10H, Ph), 4.75 (d, J = 18.8 Hz, 1H, M, CH2Ph), 4.71 (d, J = 18.8 Hz, 1H, m, CH2Ph), 4.59-4.48 (m, 2H, CH2Ph), 4.41 (d, J = 18.8 Hz, 1H, M, CH2Ph), 4.14-3.97 (m, 3H, H2-3-NH), 3.70 (d, J = 6.1 Hz, 1H, m, H4), 3.53 (d, J = 7.2 Hz, 1H, M, H4), 2.58-2.49 (m, 1H, m, H5), 2.32-2.06 (m, 1H, M, H5), 1.25 (s, 9H, C(CH3)3), 1.16 (d, J = 7.1 Hz, 3H, M, H6), 1.06 (d, J = 7.1 Hz, 3H, m, H6). 19 F NMR (282.5 MHz, CDCl3) δ -106.6 (d, J = 234.1 Hz, 1F), -120.3 (d, J = 232.7 Hz, 1F). 13 C NMR (75.5 MHz, CDCl3) δ 136.6, 136.5, 136.3, 136.2, 128.9, 128.8, 128.7, 128.6, 128.4 (x2), 128.2 (x2), 128.0, 127.9 (Ph), 126.1 (t, J = 256.1 Hz, C1), 86.9 (d, J = 7.2 Hz, M, C4), 80.6 (m, C4), 80.5, 80.4, 80.3, 80.2, 80.0 (C2 or C3), 73.0 (x2), 72.4, 72.3 (CH2Ph), 61.6 (d, J = 19.1 Hz), 61.2 (d, J = 19.1 Hz), 60.8 (d, J = 19.1 Hz), 60.5 (d, J = 19.1 Hz, C3 or C2), 56.8, 56.7 (C(CH3)3), 43.7 (t, J = 21.8 Hz, M, C5), 41.9 (t, J = 23.0 Hz, m, C5), 22.8 (C(CH3)3), 11.0 (d, J = 6.9 Hz, M, C6), 7.3 (d, J = 7.4 Hz, m, C6). MS (ESI+): m/z = 452.20 ([M+H] + ), 903.0 ([2M+H] + ). Anal. Calcd. for C24H31F2NO3S: C, 63.83; H, 6.92; N, 3.10; S, 7.10. Found: C, 63.91; H, 7.26; N, 3.09; S, 6.78. (S)-(-)-2-M<strong>et</strong>hyl-propane-2-sulfinic acid (3-(R),4-(R)-bis-benzyloxy-1,1-difluoro-5- m<strong>et</strong>hyl-cyclopentyl)-ami<strong>de</strong> (102): The same procedure was applied to 100 (149 mg, 0.25 mmol). Purification by column chromatography using cyclohexane/EtOAc (95:05 to 80:20) as eluent affor<strong>de</strong>d the <strong>de</strong>sired product 102 (87 mg, 78%, d.r. = 90:10). 6 181
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