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Helvetica Chimica Acta – Vol. 90 (2007)
Data of (ꢁ)-endo-28c. White solid. M.p. 141–1448. IR (neat): 2955w, 2906w, 2883w, 1777w, 1698s,
1654m, 1524m, 1504s, 1450w, 1425m, 1399m, 1359m, 1340m, 1308m, 1246w, 1216w, 1177m, 1144m,
1102m, 1078m, 1042m, 1017m, 980s, 924m, 892m, 871m, 858m, 832w, 734m, 722m, 696m, 686m, 639m,
619m. 1H-NMR (300 MHz, CDCl3): 1.60–1.88 (m, 2 H); 1.99–2.22 (m, 2 H); 2.66 (ddd, J=12.5, 8.0,
4.7, 1 H); 2.90 (ddd, J=12.5, 8.6, 7.0, 1 H); 3.31 (dd, J=8.4, 1.5, 1 H); 3.54 (dd, J=8.4, 8.4, 1 H); 3.82
(dd, J=8.4, 8.4, 1 H); 4.43 (d, J=8.4, 1 H); 4.62 (AB, J=10.2, 2 H); 7.24–7.37 (m, 5 H). 13C-NMR (75
MHz, CDCl3): 23.6; 29.8; 42.9; 48.8; 49.3; 51.6; 60.5; 67.9; 128.0; 128.6; 128.9; 135.2; 175.4; 177.1. HR-
MALDI-MS: 437.1276 ([M+H]+, C22H18F5N2O2þ ; calc. 437.1283). Anal. calc. for C22H17F5N2O2
(436.38): C 60.55, H 3.93, N 6.42; found: C 60.46, H 3.99, N 6.29.
Data of (ꢁ)-exo-29c. White solid. M.p. 76–798. IR (neat): 2967w (br.), 2361w, 1774w, 1699s, 1654w,
1586w, 1522m, 1499s, 1456w, 1432w, 1393m, 1341m, 1305m, 1267w, 1235w, 1169m, 1120m, 1071w, 1027m,
996m, 972m, 947w, 926w, 896m, 824w, 736m, 699m, 625m. 1H-NMR (300 MHz, CDCl3): 1.50–1.69 (m, 3
H); 1.81–1.95 (m, 1 H); 2.32–2.41 (m, 1 H); 2.85–2.93 (m, 1 H); 3.62–3.71 (m, 2 H); 3.90–3.96 (m, 1 H);
4.63 (d, J=3.6, 1 H); 4.65 (AB, J=2.7, 2 H); 7.26–7.35 (m, 3 H); 7.38–7.42 (m, 2 H). 13C-NMR (75 MHz,
CDCl3): 24.7; 26.3; 42.8; 49.0; 53.0; 53.1; 60.5; 66.9; 128.1; 128.6; 129.0; 135.0; 176.1; 177.1. HR-MALDI-
MS: 437.1275 ([M+H]+, C22H18F5N2O2þ ; calc. 437.1283).
(ꢁ)-Methyl
(1RS,2SR,3RS,7aSR)-Hexahydro-3-(pentafluorophenyl)-2-{[(phenylmethyl)amino]-
carbonyl}-1H-pyrrolizine-1-carboxylate ((ꢁ)-30c). General Procedure H with (ꢁ)-endo-28c (6.11 g, 14
mmol, 1 equiv.), 0.05M NaOH in THF/H2O 2 :1 (560 ml), MeOH (70 ml), and SOCl2 (5.1 ml, 70 mmol,
5 equiv.). The crude product was taken up in sat. aq. NaHCO3 soln. (500 ml) and CH2Cl2/i-PrOH 3 :1
(500 ml). The layers were separated. The aq. phase was extracted with CH2Cl2/i-PrOH 3 :1 (2ꢂ250
ml). The comb. org. phases were dried (MgSO4), filtered, and concentrated in vacuo to give a solid,
which was purified by CC (SiO2; CH2Cl2/MeOH/Et3N 99.5 :0.5 :1) to afford (ꢁ)-30c (5.47 g, 83%).
White solid. M.p. 192–1948. IR (neat): 3311w, 3091w, 2980w, 2950w, 2803w, 1725s, 1649s, 1557m,
1519m, 1495s, 1455m, 1435m, 1376m, 1302m, 1221s, 1208s, 1140m, 1121m, 1096m, 1030m, 1001s, 973s,
950m, 888w, 872w, 826w, 734m, 696s, 656m, 644m. 1H-NMR (300 MHz, CDCl3): 1.57–1.68 (m, 1 H);
1.84–2.04 (m, 2 H); 2.08–2.19 (m, 1 H); 2.49–2.57 (m, 1 H); 2.98–3.08 (m, 2 H); 3.64–3.70 (m, 1 H);
3.69 (s, 3 H); 4.16–4.37 (m, 4 H); 7.12–7.15 (m, 2 H); 7.23–7.29 (m, 3 H); 7.48–7.54 (m, 1 H). 13C-
NMR (75 MHz, CDCl3): 26.3; 32.2; 43.3; 51.8; 52.2; 53.3; 56.1; 64.9; 65.1; 127.3; 127.8; 128.4; 138.2;
168.9; 170.9. HR-MALDI-MS: 469.1548 ([M+H]+, C23H22F5N2Oþ3 ; calc. 469.1545). Anal. calc. for
C23H21N2O3F5 (468.42): C 58.98, H 4.52, N 5.98; found: C 59.08, H 4.58, N 5.91.
(ꢁ)-(1RS,2SR,3RS,7aSR)-Hexahydro-1-(hydroxymethyl)-3-(pentafluorophenyl)-N-(phenylmethyl)-
1H-pyrrolizine-2-carboxamide ((ꢁ)-31c). General Procedure I with (ꢁ)-30c (5.51 g, 11 mmol, 1 equiv.),
20 wt.-% DIBAL-H in toluene (27.3 ml, 33 mmol, 3 equiv.), and THF (180 ml) yielded, after purification
by CC (SiO2; Et2O/MeOH/Et3N 98 :1:1), (ꢁ)-31c (1.40 g, 29%). Pale yellow solid. M.p. 144–1478. IR
(neat): 3330m (br.), 3058w, 3028w, 2966w, 2941w, 2910w, 2872w, 2713w, 2628w, 2330w, 2222w, 1765m,
1731m, 1670s, 1652s, 1602m, 1558m, 1523s, 1495s, 1454m, 1431w, 1386w, 1328w, 1306m, 1287w, 1249m,
1223m, 1151s, 1114m, 1080m, 1030s, 1001m, 969s, 941m, 908m, 899m, 858m, 822m, 806m, 739s, 696s,
1
634w. H-NMR (300 MHz, CDCl3): 1.81–2.04 (m, 4 H); 2.46–2.58 (m, 2 H); 2.84 (dd, J=10.7, 4.1, 1
H); 2.99 (ddd, J=10.7, 6.5, 6.5, 1 H); 3.27 (dd, J=14.7, 6.6, 1 H); 3.50–3.75 (m, 3 H); 4.21 (dd,
J=14.4, 5.7, 1 H); 4.28 (d, J=3.9, 1 H); 4.49 (dd, J=14.4, 6.6, 1 H); 7.11–7.15 (m, 2 H); 7.24–7.27 (m,
3 H); 8.46–8.54 (m, 1 H). 13C-NMR (75 MHz, CDCl3): 26.3; 32.1; 43.3; 50.5; 52.8; 55.7; 62.8; 64.5;
65.2; 127.3; 127.7; 128.4; 138.0; 170.7. HR-MALDI-MS: 441.1590 ([M+H]+, C22H22F5N2O2þ ; calc.
441.1596). Anal. calc. for C22H21F5N2O2 (440.41): C 60.00, H 4.81, N 6.36; found: C 60.22, H 5.06, N 6.32.
(ꢁ)-(1RS,2SR,3RS,7aSR)-Hexahydro-3-(pentafluorophenyl)-2-{[(phenylmethyl)amino]carbonyl}-
1H-pyrrolizin-1-yl)methyl Bis(phenylmethyl) Phosphate ((ꢁ)-32c). General Procedure J with (ꢁ)-31c
(440 mg, 1.0 mmol, 1.0 equiv.), 0.45M 1H-tetrazole in MeCN (6.7 ml, 3.0 mmol, 3.0 equiv.), dibenzyl-N,
N-diisopropylphosphoramidite (0.5 ml, 1.5 mmol, 1.5 equiv.), MeCN (10 ml), and 70% pure mCPBA
(591 mg, 2.4 mmol, 2.4 equiv.) yielded, after purification by CC (SiO2; AcOEt/hexane/Et3N 50 :50 :1),
(ꢁ)-32c (557 mg, 79%). White solid. M.p. 106–1088. IR (neat): 3302w, 3066w, 3033w, 2951w, 2896w,
2818w, 1647m, 1554m, 1519m, 1493m, 1455m, 1375w, 1338w, 1303w, 1272m, 1236m, 1215m, 1189w,
1
1154w, 1140w, 1120w, 1048m, 1032m, 1017s, 999s, 974s, 900m, 882m, 816w, 791w, 770w, 736s, 695s. H-
NMR (300 MHz, CDCl3): 1.52–1.61 (m, 1 H); 1.79–2.01 (m, 3 H); 2.29–2.39 (m, 1 H); 2.45–2.53 (m,