I. Izquierdo et al. / Tetrahedron 61 (2005) 6527–6533
6531
1
off, washed with MeOH and the combined filtrate and
washings (50 mL) treated with 2 M MeONa (2 mL). After
1 h, TLC (EtAcO/hexane, 1:1) then revealed the presence of
a faster-running product. The mixture was neutralized with
aqueous 10% HCl, supported on silica gel and submitted to
chromatography (Et2O/hexane, 10:1) to afford 12. Yield:
1.32 g (83%); white foam; [a]2D7 K52 (c, 1). IR (KBr): 3373
(OH), 3069 (aromatic), 1682 (C]O), 737 and 700 cmK1
3032, 733 and 699 cmK1 (aromatic). H NMR (300 MHz,
MeOH-d4): dZ7.30–7.12 (m, 10H, 2Ph), 4.64 and 4.53 (2d,
2H, JZ11.7 Hz, CH2Ph), 4.49 and 4.42 (2d, 2H, JZ
11.6 Hz, CH2Ph), 4.37 (dd, 1H, J1,2Z6.7, J1,7aZ5.9 Hz,
H-1), 4.11 (dd, 1H, H-6), 3.97 (dd, 1H, J2,3Z9.1 Hz, H-2),
3.85 (dd, 1H, J6,7Z1.6, J7,7aZ3.8 Hz, H-7), 3.58 (dd, 1H,
0
J3,8Z3.2, J8,8 Z11.4 Hz, H-8), 3.49 (dd, 1H, H-7a), 3.41
0
0
0
(dd, 1H, J3,8 Z5.7 Hz, H-8 ), 2.93 (d, 1H, J5,5 Z11.2 Hz,
1
H-5), 2.78 (dd, 1H, J5 ,6Z3.9 Hz, H-50), and 2.73 (ddd, 1H,
0
(aromatic). H NMR (400 MHz): dZ7.61–7.56 and 7.40–
7.24 (2m, 20H, 4Ph), 4.56 and 4.52 (m, 4H, 2CH2Ph), 4.49
(br t, 1H, H-6), 4.31 (br t, 1H, J6,7ZJ7,7aZ5.2 Hz, H-7),
4.24 (br t, 1H, J1,7aZ5.2 Hz, H-7a), 4.14 (s, 1H, H-2), 4.13
H-3). 13C NMR (75 MHz), inter alia: dZ86.81 (C-2), 82.02
(C-1), 80.24 (C-6), 76.96 (C-7), 73.59 and 73.21 (2CH2Ph),
72.49 (C-3), 71.33 (C-7a), 63.61 (C-8), and 60.31 (C-5).
Anal. Calcd for C22H27NO5: C, 68.55; H, 7.06; N, 3.63.
Found: C, 68.86; H, 7.45; N, 3.38.
(d, 1H, H-1), 4.01 (m, 1H, H-5), 3.88 (dd, 1H, J5,8Z5.5,
0
0
0
J8,8 Z10.3 Hz, H-8), 3.66 (dd, 1H, J5,8 Z3.6 Hz, H-8 ), and
1.01 (s, 9H, CMe3). 13C NMR (100 MHz), inter alia: dZ
173.70 (C-3), 85.41 (C-6), 80.74 (C-7), 80.59 (C-2), 72.59
(C-1), 72.36 and 72.09 (2CH2Ph), 68.29 (C-7a), 62.32
(C-8), 60.67 (C-5), 26.91 (CMe3), and 19.29 (CMe3).
HRMS (LSIMS): m/zZ660.2762 [MCCNa]; calcd for
C38H43NO6NaSi: 660.2757 (deviation K0.8 ppm).
4.1.9. (1R,2R,3R,6R,7R,7aR)-1,2,6,7-Tetrahydroxy-3-
hydroxymethylpyrrolizidine [(C)-6,7-diepicasuarine
(15)]. Compound 14 (400 mg, 1.04 mmol) in methanol
(15 mL) and concentrated HCl (three drops) was hydrogen-
ated with 10% Pd–C (80 mg) at ambient pressure and rt
overnight. TLC (ether/methanol, 5:1) then revealed the
absence of the starting product. The catalyst was filtered off,
washed with methanol and the combined filtrate and
washings treated with Amberlite IRA-400 resin (OHK
form). Evaporation of the solvent afforded pure 15. Yield:
175 mg (87%); white foam; [a]2D4 C8.1 (c, 1, water); Lit.9
4.1.7. (1R,2R,3R,6R,7R,7aR)-1,2-Dibenzyloxy-3-tert-
butyldiphenylsilyloxymethyl-6,7-dihydroxypyrrolizi-
dine (13). To a stirred solution of 12 (1.3 g, 2.1 mmol) in
anhydrous THF (20 mL) was added dropwise a H3B:SMe2
complex solution in the same solvent (10 M, 2.1 mL) under
argon, and the mixture left at rt for 12 h. TLC (EtAcO/
hexane, 3:1) then revealed the absence of 12 and the
presence of a faster-running compound, presumably the
borane–amine complex. MeOH (2 mL) was cautiously
added and the reaction mixture was concentrated to a
residue that was dissolved in MeOH (20 mL) and refluxed
for 4 h, when the borane–amine complex was not observed
by TLC. The reaction mixture was concentrated and the
residue was supported on silica gel and chromatographed
(Et2O/hexane, 10:1) to give pure 13. Yield: 1.16 g (91%);
white foam; [a]2D3 K3, (c, 1). IR (KBr): 3401 (OH), 3069,
1
[a]2D2 C8.4 (c, 0.89, water). H NMR (400 MHz, D2O, pH
7.5): dZ4.21 (m, 1H, H-6), 4.17 (t, 1H, H-1), 4.03 (dd, 1H,
J6,7Z1.8 Hz, H-7), 3.79 (dd, 1H, J1,2Z8.2, J2,3Z9.7 Hz,
0
H-2), 3.66 (dd, 1H, J3,8Z3.2, J8,8 Z12.2 Hz, H-8), 3.49 (dd,
0
0
1H, J3,8 Z6.4 Hz, H-8 ), 3.42 (dd, 1H, J1,7aZ7, J7,7a
4.4 Hz, H-7a), 3.05 (br d, 1H, H-5b), 2.88 (dd, 1H, J5a,6
Z
Z
3.8, J5a,5bZ12.1 Hz, H-5a), and 2.71 (ddd, 1H, H-3). 13C
NMR (100 MHz): dZ80.09 (C-2), 79.25 (C-6), 75.52 (C-7),
74.37 (C-1), 72.97 (C-3), 71.65 (C-7a), 62.95 (C-8), and
60.55 (C-5). HRMS (LSIMS): m/zZ228.0849 [MCCNa];
calcd for C8H15NO5Na: 228.0848 (deviation K0.3 ppm).
1
738 and 700 cmK1 (aromatic). H NMR (400 MHz): dZ
7.70–7.62 and 7.45–7.20 (2m, 20H, 4Ph), 4.62 and 4.55 (2d,
2H, JZ11.8 Hz, CH2Ph), 4.54 and 4.51 (2d, 2H, JZ
12.6 Hz, CH2Ph), 4.28 (t, 1H, J1,2ZJ1,7aZ3.4 Hz, H-1),
4.21 (t, 1H, J2,3Z3.8 Hz, H-2), 4.13 (br s, 1H, H-6), 3.91 (br
s, 1H, H-7), 3.79 (t, 1H, J7,7aZ4.0 Hz, H-7a), 3.76 (dd, 1H,
4.1.10. (1S,2R,5R,6R,7R,7aR)-6,7-Dibenzyloxy-5-tert-
butyldiphenylsilyloxymethyl-1,2-dihydroxypyrrolizidin-
3-one (17). A solution of 8 (1.7 g, 2.12 mmol) in MeOH
(20 mL) was stirred at rt with 10% Pd–C (170 mg) in an H2
atmosphere for 3 h. TLC (EtAcO/hexane, 1:1) then showed
the presence of a compound of lower mobility, presumably
the N-deprotected pyrrolidine (16). The catalyst was filtered
off, washed with MeOH and the combined filtrate and
washings (50 mL) treated with 2 M MeONa (2 mL). After
2 h, TLC (EtAcO/hexane, 1:1) then revealed the presence of
a faster-running product. The mixture was neutralized with
aqueous 10% HCl, supported on silica gel and submitted to
chromatography (Et2O) to afford 17. Yield: 1.14 g (85%);
white foam; [a]2D6 K33 (c, 1). IR (KBr): 3386 (OH), 3069
and 3031 (aromatic), 1694 (C]O), 754 and 700 cmK1
0
0
J3,8Z7.1 Hz, H-8), 3.68 (dd, 1H, J3,8 Z6.6, J8,8 Z10.1 Hz,
H-80), 3.09 (d, 1H, H-5), 3.080 (m, 1H, H-3), 2.97 (dd, 1H,
0
0
J5 ,6Z3.7, J5,5 Z11.3 Hz, H-5 ), 2.79 (br s, 1H, HO-7), and
1.05 (s, 9H, CMe3). 13C NMR (100 MHz), inter alia: dZ
85.55 (C-2), 81.48 (C-1), 79.54 (C-6), 76.48 (C-7), 72.19
(C-3), 72.06 and 72.02 (2CH2Ph), 71.56 (C-7a), 65.75
(C-8), 60.50 (C-5), 26.96 (CMe3), and 19.30 (CMe3).
HRMS (LSIMS): m/zZ646.2965 [MCCNa]; calcd for
C38H45NO5NaSi: 646.2964 (deviation K0.1 ppm).
1
4.1.8. (1R,2R,3R,6R,7R,7aR)-1,2-Dibenzyloxy-6,7-di-
hydroxy-3-hydroxymethylpyrrolizidine (14). To a stirred
solution of 13 (920 mg, 1.47 mmol) in THF (20 mL) was
added TBAF$3H2O (700 mg, 2.2 mmol) and the reaction
mixture refluxed for 3 h. TLC (Et2O/MeOH, 5:1) then
revealed a new compound of lower mobility. The mixture
was supported on silica gel and chromatographed (Et2O/
MeOH, 5:1) to give pure 14. Yield: 510 mg (90%); white
(aromatic). H NMR (400 MHz): dZ7.59–7.56 and 7.41–
7.20 (2m, 20H, 4Ph), 4.68 and 4.48 (2d, 2H, JZ11.9 Hz,
CH2Ph), 4.52 and 4.48 (2d, 2H, JZ11.8 Hz, CH2Ph), 4.36
(t, 1H, J5,6ZJ6,7Z4 Hz, H-6), 4.33 (d, 1H, J1,2Z8.2 Hz,
H-2), 4.08–4.04 (m, 2H, H-1,5), 4.01 (br s, 1H, HO), 3.88 (t,
0
1H, J7,7aZ4.5 Hz, H-7), 3.83 (dd, 1H, J5,8Z5.3, J8,8
Z
0
0
10.6 Hz, H-8), 3.66 (dd, 1H, J5,8 Z4.3 Hz, H-8 ), 3.57 (t,
1H, J1,7aZ5.6 Hz, H-7a), and 1.02 (s, 9H, CMe3). 13C NMR
(100 MHz), inter alia: dZ172.24 (C-3), 86.79 (C-7), 84.69
(C-6), 80.55 (C-1), 78.16 (C-2), 72.01 and 71.88 (2CH2Ph),
solid; mp 174–176 8C (from ether/methanol); [a]2D4 K0.5,
24
[a] K13, (c, 0.7, methanol). IR (KBr): 3392 (OH), 3086,
405