E. Beccalli et al. / Tetrahedron: Asymmetry 15 (2004) 3181–3187
3185
3.5. General procedure for the reactions of 5a and b with
N-benzylhydroxylamine
(3H, d, J = 6.8Hz), 2.11 (1H, dqq, J = 6.8, 6.8,
8.9Hz), 3.55–3.64 (1H, m), 3.84 (1H, dd, J = 3.6,
8.9Hz), 4.10(1H, dd, J = 3.3, 3.6Hz), 4.12–4.29 (3H,
overlapping), 4.53 (1H, d, J = 7.8Hz), 6.87 (1H, s),
7.19 (1H, s), 7.26 (1H, d, J = 7.2Hz), 7.32 (2H, dd,
J = 7.2, 7.5Hz), 7.46 (2H, d, J = 7.5Hz); 13C NMR
(100MHz, CDCl3) 17.2 (q), 18.2 (q), 32.9 (d), 48.3 (t),
52.8 (d), 53.0(d), 61.0(t), 68.4 (d), 114.8 (d), 127.8
(d), 128.5 (d), 129.4 (d), 134.2 (d), 137.5 (s), 150.8 (s).
MS: m/z 283 (M+). Anal. Calcd for C17H21N3O: C,
72.06; H, 7.47; N, 14.83. Found C, 71.97; H, 7.51; N,
14.72.
A suspension of N-benzylhydroxylamine hydrochloride
(1.3g, 8.2mmol), NaHCO3 (2.0g, 23mmol) and MgSO4
(16.0g, 130mmol) in dry toluene (150mL) was stirred
for 10min, then a solution of 5a and b (6.7mmol) in tol-
uene (10mL) was added. The mixture was stirred for
24h at reflux, filtered and evaporated. The remaining
slurry was chromatographed on a silica gel column with
the eluent given below.
Entry a: elution with AcOEt/light petroleum/EtOH
(7:2:1) gave 8a (10%) and 7a (46%).
3.5.4. (5S,6R,9S)-8-Benzyl-5-isopropyl-5,6,8,9-tetrahy-
dro-6,9-methanoimidazo[2,1-d][1,2,5]oxadiazepine 7b. Oil.
23
D
3.5.1. (3aS,4S,8bS)-1-Benzyl-4-methyl-1,3a,4,8b-tetra-
hydro-3H-imidazo[10,20:1,2]pyrrolo[3,4-c]isoxazole 8a. Oil.
½a ¼ þ24:2 (c 0.48, CHCl3). 1H NMR (400MHz,
CDCl3, major invertomer) d: 0.92 (3H, d, J = 6.9Hz),
1.15 (3H, d, J = 6.9Hz), 2.19 (1H, dqq, J = 5.6, 6.9,
6.9Hz), 2.44 (1H, br s), 3.68–3.74 (2H, overlapping),
3.75–4.11 (2H, overlapping), 4.52 (1H, d, J = 4.3Hz);
4.74 (1H, br s), 7.03 (1H, br s), 7.09 (1H, br s), 7.19–
7.39 (5H, overlapping); 1H NMR (400MHz, CDCl3,
minor invertomer) d: 0.92 (3H, d, J = 6.9Hz), 1.15 (3H,
d, J = 6.9Hz), 2.19 (1H, dqq, J = 5.6, 6.9, 6.9Hz), 2.36
(1H, br s), 2.62 (1H, br s), 3.15 (1H, br s), 3.75–4.11
(2H, overlapping), 4.52 (1H, d, J = 4.3Hz), 4.88 (1H,
br s), 7.03 (1H, br s), 7.09 (1H, br s), 7.19–7.39 (5H,
overlapping); 1H NMR (400MHz, DMSO, 120ꢁC):
0.92 (3H, d, J = 6.9Hz), 1.09 (3H, d, J = 6.9Hz), 2.20
(1H, dqq, J = 5.6, 6.9, 6.9Hz), 2.36 (1H, d,
J = 11.9Hz), 2.65 (1H, ddd, J = 4.4, 6.2, 11.9Hz), 3.61,
3.81 (2H, AB system, J = 13.6Hz), 3.89 (1H, dd,
J = 1.9, 5.6Hz), 4.38 (1H, d, J = 4.4Hz), 4.82 (1H, dd,
J = 1.9, 6.2Hz), 6.87 (1H, d, J = 1.3Hz), 7.11 (1H, d,
J = 1.3Hz), 7.23–7.38 (5H, overlapping); 13C NMR
(100MHz, CDCl3, major invertomer) d: 19.0(q), 20.6
(q), 31.3 (d), 34.7 (t), 58.0(d), 59.8 (t), 68.0(d), 74.3
(d), 118.8 (d), 127.7 (d), 128.4 (d), 128.8 (d), 129.3 (d),
137.7 (s), 145.3 (s). 13C NMR (100MHz, CDCl3,
minor invertomer) 19.0(q), 20.6 (q), 31.3 (d), 34.7 (t),
58.4 (d), 63.6 (t), 69.6 (d), 74.8 (d), 117.7 (d), 127.8
(d), 128.4 (d), 128.8 (d), 129.3 (d), 137.4 (s), 145.3 (s).
MS: m/z 283 (M+). Anal. Calcd for C17H21N3O: C,
72.06; H, 7.47; N, 14.83. Found C, 72.06; H, 7.33; N,
14.88.
23
D
½a ¼ þ10:7 (c 0.23, CHCl3). 1H NMR (400MHz,
CDCl3, 55ꢁC) d: 1.48 (3H, d, J = 6.5Hz), 3.54 (1H, dddd,
J = 3.3, 3.5, 7.6, 10.8Hz), 3.92 (1H, dd, J = 3.3, 9.0Hz),
4.12–4.31 (3H, overlapping), 4.29 (1H, dq, J = 3.5,
6.5Hz), 4.56 (1H, d, J = 7.6Hz), 6.85 (1H, s), 7.19 (1H,
s), 7.24–7.47 (5H, overlapping); 13C NMR (100MHz,
CDCl3) 22.8 (q), 30.1 (t), 31.6 (d), 58.5 (d), 59.4 (d), 59.6
(t), 113.7 (d), 127.8 (d), 128.7 (d), 129.4 (d), 135.1 (d),
138.7 (s), 152.1 (s). MS: m/z 255 (M+). Anal. Calcd for
C15H17N3O: C, 70.56; H, 6.71; N, 16.46. Found C, 70.61;
H, 6.53; N, 16.26.
3.5.2. (5S,6R,9S)-8-Benzyl-5-methyl-5,6,8,9-tetrahydro-
6,9-methanoimidazo[2,1-d][1,2,5]oxadiazepine 7a. Oil.
23
D
½a ¼ ꢀ7:4 (c 0.64, CHCl3). 1H NMR (400MHz,
CDCl3, major invertomer) d: 1.27 (3H, br s), 2.29 (1H,
br s), 2.85 (1H, br s), 3.30(1H, br s), 3.84 (1H, br s),
4.11 (1H, br s), 4.49 (1H, br s), 4.55 (1H, br s), 7.00
(1H, br s), 7.10(1H, br s), 7.17–7.46 (5H, overlapping);
1H NMR (400MHz, CDCl3, minor invertomer) d: 1.27
(3H, br s), 2.02 (1H, br s), 2.75 (1H, br s), 3.65 (1H,
br s), 3.74–4.68 (3H, overlapping), 5.35 (1H, br s),
6.86 (1H, br s), 7.18 (1H, br s), 7.17–7.46 (5H, overlap-
ping); 1H NMR (400MHz, DMSO, 100ꢁC): 1.42 (3H, d,
J = 6.7Hz), 2.26 (1H, d, J = 11.6Hz), 2.70(1H, ddd,
J = 4.6, 6.2, 11.6Hz), 3.84, 3.64 (2H, AB system,
J = 13.6Hz), 4.12 (1H, dq, J = 1.6, 6.7Hz), 4.37 (1H,
d, J = 4.6Hz), 4.61 (1H, dd, J = 1.6, 6.2Hz), 6.85 (1H,
br s), 7.11 (1H, br s), 7.23–7.43 (5H, overlapping); 13C
NMR (100MHz, CDCl3, major invertomer) d: 18.4 (q),
36.8 (t), 57.2 (d), 57.4 (d), 59.6 (t), 76.5 (d), 117.4 (d),
127.8 (d), 128.8 (d), 129.5 (d), 130.2 (d), 137.6 (s),
145.0(s); 13C NMR (100MHz, CDCl3, minor inver-
tomer) 18.4 (q), 36.8 (t), 53.0(d), 53.9 (d), 59.6 (t),
76.9 (d), 117.0(d), 127.8 (d), 128.8 (d), 129.5 (d), 130.2
(d), 137.6 (s), 145.0(s). MS: m/z 255 (M+). Anal. Calcd
for C15H17N3O: C, 70.56; H, 6.71; N, 16.46. Found C,
70.39; H, 6.74; N, 16.52.
3.6. General procedure for the hydrogenation of com-
pounds 7a and b and 8a and b
A suspension of 20% Pd(OH)2/C (53mg, 0.078mmol)
and isoxazolidinic compound (0.039mmol) in a 0.09M
HCl solution in MeOH (10mL) was stirred under H2
for 24h. After filtration through Celite, the solvent
was removed under reduced pressure to give 1,3-amino-
alcohol hydrochloride as a white solid. The latter was
treated with H2O (2mL) and KOH (75mg, 1.34mmol)
and extracted with CHCl3 (5 · 50mL). The organic
solution was dried over Na2SO4 and evaporated under
reduced pressure to give 1,3-aminoalcohol.
Entry b: elution with AcOEt gave 8b (38%) and 7b
(31%).
3.5.3.
(3aS,4S,8bS)-1-Benzyl-4-isopropyl-1,3a,4,8b-
tetrahydro-3H-imidazo[10,20:1,2]pyrrolo[3,4-c]isoxazole 8b.
3.6.1. (5S,6R,8S)-8-Amino-5-methyl-5,6,7,8-tetrahydro-
imidazo[1,2-a]pyridin-6-ol
23
Oil. ½a ¼ þ6:7 (c 0.804, CHCl3). 1H NMR (400
9a. Yield:
63%.
Oil.
D
23
D
MHz, CDCl3, 55ꢁC): 0.80 (3H, d, J = 6.8Hz), 0.94
½a ¼ ꢀ15:2 (c 0.09, CHCl3). IR (nujol): 3684, 3619,