I
C. Parmeggiani et al.
Special Topic
Synthesis
N-(2-Nonyl)-N-phenylmethyleneamine N-Oxide (2c)
(2R,3R,4R)-3,4-Bis(benzyloxy)-2-[(benzyloxy)methyl]-3,4-dihy-
dro-2H-pyrrole 1-Oxide (2f)30,31,33 and (3R,4R)-3,4-Bis(benzyloxy)-
5-[(benzyloxy)methyl]-3,4-dihydro-2H-pyrrole 1-Oxide (3f)34
The general procedure was applied to hydroxylamine 1c (26 mg, 0.10
mmol). After flash chromatography (gradient eluent from PE/EtOAc
9:1 to PE/EtOAc 5:1) compound 2c (16 mg, 0.06 mmol) was isolated in
65% yield; colorless oil; Rf = 0.30 (PE/EtOAc 9:1).
The general procedure was applied to hydroxylamine 1f (70 mg, 0.17
mmol) affording the crude nitrones (>98% purity) 2f [Rf = 0.49
(PE/EtOAc 1:2)] and 3f [Rf = 0.48 (PE/EtOAc 1:2)] in 89% total yield and
5:1 ratio (63 mg, 0.15 mmol). The NMR spectra were in agreement
with those reported in the literature.
1H NMR (CDCl3, 200 MHz): δ (selected signals) = 6.92 (br s, 1 H, 2f),
4.41–4.39 (m, 1 H, 2f), 4.05–4.03 (m, 2 H, 2f), 3.82–3.73 (m, 1 H, 2f).
IR (CDCl3): 2956, 2929, 2857, 2231, 1580, 1453, 1374, 1322, 1160,
1149, 1029 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 8.27–8.24 (m, 2 H, ArH), 7.43–7.40 (m,
4 H, ArH, H-1), 4.02–3.93 (m, 1 H, H-2), 2.09–2.00 (m, 1 H, Ha-4),
1.67–1.65 (m, 1 H), 1.61–1.56 (m, 1 H, Hb-4), 1.48 (d, J = 6.4 Hz, 3 H,
H-3), 1.36–1.24 (m, 9 H), 0.85 (t, J = 6.8 Hz, 3 H, CH3).
2,3:5,6-Di[O-(1-methylethylidene)]-N-(phenylmethylene)-α-D-
mannofuranosylamine N-Oxide (21)13,35
13C NMR (CDCl3, 50 MHz): δ = 132.4 (d, C-1), 130.8 (s, Ar), 129.9–
128.4 (5 C, d, Ar), 72.7 (d, C-2), 34.4 (t, C-4), 31.7–22.5 (5 C, t, C-5 to C-
9), 14.4 (q, C-3), 13.9 (q, C-10).
The general procedure was applied to hydroxylamine 7 (88 mg, 0.24
mmol) affording nitrone 21 in 95% yield (83 mg, 0.23 mmol) with a
purity of >98%; white solid; mp 176–178 °C; Rf = 0.40 (PE/EtOAc 3:1).
1H NMR (CDCl3, 200 MHz): δ = 8.26–8.21 (m, 2 H, ArH), 7.56 (s, 1 H),
7.48–7.41 (m, 3 H, ArH), 5.47 (s, 1 H), 5.35 (d, J = 6.0 Hz, 1 H), 5.00 (dd,
J = 6.0, 3.9 Hz, 1 H), 4.58 (dd, J = 7.2, 3.9 Hz, 1 H), 4.41 (dd, J = 12.6, 5.5
Hz, 1 H), 4.11 (d, J = 7.0 Hz, 2 H), 1.53 (s, 3 H, CH3), 1.46 (s, 3 H, CH3),
1.39 (s, 3 H, CH3), 1.37 (s, 3 H, CH3).
MS (ESI): m/z = 268.99 (100) [M + Na]+.
Anal. Calcd for C16H25NO: C, 77.68; H, 10.19; N, 5.66. Found: C, 77.88;
H, 10.02; N, 5.37.
(2R,3S,4S)-3,4-Bis(benzyloxy)-2-[(benzyloxy)methyl]-3,4-dihydro-
2H-pyrrole 1-Oxide (2d)30,31 and (3S,4S)-3,4-Bis(benzyloxy)-5-
[(benzyloxy)methyl]-3,4-dihydro-2H-pyrrole 1-Oxide (3d)
The general procedure was applied to hydroxylamine 1d (162 mg,
0.17 mmol) affording nitrones 2d and 3d quantitatively (71 mg, 0.17
mmol) in 6:1 ratio with a purity of >98%.
Dimethyl (4S,5R)-2-{(3aR,4R,6aR)-Tetrahydro-2,2-dimethylfuro-
[3,4-d][1,3]dioxol-4-yl}isoxazolidine-4,5-dicarboxylate (22) and
Dimethyl (4R,5S)-2-{(3aR,4R,6aR)-Tetrahydro-2,2-dimethylfu-
ro[3,4-d][1,3]dioxol-4-yl}isoxazolidine-4,5-dicarboxylate (23)13
2d
Reaction was performed by simple addition of dimethyl maleate (17
μL, 1.7 equiv, 0.14 mmol) to the reaction mixture of the general pro-
cedure for the oxidation of hydroxylamine 5 (16 mg, 0.08 mmol) with
o-iodoxybenzoic acid (IBX). The two diastereoisomeric cycloadducts,
inseparable by column chromatography, were obtained in 50% yield
(11.8 mg, 0.04 mmol).
1H NMR (CDCl3, 400 MHz): δ (mixture of two diastereoisomers) =
4.86–4.72 (m, 3 H + 3 H), 4.65 (s, 1 H), 4.54 (s, 1 H), 3.96–3.81 (m, 3 H
+ 3 H), 3.60 (s, 3 H), 3.59 (s, 3 H), 3.58 (s, 3 H), 3.57 (s, 3 H), 3.50–3.44
(m, 1 H + 1 H), 3.27–3.15 (m, 1 H + 1 H), 1.36 (s, 3 H), 1.35 (s, 3 H),
1.25 (s, 3 H), 1.24 (s, 3 H).
Colorless oil; Rf = 0.21 (PE/EtOAc 1:3).
1H NMR (CDCl3, 400 MHz): δ = 7.38–7.25 (m, 15 H, ArH), 6.80 (br s, 1
H, H-2), 4.77–4.75 (m, 1 H, H-3), 4.68–4.56 (m, 4 H, 2 × CH2Ph), 4.51
(d, J = 11.7 Hz, 2 H, CH2Ph), 4.37 (dd, J = 7.6, 4.5 Hz, 1 H, H-4), 4.16–
4.13 (m, 1 H, H-5), 3.98 (dd, J = 9.9, 4.5 Hz, 1 H, Ha-6), 3.82 (dd, J = 9.9,
2.1 Hz, 1 H, Hb-6).
3d
Colorless oil; Rf = 0.30 (PE/EtOAc 1:3); [α]D29 +73.7 (c 0.73, CHCl3).
IR (CDCl3): 3690, 3610, 3091, 3067, 3033, 2926, 2866, 2356, 2330,
2247, 1602, 1455, 1251, 1097, 1029 cm–1
.
Benzyl 5-[Benzylidene(oxido)amino]-5-deoxy-2,3-O-(1-methyl-
ethylidene)-α-D-lyxofuranoside (25) and Benzyl 2,3-O-(1-Methyl-
ethylidene)-5-deoxy-N-benzyl-D-lyxofuranosylamine N-Oxide (26)
1H NMR (CDCl3, 400 MHz): δ = 7.38–7.16 (m, 15 H, ArH), 4.78 (br s, 1
H, H-3), 4.68–4.57 (m, 5 H, 2 × CH2Ph and Ha-6), 4.45 (s, 2 H, CH2Ph),
4.37–4.28 (m, 2 H, Ha-5 and Hb-6), 4.12 (d, J = 6.0 Hz, 1 H, H-4), 3.88
(d, J = 15 Hz, 1 H, Hb-5).
13C NMR (CDCl3, 100 MHz): δ = 143.2 (d, C-2), 137.4, 137,2, 136.8 (s, 3
C, Ar), 128.6–127.8 (d, 15 C, Ar), 83.8 (d, C-3), 76.5 (d, C-4), 73.6, 72.5,
71.6 (t, CH2Ph), 67.4 (t, C-5), 62.5 (t, C-6).
The general procedure was applied to hydroxylamine 8 (40 mg, 0.10
mmol). The disappearance of the starting material was assessed by a
TLC control (Rf = 0.54 in PE/EtOAc 2:1). The reaction mixture was sub-
sequently washed with sat. aq NaHCO3 (3 × 10 mL) and the solvent
was evaporated under vacuum, affording a 1.8:1 mixture of nitrones
25 and 26 (as attested by integration of selected signals in the 1H NMR
spectrum of the crude mixture). The crude was purified by flash col-
umn chromatography (eluent: PE/EtOAc 1:1) to afford 20 mg (0.05
mmol) of 25 and 11 mg (0.03 mmol) of 26, in 81% overall yield.
MS (ESI): m/z (%) = 440.19 (100, [M + Na]+), 418.18 (54, [M + H]+).
Anal. Calcd for C26H27NO4: C, 74.80; H, 6.52; N, 3.35. Found: C, 74.59;
H, 6.19; N, 3.36.
(2R,3R,4S)-3,4-Bis(benzyloxy)-2-[(benzyloxy)methyl]-3,4-dihydro-
2H-pyrrole 1-Oxide (2e)30,32
25
Colorless oil; Rf = 0.46 (CHCl3/Et2O 1:1); [α]D23 +78.2 (c 0.85, CHCl3).
The general procedure was applied to hydroxylamine 1e (67 mg, 0.16
mmol) affording nitrones 2e/3e in >95:5 ratio. After purification by
flash column chromatography (eluent: PE/EtOAc 1:3), only 2e was
isolated in 94% yield (63 mg, 0.15 mmol); waxy solid; Rf = 0.24
(PE/EtOAc 1:2).
IR (CDCl3): 3690, 3607, 3545, 3435, 3091, 3068, 3034, 2993, 2939,
2882, 2248, 1732, 1586, 1498, 1455, 1211, 1164, 1080 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 8.28–8.27 (m, 2 H, ArH), 7.51 (s, 1 H,
N=CHPh), 7.45–7.43 (m, 3 H, ArH), 7.34–7.26 (m, 5 H, ArH), 5.10 (s, 1
H, H-1), 4.84–4.83 (m, 2 H, H-3, H-4), 4.70 (d, J = 5.4, 1 H, H-2), 4.64 (d,
1H NMR (CDCl3, 200 MHz): δ = 7.34–7.19 (m, 15 H), 6.93 (s, 1 H),
4.73–4.38 (m, 8 H), 4.18–4.09 (m, 3 H), 3.66–3.00 (m, 1 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K