5508
P. Crotti et al. / Tetrahedron 63 (2007) 5501–5509
anti 1-(Benzyloxy)-2-azido-3-hexanol (14): a liquid. (Found:
C, 62.46; H, 7.51; N, 16.49. C13H19N3O2 requires: C,
62.63; H, 7.68; N, 16.85.) FTIR n 3450, 2102, 1454,
(0.032 g, 0.12 mmol) in 10 M LiClO4 in MeOH (1 mL) was
stirred at 80 ꢀC for 18 h. After cooling, dilution with Et2O
and evaporation of the washed (water) organic solution
afforded a crude liquid product (0.034 g, 96% yield) consist-
ing of a 95:5 mixture of MUs 32 (C-3 product) and 31 (C-2
product) (GC).
1287, 1099 cmꢂ1 1H NMR d 7.30–7.36 (m, 5H), 4.58
;
(s, 2H), 3.73 (d, 2H, J¼6.0 Hz), 3.48–3.69 (m, 2H),
1.26–1.65 (m, 4H), 0.94 (t, 3H, J¼6.8 Hz). 13C
NMR d 137.6, 128.7, 128.1, 73.8, 71.9, 70.1, 65.4, 35.7,
19.1, 14.2.
The same procedure applied to aziridine (E)-10 (0.050 g,
0.19 mmol) at 80 ꢀC for 5 days afforded a crude product
(0.047 g) consisting of a very complex reaction mixture
(GC), which was subjected to preparative TLC using a 7:3
hexane/AcOEt mixture.8a Extraction of the two most intense
bands (the slower moving band contained 50) afforded the
unreacted aziridine (E)-10 (0.030 g) and pure syn 1-(benzyl-
oxy)-3,4-dimethyl-4-methoxy-2-(methoxycarbonylamino)-
pentane (50) (0.005 g, 8% yield), as a liquid. (Found: C,
65.78; H, 8.71; N, 4.47. C17H27NO3 requires: C, 65.99; H,
5.1.4. Synthesis of MUs 31, 36, and 39: typical procedure.
A solution of azido alcohol 13 (0.094 g, 0.38 mmol) in
anhydrous THF (1 mL) was added to a stirred suspension
of NaH (0.030 g of a 60% dispersion in mineral oil,
0.75 mmol) in anhydrous THF (3 mL). After 30 min
stirring at room temperature, MeI (0.568 g, 0.25 mL,
4.0 mmol) was added and stirring was prolonged for 18 h
at the same temperature. Dilution with ether and evapora-
tion of the washed (saturated aqueous NaCl) organic solution
afforded a crude product consisting of methoxy azide 43
(0.090 g, 90% yield), which was directly used in the next
step without any further purification. FTIR n 3368, 2104,
8.80; N, 4.53.) FTIR
n 3355, 1720, 1250, 1448,
1084 cmꢂ1; H NMR d 7.25–7.38 (m, 5H), 5.82–5.96 (m,
1H, NH), 4.56 (d, 1H, J¼12.0 Hz), 4.46 (d, 1H, J¼
12.0 Hz), 3.47–3.82 (m, 3H), 3.65 (s, 3H), 3.17 (s, 3H),
1.97–2.12 (m, 1H), 1.18 (m, 3H), 1.12 (s, 3H), 0.90 (d,
3H, J¼7.1 Hz). 13C NMR d 157.7, 128.6, 127.8, 127.7,
73.3, 70.8, 59.4, 53.7, 49.1, 42.0, 24.3, 21.5, 20.1. MS
(m/z) 73, 91, 101, 188, 208, 309 (M+).
1
1
1454, 1280, 1099 cmꢂ1; H NMR d 7.30–7.36 (m, 5H),
4.58 (s, 2H), 3.65 (d, 2H, J¼3.4 Hz), 3.55–3.76 (m, 1H),
3.39 (s, 3H), 3.25–3.34 (m, 1H), 1.27–1.63 (m, 4H), 0.94
(t, 3H, J¼6.3 Hz).
A solution of 43 (0.090 g, 0.34 mmol) in anhydrous Et2O
(1 mL) was added to a stirred suspension of LiAlH4
(0.053 g, 1.39 mmol) in anhydrous Et2O (3 mL). After 2 h
stirring at the same temperature, the reaction mixture was di-
luted with Et2O and carefully treated with water and 10%
aqueous NaOH in order to destroy the excess of hydride.
Evaporation of the organic solution afforded a crude prod-
uct, consisting of amine 44 (0.069 g, 85% yield) [FTIR n
3410, 3340, 1456, 1398, 1099 cmꢂ1; 1H NMR d 7.29–7.33
(m, 5H), 4.54 (s, 2H), 3.60–3.63 (m, 2H), 3.44 (s, 3H),
3.21 (dd, 1H, J¼9.3, 4.4 Hz), 2.92–3.03 (m, 1H), 1.52–
1.67 (m, 2H, NH2), 1.20–1.50 (m, 4H), 0.92 (t, 3H, J¼
6.3 Hz)], which was dissolved in anhydrous Et2O (3 mL)
and treated with ClCOOMe (0.024 mL, 0.32 mmol) in the
presence of Et3N (0.044 mL, 0.32 mmol). After 18 h stirring
at room temperature, dilution with Et2O and evaporation of
the washed (saturated aqueous NaHCO3 and water) organic
solution afforded a crude product (0.077 g), which was sub-
jected to preparative TLC (a 7:3 hexane/AcOEt mixture was
used as the eluant). Extraction of the most intense band af-
forded pure anti 1-(benzyloxy)-2-methoxy-3-(methoxycarbo-
nylamino)-hexane (31) (0.048 g, 47% yield), as a liquid.
(Found: C, 65.37; H, 8.28; N, 4.50. C16H25NO4 requires:
C, 65.06; H, 8.53; N, 4.74.) FTIR n 3441, 1714, 1546,
The same procedure applied to aziridine (E)-11 (0.050 g,
0.19 mmol) afforded a crude product (0.040 g) essentially
consisting of the cyclic compound 53 and the benzyl methyl
ether (1H NMR), which was subjected to flash chromato-
graphy. Elution with a 9:1 hexane/AcOEt mixture afforded
the benzyl methyl ether (0.014 g, 65% yield) [FTIR n
1
1454, 1101 cmꢂ1; H NMR d 7.22–7.45 (m, 5H), 4.46 (s,
2H), 3.39 (s, 3H)] and trans 2-ethyl-3-(methoxycarbonyl-
amino)-tetrahydrofurane (53) (0.018 g, 54% yield), as a
liquid. (Found: C, 55.68; H, 8.64; N, 7.81. C8H15NO3 re-
quires: C, 55.47; H, 8.73; N, 8.09.) FTIR n 3315, 2954,
1
2879, 1705, 1543, 1458, 1244 cmꢂ1; H NMR d 4.79–4.96
(m, 1H), 3.79–4.00 (m, 3H), 3.65 (s, 3H), 3.50 (dd, 1H,
J¼12.2, 5.3 Hz), 2.14–2.36 (m, 1H), 1.65–1.84 (m, 1H),
1.38–1.65 (m, 2H), 0.95 (t, 3H, J¼7.4 Hz). 13C NMR
d 154.7, 85.8, 66.2, 55.8, 52.3, 33.4, 26.7, 10.3. MS (m/z)
59, 70, 100, 115, 144, 173 (M+).
5.2. Reactions in the gas-phase
5.2.1. Materials. Oxygen and trimethylamine were high-
purity gases from Matheson Gas Products Inc., deuterium
(99.98%) was purchased from Aldrich and all were used
without further purification. The chemical purity of the start-
ing activated aziridines 7–12 was verified by analytical gas
chromatography on the same columns used for the analysis
of their gas-phase products.
1
1454, 1249, 1089 cmꢂ1; H NMR d 7.27–7.32 (m, 5H),
5.20 (d, 1H, J¼9.3 Hz, NH), 4.54 (d, 1H, J¼12.3 Hz),
4.50 (d, 1H, J¼12.3 Hz), 3.74–3.97 (m, 1H), 3.64 (s, 3H),
3.51–3.60 (m, 2H), 3.42 (s, 3H), 3.31–3.37 (m, 1H), 1.24–
1.47 (m, 4H), 0.88 (t, 3H, J¼6.3 Hz). 13C NMR d 157.3,
138.0, 128.6, 127.9, 81.5, 73.7, 70.3, 58.6, 52.1, 51.8,
33.1, 19.4, 14.1. MS (m/z) 77, 87, 91, 142, 177, 295 (M+).
5.2.2. Procedure. The gaseous mixtures were prepared by
conventional procedures with the use of a greaseless vacuum
line. The selected aziridine derivative (0.007–0.009 mmol),
methanol (0.021–0.026 mmol), the thermal radical scaven-
ger O2, and trimethylamine were introduced into carefully
outgassed 250-mL Pyrex bulbs, each equipped with
a break-seal arm. The bulbs were filled with D2, and were
then allowed to come to room temperature; the fragile
ampoules were broken, and the gaseous components were
MUs 36 and 39 were prepared following the typical proce-
dure (see Supplementary data).
5.1.5. Methanolysis of aziridines 7–12 with 10 M LiClO4
in MeOH: typical procedure. A solution of aziridine (E)-7