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E. Kiss et al. / Tetrahedron 67 (2011) 9173e9178
at room temperature. The resulting white precipitate was filtered
off, washed with water (20 mL) and pentane (15 mL) and dissolved
in CH2Cl2 (200 mL). Saturated aqueous NaHCO3 (140 mL) was
added and the mixture was stirred at room temperature for 2 h. The
organic phase was separated and the aqueous phase was extracted
with CH2Cl2 (50 mL). The combined organic layers were dried over
MgSO4, filtered and concentrated to yield the corresponding crude
imines. These products were used in the next step without further
purification.
concentrated to yield the corresponding oxaziridine. These prod-
ucts were used without further purification.
4. 2. 2.1. (ꢁ)-trans-3-Phenyl-2-tosyl-1, 2-oxaziridine
(9a)13. Following the general procedure 9a was obtained as a white
solid in 76% yield (1.08 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼7.93
(d, J¼8.3 Hz, 2H), 7.52e7.32 (m, 7H), 5.45 (s, 1H), 2.49 (s, 3H). 13C
NMR (75 MHz, CDCl3):
d
(ppm)¼146.4, 131.5, 131.4, 130.5, 130.0,
129.4, 128.7, 128.2, 76.3, 21.8. IR (neat):
n
(cmꢀ1)¼3068, 2923, 1595,
1458, 1388, 1348s, 1240, 1167s, 1090, 837, 813, 779, 717.
4.2.1.1. (E)-Phenyl-N-tosylmethanimine (10a)11. Following the
general procedure and using non-distilled benzaldehyde, 10a was
obtained as a white solid in 48% yield (3.75 g). 1H NMR (500 MHz,
4. 2. 2. 2. (ꢁ)-trans-3-Propyl-2-tosyl-1, 2-oxaziridine
(9b). Following the general procedure 9b was obtained as a white
CDCl3):
d
(ppm)¼9.03 (s, 1H), 7.94 (d, J¼7.2 Hz, 2H), 7.89 (d,
solid in 86% yield (1.03 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼7.86
J¼8.3 Hz, 2H), 7.61 (t, J¼7.4 Hz, 1H), 7.44e7.52 (m, 2H), 7.35 (d,
(d, J¼8.3 Hz, 2H), 7.39 (d, J¼8.3 Hz, 2H), 4.65 (t, J¼4.9 Hz, 1H), 2.47
(s, 3H), 1.83e1.72 (m, 2H), 1.62e1.43 (m, 2H), 0.98 (t, J¼7.4 Hz, 3H).
J¼8.3 Hz, 2H), 2.44 (s, 3H). 13C NMR (125 MHz, CDCl3):
d
(ppm)¼
170.1, 144.6, 135.1, 134.9, 132.3, 131.3, 129.8, 129.1, 128.1, 21.6. IR
13C NMR (75 MHz, CDCl3):
32.6, 21.7, 17.0, 13.6. IR (neat):
1406, 1348s, 1242, 1218, 1167s, 1090, 840, 813, 707. MS (APCI): m/
z¼242 ([MþH]þ, 92%), 226 (100%), 200 (74%), 155 (64%), 108 (44%).
HRMS (ESꢀ): for C11H14NO3S, calculated: 240.0694, found:
240.0706.
d
(ppm)¼146.1, 131.6, 129.9, 129.2, 78.1,
(neat):
n
(cmꢀ1)¼2921,1596s,1574s,1450,1321s,1222,1155s,1088s,
n
(cmꢀ1)¼2964, 2877, 1595, 1464,
864, 810, 783, 757.
4.2.1.2. (E)-N-Tosylbutan-1-imine (10b)11. Following the general
procedure 10b was obtained as a white solid in 78% yield (5.24 g).
1H NMR (300 MHz, CDCl3):
d
(ppm)¼8.60 (t, J¼4.6 Hz, 1H), 7.81 (d,
J¼8.3 Hz, 2H), 7.34 (d, J¼8.3 Hz, 2H), 2.49 (dt, J¼7.4, 4.6 Hz, 2H),
4.2.2.3. (ꢁ)-trans-3-iso-Propyl-2-tosyl-1,2-oxaziridine
(9c). Following the general procedure 9c was obtained as a white
2.43 (s, 3H), 1.75e1.56 (m, 2H), 0.95 (t, J¼7.4 Hz, 3H). 13C NMR
(75 MHz, CDCl3):
21.6, 18.1, 13.6. IR (neat):
1159s, 1092, 813, 748.
d
(ppm)¼178.3, 144.6, 134.6, 129.8, 128.1, 37.7,
solid in 94% yield (1.14 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼
n
(cmꢀ1)¼2964, 2933, 1626s, 1458, 1321s,
7.86 (d, J¼8.3 Hz, 2H), 7.39 (d, J¼8.3 Hz, 2H), 4.48 (d, J¼5.6 Hz, 1H),
2.47 (s, 3H), 1.82e1.95 (m, 1H), 1.02 (dd, J¼6.9, 3.7 Hz, 6H). 13C
NMR (75 MHz, CDCl3):
29.5, 21.8, 16.5, 16.4. IR (neat):
1406, 1348s, 1245, 1169s, 1089, 867, 813, 759, 723s. MS (APCI): m/
z¼242 ([MþH]þ, 87%), 226 (37%), 200 (100%), 155 (48%), 108 (22%).
HRMS (ESꢀ): for C11H14NO3S, calculated: 240.0694, found:
240.0686.
d
(ppm)¼146.1, 131.7, 129.9, 129.2, 81.9,
4.2.1.3. (E)-2-Methyl-N-tosylpropan-1-imine (10c)11. Following
the general procedure 10c was obtained as a white solid in 81%
n
(cmꢀ1)¼2972, 2935, 1597, 1469,
yield (5.48 g). 1H NMR (500 MHz, CDCl3):
d
(ppm)¼8.51 (t, J¼4.3 Hz,
1H), 7.81 (d, J¼8.3 Hz, 2H), 7.34 (d, J¼8.3 Hz, 2H), 2.69 (heptd, J¼6.9,
4.3 Hz, 1H), 2.45 (s, 3H), 1.16 (d, J¼6.9 Hz, 6H). 13C NMR (125 MHz,
CDCl3):
(neat):
802, 781, 761.
d
(ppm)¼181.8, 144.6, 134.7, 129.8, 128.1, 34.6, 21.6, 18.0. IR
(cmꢀ1)¼2970, 2931, 1625s, 1463, 1321s, 1159s, 1089, 813,
n
4.2.2.4. (ꢁ)-trans-3-sec-Butyl-2-tosyl-1,2-oxaziridine
(9d). Following the general procedure an approximately 2:1 mix-
ture of diastereoisomers of 9d was obtained as colourless oil in 79%
4.2.1.4. (E)-2-Methyl-N-tosylbutan-1-imine (10d)12. Following
the general procedure 10d was obtained as a white solid in 25%
yield (1.16 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼7.86 (d, J¼8.3 Hz,
2H), 7.39 (d, J¼8.3 Hz, 2H), 4.48 (d, J¼6.0 Hz, 1H, dia1), 4.47 (d,
J¼5.8 Hz, 1H, dia2), 2.47 (s, 3H), 1.72e1.27 (m, 3H), 1.05e0.90 (m,
yield (1.79 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼8.49 (d,
J¼5.1 Hz, 1H), 7.81 (d, J¼8.3 Hz, 2H), 7.34 (d, J¼8.3 Hz, 2H),
2.44e2.58 (m, 1H), 2.44 (s, 3H), 1.75e1.40 (m, 2H), 1.13 (d, J¼6.8 Hz,
6H). 13C NMR (75 MHz, CDCl3):
81.7 (dia1), 81.6 (dia2), 36.2, 25.0 (dia1), 24.8 (dia2), 21.7, 14.0
(dia2), 13.8 (dia1), 11.1. IR (neat):
1348s, 1169s, 1090, 867, 815, 757, 723. MS (APCI): m/z¼256
([MþH]þ, 85%), 240 (100%), 200 (72%), 155 (34%). HRMS (ESꢀ): for
C12H16NO3S, calculated: 254.0851, found: 254.0843.
d
(ppm)¼146.1, 131.7, 129.9, 129.2,
3H), 0.90 (t, J¼7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d
(ppm)¼
n
(cmꢀ1)¼2968, 2940, 1597, 1462,
181.8, 144.6, 134.8, 129.8, 128.0, 41.2, 26.0, 21.6, 15.4, 11.3. IR (neat):
n
(cmꢀ1)¼2966, 2931, 1628s, 1458, 1323s, 1159s, 1092, 813, 773.
4.2.1.5. (E)-Cyclohexyl-N-tosylmethanimine (10e)10a. Following
the general procedure 10e was obtained as a white solid in 78%
4.2.2.5. (ꢁ)-trans-3-Cyclohexyl-2-tosyl-1,2-oxaziridine
(9e). Following the general procedure 9e was obtained as a white
yield (6.18 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼8.48 (d,
J¼4.4 Hz, 1H), 7.80 (d, J¼8.3 Hz, 2H), 7.33 (d, J¼8.3 Hz, 2H), 2.44 (m,
solid in 89% yield (1.25 g). 1H NMR (300 MHz, CDCl3):
d
(ppm)¼7.85
4H), 2.00e1.50 (m, 5H), 1.10e1.50 (m, 5H). 13C NMR (75 MHz,
(d, J¼8.3 Hz, 2H), 7.39 (d, J¼8.3 Hz, 2H), 4.47 (d, J¼5.7 Hz, 1H), 2.47
CDCl3):
25.0, 21.6. IR (neat):
1325s, 1161s, 1089, 813, 779.
d
(ppm)¼181.0, 144.5, 134.8, 129.7, 128.0, 43.6, 28.3, 25.6,
(s, 3H), 1.90e1.50 (m, 5H), 1.00e1.40 (m, 5H). 13C NMR (75 MHz,
n
(cmꢀ1)¼2928s, 2854, 1732, 1626s, 1450,
CDCl3):
25.0, 21.8. IR (neat):
d
(ppm)¼146.1,131.7,129.9,129.2, 81.2, 38.6, 27.0, 26.8, 25.9,
n
(cmꢀ1)¼2929, 2854, 1597, 1450, 1348s, 1169s,
1090, 860, 813, 721. MS (APCI): m/z¼282 ([MþH]þ, 62%), 266
(100%), 200 (18%), 184 (16%), 155 (15%). HRMS (ESꢀ): for
C14H18NO3S, calculated: 280.1007, found: 280.1010.
4.2.2. General procedure for the oxidation of imines. The previously
obtained imines 10aee (5 mmol) were dissolved in toluene (50 mL)
and an aqueous solution of K2CO3 (30 mL, 1.4 M) was added. This
mixture was stirred vigorously while an aqueous solution of Oxone
(30 mL, 0.4 M) was added slowly over 30 min. After an additional
30 min reaction time, if necessary, a further amount of Oxone was
added to achieve complete conversion. Then, the layers were sep-
arated and the aqueous layer was extracted with toluene (30 mL).
The combined organic phases were washed with 10% aqueous
Na2SO3 solution (20 mL), dried over MgSO4, filtered and
4.3. Preparation of (3S,aS)-tert-butyl 3-(N-benzyl-N-a-
methylbenzyl)amino-hexanoate 6
In a two-necked dry flask maintained under an argon atmo-
sphere, (S)-N-benzyl-1-phenylethanamine (335 L, 1.6 mmol,
m
1.6 equiv) was dissolved in dry, freshly distilled THF (9 mL). The
solution was cooled to ꢀ78 ꢂC and n-butyl-lithium (940
mL, 1.6 M in