ꢁ
F. Dufrasne and J. Neve
744
and conserved at ꢃ20ꢂC. 1H NMR (300 MHz, CDCl3): ꢁ ¼ 7.42 (m, 5Haromatic), 6.82 (br, NH),
5.78 (d, J ¼ 3.3 Hz, H-1), 4.39 (m, H-2), 2.91 (s, CH3), 1.22 (d, J ¼ 6.9 Hz, CH3) ppm; 13C NMR
(75 MHz, CDCl3): ꢁ ¼ 157.2 (q, J ¼ 34 Hz, C¼O), 135.3 (C-1ar), 129.9 (C-3ar, C-5ar), 129.6
(C-4ar), 126.6 (C-2ar, C-6ar), 116.3 (q, J ¼ 288 Hz, CF3), 83.9 (CH3S), 51.1 (C-1), 39.2 (C-2), 13.8
(C-3) ppm; IR (film): ꢂꢂ¼ 3320, 3060, 2925, 1789, 1725, 1700, 1549, 1453, 1365, 1212, 1143, 948,
848, 747, 700 cmꢃ1
.
l- and u-N-Trifluoroacetyl-2-amino-1-bromo-1-phenylpropane (l- and u-5, C11H11BrF3NO)
To a solution of 1 g of u-3 (4mmol) in 25cm3 of solvent 3.42 g of dibromotriphenylphosphorane
(8mmol) and imidazole were added (see Table 2 for exact conditions). The solvent was heated during
4 h. After cooling, toluene was added. The organic layer was washed with brine and evaporated. The
residue was purified by flash chromatography (silicagel, CH2Cl2) to give 5 as a white solid. Analysis of
1
ꢀ
the crude product: mixture l=u 50:50. H NMR (300MHz, CDCl3): ꢁ ¼ 7.35 (5Haromatic), 6.67 (br,
a
b
ꢀꢀ
ꢀ
ꢀꢀ
NH), 6.58 (br, NH), 5.23 (d, J ¼ 4.6 Hz, H-1), 5.04 (d, J ¼ 6.2 Hz, H-1), 4.49 (m, H-2), 4.37
(m, H-2), 1.30 (d, CH3), 1.28 (d, CH3) ppm; 13C NMR (75 MHz, CDCl3): ꢁ ¼ 156.7 (q, J ¼ 37 Hz,
ꢀ
ꢀꢀ
ꢀ
ꢀꢀ
C¼O), 138.2 (C-1ar), 137.5 (C-1ar), 129.4, 129.2, 129.1, 129, 128.5, 128.2, 116 (q, J ¼ 288 Hz,
ꢀ
ꢀꢀ
ꢀ
ꢀꢀ
ꢀ
ꢀꢀ
CF3), 59.3 (C-1), 58 (C-1), 52 (C-2), 51.9 (C-2), 19.1 (C-3), 16.4 (C-3) ppm; IR (KBr):
ꢂꢂ¼ 3315, 1718, 1696, 1558, 1448, 1248, 1217, 1160, 721, 694, 669 cmꢃ1; MS (70 eV): m=z ¼ 312
(Mþ), 310 (Mþ), 230, 196, 169, 140, 117, 91, 69.
l-N-Trifluoroacetyl-2-amino-1-azido-1-phenylpropane (l-6, C11H11F3N4O)
To a solution of 120 mg of u-4 (0.37 mmol) in 10cm3 of the appopriate solvent, 72 mg of NaN3
(1.1mmol) were added and the solution was stirred at room temperature during 4 h (see Table 1 for
exact conditions). Then H2O and toluene were added. After decantation, the organic layer was washed
with H2O, brine, dried over MgSO4, and the solvent was evaporated. The crude residue was directly
1
analyzed by H NMR. The reaction products described in entries 1 to 3 (Table 1) were purified by
column chromatography (silicagel, CH2Cl2). Diastereomer l-6 could also be recrystallized from
1
EtOH=H2O 9=1. Mp 83.5ꢂC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.40 (m, 5Haromatic), 6.52 (br, NH),
4.66 (d, J ¼ 5.5Hz, H-1), 4.25 (m, H-2), 1.23 (d, J ¼ 6.8 Hz, CH3) ppm; 13C NMR (75 MHz, CDCl3):
ꢁ ¼ 157.3 (q, J ¼ 37Hz, C¼O), 136.5 (C-1ar), 129.7 (C-3ar, C-5ar), 129.6 (C-4ar), 127.7 (C-2ar, C-6ar),
116.4 (q, J ¼ 288 Hz, CF3), 69.3 (C-1), 50.9 (C-2), 18.2 (C-3) ppm; IR (KBr): ꢂꢂ¼ 3280, 3070, 2100,
1724, 1698, 1556, 1447, 1721, 1205, 1180, 1147, 755, 725, 697 cmꢃ1; MS (70 eV): m=z ¼ 272 (Mþ),
245, 230, 160, 152, 141, 132, 125, 117, 104, 91.
u-N-Trifluoroacetyl-2-amino-1-azido-1-phenylpropane (u-6, C11H11F3N4O)
TMSCl, 1.24 cm3 (9.8mmol), and 0.64g of NaN3 (9.8 mmol) were poured into 5 cm3 of DMF. This
suspension was stirred for 1 h at room temperature. Then, a solution of 0.28 g of trans-7 (1.22 mmol) in
5 cm3 of DMF was added. The mixture was heated at 110ꢂC during 6 h. After cooling, H2O and toluene
were added. The solvents were decanted and the organic layer was washed with H2O, brine, dried with
MgSO4, filtered, and evaporated. The residue was purified by column chromatography (silicagel,
1
CH2Cl2) to give 0.23 g (70%) of u-6 as a yellowish solid. Mp 86ꢂC; H NMR (300 MHz, CDCl3):
ꢁ ¼ 7.40 (m, 5Haromatic), 6.93 (br, NH), 4.86 (d, J ¼ 4.6 Hz, H-1), 4.26 (m, H-2), 1.13 (d, J ¼ 6.8 Hz,
CH3) ppm; 13C NMR (75 MHz, CDCl3): ꢁ ¼ 157.3 (q, J ¼ 37Hz, C¼O), 136.4 (C-1ar), 129.6 (C-3ar,
C-5ar), 128.9 (C-4ar), 127.6 (C-2ar, C-6ar), 116.5 (q, J ¼ 288 Hz, CF3), 69 (C-1), 50.9 (C-2), 14.9
(C-3) ppm; IR and MS spectra were identical to those obtained for l-6.
isomer 2; a according to coupling constant: u-5; b according to coupling constant: l-5
ꢀ
ꢀꢀ
isomer 1;