Cleavage of 2-(1-Aminoalkyl)aziridines
added BF3‚OEt2 (0.025 mL, 0.2 mmol) at room temperature.
After stirring at reflux temperature for 2 h, an aqueous
saturated solution of sodium bicarbonate (5 mL) was added
and the mixture was stirred at room temperature for 5 min.
Then, the aqueous phase was extracted with diethyl ether
(3 × 5 mL), and the combined organic layers were dried
(Na2SO4), filtered, and concentrated in vacuo. Flash column
chromatography over silica gel (hexane/EtAcO 3:1) provided
pure compounds 2. (Yields are given in Table 1.)
456.3136; IR (neat) 3308, 3027, 2926, 2852, 1609, 1494, 1098
cm-1; Rf ) 0.41 (hexane/EtOAc 1:1).
(2S,3S)-N2-Allyl-N3,N3-d iben zyl-1-ter t-bu toxy-5-m eth -
ylh exa n -2,3-d ia m in e (5): [R]25D -11.3 (c 0.2, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 7.40-7.21 (m, 10 H), 6.02-5.92 (m, 1 H),
5.27-5.13 (m, 2 H), 3.82 (AB syst, J ) 13.4 Hz, 4 H), 3.81-
3.71 (m, 1 H), 3.32-3.26 (m, 2 H), 3.04-2.88 (m, 2 H), 2.79-
2.77 (m, 1 H), 1.91-1.76 (m, 1 H), 1.71 (br s, 1 H), 1.31-1.20
(m, 2 H), 1.09 (s, 9 H), 0.80 (d, J ) 6.6 Hz, 3 H), 0.77 (d, J )
6.3 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 141.1 (2 × C), 137.1,
129.4, 129.0, 128.0, 126.6 (11 × CH), 115.5 (CH2), 73.1 (C),
71.3 (CH), 58.8 (CH), 55.9 (2 × CH2), 52.4 (CH2), 45.2 (CH2),
41.7 (CH2), 28.8 (3 × CH3), 24.3 (CH), 23.1 (CH3), 22.5 (CH3);
MS (70 eV, EI) m/z (%) 422 (M+, 2), 352 (72), 296 (44), 279
(52), 91 (100), 57 (51); HRMS (70 eV) calcd for C28H42N2O
422.3292, found 422.3278; IR (neat) 3063, 3027, 2956, 2868,
2454, 1364, 1193 cm-1; Rf ) 0.30 (hexane/EtOAc 1:1).
P r ep a r a tion of (4S,5S)-4-Ben zyl-5-m eth oxym eth yltet-
r a h yd r op yr im id in -2-on e (3c). A solution of the diamine 2c
(0.3 g, 0.66 mmol) in 30 mL of MeOH/HCO2H 5% (28.5:1.5),
in the presence of Pd/C (0.3 g), was heated 2 h at reflux. Then,
the mixture was filtered through Celite and concentrated. The
residue was solved in CH2Cl2 (10 mL) and washed with a
saturated solution of K2CO3 (2 × 10 mL). The organic layer
was dried over Na2SO4 and the solvent was evaporated.
(2S,3S)-N1,N3,N3-Tr ib en zyl-2-isop r op oxybu t a n -1,3-d i-
a m in e (2a ): [R]25 -20.7 (c 1.45, CHCl3); 1H NMR (300 MHz,
D
CDCl3) δ 7.37-7.23 (m, 15 H), 3.86 (AB syst, J ) 13.4 Hz, 4
H), 3.84-3.60 (m, 2 H), 3.60 (AB syst, J ) 13.1 Hz, 2 H), 2.79-
2.71 (m, 3 H), 1.19 (d, J ) 6.6 Hz, 3 H), 1.17 (d, J ) 6.0 Hz, 3
H), 1.16 (d, J ) 6.0 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ
140.8 (2 × C), 140.4 (C), 129.0, 128.2, 128.0, 127.9, 126.6 (15
× CH), 73.1 (CH), 68.8 (CH), 61.1 (CH), 55.1 (2 × CH2), 53.6
(CH2), 46.2 (CH2), 23.6 (CH3), 22.1 (CH3), 18.2 (CH3); MS (70
eV, EI) m/z (%) 416 (M+, <1), 297 (100), 254 (26), 181 (25),
162 (25); HRMS (70 eV) calcd for C28H36N2O 416.2828, found
416.2848; IR (neat) 3313, 2970, 2928, 1748, 1494, 1454 cm-1
;
Rf ) 0.38 (hexane/EtOAc 1:1). Anal. Calcd for C28H36N2O: C,
80.73; H, 8.71; N, 6.72. Found: C, 80.76; H, 8.73; N, 6.70.
(2S,3S)-N1,N3,N3-Tr iben zyl-2-m eth oxy-5-m eth ylh exa n -
1
1,3-d ia m in e (2b): [R]25 -6.2 (c 0.72, CHCl3); H NMR (300
D
MHz, CDCl3) δ 7.40-7.22 (m, 15 H), 3.82 (AB syst, J ) 13.4
Hz, 4 H), 3.70 (AB syst, J ) 13.4 Hz, 2 H), 3.54-3.50 (m, 1
H), 3.33 (s, 3 H), 2.95-2.76 (m, 3 H), 1.80 (br s, 1 H), 1.60-
1.42 (m, 3 H), 0.93 (d, J ) 6.0 Hz, 3 H), 0.91 (d, J ) 6.0 Hz, 3
H); 13C NMR (75 MHz, CDCl3) δ 140.6 (C), 140.5 (2 × C), 128.9,
128.8, 128.2, 128.1, 128.0, 126.7 (15 × CH), 80.3 (CH), 58.7
(CH), 57.5 (CH3), 55.2 (2 × CH2), 53.7 (CH2), 45.8 (CH2), 40.3
(CH2), 24.6 (CH), 23.3 (CH3), 22.5 (CH3); MS (70 eV, EI) m/z
(%) 430 (M+, 2), 339 (24), 266 (48), 181 (46), 132 (39), 91 (100);
HRMS (70 eV) calcd for C29H38N2O 430.2984, found 430.3007;
The obtained debenzylated diamine (0.1 g, 0.52 mmol) was
treated with a solution of triphosgene (0.17 g, 0.57 mmol) and
NEt3 (0.10 mL, 1.14 mmol) in CH2Cl2 (2 mL) at 0 °C for 12 h.
Then, a saturated solution of NH4Cl (4 mL) was added to
quench the reaction. The layers were separated, and the
aqueous layer was extracted with CH2Cl2 (3 × 5 mL). The
combined organic layers were dried over Na2SO4, and the
solvent was removed in vacuo. The product was purified by
column chromatography (silica gel, EtOAc) yielding pure
compound 3c (90 mg, 0.41 mmol, 62%): [R]25 -7.9 (c 2.0,
D
IR (neat) 3320, 3084, 3062, 3027, 2821, 1603, 1494, 1454 cm-1
;
CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.34-7.10 (m, 5 H), 5.13
(br s, 1 H), 5.06 (br s, 1 H), 3.75-3.69 (m, 1 H), 3.46 (t, J ) 7.7
Hz, 1 H), 3.41-3.37 (m, 1 H), 3.36 (s, 3 H), 3.16 (t, J ) 7.7 Hz,
1 H), 2.80 (2 × dd, J ) 6.3, 4.8 Hz, 2 H); 13C NMR (75 MHz,
CDCl3) δ 163.4 (C), 137.1 (C), 129.4 (2 × CH), 128.4 (2 × CH),
126.6 (CH), 84.5 (CH), 58.7 (CH3), 55.8 (CH), 43.0 (CH2), 36.3
(CH2); Rf ) 0.10 (EtOAc). Anal. Calcd for C12H16N2O2: C, 65.43;
H, 7.32; N, 12.72. Found: C, 65.48; H, 7.35; N, 12.71.
Rf ) 0.28 (hexane/EtOAc 3:1).
(2S,3S)-N1,N3,N3-Tr iben zyl-2-m eth oxy-4-p h en ylbu ta n -
1,3-d ia m in e (2c): [R]25 +7.1 (c 1.0, CHCl3); 1H NMR (300
D
MHz, CDCl3) δ 7.39-7.19 (m, 20 H), 3.90 (AB syst, J ) 13.4
Hz, 4 H), 3.70-3.52 (m, 3 H), 3.29 (s, 3 H), 3.05-2.81 (m, 5
H), 1.78 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 140.5, 139.3
(4 × C), 129.4, 129.0, 128.2, 128.1, 127.9, 126.6, 125.8 (20 ×
CH), 84.0 (CH), 59.0 (CH), 58.2 (CH3), 55.2 (2 × CH2), 53.3
(CH2), 46.0 (CH2), 37.9 (CH2); IR (neat) 3314, 3084, 3061, 3027,
2826, 1602, 1495, 1454 cm-1; Rf ) 0.49 (hexane/EtOAc 1:1).
Anal. Calcd for C32H36N2O: C, 82.72; H, 7.81; N, 6.03. Found:
C, 82.90; H, 7.84; N, 6.01.
Gen er a l P r oced u r e for th e Syn th esis of O-Acyla ted
2,3-Dia m in oa lk a n -1-ols 6. To a stirred solution of the cor-
responding amino aziridine 1 (0.2 mmol) in acetonitrile (1 mL)
were added BF3‚OEt2 (0.025 mL, 0.2 mmol) and the corre-
sponding carboxylic acid (0.6 mmol) at room temperature. After
stirring at reflux temperature for 2 h, an aqueous saturated
solution of sodium bicarbonate (5 mL) was added and the
mixture was stirred at room temperature for 5 min. Then, the
aqueous phase was extracted with diethyl ether (3 × 5 mL),
and the combined organic layers were dried (Na2SO4), filtered,
and concentrated in vacuo. Flash column chromatography over
silica gel (hexane/EtOAc 3:1) provided pure compounds 6.
Yields are given in Table 2.
(2R,3S)-2-(Ben zyla m in o)-3-(d iben zyla m in o)-4-p h en yl-
bu tyl a ceta te (6a ): [R]25D +4.70 (c 1.0, CHCl3); 1H NMR (300
MHz, CDCl3) δ 7.40-7.10 (m, 20 H), 5.46-5.40 (m, 1 H), 3.79
(AB syst, J ) 13.4 Hz, 4 H), 3.66 (AB syst, J ) 13.4 Hz, 2 H),
3.11-3.01 (m, 3 H), 2.90-2.69 (m, 2 H), 1.96 (s, 3 H), 1.85 (br
s, 1 H); 13C NMR (75 MHz, CDCl3) δ 170.2 (C), 140.2, 140.0,
137.7 (4 × C), 129.3, 129.1, 128.2, 128.1, 128.0, 126.9, 126.8,
126.3 (20 × CH), 75.0 (CH), 59.3 (CH), 55.2 (2 × CH2), 53.5
(CH2), 45.1 (CH2), 38.7 (CH2), 21.1 (CH3); MS (70 eV, EI) m/z
(%) 492 (M+, <1), 401 (9), 373 (85), 91 (100); HRMS (70 eV)
calcd for C33H36N2O2 492.2777, found 492.2712; IR (neat) 3323,
3062, 3027, 2924, 2846, 1736, 1495, 1454, 1369, 1237 cm-1; Rf
) 0.25 (hexane/EtOAc 3:1). Anal. Calcd for C33H36N2O2: C,
80.45; H, 7.37; N, 5.69. Found: C, 80.49; H, 7.40; N, 5.67.
(2S,3S)-N1,N3,N3-Tr ib en zyl-2-isop r op oxy-4-p h en ylb u -
1
ta n -1,3-d ia m in e (2d ): [R]25 -1.4 (c 0.23, CHCl3); H NMR
D
(300 MHz, CDCl3) δ 7.42-7.10 (m, 20 H), 3.93 (AB syst, J )
13.4 Hz, 4 H), 3.90-3.85 (m, 1 H), 3.68 (AB syst, J ) 14.7 Hz,
2 H), 3.44-3.37 (m, 1 H), 3.04-2.85 (m, 5 H), 1.78 (br s, 1 H),
1.08 (d, J ) 6.0 Hz, 3 H), 0.92 (d, J ) 6.3 Hz, 3 H); 13C NMR
(75 MHz, CDCl3) δ 140.7 (2 × C), 140.5 (C), 139.9 (C), 129.4,
129.1, 128.2, 128.1, 128.0, 127.9, 126.7, 126.6, 125.6 (20 × CH),
79.2 (CH), 70.1 (CH), 59.3 (CH), 55.4 (2 × CH2), 53.6 (CH2),
45.3 (CH2), 38.6 (CH2), 22.7 (CH3), 22.1 (CH3); IR (neat) 3331,
3085, 3062, 3027, 1602, 1495 cm-1; Rf ) 0.49 (hexane/EtOAc
1:1). Anal. Calcd for C34H40N2O: C, 82.88; H, 8.18; N, 5.69.
Found: C, 82.90; H, 8.20; N, 5.71.
(2S ,3S )-N 1-Cycloh e xyl-N 3,N 3-d ib e n zyl-2-m e t h oxy-4-
p h en ylbu ta n -1,3-d ia m in e (2e): [R]25 +7.4 (c 1.0, CHCl3);
D
1H NMR (300 MHz, CDCl3) δ 7.39-7.23 (m, 15 H), 3.85 (AB
syst, J ) 13.3 Hz, 4 H), 3.66-3.64 (m, 1 H), 3.28 (s, 3 H), 3.00-
2.70 (m, 5 H), 2.07-1.98 (m, 1 H), 1.78-1.65 (m, 5 H), 1.32-
0.98 (m, 6 H); 13C NMR (75 MHz, CDCl3) δ 140.5 (2 × C), 139.1
(C), 129.4, 129.1, 128.0, 126.6, 125.9 (15 × CH), 83.7 (CH),
59.2 (CH), 58.0 (CH3), 56.2 (CH), 55.1 (2 × CH2), 43.4 (CH2),
37.8 (CH2), 33.4 (2 × CH2), 26.0 (CH2), 24.9 (CH2), 24.8 (CH2);
MS (70 eV, EI) m/z (%) 456 (M+, <1), 345 (51), 344 (100), 91
(81); HRMS (70 eV) calcd for C31H40N2O 456.3135, found
(2R,3S)-2-(Ben zyla m in o)-3-(d iben zyla m in o)-4-m eth yl-
h exyl a ceta te (6b): [R]25D +1.30 (c 1.3, CHCl3); 1H NMR (300
J . Org. Chem, Vol. 68, No. 24, 2003 9245