3.30 (1 H, m), 3.39 (1 H, m), 3.57 (1 H, m), 3.67 (1 H, d, J = 13.5
Hz), 4.13 (1 H, d, J = 13.5 Hz), 7.16 (1 H, m), 7.21–7.25 (5 H,
m), 7.30 (2 H, t, J = 7.5 Hz), 7.40 (2 H, d, J = 7.5 Hz); 13C-NMR
(125 MHz, CDCl3) 12.48, 12.64, 16.81 (C-3), 22.62, 31.55,
35.01, 39.91, 42.37, 62.74, 63.53, 126.14, 126.47, 126.80,
128.09, 128.56, 129.33, 138.71, 140.46, 171.64; HR-MS (EI)
366.2317 (Mϩ, C23H30N2O2 requires 366.2307). Found: C,
75.19; H, 9.79; N, 4.46. C23H30N2O2 requires C, 75.37; H,
8.25; N, 7.64%.
m), 1.26 (1 H, dd, H-3a, J = 4.7, 6.0 Hz), 1.38 (1 H, ddd, H-2,
J = 6.0, 8.6, 8.6 Hz), 1.65 (1 H, dd, J = 4.7, 8.6 Hz), 1.73 (1 H,
m), 2.72 (1 H, m), 3.08 (1 H, m), 3.15 (1 H, m), 3.47–3.56 (2 H,
m), 7.18–7.33 (5 H, m); 13C-NMR (125 MHz, CD3OD) 12.26,
12.35, 18.99, 20.22, 31.69, 32.51, 34.89, 39.40, 41.95, 59.74,
126.36, 128.33, 128.65, 136.17, 170.00; HR-MS (EI) 288.2193
(Mϩ, C17H26N2O requires 288.2193). Found: C, 59.78; H, 9.21;
Cl, 9.72; N, 7.73. C17H27ClN2OؒH2O requires C, 59.90; H, 9.22;
Cl, 9.82; N, 7.76%.
(1S,2R)-1-Phenyl-2-[(R)-1-(N-benzyl-N-hydroxyamino)ethyl]-
N,N-diethylcyclopropanecarboxamide (8a)
(1S,2R)-1-Phenyl-2-[(R)-1-azido-2-methylpropyl]-N,N-diethyl-
cyclopropanecarboxamide (9) and (1S, 2R)-1-phenyl-2-(2-
methylprop-1-enyl)-N,N-diethylcyclopropanecarboxamide (10)
Obtained as a solid; 1H-NMR (500 MHz, CDCl3) 0.55 (3 H, t,
J = 7.3 Hz), 1.11 (3 H, t, J = 7.3 Hz), 1.24 (1 H, dd, J = 4.3, 9.2
Hz), 1.41 (3 H, d, J = 6.6 Hz), 1.64–1.79 (2 H, m), 2.67 (1 H, m),
2.98–3.23 (2 H, m), 3.37 (1 H, m), 3.52 (1 H, m), 3.82 (1 H, d,
J = 13.2 Hz), 3.89 (1 H, d, J = 13.2 Hz), 7.17–7.31 (10 H, m);
HR-MS (EI) 366.2297 (Mϩ, C23H30N2O2 requires 366.2307).
A mixture of 4c (868 mg, 3.00 mmol), PPh3 (2.36 g, 9.00 mmol),
and CBr4 (2.98 g, 9.00 mmol) in DMF (20 ml) was stirred at
0 ЊC for 30 min. To the resulting mixture was added NaN3 (1.95
g, 30.0 mmol), and then the whole was stirred at room temper-
ature for 5 h. After addition of AcOEt and H2O, the organic
layer was separated, washed with brine, dried (Na2SO4), evap-
orated, and purified by flash column chromatography (silica
gel; AcOEt–hexane 1 : 9) to give 9 (248 mg, 26%) as white crys-
tals and 10 (251 mg, 31%) as an oil, respectively. Carboxamide
9: mp (hexane–AcOEt) 89–90 ЊC; [α]D23 Ϫ68.7 (c 1.14, CHCl3);
1H-NMR (500 MHz, CDCl3) 0.71 (3 H, t, J = 7.1 Hz), 1.00
(3 H, d, J = 6.8 Hz), 1.03 (3 H, d, J = 6.8 Hz), 1.11 (3 H, t,
J = 7.1 Hz), 1.48 (1 H, dd, J = 4.5, 8.5 Hz), 1.61 (1 H, dd,
J = 4.5, 6.0 Hz), 1.63 (1 H, ddd, J = 6.0, 8.5, 8.5 Hz), 2.12 (1 H,
m), 3.17 (1 H, m), 3.24 (1 H, m), 3.45–3.53 (3 H, m), 7.20–7.32
(5 H, m); 13C-NMR (125 MHz, CDCl3) 12.37, 12.68, 16.57,
17.71, 20.37, 29.77, 33.10, 33.30, 39.43, 41.88, 68.00, 126.15,
126.64, 128.76, 140.79, 169.30; HR-MS (EI) 314.2096 (Mϩ,
C18H26N4O requires 314.2107). Found: C, 68.78; H, 8.28;
N, 17.57. C18H26N4O requires C, 68.76; H, 8.33; N, 17.82%.
(1S,2R)-1-Phenyl-2-[(S)-1-(N-benzyl-N-hydroxyamino)propyl]-
N,N-diethylcyclopropanecarboxamide (7b)
Mp 146–147 ЊC (hexane–AcOEt); [α]D23 Ϫ123.2 (c 1.11, CHCl3);
1H-NMR (500 MHz, CDCl3) 0.53 (3 H, t, J = 7.0 Hz), 1.05–
1.09 (6 H, m), 1.32 (1 H, dd, J = 5.6, 8.9 Hz), 1.75–1.92 (4 H,
m), 2.64 (1 H, m), 3.03 (1 H, m), 3.13 (1 H, m), 3.46–3.58 (2 H,
m), 3.89 (1 H, d, J = 13.5 Hz), 4.09 (1 H, d, J = 13.5 Hz), 4.72
(1 H, br s), 7.18–7.38 (10 H, m); 13C-NMR (125 MHz, CDCl3)
11.34, 12.16, 12.26, 20.89, 24.96, 27.42, 32.71, 39.56, 42.16,
60.65, 67.23, 126.26, 126.73, 126.93, 128.18, 128.59, 129.00,
139.39, 142.20, 170.21; HR-MS (EI) 380.2439 (Mϩ, C24H32-
N2O2 requires 380.2464). Found: C, 75.19; H, 9.79; N, 4.46.
C24H32N2O2 requires C, 75.75; H, 8.48; N, 7.36%.
1
Carboxamide 9: [α]D22 Ϫ177.6 (c 2.34, CHCl3); H-NMR (500
(1S,2R)-1-Phenyl-2-[(S)-1-(N-benzyl-N-hydroxyamino)-2-
methylpropyl]-N,N-diethylcyclopropanecarboxamide (7c)
MHz, CDCl3) 0.56 (3 H, t, J = 7.1 Hz), 1.07 (1 H, dd, J = 4.7,
9.0 Hz), 1.08 (3 H, t, J = 7.1 Hz), 1.70 (3 H, s), 1.72 (1 H, dd,
J = 4.7, 6.0 Hz), 1.83 (3 H, s), 2.64 (1 H, ddd, J = 6.0, 9.0, 9.6
Hz), 2.99 (1 H, m), 3.14 (1 H, m), 3.37 (1 H, m), 3.60 (1 H,
m), 4.71 (1 H, d, J = 9.6 Hz), 7.19–7.30 (5 H, m); 13C-NMR
(125 MHz, CDCl3) 12.04, 12.39, 18.18, 23.46, 24.13, 25.51,
36.66, 38.80, 40.92, 123.03, 125.83, 126.23, 128.58, 133.99,
141.24, 170.16; HR-MS (EI) 271.1937 (Mϩ, C18H25NO
requires 271.1936).
Mp 78–80 ЊC (hexane–AcOEt); [α]D23 Ϫ55.7 (c 0.65, CHCl3);
1H-NMR (500 MHz, CDCl3) 0.55 (3 H, t, J = 7.0 Hz), 1.06–
1.09 (6 H, m), 1.16 (3 H, d, J = 6.9 Hz), 1.45 (1 H, dd, J = 4.1,
8.7 Hz), 1.89–2.01 (3 H, m), 2.81 (1 H, dd, H-1Ј, J = 5.2, 9.1
Hz), 3.02 (1 H, m), 3.13 (1 H, m), 3.46–3.55 (2 H, m), 3.92 (1 H,
d, J = 13.6 Hz), 4.15 (1 H, d, J = 13.6 Hz), 4.54 (1 H, br s), 7.18–
7.40 (10 H, m); 13C-NMR (125 MHz, CDCl3) 12.16, 12.21,
19.37, 20.28, 20.85, 26.70, 31.95, 32.39, 39.49, 42.00, 61.74,
69.74, 126.24, 126.54, 126.92, 128.18, 128.62, 129.02, 139.55,
142.23, 170.32; HR-MS (EI) 394.2612 (Mϩ, C25H34N2O2
requires 394.2620). Found: C, 76.02; H, 8.63; N, 7.12. C25H34-
N2O2 requires C, 76.10; H, 8.69; N, 7.10%.
X-Ray crystallogaraphic data of 6†
C22H26N2O2, M = 340.45, orthorhombic, P212121, a = 10.093
(2), b = 19.840 (4), c = 9.895 (2) Å, V = 1981.4 (7) Å3, Z = 4,
Dx = 11.175 Mg cmϪ1. Cell parameters were determined and
refined from 26 reflections in the range 28.3Њ < θ < 29.9Њ. A
colorless crystal (0.30 × 0.25 × 0.11 mm) was mounted on a
Mac Science MXC18 diffractometer with graphite-mono-
chromated Cu-Kα radiation (λ = 1.54178 Å). Data collection
using the ω/2θ scan technique gave 3490 reflections at room
temperature, 3340 unique, of which 2928 with I > 3.00σ(I)
reflections were used in calculations. The intensities were cor-
rected for the Lorentz and polarization factors, but not for the
absorption or the extinction effect. The structure was solved by
direct methods and refined by the full-matrix least squares
technique (Crystan-GM system17 as the computer program and
SIR9218 as the structure solution method). The non-hydrogen
atoms were refined anisotropically. The hydrogen atoms were
included by calculation, but these positions were not refined.
The unweighted and weighted values (with a weighting scheme
W = exp(15sin2 θ/λ2)/σ2(Fo)) were 0.050 and 0.065, respectively.
There was no peak above 0.13 e ÅϪ3 in the last Fourier-
difference map.
General procedure for reduction of N-benzylhydroxyamines 7
A mixture of hydroxylamine 7a–c (1.0 mmol) and 10% Pd on
carbon (50 mg) in MeOH (15 ml) was shaken under H2 at 30 psi
for 3 days. The mixture was filtered through a pad of Celite, and
the filtrate was evaporated. The residue was purified by column
chromatography (silica gel; AcOEt–hexane 1 : 1, then CHCl3–
MeOH 9 : 1) to give the free amine of 1 as an oil. The oil was
dissolved in MeOH, which was applied to a column of Diaion
WA-30 resin (ClϪ form), and the column was eluted with
MeOH. The solvent was evaporated, and the residue was treat-
ed with Et2O to give white crystals of 1a–c as a hydrochloride
(1a 98%, 1b 93%, 1c 71%). The 1H and 13C NMR spectra of 1a
and 1b were identical with those of the compounds previously
synthesized by us.3b
(1S,2R)-1-Phenyl-2-[(S)-1-amino-2-methylpropyl]-N,N-diethyl-
cyclopropanecarboxamide (1c) hydrochloride
1
Mp 83–84 ЊC (Et2O); [α]D21 ϩ105.7 (c 0.90, MeOH); H-NMR
(500 MHz, CD3OD) 0.57 (3 H, t, J = 7.0 Hz), 1.00–1.11 (9 H,
† CCDC reference number 207/507.
J. Chem. Soc., Perkin Trans. 1, 2001, 599–604
603