K. Z. Ła˛czkowski et al. / Tetrahedron: Asymmetry 19 (2008) 788–795
793
CH2), 4.53 (d, J = 10.0 Hz, 1H, CH2), 4.55 (dd, J = 8.0,
10.0 Hz, 1H, CH2), 4.63 (dd, J = 4.0, 10.0 Hz, 1H, CH2),
5.28 (br s, 2H, NH2), 5.93 (dd, J = 4.0, 8.0 Hz, 1H, CH),
6.50–6.60 (m, 2H, CH), 7.00–7.15 (m, 2H, CH), 7.20–7.40
(m, 4H, CH); 13C NMR (50 MHz, CDCl3) d 55.51
(CH3), 74.61 (CH2), 79.27 (CH2), 60.47 (CH), 96.14
(CH), 107.19 (CH), 126.34 (CH), 128.60 (2CH), 128.84
(CH), 129.18 (2CH), 115.98 (C), 134.56 (C), 161.22 (C),
162.24 (C), 163.03 (C). HRMS (m/z) calculated for
C17H18N2O4: 314.12666. Found: 314.12757.
60 mmol) in DMF (50 mL) was added and stirring was
continued for 20 h at rt. Water (500 mL) was added and
the mixture was kept in a refrigerator for 2 h. The precip-
itated product was filtered off, washed with water
(50 mL), and dried. Crystallization from n-hexane gave
19.06 g, 92%; mp 102–104 °C; E/Z 12:88; 1H NMR
(300 MHz, CDCl3) d 5.04 (s, 2H, CH2, 12%), 5.07 (s, 2H,
CH2, 88%), 5.13 (s, 2H, CH2), 5.19 (s, 2H, CH2, 88%),
5.20 (s, 2H, CH2, 12%), 6.53 (d, J = 2.1 Hz, 1H, CH),
6.63 (dd, J = 2.1, 8.7 Hz, 1H, CH), 7.30–7.45 (m, 10H,
CH), 7.50 (d, J = 8.7 Hz, 1H, CH); 13C NMR (75 MHz,
CDCl3) d 70.26 (CH2), 71.89 (CH2), 76.49 (CH2), 97.21
(CH), 109.93 (CH), 122.67 (CH), 127.42 (2CH), 127.88
(CH), 128.07 (2CH), 128.13 (CH), 128.36 (2CH), 128.62
(2CH), 112.44 (C), 136.24 (C), 137.73 (C), 156.79 (C),
163.05 (C), 167.28 (C); Anal. Calcd for C22H19NO3: C,
76.50; H 5.61; N, 4.05. Found: C, 76.26; H, 5.54; N, 4.07.
4.12. (S)-(+)-N-(6-Methoxy-2,3-dihydrobenzofuran-3-yl)-N-
hydroxyurea 14
To a solution of 13 (0.88 g, 2.8 mmol) in methanol (40 mL),
20% Pd(OH)2/C (0.10 g) was added and the mixture was
vigorously stirred under hydrogen at 30 °C for 4 h. The cat-
alyst was filtered off, the solvent was removed, and the
product was obtained: 0.49 g, 93%; mp 158–160 °C;
4.15. (Z)-6-Benzyloxy-2,3-dihydrobenzofuran-3-one oxime
O-2-nitrobenzyl ether
20
½aꢁD ¼ þ72:6 (c 1.5, DMSO), 57% ee. 1H NMR
(200 MHz, DMSO-d6) d 3.70 (s, 3H, CH3), 4.45 (dd,
J = 4.4, 9.8 Hz, 1H, CH2), 4.56 (dd, J = 9.0, 9.8 Hz, 1H,
CH2), 5.78 (dd, J = 4.4, 9.0 Hz, 1H, CH), 6.36 (d,
J = 2.2 Hz, 1H, CH), 6.41 (dd, J = 2.2, 8.2 Hz, 1H, CH),
6.50 (s, 2H, NH2), 7.08 (d, J = 8.2 Hz, 1H, CH), 9.12 (s,
1H, OH); 13C NMR (50 MHz, DMSO-d6) d 55.29 (CH3),
73.17 (CH2), 58.94 (CH), 95.51 (CH), 106.33 (CH),
125.53 (CH), 117.51 (C), 161.09 (C), 161.78 (C), 162.10
(C); MS (EI, 70 eV) m/z 224 (M+, 0.3), 163 (10.46), 150
(15.39), 149 (100.00), 148 (53.88), 134 (15.07), 133
(37.60), 121 (82.78), 91 (10.92), 78 (11.02), 77 (25.48), 63
(11.22), 51 (14.12), 43 (14.46); Anal. Calcd for
C10H12N2O4: C, 53.08; H, 5.53; N, 12.69. Found: C,
53.56; H, 5.39; N, 12.49.
Prepared from 15 (2.55 g, 10 mmol) and 2-nitrobenzyl bro-
mide (2.38 g, 11 mmol) following the procedure described
above. The product was crystallized from ethanol and then
from 1-chlorobutane: 1.79 g, 46%; mp 105–107 °C (>99%
Z); 1H NMR (200 MHz, CDCl3) d 5.07 (s, 2H, CH2),
5.19 (s, 2H, CH2), 5.58 (s, 2H, CH2), 6.55 (d, J = 2.0 Hz,
1H, CH), 6.63 (dd, J = 2.0, 8.4 Hz, 1H, CH), 7.30–7.49
(m, 7H, CH), 7.60–7.65 (m, 2H, CH), 8.08 (d, J = 8.0 Hz,
1H, CH); 13C NMR (50 MHz, CDCl3) d 70.30 (CH2),
71.72 (CH2), 72.92 (CH2), 97.27 (CH), 110.13 (CH),
122.83 (CH), 124.70 (CH), 127.40 (2CH), 128.16 (2CH),
128.63 (2CH), 128.99 (CH), 133.43 (CH), 112.10 (C),
134.75 (C), 136.19 (C), 147.62 (C), 157.59 (C), 163.31 (C),
167.43 (C).
4.13. (E/Z)-6-Benzyloxy-2,3-dihydrobenzofuran-3-one
oxime 15
4.16. (S)-(+)-N-(6-Benzyloxy-2,3-dihydrobenzofuran-3-
yl)hydroxylamine O-benzyl ether 17
A mixture of 1 (12.01 g, 50 mmol), hydroxylamine hydro-
chloride (6.95 g, 100 mmol), sodium acetate (8.20 g,
100 mmol), and ethanol (200 mL) was refluxed for 3 h.
After cooling, water (300 mL) was added, and the precipi-
tated product was filtered off: 11.51 g, 90%; mp 159–160 °C
A 1.5 M borane–tetrahydrofuran solution (40 mL, 60
mmol) was added to a solution of (1S,2R)-(+)-norephe-
drine (4.54 g, 30 mmol) in tetrahydrofuran (30 mL) at 0 °C
and the mixture was stirred for 5 h. A solution of 16
(6.91 g, 20 mmol) in tetrahydrofuran (60 mL) was added,
and the mixture was stirred for 20 h at rt. A 3 M hydro-
chloric acid (80 mL) was added and stirring was continued
for 30 h. Tetrahydrofuran was removed on rotary evapora-
tor and the remaining solution was alkalized to pH ꢃ 10
with 35% sodium hydroxide solution. The product was ex-
tracted with ethyl acetate (3 ꢂ 50 mL) and dried with anhy-
drous magnesium sulfate. The solvent was removed and the
1
(decomposition); H NMR (300 MHz, DMSO-d6) d 5.05
(s, 2H, CH2, 12% E), 5.12 (s, 2H, CH2, 88% Z), 6.64 (dd,
J = 2.1, 8.4 Hz, 1H, CH), 6.70 (d, J = 2.1 Hz, 1H, CH),
7.30–7.45 (m, 6H, CH), 11.00 (s, 1H, OH, 88% Z), 11.01
(s, 1H, OH, 12% E). Lit.18 NMR reported. 13C NMR
(75 MHz, DMSO-d6) the major isomer, d 69.58 (CH2),
71.47 (CH2), 97.28 (CH), 109.63 (CH), 121.82 (CH),
127.72 (2CH), 127.92 (CH), 128.44 (2CH), 112.93 (C),
136.58 (C), 154.66 (C), 162.39 (C), 166.92 (C); Anal. Calcd
for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C,
70.32; H, 5.13; N, 5.26.
product isolated by column chromatography on silica gel
20
(n-hexane/ethyl acetate, 4:1): 1.25 g, 19%; ½aꢁD ¼ þ12:1 (c
1.1, CHCl3). HPLC analysis on a chiral OD-H column
(n-hexane/isopropanol, 95:5), 62% ee, 0.6 mL/min, tR
1
4.14. (E/Z)-6-Benzyloxy-2,3-dihydrobenzofuran-3-one
oxime O-benzyl ether 16
30.03S, 35.82R. H NMR (200 MHz, CDCl3) d 4.49 (dd,
J = 7.2, 10.0 Hz, 1H, CH2), 4.58 (dd, J = 3.2, 10.0 Hz,
1H, CH2), 4.69 (m, 1H, CH), 4.72 (s, 2H, CH2), 5.03 (s,
2H, CH2), 5.49 (br s, 1H, NH), 6.48 (d, J = 2.2 Hz, 1H,
CH), 6.52 (dd, J = 2.2, 8.0 Hz, 1H, CH), 7.21 (d,
J = 8.0 Hz, 1H, CH), 7.23–7.42 (m, 10H, CH); 13C NMR
(50 MHz, CDCl3) d 70.23 (CH2), 76.08 (CH2), 76.52
A solution of 15 (12.76 g, 50 mmol) in DMF (100 mL) was
added to a mixture of sodium hydride (1.44 g, 60 mmol)
and DMF (50 mL) at 0 °C. The mixture was stirred for
3 h at rt, and a solution of benzyl chloride (7.60 g,