Notes
J . Org. Chem., Vol. 67, No. 12, 2002 4383
pad of Celite, and the filtrate was then diluted with water,
extracted with dichlorometane, and dried over MgSO4. After
filtration, the filtrate was concentrated in a vacuum and the
residue was purified by column flash chromatography as de-
scribed in method A.
(3aSR,6aRS)-1-Meth yltetr ah ydr o-3H,6H-fu r o[3,4-c]isoxa-
zol-6-on e (7a ). Following m eth od A, 5a (3.01 g) afforded 7a
(1.80 g, 72%) as pale yellow solid: mp 74-75 °C; IR (KBr) 3529,
2980, 1778, 1447, 1199, 1194 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 2.75 (s, 3H, N-CH3), 3.60 (m, 1H, H3a), 3.85 (dd, 1H, J ) 3.0,
9.1 Hz, H3′), 3.92 (d, 1H, J ) 8.1 Hz, H6a), 4.25 (dd, 1H, J ) 7.5,
10.0 Hz, H4′), 4.30 (dd, 1H, J ) 3.3, 9.1 Hz, H3”), 4.53 (dd, 1H, J
) 8.1, 10.0 Hz H4”); 13C NMR (CDCl3, 75 MHz) δ 44.9, 47.8, 66.5,
68.3, 71.2, 168.9; MS (70 eV) 143 (M+, 65), 143 (25), 99 (30), 42
(100); HRMS (EI) calcd for [M+] C6H9NO3 143.0582, found
143.0580. Anal. Calcd for C6H9NO3: C, 50.33; H, 6.34; N, 9.79.
Found: C, 50.24; H, 6.32; N, 9.82.
(3a SR,4RS,6a SR)-1-Ben zyl-4-m et h ylt et r a h yd r o-3H,6H-
fu r o[3,4-c]isoxa zol-6-on e (13). Following m eth od B with 4b
(1.25 g) and 10 (2.24 g) afforded 13 (1.05 g, 39%) as white solid:
mp 161-162 °C; first eluted product; IR (KBr) 3453, 2980, 1771,
1560, 1460, 1390 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.42 (d,
;
3H, J ) 6.3 Hz), 3.17 (m, 1H, H3a), 3.97 (m, 1H, H3′), 4.02 (m,
1H, H3′′), 4.07 (d, 1H, J ) 4.8 Hz, H6a), 4.10 (d, 1H, J ) 12.8 Hz,
PhCH), 4.12 (d, 1H, J ) 12.8 Hz, PhCH), 4.75 (dq, 1H, J ) 3.6,
6.3 Hz, H4), 7.29-7.44 (m, 5H, aromatic protons); 13C NMR
(CDCl3, 75 MHz) δ 22.5, 46.3, 65.5, 70.2, 75.3, 80.9, 127.8, 128.92,
128.98, 135.7, 168.9; MS (70 eV) 233 (M+, 18), 98 (40) 91 (100).
HRMS (EI) calcd for [M+] C13H15NO3 233.1052, found 233.1050.
Anal. Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.00. Found:
C, 66.79; H, 6.49; N, 6.03.
Following m et h od
B with (R)-(-)-4b (1.25 g) afforded
(3aS,4R,6aS)-13: [R]25 ) +30.5 (c 1.20, CHCl3).
D
Gen er al P r ocedu r e for th e P r epar ation of 3-Alkylam in o-
2(5H)fu r a n on es 14-17. To a solution of furoisoxazolidine 7,
8, or 11-13 (2.0 mmol) in dry THF (10 mL) was added NaH (48
mg, 2.0 mmol), and the mixture was stirred for 5 h at room
temperature, until the TLC showed the disappearance of the
starting material. The reaction mixture was then charged with
water, extracted with chloroform, and the combined organic
phases, dried over Na2SO4, evaporated under reduced pressure.
The residue was then purified by column flash chromatography
(hexane/EtOAc, 9:1).
Following m eth od B, 4a (1.01 g) and 9 (1.36 g) afforded 7a
(1.08 g, 65%).
(3a RS,4RS,6a RS)-1,4-Dim et h ylt et r a h yd r o-3H ,6H -fu r o-
[3,4-c]isoxa zol-6-on e (7b). Following m eth od A, 5b (3.50 g)
afforded 7b (848 mg, 31%) as light yellow oil: first eluted
product; IR (neat) 3453, 2980, 1771, 1560, 1460, 1390 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 1.40 (d, 3H, J ) 6.6 Hz), 2.76 (s, 3H,
N-CH3), 3.35 (dddd, 1H, J ) 3.9, 6.0, 7.9, 8.3, H3a), 3.51 (d, 1H,
J ) 7.9 Hz, H6a), 4.09 (dq, 1H, J ) 6.0, 6.6 Hz, H4), 4.25 (dd,
3-Meth yla m in o-2(5H)fu r a n on e (14). Compound 7a (286
mg) gave 14 (115 mg, 51%) as a light yellow oil: IR (neat)
3380, 2934, 2880, 1750, 1660, 1140, 1037 cm-1; 1H NMR (CDCl3,
300 MHz) δ 2.77 (d, 3H, J ) 3.1 Hz, N-CH3), 3.90 (bs, 1H, NH),
4.85 (d, 2H, J ) 2.9 Hz, H5), 6.93 (t, 1H, J ) 5.0 Hz, H4); 13C
NMR (CDCl3, 75 MHz) δ 32.8, 67.5, 122.1, 136.6, 172.3; MS (70
eV) 113 (M+, 43), 85 (40), 69 (100); HRMS (EI) calcd for [M+]
C5H7NO2 113.0476, found 113.0472. Anal. Calcd for C5H7NO2:
C, 53.09; H, 6.24; N, 12.38. Found: C, 52.91; H, 6.22; N, 12.40.
(5RS)-5-Meth yl-3-m eth ylam in o-2(5H)fu r an on e (15). Com-
pounds 7b and 8b (314 mg) gave 15 (130 mg, 51%) as a light
1H, J ) 3.9, 9.8 Hz, H3′), 4.45 (dd, 1H, J ) 8.3, 9.8 Hz, H3”); 13
C
NMR (CDCl3, 75 MHz) δ 17.3, 46.1, 50.4, 71.0, 75.4, 81.0, 168.7;
MS (70 eV) 157 (M+, 20), 113 (100); HRMS (EI) calcd for [M+]
C7H11NO3 157.0739, found 157.0736. Anal. Calcd for C7H11NO3:
C, 53.49; H, 7.05; N, 8.91. Found: C, 53.28; H, 7.06; N, 8.94.
Following m eth od B, 4b (1.25 g) and 9 (1.36 g) afforded 7b
(711 mg, 39%). Following m et h od B, (R)-(-)-4b afforded
(3aR,4R,6aR)-7b: [R]25 ) +38.2 (c 1.15, CHCl3).
D
(3a SR,4RS,6a SR)-1,4-Dim et h ylt et r a h yd r o-3H ,6H -fu r o-
[3,4-c]isoxa zol-6-on e (8b). Following m eth od A, 5b (3.50 g)
afforded 8b (821 mg, 30%) as light yellow oil: further eluted
yellow oil: IR (neat) 3370, 2900, 1750, 1650, 1140, 1020 cm-1
;
1
product; IR (neat) 3429, 2970, 1778, 1447, 1399 cm-1; H NMR
1H NMR (CDCl3, 300 MHz) δ 1.40 (d, 3H, J ) 6.6 Hz, CH3),
2.77 (d, 3H, J ) 4.8, N-CH3), 3.90 (bs, 1H, NH), 5.04 (dq, 1H, J
) 6.6 and 2.0 Hz, H5), 5.55 (d, 1H, J ) 2.0, H4); 13C NMR (CDCl3,
75 MHz) δ 20.9, 31.1, 75.9, 111.1, 144.7, 172.5; MS (70 eV) 127
(M+, 33), 99 (15), 83 (100); HRMS (EI) calcd for [M+] C6H9NO2
127.0633, found 127.0631. Anal. Calcd for C6H9NO2: C, 56.68;
H, 7.13; N, 11.02. Found: C, 56.59; H, 7.13; N, 11.00. Compounds
(CDCl3, 300 MHz) δ 1.44 (d, 3H, J ) 6.6 Hz), 2.74 (s, 3H, N-CH3),
3.56 (dddd, 1H, J ) 3.4, 3.5, 3.8, 9.7, H3a), 3.86 (d, 1H, J ) 9.7
Hz, H6a), 3.90 (dd, 1H, J ) 3.4, 9.6 Hz, H3′), 3.95 (dd, 1H, J )
3.5, 9.6 Hz, H3′′), 4.74 (dq, 1H, J ) 3.8, 6.6 Hz, H4); 13C NMR
(CDCl3, 75 MHz) δ 18.4, 46.1, 51.5, 64.9, 70.1, 76.6, 168.5; MS
(70 eV) 157 (M+, 25), 142 (10), 113 (100); HRMS (EI) calcd for
[M+] C7H11NO3 157.0739, found 157.0737. Anal. Calcd for C7H11
-
(3aR,4R,6aR)-7b and (3aS,4R,6aS)-8b afforded (5R)-15; [R]25
) +8.6 (c 0.58, CHCl3).
D
NO3: C, 53.49; H, 7.05; N, 8.91. Found: C, 53.35; H, 7.04; N, 8.93.
Following m et h od B, 4b (1.25 g) and 9 (1.36 g) afforded
8b (674 mg, 37%). Following m eth od B, (R)-(-)-4b afforded
3-Ben zyla m in o-2(5H)fu r a n on e (16). Compound 11 (438
mg) gave 16 (193 mg, 51%) as a light yellow oil: IR (neat) 3350,
2834, 1760, 1630, 1180, 1120, 1057 cm-1; 1H NMR (CDCl3, 300
MHz) δ 4.34 (s, 2H, PhCH2), 4.72 (d, 2H, J ) 3.0, H5), 7.06 (t,
1H, J ) 3.0 Hz, H4), 7.22-7.63 (m, 5H, aromatic protons), 8.57
(bs, 1H, NH); 13C NMR (CDCl3, 75 MHz) δ 44.3, 67.9, 126.6,
127.5, 129.3, 129.6, 133.9, 135.0, 173.4; MS (70 eV) 189 (M+,
33), 161 (28), 145 (40), 91 (100); HRMS (EI) calcd for [M+]
C11H11NO2 189.0789, found 189.0791. Anal. Calcd for C11H11NO2:
C, 69.83; H, 5.86; N, 7.40. Found: C, 69.91; H, 5.87; N, 7.38.
(5RS)-3-Ben zyla m in o-5-m eth yl-2(5H)fu r a n on e (17). Com-
pounds 12 and 13 (466 mg) gave 17 (223 mg, 55%) as a light
(3aS,4R,6aS)-8b: [R]25 ) +25.0 (c 1.07, CHCl3).
D
(3aSR,6aRS)-1-Ben zyltetr ah ydr o-3H,6H-fu r o[3,4-c]isoxa-
zol-6-on e (11). Following m eth od B, 4a (1.01 g) and 10 (2.24
g) afforded 11 (1.52 g, 60%) as white needles: mp 163-164 °C;
1
IR (KBr) 3539, 2960, 1782, 1221, 1210 cm-1; H NMR (CDCl3,
300 MHz) δ 3.55 (ddddd, 1H, J ) 3.0, 3.3, 7.6, 8.4, 8.6, H3a),
3.92 (dd, 1H, J ) 3.0, 10.2 Hz, H3′), 4.00 (dd, 1H, J ) 8,6, 10.2
Hz, H3′′), 4.05 (d, 1H, J ) 13.2 Hz, PhCH), 4,17 (d, 1H, J ) 13.2
Hz, PhCH), 4.27 (dd, 1H, J ) 3.3, 9.6 Hz, H4′), 4.31 (d, 1H, J )
8.4 Hz, H6a), 4.50 (dd, 1H, J ) 7.6, 9.6 H4′′), 7.26-7.44 (m, 5H,
aromatic protons); 13C NMR (CDCl3, 75 MHz) δ 30.9, 42.7, 64.5,
71.6, 72.6, 127.8, 128.5, 128.9, 135.9, 169.4; MS (70 eV) 219 (M+,
19), 92 (10), 91 (100); HRMS (EI) calcd for [M+] C12H13NO3
219.0895, found 219.0896. Anal. Calcd for C12H13NO3: C, 65.74;
H, 5.98; N, 6.39. Found: C, 65.81; H, 5.99; N, 6.40.
yellow oil: IR (neat) 3350, 2900, 2830, 1760, 1140, 1017 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.28 (d, 3H, J ) 6.8 Hz, CH3),
4.34 (d, 2H, J ) 13.5, PhCH2), 4.57 (dq, 1H, J ) 2.7 and 6.8 Hz,
H5), 6.80 (t, 1H, J ) 2.7 H4), 7.22-7.63 (m, 5H, aromatic
protons), 8.44 (bs, 1H, NH); 13C NMR (CDCl3, 75 MHz) δ 18.4,
44.3, 75.2, 126.6, 129.3, 129.6, 133.5, 134.9, 150.7, 172.6; MS
(70 eV) 203 (M+, 25), 175 (15), 159 (50), 91 (100); HRMS (EI)
calcd for [M+] C12H13NO2 203.0946, found 203.0948. Anal. Calcd
for C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 71.11; H,
6.50; N, 6.87. Compounds (3aR,4R,6aR)-12 and (3aS,4R,6aS)-
(3a RS,4RS,6a RS)-1-Ben zyl-4-m et h ylt et r a h yd r o-3H,6H-
fu r o[3,4-c]isoxa zol-6-on e (12). Following m eth od B, 4b (1.25
g) and 10 (2.24 g) afforded 12 (1.08 g, 40%) as a white solid: mp
150-152 °C; first eluted product; IR (KBr) 3425, 2980, 1802,
1250, 1210 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.46 (d, 3H, J )
6.6 Hz), 3.48 (m, 1H, H3a), 3.97 (d, 1H, J ) 6.8 Hz, H6a), 4.05 (m,
2H, H3), 4.12 (d, 1H, J ) 12.8 Hz, PhCH), 4,18 (d, 1H, J ) 12.8
Hz, PhCH), 4.73 (dq, 1H, J ) 5.4, 6.6 Hz, H4), 7.30-7.44 (m, 5H,
aromatic protons); 13C NMR (CDCl3, 75 MHz) δ 17.3, 46.0, 50.4,
65.9, 75.2, 80.9, 128.5, 128.9, 129.0, 135.7, 168.8; MS (70 eV)
233 (M+, 20), 142 (15), 98 (60), 91 (100); HRMS (EI) calcd for
13 afforded (5R)-17: [R]25 ) +12.5 (c 0.75, CHCl3).
D
Ack n ow led gm en t. We thank MURST and CNR for
their financial support.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails. This material is available free of charge via the Internet
at http://pubs.acs.org.
[M+] C13H15NO3 233.1052, found 233.1055. Anal. Calcd for C13H15
NO3: C, 66.94; H, 6.48; N, 6.00. Found: C, 66.87; H, 6.47; N, 5.98.
Following m et h od with (R)-(-)-4b (1.25 g) afforded
(3aR,4R,6aR)-12: [R]25 ) +10.0 (c 1.35, CHCl3).
-
B
D
J O025626H