3320 J . Org. Chem., Vol. 67, No. 10, 2002
Zhao et al.
Gen er a l P r oced u r e for P r ep a r a tion of Nitr on es. (2R)-
2-[(Z)-{[2-(Allyloxy)-1-n aph th yl]m eth ylen e}(oxido)am in o]-
2-p h en yleth a n ol (4). To a solution of N-hydroxyamine 2 (153
mg, 1 mmol) in CH2Cl2 (3 mL) was added 2-allyloxy-1-
naphthaldehyde (233 mg, 1.1 mmol), glacial acetic acid (0.003
mL), and MgSO4 (140 mg). The mixture was stirred at room
temperature for 5 h. The mixture was filtered at room
temperature and washed with CH2Cl2. The organic phase was
washed with saturated NaHCO3 solution, H2O, and brine. The
organic layer was dried (Na2SO4) and concentrated. Flash
chromatography (33% ethyl acetate in hexanes) afforded
nitrone 4 (300 mg, 86%) as a white solid: Rf 0.3 (50% ethyl
124.67, 120.24, 119.6, 111.19, 81.58, 77.76, 77.44, 69.63, 64.07;
HRMS (FAB) m/e 343.1289 (C18H18N2O5 + H requires 343.1294).
(2R)-2-[(Z)-[2-(Allyloxy)-4,6-d ich lor oben zylid en e](oxi-
d o)a m in o]-2-p h en yleth a n ol (18): 88% yield; Rf 0.56 (50%
ethyl acetate in hexanes); [R]23D -21.2 (c 0.65, CH2Cl2); IR (thin
1
film) 3392, 1570 cm-1; H NMR (400 MHz, CDCl3) δ 9.21 (d,
1H, J ) 3 Hz), 7.82 (s, 1H), 7.49-7.3 (m, 6 H), 5.89 (m, 1H),
5.4-5.1 (m, 3H), 4.6 (dd, 1H, J ) 12, 9 Hz), 4.42 (A of ABX,
1H, J AB ) 12 Hz, J AX ) 6 Hz), 4.3 (B of ABX, 1H, J AB ) 12 Hz,
J BX ) 6 Hz), 3.91 (dd, 1H, J ) 12, 3 Hz), 3.8 (br, 1H); 13C NMR
(100 MHz, CDCl3) δ 153.05, 136.27, 133.66, 131.59, 131.09,
130.61, 129.84, 129.15, 128.48, 127.67, 127.08, 121.05, 82.83,
acetate in hexanes); [R]23 -28.5 (c 0.778, CH2Cl2); IR (thin
78.98, 78.67, 77.1, 65.94; HRMS (FAB) m/e 366.0667 (C18H17-
D
film) 3295, 1591, 1512 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.96
(1 H, s), 7.9 (d, 1 H, J ) 9 Hz), 7.79 (d, 1H, J ) 8.1 Hz), 7.64-
7.35 (m, 8H), 7.24 (d, 1H, J ) 9 Hz), 6.0 (m, 1H), 5.4-5.25 (m,
3H), 4.68 (dd, 2H, J ) 4, 1.5 Hz), 4.59 (dd, 1H, J ) 12, 9 Hz),
4.02 (dd, 1H, J ) 12, 3 Hz). 13C NMR (75 MHz, CDCl3) δ
155.63, 135.33, 133.62, 132.95, 132.37, 131.09, 129.11, 129.04,
128.89, 128.37, 127.75, 127.22, 124.97, 124.21, 117.97, 113.86,
112.6, 79.07, 77.26, 70.05, 64.3; HRMS HRMS (FAB) m/e
348.1589 (C22H21NO3 + H requires 348.1599). Anal. Calcd for
NO3Cl2 + H requires 366.0663). Anal. Calcd for C18H17NO3-
Cl2: C, 59.03%; H, 4.68%; N, 3.82%; Cl, 19.36%. Found: C,
59.89%; H, 5.06%; N, 3.62%; Cl, 17.61%.
(2R)-2-[(Z)-[2-(Allyloxy)-5-m eth oxyben zyliden e](oxido)-
a m in o]-2-p h en yleth a n ol (19): 85% yield; Rf 0.34 (50% ethyl
acetate in hexanes); [R]23D -18.8 (c 0.68, CH2Cl2); IR (thin film)
1
3225, 1485 cm-1; H NMR (400 MHz, CDCl3) δ 8.85 (d, 1H, J
) 3 Hz), 7.91 (s, 1H), 7.49-7.42 (m, 5 H), 6.84 (dd, 1H, J ) 9,
3 Hz), 6.71 (d, 1H, J ) 9 Hz), 5.85 (m, 1H), 5.2-5.1 (m, 3 H),
4.69 (dd, 1 H, J ) 9.2, 9 Hz), 4.38 (m, 2H), 3.92 (dd, 1H, J )
9.4, 3 Hz), 3.72 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 153.74,
151.47, 135.46, 133.21, 132.76, 129.53, 128.1, 120.1, 119.62,
118.1, 113.37, 113.17, 80.53, 77.65, 70.4, 68.6, 56.22; HRMS
(FAB) m/e 328.1552 (C18H21NO4 + H requires 328.1548).
(2R)-2-[(Z)-[2-(Allyloxy)-4-m eth oxyben zyliden e](oxido)-
a m in o]-2-p h en yleth a n ol (20): 89% yield; Rf 0.35 (50% ethyl
acetate in hexanes); [R]23D -25.5 (c 0.88, CH2Cl2); IR (thin film)
C
22H21NO3: C, 76.06%; H, 6.09%; N, 4.03%. Found: C, 75.69%;
H, 6.21%; N, 4.00%.
(Z)-{[2-(Allyloxy)-1-n a p h th yl]m eth ylen e}[(1R)-2-(ben -
zyloxy)-1-p h en yleth yl]a za n e oxid e (5): 85% yield; Rf 0.46
(40% ethyl acetate in hexanes); [R]23 -23.6 (c 0.63, CH2Cl2);
D
IR (thin film) 3088, 1591, 1509 cm-1
;
1H NMR (300 MHz,
CDCl3) δ 8.08 (s, 1H), 7.84 (d, 1H, J ) 9 Hz), 7.75 (d, 1H, J )
7.5 Hz), 7.72-7.6 (m, 4H), 7.45-7.2 (m, 9H), 7.19 (d, 1H, J )
9 Hz), 5.92 (m, 1H), 5.4 (dd, 1H, J ) 9, 3 Hz), 5.3 (dd, 1H, J )
16, 1.5 Hz), 5.17 (d, 1H, J ) 10.5 Hz), 4.82 (A of ABq, J AB)12
Hz), 4.75-4.5 (m, 4H), 3.9 (dd, 1H, J ) 10, 3.6 Hz); 13C NMR
(75 MHz, CDCl3) δ 155.78, 138.02, 135.03, 133.13, 131.96,
131.66, 131.11, 128.98, 128.91, 128.67, 128.47, 128.08, 128.03,
127.83, 127.76, 126.88, 125.91, 124.02, 117.27, 113.95,
113.5478.7, 73.73, 69.97, 69.94; HRMS (FAB) m/e 438.2080
1
3100, 1601, 1568 cm-1; H NMR (400 MHz, CDCl3) δ 9.15 (d,
1H, J ) 9 Hz), 8.2 (s, 1H), 7.55-7.52 (m, 2H), 7.36-7.34 (m,
3H), 6.49 (dd, 1H, J ) 9, 2.4 Hz), 6.31 (d, 1H, J ) 2.4 Hz), 5.9
(m, 1H), 5.54 (dd, 1H, J ) 9, 3 Hz), 5.23-5.18 (m, 3H), 4.64
(dd, 1H, J ) 12, 9 Hz), 4.45 (d, 2H, J ) 4 Hz), 4.17 (dd, 1H, J
) 12, 3 Hz), 3.78 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 165.7,
160.67, 141.2, 134.56, 132.38, 129.77, 129.49, 128.71, 118.64,
110.94, 106.09, 99.58, 79.04, 77.65, 69.86, 69.61, 63.08, 56.12;
HRMS (FAB) m/e 328.1553 (C18H21NO4 + H requires 328.1548).
Gen er a l P r oced u r e for Cycliza tion of Nitr on es. (2R)-
2-((3a S,11cR)-3a ,11c-Dih yd r o-3H -b en zo[5,6]ch r om en o-
[4,3-c]isoxazol-1(4H)-yl)-2-ph en yleth an ol (8). Zn(OTf)2 (363
mg, 1 mmol) was added to a solution of 4 (173 mg, 0.5 mmol)
and Et3N (0.35 mL, 2.5 mmol) in CH2Cl2 (3 mL). The reaction
was then heated to 40 °C and stirred for 68 h. The reaction
was then analyzed by HPLC, and the ratio of products was
determined. The reaction was then diluted with CH2Cl2 and
H2O. The aqueous phase was extracted with CH2Cl2, and the
organic phases were combined, dried (Na2SO4), and concen-
trated. Purification via flash chromatography (50% ethyl
acetate in hexanes) afforded 8 (156 mg, 89%) and 9 (6 mg,
(C29H27NO3 + H requires 438.2069). Anal. Calcd for C29H27
-
NO3: C, 79.61%; H, 6.22%; N, 3.20%. Found: C, 79.19%; H,
6.43%; N, 3.20%.
(Z)-{[2-(Allyloxy)-1-n a p h th yl]m eth ylen e}[(1R)-2-m eth -
oxy-1-p h en yleth yl]a za n e oxid e (6): 86% yield; Rf 0.38 (40%
ethyl acetate in hexanes); [R]23D -19.2 (c 0.68, CH2Cl2); IR (thin
film) 1608, 1598, 1571 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.05
(s, 1H), 7.83 (d, 1H, J ) 9 Hz), 7.75 (d, 1H, J ) 8.2 Hz), 7.72-
7.6 (m, 2H), 7.57 (d, 1H, J ) 8.4 Hz), 7.48 (dd, 1H, J ) 6.6, 1
Hz), 7.45-7.3 (m, 4H), 7.18 (d, 1H, J ) 9 Hz), 5.96 (m, 1H),
5.4-5.26 (m, 2H), 5.21 (dd, 1H, J ) 10.5, 2 Hz), 4.7-4.5 (m,
3H), 3.81 (dd, 1H, J ) 10, 3.6 Hz), 3.55 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 155.78, 135.05, 133.17, 132, 131.6, 131.09, 129,
128.91, 128.69, 128.1, 128.04, 126.92, 125.83, 124, 117.25,
113.92, 113.49, 78.5, 72.04, 69.95, 59.28; HRMS (FAB) m/e
362.1751 (C22H23NO3 + H requires 362.1756).
3%): Rf 0.56 (50% ethyl acetate in hexanes); [R]23 -32.6 (c
D
1
0.69, CH2Cl2); IR (thin film) 3592, 1599, 1470 cm-1; H NMR
(2R)-2-[(Z)-[2-(Allyloxy)ben zylid en e](oxid o)a m in o]-2-
p h en yleth a n ol (16): 85% yield; Rf 0.38 (50% ethyl acetate in
(300 MHz, CDCl3) δ 7.68 (d, 1H, J ) 9 Hz), 7.63 (d, 1H, J ) 9
Hz), 7.6-7.48 (m, 5H), 7.27 (t, 1H, J ) 7.8 Hz), 7.14 (t, 1H, J
) 7.8 Hz), 7.01 (d, 1H, J ) 9 Hz), 6.96 (d, 1H, J ) 9 Hz), 4.87
(d, 1H, J ) 8 Hz), 4.6 (dd, 1H, J ) 9.6, 7.8 Hz), 4.4-4.2 (m,
3H), 4.12 (dd, 1H, J ) 6.6, 3.6 Hz), 4.06 (dd, 1H, J ) 11, 2
Hz), 3.9 (m, 1H), 3.58 (m, 1H), 2.9 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 155.67, 137.43, 132.49, 129.99, 129.76, 129.24, 128.93,
128.31, 125.62, 124.13, 123.54, 118.55, 114.37, 68.84, 68.3,
hexanes); [R]23 -27.2 (c 0.78, CH2Cl2); IR (thin film) 3395,
D
1595, 1564 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.3 (d, 1H, J )
8 Hz), 8.02 (s, 1H), 7.6-7.3 (m, 6H), 7.02 (t, 1H, J ) 8.2 Hz),
6.86 (d, 1H, J ) 8 Hz), 6.02 (m, 1H), 5.4-5.1 (m, 3H), 4.7-4.4
(m, 3H), 4.0 (dd, 1H, J ) 12, 3 Hz), 4.78 (br, 1H); 13C NMR
(100 MHz, CDCl3) δ 156.63, 135.8, 133.08, 133.03, 132.27,
131.4, 130.37, 129.51, 129.24, 128.82, 121.22, 120.3, 119.3,
111.87, 80.91, 77.87, 69.26, 64.79; HRMS (FAB) m/e 298.1441
67.07, 65.5, 58.96, 41.17; HRMS (FAB) m/e 348.1597 (C22H21
-
NO3 + H requires 348.1599). Anal. Calcd C22H21NO3: C,
76.06%; H, 6.09%; N, 4.03%. Found: C, 74.44%; H, 6.05%; N,
3.96%. Single crystals of 8 suitable for X-ray structure deter-
mination were obtained by slowly evaporating a saturated 5:2
CH2Cl2/hexanes solution of 8 (complete crystallographic data
can be found in the Supporting Information).
(2R )-2-((3a R ,11c S )-3a ,11c -D ih y d r o -3H -b e n zo [5,6]-
ch r om en o[4,3-c]isoxa zol-1(4H)-yl)-2-p h en yleth a n ol (9): Rf
0.38 (50% ethyl acetate in hexanes); [R]23D -26.6 (c 0.75, CH2-
Cl2); IR (thin film) 3418, 1600, 1516 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.98 (d, 1H, J ) 9 Hz), 7.78 (d, 1H, J ) 7.8 Hz), 7.68
(d, 1H, J ) 9 Hz), 7.58 (td, 1H, J ) 7.2, 1.5 Hz), 7.52-7.3 (m,
6H), 7.02 (d, 1H, J ) 9 Hz), 5.13 (d, 1H, J ) 8.1 Hz), 4.27-4.2
(C18H19NO3 + H requires 298.1443). Anal. Calcd for C18H19
-
NO3: C, 72.71%; H, 6.44%; N, 4.71%. Found: C, 72.33%; H,
6.44%; N, 4.74%.
(2R)-2-[(Z)-[2-(Allyloxy)-5-n it r ob en zylid en e](oxid o)-
a m in o]-2-p h en yleth a n ol (17): 89% yield; Rf 0.28 (50% ethyl
acetate in hexanes); [R]23D -31.2 (c 0.75, CH2Cl2); IR (thin film)
1
3347, 1608, 1574 cm-1; H NMR (400 MHz, CDCl3) δ 10.1 (d,
1H, J ) 3 Hz), 8.2 (dd, 1H, J ) 9, 3 Hz), 7.89 (s, 1H), 7.55-7.2
(m, 5 H), 6.8 (d, 1H, J ) 9 Hz), 5.93 (m, 1H), 5.35-5.2 (m,
2H), 5.15 (dd, 1H, J ) 9, 3 Hz), 4.65-4.5 (m, 2H), 3.86 (dd,
1H, J ) 12, 3 Hz); 13C NMR (100 MHz, CDCl3) δ 160.51,
141.52, 135.22, 131.68, 129.61, 129.25, 128.95, 127.9, 127.6,