COMMUNICATIONS
Table 1. Trapping reactions of o-azaxylylenes with p-electron-rich dienophiles.
an additional 30 min. This solution of chloroformate was
transferred by cannula to a solution of o-aminobenzyl
alcohol (Alfa, 185 mg, 1.5 mmol) and pyridine (0.14 mL,
1.7 mmol) in dichloromethane (5 mL) over 15 min at 08C.
The reaction mixture was warmed to 238C and stirred for
an additional 2 h. Aqueous workup and chromatography on
silica gel with hexane/ethyl acetate (6/1) afforded the
hydroxy carbamate coupling product as a colorless crystal-
line solid (282 mg, 76%). M.p. 91 ± 928C; [a]2D5 150 (c
0.77 in CHCl3); IR (film): nÄ 3348, 3344, 2939, 1731, 1702,
Substrate
Dienophile Conditions[a]
Product
Yield [%][b]
C
95
1593, 1529, 1454, 1305, 1231, 1219, 1192, 1040, 1008,
1
938 cm
;
1H NMR (400 MHz, CDCl3, 258C): d 7.94 (d,
A
B
91
90
J 8 Hz, 1H), 7.82 (brs, 1H, NH), 7.32 (t, J 7.4 Hz, 1H),
7.17 (d, J 7.4 Hz, 1H), 7.03 (t, J 7.4 Hz, 1H), 5.95 ± 6.00
(m, 1H), 5.78 ± 5.83 (m, 1H), 5.26 ± 5.29 (m, 1H), 4.69 (d,
J 5.2 Hz, 2H), 2.16 (t, J 5.6 Hz, 1H, OH), 1.60 ± 2.14 (m,
6H); 13C NMR (100 MHz, CDCl3, 258C): d 153.98,
137.82, 132.70, 129.25, 129.00, 128.96, 126.00, 123.38,
121.12, 69.04, 64.28, 28.57, 24.94, 18.94; HR-MS (EI): calcd
(found) for C14H17NO3 [M ]: 247.1208 (247.1218). A solu-
tion of thionyl chloride (102 mL, 1.40 mmol) in dichloro-
methane (4 mL) was added over 15 min to a solution
containing the hydroxy carbamate (240 mg, 0.97 mmol) and
triethylamine (195 mL, 1.40 mmol) in dichloromethane
(4 mL). The solution was stirred for 2 h and the solvent
was removed in vacuo. Chromatography of the crude
product on silica gel with hexane/ethyl acetate (6/1)
afforded 7 as a colorless crystalline solid (230 mg, 89%).
M.p. 120 ± 1218C; [a]D25 141 (c 0.95 in CHCl3); IR
A
B
90
40
(film): nÄ 3285, 3037, 3029, 2945, 2913, 1687, 1590, 1527,
1
1456, 1296, 1248, 1049 cm
;
1H NMR (400 MHz, CDCl3,
258C): d 7.87 (d, J 7.8 Hz, 1H), 7.37 (t, J 1.4, 7.8 Hz,
1H), 7.28 (d, J 1.4, 7.6 Hz, 1H), 7.09 (t, J 7.5 Hz, 1H),
6.87 (brs, 1H, NH), 5.98 ± 6.02 (m, 1H), 5.79 ± 5.83 (m, 1H),
5.29 ± 5.31 (m, 1H), 4.62 (s, 2H), 1.65 ± 2.14 (m, 6H);
13C NMR (100 MHz, CDCl3, 258C): d 153.66, 136.89,
132.94, 130.14, 130.08, 127.19, 125.83, 124.30, 122.82, 69.40,
44.03, 28.56, 24.94, 18.92; HR-MS (EI): calcd (found) for
B
B
60
95
C14H16NO2Cl [M ]: 265.0869 (265.0878).
8:
A suspension of 7 (53 mg, 0.2 mmol) and cesium
carbonate (163 mg, 0.5 mmol) in dichloromethane (5 mL)
was stirred for 40 h at 238C. The reaction mixture was
filtered through
a pad of celite and the solvent was
evaporated in vacuo. Chromatography of the crude product
on silica gel with hexane/ethyl acetate (6/1) gave 8 as a
colorless crystalline solid (35 mg, 76%). M.p. 149 ± 1508C;
[a]2D5 82 (c 0.95 in CHCl3); IR (film): nÄ 2929, 1744,
1494, 1459, 1390, 1364, 1349, 1339, 1324, 1293, 1227, 1209,
[a] A: 2 h, 788C, 10 equiv dienophile, addition of substrate over 15 min; B: 24 ± 48 h, rt,
10 equiv dienophile, addition of substrate over 1 min; C: 24 h, rt, 2 equiv dienophile,
addition of substrate by syringe pump over 24 h; [b] yields of isolated products after
chromatography on silica gel with mixtures of hexane/EtOAc (1% NEt3 for 14 and 15)
for elution.
1
1185, 1135, 1104, 1060, 994, 946 cm 1; H NMR (400 MHz,
CDCl3, 258C): d 8.40 (d, J 8.4 Hz, 1H), 7.21 (t, J
7.8 Hz, 1H), 7.10 (d, J 7.5 Hz, 1H), 6.98 (t, J 7.4 Hz,
1H), 4.64 (dt, J 6.6, 8.6 Hz, 1H), 4.26 (dd, J 3.8, 6.6 Hz,
1H), 3.12 (dd, J 5.9, 16.7 Hz, 1H), 2.65 (d, J 16.4 Hz,
1H), 2.08 ± 2.22 (m, 2H), 1.71 ± 1.77 (m, 1H), 1.44 ± 1.61 (m,
2H), 1.31 ± 1.36 (m, 1H), 1.15 ± 1.22 (m, 1H); 13C NMR (100 MHz, CDCl3,
258C): d 154.28, 134.50, 129.47, 127.06, 122.74, 122.09, 116.31, 73.06, 56.03,
32.55, 29.19, 27.14, 24.44, 19.66; HR-MS (FAB): calcd (found) for
([a]2D5 53, c 0.9 in CHCl3), and the sulfonamide 12
underwent cyclization with HBr/phenol to the bicyclic lactam
17 in 95% yield.
The reactions described herein define a practical and
versatile method for the generation and use of o-azaxylylenes
in aza-Diels ± Alder reactions which proceed from readily
available precursors and under mild conditions.
C14H15NO2Na [M Na ]: 252.1000 (252.1008).
16: A solution of 8 (31.5 mg, 0.137 mmol) in 10% ethanolic NaOH (2 mL)
was heated at reflux for 1 h. After evaporation of the solvent in vacuo the
mixture was suspended in water (5 mL) and extracted with chloroform
(10 mL Â 3). The combined organic layers were dried over sodium sulfate,
filtered, and the solvent was removed in vacuo. Chromatography of the
crude mixture on silica gel with hexane/ethyl acetate (6/1) afforded the
chiral aminoalcohol 16 as a colorless crystalline solid (25 mg, 90%).
M.p. 134 ± 1358C; [a]2D5 53 (c 0.9 in CHCl3); IR (film): nÄ 3419, 3405,
Experimental Section
All reactions were carried out under an inert atmosphere with anhydrous
solvents.
3378, 3371, 3300, 3235, 3225, 3201, 3017, 2936, 2920, 2895, 2855, 1606, 1504,
1
1496, 1486, 1444, 1374, 1289, 1104, 1054, 1043, 1008 cm
;
1H NMR
7: A solution of (R)-2-cyclohexen-1-ol[10] (147 mg, 1.5 mmol) in diethyl
ether (1 mL) was added to a solution of phosgene (3 mmol) in toluene
(1.6 mL) at 788C. The mixture was stirred at 158C for 3 h and at 08C for
(500 MHz, CDCl3, 258C): d 6.97 (t, J 7.6 Hz, 1H), 6.93 (d, J 7.4 Hz,
1H), 6.57 (t, J 7.3 Hz, 1H), 6.49 (d, J 8 Hz, 1H), 4.21 (brs, 1H, NH),
3.81 ± 3.85 (m, 1H), 3.64 (t, J 3 Hz, 1H), 3.03 (dd, J 5.6, 16.2 Hz, 1H),
1930
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1433-7851/99/3813-1930 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1999, 38, No. 13/14