8056 J . Org. Chem., Vol. 64, No. 21, 1999
Notes
(2H, t, J ) 7.1 Hz), 7.51 (1H, t, J ) 7.1 Hz), 7.77 (2H, d, J ) 7.1
Hz), 8.15 (1H, br); 13C NMR (75 MHz, CDCl3) δ 32.42, 51.08,
116.34, 126.81, 128.52, 131.67, 132.78, 135.77, 167.12; IR (film)
3223, 1638, 1543 cm-1; HRMS calcd for C11H13N2O (M+ - 1),
189.1028; found, 189.1052.
Meth yl 3-(N′-ben zoylh ydr azin o)-2,2-dim eth ylpr opan oate.
1H NMR (300 MHz, CDCl3) δ 1.26 (6H, s), 3.10 (2H, brs), 3.67
(3H, s), 5.04 (1H, br), 7.40-7.45 (2H, m), 7.48-7.54 (2H, m),
7.73-7.77 (2H, m), 7.94 (1H, brs); 13C NMR (75 MHz, CDCl3) δ
23.63, 42.93, 52.02, 60.73, 126.82, 128.68, 131.84, 132.67, 167.06,
177.86; IR (neat) 3300, 2974, 1729, 1646, 1469, 1151 cm-1
HRMS calcd for C13H18N2O3, 250.1317; found, 250.1330.
;
N′-(2-(Ben zyloxyca r bon yl)a m in o-1-p h en yl-5-h exen -3-yl)-
ben zoh yd r a zid e. A mixture of two diastereomers: 1H NMR
for one isomer (400 MHz, CDCl3) δ 2.08 (1H, dt, J ) 13.9, 9.5
Hz), 2.39 (1H, brd, J ) 13.9 Hz), 2.70 (1H, dd, J ) 14.4, 9.8 Hz),
2.75 (1H, dd, J ) 14.4, 5.4 Hz), 3.12 (1H, dt, J ) 9.8, 2.9 Hz),
4.33-4.36 (1H, m), 5.02 (1H, d, J ) 12.5 Hz), 5.03 (1H, d, J )
9.5 Hz), 5.12 (1H, d, J ) 12.5 Hz), 5.24 (1H, d, J ) 12.0 Hz),
5.28 (1H, d, J ) 19.0 Hz), 5.90-6.00 (1H, m), 7.14-7.31 (10H,
m), 7.42 (2H, t, J ) 7.3 Hz), 7.49 (1H, t, J ) 7.3 Hz), 7.83 (2H,
d, J ) 7.3 Hz), 8.98 (1H, s); for the another isomer (300 MHz,
DMSO-d6) δ 2.05-2.15 (1H, m), 2.33-2.38 (1H, m), 2.60 (1H, t,
J ) 12.6 Hz), 2.96 (1H, brs), 3.10 (1H, d, J ) 12.6 Hz), 3.95 (1H,
t, J ) 9.5 Hz), 4.90 (1H, d, J ) 12.8 Hz), 4.93 (1H, d, J ) 12.8
Hz), 5.07 (1H, d, J ) 10.4 Hz), 5.14 (1H, d, J ) 17.2 Hz), 5.85-
5.98 (1H, m), 7.16-7.32 (11H, m), 7.43-7.54 (3H, m), 7.85 (2H,
d, J ) 7.3 Hz), 10.12 (1H, s); 13C NMR for one isomer (100 MHz,
CDCl3) δ 31.69, 37.26, 52.34, 60.41, 66.79, 118.83, 126.55, 126.82,
127.53, 127.96, 128.42, 128.54, 128.56, 128.58, 131.62, 132.51,
134.09, 136.24, 137.63, 157.56, 166.26; for the another isomer
(75 MHz, DMSO-d6) δ 32.81, 34.90, 53.26, 62.35, 64.83, 117.04,
125.80, 127.15, 127.19, 127.55, 127.94, 128.26, 128.37, 129.26,
131.31, 133.32, 136.15, 137.34, 139.76, 155.69, 165.94; IR (film)
3297, 1703, 1535 cm-1; HRMS calcd for C27H29N3O3, 443.2209;
found, 443.2194.
Eth yl 2-(N′-Ben zoylh yd r a zin o)-4-p en ten oa te. 1H NMR
(300 MHz, CDCl3) δ 1.27 (3H, t, J ) 7.1 Hz), 2.42-2.52 (1H, m),
2.58-2.66 (1H, m), 3.85 (1H, t, J ) 5.9 Hz), 4.08-4.28 (2H, m),
5.16 (1H, d, J ) 8.6 Hz), 5.20 (1H, d, J ) 15.4 Hz), 5.80-5.94
(1H, m), 7.42 (2H, t, J ) 7.1 Hz), 7.51 (1H, t, J ) 7.1 Hz), 7.77
(2H, d, J ) 7.1 Hz), 8.41 (1H, br); 13C NMR (75 MHz, CDCl3) δ
14.21, 35.24, 61.14, 62.13, 118.85, 127.03, 128.62, 131.90, 132.59,
132.93, 167.09, 172.68; IR (neat) 3290, 1736, 1647, 1465, 1200
cm-1; HRMS calcd for C14H18N2O3, 262.1317; found, 262.1281.
N′-(1,1,1-Tr ich lor o-4-pen ten -2-yl)ben zoh ydr azide. 1H NMR
(300 MHz, CDCl3) δ 2.45 (1H, dt, J ) 15.0, 9.7 Hz), 2.94-3.00
(1H, m), 3.71 (1H, dd, J ) 9.7, 2.9 Hz), 5.19 (1H, br), 5.31 (1H,
d, J ) 12.3 Hz), 5.31 (1H, d, J ) 13.9 Hz), 6.13-6.26 (1H, m),
7.44 (2H, t, J ) 7.7 Hz), 7.59 (1H, t, J ) 7.7 Hz), 7.74 (2H, d, J
) 7.7 Hz), 7.97 (1H, brs); 13C NMR (75 MHz, CDCl3) δ 35.47,
74.70, 103.85, 119.43, 126.86, 128.77, 132.15, 132.24, 133.37,
166.96; IR (film) 3294, 1643, 1528, 1469 cm-1; HRMS calcd for
Meth yl 3-(N′-Ben zoylh yd r a zin o)-4-ben zyloxyca r bon yl-
a m in o-2,2-d im eth yl-5-p h en ylp en ta n oa te. A mixture of two
diastereomers, 1H NMR (300 MHz, CDCl3) δ 1.11 (2.64H, s), 1.14
(2.64H, s), 1.40 (0.36H, s), 1.44 (0.36H, s), 2.77-3.05 (2H, m),
3.21 (0.88H, brs), 3.31 (0.12H, d, J ) 4.0 Hz), 3.58 (2.64H, s),
3.65 (0.36H, s), 4.17-4.30 (1H, m), 4.88-5.09 (2H, m), 5.14 (1H,
br), 6.47 (0.12H, brd, J ) 10.0 Hz), 6.73 (0.88H, d, J ) 10.0 Hz),
7.14-7.31 (10H, m), 7.41-7.56 (3H, m), 7.74-7.79 (2H, m), 8.07
(0.88H, brs), 8.34 (0.12H, br); 13C NMR (75 MHz, CDCl3) for
major isomer δ 19.68, 23.60, 42.55, 46.78, 51.18, 52.01, 66.41,
66.69, 126.43, 126.84, 127.80, 127.86, 128.32, 128.37, 128.80,
129.40, 132.10, 132.22, 136.77, 137.84, 156.06, 167.55, 177.93;
IR (neat) 3317, 2951, 1720, 1641 cm-1; HRMS calcd for
C
29H33N3O5, 503.2420; found, 503.2390.
1-Meth yl Eth yl 3-(N′-ben zoylh yd r a zin o)-2,2-d im eth yl-
su ccin a te. Colorless prisms; mp 101-103 °C; 1H NMR (300
MHz, CDCl3) δ 1.24 (3H, s), 1.25 (3H, t, J ) 7.1 Hz), 1.36 (3H,
s), 3.72 (3H, s), 3.95 (1H, d, J ) 5.1 Hz), 4.12-4.28 (2H, m),
5.44 (1H, t, J ) 5.1 Hz), 7.41 (2H, t, J ) 7.1 Hz), 7.51 (1H, t, J
) 7.1 Hz), 7.74 (2H, d, J ) 7.1 Hz), 8.15 (1H, d, J ) 5.1 Hz); 13
C
NMR (75 MHz, CDCl3) δ 14.10, 21.66, 21.99, 45.69, 52.19, 61.37,
69.37, 126.98, 128.61, 131.85, 132.59, 167.12, 171.38, 176.24; IR
(KBr) 3304, 1740, 1640, 1510, 1211 cm-1; MS m/z 322 (M+); Anal.
Calcd for C16H22N2O5: C,59.62; H, 6.88; N, 8.69. Found: C,
59.50; H, 6.74; N, 8.45.
Gen er a l P r oced u r e for Cya n id e Ad d ition Rea ction s. To
a solution of a hydrazone (0.40 mmol) in acetonitrile (2.4 mL)
was added trimethylsilyl cyanide (1.2 mmol) in acetonitrile
(0.8 mL) at room temperature. After stirring for 5 min, 0.04 M
Hf(OTf)4 (0.020 mmol) in acetonitrile was added and the whole
was stirred at the same temperature. The reaction was quenched
with saturated aqueous NaHCO3 solution, and the aqueous layer
was extracted with CH2Cl2. After a usual workup, the crude
product was purified by silica gel chromatography to give the
desired product.
N′-(1-Cyan o-2,3-dih yr doxypr opyl)ben zoh ydr azide. A mix-
ture of two diastereomers, 1H NMR (300 MHz, acetone-d6) δ
3.71-4.25 (5H, m), 4.91 (0.27H, d, J ) 5.3 Hz, secondary OH),
5.17 (0.73H, d, J ) 4.6 Hz, secondary OH), 5.88 (0.73H, t, J )
5.5 Hz, NH), 5.96 (0.27H, t, J ) 7.5 Hz, NH), 7.45-7.57 (3H,
m), 7.89-7.94 (2H, m), 9.64 (1H, brs, CONH); 13C NMR (75 MHz,
acetone-d6) for major isomer δ 55.28, 63.18, 71.25, 118.59, 127.82,
129.01, 132.40, 133.09, 168.02; for minor isomer δ 56.42, 63.48,
70.87, 117.96, 127.73, 129.01, 132.30, 133.19, 167.43; IR (KBr)
3511, 3276, 2238, 1635 cm-1; HRMS calcd for C11H13N3O3,
235.0957; found, 235.0939.
N′-(1-Cya n o-2-p h en ylet h yl)b en zoh yd r a zid e. Colorless
plates; mp 138-139 °C; 1H NMR (300 MHz, DMSO-d6) δ 2.99
(1H, dd, J ) 13.7, 8.1 Hz), 3.10 (1H, dd, J ) 13.7, 6.2 Hz), 4.32
(1H, dt, J ) 8.1, 6.2 Hz), 6.08 (1H, t, J ) 6.2 Hz), 7.14-7.32
(5H, m), 7.41 (2H, t, J ) 7.1 Hz), 7.48 (1H, t, J ) 7.1 Hz), 7.80
(2H, d, J ) 7.1 Hz), 10.30 (1H, d, J ) 6.2 Hz); 13C NMR (75
MHz, DMSO-d6) δ 36.64, 53.47, 119.65, 127.06, 127.36, 128.44,
128.49, 129.61, 131.77, 132.58, 136.12, 166.19; IR (KBr) 3283,
2249, 1637, 1517, 1471 cm-1; MS m/z 265 (M+). Anal. Calcd for
C16H15N3O: C, 72.43; H, 5.70; N, 15.84. Found: C, 72.22; H,
5.84; N, 15.57.
C
12H13Cl3N2O, 306.0093; found, 306.0067.
Gen er a l P r oced u r e for Ma n n ich -Typ e Rea ction s. To a
solution of Sc(OTf)3 (0.020 mmol) and a hydrazone (0.40 mmol)
in acetonitrile (2.4 mL) was added a ketene silyl acetal (0.60
mmol) in acetonitrile (0.8 mL) at room temperature. After
stirring at the same temperature, the reaction was quenched
with saturated aqueous NaHCO3 solution, and the aqueous layer
was extracted with CH2Cl2. After a usual workup, the crude
product was purified by silica gel chromatography to give the
desired product.
(3R,4S)-3-(N′-Ben zoylh yd r a zin o)-4-h yd r oxym et h yl-2,2-
d im eth yl-4-bu ta n olid e (8). Colorless plates; mp 151.5-153.0
°C; 1H NMR (300 MHz, CD3OD) δ 1.25 (3H, s), 1.29 (3H, s), 3.62
(1H, d, J ) 6.2 Hz), 3.92 (1H, dd, J ) 12.3, 5.9 Hz), 3.98 (1H,
dd, J ) 12.3, 4.6 Hz), 4.62 (1H, ddd, J ) 6.2, 5.9, 4.6 Hz), 7.34-
7.40 (2H, m), 7.43-7.49 (1H, m), 7.67-7.72 (2H, m); 13C NMR
(75 MHz, CD3OD) δ 19.53, 25.56, 44.67, 61.28, 67.79, 81.48,
128.21, 129.62, 132.97, 134.02, 169.50, 183.14; IR (KBr) 3334,
1750, 1646, 1352, 1139, 1053 cm-1; MS m/z 278 (M+); Anal.
Calcd for C14H18N2O4: C, 60.42; H, 6.52; N, 10.07. Found: C,
60.19; H, 6.67; N, 9.95.
Meth yl 3-(N′-ben zoylh yd r a zin o)-2,2-d im eth yl-4-p h en yl-
bu ta n oa te. 1H NMR (300 MHz, CDCl3) δ 1.30 (3H, s), 1.37 (3H,
s), 2.64 (1H, dd, J ) 13.9, 9.9 Hz), 2.92 (1H, dd, J ) 13.9, 3.1
Hz), 3.56 (3H, s), 3.62 (1H, dd, J ) 9.9, 3.1 Hz), 7.19-7.32 (8H,
m), 7.38-7.44 (3H, m); 13C NMR (75 MHz, CDCl3) δ 20.75, 22.65,
36.46, 45.79, 51.89, 67.11, 126.34, 126.60, 128.23, 128.60, 129.01,
131.44, 132.28, 139.38, 165.98, 177.82; IR (KBr) 3275, 31.93,
3076, 2983, 1735, 1629, 1605, 1570 cm-1; HRMS calcd for
N′-(Cya n om eth yl)ben zoh yd r a zid e. Colorless plates; mp
1
152-155 °C; H NMR (300 MHz, DMSO-d6) δ 3.91 (2H, d, J )
5.1 Hz), 5.98 (1H, q, J ) 5.1 Hz), 7.44-7.57 (3H, m), 7.84 (2H,
dd, J ) 8.3, 1.3 Hz), 10.31 (1H, d, J ) 5.9 Hz); 13C NMR (75
MHz, DMSO-d6) δ 39.06, 118.53, 127.21, 128.46, 131.68, 132.60,
165.90; IR (KBr) 3286, 2246, 1639, 1563, 1308 cm-1; MS m/z
175 (M+). Anal. Calcd for C9H9N3O: C, 61.70; H, 5.18; N, 23.99.
Found: C, 61.62; H, 5.24; N, 24.00.
N′-(2-Ben zyloxyca r b on yla m in o-1-cya n o-3-p h en yl)b en -
zoh yd r a zid e. For major isomer 1H NMR (300 MHz, acetone-
d6) δ 3.01 (1H, dd, J ) 13.7, 9.7 Hz), 3.27 (1H, dd, J ) 13.7, 4.6
Hz), 4.31-4.46 (2H, m), 5.04 (2H, s), 5.95 (1H, t, J ) 6.2 Hz),
6.90 (1H, d, J ) 8.8 Hz), 7.19-7.36 (10H, m), 7.48 (2H, tt, J )
C
20H24N2O3, 340.1787; found, 340.1740.