Synthesis of â-Amino Cyclic Ethers
J . Org. Chem., Vol. 64, No. 13, 1999 4907
94%): colorless oil; Rf ) 0.80 (hexane/AcOEt, 4:1); 1H NMR
(270 MHz, CDCl3) δ 7.40-7.06 (m, 10H), 6.45 (t, J ) 5.1 Hz,
1H), 5.77 (dt, J ) 6.2, 1.1 Hz, 1H), 4.51 (dt, J ) 6.2, 9.1 Hz,
1H), 3.72 (t, J ) 6.6 Hz, 2H), 2.37 (dt, J ) 5.1, 7.0 Hz, 2H),
1.87 (quint, J ) 7.0 Hz, 2H), 1.65 (dt, J ) 9.1, 1.1 Hz, 2H),
1.55-0.81 (m, 27H); IR (neat) 3034, 1650, 1091 cm-1; HRMS
m/z calcd for C31H48N2OSn 584.2789, found 584.2751.
142 °C; Rf ) 0.15 (hexane/AcOEt, 3:1); 1H NMR (270 MHz,
CDCl3) δ 7.72-7.40 (m, 5H), 5.93 (ddd, J ) 17.3, 10.5, 8.0 Hz,
1H), 5.63 (br, 1H), 5.33 (ddd, J ) 17.3, 1.4, 0.9 Hz, 1H), 5.24
(ddd, J ) 10.5, 1.4, 0.7 Hz, 1H), 4.04 (m, 2H), 3.67 (dd, J )
8.4, 8.0 Hz, 1H), 3.48 (ddd, J ) 11.4, 10.0, 3.3 Hz, 1H), 2.26-
2.23 (m, 1H), 1.83-1.70 (m, 2H), 1.56-1.46 (m, 1H); IR (KBr)
2956, 1580, 1091 cm-1. Anal. Calcd for C14H17O2N: C, 72.70;
H, 7.41; N, 6.05. Found: C, 72.30; H, 7.20; N, 6.02.
tr a n s-3-(Tosylh yd r a zin o)-2-vin yltetr a h yd r op yr a n (3a ).
To a solution of 1 (152 mg, 0.26 mmol) in CH2Cl2 (5 mL) at
-78 °C was added a solution of TiCl2(OiPr)2 (1.0 M in CH2Cl2,
0.52 mL, 0.52 mmol), and the mixture was stirred for 5 min
at the same temperature. The reaction mixture was allowed
to warm to room temperature, quenched with satd NaHCO3,
extracted with ether. The organic layer was washed with brine,
and dried (Na2SO4). Concentration and silica gel column
chromatography gave 3a (72 mg, 94%): white solid; Rf ) 0.33
3-(N-Ben zoylam in o)-2-vin yltetr ah ydr ofu r an (17): white
1
solid; mp 85-87 °C; Rf ) 0.20 (hexane/AcOEt, 2:1); H NMR
(270 MHz, CDCl3) δ 7.77-7.39 (m, 5H), 6.25 (br, 1H),5.90 (ddd,
J ) 17.3, 10.5, 5.3 Hz, 1H), 5.34 (ddd, J ) 17.3, 1.7, 1.7 Hz,
1H), 5.19 (ddd, J ) 10.5, 1.7, 1.4 Hz, 1H), 4.48 (ddd, J ) 11.2,
7.5, 4.1 Hz, 1H), 4.29 (dd, J ) 5.3, 4.1 Hz, 1H), 4.05 (ddd, J )
8.5, 8.5, 5.1 Hz, 1H), 4.00 (ddd, J ) 8.5, 8.5, 7.4 Hz, 1H), 2.36
(m, 1H), 1.94 (m, 1H); IR (KBr) 3080, 1632 cm-1. Anal. Calcd
for C13H15O2N: C, 71.87; H, 6.96; N, 6.44. Found: C, 71.81;
H, 7.21; N, 6.64.
1
(hexane/AcOEt, 2:1); H NMR (270 MHz, CDCl3) δ 7.77 (d, J
) 8.2 Hz, 2H), 7.31 (d, J ) 8.6 Hz, 2H), 6.05 (s, 1H), 5.76 (ddd,
J ) 17.4, 10.4, 7.6 Hz, 1H), 5.29 (ddd, J ) 17.4, 1.6, 0.9 Hz,
1H), 5.23 (ddd, J ) 10.4, 1.6, 0.5 Hz, 1H), 3.88 (ddd, J ) 11.3,
4.4, 2.3 Hz, 1H), 3.43 (dd, J ) 8.4, 8.2 Hz, 1H), 3.31 (ddd, J )
14.4, 11.3, 3.1 Hz, 1H), 2.56 (ddd, J ) 12.0, 8.2, 4.2 Hz, 1H),
2.44 (s, 3H), 2.01 (m, 1H), 1.57 (m, 2H), 1.24 (m, 1H); IR (KBr)
3224, 1597, 1090 cm-1. Anal. Calcd for C14H20O3N2S: C, 56.73;
H, 6.80; N, 9.45; S, 10.81. Found: C, 56.63; H, 6.84; N, 9.35;
S, 10.52.
(2S,3R)-3-(2-P h en yleth yla m in o)-2-vin yltetr a h yd r op y-
r a n (6a ): colorless oil; Rf ) 0.42 (hexane/AcOEt, 2:1); 1H NMR
(300 MHz, CDCl3) δ 7.56-7.03 (m, 5H), 5.95 (ddd, J ) 17.4,
10.4, 7.1 Hz, 1H), 5.38 (dd, J ) 17.4, 1.5 Hz, 1H), 5.29 (dd, J
) 10.4, 1.3 Hz, 1H), 3.90 (m, 1H), 3.84 (quartet, J ) 6.6 Hz,
1H), 3.49 (dd, J ) 9.0, 7.1 Hz, 1H), 3.35 (m, 1H), 2.34 (ddd, J
) 9.0, 8.1, 4.2 Hz, 1H), 1.81 (m, 1H), 1.53 (m, 2H), 1.27 (d, J
) 6.6 Hz, 3H), 1.16 (m, 1H); 13C NMR (300 MHz, CDCl3) δ
146.7, 137.4, 128.3, 126.7, 126.4, 117.9, 84.0, 67.4, 56.3, 56.1,
31.3, 28.1, 26.7, 25.4, 24.2; IR (neat) 3026, 1492 cm-1. Anal.
Calcd for C15H21NO: C, 77.85; H, 9.14; N, 6.05. Found: C,
cis-3-(Tosylh yd r a zin o)-2-vin yltetr a h yd r op yr a n (3b):
colorless oil; Rf ) 0.37 (hexane/AcOEt, 2:1); 1H NMR (270 MHz,
CDCl3) δ 7.78 (d, J ) 8.2 Hz, 2H), 7.31 (d, J ) 8.6 Hz, 2H),
5.99 (s, 1H), 5.84 (ddd, J ) 17.4, 10.8, 4.2 Hz, 1H), 5.29 (ddd,
J ) 17.4, 1.8, 1.8 Hz, 1H), 5.19 (ddd, J ) 10.8, 1.8, 1.8 Hz,
1H), 3.97 (m, 1H), 3.95 (dd, J ) 4.2, 2.0 Hz, 1H), 3.45 (ddd, J
) 14.1, 12.0, 2.5 Hz, 1H), 3.00 (m, 1H), 2.43 (s, 3H), 2.02 (m,
1H), 1.73 (m, 2H), 1.51 (m, 1H), 1.31 (m, 1H); IR (neat) 3244,
1597, 1091 cm-1. Anal. Calcd for C14H20O3N2S: C, 56.73; H,
6.80; N, 9.45; S, 10.81. Found: C, 56.63; H, 6.84; N, 9.35; S,
10.52.
77.63; H, 9.17; N, 6.10. [R]19 ) 2.04 (c ) 0.20, CHCl3). The
D
specific rotation of the minor diastereomer of the trans product
6a was [R]18 ) 33.12 (c ) 0.20, CHCl3).
D
(2R,3R)-3-(2-P h en yleth yla m in o)-2-vin yltetr a h yd r op y-
r a n (6b): colorless oil; Rf ) 0.75 (hexane/AcOEt, 2:1); 1H NMR
(300 MHz, CDCl3) δ 7.56-7.03 (m, 5H), 6.00 (ddd, J ) 17.5,
10.6, 5.2 Hz, 1H), 5.35 (dd, J ) 17.5, 1.6 Hz, 1H), 5.24 (dd, J
) 10.6, 1.6 Hz, 1H), 3.97 (m, 2H), 3.82 (quartet, J ) 6.6 Hz,
1H), 3.46 (ddd, J ) 11.2, 11.2, 2.8 Hz, 1H), 2.63 (m, 1H), 1.86
(m, 1H), 1.66 (br, 1H), 1.61 (m, 1H), 1.46 (m, 1H), 1.32 (m,
1H), 1.25 (d, J ) 6.6 Hz, 3H); 13C NMR (300 MHz, CDCl3) δ
146.7, 136.6, 128.2, 127.1, 126.7, 115.7, 80.5, 67.5, 57.3, 53.2,
29.1, 24.5, 21.3; IR (neat) 3024, 1450, 1114 cm-1. Anal. Calcd
for C15H21NO: C, 77.85; H, 9.14; N, 6.05. Found: C, 77.70; H,
tr a n s-3-(Dip h en ylh yd r a zin o)-2-vin ylt et r a h yd r op yr -
a n (4a ): white solid; mp 85-87 °C; Rf ) 0.65 (hexane/AcOEt,
1
4:1); H NMR (270 MHz, CDCl3) δ 7.29-6.95 (m, 10H), 5.76
(ddd, J ) 17.3, 10.5, 8.0 Hz, 1H), 5.38 (ddd, J ) 17.4, 1.7, 0.9
Hz, 1H), 5.28 (ddd, J ) 10.5, 1.7, 0.5 Hz, 1H), 4.12 (br, 1H),
3.94 (ddd, J ) 11.2, 4.1, 1.9 Hz, 1H), 3.68 (dd, J ) 8.0, 8.4 Hz,
1H), 3.44 (ddd, J ) 14.4, 11.2, 3.1 Hz, 1H), 2.72 (ddd, J ) 10.2,
8.4, 4.1 Hz, 1H), 2.20-2.16 (m, 1H), 1.62-1.46 (m, 3H); IR
(KBr) 2952, 1588, 1041 cm-1. Anal. Calcd for C19H22N2O: C,
77.52; H, 7.53; N, 9.52. Found: C, 76.59; H, 7.56; N, 9.32.
3-(N1-Ben zoyl-N2,N2-diph en ylh ydr azin o)-2-vin yltetr ah y-
d r op yr a n (11). To a solution of 4a (110 mg, 0.373 mmol) in
THF (2 mL) at -78 °C was added n-BuLi (0.44 mL of a 1.7 M
solution in n-hexane, 0.747 mmol), and the resulting mixture
was stirred for 20 min. To this yellow solution was added
benzoic anhydride (84 µL, 0.447 mmol), and the mixture was
allowed to warm to room temperature and stirred for 20 min.
The reaction was quenched with saturated sodium hydrogen
carbonate, diluted with ether, washed with brine, dried
(MgSO4), and concentrated in vacuo. Purification of the residue
by recrystallization (hexane/AcOEt) furnished 124 mg (83%)
of 11 as a white solid: mp 167-171 °C; Rf ) 0.50 (hexane/
AcOEt, 3:1); 1H NMR (270 MHz, CDCl3) δ 7.70-6.80 (m, 15H),
5.91 (ddd, J ) 17.4, 10.2, 8.0 Hz, 1H), 5.31 (dd, J ) 17.4, 1.4
Hz, 1H), 5.22 (dd, J ) 10.2, 1.4 Hz, 1H), 4.40 (m, 1H), 4.06
(dd, J ) 8.0, 8.0 Hz, 1H), 3.91 (dd, J ) 11.0, 5.0 Hz, 1H), 3.31
(ddd, J ) 11.0, 11.0, 2.3 Hz, 1H), 2.26-1.60 (m, 4H); IR (KBr)
2956, 1664, 1490 cm-1. Anal. Calcd for C26H26N2O2: C, 78.36;
H, 6.57; N, 7.02. Found: C, 78.30; H, 6.47; N, 7.01.
9.04; N, 6.20. [R]19 ) 77.05 (c ) 0.62, CHCl3).
D
(2S,3R)-3-(2-P h en yleth yla m in o)-2-vin yltetr a h yd r ofu -
r a n (26a ): colorless oil; Rf ) 0.18 (hexane/AcOEt, 3:1); 1H
NMR (300 MHz, CDCl3) δ 7.35-7.23 (m, 5H), 5.71 (ddd, J )
17.3, 10.4, 6.8 Hz, 1H), 5.32 (dd, J ) 17.3, 1.4 Hz, 1H), 5.13
(dd, J ) 10.4, 1.4 Hz, 1H), 3.85 (m, 4H), 2.83 (ddd, J ) 7.0,
7.0, 6.1 Hz, 1H), 1.90 (m, 1H), 1.61 (m, 1H), 1.36 (d, J ) 6.6
Hz, 3H). Anal. Calcd for C14H19NO: C, 77.38; H, 8.81; N, 6.44.
Found: C, 77.41; H, 8.79; N, 6.40.
(2R,3R)-3-(2-P h en yleth yla m in o)-2-vin yltetr a h yd r ofu -
r a n (26b): colorless oil; Rf ) 0.38 (hexane/AcOEt, 3:1); 1H
NMR (400 MHz, CDCl3) δ 7.34-7.24 (m, 5H), 5.97 (ddd, J )
17.3, 10.7, 4.1 Hz, 1H), 5.40 (dd, J ) 17.3, 1.4 Hz, 1H), 5.31
(dd, J ) 10.7, 1.4 Hz, 1H), 4.35 (dd, J ) 6.1, 4.1 Hz, 1H), 3.95
(ddd, J ) 8.3, 8.3, 4.3 Hz, 1H), 3.79 (quartet, J ) 6.6 Hz, 1H),
3.69 (ddd, J ) 15.8, 8.0, 7.8 Hz, 1H), 3.23 (ddd, J ) 7.0, 7.0,
6.1 Hz, 1H), 1.95 (m, 1H), 1.66 (m, 1H), 1.29 (d, J ) 6.6 Hz,
3H). Anal. Calcd for C14H19NO: C, 77.38; H, 8.81; N, 6.44.
Found: C, 77.40; H, 8.78; N, 6.42.
(2S,3R)-3-(2-P h en yleth ylam in o)-2-vin yl-1-oxocycloh ep-
ta n e (28): colorless oil; Rf ) 0.38 (hexane/AcOEt, 3:1); 1H NMR
(400 MHz, CDCl3) δ 7.31-7.22 (m, 5H), 6.04 (ddd, J ) 17.2,
10.4, 6.0 Hz, 1H), 5.21 (dd, J ) 17.2, 1.3 Hz, 1H), 5.19 (dd, J
) 10.4, 1.1 Hz, 1H), 3.91-3.78 (m, 2H), 3.65-3.60 (m, 2H),
2.64 (m, 1H), 1.70-1.23 (m, 6H), 1.28 (d, J ) 6.6 Hz, 3H); IR
(neat) 3084, 1492, 1109 cm-1. Anal. Calcd for C16H23NO: C,
78.29; H, 9.44; N, 5.70. Found: C, 77.41; H, 9.54; N, 6.47.
(2S,3R)-3-(Dip h en ylm eth yla m in o)-2-vin yltetr a h yd r o-
p yr a n (8a ): white solid; Rf ) 0.42 (hexane/AcOEt, 7:1); 1H
NMR (400 MHz, CDCl3) δ 7.35-7.17 (m, 10H), 5.90 (ddd, J )
17.5, 10.2, 6.3 Hz, 1H), 5.39 (dd, J ) 17.5, 1.1 Hz, 1H), 5.31
(dd, J ) 10.2, 1.1 Hz, 1H), 4.99 (s, 1H), 3.91 (m, 1H), 3.59 (dd,
3-(N-Ben zoyla m in o)-2-vin yltetr a h yd r op yr a n (12). To a
solution of 11 (40 mg, 0.10 mmol) in THF (2 mL) at room
temperature were slowly added HMPA (0.15 mL, 0.85 mmol)
and SmI2 (4.0 mL of a 0.1 M solution in THF, 0.4 mmol), and
the resulting mixture was stirred for 10 min. The reaction was
quenched with saturated NaHCO3, diluted with ethyl acetate,
washed with brine, dried (MgSO4), and concentrated in vacuo.
Purification by silica gel column chromatography (CH2Cl2/
ether, 3:1) gave 12 (23 mg, 98%) as a white solid: mp 140-