Stereoselective Intramolecular Cyclization
J . Org. Chem., Vol. 64, No. 26, 1999 9457
1H NMR): 99% yield; syn -12b; colorless needles; mp 147-148
10.5 Hz, 1 H), 5.40 (dt, J ) 1.2, 17.3 Hz, 1 H), 5.94 (ddd, J )
6.8, 10.5, 17.3 Hz, 1 H), 7.22-7.49 (m, 8 H), 7.98-8.00 (m, 2
H).
°C (light petroleum/hexane); [R]20 -72.6° (c 1.0, CHCl3); IR
D
(neat) 3020, 1739, 1656 cm-1; 1H NMR (500 MHz) δ 2.93 (dd,
J ) 3.0, 7.0 Hz, 2 H), 4.67 (m, 1 H), 5.25 (dt, J ) 1.1, 10.5 Hz,
1 H), 5.28 (dt, J ) 1.1, 17.3 Hz, 1 H), 5.40 (m, 1 H), 5.84 (ddd,
J ) 5.6, 10.5, 17.3 Hz, 1 H), 6.24 (d, J ) 8.5 Hz, 1 H), 7.21-
7.52 (m, 8 H), 7.67-7.70 (m, 2 H); 13C NMR (125 MHz) δ 21.7,
38.7, 53.7, 75.2, 119.2, 127.5, 129.3, 123.0, 132.3, 134.3, 135.2,
137.7, 167.8, 170.6; HRMS calcd for C20H21NO3 323.1521, found
323.1519.
(4S-tr a n s)-4,5-Dih yd r o-4-isobu tyl-2-p h en yl-5-vin yl-ox-
a zolin e (3c). According to the general procedure, allyl ben-
zamide 4c or homoallyl benzamide 12c gave a mixture of 3c
and 8c (172 mg, 75% yield; 3c:8c ) 13:1). Purification by flash
column chromatography (ethyl acetate/hexane ) 1:20) gave
pure 3c as a colorless oil: [R]20D -39.2° (c 1.0, CHCl3); IR (neat)
1
1652 cm-1; H NMR (500 MHz) δ 0.98 (dd, J ) 6.6 Hz, 6 H),
1.41 (m, 1 H), 1.65 (m, 1 H), 1.89 (m, 1 H), 4.01 (dd, J ) 7.0,
9.5 Hz, 1 H), 4.63 (dd, J ) 7.0 Hz, 1H), 5.25 (dt, J ) 1.2, 10.5
Hz, 1 H), 5.39 (d, J ) 1.2, 17.1 Hz, 1 H), 5.96 (ddd, J ) 7.0,
10.5, 17.1 Hz, 1 H), 7.39-7.49 (m, 3 H), 7.95-7.98 (m, 2 H);
13C NMR (100 MHz) δ 22.6, 22.9, 25.0, 45.2, 70.8, 86.3, 117.1,
128.0, 128.2, 128.3, 131.2, 136.5, 162.4; HRMS (EI, 70 eV) calcd
for C15H19NO 229.1467, found 229.1470.
(-)-N-((3S,4S)-3-Acet oxy-6-m et h yl-1-h ep t en yl)b en za -
m id e (syn -12c). Purification by silica gel chromatography
(ethyl acetate/hexane ) 8:1) gave 12c (ca. 1.3:1 syn:anti by
1H NMR): 99% yield; syn -12c; colorless needles; mp 144-145
°C (ethyl acetate/hexane); [R]20D -58.0° (c 1.0, CHCl3); IR (neat)
3323, 1742, 1640 cm-1; 1H NMR (500 MHz) δ 0.96 (d, J ) 6.5
Hz, 6 H), 1.39-1.71 (m, 3 H), 4.52 (m, 1 H), 5.25 (d, J ) 10.5
Hz, 1 H), 5.29 (d, J ) 17.5 Hz, 1 H), 5.40 (q, J ) 5.0, 6.0 Hz,
1 H), 5.86 (ddd, J ) 6.0, 10.5, 17.5 Hz, 1 H), 6.02 (d, J ) 9.5
Hz, 1 H), 7.43-7.52 (m, 3 H), 7.74-7.75 (m, 2 H); 13C NMR
(125 MHz) δ 21.7, 22.8, 24.0, 25.6, 41.9, 50.8, 77.0, 119.1, 127.5,
Minor isomer 8c: 1H NMR (400 MHz) δ 0.97 (d, J ) 6.6 Hz,
6 H), 1.31-1.93 (m, 3 H), 3.66 (ddd, J ) 5.8, 9.3, 9.5 Hz, 1 H),
5.11 (dd, J ) 7.6, 9.3 Hz, 1 H), 5.31 (d, J ) 10.5 Hz, 1 H), 5.39
(d, J ) 17.5 Hz, 1 H), 5.92 (ddd, J ) 7.6, 10.5, 17.5 Hz, 1 H),
7.38-7.47 (m, 3 H), 7.97-7.98 (m, 2 H).
129.3, 132.2, 134.4, 135.3, 167.9, 170.7; HRMS calcd for C17H23
NO3 289.1678, found 289.1678.
-
(4S-tr a n s)-4,5-Dih yd r o-4-cycloh exylm et h yl-2-p h en yl-
5-vin yloxa zolin e (3d ) According to the general procedure,
allyl benzamide 4d or homoallyl benzamide 12d gave a
mixture of 3d and 8d (194 mg, 72% yield; 3d :8d ) 14:1).
Purification by flash column chromatography (ethyl acetate/
(-)-N-((2S,3S)-3-Acetoxy-1-cycloh exyl-4-p en ten yl)ben -
za m id e (syn -12d ). Purification by silica gel chromatography
(ethyl acetate/hexane ) 8/1) gave 12d (ca. 1.1:1 syn:anti by
1H NMR): 98% yield; syn -12d ; colorless needles; mp 135-136
°C (ethyl acetate/hexane); [R]20D -54.7° (c 1.0, CHCl3); IR (neat)
hexane ) 20:1) gave pure 3d as a colorless oil: [R]20 -40.2°
D
(c 1.0, CHCl3); IR (neat) 1651 cm-1
;
1H NMR (500 MHz) δ
1
3423, 1742, 1639 cm-1; H NMR (500 MHz) δ 0.83-1.69 (m,
0.95-0.98 (m, 2 H), 1.21-1.28 (m, 5 H), 1.41-1.44 (m, 1 H),
1.64-1.72 (m, 3 H), 1.80 (m, 2 H), 4.04 (dd, J ) 7.0, 7.5 Hz, 1
H), 4.62 (dd, J ) 7.0 Hz, 1 H), 5.24 (dt, J ) 1.2, 10.5 Hz, 1 H),
5.37 (dt, J ) 1.2, 17.1 Hz, 1 H), 5.96 (ddd, J ) 7.0, 10.5, 17.1
Hz, 1 H), 7.38-7.48 (m, 3 H), 7.95-7.97 (m, 2 H); 13C NMR
(100 MHz) δ 26.2, 26.5, 26.6, 33.3, 33.5, 34.3, 43.7, 70.1, 86.3,
117.0, 128.23, 128.25, 128.26, 131.2, 136.4, 162.4; HRMS (EI,
70 eV) calcd for C18H23NO 269.1780, found 269.1781.
12 H), 1.89 (br d, 1 H), 2.09 (s, 3 H), 4.53 (m, 1 H), 5.24 (dt, J
) 1.1, 10.5 Hz, 1 H), 5.28 (dt, J ) 1.1, 17.3 Hz, 1 H), 5.38
(ddd, J ) 1.1, 4.3, 6.0 Hz, 1 H), 5.85 (ddd, J ) 6.0, 10.5, 17.3
Hz, 1 H), 6.00 (d, J ) 10.0 Hz, 1 H), 7.43-7.52 (m, 3 H), 7.74-
7.75 (m, 2 H); 13C NMR (125 MHz) δ 21.7, 26.8, 26.9, 27.1,
33.4, 34.7, 34.9, 40.4, 50.1, 77.1, 119.0, 127.5, 129.3, 132.2,
134.4, 135.4, 167.8, 170.9; HRMS calcd for C20H27NO3 329.1991,
found 329.1991.
1
Minor isomer 8d : H NMR (400 MHz) δ 0.87-1.72 (m, 13
Gen er a l P r oced u r e for Oxa zolin es 3. Pd(PPh3)4 (57.8
mg, 0.05 mmol), was added under N2 to a stirred solution of
allyl benzamide 4 or homoallyl benzamide 12 (1.0 mmol) and
K2CO3 (0. 414 g, 3.0 mmol, 3 equiv) in 20 mL of CH3CN. The
resulting mixture was refluxed for 24 h, whereupon it was
allowed to cool to room temperature and filtered through a
pad of silica, and was then evaporated under reduced pressure
to give the crude product. Purification of this material by silica
gel chromatography gave pure 3.
H), 4.39 (ddd, J ) 5.9, 9.3, 9.5 Hz, 1 H), 5.10 (dd, J ) 7.3, 9.3
Hz, 1 H), 5.30 (d, J ) 10.5 Hz, 1 H), 5.39 (d, J ) 17.1 Hz, 1 H),
5.92 (ddd, J ) 7.3, 10.5, 17.1 Hz, 1 H), 7.38-7.47 (m, 3 H),
7.96-7.98 (m, 2 H).
Gen er a l P r oced u r e for Oxa zolin e Ca r boxylic Acid
Meth yl Ester s 13. NaHCO3 (817 mg, 9.76 mmol) and, in small
portions, 1.76 g (8.24 mmol) of NaIO4 were added to a stirred
solution of 1.5 mmol of oxazoline 3 in 1.5 mL of CH3CN, 1.5
mL of CCl4, and 2.25 mL of H2O at room temperature under
argon. The mixture was stirred for 5 min after the addition,
50.8 mg (0.24 mmol) of RuCl3 was then added, and stirring
continued for 48 h. The reaction mixture was extracted with
ether, and then carefully acidified with aqueous HCl, and the
product was isolated with CH2Cl2 to give pure 1. Diazomethane
was added to the resulting solution of 1 in ether, after 10 min,
the solvent was distilled off under reduced pressure and the
oily substance obtained was subjected to silica gel column
chromatography (ethyl acetate/hexane ) 1:4).
Meth yl (4S,tr a n s)-4,5-d ih yd r o-2,4-d ip h en yl-5-ca r boxy-
la te (13a ): 75% yield; colorless oil; [R]20D +12.9° (c 1.0, CHCl3);
IR (neat) 1760, 1655 cm-1; 1H NMR (500 MHz) δ 3.87 (s, 3 H),
4.93 (d, J ) 6.5 Hz, 1 H), 5.46 (d, J ) 6.5 Hz, 1 H), 7.31-7.57
(m, 8 H), 8.09-8.12 (m, 2 H); 13C NMR (125 MHz) δ 53.5, 75.4,
83.9, 127.2, 127.5, 128.8, 129.2, 129.4, 129.6, 132.7, 141.8,
164.7, 171.4; HRMS (EI, 70 eV) calcd for C17H15NO3 281.1052,
found 281.1050.
(4S-tr a n s)-4,5-d ih yd r o-2,4-d ip h en yl-5-vin yloxa zolin e
(3a ). Purification by flash column chromatography (ethyl
acetate/hexane ) 1:10) gave pure 3a as a colorless oil (73%
1
yield): [R]20 -11.6° (c 1.0, CHCl3); IR (neat) 1649 cm-1; H
D
NMR (500 MHz) δ 4.88 (dd, J ) 7.0, 8.0 Hz, 1 H), 5.05 (d, J )
8.0 Hz, 1 H), 5.33 (d, J ) 10.5 Hz, 1 H), 5.38 (d, J ) 17.5 Hz,
1 H), 6.09 (ddd, J ) 7.0, 10.5, 17.5 Hz, 1 H), 7.31-7.53 (m, 8
H), 8.08 (m, 2 H); 13C NMR (100 MHz) δ 76.8, 89.2, 118.6,
127.4, 128.3, 128.4, 129.1, 129.2, 129.5, 132.3, 136.6, 142.4,
164.7; HRMS (EI, 70 eV) calcd for C17H15NO 249.1154, found
249.1156.
(4S-tr a n s)-4,5-Dih yd r o-4-b en zyl-2-p h en yl-5-vin ylox-
a zolin e (3b). According to the general procedure, allyl ben-
zamide 4b or homoallyl benzamide 12b gave a mixture of 3b
and 8b (205 mg, 78% yield; 3b:8b ) 14:1). Purification by flash
column chromatography(ethyl acetate/hexane ) 20:1) gave
pure 3b as a colorless oil: [R]20D +36.1° (c 1.0, CHCl3); IR (neat)
1650 cm-1; 1H NMR (500 MHz) δ 2,79 (dd, J ) 7.5, 13.0 Hz, 1
H), 3.26 (dd, J ) 5.5, 13.0 Hz, 1 H), 4.26 (ddd, J ) 5.5, 7.0, 7.5
Hz, 1 H), 4.76 (dd, J ) 6.5, 7.0 Hz, 1 H), 5.06 (dt, J ) 1.2, 10.2
Hz, 2 H), 5.07 (dt, J ) 1.2, 17.3 Hz, 1 H) 5.72 (ddd, J ) 6.5,
10.2, 17.3 Hz, 1 H), 7.22-7.51 (m, 8 H), 7.97-8.01 (m, 2 H);
13C NMR (100 MHz) δ 42.2, 74.5, 84.6, 116.5, 126.5, 128.3,
128.4, 129.2, 129.5, 131.3, 136.2, 137.5, 163.0; HRMS (EI, 70
eV) calcd for C18H18NO 264.1388, found 264.1390. Minor
isomer 8b: 1H NMR (400 MHz) δ 2.86 (dd, J ) 6.8, 14.2 Hz,
1 H), 2.94 (dd, J ) 8.0, 14.2 Hz, 1 H), 4.64 (m, J ) 6.8, 8.0, 9.2
Hz, 1 H), 5.18 (m, J ) 1.2, 6.8, 9.2 Hz, 1 H), 5.32 (dt, J ) 1.2,
Meth yl (4S,tr a n s)-4,5-d ih yd r o-2-ben zyl-4-p h en yl-5-ca r -
boxyla te (13b): 75% yield; colorless oil; [R]20 +47.7° (c 1.0,
D
CHCl3); IR (neat) 1758, 1656 cm-1; 1H NMR (400 MHz) δ 2.89
(dd, J ) 7.1, 13.9 Hz, 1 H), 3.12 (dd, J ) 6.1, 13.9 Hz, 1 H),
3.62 (s, 3 H), 4.57 (dd, J ) 6.1, 7.1 Hz, 1 H), 4.65 (d, J ) 6.1
Hz, 1 H), 7.13-7.43 (m, 8 H), 7.88-7.90 (m, 2 H); 13C NMR
(100 MHz) δ 41.5, 52,4, 72.7, 79.5, 126.7, 127.0, 128.3, 128.4,
128.5, 129.6, 131.6, 136.6, 163.2, 170.8; HRMS (EI, 70 eV) calcd
for C18H17NO3 295.1208, found 295.1206.
Meth yl (4S,tr a n s)-4,5-d ih yd r o-2-isobu tyl-4-p h en yl-5-
ca r boxyla te (13c): 77% yield; colorless oil; [R]20 +10.9° (c
D