Notes
J . Org. Chem., Vol. 63, No. 18, 1998 6419
(CHCl3) 3412, 1725 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.22 (d,
J ) 7.0 Hz, 2H), 7.43 (m, 2H), 7.15 (m, 4H), 6.26 (s, 2H), 1.54 (s,
18H) ppm; 13C NMR (75 MHz, CDCl3) δ 152.9, 136.6, 130.6,
129.6, 129.1, 126.5, 123.4, 120.1, 80.8, 28.4 ppm; EIMS m/z 384
(M+•).
P r ep a r a tion of Am in es 13a -e. Gen er a l P r oced u r e. To
a solution of biaryl 11a , 11b (87%), 11c, 11d (90%), or 11e (96%)
(0.136 mmol) in methylene chloride (1 mL) was added at 0 °C 1
mL of trifluoroacetic acid. The mixture was stirred at 0 °C for
15 min. After neutralization with aqueous saturated Na2CO3
and extraction with AcOEt, the organic phase was dried and
filtered and the solvent was removed to give the crude extract
which was chromatographed.
4-(2′-Am in obip h en yl-2-yl)p en ta n oic Acid Eth yl Ester
13a (R,a S/S,a R a n d R,a R/S,a S). Purified by preparative thin-
layer chromatography (8:2 heptane-AcOEt): yield 86% of a
white amorphous solid. 13a : IR (CHCl3) 3450, 3350, 1725, 1620
cm-1; 1H NMR (250 MHz, CDCl3) δ 7.40-7.19 (m, 6H), 7.09 (d,
J ) 8.0, 1H), 6.95 (t, J ) 8.0, 1H), 4.06 (q, J ) 7.0, 2H), 3.87 (bs,
2H), 2.63 (m, 1H), 2.07-1.82 (m, 4H), 1.15 (m, 6H) ppm; 13C
NMR (62.5 MHz, CDCl3) δ 173.9, 145.4, 144.0, 135.8, 131.2,
130.6, 130.4, 128.4, 126.6, 126.4, 126.3, 126.1, 118.2, 117.9, 115.1,
114.9, 61.1, 60.4, 35.0, 34.8, 33.6, 33.0, 32.6, 32.5, 23.2, 22.3,
14.2, 14.0 ppm; EIMS m/z 297 (M+•).
N HCl. After extraction with AcOEt, the organic layers were
dried over Na2SO4. After removal of the solvent, the crude
extracts were chromatographed if necessary.
4-(2′-Am in obip h en yl-2-yl)p en ta n oic Acid 14a (R,a S/S,a R
a n d R,a R/S,a S). Yield: 100% of a white amorphous solid.
14a : IR (CHCl3) 3488, 3394, 1713, 1612 cm-1 1H NMR (250
;
MHz, CDCl3) δ 7.35-7.25 (m, 5H), 6.98 (d, J ) 8.0 Hz, 1H), 6.64
(m, 2H), 5.12 (bs, 3H), 2.61 (m, 1H), 2.09 (m, 2H), 1.80 (m, 2H),
1.17 and 1.15 (2d, J ) 7.0 Hz, 3H) ppm; 13C NMR (75 MHz,
CDCl3) δ 179.8, 145.1, 144.0, 143.7, 138.4, 130.6, 130.4, 128.5,
127.2, 126.9, 126.3, 126.6, 126.4, 126.1, 118.2, 115.4, 115.0, 34.9,
34.5, 33.4, 32.7, 32.0, 23.2, 22.4 ppm; CIMS m/z 270 (MH+).
4-(2′-Am in obip h en yl-2-yl)-4-m eth ylp en ta n oic Acid 14b
(a S/a R). Purified by preparative thin-layer chromatography
(92:8 CH2Cl2-MeOH): yield 91% of a white amorphous solid.
14b: IR (CHCl3) 3394, 1730, 1612 cm-1 1H NMR (250 MHz,
;
CDCl3) δ 7.47 (d, J ) 8.0 Hz, 1H), 7.32 (J ) 8.0 and 1.0 Hz, 1H),
7.23 (bt, J ) 8.0 Hz, 1H), 7.16 (bt, J ) 8.0 Hz, 1H), 7.03 (2bd, J
) 8.0 Hz, 2H), 6.79 (bt, J ) 8.0 Hz, 1H), 6.73 (bd, J ) 8.0 Hz,
1H), 5.10 (bs, 3H), 2.01 (m, 4H), 1.22 (s, 3H), 1.19 (s, 3H) ppm;
13C NMR (62.5 MHz, CDCl3) δ 181, 146.0, 143.6, 138.1, 133.0,
130.9, 130.6, 128.6, 128.5, 128.0, 126.6, 118.1, 115.6, 50.9, 39.5,
31.3, 30.2, 29.5 ppm; CIMS m/z 284 (MH+).
4-(2′-Am in obip h en yl-2-yl)h exa n oic Acid 14c (R,a S/S,a R
a n d R,a R/S,a S). Purified by preparative thin-layer chroma-
tography (91:9 CH2Cl2-MeOH): yield 96% of a white amorphous
4-(2′-Am in obip h en yl-2-yl)-4-m eth ylp en ta n oic Acid Eth yl
Ester 13b (a S/a R). Purified by column chromatography (6:4
heptane-AcOEt): yield 78% of a white amorphous solid. 13b:
solid. 14c: IR (CHCl3) 3400, 1720, 1600 cm-1 1H NMR (250
;
IR (CHCl3) 3494, 3394, 1725, 1613 cm-1
;
1H NMR (250 MHz,
MHz, CDCl3) δ 7.30 (m, 5H), 7.05 (d, J ) 8.0 Hz, 1H), 6.84 (m,
2H), 6.40 (s, 3H), 2.61 (m, 1H), 2.19 (m, 2H), 1.95 (m, 2H), 1.63
(2q, J ) 7.0 Hz, 2H), 0.84 and 0.82 (2t, J ) 7.0 Hz, 3H) ppm;
13C NMR (75 MHz, CDCl3) δ 143.5, 138.6, 130.4, 130.3, 130.1,
129.9, 128.0, 127.8, 126.6, 126.0, 125.9, 117.6, 114.9, 114.7, 41.1,
30.9, 30.2, 29.6, 28.5, 12.4, 11.8, 11.5 ppm; CIMS m/z 284 (MH+).
4-(2′-Am in obip h en yl-2-yl)-4-eth ylh exa n oic Acid 14d (a S/
a R). Purified by preparative thin-layer chromatography (92:8
CH2Cl2-MeOH): yield 77% of a white amorphous solid. 14d :
CDCl3) δ 7.49 (dd, J ) 8.0 and 1.0 Hz, 1H), 7.33 (td, J ) 8.0 and
1.0 Hz, 1H), 7.22 (td, J ) 8.0 and 1.0 Hz, 1H), 7.16 (td, J ) 8.0
and 1.0 Hz), 1H, 7.04 (2dd, J ) 8.0 and 1.0 Hz, 2H), 6.78 (td, J
) 8.0 and 1.0 Hz, 1H), 6.72 (bd, J ) 8.0 Hz, 1H), 4.08 (q, J ) 7.0
Hz, 2H), 3.42 (bs, 2H), 2.09 (m, 3H), 1.82 (m, 1H), 1.28 (s, 3H),
1.22 (t, J ) 7.0 Hz, 3H), 1.18 (s, 3H) ppm; 13C NMR (62.5 MHz,
CDCl3) δ 174.6, 146.1, 144.1, 138.2, 133.1, 130.7, 130.6, 128.6,
127.8, 126.5, 126.0, 117.5, 115.1, 60.3, 39.5, 38.9, 30.9, 29.9, 29.4,
14.3 ppm; CIMS m/z 312 (MH+).
1
IR (CHCl3) 3400, 1712, 1612 cm-1; H NMR (200 MHz, CDCl3)
4-(2′-Am in obip h en yl-2-yl)h exa n oic Acid Eth yl Ester 13c
(R,a S/S,a R a n d R,a R/S,a S). Purified by column chromatog-
raphy (7:3 heptane-AcOEt): yield 62% of a white amorphous
solid. 13c: IR (CHCl3) 34580, 3400, 1725, 1618 cm-1; 1H NMR
(250 MHz, CDCl3) δ 7.30 (m, 5H), 6.98 (m, 1H), 6.79 (m, 2H),
4.02 (2q, J ) 7.0 Hz, 2H), 3.49 (bs, 2H), 2.52 (m, 1H), 2.18-1.58
(m, 6H), 1.20 (2t, J ) 7.0 Hz, 3H), 0.80 (2t, J ) 7.0 Hz, 3H)
ppm; 13C NMR (62.5 MHz, CDCl3) δ 174.0, 144.1, 139.0, 130.9,
130.8, 130.5, 130.4, 128.4, 128.2, 126.8, 126.3, 117.9, 117.8, 115.0,
60.2, 41.6, 32.9, 32.5, 31.5, 30.6, 30.1, 29.1, 14.2, 12.3, 12.0 ppm;
CIMS m/z 312 (MH+).
δ 7.59 (bd, J ) 8.0 Hz, 1H), 7.43 (t, J ) 8.0 Hz, 1H), 7.37 (d, J
) 8.0 Hz, 1H), 7.27 (t, J ) 8.0 Hz, 1H), 7.14 (m, 2H), 6.91 (m,
2H), 5.40 (bs, 3H), 2.12-1.64 (m, 8H), 0.85 and 0.75 (t, J ) 7.0
Hz, 6H) ppm; 13C NMR (60 MHz, CDCl3) δ 144.5, 143.3, 138.3,
133.3, 131.0, 130.4, 129.7, 128.4, 127.8, 126.4, 118.4, 115.9, 45.4,
31.2, 30.8, 27.8, 27.2, 8.5, 8.3 ppm; EIMS m/z 311 (M+•).
3-[1-(2′-Am in obip h en yl-2-yl)cyclop en tyl)]p r op ion ic Acid
14e (a S/a R). Purified by preparative thin-layer chromatogra-
phy (92:8 CH2Cl2-MeOH): yield 84% of a white amorphous
solid. 14e: IR (CHCl3) 3400, 1725 cm-1 1H NMR (250 MHz,
;
CDCl3) δ 7.34 (t, J ) 8.0 Hz, 1H), 7.28 (d, J ) 8.0 Hz, 1H), 7.22
(t, J ) 8.0 Hz, 1H), 7.14 (t, J ) 8.0 Hz, 1H), 7.05 (m, 2H), 6.78
(t, J ) 8.0 Hz, 1H), 6.72 (d, J ) 8.0 Hz, 1H), 5.52 (bs, 3H), 2.01-
1.57 (3m, 12H) ppm; 13C NMR (62.5 MHz, CDCl3) δ 146.5, 143.8,
138.2, 132.4, 131.0, 130.0, 129.8, 128.4, 127.4, 126.5, 118.0, 115.6,
51.7, 38.6, 36.0, 33.0, 31.7, 22.6, 22.4 ppm; CIMS m/z 310 (MH+).
Cycliza tion of Am in o Acid s 14a -e. Gen er a l P r oced u r e.
A solution of 14a , 14b, 14c, 14d , or 14e (0.177 mmol) and NEt3
(0.177 mmol) in dry CH2Cl2 (10 mL) was added dropwise to a
solution of EDCI (0.177 mmol) and HOBT (0.177 mmol) in dry
CH2Cl2 (150 mL) at 0 °C. The mixture was stirred for 84 h.
After evaporation of the solvent, the solid mixture was dissolved
in AcOEt and the solution was washed with aqueous saturated
Na2CO3 and water. After drying over Na2SO4 and filtration, the
organic phase was evaporated. The crude extract was then
chromatographed to give compound 4a , 4b, 4c, 4d , or 4e.
9-Meth yl-5,7,8,9-tetr ah ydr o-5-azadiben zo[a ,c]cyclon on en -
6-on e 4a (R,a R/S,a S). Purified by preparative thin-layer
chromatography (97:3 CH2Cl2-MeOH): yield 71% of a white
amorphous solid. 4a : IR (CHCl3) 3381, 1665 cm-1; 1H NMR (250
MHz, CDCl3) δ 7.40 (m, 7H), 6.96 (d, J ) 8.0 Hz, 1H), 6.60 (bs,
1H), 2.42 (m, 1H), 2.14 (m, 2H), 1.81 (m, 2H), 1.23 (d, J ) 7.0
Hz, 3H) ppm; 13C NMR (50 MHz, CDCl3) δ 176.4, 144.0, 129.3,
129.0, 128.7, 127.7, 126.1, 126.0, 37.0, 36.4, 33.9, 23.1 ppm; EIMS
m/z 251 (M+•); HRMS calcd for C17H17NO (MH+) 251.1310, found
251.1319.
4-(2′-Am in obip h en yl-2-yl)-4-eth ylh exa n oic Acid Eth yl
Ester 13d (a S/a R). Purified by column chromatography (8:2
hexanes-Et2O): yield 95% of a white amorphous solid. 13d :
IR (CHCl3) 3488, 3400, 1725, 1613 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.48 (dd, J ) 8.0 and 2.0 Hz, 1H), 7.33 (td, J ) 8.0 and
2.0 Hz, 1H), 7.23 (td, J ) 8.0 and 2.0 Hz, 1H), 7.14 (td, J ) 8.0
and 2.0 Hz, 1H), 7.02 (m, 2H), 6.72 (m, 2H), 4.10 (q, J ) 8.0 Hz,
2H), 3.42 (s, 2H), 1.89 (m, 4H), 1.63 (m, 4H), 1.24 (t, J ) 8.0 Hz,
3H), 0.69 (t, J ) 8.0 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3) δ
174.4, 144.8, 144.3, 139.0, 133.7, 130.5, 129.7, 128.4, 127.7, 126.4,
117.5, 115.3, 60.4, 45.8, 31.2, 30.1, 28.1, 27.8, 14.5, 8.7 ppm;
CIMS m/z 340 (MH+).
4-(2′-Am in obiph en yl-2-yl)cyclopen tylpr opion ic Acid Eth -
yl Ester 13e (a S/a R). Purified by preparative thin-layer
chromatography (8:2 heptane-AcOEt): yield 95% of a white
amorphous solid. 13e: IR (CHCl3) 3488, 3394, 1725, 1612 cm-1
;
1H NMR (250 MHz, CDCl3) δ 7.35 (td, J ) 8.0 and 1.0 Hz, 1H),
7.29 (dd, J ) 8.0 and 1.0 Hz, 1H), 7.24 (td, J ) 8.0 and 1.0 Hz,
1H), 7.17 (td, J ) 8.0 and 1.0 Hz, 1H), 7.08 (m, 2H), 6.78 (td, J
) 8.0 and 1.0 Hz, 1H), 6.72 (bd, J ) 8.0 Hz, 1H), 4.04 (q, J )
8.0, 2H), 3.46 (bs, 2H), 2.10-1.42 (m, 12H), 1.24 (t, J ) 7.0 Hz,
3H) ppm; 13C NMR (75 MHz, CDCl3) δ 174.2, 138.0, 130.8, 129.9,
129.7, 128.4, 127.3, 126.4, 117.4, 115.1, 60.3, 51.7, 37.9, 35.9,
32.9, 31.0, 22.7, 22.1, 14.3; CIMS m/z 338 (MH+).
P r ep a r a tion of Acid s 14a -e. Gen er a l P r oced u r e. To a
solution of amine 13a , 13b, 13c, 13d or 13e (0.1 mmol) in
methanol (1 mL) was added an aqueous solution of NaOH (50%).
After refluxing the mixture for 3 h, the solution was extracted
with AcOEt. The aqueous phase was acidified (pH ) 5) with 1
9,9-Dim eth yl-5,7,8,9-tetr a h yd r o-5-a za d iben zo[a ,c]cyclo-
n on en -6-on e 4b (a R/a S). Purified by preparative thin-layer
chromatography (97:3 CH2Cl2-MeOH): yield 78% of a white
amorphous solid. 4b: IR (CHCl3) 3381, 1662 cm-1 1H NMR
;