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A. Luxenburger / Tetrahedron 59 (2003) 3297–3305
(17), 117 (14), 115 (45), 103 (20), 91 (35), 77 (24), 67 (24),
55 (21), 51 (18), 44 (26), 43 (26). Anal. calcd for
C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found C, 73.98;
H, 7.15; N, 5.81.
(m, 4H), 1.59–1.40 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 172.44, 160.16, 140.77, 130.15, 120.39, 118.19, 113.30,
112.27, 55.35, 51.58, 50.31, 41.67, 39.72, 37.05, 29.65,
25.26, 23.62; MS (CI) m/z (%) 288 (Mþþ1, 8), 287 (Mþ,
27), 181 (19), 180 (100), 121 (60), 91 (20).
4.1.6. 9-Oxo-trans-1,3,4,9,10,10a-hexahydro-4a(2H)-
phenanthrenecarboxylic acid (5a). The amide 7a
(2.00 g, 8.22 mmol) was heated to reflux with 37% HCl
(100 ml) for 48 h. The mixture was cooled to rt, water
(100 ml) was added and extracted with diethyl ether
(3£70 ml). The combined organic layers were extracted
with saturated NaHCO3 solution (4£80 ml). The aqueous
NaHCO3 extracts were combined, acidified to pH 1 by the
dropwise addition of 37% HCl and subsequently extracted
with diethyl ether (3£100 ml). The combined ethereal
extracts were washed with brine, dried over MgSO4 and
concentrated to yield 1.16 g (58%) of 5a as a colourless
solid. An analytical sample was obtained by recrystallisa-
tion from water/ethanol. Mp 152–1548C; IR (KBr) 3070,
2925, 2860, 1725, 1630 cm21; 1H NMR (400 MHz, CDCl3)
d 8.05 (d, J¼8.0 Hz, 1H), 7.60–7.52 (m, 2H), 7.38 (td,
J¼7.1, 1.8 Hz, 1H), 3.30 (dd, J1¼18.6 Hz, J2¼14.1 Hz,
1H), 3.01–2.96 (m, 1H), 2.51 (dd, J1¼18.6 Hz, J2¼5.1 Hz,
1H), 2.22–2.13 (m, 1H), 1.90–1.31 (m, 7H); 13C NMR
(100 MHz, CDCl3) d 197.96, 178.90, 144.72, 133.63,
132.71, 127.91, 127.78, 126.29, 49.46, 42.03, 35.53,
29.44, 25.62, 23.66; MS (EI) m/z (%) 244 (Mþ, 12), 199
(20), 198 (55), 197 (100), 196 (18), 170 (23), 169 (96), 168
(25), 167 (14), 166 (17), 165 (45), 142 (19), 141 (45), 139
(14), 131 (21), 115 (51), 91 (23), 89 (15), 50 (15), 41 (15),
39 (32). Anal. calcd for C15H16O3: C, 73.75; H, 6.60. Found
C, 73.82; H, 6.69.
4.1.9. [2-Cyano-2-(3-methoxyphenyl)cyclohexyl]acetic
acid (8b). A solution of the nitrile methyl ester 16b
(10.7 g, 37.3 mmol) in methanol (135 ml) was reacted with
20% aqueous NaOH solution (37 ml) according to the
procedure outlined for the preparation of 8a. The crude
product was recrystallised from water/ethanol to yield
8.45 g (85%) of 8b as a colourless solid. Mp 119–1188C; IR
(KBr) 3010, 2950, 2860, 2230, 1710, 1610, 1585 cm21; 1H
NMR (400 MHz, CDCl3) d 7.29 (t, J¼8.0 Hz, 1H), 7.09–
7.01 (m, 2H), 6.86–6.81 (m, 1H), 3.81 (s, 3H), 2.43–2.37
(m, 1H), 2.24–2.18 (m, 2H), 2.13–2.06 (m, 1H), 2.04–1.97
(m, 1H), 1.93–1.76 (m, 4H), 1.61–1.38 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 178.02, 160.18, 140.61, 130.22,
120.26, 118.15, 113.34, 112.26, 55.35, 50.19, 41.51,
39.68, 36.96, 29.57, 25.23, 23.57; MS (EI) m/z (%) 273
(Mþ, 24), 227 (18), 166 (69), 159 (57), 122 (23), 121 (100),
91 (53), 79 (16), 78 (28), 77 (31), 71 (21), 65 (17), 55 (18),
51 (21), 45 (42), 43 (16), 41 (32). Anal. calcd for
C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found C, 70.21;
H, 7.07; N, 5.22.
4.1.10. 6-Methoxy-9-oxo-trans-1,3,4,9,10,10a-hexahydro-
4a(2H)-phenanthrenecarboxylic acid amide (7b). Using
the procedure described for the preparation of 7a, the nitrile
carboxylic acid 8b (5.00 g, 18.3 mmol) was treated with
concentrated sulphuric acid (175 ml) to afford 3.72 g (74%)
of 7b as a colourless solid. Mp 219–2208C (Ref. 10 225–
1
4.1.7. trans-1,3,4,9,10,10a-Hexahydro-4a(2H),9-phenan-
threnecarbolactone (2a). To a solution of the keto-
carboxylic acid 5a (1.15 g, 4.71 mmol) dissolved in a 2:1
mixture of ethanol and water (120 ml) was added NaBH4
(1.07 g, 28.3 mmol) in portions at 08C. The reaction mixture
was stirred for further 24 h at rt and 37% HCl (14.5 ml)
was dropwise added (ice-cooling). After being stirred
for further 1.5 h at rt, water (100 ml) was added and
the mixture was extracted with chloroform (3£70 ml).
The combined organic layers were dried over MgSO4, the
solvent was evaporated and the crude product was
purified by column chromatography (silica gel, chloroform)
to give 860 mg (80%) of 2a as a colourless solid. Mp 1168C
(Ref. 9 79–808C); The spectroscopical data for 2a were
completely identical with those published for compound
2a.9
2288C) H NMR (400 MHz, CDCl3) d 8.10 (d, J¼8.8 Hz,
1H), 6.99 (d, J¼2.7 Hz, 1H), 6.92 (dd, J1¼8.8 Hz, J2¼
2.6 Hz, 1H), 5.31 (sb, 1H, NH2), 5.15 (sb, 1H, NH2), 3.90 (s,
3H), 3.01 (dd, J1¼18.6 Hz, J2¼13.7 Hz, 1H), 2.66–2.59 (m,
1H), 2.51 (dd, J1¼18.6 Hz, J2¼4.0 Hz, 1H), 2.21–2.19 (m,
1H), 2.14–1.64 (m, 5H), 1.56–1.49 (m, 1H), 1.41–1.38 (m,
1H); 13C NMR (100 MHz, CDCl3) d 196.89, 175.07,
164.08, 149.87, 131.02, 126.45, 112.40, 110.97, 55.62,
48.95, 43.07, 42.74, 35.47, 28.63, 25.57, 22.62.
4.1.11. 6-Methoxy-9-oxo-trans-1,3,4,9,10,10a-hexahydro-
4a(2H)-phenanthrenecarboxylic acid (5b). The amide 7b
(2.00 g, 7.32 mmol) was reacted with 37% HCl (100 ml)
according to the procedure described for the preparation of
5a to yield 625 mg (31%) of 5b as a colourless solid. Mp
184–1858C; IR (KBr) 2935, 2865, 1710, 1640, 1590 cm21
;
1H NMR (400 MHz, CDCl3) d 8.04 (d, J¼8.8 Hz, 1H), 7.03
(d, J¼2.7 Hz, 1H), 6.88 (dd, J1¼8.8 Hz, J2¼2.7 Hz, 1H),
3.86 (s, 3H), 3.26 (dd, J1¼18.6 Hz, J2¼13.7 Hz, 1H), 2.96–
2.89 (m, 1H), 2.46 (dd, J1¼18.6 Hz, J2¼4.9 Hz, 1H), 2.20–
2.09 (m, 1H), 1.89–1.56 (m, 5H), 1.53–1.31 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 197.01, 178.71, 163.88, 147.14,
130.25, 126.34, 113.24, 111.79, 55.51, 49.66, 42.18, 41.86,
35.56, 29.44, 25.62, 23.69; MS (EI) m/z (%) 275 (Mþþ1,
50), 274 (Mþ, 100), 231 (25), 230 (68), 229 (87), 228 (28),
215 (17), 211 (15), 204 (24), 201 (37), 188 (23), 187 (48),
177 (19), 162 (20), 161 (61), 159 (34), 128 (21), 121 (19),
115 (29), 91 (17), 77 (19), 74 (28), 59 (38), 45 (36). Anal.
calcd for C16H18O4: C, 70.06; H, 6.61. Found C, 70.01; H,
6.72.
4.1.8. Methyl [2-cyano-2-(3-methoxyphenyl)cyclohexyl]-
acetate (16b). Using the procedure described for the
preparation of 16a, a solution of the (3-methoxyphenyl)-
acetonitrile 11b (7.01 ml, 51.4 mmol) in dry THF (110 ml)
and NaH (60% in mineral oil; 2.21 g, 55.3 mmol) suspended
in dry THF (120 ml) were reacted with a solution of the
a,b-unsaturated methyl ester 1210 (15.0 g, 48.1 mmol) in
dry THF (110 ml) to give 11.4 g (83%) of 16b as a
colourless oil. IR (film) 3000, 2935, 2855, 2235, 1735, 1600,
1585 cm21
;
1H NMR (400 MHz, CDCl3) d 7.30 (t,
J¼8.0 Hz, 1H), 7.10–7.04 (m, 2H), 6.86–6.82 (m, 1H),
3.82 (s, 3H), 3.56 (s, 3H), 2.47–2.39 (m, 1H), 2.21–2.17
(m, 2H), 2.11–2.06 (m, 1H), 1.99–1.92 (m, 1H), 1.90–1.74