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H.-J. Liu et al. / Tetrahedron 59 (2003) 1209–1226
dropwise and the cooling bath was removed. The slightly
cloudy reaction mixture was allowed to stir at room
temperature for 24 h, at which time it was poured into ice-
cold dilute hydrochloric acid solution. The aqueous layer
was extracted with ether (4£30 mL) and the combined
organic extracts were washed sequentially with water
(50 mL), saturated sodium bicarbonate (50 mL), and
brine (50 mL), dried, filtered, and concentrated in vacuo.
The resulting light yellow oil was purified by flash
chromatography using 15% EtOAc/hexane as eluent to
furnish, after evaporation of solvent, the desired Michael
adduct 48 as a light yellow oil in a 2:1 mixture of
diastereomers (284 mg, 78% yield): IR (CDCl3 cast, cm21):
2232 (CN), 1727 (CvO); HRMS (EI): calcd for
C14H19NO2: 233.1416; found: 233.1408; Anal. calcd for
C14H19NO2: C 72.07, H 8.21, N 6.00; found C 72.15, H
8.47, N 5.68. An aliquot of the mixture was subjected to
extensive flash chromatography using 10% EtOAc/hexane
as eluent to furnish the individual diastereomers for further
characterization. Isomer 1 (minor product): 1H NMR
(400 MHz, CDCl3) d 5.82 (dd, J¼18, 11 Hz, 1H), 5.09 (d,
J¼11 Hz, 1H), 5.08 (d, J¼18 Hz, 1H), 2.56–2.82 (m, 4H),
2.30–2.50 (m, 2H), 2.20 (dd, J¼14, 2 Hz, 1H), 2.16 (s, 3H),
1.96 (d, J¼14 Hz, 1H), 1.80–1.92 (m, 2H), 1.35 (s, 3H); 13C
NMR (100 MHz, CDCl3, APT) d 206.3 (p), 203.5 (p), 145.8
(a), 119.7 (p), 112.3 (p), 48.3 (p), 42.7 (p), 39.1 (p), 37.4 (p),
36.3 (p), 35.1 (p), 29.9 (a), 29.2 (p), 26.4 (a); HRMS (EI):
calcd for C14H19NO2: 233.1416; found: 233.1405; Isomer 2
diastereomers (420 mg, 86% yield): IR (neat, cm21): 2228
(CN), 1674 (CvO), 1622 (CvC); HRMS (EI): calcd for
C15H19NO: 229.1467; found: 229.1472. A portion of the
mixture was then subjected to extensive flash chromatog-
raphy using 10% ethyl acetate/ n-hexane as eluent to give
the individual diastereomers for further characterization. 1H
NMR (400 MHz, CDCl3): Isomer 1: d 5.75 (dd, J¼18. 11,
Hz, 1H), 4.99 (d, J¼ 18 Hz, 1H), 4.98 (d, J¼11 Hz, 1H),
2.72–2.84 (m, 2H), 2.47–2.61 (m, 2H), 2.34 (ddd, J¼14, 5,
3 Hz, 1H), 2.06 (dd, J¼14, 3 Hz, 1H), 1.94 (ddd, J¼15, 14,
4 Hz, 1H), 1.84 (s, 3H), 1.78 (dddd, J¼14, 4, 4, 3 Hz, 1H),
1.53 (ddd, J¼14, 13, 4 Hz, 1H), 1.52 (d, J¼14 Hz, 1H), 1.45
(s, 3H); Isomer 2: 6.16 (ddd, J¼18, 11, 1 Hz, 1H), 5.26 (dd,
J¼11, 1 Hz, 1H), 5.21 (dd, J¼18, 1 Hz, 1H), 2.68–2.81 (m,
2H), 2.48–2.60 (m, 2H), 2.33 (ddd, J¼14, 5, 3 Hz, 1H), 2.21
(dd, J¼14, 3 Hz, 1H), 2.14 (ddd, J¼14, 7, 3 Hz, 1H), 1.92
(ddd, J¼15, 14, 4 Hz, 1H), 1.83 (s, 3H), 1.43 (d, J¼14 Hz,
1H), 1.39 (dddd, J¼14, 14, 4, 1 Hz, 1H), 1.04 (s, 3H); 13C
NMR (75 MHz, CDCl3, APT): Isormer 1: d 196.4 (p), 150.1
(p), 148.0 (a), 132.7 (p), 121.8 (p), 111.0 (p), 47.9 (p), 36.1
(p), 36.0 (p), 35.6 (p), 35.4 (p), 34.3 (p), 25.2 (p), 22.7 (a),
11.3 (a); Isomer 2: 196.4 (p), 150.4 (p), 143.1 (a), 132.3 (p),
120.9 (p), 114.0 (p), 50.0 (p), 36.7 (p), 36.3 (p), 35.3 (p),
34.8 (p), 34.1 (p), 31.1 (a), 25.5 (p), 11.2 (a). HRMS (EI):
Isomer 1: calcd for C15H19NO: 229.1467; found: 229.1464;
Isomer 2: calcd for C15H19NO: 229.1467; found: 229.1467.
Isomer 1: Anal. calcd for C15H19NO: C 78.56, H 8.35, N
6.11; found: C 78.56, H 8.32, N 5.82; Isomer 2: Anal. calcd
for C15H19NO: C 78.56, H 8.35, N 6.11; found: C 78.13, H
8.36, N 5.72.
1
(major product): H NMR (600 MHz, CDCl3) d 6.12 (ddd,
J¼18, 11, 1 Hz, 1H), 5.29 (d, J¼11 Hz, 1H), 5.24 (d,
J¼18 Hz, 1H), 3.00 (ddd, J¼13, 13, 5 Hz, 1H), 2.77 (ddd,
J¼18, 1, 5 Hz, 1H), 2.58 (ddd, J¼ 18, 10, 5 Hz, 1H), 2.37
(ddd, J¼14, 4, 4 Hz, 1H), 2.24–2.33 (m, 2H), 2.13–2.19
(m, 1H), 2.15 (s, 3H), 1.78 (ddd, J¼14, 10, 5 Hz, 1H), 1.70
(dddd, J¼13, 13, 4, 1 Hz, 1H), 1.66 (d, J¼14 Hz, 1H), 1.05
(s, 3H); 13C NMR (100 MHz, CDCl3, APT) d 206.6 (p),
203.5 (p), 143.0 (a), 119.1 (p), 114.4 (p), 49.8 (p), 47.2 (p),
39.0 (p), 36.9 (p), 36.3 (p), 35.9 (p), 30.3 (a), 30.0 (a), 29.2
(p); HRMS (EI): calcd for C14H19NO2: 233.1416; found:
233.1416.
4.17. 3-Methyl-7-oxo-3-vinyl-1,3,4,5,6,7-hexahydro-2H-
naphthalene-4a-carbonitrile (41)
This compound was prepared from 48 following a similar
method to that described for 40. The desired cyano enone 41
was obtained as a white solid in a 2:1 mixture of
diastereomers (623 mg, 55% yield): mp 54–588C; IR
(CHCl3 cast, cm21): 2228 (CN) and 1684 cm21 (CvO);
HRMS (EI): calcd for C14H17NO: 215.1310; found:
215.1312; Anal. calcd for C14H17NO: C 78.10, H 7.96, N
6.51; found: C 78.14, H 8.11, N 6.19; A portion of the
mixture was subjected to extensive flash chromatographic
separation using 10% EtOAc/hexane as eluent to give the
individual diastereomers for further characterization. Iso-
mer 1 (minor product): 1H NMR (300 MHz, CDCl3): d 5.98
(d, J¼2 Hz, 1H), 5.74 (dd, J¼18, 11 Hz, 1H), 5.01 (dd,
J¼18, 1 Hz, 1H), 4.98 (dd, J¼11, 1 Hz, 1H), 2.69–2.85 (m,
2H), 2.36–2.58 (m, 3H), 2.12 (dd, J¼14, 3 Hz, 1H), 1.98
(ddd, J¼15, 14, 4 Hz, 1H), 1.74 (ddd, J¼14, 5, 5 Hz, 1H),
1.74 (dd, J¼14, 5 Hz, 1H), 1.55 (d, J¼15 Hz, 1H), 1.46 (s,
3H); 13C NMR (75 MHz, CDCl3, APT): d 196.6 (p), 156.9
(p), 147.8 (a), 127.3 (a), 120.9 (p), 111.2 (p), 47.5 (p), 36.5
(p), 36.2 (p), 35.9 (p), 34.4 (p), 31.6 (p), 29.3 (p), 21.9 (a);
HRMS (EI): calcd for C14H17NO: 215.1310; found:
4.16. 3,8-Methyl-7-oxo-3-vinyl-1,3,4,5,6,7-hexahydro-
2H-naphthalene-4a-carbonitrile (40)
To a 100 mL round bottom flask mounted with a Dean–
Stark apparatus, was added p-toluenesulfonic acid hydrate
(0.32 g, 1.6 mmol) and benzene (50 mL). The clear solution
was heated to reflux, and the water–benzene azeotrope was
drained. After no more water was evident in the distillate
(,30 mL was drained), the solution was cooled to room
temperature, and a solution of the starting diketone 47
(520 mg, 2.0 mmol) in anhydrous benzene (30 mL) was
quickly introduced. The resulting solution was heated to
reflux, and the water–benzene azeotrope was drained. After
refluxing for 2 h, the solution was then cooled to room
temperature, and ether was added (20 mL). Saturated
sodium bicarbonate was added, and the aqueous layer was
extracted with ethyl acetate (3£20 mL). The combined
organic layers were washed sequentially with water and
brine, dried, filtered, and concentrated in vacuo to give the
crude product. Flash chromatographic purification of the
crude product (20% ethyl acetate in n-hexane) gave the title
compound as a light yellow oil in a 1:1 mixture of
1
215.1310; Isomer 2 (major product): H NMR (300 MHz,
CDCl3): d 6.14 (ddd, J¼18, 11, 1 Hz, 1H), 5.95 (d, J¼2 Hz,
1H), 5.28 (d, J¼11 Hz, 1H), 5.21 (d, J¼18 Hz, 1H), 2.65–
2.86 (m, 2H), 2.49 (dddd, J¼17, 4, 4, 1 Hz, 1H), 2.31–2.44
(m, 2H), 2.26 (dd, J¼14, 3 Hz, 1H), 2.12 (ddd, J¼14, 5,
5 Hz, 1H), 2.12 (dd, J¼14, 5 Hz, 1H), 1.96 (ddd, J¼15, 14,
4 Hz, 1H), 1.44 (d, J¼14 Hz, 1H), 1.05 (s, 3H); 13C NMR
(75 MHz, CDCl3, APT): 195.8 (p), 156.5 (p), 141.5 (a),