The Journal of Organic Chemistry
ARTICLE
Anal. Calcd for C22H32O3: C, 76.70; H, 9.36. Found: C, 76.55; H,
9.45.
cmꢀ1; 1H NMR (400 MHz; CDCl3) δ 1.56 (s, 3H, CH3), 1.66ꢀ1.78 (m,
2H, H-6R, H-6β), 1.78ꢀ1.96 (m, 2H, H-5R, H-5β), 2.46 (m, 1H, H-1),
3.43 (s, 3H, CH3OCdO), 3.62 (s, 3H, OCH3), 3.63 (s, 3H, OCH3), 3.90
(s broad, 1H, H-2), 5.12 (s, 1H, H-3), 6.27 (s broad, 2H, H-30, H-50), 6.87
(d, 1H, J= 8.9 Hz, H-60); 13C NMR(400 MHz;CDCl3) δ23.6, 24.2, 28.4,
36.5, 45.2, 51.4, 55.2, 55.4, 98.4, 103.8, 115.7, 123.5, 124.9, 129.1, 133.8,
157.9, 159.3, 175.8; MS m/e (rel intensity) 77 (13), 91 (14), 115 (18),
128 (14), 138 (41), 139 (10), 151 (26), 158 (14), 165 (20), 173 (21), 174
(12), 189 (100), 190 (14), 203 (62), 204 (48), 215 (37), 230 (87), 231
(19), 290 (Mþ, 61). Anal. Calcd for C17H22O4: C, 70.32; H, 7.64. Found:
C, 70.25; H, 7.70.
rel-(1S,2R)-Methyl 2-(20,60-Dimethoxy-40-pentylphenyl)-
4-methylcyclohex-3-enecarboxylate (7dy). White solid, mp
1
29ꢀ30 °C (n-hexane); IR (CHCl3) 1728 (CdO) cmꢀ1; H NMR
(400 MHz; CDCl3) δ 0.80 (t, 3H, J = 7.0 Hz, CH3), 1.19ꢀ1.27 (m, 4H,
CH2CH2), 1.46ꢀ1.56 (m, 2H, CH2), 1.57 (m, 1H, H-6β), 1.61 (s, 3H,
CH3), 1.71 (m, 1H, H-5R), 1.89 (m, 1H, H-5β), 2.17 (m, 1H, H-6R),
2.44 (t, 2H, J = 7.8 Hz, CH2), 2.78 (ddd, 1H, J = 11.0, 7.5, 3.6 Hz, H-1),
3.23 (s, 3H, CH3OCdO), 3.63 (s, 6H, OCH3, OCH3), 4.30 (s broad,
1H, H-2), 5.23 (s, 1H, H-3), 6.23 (s, 2H, H-30, H-50); 13C NMR (400
MHz; CDCl3) δ 14.1, 22.5, 22.9, 23.8, 28.4, 31.0, 31.6, 32.6, 36.4, 42.9,
50.6, 55.7 (2C), 104.5 (2C), 115.8, 131.5, 142.7, 158.7, 175.1; MS m/e
(rel intensity) 152 (36), 173 (23), 208 (100), 209 (23), 221 (18), 235
(16), 243 (40), 274 (46), 300 (79), 301 (18), 360 (Mþ, 4). Anal. Calcd
for C22H32O4: C, 73.30; H, 8.95. Found: C, 73.35; H, 8.89.
rel-1-((1R,2R)-2-(20,60-Dimethoxyphenyl)-4-methylcyclo-
hex-3-enyl)ethanone (8cx). Light yellow oil; IR (CHCl3) 1702
(CdO) cmꢀ1; 1H NMR (400 MHz; CDCl3) δ 1.51 (s, 3H, CH3), 1.65
(dd, 1H, J = 12.5, 11.0, 5.0 Hz, H-6β), 1.73 (s, 3H, CH3CdO),
1.73ꢀ1.78 (m, 1H, H-6R), 1.85 (dd broad, 1H, J = 16.9, 5.0 Hz,
H-5β), 1.95ꢀ2.03 (m, 1H, H-5R), 3.14 (ddd, 1H, J = 10.6, 9.6, 3.5 Hz,
H-1), 3.60 (s, 6H, OCH3, OCH3), 4.06 (d broad, 1H, J = 9.4 Hz, H-2),
4.99 (s, 1H, H-3), 6.36 (d, 2H, J = 8.3 Hz, H-30, H-50), 6.96 (t, 1H, J = 8.3
Hz, H-40); 13C NMR (400 MHz; CDCl3) δ 23.3 (4-CH3), 26.5 (C-6),
28.6 (CH3CdO), 29.5 (C-5), 34.7 (C-2), 50.9 (C-1), 55.9 (20-OCH3,
60-OCH3), 104.7 (C-30, C-50), 120.0 (C-10), 124.5 (C-3), 127.6 (C-40),
131.2 (C-4), 158.7 (C-20, C-60), 213.3 (CdO); MS m/e (rel intensity)
43(22), 91 (28), 121 (21), 138 (100), 151 (100), 173 (50), 231 (43),
243 (33), 274 (Mþ, 31). Anal. Calcd for C17H22O3: C, 74.42; H, 8.08.
Found: C, 74.58; H, 8.15.
Epimerization of endo-Adducts 7 to exo-Adducts 8. A
solution of 0.56 mmol of endo-adduct 7 in absolute methanol (1 mL)
was added to a 1 M freshly prepared solution (2 mL) of sodium
methoxide in dry methanol under nitrogen. The mixture was stirred at
the indicated temperature for the time needed to establish equilibrium
(as monitored by GC analysis) (Table 3). Next, the reaction mixture was
quenched with dilute HCl, taken up in 25 mL of ether, and washed with
saturated aqueous NaCl. The dried extract (Na2SO4) was concentrated
under vacuum and chromatographed over silica gel. Elution with 10% to
20% diethyl ether/petroleum ether gave cycloadducts 8.
rel-1-((1R,2R)-2-(20-Methoxyphenyl)-4-methylcyclohex-3-
enyl)ethanone (8ax). Light yellow oil; IR (CHCl3) 1703 (CdO)
cmꢀ1; 1H NMR (400 MHz; CDCl3) δ 1.57 (s, 3H, CH3), 1.62 (m, 1H,
J = 9.6, 6.0, 3.6 Hz H-6β), 1.71 (ddd, 1H, J = 13.2, 6.5, 2.0 Hz, H-6R),
1.86ꢀ1.91 (m, 2H, H-5R, H-5β), 1.91 (s, 3H, CH3CdO), 2.51 (ddd,
1H, J = 9.7, 6.7, 3.6 Hz, H-1), 3.64 (s, 3H, OCH3), 3.97 (s broad, 1H,
H-2), 5.14 (s broad, 1H, H-3), 6.68 (d, 1H, J = 8.2 Hz, H-30), 6.75 (t, 1H,
J = 7.5 Hz, H-50), 6.98ꢀ7.03 (m, 2H, H-40, H-60); 13C NMR (400 MHz;
CDCl3) δ 23.4, 23.6, 28.2, 28.3, 36.1, 53.1, 55.3, 110.3, 120.4, 123.0,
127.4, 128.8, 132.7, 134.4, 156.8, 211.5; MS m/e (rel intensity) 67 (41),
77 (17), 82 (100), 91 (19), 115 (16), 118 (51), 146 (68), 147 (90), 185
(16), 228 (80), 229 (23), 244 (Mþ, 3). Anal. Calcd for C16H20O2: C,
78.65; H, 8.25. Found: C, 78.48; H, 8.19.
rel-(1R,2R)-Methyl 2-(20,60-Dimethoxyphenyl)-4-methyl-
cyclohex-3-enecarboxylate (8cy). Oil; IR (CHCl3) 1727
1
(CdO) cmꢀ1; H NMR (400 MHz; CDCl3) δ 1.57 (s, 3H, CH3),
1.80 (ddd, 1H, J = 12.5, 10.2, 5.2 Hz, H-6β), 1.85ꢀ1.98 (m, 1H, H-6R),
2.05ꢀ2.20 (m, 2H, H-5R, H-5β), 3.1 (ddd, 1H, J = 10.2, 9.6, 3.5 Hz,
H-1), 3.37 (s, 3H, CH3OCdO), 3.67 (s, 6H, OCH3, OCH3), 4.20
(d broad, 1H, J = 9.1 Hz, H-2), 5.06 (s, 1H, H-3), 6.43 (d, 2H, J = 8.3 Hz,
H-30, H-50), 7.03 (t, 1H, J = 8.3 Hz, H-40); 13C NMR (400 MHz;
CDCl3) δ 23.3, 27.1, 29.4, 34.9, 43.2, 51.1, 56.0 (2C), 104.7 (2C), 120.3,
124.3, 127.4, 131.1, 158.9 (2C), 176.6; MS m/e (rel intensity) 91 (15),
138 (41), 151 (33), 165 (15), 173 (33), 215 (28), 230 (100), 231 (18),
290 (Mþ, 13). Anal. Calcd for C17H22O4: C, 70.32; H, 7.64. Found: C,
70.43; H, 7.58.
rel-1-((1R,2R)-2-(20,60-Dimethoxy-40-pentylphenyl)-4-methyl-
cyclohex-3-enyl)ethanone (8dx). Oil; IR (CHCl3) 1702 (CdO)
cmꢀ1; 1H NMR (400 MHz; CDCl3) δ 0.80 (t, 3H, J = 7.0 Hz, CH3-),
1.14ꢀ1.29 (m, 4H, CH2CH2), 1.46ꢀ1.58 (m, 2H, CH2), 1.57 (s, 3H,
CH3), 1.64ꢀ1.77 (m, 1H, H-6β), 1.77ꢀ1.85 (m, 1H, H-6R), 1.80 (s, 3H,
CH3CdO), 1.89 (dd broad, 1H, H-5β), 2.00ꢀ2.08 (m, 1H, H-5R), 2.43
(t, 2H, J = 7.7 Hz, CH2), 3.18 (ddd broad, 1H, J = 11.2, 9.7, 3.0 Hz,
H-1), 3.65 (s, 6H, OCH3, OCH3), 4.07 (d broad, 1H, H-2), 5.06 (s,
1H, H-3), 6.25 (s, 2H, H-30, H-50); 13C NMR (400 MHz; CDCl3) δ 14.0
(C-500), 22.5 (C-400), 23.3 (4-CH3), 26.5 (C-6), 28.6 (CH3CdO), 29.5
(C-5), 31.0 (C-200), 31.6 (C-300), 34.6 (C-2), 36.4 (C-100), 51.1 (C-1),
55.9 (20-OCH3, 60-OCH3), 104.9 (C-30, C-50), 117.2 (C-10), 124.8
(C-3), 131.0 (C-40), 142.8 (C-4), 158.4 (C-20, C-60), 213.6 (CdO);
MS m/e (rel intensity) 43 (17), 152 (36), 166 (11), 173 (26), 208
(100), 209 (19), 221 (97), 222 (16), 243 (42), 274 (56), 301 (29),
344 (Mþ, 5). Anal. Calcd for C22H32O3: C, 76.70; H, 9.36. Found: C,
76.61; H, 9.30.
rel-(1R,2R)-Methyl 2-(20-Methoxyphenyl)-4-methylcyclo-
hex-3-enecarboxylate (8ay). Oil; IR (CHCl3) 1727 (CdO) cmꢀ1
;
1H NMR (400 MHz; CDCl3) δ 1.57 (s, 3H, CH3), 1.66ꢀ1.81 (m, 2H,
H-6R, H-6β), 1.83ꢀ1.94 (m, 2H, H-5R, H-5β), 2.51 (ddd, 1H, J = 10.7, 7.1,
3.6 Hz, H-1), 3.43 (s, 3H, CH3OCdO), 3.65 (s, 3H, OCH3), 4.00 (s broad,
1H, H-2), 5.13 (s broad, 1H, H-3), 6.68 (d, 1H, J=8.1Hz, H-30), 6.74 (t, 1H,
J = 7.5 Hz, H-50), 6.97ꢀ7.05 (m, 2H, H-40, H-60); 13C NMR (400 MHz;
CDCl3) δ 23.6, 24.2, 28.4, 36.9, 45.0, 51.4, 55.4, 110.4, 120.3, 123.2, 127.4,
128.8, 132.5, 134.0, 157.1, 175.8; MS m/e (rel intensity) 91 (18), 121 (22),
159 (32), 185 (31), 200 (100), 201 (23), 260 (Mþ, 14). Anal. Calcd for
C16H20O3: C, 73.82; H, 7.74. Found: C, 73.92; H, 7.69.
rel-1-((1R,2R)-2-(20,40-Dimethoxyphenyl)-4-methylcyclo-
hex-3-enyl)ethanone (8bx). Oil; IR (CHCl3) 1704 (CdO) cmꢀ1
;
1H NMR (400 MHz; CDCl3) δ 1.63 (s, 3H, CH3), 1.65ꢀ1.71 (m, 1H,
H-6β), 1.73ꢀ1.82 (m, 1H, H-6R), 1.89 (m, 2H, H-5R, H5β), 1.97 (s,
3H, CH3CdO), 2.53 (ddd broad, 1H, J = 10.4, 6.9, 3.6 Hz, H-1), 3.68 (s,
3H, OCH3), 3.69 (s, 3H, OCH3), 3.92 (s broad, 1H, H-2), 5.18 (s broad,
1H, H-3), 6.34 (s, 1H, H-30), 6.35 (d, 1H, J = 7.5 Hz, H-50), 6.94 (d, 1H,
J = 7.2 Hz, H-60); 13C NMR (400 MHz; CDCl3) δ 23.5, 23.6, 28.3, 28.4,
53.4, 55.3 (2C), 98.4, 104.0, 123.4, 125.1, 129.2, 134.1, 157.7, 159.3, 211.7;
MS m/e (rel intensity) 43 (19), 121 (20), 138 (48), 151 (72), 173 (20),
189 (100), 190 (17), 203 (63), 204 (61), 231 (68), 243 (15), 274 (Mþ,
88). Anal. Calcd for C17H22O3: C, 74.42; H, 8.08. Found: C, 74.35; H, 8.02.
rel-(1R,2R)-Methyl 2-(20,40-Dimethoxyphenyl)-4-methylcy-
clohex-3-enecarboxylate (8by). Oil; IR (CHCl3) 1727 (CdO)
rel-(1R,2R)-Methyl 2-(20,60-Dimethoxy-40-pentylphenyl)-
4-methylcyclohex-3-enecarboxylate (8dy)7m. White solid, mp
89ꢀ90 °C (n-hexane); IR (CHCl3) 1736 (CdO) cmꢀ1; 1H NMR (400
MHz; CDCl3) δ 0.90 (t, 3H, J = 7.0 Hz, CH3-), 1.26ꢀ1.39 (m, 4H,
CH2CH2), 1.52ꢀ1.64 (m, 2H, CH2), 1.63ꢀ1.73 (m, 1H, H-6 β), 1.64
(s, 3H, CH3), 1.84ꢀ1.96 (m, 2H, H-6R, H-5β), 2.05ꢀ2.13 (m, 1H,
H-5R), 2.50 (t, 2H, J = 7.9 Hz, CH2), 3.04 (ddd, 1H, J = 11.7, 10.7, 2.4
Hz, H-1), 3.22 (s, 3H, CH3OCdO), 3.60 (s, 6H, OCH3, OCH3), 4.06
5400
dx.doi.org/10.1021/jo200796b |J. Org. Chem. 2011, 76, 5392–5403