8706
S.-R. Li et al. / Tetrahedron 65 (2009) 8702–8707
obtained as viscous yellow liquid. trans-2-(4-methylbenzoyl)-5,6-
dimethoxy-3-methylchroman (trans-5c) (2.1 g, 64%) was obtained
as yellowish crystal, mp 120–121 ꢀC, Rf¼0.61 (ethyl acetate/
111.4, 111.6, 115.7, 128.6, 130.2, 132.0, 134.4, 146.9, 147.4, 147.7, 196.2;
EIMS (70 eV) m/z (rel intensity, %) 392 ([Mþ2]þ,15), 390 (Mþ, 21), 207
(100), 192 (23), 179 (14), 151 (18); ESI-HRMS calcd for C19H19BrO4Na
[MþNa]þ: 413.0364. Found: 413.0362.
n-hexane¼1:4), 1H NMR (CDCl3, 400 MHz)
d
1.07 (d, J¼6.0 Hz, 3H,
CH3-3), 2.42 (s, 3H, CH3-40), 2.43–2.50 (m, 1H, H-3), 2.47 (dd,
J¼20.0 Hz, 8.4 Hz, 1H, Ha-4), 2.89 (dd, J¼20.0 Hz, 8.4 Hz, 1H, Hb-4),
3.82, 3.82 (each s, 2ꢂ3H, 2ꢂOCH3), 4.93 (d, J¼7.6 Hz, 1H, H-2), 6.62
(d, J¼8.8 Hz, 1H, ArH), 6.74 (d, J¼8.8 Hz, 1H, ArH), 7.27 (d, J¼8.4 Hz,
2H, ArH), 7.95 (d, J¼8.4 Hz, 2H, ArH), 13C NMR (CDCl3, 100 MHz)
4.4. General procedure for the preparation of 2-benzoyl-
5,6-dimethoxy-3-methylchromen-4-ones (6a–e)
The diastereomeric mixture of 5a–e (5.0 mmol) dissolved in 1,4-
dioxane (10.0 mL) was stirred and added DDQ (3.4 g, 15.0 mmol).
The resultant mixture was heated to the reflux for 3 days until TLC
analysis showed the consumption of the starting material. The re-
sultant mixture, which was cooled to room temperature was added
water (30 mL) and extracted with dichloromethane (20 mLꢂ3). The
organic extracts were combined, washed with brine (10 mLꢂ2),
and dried with anhydrous MgSO4. After filtration, the filtrate was
concentrated in vacuo to remove the solvent. The residue was
purified by silica gel column chromatography (ethyl acetate/
n-hexane¼1:5) to give 6a–e.
d
17.7, 21.7, 26.4, 28.5, 56.4, 60.2, 81.9, 110.9, 111.7, 116.0, 129.2, 129.3,
132.7, 144.4, 146.5, 146.9, 147.7, 196.7; cis-5c (0.81 g, 25%) was
obtained as yellow liquid, Rf¼0.56 (ethyl acetate/n-hexane¼1:4), 1H
NMR (CDCl3, 400 MHz)
d
0.91 (d, J¼6.8 Hz, 3H, CH3-3), 2.43 (s, 3H,
CH3-40), 2.59–2.66 (m, 1H, H-3, H-3), 2.73 (dd, J¼17.2, 2.8 Hz, 1H,
Ha-4), 3.01 (dd, J¼17.2, 6.4 Hz, 1H, Hb-4), 3.82, 3.84 (each s, 2ꢂ3H,
2ꢂOCH3), 5.33 (d, J¼2.4 Hz, 1H, H-2), 6.72 (d, J¼9.0 Hz, 1H, ArH),
6.76 (d, J¼9.0 Hz, 1H, ArH), 7.28 (d, J¼8.8 Hz, 2H, ArH), 7.87 (d,
J¼8.8 Hz, 2H, ArH); 13C NMR (CDCl3, 100 MHz)
d 13.5, 21.7, 28.0,
28.5, 56.3, 60.2, 79.5, 111.5, 111.6, 115.6, 128.5, 128.7, 133.4, 135.6,
147.8,147.4,147.9,196.9; EIMS (70 eV) m/z (rel intensity, %) 326 (Mþ,
71), 207 (100), 192 (38), 179 (21), 176 (18), 151 (28), 119 (17); ESI-
HRMS calcd for C20H22O4Na [MþNa]þ: 349.1416. Found: 349.1414.
4.4.1. 2-Benzoyl-5,6-dimethoxy-3-methyl-1-chromen-4-one (6a). Pure
6a (1.0 g, 62%) was obtained as yellow crystal, mp 118–120 ꢀC, Rf¼0.44
(ethyl acetate/n-hexane¼1:2), IR (KBr) cmꢁ1
, nmax: 2932, 1646, 1482,
4.3.4. Thediasteromericmixtureof2-(4-chlorobenzoyl)-5,6-dimethoxy-
3-methylchroman (5d). Compound 5d (2.74 g, 79%) was obtained as
viscous yellow liquid. trans-2-(4-chloro-benzoyl)-5,6-dimethoxy-3-
methylchroman (trans-5d) (1.73 g, 50%) was obtained as orange color
crystal, mp 101–102 ꢀC, Rf¼0.62 (ethyl acetate/n-hexane¼1:4), 1H
1368, 1260, 1168, 1095, 1054, 1012, 936, 800, 716; 1H NMR (CDCl3,
400 MHz)
d
2.03 (s, 3H, CH3), 3.93, 3.99 (each s, 2ꢂ3H, 2ꢂOCH3), 7.15
(d, J¼9.6 Hz, 1H, H-8), 7.31 (d, J¼9.6 Hz, 1H, H-7), 7.51–7.56 (m, 2H,
H-30), 7.66–7.70 (m, 1H, H-40), 7.91–7.94 (m, 2H, H-20); 13C NMR
(CDCl3, 100 MHz)
d 10.1, 57.1, 61.8, 113.5, 118.4, 119.4, 119.5, 129.0,
NMR (CDCl3, 400 MHz)
d
1.08 (d, J¼6.4 Hz, 3H, CH3-3), 2.43–2.50 (m,
130.0, 134.7, 134.9, 147.6, 150.1, 150.6, 154.1, 177.8, 188.9; EIMS (70 eV)
m/z (rel intensity, %) 324 (Mþ, 49), 310 (21), 309 (100), 295 (34), 281
(36), 105 (43), 77 (19); ESI-HRMS calcd for C19H16O5Na [MþNa]þ:
347.0895. Found: 347.0897. Anal. Calcd for C19H16O5: C, 70.36%; H,
4.97%. Found: C, 70.12%; H, 5.01%.
1H, H-3), 2.46 (dd, J¼20.4, 8.8 Hz, 1H, Ha-4), 2.88 (dd, J¼20.4, 8.8 Hz,
1H, Hb-4), 3.82, 3.83 (each s, 2ꢂ3H, 2ꢂOCH3), 4.84 (d, J¼7.6 Hz,1H, H-
2), 6.60 (d, J¼8.8 Hz, 1H, ArH), 6.74 (d, J¼8.8 Hz, 1H, ArH), 7.44 (d,
J¼8.4 Hz, 2H, ArH), 8.01 (d, J¼8.8 Hz, 2H, ArH); 13C NMR (CDCl3,
100 MHz)
d 17.6, 26.6, 28.3, 56.4, 60.2, 82.5, 110.9, 111.8, 116.0, 128.9,
130.6, 133.6, 140.0, 146.7, 146.9, 147.4, 196.1; cis-5d (1.01 g, 29%) was
4.4.2. 5,6-Dimethoxy-2-(4-methoxybenzoyl)-3-methyl-1-chromen-4-
obtained as yellow liquid, Rf¼0.57 (ethyl acetate/n-hexane¼1:4), 1H
one (6b). Pure 6b (1.01 g, 57%) was obtained as yellow crystal, mp
NMR (CDCl3, 400 MHz)
d
0.93 (d, J¼6.8 Hz, 3H, CH3-3), 2.60–2.65 (m,
171–173 ꢀC, Rf¼0.24 (ethyl acetate/n-hexane¼1:2), IR (KBr) cmꢁ1
,
1H, H-3), 2.74 (dd, J¼16.8, 2.8 Hz, 1H, Ha-4), 3.06 (dd, J¼16.8, 6.0 Hz,
1H, Hb-4), 3.82, 3.84 (each s, 2ꢂ3H, 2ꢂOCH3), 5.24 (d, J¼2.4 Hz, 1H,
H-2), 6.69 (d, J¼9.2 Hz, 1H, ArH), 6.75 (d, J¼9.2 Hz, 1H, ArH), 7.46 (d,
J¼8.6 Hz, 2H, ArH), 7.94 (d, J¼8.6 Hz, 2H, ArH); 13C NMR (CDCl3,
nmax: 2931, 2837, 1652, 1599, 1479, 1429, 1367, 1256, 1168, 1096, 1052,
1012, 934, 837, 799; 1H NMR (CDCl3, 400 MHz)
d 1.99 (s, 3H, CH3),
3.91, 3.93, 3.99 (each s, 3ꢂ3H, 3ꢂOCH3), 6.99 (d, J¼8.8 Hz, 2H, H-30),
7.16 (d, J¼8.8 Hz, 1H, H-8), 7.31(d, J¼8.8 Hz, 1H, H-7), 7.91 (d,
100 MHz)
d
13.6, 27.9, 28.4, 56.4, 60.2, 79.7, 111.4, 111.7, 115.7, 129.0,
J¼8.8 Hz, 2H, H-20); 13C NMR (CDCl3,100 MHz)
d 10.4, 55.9, 57.3, 62.0,
130.2, 133.9, 139.8, 146.9, 147.4, 147.7, 196.0; EIMS (70 eV) m/z (rel
intensity, %) 348 ([Mþ2]þ, 9), 346 (Mþ, 26), 207 (100), 192 (22), 179
(17), 151 (20); ESI-HRMS calcd for C19H19ClO4Na [MþNa]þ: 369.0870.
Found: 369.0871.
113.8, 114.5, 114.6, 118.7, 119.0, 119.5, 128.0, 132.8, 147.8, 150.3, 151.0,
155.0, 165.2, 187.5; EIMS (70 eV) m/z (rel intensity, %) 354 (Mþ, 51),
340 (21), 339 (100), 325 (18), 311 (28), 135 (76), 77 (14); ESI-HRMS
calcd for C20H18O6Na [MþNa]þ: 377.1001. Found: 377.1002. Anal.
Calcd for C20H18O6: C, 67.79%; H, 5.12%. Found: C, 67.74%; H, 5.12%.
4.3.5. The diasteromeric mixture of 2-(4-bromo-benzoyl)-5,6-dime-
thoxy-3-methylchroman (5e). Compound 5e (3.12 g, 80%) was
obtained as viscous yellow liquid. trans-2-(4-bromobenzoyl)-5,6-
dimethoxy-3-methylchroman (trans-5e) (2.29 g, 59%) was obtained
as orange color crystal, mp 99–100 ꢀC, Rf¼0.59 (ethyl acetate/
4.4.3. 5,6-Dimethoxy-3-methyl-2-(4-methylbenzoyl)-1-chromen-4-
one (6c). Pure 6c (1.02 g, 60%) was obtained as brown crystal, mp
153–155 ꢀC, Rf¼0.40 (ethyl acetate/n-hexane¼1:2), IR (KBr) cmꢁ1
,
nmax: 2933, 1631, 1478, 1425, 1368, 1264, 1163, 1095, 1054, 1003, 931,
n-hexane¼1:4), 1H NMR (CDCl3, 400 MHz)
d
1.08 (d, J¼6.0 Hz, 3H,
799, 764, 616; 1H NMR (CDCl3, 400 MHz)
d 2.00 (s, 3H, CH3-3), 2.46
CH3-3), 2.43–2.50 (m, 1H, H-3), 2.46 (dd, J¼20.4, 8.4 Hz, 1H, Ha-4),
2.93 (dd, J¼20.4, 8.4 Hz,1H, Hb-4), 3.82, 3.83 (each s, 2ꢂ3H, 2ꢂOCH3),
4.84 (d, J¼7.6 Hz, 1H, H-2), 6.60 (d, J¼9.0 Hz, 1H, ArH), 6.74 (d,
J¼9.0 Hz, 1H, ArH), 7.61 (d, J¼8.6 Hz, 2H, ArH), 7.93 (d, J¼8.6 Hz, 2H,
(s, 3H, CH3-40), 3.94, 4.00 (each s, 2ꢂ3H, 2ꢂOCH3), 7.16 (d, J¼9.2 Hz,
1H, H-8), 7.32 (d, J¼9.2 Hz, 1H, H-7), 7.33 (d, J¼8.0 Hz, 2H, H-30),
7.83 (d, J¼8.4 Hz, 2H, H-20); 13C NMR (CDCl3, 100 MHz)
d 10.1, 21.9,
57.0, 61.7, 113.5, 118.4, 119.1, 119.3, 129.70, 130.1, 132.3, 146.0, 147.6,
150.0, 150.6, 154.4, 177.8, 188.4; EIMS (70 eV) m/z (rel intensity, %)
338 (Mþ, 35), 324 (20), 323 (100), 309 (15) 295 (29), 119 (41), 91
(19); ESI-HRMS calcd for C20H18O5Na [MþNa]þ: 361.1052. Found:
361.1050. Anal. Calcd for C20H18O5: C, 70.99%; H, 5.36%. Found: C,
70.85%; H, 5.35%.
ArH); 13C NMR (CDCl3, 100 MHz)
d 17.6, 26.5, 28.3, 56.4, 60.2, 82.5,
110.9, 111.7, 116.0, 128.7, 130.7, 131.9, 133.9, 146.7, 146.9, 147.3, 196.3;
cis-5e (0.83 g, 21%) was obtained as yellow liquid, Rf¼0.55 (ethyl
acetate/n-hexane¼1:4),1H NMR (CDCl3, 400 MHz)
0.93 (d, J¼7.2 Hz,
d
3H, CH3-3), 2.60–2.65 (m,1H, H-3), 2.74 (dd, J¼16.8, 2.8 Hz,1H, Ha-4),
3.06 (dd, J¼16.8, 6.4 Hz,1H, Hb-4), 3.82, 3.84 (each s, 2ꢂ3H, 2ꢂOCH3),
5.23 (d, J¼2.0 Hz, 1H, H-2), 6.69 (d, J¼8.6 Hz, 1H, ArH), 6.75 (d,
J¼8.6 Hz, 1H, ArH), 7.63 (d, J¼8.8 Hz, 2H, ArH), 7.86 (d, J¼8.8 Hz, 2H,
4.4.4. 2-(4-Chlorobenzoyl)-5,6-dimethoxy-3-methyl-1-chromen-4-
one (6d). Pure 6d (1.08 g, 60%) was obtained as yellow crystal, mp
ArH); 13C NMR (CDCl3, 100 MHz)
d
13.6, 27.9, 28.4, 56.3, 60.2, 79.7,
161–162 ꢀC, Rf¼0.46 (ethyl acetate/n-hexane¼1:2), IR (KBr) cmꢁ1
,