D. Sarkar, R.V. Venkateswaran / Tetrahedron 67 (2011) 4559e4568
4565
CDCl3)
d
13.47 (s, 1H); 6.19 (s, 1H); 6.17 (s, 1H); 3.7 (s, 3H); 2.52
THF (2 mL) was added dropwise under argon and the reaction
mixture stirred for 30 min. Then the reaction mixturewas allowed to
warm to ꢀ30 ꢁC and kept at that temperature for another 30 min.
Again the reaction mixture was cooled to ꢀ78 ꢁC and HMPA (0.2 mL)
followed by phenyl selenyl bromide (252 mg, 1.4 mmol) in THF
(2 mL) were added dropwise. After 2 h the reaction mixture was
allowed to attain room temperature and stirred for 1 h. The reaction
mixture was then cooled to 0 ꢁC followed by addition of H2O2 (5 mL,
30%) and stirred for 3 h and allowed to attain room temperature. The
reaction mixture was quenched with saturated aqueous NH4Cl so-
lution and extracted with ether (3ꢂ15 mL). The combined ethereal
extracts were washed with water, dried, and the solvent removed.
The residue was subjected tocolumnchromatographyover silica gel.
Elution with ethyl acetate/petroleum ether (3:5) afforded the
chromene carboxylate 20 as a colourless liquid (169 mg, 90%).
(s, 3H); 2.45 (s, 3H). 13C NMR (75 MHz, CDCl3)
d 204.3, 167.5, 164.7,
142.2, 115.5, 112.2, 99.4, 55.7, 33.4, 25.5. HRMS (ESI) MþNaþ, found:
203.0682; C10H12O3Na requires 203.0684.
3.1.8. Ethyl 7-methoxy-5-methyl-4-oxo-4H-chromene-2-carboxylate
(18). To a cooled (ice-bath), stirred slurry of sodium hydride (0.7 g,
0.028 mol, 50% dispersion in oil) in anhydrous THF (10 mL) under
argon, a mixture of 1-(2-hydroxyl-4-methoxy-6-methyl phenyl)
ethanone 17 (2.53 g, 0.014 mol) and diethyl oxalate (3.9 mL,
0.028 mol) in THF (20 mL) was added slowly and the reaction
mixture left overnight at room temperature. It was then poured
into ice-water (70 mL) and acidified with cold dilute HCl (6 N,
20 mL) and extracted with ether (3ꢂ40 mL). The ether extract was
washed with water (2ꢂ20 mL), dried and concentrated. The solid
residue was dissolved in benzene (120 mL), toluene-p-sulfonic acid
(150 mg) was added and refluxed for 8 h, using a DeaneStark water
separator. It was then cooled, washed with saturated aqueous
NaHCO3 solution, water, and solvent removed to get a yellowish
solid. This was subjected to chromatography over silica gel. Elution
with ethyl acetate/petroleum ether (1:4) furnished the chromene
carboxylate 18 (3.3 g, 90%) as a colourless solid. Rf (20% EtOAc/pe-
troleum ether (60:80)) 0.44; crystallized from dichloꢀro1methane/
3.1.11. (7-Methoxy-5-methyl-4H-chromen-2-yl) methanol (21). To
a well stirred slurry of LAH (60 mg, 1.37 mmol) in THF (3 mL)
at ꢀ40 ꢁC, the chromene carboxylate 20 (170 mg, 0.68 mmol) in THF
(2 mL) was added slowly via a syringe and stirred for 1 h at the
same temperature. Then the reaction was allowed to attain 0 ꢁC and
quenched with saturated aqueous Na2SO4 solution. The reaction
mixture was extracted with ether (3ꢂ5 mL) and dried. Removal of
the solvent furnished the allylic alcohol 21 as a colourless solid
(132 mg, 93%); crystallized from dichloromethane/petroleum ether
petroleum ether; mp 132e134 ꢁC; IR 1645, 1737 cm
.
1H NMR
(300 MHz, CDCl3)
d 6.88 (s, 1H); 6.77 (s, 1H); 6.66 (s, 1H); 4.37
(q, J¼6.9 Hz, 2H); 2.72 (s, 3H); 3.80 (s, 3H); 1.35 (t, J¼6.9 Hz, 3H). 13C
(1:1). Mp 129e130 ꢁC; 1H NMR (300 MHz, CDCl3)
d 6.37 (d,
NMR (75 MHz, CDCl3)
d
179.4, 163.4, 160.8, 159.5, 150.4, 142.8, 117.4,
J¼2.4 Hz, 1H); 6.23 (d, J¼2.4 Hz, 1H); 4.94 (t, J¼3.3 Hz, 1H); 4.05 (d,
117.2, 116.36, 98.8, 62.8, 55.8, 22.9, 14.2. HRMS (EI) MþHþ, found:
J¼5.4 Hz, 2H); 3.6 (s, 3H); 3.15 (d, J¼3.2 Hz, 2H); 2.09 (s, 3H). 13C
263.0920; C14H15O5 requires 263.0919.
NMR (75 MHz, CDCl3) d 158.9, 152.5, 149.9, 138.5, 111.4, 109.4, 99.4,
97.9, 63.1, 55.6, 22.2, 19.5. HRMS (ESI) MþNaþ, found: 229.0843;
3.1.9. Ethyl-7-methoxy-5-methylchroman-2-carboxylate (19). The
chromone carboxylate 18 (260 mg, 1 mmol) was subjected to hy-
drogenation (60 mmHg) in the presence of palladium charcoal
(10%, 80 mg) in ethanol (5 mL) for 9 h. The catalyst was then fil-
tered, the solvent removed and the residue subjected to chroma-
tography over silica gel. Elution with ethyl acetate/petroleum ether
(1:4) furnished the chromane carboxylate 19 as a colourless liquid
(238 mg, 96%). Rf (20% EtOAc/petroleum ether (60:80)) 0.82; IR
C12H14O3Na requires 229.0841.
3.1.12. (S
*
)-Ethyl 2-((R )-7-methoxy-5-methyl-2-methylenechroman-
*
3-yl) propanoate (22b). A mixture of the allylic alcohol 21 (100 mg,
0.48 mmol), triethyl orthopropionate (0.7 mL, 3.4 mmol) and pro-
pionic acid (0.06 mL) was heated with stirring in xylene (5 mL)
maintaining the temperature at 140 ꢁC. Heating was continued for
8 h; the reaction mixture was allowed to cool to room temperature
and the solvent was removed by distillation under reduced pressure
(50e60 ꢁC at 20 mmHg). The residue was purified by column chro-
matography over silica gel. Elution with ethyl acetate/petroleum
ether (1:20) afforded the ester 22b (12 mg, 8.5%) as a colourless oil. Rf
(20% EtOAc/petroleum ether (60:80)) 0.76; IR (neat) 1734 cmꢀ1. 1H
(neat) 1755 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d 6.38 (s, 1H); 6.37 (s,
1H); 4.63 (dd, J¼3.3, 7.8 Hz, 1H); 4.25 (q, J¼7.2 Hz, 2H); 3.73 (s, 3H);
2.57 (m, 2H); 2.25 (m, 2H); 2.16 (s, 3H); 1.29 (t, J¼7.2 Hz, 3H). 13C
NMR (75 MHz, CDCl3)
d 170.9, 158.6,154.3, 138.1, 112.3, 109.7, 99.4,
73.5, 61.4, 55.2, 24.9, 20.7, 19.3, 14.2. HRMS (EI) MþHþ, found:
251.1285; C14H19O4 requires 251.1283.
NMR (300 MHz, CDCl3) d 6.38 (s,1H); 6.30 (s,1H); 4.66 (s,1H); 4.25 (s,
1H); 4.13 (q, J¼6.9 Hz, 2H); 3.74 (s, 3H); 2.82e2.87 (m, 1H); 2.73 (dd,
J¼5.1, 16.2 Hz, 1H); 2.61 (dd, J¼2.1, 16.2 Hz, 2H); 2.43e2.47 (m, 1H);
2.14 (s, 3H); 1.24 (t, J¼7.2 Hz, 3H); 1.19 (d, J¼6.9 Hz, 3H). 13C NMR
3.1.10. Ethyl 7-methoxy-5-methyl-4H-chromene-2-carboxylate (20).
(I) Method 1: To a solution of chromone carboxylate 18 (100 mg,
0.46 mmol) in THF (4 mL), BF3$OEt2 (0.18 mL, 1.38 mmol) and so-
dium cyanoborohydride (115 mg, 1.832 mmol) were added and
refluxed for 3 h. Then the reaction mixture was cooled and
quenched with saturated aqueous NH4Cl solution. The aqueous
layer was extracted with ether (3ꢂ10 mL) and dried. The solvent
was evaporated to get a yellow liquid, which was subjected to
chromatography over silica gel. Elution with ethyl acetate/petro-
leum ether (3:5) furnished the chromene carboxylate 20 as a col-
ourless liquid (30 mg, 25%). Rf (20% EtOAc/petroleum ether (60:80))
(75 MHz, CDCl3)
d 176.0,158.8, 155.4, 153.3, 138.1, 111.1, 109.9, 98.7,
92.7, 60.6, 55.3, 39.8, 39.7, 26.3, 19.4, 16.4, 14.4. HRMS (EI) MHþ,
found: 291.1598; C17H23O4 requires 291.1596.
3.1.13. (R
*
)-Ethyl
2-((R )-7-methoxy-5-methyl-2-methylenechro-
*
man-3-yl) propanoate (22a). Further elution with ethyl acetate/
petroleum ether (1:20) afforded the isomeric ester 22a (124 mg,
88%) in major amounts as a colourless oil. Rf (20% EtOAc/petroleum
ether (60:80)) 0.75; IR (neat) 1732 cmꢀ1. 1H NMR (300 MHz, CDCl3)
0.65; IR (neat) 1732 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d
6.38 (s, 1H);
d
6.38 (s, 1H); 6.33 (s, 1H); 4.56 (s, 1H); 4.17 (s, 1H); 4.10 (q, J¼6.9 Hz,
6.37 (s, 1H); 6.13 (t, J¼4.2 Hz, 1H); 4.23 (q, J¼7.2 Hz, 2H); 3.66 (s,
2H); 3.74 (s, 3H); 2.86e2.89 (m, 1H); 2.70 (d, J¼4.8 Hz, 2H);
2.52e2.57 (m, 1H); 2.2 (s, 3H); 1.26 (t, J¼7.2 Hz, 3H); 1.16 (d,
3H); 3.29 (d, J¼4.2 Hz, 2H); 2.09 (s, 3H); 1.28 (t, J¼7.2 Hz, 3H). 13C
NMR (75 MHz, CDCl3)
d
162.1, 159.2,152.1, 141.8, 138.3, 112.4, 110.6,
J¼6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3)
d 175.8, 159.3, 157.3, 153.7,
109.4, 99.7, 61.8, 55.7, 22.8, 19.6, 14.6. HRMS (ESI) MþNaþ, found:
137.8,111.3, 110.1, 99.1, 90.9, 60.8, 55.6, 41.0, 39.2, 24.1, 19.6, 15.2,
271.0946; C14H16O4Na requires 271.0946.
14.5. HRMS (EI) MHþ, found: 291.1589; C17H23O4 requires 291.1596.
(II) Method 2: To a well-stirred solution of LDA, prepared from
n-butyllithium (0.7 mL of 1.6 M solution in hexane, 0.912 mmol) and
diisopropylamine (0.15 mL, 1.06 mmol) in THF (3 mL) at ꢀ78 ꢁC,
a solution of the chromane carboxylate 19 (190 mg, 0.76 mmol) in
3.1.14. (R
*
)-2-((R )-7-Methoxy-5-methyl-2-methylenechroman-3yl)
*
propan-1-ol (23). To a well stirred slurry of LAH (57 mg, 1.5 mmol)
in THF (2 mL) at 0 ꢁC, the ester 22a (310 mg, 1.07 mmol) in THF