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X. Huo et al. / Tetrahedron: Asymmetry 19 (2008) 343–347
4.4. Compound 7
3H), 4.22 (q, J = 7.2 Hz, 2H), 4.40 (d, J = 7.2 Hz, 1H),
4.46 (d, J = 7.2 Hz, 1H), 4.78 (d, J = 9.0 Hz, 1H), 5.04 (s,
2H), 5.17 (d, J = 9.0 Hz, 1H), 6.54 (d, J = 2.4 Hz, 1H),
6.60 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 7.33–7.46 (m,
6H). 13C NMR (75 MHz, CDCl3): d 14.0, 19.1, 25.7,
28.1, 55.7, 56.4, 61.3, 70.0, 82.0, 82.7, 94.2, 99.3, 105.6,
109.4, 119.6, 127.6, 128.0, 128.6, 129.7, 136.8, 159.2,
159.8, 173.0. HRMS (m/z): [M]+ calcd for C26H34O8,
474.2254; found, 474.2046.
To a stirred solution of aldehyde 8 (443 mg, 1.4 mmol) in
dry toluene (25 mL) was added Ph3P@CH(Me)CO2Et
(760 mg, 2.1 mmol), and the mixture was then heated at
100 °C with stirring for 12 h. The solvent was removed in
vacuo and the residue washed with brine and extracted
with EtOAc (3 ꢁ 20 mL). The combined organic phase
was washed with brine, dried over anhydrous Na2SO4
and concentrated in vacuo. Flash chromatography (10:1,
petrol/EtOAc) afforded 7 (555 mg, 1.4 mmol) as a colorless
4.7. Compound 16
25
oil. ½aꢂD ¼ þ2:7 (c 10.1, CHCl3); IR (neat): 3032, 1710,
1652, 1242, 1201 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d
To a solution of 15 (237 mg, 0.5 mmol) in ethanol (8 mL)
and methanol (2 mL) was added Raney-Ni (100 mg) in
one portion. The reaction mixture was stirred under atmo-
sphere of H2 for 24 h before filtering through a pad of Cel-
ite. The pad was washed repeatedly with ethyl acetate and
the wash was combined with filtrate. Concentration in va-
1.28 (t, J = 7.2 Hz, 3H), 1.94 (s, 3H), 3.37 (s, 3H), 3.79
(s, 3H), 4.17 (q, J = 7.2 Hz, 2H), 4.62 (s, 2H), 5.05 (s,
2H), 5.80 (d, J = 8.8 Hz, 1H), 6.52 (d, J = 2.4 Hz, 1H),
6.58 (dd, J1 = 2.4 Hz, J2 = 8.0 Hz, 1H), 6.80 (d,
J = 8.8 Hz, 1H), 7.33–7.44 (m, 6H); 13C NMR (75 MHz,
CDCl3): d 12.7, 14.1, 55.3, 55.4, 60.6, 67.8, 70.0, 93.7,
99.2, 105.3, 120.8, 127.5, 128.0, 128.6, 128.7, 136.7, 140.2,
157.8, 159.7, 168.0. HRMS (m/z): [M]+ calcd for
C23H28O6, 400.1886; found, 400.2312.
cuo provided compound 16 as a white solid (346 mg, 90%).
25
Mp: 97–99 °C; ½aꢂD ¼ þ90 (c 4.2, CHCl3); IR (neat) 3409,
1615, 1510, 1272, 1200, 1023, 1075 cmꢀ1
.
1H NMR
(300 MHz, CDCl3): d 1.27 (t, J = 7.2 Hz, 3H), 1.37 (s,
3H), 1.39 (s, 3H), 1.54 (s, 3H), 3.31 (s, 3H), 3.72 (s, 3H),
4.22 (q, J = 7.2 Hz, 2H), 4.39 (d, J = 7.8 Hz, 1H), 4.46
(d, J = 7.8 Hz, 1H), 4.77 (d, J = 8.7 Hz, 1H), 5.13 (d,
J = 8.7 Hz, 1H), 6.05 (br, 1H), 6.27 (s, 1H), 6.32 (d,
J = 8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H). 13C NMR
(75 MHz, CDCl3): d 14.0, 19.1, 25.7, 28.0, 55.5, 56.4,
61.5, 82.1, 82.8, 94.1, 99.1, 107.6, 109.6, 118.3, 129.7,
157.1, 159.3, 173.0. HRMS (m/z): [M]+ calcd for
C19H28O8, 384.1784; found, 384.2086.
4.5. Compound 14
To a solution of 7 (100 mg, 0.25 mmol) in THF (12 mL)
and H2O (4 mL) were added OsO4 (4.5 mg, 0.0125 mmol)
and NMO (32 mg, 0.275 mmol), and the reaction was stir-
red at room temperature for 4 h before being quenched
with saturated Na2SO3 solution. The mixture was extracted
with EtOAc. The combined organic extracts were dried
over anhydrous Na2SO4 and concentrated in vacuo to give
the diol mixture. Careful flash chromatography (100:1,
4.8. Compound 6
CH2Cl2/CH3COCH3) afforded the desired diol as a color-
25
less oil (64 mg, 70%). ½aꢂD ¼ þ20 (c 2.0, CHCl3); IR (neat):
Dicyclohexylcarbodiimide (DCC) (272 mg, 1.0 mmol) was
added to a solution of propiolic acid (93 mg, 1.0 mmol),
dimethylaminopyridine (DMAP) (10 mg, 10% mmol), and
phenol 16 (255 mg, 0.66 mmol) in 20 mL CH2Cl2 at 0 °C
under argon. The reaction mixture was stirred at the same
temperature overnight. After filtering off the precipitate,
the filtrate was concentrated and purified by flash chroma-
3502, 1733, 1252, 1157, 1029 cmꢀ1. H NMR (300 MHz,
1
CDCl3): d 1.28 (t, J = 7.2 Hz, 3H), 1.54 (s, 3H), 2.62 (br,
1H), 3.35 (s, 3H), 3.78 (d, J = 6.3 Hz, 1H), 3.80 (s, 3H),
3.97 (br, 1H), 4.15 (q, J = 7.2 Hz, 2H), 4.50 (s, 2H),
5.04 (s, 2H), 5.23 (d, J = 6.3 Hz, 1H), 6.53 (d, J = 2.1 Hz,
1H), 6.60 (dd, J1 = 2.1 Hz, J2 = 8.1 Hz, 1H), 7.30–7.44
(m, 6H). 13C NMR (75 MHz, CDCl3): d 14.1, 23.4, 55.6,
56.4, 61.8, 70.1, 76.6, 78.0, 94.6, 99.2, 105.7, 119.0, 127.5,
128.1, 128.6, 129.2, 136.8, 158.7, 159.9, 175.8. HRMS
(m/z): [M]+ calcd for C23H30O8, 434.1941; found, 434.1985.
tography. Compound 6 was obtained as a white solid
25
(305 mg, 70%). Mp: 134–136 °C; ½aꢂD ¼ þ55 (c 1.6, CHCl3);
IR (neat) 2121, 1736, 1263, 1197, 1102, 1025 cmꢀ1 1H
.
NMR (300 MHz, CDCl3): d 1.28 (t, J = 7.2 Hz, 3H), 1.33
(s, 3H), 1.37 (s, 3H), 1.52 (s, 3H), 3.07 (s, 1H), 3.30 (s,
3H), 3.82 (s, 3H), 4.22 (q, J = 7.2 Hz, 2H), 4.44 (s, 2H),
4.68 (d, J = 6.3 Hz, 1H), 5.21 (d, J = 6.3 Hz, 1H), 6.67 (d,
J = 1.5 Hz, 1H), 6.79 (dd, J1 = 1.5 Hz, J2 = 6.3 Hz, 1H),
7.44 (d, J = 6.3 Hz, 1H). 13C NMR (75 MHz, CDCl3): d
14.0, 19.3, 25.6, 28.0, 55.9, 56.5, 61.4, 69.6, 74.2, 76.6,
82.1, 82.7, 94.7, 104.5, 109.5, 113.2, 125.7, 129.3, 150.3,
150.7, 158.8, 172.9. HRMS (m/z): [M]+ calcd for
C22H28O9, 436.1733; found, 436.1784.
4.6. Compound 15
Upon the addition of para-toluenesulfonic acid monohy-
drate (10 mg, 0.1 mmol) to a stirred solution of diol l4
(434 mg, 1.0 mmol) and 2,2-dimethoxypropane (0.2 mL,
2 mmol) in CH2Cl2 (30 mL), the reaction was heated at
50 °C for 8 h before being quenched with H2O (20 mL).
The aqueous layer was extracted with CH2Cl2
(3 ꢁ 20 mL) after separated from the organic layer. The
combined organic phase was washed with brine, dried over
anhydrous Na2SO4 and concentrated in vacuo. Flash chro-
4.9. Compound 5
matography (20:1, petrol/EtOAc) afforded acetonide 15 as
A solution of 6 (436 mg, 1.0 mmol) in 8 mL THF and 2 mL
6 M HCl was stirred at room temperature for 4 h. The sol-
vent was removed in vacuo and the residue was washed
with brine and extracted with EtOAc (3 ꢁ 10 mL). The
combined organic phase was washed with brine, dried over
25
a colorless oil (393 mg, 83%). ½aꢂD ¼ þ34 (c 2.1, CHCl3);
1
IR (neat): 2988, 1739, 1611, 1505, 1060, 1022 cmꢀ1. H
NMR (300 MHz, CDCl3): d 1.30 (t, J = 7.2 Hz, 3H), 1.36
(s, 3H),1.39 (s, 3H), 1.54 (s, 3H), 3.32 (s, 3H), 3.80 (s,