mixture was stirred at 0 °C for 45 min. The reaction was
quenched with sat. aqueous NaHCO3 (5 mL) and diluted with
CH2Cl2 (5 mL). The layers were separated and the aqueous layer
was extracted with CH2Cl2 (2 × 7 mL). The combined organic
layers were dried over Na2SO4, filtered and concentrated in
vacuo. The crude product was purified by flash chromatography
to give the respective product.
123 μL, 1.00 mmol, 4.00 equiv.) and Sc(OTf)3 (6.15 mg,
12.5 μmol, 0.05 equiv.) yielded after flash chromatography
(P–Et2O: 4 : 1 → 1 : 1) 8b (26.0 mg, 91.4 μmol, 37%) as a
colourless oil (d.r. syn–anti 71 : 29). Rf = 0.41 + 0.50 (P–Et2O
1 : 1) [UV, CAM]; IR: ν˜ = 3469 (br, OH), 3025 (w, CarH), 2948
(w, CalH), 2912 (w, CalH), 1733 (vs, CvO), 1557 (m), 1494
(s, CvCar), 1451 (s), 1438 (s, CH3), 1228 (vs, COC), 1122 (m),
1091 (vs), 802 (m, CarH), 699 cm−1 (vs).
Methyl
3-(2,4-dimethoxyphenyl)-2-hydroxy-3-(4–methoxy-
phenyl)propanoate (6a). Following general procedure I, reaction
of 2a (52.1 mg, 250 μmol, 1.00 equiv.) with 1,3–dimethoxyben-
zene (138 mg, 132 μL, 1.00 mmol, 4.00 equiv.) and Sc(OTf)3
(6.15 mg, 12.5 μmol, 0.05 equiv.) yielded after flash chromato-
graphy (P–Et2O: 4 : 1 → 2 : 1) 6a (66.0 mg, 191 μmol, 76%) as
a colourless solid (d.r. syn–anti 83 : 17). Rf = 0.21 (P–Et2O:
1 : 1) [UV, CAM]; m.p.: 130–132 °C; IR: ν˜ = 3556 (br, OH),
2954 (w, CalH), 2837 (w, OMe), 2353 (m), 1732 (vs, CvO),
1610 (s), 1584 (s), 1501 (vs), 1473 (m, CH3), 1246 (vs, COC),
1181 (m), 1112 (vs), 1087 (m), 1028 (s), 841 cm−1 (s, CarH).
syn-Diastereoisomer (syn-8b). 1H-NMR (500 MHz, CDCl3):
3
δ [ppm] = 2.20 (s, 3 H), 2.28 (s, 3 H), 2.74 (d, J = 5.1 Hz,
3
1 H), 3.58 (s, 3 H), 4.59 (d, J = 5.9 Hz, 1 H), 4.88–4.91 (m,
3
1 H), 6.96 (bs, 1 H), 7.02 (d, J = 7.8 Hz, 1 H), 7.18–7.27 (m,
5 H), 7.47 (d, 3J = 7.8 Hz, 1 H); 13C-NMR (90.6 MHz, CDCl3):
δ [ppm] = 19.7 (q), 20.9 (q), 50.1 (d), 52.2 (q), 74.0 (d), 126.6
(d), 126.7 (d), 128.0 (d), 128.4 (d), 128.6 (d), 131.6 (d), 134.5
(s), 136.4 (s), 136.5 (s), 140.5 (s), 174.2 (s); MS (ESI): m/z (%)
= 307 [(M + Na)+], 285 [(M + H)+]; HRMS (ESI): C18H21O3
[(M + H)+]: calcd: 285.1485, found: 285.1485.
syn-Diastereoisomer (syn-6a). 1H-NMR (500 MHz, CDCl3):
δ [ppm] = 2.76 (bs, 1 H), 3.67 (s, 3 H), 3.76 (s, 3 H), 3.77
(s, 3 H), 3.78 (s, 3 H), 4.82–4.85 (m, 2 H), 6.40–6.44 (m, 2 H),
General procedure II for the Friedel–Crafts reactions with
3-arylglycidate 5. A flame-dried Schlenk flask was purged with
argon and charged with glycidate 5 (37.5 mg, 150 μmol, 1.00
equiv.) and the aryl nucleophile (600 μmol, 4.00 equiv.) in dry
nitromethane (2 mL). The solution was cooled to −25 °C and
Sc(OTf)3 (3.69 mg, 7.50 μmol, 0.05 equiv.) was added. The
resulting mixture was stirred at −25 °C for 4 h. The reaction was
quenched with sat. aqueous NaHCO3 (5 mL) and diluted with
CH2Cl2 (5 mL). The layers were separated and the aqueous layer
was extracted with CH2Cl2 (2 × 7 mL). The combined organic
layers were dried over Na2SO4, filtered and concentrated
in vacuo. The crude product was purified by flash chromato-
graphy to give the respective product.
3
6.83 (virt. d, J ≅ 8.4 Hz, 2 H), 7.11 (d, J = 8.4 Hz, 1 H), 7.30
(virt. d, J ≅ 8.4 Hz, 2 H); 13C-NMR (90.6 MHz, CDCl3):
δ [ppm] = 45.7 (d), 52.1 (q), 55.2 (q), 55.2 (q), 55.5 (q), 73.2
(d), 98.5 (d), 104.2 (d), 113.6 (d), 119.8 (s), 129.5 (d), 131.2 (d),
134.0 (s), 157.9 (s), 158.0 (s), 159.7 (s), 174.4 (s); MS (EI,
70 eV): m/z (%) = 346 (1) [M+], 328 (3) [(M − H2O)+], 257 (75)
[(M − C3H5O3)+], 196 (94), 165 (84), 135 (100); HRMS (EI)
m/z calcd for C19H20O5 [(M − H2O)+]: calcd: 328.1305, found:
328.1306; CH: calcd for C19H22O6: C: 65.88, H: 6.40, found: C:
65.89, H: 6.61.
Methyl 2-hydroxy-3-(4-methoxyphenyl)-3-(5-methyl-thiophen-
2-yl)propanoate (7a). Following general procedure I, reaction of
2a (52.1 mg, 250 μmol, 1.00 equiv.) with 2–methylthiophene
(98.2 mg, 96.8 μL, 1.00 mmol, 4.00 equiv.) and Sc(OTf)3
(6.15 mg, 12.5 μmol, 0.05 equiv.) yielded after flash chromato-
graphy (P–Et2O: 4 : 1 → 1 : 1) 7a (64.0 mg, 209 μmol, 84%) as
a yellow oil (d.r. syn–anti 75 : 25). Rf = 0.18 (P–Et2O: 2 : 1) [UV,
CAM]; IR: ν˜ = 3484 (br, OH), 2928 (w, CalH), 2837 (w, OMe),
1735 (vs, CvO), 1610 (m), 1511 (vs), 1439 (m, CH3), 1246 (vs,
COC), 1179 (s), 1113 (m), 1031 (s), 834 (m, CarH), 802 (m),
731 cm−1 (m).
tert-Butyl 3-(2,4-dimethoxyphenyl)-2-hydroxy-3-(4–methoxy-
phenyl)propanoate (11a). Following general procedure II, reac-
tion of 5 (37.5 mg, 150 μmol, 1.00 equiv.) with 1,3–
dimethoxybenzene (82.9 mg, 79.0 μL, 600 μmol, 4.00 equiv.)
and Sc(OTf)3 (3.69 mg, 7.50 μmol, 0.05 equiv.) yielded after
flash chromatography (P–Et2O: 4 : 1 → 1 : 1) 11a (45.0 mg,
116 μmol, 77%) as a colourless solid (d.r. syn–anti 93 : 7). Rf =
0.21 (P–Et2O: 2 : 1) [UV, CAM]; IR: ν˜ = 3490 (br, OH), 2984
(w, CalH), 2939 (w), 2911 (w), 2837 (m, OMe), 1717
(vs, CvO), 1608 (s), 1507 (vs), 1469 (m, CH3), 1260
(s, COC), 1207 (s), 1157 (vs), 1124 (s), 1034 (s), 834 (m, CarH),
737 cm−1 (m).
syn-Diastereoisomer (syn-7a). 1H-NMR (360 MHz, CDCl3):
δ [ppm] = 2.41 (d, 4J = 1.1 Hz, 3 H), 3.03 (d, 3J = 5.8 Hz, 1 H),
3.73 (s, 3 H), 3.79 (s, 3 H), 4.63 (d, 3J = 3.6 Hz, 1 H), 4.72 (dd,
3J = 3.6 Hz, 3J = 5.8 Hz, 1 H), 6.56–6.58 (m, 1 H), 6.69 (d, 3J =
3.4 Hz, 1 H), 6.84–6.88 (m, 2 H), 7.36–7.40 (m, 2 H);
13C-NMR (90.6 MHz, CDCl3): δ [ppm] = 15.2 (q), 49.5 (d),
52.6 (q), 55.2 (q), 74.2 (d), 113.8 (d), 124.5 (d), 126.1 (d), 129.3
(d), 133.0 (s), 139.0 (s), 139.4 (s), 158.5 (s), 173.7 (s); MS (EI,
70 eV): m/z (%) = 306 (1) [M+], 217 (100) [(M − C3H5O3)+],
135 (34), 121 (26); HRMS (EI) m/z calcd for C16H18O4S [M+]:
calcd: 306.0920, found: 306.0917.
syn-Diastereoisomer (syn-11a). 1H-NMR (500 MHz, CDCl3):
δ [ppm] = 1.25 (s, 9 H), 3.01 (bs, 1 H), 3.76 (s, 3 H), 3.76 (s, 3
3
3
H), 3.77 (s, 3 H), 4.70 (d, J = 5.8 Hz, 1 H), 4.77 (d, J = 5.8
Hz, 1 H), 6.43 (d, J = 2.5 Hz, 1 H), 6.46 (dd, 3J = 8.5 Hz, J =
2.5 Hz, 1 H), 6.80–6.82 (m, 2 H), 7.25–7.27 (m, 2 H), 7.42
(d, 3J = 8.5 Hz, 1 H); 13C-NMR (90.6 MHz, CDCl3): δ [ppm] =
27.7 (q), 45.4 (d), 55.2 (q), 55.3 (q), 55.4 (q), 74.0 (d), 82.0 (s),
98.6 (d), 104.1 (d), 113.6 (d), 121.2 (s), 129.7 (d), 130.2 (d),
133.6 (s), 158.0 (s), 158.0 (s), 159.5 (s), 173.2 (s); MS (ESI):
m/z (%) = 799 (100) [(2M + Na)+], 735 (38), 411 (34)
[(M + Na)+], 333 (20), 225 (9); HRMS (ESI): C22H28O6Na
[(M+Na)+]: calcd: 411.1778, found: 411.1776.
4
4
Methyl 3-(2,4-dimethylphenyl)-2-hydroxy-3-phenyl-propano-
ate (8b). Following general procedure I, reaction of 2b
(44.5 mg, 250 μmol, 1.00 equiv.) with m–xylene (106 mg,
6502 | Org. Biomol. Chem., 2012, 10, 6498–6503
This journal is © The Royal Society of Chemistry 2012