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H.-X. Wei et al. / Tetrahedron 60 (2004) 11829–11835
128.7!2, 128.5!2, 128.4!2, 127.8, 126.5, 75.3, 46.3,
15.4; MS: (EI, 70 eV) 248 (MKH2O, 52), 175 (9), 134 (87),
132 (28), 106 (11), 105 (100) 91 (18), 77 (71); HRMS: cald
for C18H18O2: 266.1307; found: 266.1311.
(m, 2H), 7.28–7.24 (m, 2H), 4.76 (dd, JZ8.5, 2.5 Hz, 1H),
3.98 (d, JZ3.0 Hz, OH), 2.60–2.52 (m, 1H), 2.51–2.45
(m, 1H), 2.40–2.31 (m, 1H), 2.13–2.02 (m, 1H), 1.82–1.77
(m, 1H), 1.72–1.62 (m, 1H), 1.61–1.51 (m, 2H), 1.33–1.22
(m, 1H); 13C NMR: (125 MHz, CDCl3) 215.3, 139.4, 133.5,
128.5!2, 128.3!2, 74.1, 57.3, 42.6, 30.74, 27.7, 24.7; MS:
(EI, 70 eV) 220 (MKH2O, 36), 140 (52), 132 (100), 104
(44), 89 (31); HRMS: cald for C13H15O2Cl: 238.0761;
found: 238.0766. Data for syn-isomer: 1H NMR: (500 MHz,
CDCl3) 7.32–7.29 (m, 2H), 7.27–7.22 (m, 2H), 5.35 (m,
1H), 3.04 (d, JZ3.0 Hz, OH), 2.60–2.52 (m, 1H), 2.49–2.41
(m, 1H), 2.41–2.32 (m, 1H), 2.13–2.06 (m, 1H), 1.89–1.82
(m, 1H), 1.73–1.64 (m, 3H), 1.57–1.47 (m, 1H); 13C NMR:
(125 MHz, CDCl3) 214.6, 139.9, 132.6, 128.3!2, 127.1!
2, 70.11, 57.0, 42.6, 27.9, 25.9, 24.8.
Data for syn-isomer: 1H NMR: (500 MHz, CDCl3) 7.98 (d,
JZ8.0 Hz, 2H), 7.61 (t, JZ8 Hz, 1H), 7.50 (t, JZ8.0 Hz,
2H), 7.39 (d, JZ7.5 Hz, 2H), 7.33 (t, JZ7.5 Hz, 2H), 7.24
(t, JZ7.5 Hz, 1H), 6.73 (d, JZ16.0 Hz, 1H), 6.26 (dd, JZ
16.0, 6.0 Hz, 1H), 4.83–4.79 (m, 1H), 3.65 (dq, JZ7.0,
3.5 Hz, 1H), 3.34 (d, JZ2.5 Hz, OH), 1.32 (d, JZ7.0 Hz,
3H); 13C NMR: (125 MHz, CDCl3) 205.3, 136.7, 135.7,
133.6, 131.2, 129.1!2, 128.7!2, 128.5!2, 127.7!2,
126.5!2, 72.0, 45.4, 11.7.
Compound 6. 183 mg, 90%, a colorless oil. Data for anti-
isomer: IR: (CHCl3) 3610 (w), 3604 (w), 1671 (s), 1446 (m),
Compound 10. 134 mg, 70%, a colorless oil, inseparable; 1H
NMR: (500 MHz, CDCl3) 7.40–7.20 (m, 5H), 5.03 (d, JZ
4.0 Hz, 0.24H, syn-isomer), 4.74 (d, JZ8.1 Hz, 0.76H, anti-
isomer), 2.83 (dq, JZ7.2, 4.0 Hz, 1H), 2.20–2.55 (m, 2H),
1.07 (d, JZ7.2 Hz, 3H), 0.99 (t, JZ7.0 Hz, 3H).
1
1211 (m), 970 (s); H NMR: (500 MHz, CDCl3) 7.96 (m,
2H), 7.60–7.56 (m, 1H), 7.50–7.46 (m, 2H), 5.77 (dq, JZ
15.1, 6.0 Hz, 1H), 5.54 (ddq, JZ15.1, 7.2, 1.1 Hz, 1H), 4.53
(m, 1H), 3.53 (q, JZ7.2 Hz, 1H), 2.74 (d, JZ6.0 Hz, OH),
1.71 (dd, JZ7.2, 1.1 Hz, 3H), 1.18 (d, JZ7.4 Hz, 3H); 13C
NMR: (125 MHz, CDCl3) 204.9, 136.7, 133.2, 131.5,
128.9!2, 128.7!2, 128.4, 75.3, 46,2, 17.7, 15.3; MS:
(EI, 70 eV) 186 (MKH2O, 78), 148 (8), 135 (15), 134 (100),
133 (61), 105 (91), 78 (5), 71 (26); HRMS: cald for
C13H16O2: 204.115; found: 204.110. Data for syn-isomer:
1H NMR: (500 MHz, CDCl3) 7.94 (d, JZ7.5 Hz, 2H), 7.61–
7.57 (m, 1H), 7.49 (t, JZ7.5 Hz, 2H), 5.78 (ddq, JZ15.0,
6.5, 1.5 Hz, 1H), 5.55 (ddq, JZ15.0, 6.5, 1.5 Hz, 1H), 4.52
(t, JZ5.0 Hz, 1H), 3.54 (dq, JZ7.3, 3.5 Hz, 1H), 2.98 (s,
1H, OH), 1.71 (d, JZ6.5 Hz, 3H), 1.27 (d, JZ7.3 Hz, 3H);
13C NMR: (125 MHz, CDCl3) 205.2, 136.1, 133.3, 130.8,
128.7!2, 128.4!2, 127.8, 72.5, 45.5, 17.7, 11.8.
2.1.2. General procedure B (Table 3). Regio selective
aldol addition with unmodified ketones using N,N-
diisopropylethylamine as base. Dichloromethane
(5.0 mL), aldehyde (1.0 mmol, 1.0 equiv), ketone
(1.2 mmol, 1.2 equiv), and magnesium iodide (1.2 mmol,
340.0 mg, 98% purity) were added to a dry 25 mL flask. The
resulting mixture was protected by nitrogen gas and at room
temperature N,N-diisopropylethylamine (1.3 mmol,
0.226 mL) was added dropwise via a syringe. The resulting
mixture was stirred for 30 min at room temperature and
quenched by addition of dilute 2 N HCl (4.0 mL).
Dichloromethane was completely evaporated and 8.0 mL
of ethyl acetate was added to the mixture. The ethyl acetate
layer was separated and the aqueous layer was extracted
with ethyl acetate two more times (2!8.0 mL). The
combined organic layers were dried over anhydrous
magnesium sulfate and concentrated. Purification was
carried out by column chromatography (hexane/ethyl
acetateZ10:1) to give the pure product.
Compound 7. 180 mg, 82%, a colorless oil. IR: (CHCl3)
3610 (w), 3500 (w), 1711 (s), 970 (s); 1H NMR: (500 MHz,
CDCl3) 7.96 (m, 2H), 7.59 (m, 1H), 7.50 (m, 2H), 4.73 (d,
JZ9.0 Hz, OH), 3.80 (dq, JZ7.5, 2 Hz, 1H), 3.43 (dd, JZ
9.0, 2.0 Hz, 1H), 1.45 (d, JZ7.0 Hz, 3H), 0.88 (s, 9H); 13C
NMR: (125 MHz, CDCl3) 208.2, 136.3, 133.6, 128.8!2,
128.1!2, 84.9, 37.5, 36.2, 26.80!3, 18.9; HRMS: cald for
C14H20O2: 220.1463; found: 220.1459.
Compound 11. 241 mg, 85%, a colorless oil. Major isomer:
mp: 80–82 8C. IR: (CHCl3) 3609 (s), 3514 (w), 3019 (m),
1678 (s), 1214 (s), 969 (s); H NMR: (500 MHz, CDCl3)
1
Compound 8. 139 mg, 68%, a white solid, mp: 40–42 8C.
Data for anti-isomer: H NMR: (500 MHz, CDCl3) 7.36–
1
7.45–7.40 (m, 2H), 7.40–7.35 (m, 2H), 7.34–7.30 (m, 1H),
7.29 (m, 2H), 6.97–6.92 (m, 2H), 5.13–5.08 (dt, JZ9.5,
3 Hz, 1H), 5.05 (s, 2H), 3.27 (d, JZ3.0 Hz, OH), 2.88–2.72
(m, 2H), 2.44 (q, JZ7.5 Hz, 2H), 1.06 (t, JZ7.5 Hz, 3H);
13C NMR: (125 MHz, CDCl3) 212.1, 158.5, 137.1, 135.5,
128.8!2, 128.2, 127.6!2, 127.1!2, 115.1!2, 70.2, 69.8,
50.8, 37.1, 7.7; MS: (EI, 70 eV) 266 (MKH2O, 16), 212 (8),
153 (0.6), 105 (0.3), 91 (100), 65 (13); HRMS: cald for
C18H20O3: 284.3550; found: 284.3556.
7.27 (m, 5H), 4.78 (dd, JZ9.2, 2.4 Hz, 1H), 3.98(d, JZ
2.4 Hz, OH), 2.64–2.58 (m, 1H), 2.50–2.45 (m, 1H), 2.40–
2.31 (m, 1H), 2.10–2.03 (m, 1H), 1.81–1.74 (m, 1H), 1.71–
1.46 (m, 3H), 1.34–1.22 (m, 1H); 13C NMR: (125 MHz,
CDCl3) 215.5, 140.8, 128.2!2, 127.8, 126.9!2, 74.6, 57.3,
42.6, 30.7, 27.7, 24.6; HRMS: cald for C13H16O2: 204.115;
found: 204.119. Data for syn-isomer: 1H NMR: (500 MHz,
CDCl3) 7.36–7.21 (m, 5H), 5.39 (m, 1H), 3.05 (d, JZ
2.1 Hz, 1H), 2.62–2.57 (m, 1H), 2.47–2.43 (m, 1H), 2.42–
2.32 (m, 1H), 2.11–2.06 (m, 1H), 1.87–1.82 (m, 1H), 1.75–
1.60 (m, 3H), 1.57–1.43 (m, 1H); 13C NMR: (125 MHz,
CDCl3) 214.9, 141.3, 128.1!2, 126.8, 125.5!2, 70.5, 57.1,
42.6, 27.9, 25.9, 24.8.
Compound 12. 196 mg, 86%, a colorless oil; Major isomer:
mp: 58–60 8C. IR: (CHCl3) 3607 (w), 3551 (w), 3001 (w),
1675 (s), 1521 (m), 969 (s); H NMR: (500 MHz, CDCl3)
1
7.85–7.80 (m, 4H), 7.49–7.44 (m, 3H), 5.33 (dt, JZ8.5,
2.5 Hz, 1H), 3.49 (d, JZ3.0 Hz, OH), 2.97–2.84 (m, 2H),
2.47 (q, JZ7.5 Hz, 2H), 1.07 (t, JZ7.5 Hz, 3H); 13C NMR:
(125 MHz, CDCl3) 211.8, 140.2, 133.2, 132.9, 128.3, 127.9,
127.6, 126.1, 125.8, 124.3, 123.7, 70.1, 50.6, 36.8, 7.4; MS:
Compound 9. 167 mg, 70%, a colorless oil. Data for anti-
isomer: IR: (CHCl3) 3591 (w), 3077 (w), 1771 (s), 1452 (s),
1209 (m), 902 (m); 1H NMR: (500 MHz, CDCl3) 7.34–7.30