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J. Nebot et al. / Tetrahedron 62 (2006) 11090–11099
4.3.7. (1R,2R,4S)-4-tert-Butyldimethylsilyloxy-1-
hydroxy-2-methyl-1-phenyl-3-pentanone (10e). Colorless
oil; Rf¼0.15 (hexanes/EtOAc 9:1); HPLC (hexanes/i-PrOH
99:1) tR¼5.2 min (minor diastereomer, tR¼5.6 min); [a]D
+4.2 (c 1.0, CHCl3); IR (film): n 3500 (br), 1713; 1H NMR
(CDCl3, 500 MHz) d 7.34–7.30 (4H, m, ArH), 7.26–7.21
(1H, m, ArH), 5.03 (1H, d, J¼3.7, CHOH), 4.14 (1H,
q, J¼6.9, CHOTBS), 3.37 (1H, qd, J¼7.2, J¼3.7,
COCHCH3CHOH), 1.27 (3H, d, J¼6.9, CH3CHOTBS), 1.05
(3H, d, J¼7.2, COCHCH3CHOH), 0.90 (9H, s, SiC(CH3)3),
0.08 (3H, s, SiCH3), 0.06 (3H, s, SiCH3); 13C NMR (CDCl3,
75.4 MHz) d 218.7, 141.7, 128.2, 127.2, 125.9, 74.6, 72.8,
46.9, 25.7, 21.0, 18.0, 10.4, ꢀ4.7, ꢀ5.0; HRMS (+FAB):
m/z calcd for [M+H]+ C18H31O3Si: 323.2042; found:
323.2045.
4.3.11. (2S,4R,5S,6E)-2-tert-Butyldimethylsilyloxy-5-
hydroxy-4-methyl-6-octen-3-one (10i). Yellowish oil;
Rf¼0.2 (hexanes/EtOAc 9:1); [a]D ꢀ6.3 (c 1.3, CHCl3);
IR (film): n 3475 (br), 1709, 1640; 1H NMR (CDCl3,
500 MHz) d 5.72 (1H, dqd, J¼15.7, J¼6.5, J¼1.2, HC]
CHCH3), 5.44 (1H, ddq, J¼15.7, J¼6.5, J¼1.7, HC]
CHCH3), 4.36–4.32 (1H, m, CHOH), 4.21 (1H, q, J¼6.9,
CHOTBS), 3.19 (1H, qd, J¼7.2, J¼3.8, COCHCH3CHOH),
1.70 (3H, ddd, J¼6.5, J¼1.7, J¼0.9, HC]CHCH3), 1.30
(3H, d, J¼6.9, CH3CHOTBS), 1.11 (3H, d, J¼7.2,
COCHCH3CHOH), 0.90 (9H, s, SiC(CH3)3), 0.07 (6H, s,
Si(CH3)2); 13C NMR (CDCl3, 75.4 MHz) d 217.7, 130.7,
127.7, 74.6, 72.2, 45.2, 25.7, 21.0, 18.0, 17.7, 11.1, ꢀ4.6,
ꢀ5.0; HRMS (+FAB): m/z calcd for [M+H]+ C15H31O3Si:
287.2042; found: 287.2050.
4.3.8. (1R,2R,4S)-4-tert-Butyldimethylsilyloxy-1-
hydroxy-2-methyl-1-(4-nitrophenyl)-3-pentanone (10f).
Colorless oil; Rf¼0.30 (CH2Cl2); HPLC (hexanes/EtOAc
97.5:2.5) tR¼35.3 min (minor diastereomer, tR¼50.1 min);
[a]D ꢀ0.6 (c 1.1, CHCl3); IR (film): n 3512 (br), 1710,
4.3.12. Hemiacetal from i-PrCHO (11a). Colorless oil;
Rf¼0.6 (hexanes/EtOAc 9:1); [a]D ꢀ22.7 (c 0.6, CHCl3);
IR (film): n 3525, 2957, 2929; 1H NMR (CDCl3,
300 MHz) d 4.84 (1H, d, J¼4.5, OCHO), 3.83 (1H, q,
J¼6.3, CHOTBS), 3.64 (1H, s, OH), 3.59 (1H, dd, J¼9.7,
J¼2.0, OCHCH(CH3)2), 1.85–1.60 (3H, m, CHCH3 and
2ꢃCH(CH3)2), 1.13 (3H, d, J¼6.0, CH3), 1.03 (3H, d,
J¼6.3, CH3), 0.98 (3H, d, J¼6.9, CH3), 0.96 (3H, d,
J¼6.9, CH3), 0.93 (9H, s, SiC(CH3)3), 0.89 (3H, d, J¼6.6,
CH3), 0.83 (3H, d, J¼6.9, CH3), 0.14 (3H, s, SiCH3), 0.12
(3H, s, SiCH3); 13C NMR (CDCl3, 75.4 MHz) d 98.5,
98.3, 80.1, 71.2, 33.7, 32.4, 28.7, 25.8, 19.8, 18.1, 17.3,
17.2, 16.9, 16.4, 6.9, ꢀ4.6, ꢀ4.9.
1
1524, 1349; H NMR (CDCl3, 300 MHz) d 8.25–8.15 (2H,
m, ArH), 7.55–7.45 (2H, m, ArH), 5.17 (1H, br s, CHOH),
4.23 (1H, q, J¼6.9, CHOTBS), 3.41 (1H, qd, J¼7.2, J¼
2.9, COCHCH3CHOH), 1.35 (3H, d, J¼6.9, CH3CHOTBS),
1.03 (3H, d, J¼7.2, COCHCH3CHOH), 0.92 (9H, s,
SiC(CH3)3), 0.11 (6H, s, Si(CH3)2); 13C NMR (CDCl3,
75.4 MHz) d 218.8, 149.1, 147.2, 126.7, 123.5, 74.7, 71.9,
46.3, 25.7, 21.4, 18.0, 9.8, ꢀ4.6, ꢀ5.0; HRMS (+FAB):
m/z calcd for [M+H]+ C18H30NO5Si: 368.1893; found:
368.1882.
4.3.13. Hemiacetal from CH3CHO (11d). Colorless oil;
Rf¼0.5 (hexanes/EtOAc 9:1); [a]D ꢀ22.9 (c 1.3, CHCl3);
IR (film): n 3527, 2933; 1H NMR (CDCl3, 300 MHz)
d 5.27 (1H, q, J¼5.2, OCHO), 4.34 (1H, qd, J¼6.6,
J¼2.1, C(OH)–CHCHCH3), 3.78 (1H, q, J¼6.3, CHOTBS),
3.63 (1H, s, OH), 1.40 (1H, qd, J¼6.8, J¼2.1,
C(OH)CH(CH3)CH), 1.26 (3H, d, J¼5.2, OCH(CH3)O),
1.13 (3H, d, J¼6.6, C(OH)CHCHCH3), 1.07 (3H, d, J¼6.3,
CH3CHOTBS), 0.90 (3H, d, J¼6.8, C(OH)CH(CH3)CH),
0.89 (9H, s, SiC(CH3)3), 0.08 (3H, s, SiCH3), 0.07 (3H, s,
4.3.9. (1R,2R,4S)-4-tert-Butyldimethylsilyloxy-
1-hydroxy-1-(4-methoxyphenyl)-2-methyl-3-pentanone
(10g). Colorless oil; Rf ¼0.25 (CH2Cl2); [a]D +1.7 (c 1.0,
CHCl3); HPLC (hexanes/i-PrOH 99:1) tR¼6.5 min (minor
diastereomer, tR¼8.0 min); IR (film): n 3504 (br), 1713;
1H NMR (CDCl3, 300 MHz) d 7.28–7.20 (2H, m, ArH),
6.92–6.84 (2H, m, ArH), 4.99 (1H, dd, J¼4.0, J¼1.8,
CHOH), 4.13 (1H, q, J¼6.8, CHOTBS), 3.80 (3H, s,
OCH3), 3.35 (1H, qd, J¼7.1, J¼4.0, COCHCH3CHOH),
1.27 (3H, d, J¼6.8, CH3CHOTBS), 1.08 (3H, d, J¼7.1,
COCHCH3CHOH), 0.92 (9H, s, SiC(CH3)3), 0.09 (3H, s,
SiCH3), 0.08 (3H, s, SiCH3); 13C NMR (CDCl3, 75.4 MHz)
d 218.5, 158.8, 134.0, 127.1, 113.6, 74.6, 72.6, 55.2,
47.1, 25.7, 20.9, 18.0, 10.8, ꢀ4.7, ꢀ5.0; HRMS (+FAB):
m/z calcd for [M+H]+ C19H33O4Si: 353.2148; found:
353.2141.
1
SiCH3); H NMR (C6D6, 400 MHz) d 5.41 (1H, q, J¼5.2,
OCHO), 4.50 (1H, qd, J¼6.5, J¼2.2, C(OH)CHCHCH3),
3.79 (1H, q, J¼6.2, CHOTBS), 3.64 (1H, s, OH), 1.34 (3H,
d, J¼5.2, OCH(CH3)O), 1.31(1H, qd, J¼6.8, J¼2.2, C(OH)–
CH(CH3)CH), 1.04 (3H, d, J¼6.5, C(OH)CHCHCH3), 1.01
(3H, d, J¼6.2, CH3CHOTBS), 0.94 (9H, s, SiC(CH3)3),
0.83 (3H, d, J¼6.8, C(OH)CH(CH3)CH), 0.09 (3H, s,
SiCH3), 0.07 (3H, s, SiCH3); 13C NMR (CDCl3, 75.4 MHz)
d 98.4, 91.9, 71.2, 70.1, 36.7, 25.8, 20.7, 18.2, 18.0, 16.7,
6.7, ꢀ4.6, ꢀ5.1.
4.3.10. (2S,4R,5R)-2-tert-Butyldimethylsilyloxy-5-hy-
droxy-4,6-dimethyl-6-hepten-3-one (10h). Colorless oil;
Rf¼0.1 (hexanes/EtOAc 94:6); [a]D +12.4 (c 1.0, CHCl3);
IR (film): n 3500 (br), 1702, 1653; 1H NMR (CDCl3,
4.4. General procedure for TBS removal
500 MHz)
d
5.12–5.09 (1H, m, C]CHxHy), 4.95–
A 48% aq solution of HF (3 equiv) is added dropwise to
a 0.2 M solution of aldol 10 in CH3CN at rt. The reaction
mixture is stirred for 1 h and diluted with CH2Cl2. The or-
ganic layer is washed with satd NaHCO3, dried (MgSO4)
and concentrated. The resulting oil is purified by flash chro-
matography (hexanes/EtOAc), which affords dihydroxy
ketones 12 in 74–87% yield.
4.93 (1H, m, C]CHxHy), 4.32 (1H, br s, CHOH), 4.21
(1H, q, J¼6.9, CHOTBS), 3.30 (1H, qd, J¼7.2, J¼2.8,
COCHCH3CHOH), 1.67–1.65 (3H, m, CH3C]CH2), 1.28
(3H, d, J¼6.9, CH3CHOTBS), 1.06 (3H, d, J¼7.2,
CH3CHOTBS), 0.91 (9H, s, SiC(CH3)3), 0.08 (6H, s,
Si(CH3)2); 13C NMR (CDCl3, 75.4 MHz) d 219.2, 143.2,
111.8, 74.6, 73.2, 41.8, 25.7, 21.3, 19.6, 18.0, 9.6, ꢀ4.6,
ꢀ5.0; HRMS (+FAB): m/z calcd for [M+H]+ C15H31O3Si:
287.2042; found: 287.2035.
4.4.1. (2S,4R,5S)-2,5-Dihydroxy-4,6-dimethyl-3-hepta-
none (12a). Yield: 74%. Colorless oil; Rf¼0.25 (hexanes/