T. Washio et al. / Tetrahedron: Asymmetry 18 (2007) 2606–2612
2611
column chromatography (silica gel, 19:1 hexane/EtOAc)
H), 6.39 (s, 2H, Ar), 6.85–6.88 (m, 2H, Ar), 6.93–6.97 (m,
2H, Ar), 7.08–7.13 (m, 2H, Ar), 7.28–7.39 (m, 2H, Ar),
7.50–7.55 (m, 4H, Ar), 7.64–7.68 (m, 2H, Ar), 7.81–7.86
provided 13 (408 mg, 85%) as a colorless oil; TLC
Rf = 0.31 (9:1 hexane/EtOAc);IR (film) 1249, 1043 cmꢀ1
;
1H NMR (270 MHz, CDCl3) d ꢀ0.01 (s, 18H, Si(CH3)3),
0.91–0.98 (m, 4H, CH2CH2Si(CH3)3), 3.76 (s, 3H,
OCH3), 3.79 (m, 4H, CH2CH2Si(CH3)3), 5.25 (s, 4H, OC
H2O), 6.47 (s, 2H, Ar); 13C NMR (100 MHz, CDCl3) d
ꢀ1.4 (CH3), 18.0 (CH2), 55.5 (CH3), 66.6 (CH2), 93.5
(CH2), 94.7 (C), 96.2 (CH), 155.3 (C), 159.9 (C); HRMS
(EI): (M)+ calcd for C19H35BrO5Si2, 478.1206; found,
478.1208; Anal. Calcd for C19H35BrO5Si2: C, 47.59; H,
7.36; Br; 16.66. Found: C, 47.52; H, 7.17; Br, 16.64.
(m, 4H, Ar); H NMR (400 MHz, CDCl3 for 15) d ꢀ0.03
1
(s, 18H, Si(CH3)3), 0.89–0.94 (m, 4H, CH2CH2Si(CH3)3),
1.73–2.01 (m, 2H, CH2CH2CH), 2.15–2.45 (m, 2H, C3-
H), 2.65–2.89 (m, 2H, CH2CH2CH), 3.65–3.71 (m, 5H,
CH2CH2Si(CH3)3 and C2–H), 3.77 (s, 3H, OCH3), 5.12
(s, 4H, OCH2O), 5.20 (br, 1H, C6–H), 5.52 (s, 1H, C5–
H), 6.39 (s, 2H, Ar), 6.85–6.88 (m, 2H, Ar), 6.93–6.97 (m,
2H, Ar), 7.08–7.13 (m, 2H, Ar), 7.28–7.39 (m, 2H, Ar),
7.50–7.55 (m, 4H, Ar), 7.64–7.68 (m, 2H, Ar), 7.81–7.86
(m, 4H, Ar); 13C NMR (100 MHz, CDCl3) d ꢀ1.44
*
4.3.2. 4-Methoxy-2,6-bis-[2-(trimethylsilyl)ethoxymethoxy]-
phenylboronic acid 8. To a solution of 13 (390 mg,
0.82 mmol) in THF (5 mL) was added 1.59 M solution of
n-BuLi in hexane (0.57 mL, 0.90 mmol) at ꢀ78 ꢁC. The
mixture was stirred at ꢀ78 ꢁC for 0.5 h, and trimethyl bo-
rate (0.18 mL, 1.6 mmol) was added. The mixture was al-
lowed to warm to 23 ꢁC and stirring was continued for
an additional 12 h. The mixture was acidified with 10%
HCl and stirred for 5 min. The whole was extracted with
EtOAc (2 · 15 mL), and the combined organic layers were
washed with water (5 mL) and brine (2 · 5 mL), and dried
over anhydrous Na2SO4. Filtration and evaporation in
vacuo followed by column chromatography (silica gel, 9:1
hexane/EtOAc) provided 8 (256 mg, 70%) as a colorless
oil; TLC Rf = 0.22 (4:1 hexane/EtOAc); 1H NMR
(270 MHz, C6D6) d ꢀ0.06 (s, 18H, Si(CH3)3), 0.81 (t,
J = 8.2 Hz, 4H, CH2CH2Si(CH3)3), 3.38 (s, 3H, OCH3),
3.54 (t, J = 8.2 Hz, 4H, CH2CH2Si(CH3)3), 4.78 (s, 2H,
OCH2O), 6.60 (s, 2H, Ar), 7.50 (s, 2H, B(OH)2); 13C
NMR (100 MHz, C6D6) d ꢀ1.3 (CH3), 18.1 (CH2), 55.0
(CH), 67.0 (CH2), 93.4 (CH2), 95.4 (CH), 163.8 (C),
165.1 (C).
(CH3), ꢀ1.40 (CH3), 17.88 (CH2), 17.91 (CH2), 30.3
(CH2), 31.0 (CH2), 34.8 (CH2), 36.9 (CH2), 37.0 (CH2),
37.1 (CH2), 55.3 (CH3), 66.10 (CH2), 66.14 (CH2), 73.6
(CH), 74.5 (CH), 74.8 (CH), 77.0 (CH), 92.9 (CH2), 94.8
(CH), 113.8 (C), 113.9 (C), 121.9 (CH), 122.0 (CH), 126.7
(CH), 128.0 (CH), 128.23 (CH), 128.25 (CH), 128.6 (CH),
128.89 (CH), 128.93 (CH), 128.95 (CH), 129.3 (CH),
129.4 (CH), 129.7 (C), 130.0 (C), 133.9 (CH), 134.0 (CH),
135.1 (C), 135.18 (C), 135.24 (C), 135.3 (C), 140.8 (C),
141.1 (C), 141.5 (C), 141.8 (C), 147.32 (C), 147.34 (C),
148.3 (C), 148.7 (C), 155.6 (C), 159.69 (C), 159.72 (C);
*HRMS (FAB): (M+Na)+ calcd for C50H62O12S2Si2Na,
*
997.3119; found, 997.3124; Anal. Calcd for C50H62O12S2-
Si2: C, 61.57; H, 6.41; S, 6.58. Found: C, 61.29; H, 6.28;
S, 6.55 (* data for mixed dihydropyrans 14 and 15).
4.4.2. (2S,4R,6S)-2-(4-Benzenesulfonyloxyphenyl)-6-[2-(4-
benzenesulfonyloxyphenyl)ethyl]-4-{4-methoxy-2,6-bis-[2-
(trimethylsilyl)ethoxymethoxy]phenyl}tetrahydropyran 6.4
To a mixture of 14 and 15 (50 mg, 0.05 mmol) in EtOAc
(2 mL)–EtOH (2 mL) was added 10% Pd/C (10 mg), and
the resulting mixture was stirred under hydrogen at an
atmospheric pressure at 23 ꢁC for 2 h. The reaction mixture
was then filtered through a plug of Celite, and the Celite fil-
ter cake was washed with EtOAc (5 mL). The filtrate was
concentrated in vacuo, and the residue was purified by col-
umn chromatography (silica gel, 4:1 hexane/EtOAc) to af-
4.4. Synthesis of Rychnovsky’s intermediate 6
4.4.1. (2S,6S)-2-(4-Benzenesulfonyloxyphenyl)-6-[2-(4-benz-
enesulfonyloxyphenyl)ethyl]-4-{4-methoxy-2,6-bis-[2-(trimeth-
ylsilyl)ethoxymethoxy]phenyl}-3,6-dihydro-2H-pyran 14 and
(2S,6S)-6-(4-benzenesulfonyloxyphenyl)-2-[2-(4-benzenesulfo-
nyloxyphenyl)ethyl]-4-{4-methoxy-2,6-bis-[2-(trimethylsilyl)-
ford 6 (44.6 mg, 89%) as a white amorphous solid; TLC
24
Rf = 0.39 (2:1 hexane/EtOAc); ½aꢁD ¼ ꢀ6:7 (c 1.05, CHCl3)
24
{lit.,4 ½aꢁD ¼ ꢀ4:9 (c 0.45, CHCl3)}; IR (film) 2952, 2923,
ethoxymethoxy]phenyl}-3,6-dihydro-2H-pyran 15. To
a
1607, 1589, 1376, 1152 cmꢀ1; 1H NMR (500 MHz, CDCl3)
mixture of 7 and 11 (190 mg, 0.27 mmol) in THF (6 mL)
was added 8 (140 mg, 0.32 mmol), PdCl2(PPh3)2 (9.3 mg,
0.013 mmol, 5 mol %) and 2 M K2CO3 (2.1 mL, 4.2 mmol),
and the mixture was refluxed for 0.5 h. After cooling, the
reaction mixture was extracted with EtOAc (30 mL), and
the organic layer was washed with water (5 mL) and brine
(2 · 5 mL), and dried over anhydrous Na2SO4. Filtration
and evaporation in vacuo followed by column chromatog-
raphy (silica gel, 3:1 hexane/EtOAc) provided an insepara-
ble mixture of 14 and 15 (182 mg, 86%) as a white
amorphous solid; *TLC Rf = 0.20 (3:1 hexane/EtOAc);
d
ꢀ0.03 (s, 18H, Si(CH3)3), 0.92–0.96 (m, 4H,
CH2CH2Si(CH3)3), 1.51 (d, J = 12.6 Hz, 1H, C5–H),
1.73–1.77 (m, 1H, C3–H), 1.88–1.95 (m, 1H,
CH2CHHCH), 1.88–1.95 (m, 1H, CH2CHHCH), 2.06–
2.15 (m, 1H, C5–H), 2.18–2.27 (m, 1H, C3–H), 2.65–2.73
(m, 1H, CHHCH2CH), 2.75–2.83 (m, 1H, CHHCH2CH),
3.50–3.61 (m, 2H, C4–H and C6–H), 3.69–3.73 (m, 4H,
CH2CH2Si(CH3)3), 3.75 (s, 3H, CH3), 4.41 (d,
J = 9.8 Hz, 1H, C2-H), 5.19 (s, 4H, OCH2O), 6.40 (s,
2H, Ar), 6.85–6.88 (m, 2H, Ar), 6.91–6.94 (m, 2H, Ar),
7.06–7.09 (m, 2H, Ar), 7.29–7.32 (m, 2H, Ar), 7.50–7.54
(m, 4H, Ar), 7.64–7.68 (m, 2H, Ar), 7.82–7.85 (m, 4H,
Ar); 13C NMR (125 MHz, CDCl3) d ꢀ1.34 (CH3), 18.1
(CH2), 31.2 (CH2), 32.4 (CH), 35.1 (CH2), 36.8 (CH2),
37.8 (CH2), 55.3 (CH3), 66.3 (CH2), 77.5 (CH), 78.8
(CH), 93.0 (CH2), 94.9 (CH), 114.2 (CH), 121.9 (CH),
122.0 (CH), 126.9 (CH), 128.4 (CH), 128.97 (CH), 129.00
(CH), 129.5 (CH), 134.0 (C), 135.36 (C), 135.40 (C),
23
ꢂ
½aꢁD ¼ ꢀ11:8 (c 1.01, CHCl3); *IR (KBr) 1902, 1606,
1
1376, 1200, 1178, 1153 cmꢀ1; H NMR (400 MHz, CDCl3
for 14) d ꢀ0.05 (s, 18H, Si(CH3)3), 0.89–0.94 (m, 4H,
CH2CH2Si(CH3)3), 1.73–2.01 (m, 2H, CH2CH2CH),
2.15–2.45 (m, 2H, C3-H), 2.65–2.89 (m, 2H, CH2CH2CH),
3.65–3.71 (m, 4H, CH2CH2Si(CH3)3), 3.78 (s, 3H, OCH3),
4.48 (br, 1H, C6–H), 5.15 (s, 4H, OCH2O), 5.53 (s, 1H, C5–