Methyl 3,5-Di(3,5-di-tert-butyl-4-methoxybenzyloxy)-
benzoate ([G-1]-CO2CH3, 5). To a cold (0 °C), stirred solution
of 3 (3.35 g, 13.4 mmol), 4 (1.07 g, 6.4 mmol), PPh3 (3.51 g, 13.4
mmol) and dry THF (75 mL) was added DIAD (2.71 g, 13.4 mmol,
2.6 mL) dropwise via syringe. After complete addition, the
resulting mixture was stirred for 10 min at 0 °C and was then
sonicated12 for approximately 2 h until the disappearance of 3
was observed by TLC (SiO2, 4:1 hexanes-EtOAc). The reaction
mixture was then concentrated in vacuo, and the resulting solid
was recrystallized from MeOH/H2O (10:1) to yield 5 as a white
powder (3.92 g, 97%; purity >95% by NMR): mp 62-64 °C; 1H
NMR (300 MHz, CDCl3) δ 7.32 (t, J ) 1.8 Hz, 2H), 7.31 (s, 4H),
6.85 (t, J ) 1.8 Hz, 1H), 4.97 (s, 4H), 3.92 (s, 3H), 3.71 (s, 6H),
1.42 (s, 36H); 13C NMR (75.4 MHz, CDCl3) δ 166.8, 160.0, 159.5,
143.9, 131.9, 130.2, 126.5, 108.3, 107.3, 70.9, 64.2, 52.2, 35.8,
32.0; MS (FAB+) m/z 631.67 (M - H+, C40H56O6 requires 631.40).
3,5-Di(3,5-di-tert-butyl-4-methoxybenzyloxy)benzyl Al-
cohol ([G-1]-CH2OH, 6). To a stirred slurry of LAH (0.10 g,
2.6 mmol) and dry THF (10 mL) was slowly added 5 (2.5 g, 4.0
mmol). The resulting mixture was allowed to react at rt for
approximately 4 h until disappearance of starting material was
observed by TLC (SiO2, 4:1 hexanes-EtOAc). The reaction was
quenched sequentially with water (0.1 mL), 4 N NaOH (0.1 mL),
and water (0.3 mL) and dried (MgSO4). The resulting mixture
was filtered through SiO2 (about 1.5 in. and washed with Et2O).
The resulting clear filtrate was concentrated in vacuo and the
solid recrystallized from MeOH/H2O (40:1) to yield 6 as a white
powder (2.08 g, 87%): mp 148-150 °C; 1H NMR (300 MHz,
CDCl3) δ 7.31 (s, 3H), 6.67 (d, J ) 2.9 Hz, 2H), 6.61 (t, J ) 2.7
Hz, 1H), 4.94 (s, 4H), 4.65 (d, J ) 3.6 Hz, 2H), 3.70 (s, 6H), 1.76
(t, J ) 5.4 Hz, 1H), 1.41 (s, 36H); 13C NMR (75.4 MHz, CDCl3)
δ 160.4, 159.4, 143.8, 143.3, 130.4, 126.5, 105.7, 101.2, 70.7, 65.4,
64.2, 35.8, 32.0; MS (FAB+) m/z 605.85 (M + H+, C39H57O5
requires 605.42). Anal. Calcd for C39H57O5: C, 77.44; H, 9.33.
Found: C, 77.27; H, 8.93.
dry THF (10 mL) yielded 8 as a colorless glass (0.39 g, 80%;
purity >95% by NMR) after flash chromatography (SiO2, CH2-
1
Cl2): mp 82-84 °C; H NMR (300 MHz, CDCl3) δ 7.31 (s, 8H),
6.73 (d, J ) 1.8 Hz, 4H), 6.64 (m, 4H), 6.57 (t, J ) 1.8 Hz, 1H),
5.00 (s, 4H), 4.94 (s, 8H), 4.64 (d, J ) 3.9 Hz, 2H), 3.70 (s, 12H),
1.61 (t, J ) 6.3 Hz, 1H), 1.43 (s, 72H); 13C NMR (75.4 MHz,
CDCl3) δ 160.4, 160.2, 159.5, 143.8, 143.4, 139.1, 130.4, 126.6,
106.4, 105.7, 101.5, 101.3, 70.8, 70.1, 65.3, 64.2, 35.8, 32.0; MS
(MALDI) m/z 1335.77 (M + Na+, C85H116NaO11 requires 1335.84),
1351.74 (M + K+, C85H116KO11 requires 1351.82).
Methyl 3,5-Bis(3,5-bis(3,5-Di(3,5-di-tert-butyl-4-methoxy-
benzyloxy)benzyloxy)benzyloxybenzoate ([G-3]-CO2CH3,
9). Following the procedure for 5, 8 (0.1 g, 0.086 mmol), 4 (0.0072
g, 0.043 mmol), PPh3 (0.025 g, 0.095 mmol), DEAD (0.0165 g,
0.095 mmol, 0.015 mL), and dry THF (3 mL) yielded 9 as a
colorless glass (0.075 g, 63%) after flash chromatography (SiO2,
6:1 hexanes-EtOAc): 1H NMR (600 MHz, CDCl3) δ 7.31 (s,
16H), 6.83 (t, J ) 2.4 Hz, 1H), 6.73 (s, 2H), 6.73 (s, 8H), 6.71 (d,
J ) 1.8 Hz, 4H), 6.64-6.63 (m, 4H), 6.60 (t, J ) 2.4 Hz, 2H),
5.01 (s, 4H), 5.00 (s, 8H), 4.938 (s, 16H), 3.89 (s, 3H), 3.69 (s,
24H), 1.43 (s, 144H); 13C NMR (150.8 MHz, CDCl3) δ 166.7,
160.4, 160.2, 159.8, 159.5, 143.8, 139.0, 138.8, 132.1, 130.4, 126.6,
108.4, 107.1, 106.5, 101.7, 101.6, 70.8, 70.23, 70.17, 64.2, 52.2,
35.8, 32.0; MS (MALDI) m/z 2782.80 (M + Na+, C178H236O24Na
requires 2780.71), 2798.74 (M + K+, C178H236O24K requires
2796.69). Anal. Calcd for C178H236O24: C, 77.47; H, 8.62. Found:
C, 77.08; H, 8.34.
3,5-Bis(3,5-bis(3,5-di(3,5-di-tert-butyl-4-methoxybenzyl-
oxy)benzyloxy)benzyloxybenzyl Alcohol ([G-3]-CH2OH,
10). Following the procedure for 6, 9 (0.075 g, 0.027 mmol), LAH
(0.0022 g, 0.054 mmol)), and dry THF (5 mL) yielded 10 as a
colorless glass (0.059 g, 79% yield) after flash chromatography
(SiO2, CH2Cl2): 1H NMR (600 MHz, CDCl3) δ 7.31 (s, 16H), 6.72
(d, J ) 2.4 Hz, 8H), 6.70 (d, J ) 2.4 Hz, 4H), 6.64 (t, J ) 2.4 Hz,
4H), 6.61 (d, J ) 1.8 Hz, 2H), 6.60 (t, J ) 2.4 Hz, 2H), 6.56 (t, J
) 3.0 Hz, 1H), 5.00 (s, 8H), 4.98 (s, 4H), 4.94 (s, 16H), 4.59 (d,
J ) 6.0 Hz, 2H), 3.69 (s, 24H), 1.67 (t, J ) 5.4 Hz, 1H), 1.43 (s,
144H); 13C NMR (150.8 MHz, CDCl3) δ 160.4, 160.2, 160.1, 159.5,
143.8, 143.5, 139.3, 139.0, 130.4, 126.6, 106.44, 106.39, 105.8,
101.6, 101.2, 70.8, 70.1, 70.0, 65.2, 64.2, 35.8, 32.2, 32.0; MS
(MALDI) m/z 2754.85 (M + Na+, C177H236O23Na requires 2754.73),
2770.83 (M + K+, C177H236O23K requires 2770.70). Anal. Calcd
for C177H236O23: C, 77.82; H, 8.71. Found: C, 77.45; H, 8.84.
Methyl 3,5-Bis(3,5-Di(3,5-di-tert-butyl-4-methoxybenzyl-
oxy)benzyloxybenzoate ([G-2]-CO2CH3, 7). Following the
procedure for 5, 6 (1.4 g, 2.3 mmol), 4 (0.185 g, 1.1 mmol), PPh3
(0.734 g, 2.8 mmol), DIAD (0.56 g, 2.8 mmol, 0.53 mL), and dry
THF (15 mL) yielded 7 as a colorless glass (1.03 g, 70%) after
flash chromatography (SiO2, 5:1 hexanes-EtOAc): mp 90-92
°C; 1H NMR (300 MHz, CDCl3) δ 7.31 (s, 8H), 6.83 (t, J ) 2.1
Hz, 1H), 6.73 (s, 2H), 6.72 (s, 4H), 6.64 (t, J ) 2.4 Hz, 2H), 5.04
(s, 4H), 4.94 (s, 8H), 3.91 (s, 3H), 3.70 (s, 12 H), 1.43 (s, 72H);
13C NMR (75.4 MHz, CDCl3) δ 167.0, 160.7, 160.0, 159.8, 144.1,
138.9, 132.3, 130.6, 126.8, 108.6, 107.5, 106.7, 101.9, 71.0, 70.5,
64.5, 52.5, 36.0, 32.3; MS (MALDI) m/z 1363.93 (M + Na+,
Acknowledgment. This work was funded in part
by the National Science Foundation (CHE-0213537).
C.S.S. thanks the University of Arizona Undergraduate
Biology Research Program (UBRP) funded by the Howard
Hughes Medical Institute for a fellowship. D.V.M. is a
Dreyfus Teacher-Scholar.
C
86H116NaO12 requires 1363.84), 1379.89 (M + K+, C86H116KO12
requires 1379.81). Anal. Calcd for C86H116O12: C, 76.98; H, 8.71.
Found: C, 76.59; H, 8.75.
3,5-Bis(3,5-Di(3,5-di-tert-butyl-4-methoxybenzyloxy)ben-
zyloxybenzyl Alcohol ([G-2]-CH2OH, 8). Following the pro-
cedure for 6, 7 (0.5 g, 0.37 mmol), LAH (0.02 g, 0.55 mmol), and
Supporting Information Available: NMR and MS char-
acterization data for compounds 2, 3, and 5-10. This material
(11) Campi, E. M.; Gatehouse, B. M. K.; Jackson, W. R.; Rae, I. D.;
Wong, M. G. Can. J. Chem. 1984, 62, 2566-2569.
(12) Lepore, S. D.; Yuanjun, H. J. Org. Chem. 2003, 68, 8261-8263.
JO0483419
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