The Journal of Organic Chemistry
kept in a rotavapor at 60-65 °C and at 30 psi for 2h and Preparation cis-3,5-O-benzylidenecyclohexanol 11a
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then dried under high vacuum overnight. Compound 10a
was obtained as white solid (339 g, 98%) (Rf: 0.42,
PE:AcOEt:DCM 8:2:1): mp 182-184 °C;20 IR (KBr) 2966,
2927, 2852, 1948, 1452,1362, 1310, 1121, 995, 979 cm-1;
1H NMR (400 MHz, CDCl3) δ 7.71 – 7.65 (m, 2H), 7.40 –
7.33 (m, 3H), 4.64 – 4.53 (m, 3H), 2.81 – 2.72 (m, 3H),
1.82 (d, J = 12.8 Hz, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 139.4, 128.9, 127.8, 124.8, 108.7, 68.7, 32.7;
HRMS (EI+) m/z: [M+H]+ Calculated for C13 H15 O3
219.1021; Found 219.1014.
In a 2L reactor, HMPA (54 mL) was added to a
dispersion of 3-phenyl-2,4,10-trioxaadamantane 10a (60 g,
275 mmol, 1.00 eq.) in dry THF (600 mL) and kept under a
N2 atmosphere at 0°C. A BH3∙THF solution (1M in THF,
630 mmol, 630 mL, 2.29 eq.) was then added dropwise
over a period of 1h and the mixture left stirring for the next
21 h. At this point, TBME (1.5 L) was added and the
mixture was cooled at -10 °C by an ice-ethanol bath. After
this time, H2O (600 mL) was added dropwise and then the
temperature was allowed reaching room temperature
(20°C). The organic layer was separated and the water
phase extracted with additional TBME (600 mL). The
combined organic layers were washed with brine (1 L),
dried over Na2SO4 and the solvent removed under reduced
pressure until reached a volume of 60-70 mL. This crude
mixture was then charged into a silica gel column (600 g
silica, 9 cm diameter column). Elution using a mixture 4:1
PE:EtOAc, v/v (4L) gave the orthoester contaminated by
benzaldehyde; Elution using a mixture 2:3 PE:EtOAc, v/v
(2.5L) gave product 11a as a white solid (25.9 g, 43%) (Rf:
0.43, PE:AcOEt 1:1): mp 185-187 °C;5 IR (KBr) 3566,
2924, 2853, 1470, 1384, 1301, 1210, 1124, 1076, 742, 694
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.50 (m, 2H), 7.44 -
7.31 (m, 3H), 6.20 (s, 1H), 4.72 (br s, 2H), 4.09 (dt, J =
10.4, 4.9 Hz, 1H), 3.80 (d, J = 11.1 Hz, 1H), 3.02 (dtt, J =
14.7, 4.9, 2.4 Hz, 1H), 2.51 (d, J = 15.4 Hz, 2H), 1.78 (dd,
J = 15.0, 5.0 Hz, 2H), 1.57 (d, J = 14.6 Hz, 1H); 13C{1H}
NMR (101 MHz, CDCl3) δ 138.2, 128.8, 128.3, 126,3,
91.8, 69.2, 65.9, 39.2, 26.9; HRMS (ES+) m/z: [M + H]+
Calculated for C13H17O3 221.1178; Found 221.1162.
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Preparation of 3-(p-tolyl)-2,4,10-trioxaadamantane 10b
Following the procedure for compound 10a and starting
from 1-methyl-4-(trimethoxymethyl)benzene (900 mg, 6.8
mmol, 1 eq.), compound 10b was obtained pure after flash
column chromatography (4:1 PE:EtOAc, v/v) as a white
crystals (1.2 g, 76 %) (Rf: 0.39, PE:EtOAc 8:2): mp 177-
179 °C;21 IR (KBr) 3034, 2943, 2845, 1914, 1622,
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1453,1366, 1331, 1311, 1129, 809 cm-1; H NMR (400
MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0
Hz, 2H), 4.55 (s, 3H), 2.75 (d, J = 13.3 Hz, 3H), 2.33 (s,
3H), 1.80 (d, J = 12.8 Hz, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 138.9, 136.9, 128.8, 125.0, 109.1, 68.9, 33.1,
21.4; HRMS (ES+) m/z: [M + H]+ Calculated for C14H16O3
232.1099; Found 232.1091.
Preparation
of
3-(4-chlorophenyl)-2,4,10-
trioxaadamantane 10c
Following the procedure for compound 10a and starting
from 1-chloro-4-(trimethoxymethyl)benzene 9c (800 mg,
6.05 mmol, 1 eq.), compound 10c was obtained pure after
flash column chromatography (4:1 PE:EtOAc, v/v) as a
white solid (1.48 g, 97%) (Rf: 0.43, PE:AcOEt 8:2): mp
146-148 °C;6 IR (KBr) 2960, 2925, 2850, 1941, 1605,
1357,1325, 1309, 1128, 1010, 974, 809 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0
Hz, 2H), 4.58 (s, 3H), 2.76 (d, J = 8 Hz, 3H), 2.33 (s, 3H),
1.83 (d, J = 16 Hz, 3H); 113C{1H} NMR (101 MHz, CDCl3)
δ 138.3, 134.9, 128.2, 126.7, 108.6, 68.9, 32.9; HRMS
(ES+) m/z: [M + H]+ Calculated for C13H14O3Cl 253.0631;
Found 253.0633.
Preparation of 3-(p-tolyl)-2,4-dioxabicyclo[3.3.1]nonan-
7-ol 11b
Following the procedure for compound 11a and starting
from 1-methyl-4-(trimethoxymethyl)benzene 10b (300 mg,
1.29 mmol) compound 11b was obtained pure after flash
column chromatography (1:1 PE:EtOAc, v/v) as a white
solid (145 mg, 48%): mp 176-178 °C; IR (KBr) 3549,
2842, 1466, 1343, 1305, 1217, 1124, 1213, 725, 701 cm-1;
1H NMR (400 MHz, MeOD) δ 7.37 (d, J = 8.1 Hz, 2H),
7.18 (d, J = 8.1 Hz, 2H), 6.21 (s, 1H), 4.64 (bs, 2H), 4.06
(bs, 1H), 3.04 (dtt, J = 14.7, 4.9, 2.3 Hz, 1H), 2.37 (bs, 2H),
2.35 (s, 2H), 1.87 (dd, J = 15.0, 4.9 Hz, 2H), 1.66 (d, J =
14.7 Hz, 1H).; 113C{1H} NMR (101 MHz, MeOD) δ 139.8,
137.7, 129.9, 127.4, 93.2, 70.8, 67.8, 40.0, 27.6, 21.2;
HRMS (ES+) m/z: [M + Na]+ Calculated for C14H18O3Na
257.1154; Found 257.1143.
Preparation
trioxaadamantane 10d
of
3-(4-methoxyphenyl)-2,4,10-
Following the procedure for compound 10a and starting
from 1-methoxy-4-(trimethoxymethyl)benzene 9d (480 mg,
3.6 mmol, 1 eq.) compound 10d was obtained pure after
flash column chromatography (4:1 PE:EtOAc, v/v) as
white crystals (510 mg, 58 %) (Rf: 0.35, PE:EtOAc 8:2):
mp 106-108 °C; IR (KBr) 2943, 2841, 1614, 1520,1354,
1318, 1263, 1125 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.60
(d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.56 (s, 3H),
2.74 (d, J = 14.0 Hz, 3H), 1.80 (d, J = 12.8 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 160.2, 132.4, 126.6,
113.4, 109.1, 69.0, 55.4, 33.1. HRMS (ES+) m/z: [M]+
Calculated for C14H17O4 249.1119; Found 249.1127.
Preparation
of
3-(p-chlorophenyl)-2,4-
dioxabicyclo[3.3.1]nonan-7-ol 11c
Following the procedure for compound 11a and starting
from 1-methyl-4-(trimethoxymethyl)benzene 10c (1 g, 3.96
mmol, 1 eq.) and using 4 eq. of BH3∙THF complex solution
(1M in THF, 15.84 mmol, 15.84 mL). Purification by flash
column chromatography (1:1 PE:EtOAc, v/v) gave pure
11c as a white solid (854 mg, 85%): mp 130-132; IR (KBr)
3557, 2962, 2856, 1572, 1358, 1312, 1125, 1012, 726 cm-1;
1H NMR (400 MHz, MeOD) δ 7.50 (d, J = 8.4 Hz, 2H),
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