374
J.W. Gathirwa, T. Maki / Tetrahedron 68 (2012) 370e375
1.935 (1H, t, J¼2.7 Hz), 2.32 (2H, m), 3.57 (3H, t, J¼6.0 Hz), 4.52 (2H,
s), 7.34 (5H, m); 13C NMR (400 MHz, CDCl3, TMS, rt)
(ppm): 15.21,
28.60, 68.40, 68.65, 72.98, 83.96, 127.61, 127.66, 128.42, 138.54; IR
(KBr, cmꢁ1): 1028, 1105, 1365, 1454, 2861, 3295. HRMS calcd for
C12H14O m/z 174.1045, found HR-EI (þ) m/z 174.1017.
d
(ppm): 0.71 (3H, d, J¼6.9 Hz), 0.88 (9H, m), 1.33 (2H, m), 1.63 (3H,
d
m), 2.3 (1H, m), 3.17 (1H, m), 4.4 (1H, d, J¼11.3 Hz), 4.66 (1H, d,
J¼11.5 Hz), 7.32 (5H, m); 13C NMR (400 MHz, CDCl3, TMS, rt)
d
(ppm): 15.96, 20.91, 22.26, 23.19, 25.42, 31.48, 34.51, 40.24, 48.26,
70.35, 78.68, 127.37, 127.83, 128.27, 139.19; IR (cmꢁ1): 1069, 1110,
1344, 1369, 1454, 2869, 2955. HRMS calcd for C17H26O m/z
246.3877, found HR-EI (þ) m/z 246.1975.
3.1.15. 1-Methoxy-4-((1-phenylethoxy)methyl)benzene (18b). A col-
ourless oil, 1H NMR (300 MHz, CDCl3, TMS, rt)
d (ppm): 1.46 (3H, d,
J¼6.3 Hz), 3.79 (3H, s), 4.22 (1H, d, J¼6.2 Hz), 4.38 (1H, d, J¼6.2 Hz),
3.2.3. 1-Methoxy-4-(((2-methyl-1-phenylpropan-2-yl)oxy)methyl)
4.48 (1H, q, J¼6.3 Hz), 6.87 (2H, d, J¼8.5 Hz), 7.38 (7H, m); 13C NMR
benzene (24a). A colourless oil, 1H NMR (300 MHz, CDCl3, TMS, rt)
(400 MHz, CDCl3, TMS, rt)
d
(ppm): 25.19, 47.26, 55.20, 63.45, 75.66,
d
(ppm): 1.23 (6H, s), 2.87 (2H, s), 3.79 (3H, s), 4.46 (2H, s), 6.87 (2H,
113.73, 126.09, 127.81, 128.70, 130.66, 131.94, 138.51, 158.89; IR (KBr,
cmꢁ1): 1036, 1250, 1450, 1609, 1612, 2973; HRMS calcd for C16H18O2
m/z 242.1307, found HR-EI (þ) m/z 242.1301.
m) 7.25 (7H, m); 13C NMR (400 MHz, CDCl3, TMS, rt)
d
(ppm): 25.16,
39.01, 49.65, 55.16, 63.41, 71.37, 75.63, 113.70, 126.05, 126.44, 127.77,
128.67, 130.44, 130.63, 131.91, 138.47, 158.85; IR (KBr, cmꢁ1): 1035,
1174, 1247, 1513, 1612, 1699, 2970; HRMS calcd for C18H22O2 m/z
270.1620, found HR-EI (þ) m/z 270.1621.
3.1.16. 4-Methoxybenzyl benzoate (19b). A white solid, mp:
37e38 ꢀC; 1H NMR (300 MHz, CDCl3, TMS, rt)
d (ppm): 3.82 (3H, s),
5.30 (2H, s), 6.90 (2H, d, J¼8.4 Hz), 7.42 (4H, m), 7.44 (1H, t, J¼3.7 Hz),
3.2.4. (2-(Benzyloxy)-2-methylpropyl)benzene (24b). A colourless
8.05 (2H, d, J¼6.9 Hz); 13C NMR (400 MHz, CDCl3, TMS, rt)
d
(ppm):
oil, 1H NMR (300 MHz, CDCl3, TMS, rt)
d
(ppm): 1.26 (6H, s), 2.92
69.87, 114.89, 120.97, 127.51, 127.96, 128.60, 129.52, 137.14, 158.88. IR
(KBr, cmꢁ1): 1029, 1242, 1496, 1599, 2866, 3032; HRMS calcd for
C13H12O m/z 184.0888, found HR-EI (þ) m/z 184.0880.
(2H, s), 4.57 (2H, s), 7.31 (10H, m); 13C NMR (400 MHz, CDCl3, TMS,
rt) d (ppm): 25.10, 47.26, 63.72, 75.68, 126.07, 127.00, 127.15, 127.78,
128.21, 130.63, 138.39, 139.84; IR (KBr, cmꢁ1): 697, 1061, 1454, 2972;
HRMS calcd for C17H20O m/z 240.1514, found HR-EI (þ) m/z
240.1512.
3.1.17. 4-Methoxy benzoate (20a). A colourless oil, 1H NMR
(300 MHz, CDCl3, TMS, rt)
d (ppm): 3.77 (3H, s), 5.28 (2H, s), 4.53
(2H, s), 6.89 (2H, d, J¼7.4 Hz), 7.37 (4H, d, J¼7.4 Hz), 7.5 (1H, s), 8.05
3.2.5. tert-Butyl(2-((4-methoxybenzyl)oxy)propoxy)dimethylsilane
(2H, d, J¼6.9 Hz); 13C NMR (400 MHz, CDCl3, TMS, rt)
d
(ppm): 55.11,
(26). A colourless oil, 1H NMR (300 MHz, CDCl3, TMS, rt)
d (ppm):
66.41, 113.93, 128.16, 128.30, 129.62, 130.03, 130.27, 132.90, 159.68,
166.47; IR (KBr, cmꢁ1): 712, 1272, 1515, 1720, 2837, 2957. HRMS
calcd for C15H14O3 m/z 242.0943, found HR-EI (þ) m/z 242.0933.
0.05 (6H, s), 0.90 (9H, s), 1.15 (3H, d, J¼6.04 Hz), 3.57 (3H, m), 3.80
(3H s), 4.54 (2H, s), 6.87 (2H, d, J¼8.79 Hz), 7.28 (2H m); 13C NMR
(400 MHz, CDCl3, TMS, rt) d (ppm): 16.98, 18.23, 25.84, 55.22, 67.17,
70.86, 75.39, 113.74, 129.20, 131.22, 159.12. IR (KBr, cmꢁ1): 1103,
1249, 1513, 1612, 2857, 2955; HRMS calcd for C17H30NaO3Si m/z
333.1964, found HR-ESI (þNa) m/z 333.1862.
3.1.18. Benzyl benzoate (20b). A colourless oil, 1H NMR (300 MHz,
CDCl3, TMS, rt)
d (ppm): 5.3 (2H, s), 7.32 (8H, m), 8.05 (2H, d,
J¼8 Hz); 13C NMR (400 MHz, CDCl3, TMS, rt)
d (ppm): 68.67, 128.27,
128.34, 128.48, 128.71, 129.81, 130.31, 133.11, 136.26, 166.49; IR (KBr,
3.2.6. (S)-Ethyl 2-((4-methoxybenzyl)oxy)propanoate (28). A col-
cmꢁ1): 1026, 1070, 1110, 1272, 1314, 1452, 1720, 3034, 3065. HRMS
ourless oil, ½a 2D0
ꢂ
ꢁ82.1 (c 2.50, CHCl3). 1H NMR (300 MHz, CDCl3,
calcd for C14H12
O
2 m/z 212.0806, found HR-EI (þ) m/z 212.080.
TMS, rt)
d
(ppm): 1.30 (3H, t, J¼7.14 Hz), 1.41 (3H, d, J¼6.87 Hz), 3.80
(3H, s), 4.03 (1H, q, J¼6.87 Hz), 4.22 (2H, q, J¼7.14 Hz), 4.39 (1H, d,
J¼11.26 Hz), 4.62 (1H, d, J¼11.26 Hz), 6.88 (2H, d, J¼8.52 Hz), 7.29
3.2. Reaction of various types of alcohols
(2H, m); 13C NMR (400 MHz, CDCl3, TMS, rt)
d (ppm): 13.96, 18.43,
Benzylation of sterically hindered alcohols, such as menthol (21)
and 1,1-dimethylphenylethanol (22) that were otherwise slow un-
der the standard reaction condition were activated by a catalytic
amount of NaI. Menthol (1 mmol) or 1,1-dimethylphenylethanol
(1 mmol) were added to the reaction vessel containing DIPEA
(1.6 mmol), then 1.5 equiv of alkyl halide (R2eX) and 10 mol % of NaI
added. The mixture was stirred for 1 h at 150 ꢀC. Upon cooling, to the
resulting mixture ethyl acetate (5 mL) and 10% aqueous sodium
bisulphate (5 mL) were added and the organic phase extracted by
three potions of EtOAc. Combined organic layer was dried over
magnesium sulfate and the solvent evaporated in vacuo. Further
purification was carried out by silica gel column chromatography.
54.99, 60.54, 71.41, 73.51, 113.65, 129.50, 159.29, 173.25. IR (KBr,
cmꢁ1): 1143, 1243, 1612, 1754, 2984; HRMS calcd for C13H18NaO4 m/
z 261.1205, found HR-ESI (þNa) m/z 261.1103.
3.2.7. ((2R,3S,4S,5R,6S)-5-(Benzoyloxy)-3,4-dihydroxy-6-
methoxytetrahydro-2H-pyran-2-yl)methyl benzoate (30). A white
solid, mp: 139e140 ꢀC. 1H NMR (300 MHz, CDCl3, TMS, rt)
d (ppm):
3.35 (3H, s), 3.61 (1H, t, J¼8.9 Hz), 3.95 (1H, d, J¼7.1 Hz), 4.19 (1H, t,
J¼8.9 Hz), 4.53 (1H, d, J¼12.1 Hz), 4.78 (1H, dd, J¼11.9, 3.2 Hz), 4.95
(1H, dd, J¼9.6, 3.0 Hz), 5.05 (1H, d, J¼3.3 Hz), 7.4 (4H, m), 7.54 (2H,
q, J¼6.8 Hz), 8.08 (4H, d, J¼7.4 Hz); 13C NMR (400 MHz, CDCl3, TMS,
rt)
d (ppm): 55.37, 63.60, 69.55, 70.66, 71.54, 73.69, 97.34, 128.49,
128.53, 129.53, 129.59, 129.90, 129.99, 133.43, 133.45, 166.52,
167.40; IR (KBr, cmꢁ1): 1291,1453,1694, 2948, 3468. HRMS calcd for
C21H22O8 m/z 402.1315, found HR-EI (þ) m/z 402.1302.
3.2.1. 1-((((1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl)oxy)methyl)-
4-methoxybenzene (23a). A colourless oil, 1H NMR (300 MHz,
CDCl3, TMS, rt)
d
(ppm): 0.7 (3H, d, J¼6.8 Hz), 0.91 (9H, m), 1.3 (2H,
m), 1.63 (2H, m), 2.25 (2H, m), 3.15 (1H, td, J¼10.4 Hz), 3.79 (3H, m),
4.31 (1H, d, J¼10.5 Hz), 4.57 (1H, d, J¼10.5 Hz), 6.83 (2H, m), 7.29
3.2.8. ((2R,3R,4S,5R,6S)-5-(Benzoyloxy)-6-methoxy-3,4-bis((4-
methoxybenzyl)oxy)tetrahydro-2H-pyran-2-yl)methyl
benzoate
(ppm):
(2H, m); 13C NMR (400 MHz, CDCl3, TMS, rt)
d
(ppm): 15.90, 20.86,
(31a). A colourless oil, 1H NMR (300 MHz, CDCl3, TMS, rt)
d
22.22, 23.14, 25.35, 31.42, 34.47, 40.21, 48.19, 55.08, 69.93, 78.30,
113.66, 129.31, 159.07; IR (KBr, cmꢁ1): 1084, 1171, 1248, 1456, 1513,
1613, 2963. HRMS calcd for C18H28O2 m/z 276.2089, found HR-EI (þ)
m/z 276.2078.
3.38 (3H, s), 3.74 (6H, m), 4.0 (1H, m), 4.22 (1H, t, J¼9.4 Hz), 4.54
(3H, m), 4.8 (4H, m), 5.01 (1H, d, J¼3.7 Hz), 5.14 (1H, dd, J¼10.0,
3.7 Hz), 6.78 (4H, m), 7.17 (4H, m), 7.45 (4H, q, J¼8.0 Hz), 7.58 (2H,
m), 8.05 (4H, m); 13C NMR (400 MHz, CDCl3, TMS, rt)
d (ppm): 55.17,
55.22, 63.16, 68.86, 73.96, 74.77, 75.35, 77.08, 80.01, 97.23, 113.78,
113.90, 128.39, 128.45, 129.63, 129.76, 129.82, 130.19, 133.08, 133.27,
159.23, 159.36, 165.89, 166.20; IR (KBr, cmꢁ1): 711, 1067, 1271, 1513,
3.2.2. ((((1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl)oxy)methyl)
benzene (23b). A brown oil, 1H NMR (300 MHz, CDCl3, TMS, rt)