The Journal of Organic Chemistry
Article
2G9Cl (13). Thionyl chloride (1.08 mL, 14.67 mmol), was added
dropwise at rt to a solution of alcohol 12 (0.40 g, 0.48 mmol), in
dichloromethane (DCM)/DMF (10 mL (10/1 v/v) and the reaction
was heated to reflux for 16 h. After completion, the reaction was
quenched with saturated NaHCO3 solution, and extracted three times
with DCM washed with water and brine, and dried over magnesium
sulfate. The solvent was removed under reduced pressure until a small
amount was left and then was poured into a beaker containing
pentane. After cooling with an ice bath, the desired compound 3
(2G9Cl) precipitated as a white solid with a yield of (0.405 g, 0.412
mmol, 84%). 1H NMR (300 MHz, CDCl3): δ 8.19 (dd, J = 1.10, 8.25
Hz, 1H), 8.15 (d, J = 7.79 Hz, 1H), 7.98 (s, 2H), 7.77 (td, J = 1.10,
7.61 Hz, 1H), 7.49−7.57 (m, 3H), 7.44 (s, 4H), 5.47 (s, 2H), 5.26 (s,
4H), 5.24 (br s, 2H), 4.73 (s, 4H), 4.60 (br s, 2H), 4.59 (s, 8H), 4.56
(s, 4H). 13C{1H} NMR (101 MHz, CDCl3): δ 155.1, 155.1, 154.5,
145.9, 134.6, 134.5, 134.3, 134.0, 133.6, 132.1, 132.0, 132.0, 131.9,
131.0, 129.9, 128.3, 127.6, 124.9, 76.4, 73.6, 73.6, 72.0, 72.0, 45.0,
45.0, 40.6, 40.5. MALDI-TOF m/z: (M + Na) calcd for
C43H38Cl9NO6Na, 1005.9729; found, 1005.9749. FT-IR (golden
gate, 600−4000 cm−1) 1528, 1475, 1367, 1342, 1265, 1211, 1131,
992, 968, 888, 789, 727, 678. mp (99−102 °C).
600−4000 cm−1) 32867, 2971, 2877, 1632, 1477, 1462, 1401, 1362,
1266, 1247, 1223, 1164, 1106, 1082, 1006, 949, 882. mp (81−84 °C).
3G27DIOXOLANE (16). A solution of 2,4,6-tri(1,3-dioxolan-2-
yl)phenol 15 (0.189 g, 0.610 mmol), 13 (2G9Cl) (0.04 g, 0.041
mmol), K2CO3 (0.169 g, 1.220 mmol), and potassium iodide (0.061
g, 0.366 mmol) in acetone (4.07 mL) was stirred at 55 °C overnight.
The reaction mixture was quenched with water and extracted four
times with ethyl acetate washed with water and brine, and dried over
magnesium sulfate. The crude product was purified by flash
chromatography using ethyl acetate/acetone (EtOAc 100% then
30% acetone) to give the desired product 16 (3G27dioxolane) as a
white solid (0.081 g, 0.023 mmol, 58%). 1H NMR (300 MHz,
acetone-d6): δ 7.96 (s, 2H), 7.94 (s, 2H), 7.82 (s, 5H), 7.76 (s, 2H),
7.72 (s, 4H), 7.68 (s, 5H), 7.64 (s, 9H), 7.12−7.21 (m, 1H), 7.03−
7.12 (m, 1H), 6.21 (s, 2H), 6.14 (s, 4H), 6.10 (s, 4H), 5.95 (s, 8H),
5.77 (s, 1H), 5.75 (s, 2H), 5.72 (s, 4H), 5.69 (s, 2H), 5.32 (s, 4H),
5.24 (br s, 6H), 5.15−5.21 (m, 10H), 5.13 (s, 6H), 3.63−4.24 (m,
108H). 13C{1H} NMR (101 MHz, acetone-d6): δ 171.0, 158.1, 158.0,
157.9, 155.3, 155.2, 154.7, 146.7, 135.6, 135.5, 135.4, 134.8, 134.7,
134.6, 134.3, 132.9, 132.9, 132.9, 132.8, 132.4, 132.3, 130.2, 130.0,
129.4, 129.0, 128.4, 127.9, 127.8, 127.8, 127.7, 125.3, 104.0, 103.9,
103.9, 103.8, 99.8, 99.7, 99.6, 79.2, 79.1, 76.9, 74.4, 74.3, 74.0, 72.7,
66.2, 66.1, 66.0, 66.0, 66.0, 60.6, 20.9, 14.6. MALDI-TOF m/z: (M +
Na+) calcd for C178H191NO69Na, 3470.1393; found, 3471.1424.
MALDI-TOF m/z: (M + Ag+) calcd for C178H191NO69Ag, 3554.0547;
found, 3556.05. FT-IR (golden gate, 400−4000 cm−1) 2955, 2887,
1733, 1615, 1526, 1473, 1361, 1232, 1113, 1007, 967, 943, 890, 730,
661. mp (119.8−122.2 °C).
4-(((tert-Butyldimethylsilyl)oxy)methyl)-2,6-bis-
(((tetrahydro-2H-pyran-2-yl)oxy)methyl)phenol (17). Pyridin-1-
ium 4-methylbenzenesulfonate (0.044 g, 0.176 mmol) was added to a
cooled (ice bath) solution of (5-(((tert-butyldimethylsilyl)oxy)-
methyl)-2-hydroxy-1,3-phenylene)dimethanol 9 (1.052 g, 3.52
mmol), and 3,4-dihydro-2H-pyran (0.696 mL, 7.40 mmol) in DCM
(22 mL) and stirred under the same condition (ice bath) for 10 min.
The ice bath was removed and stirring at rt was continued for 22 h.
The reaction was quenched with saturated NaHCO3 solution and
extracted three times with DCM washed with water and brine, and
dried over sodium sulfate. Purification by flash chromatography using
pentane/ethyl acetate (8.5/1.5 v/v) gave the desired compound as a
colorless liquid (1.56 g, 3.31 mmol, 94%). 1H NMR (400 MHz,
CDCl3): δ 7.74 (s, 1H), 7.16 (s, 2H), 4.90 (d, J = 2.93 Hz, 1H), 4.86
(d, J = 2.93 Hz, 1H), 4.75 (dt, J = 2.41, 4.46 Hz, 2H), 4.67 (d, J =
1.83 Hz, 1H), 4.65 (s, 2H), 4.64 (d, J = 1.83 Hz, 1H), 3.96 (ddd, J =
3.12, 7.55, 11.10 Hz, 2H), 3.54−3.63 (m, 2H), 1.72−1.98 (m, 4H),
1.48−1.71 (m, 10H), 0.93−0.95 (m, 9H), 0.05−0.16 (m, 6H).
13C{1H} NMR (75 MHz, CDCl3): δ 152.95, 132.42, 126.97, 123.78,
2G9PNP (2). A solution of 13 (84 mg, 0.06 mmol), p-nitrophenol
(127 mg, 0.910 mmol), potassium iodide (10.20 mg, 0.06 mmol), and
K2CO3 (377 mg, 2.73 mmol) in acetone (5 mL), was stirred under
reflux overnight. The reaction mixture was diluted with acetone and
filtered, the filtrate was concentrated until a small amount of the
solvent was left and poured into a beaker containing water/methanol
(1/1 v/v). The solid formed was filtered and washed with methanol
to get the desired compound 2 (2G9PNP) as a light green solid (91
1
mg, 0.048 mmol, 78%). H NMR (400 MHz, acetone-d6): δ 8.15−
8.24 (m, 6H), 7.97−8.12 (m, 13H), 7.85 (dd, J = 0.79, 7.76 Hz, 1H),
7.78 (s, 2H), 7.68−7.73 (m, 1H), 7.67 (s, 4H), 7.52 (s, 3H), 7.12−
7.26 (m, 10H), 7.03 (d, J = 9.29 Hz, 1H), 6.92−7.00 (m, 7H), 5.35
(s, 2H), 5.29 (s, 4H), 5.27 (s, 4H), 5.24 (s, 2H), 5.12 (s, 8H), 5.09 (s,
4H), 4.93 (s, 2H). 13C{1H} NMR (400 MHz, acetone-d6): δ 164.8,
164.7, 164.6, 164.4, 157.2, 157.1, 154.8, 147.2, 142.7, 142.6, 142.6,
142.5, 135.3, 135.0, 134.4, 134.1, 134.0, 132.4, 131.9, 131.5, 131.1,
131.0, 130.5, 129.6, 128.5, 126.7, 126.7, 126.6, 126.6, 125.7, 116.1,
116.1, 115.8, 115.7, 77.9, 73.9, 73.3, 70.7, 70.7, 67.1, 66.9. HRMS
(ESI-ITMS) m/z: (M + Na+) calcd for C97H74N10O33Na, 1929.4311;
found, 1929.4297. FT-IR (golden gate, 600−4000 cm−1) 1589, 1508,
1495, 1331, 1247, 1172, 1109, 996, 863, 843, 751. mp (96−98 °C).
2-Hydroxy-1,3,5-benzenetricarbaldehyde (14). This proce-
dure was adapted from a similar transformation.52 Trifluoroacetic acid
(57.2 mL) was added slowly while cooling (ice bath) to a solid
mixture of phenol (5.00 g, 53.10 mmol), and hexamethylenetetramine
(16.39 g, 117.00 mmol. Caution: exothermic reaction). The reaction
mixture was heated to 125 °C for 20 h, at which point the
temperature was raised to 150 °C and stirred for another 3 h. After
cooling to 100 °C, the reaction mixture was treated with 50 mL 3N
HCl and stirred for another 30 min. The reaction mixture was allowed
to cool overnight to room temperature. The brown solid formed was
filtered off and washed with water and dried under high vacuum to
give the desired compound 14 as a brown solid with a yield of (6.20 g,
34.8 mmol, 65%). 1H NMR (300 MHz, acetone-d6): δ 10.38 (s, 2H),
10.08 (s, 1H), 8.63 (s, 2H).
98.27, 98.23, 65.95, 64.70, 62.71, 60.37, 30.52, 25.99, 25.31, 21.03,
19.56, 18.44, 14.19, −5.18. HRMS (ESI-ITMS) m/z: (M + Na+)
calcd for C25H42O6SiNa, 489.2642; found, 489.2615. FT-IR (golden
gate, 400−4000 cm−1) 3394, 2937, 2855, 1740, 1612, 1463, 1360,
1253, 1201, 1121, 1074, 1023, 901, 835, 775, 667.
4-(Hydroxymethyl)-2,6-bis(((tetrahydro-2H-pyran-2-yl)oxy)-
methyl)phenol (18). TBAF (33.5 mL, 33.5 mmol) was added to a
cooled (ice bath) solution of 17 (4.428 g, 22.34 mmol). The ice bath
was removed and the temperature was allowed to raise to rt and
stirring was continued for 18.5 h. After completion, the reaction
mixture was quenched with water and extracted three times with ethyl
acetate washed with water and brine, and dried over sodium sulfate.
The crude product was purified by flash chromatography using
pentane/ethyl acetate (7/3 v/v) to give the desired compound 18 as a
2,4,6-Tri(1,3-dioxolan-2-yl)phenol (15). A solution of PPTS
(1.00 g, 3.99 mmol), 2-hydroxybenzene-1,3,5-tricarbaldehyde 14
(1.00 g, 5.61 mmol), and ethylene glycol (3.78 mL, 67.4 mmol) in
benzene (112 mL) was refluxed for 24 h with a Dean−Stark
apparatus. The reaction mixture was quenched with saturated
NaHCO3 solution and extracted two times with benzene washed
with water and brine, and dried over sodium sulfate. Removal of the
solvent under reduced pressure gave the desired compound 15 as a
yellow solid (1.30 g, 4.21 mmol, 75%) which was launched in the next
reaction without further purification. 1H NMR (300 MHz, CDCl3): δ
8.35 (s, 1H), 7.50 (s, 2H), 6.07 (s, 2H), 5.75 (s, 1H), 3.95−4.18 (m,
12H). 13C{1H} NMR (75 MHz, CDCl3): δ 154.5, 129.1, 126.7, 123.2,
103.3, 101.6, 65.1, 64.9. HRMS (ESI-ITMS) m/z: (M + Na+) calcd
for C15H18O7Na, 333.0944; found, 333.0937. FT-IR (golden gate,
1
slightly yellow gel (6.62 g, 18.78 mmol, 84%). H NMR (300 MHz,
CDCl3): δ 7.87 (s, 1H), 7.22 (s, 2H), 4.91 (d, J = 3.12 Hz, 1H), 4.87
(d, J = 3.12 Hz, 1H), 4.70−4.80 (m, 2H), 4.66 (d, J = 2.02 Hz, 1H),
4.62 (d, J = 2.11 Hz, 1H), 4.60 (br s, 2H), 3.88−4.04 (m, 2H), 3.51−
3.66 (m, 2H), 1.71−2.01 (m, 4H), 1.45−1.71 (m, 8H). 13C{1H}
NMR (75 MHz, CDCl3): δ 153.6, 132.0, 128.2, 124.2, 98.5, 98.4,
65.8, 65.1, 62.8, 30.5, 25.3, 19.6. HRMS (ESI-ITMS) m/z: (M + Na+)
calcd for C19H28O6Na, 375.1778; found, 375.1771. FT-IR (golden
G
J. Org. Chem. XXXX, XXX, XXX−XXX