The Journal of Organic Chemistry
Article
5.11 (d, J = 6.1 Hz, 1H), 7.20−7.60 (m, 8H), 7.88−8.00 (m, 2H); anti-
3-hydroxy-2-methoxy-1,3-diphenylpropan-1-one (anti-5). 1H NMR
(CDCl3, 200 MHz):21 δ 3.39 (s, 3H), 4.67 (d, J = 6.6 Hz, 1H),
4.99 (d, J = 6.6 Hz, 1H), 7.22−7.62 (m, 8H), 7.86−8.05 (m, 2H).
Effect of Temperature. In Table 4, the yields of the products 3a−3c
and 5 obtained from the domino reaction in the presence of InCl3 at
different reaction temperatures are depicted.
1224, 1193, 1156, 1109, 1088, 1023, 1004, 967, 953, 919, 882, 840,
806, 778, 757, 723, 700, 628 cm−1. Anal. for C25H25FO5 (424.46 g
mol−1): Calcd, C 70.74, H 5.94, O 18.85; found, C 70.53, H 5.85, O
18.94.
(l,u,l,l)-3,5-Dimethoxy-6-(4-methoxyphenyl)-2,4-diphenyltetrahy-
dro-2H-pyran-2,4-diol (7a). InCl3 (555 mg, 2.50 mmol) and 4-
methoxybenzaldehyde (300 μL, 2.50 mmol) provided 458 mg (1.05
mmol, 42%) of 7a as a colorless solid after recrystallization of crude
Effect of Metal Halides. In Table 5, the yields of 3a using different
metal halides are listed.
1
product from ethanol. Mp, 151 °C. H NMR (400 MHz, CDCl3): δ
2.44 (s, 3H), 2.59 (s, 3H), 3.54 (s, 1H), 3.66 (d, J = 9.2 Hz, 1H), 3.67
(s, 1H), 3.81 (s, 3H), 5.06 (d, J = 9.6 Hz, 1H), 6.21 (s, 1H), 6.93 (d, J
= 8.8 Hz, 2H), 7.27−7.41 (m, 6H), 7.51 (d, J = 8.4 Hz, 2H), 7.61−
7.63 (m, 2H), 7.79−7.83 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
55.2, 60.8, 61.7, 70.5, 79.9, 85.6, 85.7, 98.3, 113.4, 125.5, 126.5, 127.5,
127.9, 128.1, 128.3, 128.7, 131.5, 141.7, 141.9, 159.4. IR [KBr]: 3431,
3061, 2932, 2831, 1606, 1510, 1450, 1367, 1295, 1260, 1224, 1193,
1156, 1109, 1088, 1023, 1004, 967, 953, 919, 882, 840, 806, 778, 757,
723, 700, 628 cm−1. Anal. for C26H28O6 (436.50 g mol−1): Calcd, C
71.54, H 6.47, O 21.99; found, C 71.50, H 6.43, O 21.78.
(l,u,l,l)-6-(Anthracen-9-yl)-3,5-dimethoxy-2,4-diphenyltetrahy-
dro-2H-pyran-2,4-diol (8a). InCl3 (555 mg, 2.50 mmol) and 9-
anthracenylcarbaldehyde (524 mg, 2.50 mmol) furnished 937 mg
(1.85 mmol, 74%) of 8a as a colorless solid after two times
crystallization from ethanol. Mp, 172 °C. 1H NMR (400 MHz,
CDCl3): δ 2.17 (s, 3H), 2.53 (s, 3H), 3.83 (s, 1H), 4.01 (s, 1H), 4.81
(d, J = 10 Hz, 1H), 6.67 (s, 1H), 6.81 (d, J = 10 Hz, 1H), 7.29−7.58
(m, 10H), 7.79−7.89 (m, 3H), 7.80−8.10 (m, 2H), 8.31−8.33 (m,
1H), 8.48 (s, 1H), 8.55 (d, J = 9.2 Hz, 1H), 9.20 (d, J = 9.2 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 60.2, 61.8, 66.6, 80.4, 83.3, 86.0, 99.0,
Table 5. Effect of Metal Halides on the Yields of 3a
3a
entry
metal halide
mg
mmol
%
1
2
3
4
5
zinc(II) chloride
163
569
0.400
1.40
1.90
1.30
2.48
15
56
76
52
99
titan(IV) chloride
zirconium(IV) chloride
aluminum(III) chloride
indium(III) chloride
774
528
1010
(l,u,l,l)-3,5-Dimethoxy-2,4,6-triphenyltetrahydro-2H-pyran-2,4-
diol (3a). The reaction mixture containing indium(III) chloride (555
mg, 2.50 mmol) was stirred for 30 min at −40 °C and for 1 h at room
temperature. Then, a solution of benzaldehyde (250 μL, 2.50 mmol)
in 30 mL of THF was added. The crude product was purified by
crystallization from ethanol furnishing 437 mg (1.08 mmol, 43%) of 3a
as a colorless solid. Mp, 135 °C. 1H NMR (400 MHz, CDCl3): δ 2.36
(s, 3H), 2.49 (s, 3H), 3.47 (s, 1H), 3.60 (d, J = 12 Hz, 1H), 3.62 (s,
1H), 5.03 (d, J = 12 Hz, 1H), 6.14 (s, 1H), 7.18−7.33 (m, 9H), 7.51−
7.55 (m, 4H), 7.73−7.75 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
60.8, 61.7, 70.9, 79.9, 85.6, 85.8, 98.3, 125.5, 126.5, 127.5, 127.9, 128.0,
128.2, 128.3, 139.4, 141.6, 141.8. IR [KBr]: 3531, 3444, 3391, 3057,
3032, 2993, 2931, 2835, 1495, 1450, 1364, 1338, 1313, 1295, 1257,
1223, 1195, 1152, 1102, 1083, 1025, 1005, 951, 920, 874, 841, 751,
723 cm−1. Anal. for C25H26O5 (406.47 g mol−1): calcd, C 73.87, H
6.45, O 19.68; found, C 73.54, H 6.50, O 19.83.
124.2, 124.6, 125.4, 125.5, 126.2, 126.3, 126.6, 127.0, 127.2, 128.0,
128.2, 128.4, 128.9, 129.1, 130.0, 130.4, 131.4, 131.7, 132.0, 134.1,
141.7, 141.9. IR [KBr]: 3544, 3456, 3062, 2989, 2932, 2829, 1676,
1624, 1592, 1527, 1494, 1447, 1404, 1333, 1251, 1158, 1104, 1026,
996, 890, 763, 728, 705, 630 cm−1. Anal. for C33H30O5 (506.59 g
mol−1): Calcd, C 78.24, H 5.97, O 15.79; found, C 78.00, H 6.03, O
15.63.
(l,u,l,l)-3,5-Bis(benzyloxy)-2,4,6-triphenyltetrahydro-2H-pyran-
2,4-diol (10a). A mixture of 1.70 g (7.50 mmol) of 2-benzyloxy-1-
phenylethanone (9) and InCl3 (555 mg, 2.50 mmol) was treated with
a solution of benzaldehyde (250 μL, 2.50 mmol) in THF (30 mL)
under reflux conditions for 2 h. The crude product was purified by
crystallization from ethanol furnishing 558 mg (1.00 mmol, 40%) of
10a as a colorless solid. Mp, 148 °C. 1H NMR (CDCl3, 400 MHz): δ
3.35 (d, J = 10 Hz, 1H), 3.47 (d, J = 10 Hz, 1H), 3.53 (d, J = 12 Hz,
1H), 3.55 (d, J = 12 Hz, 1H), 3.68 (d, J = 1.0 Hz, 1H) 3.91 (d, J = 1.0
Hz, 1H), 4.01 (d, J = 9.6 Hz, 1H), 5.22 (d, J = 9.6 Hz, 1H), 6.43 (s,
1H), 6.50−6.55 (m, 4H), 7.04−7.20 (m, 6H), 7.36−7.45 (m, 9H),
7.63−7.66 (m, 4H), 7.87−7.89 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 71.1 74.9, 75.4, 80.3, 83.3, 84.1, 98.6, 126.8, 127.6, 127.7,
127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6, 136.4,
136.6, 139.3, 141.8, 141.9. IR [KBr]: 3089, 3080, 3059, 2978, 2927,
2870, 2760, 2720, 2488, 1954, 1816, 1602, 1586, 1497, 1453, 1397,
1358, 1334, 1315, 1294, 1256, 1224, 1155, 1091, 1077, 1013, 917, 752,
697 cm−1. Anal. for C37H34O5 (558.66 g mol−1): Calcd, C 79.55, H
6.13; found, C 79.78, H 6.43.
(l,u,l,u)-3,5-Dimethoxy-2,4,6-triphenyltetrahydro-2H-pyran-2,4-
1
diol (3b). Mp, 128 °C. H NMR (400 MHz, CDCl3): δ 2.32 (s, 3H),
2.74 (s, 3H), 3.26 (s, 1H), 4.23 (s, 1H), 4.31 (s, 1H), 5.65 (s, 1H),
5.66 (s, 1H), 7.26−7.47 (m, 9H), 7.56 (d, J = 7.4 Hz, 2H), 7.64 (d, J =
9.4 Hz, 2H), 7.94 (d, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3):
δ 61.0, 61.36, 70.0, 78.5, 80.2, 87.4, 98.9, 126.3, 126.6, 126.8, 127.1,
127.4, 127.8 (2C), 128.0, 128.2, 138.5, 142.1, 142.7. IR [KBr]: 3435,
3090, 3060, 3030, 2930, 2830, 1965, 1496, 1450, 1412, 1345, 1315,
1234, 1194, 1122, 1087, 1064, 1029, 1004, 951, 926, 906, 874, 856,
841, 759, 703 cm−1. Anal. for C25H26O5 (406.47 g mol−1): Calcd, C
73.87, H 6.45; found, C 73.64, H 6.72.
(u,l,l,l)-3,5-Dimethoxy-2,4,6-triphenyltetrahydro-2H-pyran-2,4-
1
diol (3c). Mp, 118 °C. H NMR (400 MHz, CDCl3): δ 2.16 (s, 3H),
2.74 (s, 3H), 3.15 (s, 1H), 3.89 (s, 1H), 4.14 (d, J = 9.4 Hz, 1H), 5.13
(d, J = 9.4 Hz, 1H), 6.62 (s, 1H), 7.28−7.46 (m, 9H), 7.59−7.71 (m,
4H), 7.78 (d, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 60.5,
60.6, 71.6, 78.6, 80.4, 85.5, 98.4, 126.8 (2C), 126.9 (2C), 127.4, 127.6,
127.8, 128.0, 128.2, 139.9, 141.2, 141.9. IR [KBr]: 3512, 3090, 3061,
3033, 2930, 2830, 2246, 1954, 1496, 1449, 1422, 1296, 1259, 1227,
1197, 1141, 1098, 1082, 1064, 1040, 1025, 1005, 995, 978, 939, 911,
779, 752, 701 cm−1. Anal. for C25H26O5 (406.47 g mol−1): Calcd, C
73.87, H 6.45; found, C 73.54, H 6.50.
(l,u,l,l)-3,5-Bis(benzyloxy)-6-(4-fluorophenyl)-2,4,-diphenyltetra-
hydro-2H-pyran-2,4-diol (11a). A mixture of 1.70 g (7.50 mmol) of
2-benzyloxy-1-phenylethanone (9) and InCl3 (555 mg, 2.50 mmol)
was reacted with a solution of 4-fluorobenzaldehyde (260 μL, 2.50
mmol) in THF (30 mL) under reflux conditions for 2 h. The crude
product was purified by crystallization from ethanol providing 908 mg
(l,u,l,l)-6-(4-Fluorphenyl)-3,5-dimethoxy-2,4-diphenyltetrahydro-
2H-pyran-2,4-diol (6a). The use of InCl3 (555 mg, 2.50 mmol) and 4-
flouorobenzaldehyde (260 μL, 2.50 mmol) resulted in 669 mg (1.58
mmol, 63%) of 6a as a colorless solid after crystallization from ethanol.
1
(1.57 mmol, 63%) of 11a as a colorless solid. Mp, 158 °C. H NMR
(200 MHz, CDCl3): δ 3.34 (d, J = 10 Hz, 1H), 3.47 (d, J = 10 Hz,
1H), 3.52 (d, J = 4.0 Hz, 2H), 3.69 (s, 1H), 3.91 (s, 1H), 4.00 (d, J =
9.6 Hz, 1H), 5.21 (d, J = 9.6 Hz, 1H), 6.42 (s, 1H), 6.48−6.56 (m,
4H), 7.05−7.15 (m, 5H), 7.32−7.47 (m, 9H), 7.60−7.66 (m, 4H),
7.85−7.89 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 70.5, 74.9, 75.5,
80.3, 83.2, 84.0, 98.6, 115.1, 115.3, 126.7, 127.6, 127.8, 127.9, 128.0
(2C), 128.1, 128.4, 128.5, 128.6, 129.4, 129.5, 135.1, 136.2, 136.5,
141.6, 141.7, 161.4. IR [KBr]: 3462, 3063, 3029, 2905, 2859, 1894,
1
Mp, 153 °C. H NMR (200 MHz, CDCl3): δ 2.44 (s, 3H), 2.56 (s,
3H), 3.56 (s, 1H), 3.68 (d, J = 9.5 Hz, 1H), 3.86 (s, 1H), 5.13 (d, J =
9.5 Hz, 1H), 6.30 (s, 1H), 7.31−7.42 (m, 8H), 7.59−7.64 (m, 4H),
7.81−7.86 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 60.9, 61.7, 70.2,
79.9, 85.6, 85.9, 98.4, 115.1 (d, J = 21 Hz), 125.4, 126.5, 127.6, 127.9,
128.2, 128.3, 129.1 (d, J = 8.2 Hz), 135.2, 141.5, 141.7, 161.3. IR
[KBr]: 3431, 3061, 2932, 2831, 1606, 1510, 1450, 1367, 1295, 1260,
F
J. Org. Chem. XXXX, XXX, XXX−XXX