Reductions with an Aqueous TiCl3/NH3 System
FULL PAPER
°C (ref.[29b] 94Ϫ95). 13C NMR (CDCl3): δ ϭ 22.17 (CH2), 38.67 (2 CH2), 2.3 (s, br, 2 H, 2OH, D2O exch.), 3.80 (s, 3 H, OCH3), 3.85
CH2), 74.19 (2 CϪOH), 125.8 (4 Ar-C), 127.4 (2 Ar-C), 128.4 (4 (m, 2 H, CH2), 4.85 (dd, J ϭ 3.8, 8.7 Hz, 1 H, CH), 6.88 (d, J ϭ
Ar-C), 144.7 (2 Ar-Cq) ppm. anti-5h:[29b] 13C NMR (CDCl3): δ ϭ
22.08 (CH2), 38.73 (2 CH2), 74.31 (2 CϪOH), 125.8 (4 ArϪC),
127.4 (2 ArϪC), 128.4 (4 ArϪC), 144.7 (2 Ar-Cq) ppm.
8.7 Hz, 2 H, Ar H), 7.25 (d, J ϭ 8.7 Hz, 2 H, Ar H) ppm.
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2-Methyl-1-phenyl-1,3-propanediol (5n): The H NMR spectrum of
the crude residue showed the presence of 5n as a mixture of two
isomers (syn/anti, 70:30) which were separated by thin layer chro-
matography (CHCl3/MeOH, 9:1). syn-5n[36] (0.49 g, 60%, pale yel-
1,6-Diphenyl-1,6-hexanediol (5i): Because of the low solubility of
the substrate, the reduction was performed on 2.5 mmol of 4i, dis-
solved in MeOH (40 mL) and CH3CN (20 mL). After the usual
workup, 5i was recovered in quantitative yield (0.67 g, 1H NMR
purity Ͼ 95%) as a white solid melting at 118Ϫ120 °C. The 1H
NMR spectrum, run at 400 MHz, showed the presence of a 1:1
1
low oil): H NMR (CDCl3): δ ϭ 0.81 (d, J ϭ 6.9 Hz, 3 H, CH3),
2.04 (m, 1 H, CH), 3.0 (s, 2 H, 2 OH, D2O exch.), 3.62 (ABX
system, J ϭ 10.9, 5.9, 4.9 Hz, 2 H, CH2), 4.91 (d, J ϭ 3.5 Hz, 1 H,
CH), 7.2Ϫ7.4 (5 H, Ar H, m). anti-5n[36] (0.21 g, 26%, pale yellow
1
1
mixture of the two isomers: H NMR (CDCl3): δ ϭ 1.2Ϫ1.5 (m, 4
oil): H NMR (CDCl3): δ ϭ 0.68 (d, J ϭ 7.4 Hz, 3 H, CH3, 2.04
H, 2 CH2), 1.6Ϫ1.8 (m, 4 H, 2 CH2), 1.82 (s, 2 H, 2 OH, D2O
exch.), 4.630 (dd, J ϭ 5.8. 7.3 Hz, 2 H, 2 CH, meso isomer), 4.636
(dd, J ϭ 6.0, 7.5. Hz, 2 H, 2CH, dl isomer), 7.2Ϫ7.4 (m, 10 H, Ph
H) ppm. The crude 5i, dissolved in hot CHCl3, afforded a crop of
pure dl isomer on standing overnight: M.p. 131Ϫ133 °C (ref.[29b]
(m, 1 H, CH), 3.0 (s, 2 H, 2 OH, D2O exch.), 3.65 (dd, J ϭ 10.9,
7.4 Hz, 1 H, CH2), 3.73 (dd, J ϭ 10.9, 3.9 Hz, 1 H, CH2), 4.50 (d,
J ϭ 8.4 Hz, 1 H, CH), 7.2Ϫ7.4 (m, 5 H, Ar H).
Methyl 3-Hydroxy-3-phenylpropanoate (5o): After workup, 5o was
recovered in quantitative yield (0.90 g) as an oil and identified by
comparison with the spectroscopic data reported in the literat-
ure.[37]
1
132Ϫ134 °C from MeOH), which allowed the above H NMR as-
signment. The 13C NMR spectra of the two isomers were identical:
13C NMR (CDCl3): δ ϭ 25.5 (2 CH2), 38.8 (2 CH2), 74.5 (2 CH),
125.8 (2 Ar-C), 127.5 (Ar-C), 128.4 (2 Ar-C), 144.7 (Ar-Cq) ppm.
IR (KBr): ν˜ ϭ 3360, 2941, 2857, 1455, 1385, 1017, 761 cmϪ1. MS
(EI): m/z (%) ϭ 234 (3) [Mϩ·Ϫ 2 H2O], 146 (71), 130 (21), 117 (52),
107 (73), 105 (24), 104 (51), 91 (25), 79 (100), 77 (60).
5-Phenyldihydrofuran-2-one (5p): The reaction mixture was acidi-
fied with an HCl solution (1.0 ) and then extracted with EtOAc
(3 ϫ 50 mL). Upon evaporation of the solvent in vacuo, 5p was
1
recovered in quantitative yield (0.80 g, H NMR purity Ͼ 95%) as
an oil that solidified on standing, m.p. 36Ϫ37 °C. The spectro-
scopic data were identical to those of an authentic commercial
sample (Aldrich).
Indan-1,3-diol (5j): After workup, 5j was recovered in quantitative
yield (0.75 g) as a white, solid mixture of two isomers (cis/trans ϭ
60:40) as shown by H NMR. Two recrystallizations of the crude
1
5j from hot EtOAc afforded two crops (0.35 g) of analytically pure
cis-5j as white crystals, m.p. 195 °C. H NMR (CDCl3 ϩ DMSO):
6-Phenyltetrahydropyran-2-one (5q): After workup as for 5p, 5q was
1
1
recovered in quantitative yield (0.88 g, H NMR purity Ͼ 95%) as
δ ϭ 1.60 (dt, J ϭ 12.3, 7.8 Hz,1 H, CH2,), 2.81 (dt, J ϭ 12.3,
7.3 Hz, 1 H, CH2), 4.85 (2 t, J ϭ 7.8, 7.3 Hz, 2 H, 2 CH), 7.25 (m,
2 H, Ar H), 7.33 (m, 2 H, Ar H) ppm. 13C NMR (DMSO): δ ϭ
46.4 (CH2), 69.9 (2 CϪOH), 123.1 (2 Ar-C), 126.8 (2 Ar-C), 145.0
(2 Ar-Cq) ppm. IR (KBr): ν˜ ϭ 3311, 1324, 1038, 767 cmϪ1. MS
(EI, 70 eV): m/z (%) ϭ 150 (22) [Mϩ], 132 (95), 131 (65), 104 (100),
103 (58), 77 (83). HRMS (C9H10O2): calcd. 150.06808; found
150.06810. All efforts to obtain analytically pure trans-5j were un-
successful: 1H NMR (CDCl3 ϩ DMSO): δ ϭ 2.12 (2 t, J ϭ 5.6,
5.0 Hz, 2 H, CH2), 5.18 (2 t, J ϭ 5.6, 5.0 Hz, 2 H, 2 CH), 7.26 (m,
2 H, Ar H), 7.33 (m, 2 H, Ar H) ppm.
an oil that slowly solidified, m.p. 73Ϫ75 °C (ref.[38] 74Ϫ76). The
spectroscopic data were identical to those reported in the literat-
ure.[39]
3-Hydroxy-3-phenylpropionanilide (5r): After workup, 5r was reco-
vered in quantitative yield (1.20 g, 1H NMR purity Ͼ 95%) as a
white solid, m.p. 152 °C (CHCl3). 1H NMR (DMSO): δ ϭ 2.61
(dd, J ϭ 14.1, 4.8 Hz, 1 H, CH2), 2.71 (dd, J ϭ 14.1, 8.8 Hz, 1 H,
CH2), 5.06 (m, after D2O exchange dd, J ϭ 8.8, 4.8 Hz, 1 H, CH),
5.55 (d, J ϭ 4.1 Hz, D2O exch., 1 H, OH), 7.1 (m, 1 H, Ph H), 7.3
(m, 7 H, Ph H), 7.6 (m, 2 H, Ph H), 9.9 (D2O exch., 1 H, NH)
ppm. 13C NMR (DMSO): δ ϭ 47.0 (CH2), 69.7 (CH), 118.9 (2 Ar-
C), 123.0 (Ar-C), 125.6 (2 Ar-C), 126.9 (Ar-C), 128.0 (2 ArϪC),
128.6 (2 ArϪC), 139.1 (Ar-Cq), 145.3 (Ar-Cp), 169.1 (CO) ppm. IR
(KBr): ν˜ ϭ 3296, 1664, 1605, 1558, 1443, 752 cmϪ1. MS (EI): m/z
(%) ϭ 241 (10) [Mϩ], 107 (10), 104 (11), 93 (100), 79 (32), 77 (50),
65 (20). C15H15NO2 (241.3): calcd. C 74.67, H 6.27; found C 74.52,
H 6.30.
1-Phenyl-1,3-propanediol (5k): After workup and purification by
flash column chromatography (hexane/EtOAc, 7:3), 5k was reco-
vered as an oil (0.66 g, 87%), which was identified by comparison
1
of the H and 13C NMR spectra with those reported in the literat-
ure.[34]
1-(4-Chlorophenyl)-1,3-propanediol (5l): After workup and purifica-
tion of the crude residue by flash column chromatography (hexane/
EtOAc, 6:4), 5l was recovered as a pale yellow oil (0.79 g, 85%): 1H
NMR (CDCl3): δ ϭ 1.90 (m, 2 H, CH2), 3.40 (s, br, 2 H, 2 OH,
D2O exch.), 3.80 (2 dd, J ϭ 1.9, 4.6 and 1.2, 5.8 Hz, 2 H, CH2OH),
4.88 (dd, J ϭ 4.6, 8.1 Hz, 1 H, CHOH), 7.2Ϫ7.4 (m, 4 H, Ar H)
ppm. 13C NMR (CDCl3): δ ϭ 40.3 (CH2), 61.0 (CH2OH), 73.2
(CHOH), 127 (2 Ar-C), 128.5 (2 Ar-C), 133.1 (Ar-Cq), 142.7 (Ar-
3,3-Dimethoxy-1-phenylpropan-1-ol (8k): The crude 8k (0.84 g,
86%, pale yellow oil) was not subjected to further purification (1H
1
NMR purity Ͼ 95%). H NMR (CDCl3): δ ϭ 1.93Ϫ2.15 (m, 2 H,
CH2), 2.6 (s, br, D2O exch., 1 H, OH), 3.36 (s, 3 H, OCH3), 3.40
(s, 3 H, OCH3), 4.57 (t, J ϭ 5.4 Hz, 1 H, CH), 4.89 (dd, J ϭ 3.5,
8.9 Hz, 1 H, CH), 7.35 (m, 5 H, Ar H) ppm. 13C NMR (CDCl3):
δ ϭ 41.43 (CH2), 50.61 (OCH3), 53.61 (OCH3), 70.75 (CHOH),
103.33 (CH), 125.68 (2 Ar-C), 127.36 (2 Ar-C), 128.36 (Ar-C),
143.92 (Ar-Cq) ppm. IR (film): ν˜ ϭ 3433, 2935, 1453, 1126, 1056,
702 cmϪ1. MS (EI): m/z (%) ϭ 165 (25) [Mϩ Ϫ OCH3], 135 (20),
121 (45), 105 (100), 75 (83), HRMS (C11H16O3): calcd. 196.1099;
found 196.1095.
Cq).) ppm. IR (neat): ν˜ ϭ 3345, 1492, 1091, 1052, 1014, 828 cmϪ1
.
MS (EI, 70 eV): m/z (%) ϭ 188 (16) [Mϩ], 186 (44) [Mϩ], 169 (10),
143 (30), 141 (100), 133 (16), 113 (10), 77 (25). HRMS
(C9H11ClO2): calcd. 186.0448; found 186.0445.
1-(4-Methoxyphenyl)-1,3-propanediol (5m): After purification by
flash column chromatography (hexane/EtOAc, 7:3), 5m was reco-
vered (0.78 g, 86%) as a yellow liquid, which crystallized on
1-(4-Chlorophenyl)-3,3-dimethoxypropan-1-ol (8l): The crude 8l
1
standing, m.p. 34Ϫ36 °C. H NMR[35] (CDCl3): δ ϭ 2.0 (m, 2 H, (0.98 g, 85%, pale yellow oil) was not subjected to further purifica-
Eur. J. Org. Chem. 2002, 3326Ϫ3335
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