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M. Azizoglu et al. / Tetrahedron: Asymmetry 27 (2016) 614–622
The ee values were determined were using chiral HPLC on a
1H, PhCH2), B part of AB spin system: 2.99 (dd, J = 6.0 and
13.6 Hz, 1H, PhCH2), 3.51–3.58 (m, 2H, CH2OH), 4.24–4.32 (m,
1H, ACHANH), 4.99 (t, J = 5.0 Hz, 1H, OH), 7.15–7.19 (m, 1H, ArAH),
7.25–7.37 (m, 6H, ArAH), 7.48–7.51 (m, 1H, ArAH), 7.73 (d,
J = 8.3 Hz, 1H, ArAH), 7.86 (d, J = 8.2 Hz, 1H, ArAH), 8.54 (s, 1H,
ArAH), 8.86 (d, J = 8.3 Hz, 1H, NH), 11.95 (s, 1H, ArAOH). 13C
NMR (DMSO-d6): d (ppm) 37.00 (PhCH2), 53.54 (PhCH2CH), 62.74
(CH2OH), 111.12 (ArAC), 119.21 (ArAC), 124.14 (ArAC), 126.21
(ArAC), 126.53 (ArAC), 127.05 (ArAC), 128.67 (ArA2C, overlapped
from HETCOR), 129.15 (ArAC), 129.59 (ArAC), 130.23 (ArAC),
136.41 (ArAC), 139.42 (ArAC), 155.68 (ArACAOH), 167.9 (C@O).
Anal. Calcd for C20H19NO3 (Mw: 321 g/mol) C, 74.76; H, 5.92; N,
4.36. Found: C, 74.80; H, 5.90; N, 4.40.
DaicelÒChiralcel OD-H and Chiralcel AS-3 column on BIORAD
model 2800 pump and BIORAD UV-detector. The absolute configu-
ration of the major enantiomer was assigned according to the sign
of the specific rotation based on literature values.
It is known that amides can be reduced to amino alcohols by
BH3 and many applications involve in situ preparation of amino
alcohols from lactams.42 However, the transformation can be
achieved with high concentrations of BH3. We did not observe
the formation of amino alcohols from amides under experimental
conditions (low BH3 concentration). However, to investigate the
possible role of amino alcohols on the selectivity, we isolated the
corresponding amine from the reduction of amide 1 in the pres-
ence of a high concentration of BH3 and tested its effect on the
reduction of acetophenone. The enantioselectivity by this amine
was very low (15%) compared with the parent amide (60%).
4.2.3. 3-Hydroxy-N-[(2S)-1-hydroxy-3-methyl-1,1-diphenylbutane-
2-yl]naphthalene-2-carboxamide 3
Amide 3 was prepared as described above for 1 starting from
3-hydroxy-2-naphthoic acid (1.00 g, 5.31 mmol), dry THF (5 mL),
N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride
(EDCI) (1.53 g, 7.965 mmol), HOBt (0.83 g, 5.416 mmol) and (2S)-
4.2. Synthesis
4.2.1. 3-Hydroxy-N-[(2S)-2-hydroxy-1-phenylethyl]naphthalene-
2-carboxamide 1
(ꢁ)-2-amino-3-methyl-1,1-diphenylbutane-1-ol
(1.49 g,
3-Hydroxy-2-naphthoic acid (1.0 g, 5.31 mmol) was dissolved
in dry THF (10 mL). The mixture was cooled to ꢁ15 °C, then N-
5.84 mmol). The crude product was purified by column chro-
matography through silica gel, eluted with 20:1 EtOAc:MeOH sol-
vent mixture (TLC Rf = 0.34), then recrystallized from EtOAc:
Hexane (3:1) mixture to give amide 3 as a yellow solid (1.51 g,
(3-dimethylaminopropyl)-N0-ethylcarbodiimide
hydrochloride
(EDCI) (1.53 g, 7.965 mmol), and HOBt (0.83 g, 5.416 mmol) were
added. solution of (2S)-2-amino-2-phenylethanol (0.80 g,
A
67%) yield. Mp: 173–176 °C, [
mmax): 3350, 3057, 3030, 2960, 1648, 1616, 1520, 1447, 1305,
a
]
20 = ꢁ21.8 (c 1, CHCl3), IR (KBr,
D
5.841 mmol) in dry THF (5 mL) was then introduced by the drop-
wise addition over a period of 0.5 h under an argon atmosphere
at the same temperature. After the addition was completed, the
mixture was allowed to the warm to room temperature and stirred
for an appropriate time (monitored by TLC). When the reaction was
completed, the THF was removed under reduced pressure. Water
(10 mL) was then added. The mixture was extracted with CHCl3
(2 ꢂ 10 mL) and dried over anhydrous Na2SO4. The organic phase
was evaporated under reduced pressure to give the crude product,
which was purified by column chromatography through silica gel,
eluted with 1:1 hexane:ethyl acetate solvent mixture (TLC
Rf = 0.45), to give amide 1 as a white solid (0.93 g, 90%) yield.
1226, 1172, 1061, 746, 700 cmꢁ1 1H NMR (DMSO-d6): d (ppm)
,
0.84 (d, J = 6.8 Hz, 3H, ACH3), 1.02 (d, J = 6.8 Hz, 3H, ACH3), 1.83–
1.89 (m, 1H, ANHCHA), 5.22 (dd, J = 1.8 and 10.0 Hz, 1H, CH(i-
Pro)), 6.04 (s, 1H, OH), 7.05–7.62 (m, 13H, ArAH), 7.71 (d,
J = 8.2 Hz, 1H, ArAH), 7.86 (d, J = 8.2 Hz, 1H, ArAH), 8.31 (s, 1H,
ArAH), 8.62 (d, J = 10.0 Hz, 1H, NH), 11.37 (s, 1H, ArAOH). 13C
NMR (DMSO-d6): d (ppm) 18.59 (ACH3), 23.51 (ACH3), 29.30
(CHNH), 58.51 (CH(i-Pro)), 81.51 (ACAOH), 110.86 (ArAC),
121.47 (ArAC), 124.12 (ArAC), 125.82 (ArAC), 126.12 (ArAC),
126.22 (ArAC), 126.68 (ArAC), 126.75 (ArAC), 127.20 (ArAC),
128.18 (ArAC), 128.46 (ArAC), 128.55 (ArAC), 129.12 (ArAC),
130.99 (ArAC), 136.05 (ArAC), 146.88 (ArAC), 147.88 (ArAC),
154.30 (ArACAOH), 166.81 (C@O). Anal. Calcd for C28H27NO3
(Mw: 425 g/mol): C, 79.05; H, 6.35; N, 3.29. Found: C, 79.10; H,
6.40; N, 3.45.
Mp: 131–133 °C, [
a]
20 = ꢁ188.9 (c 1, CHCl3). IR (KBr,
mmax): 3321,
D
3025, 2933, 1644, 1623, 1558, 1449, 1357, 1236, 1089, 1038,
871, 743, 696 cmꢁ1,1H NMR (DMSO-d6): d (ppm) 3.76–3.79 (m,
2H, CH2), 5.10 (app. t, J = 5.2 Hz, 1H, OH), 5.17 (app. q, J = 6.8 Hz,
1H, PhCH), 7.25–7.53 (m, 8H, ArAH), 7.75 (d, J = 8.3 Hz, 1H, ArAH),
7.90 (d, J = 9.5 Hz, 1H, ArAH), 8.64 (s, 1H, ArAH), 9.35 (d, J = 7.8 Hz,
1H, NH), 11.87 (s, 1H, ArAOH).13C NMR (DMSO-d6): d (ppm) 56.13
(PhCH), 64.84 (CH2OH), 111.16 (ArAC), 119.60 (ArAC,), 124.19
(ArAC), 126.24 (ArAC), 127.16 (ArAC), 127.39 (ArAC), 127.46
(ArAC), 128.71 (ArA2C, overlapped from HETCOR), 129.19 (ArAC),
130.64 (ArAC), 136.44 (ArAC), 141.28 (ArAC), 155.41 (ArACAOH),
167.74 (C@O). Anal. Calcd for C19H17NO3 (Mw: 307 g/mol): C,
74.26; H, 5.53; N, 4.56. Found: C, 74.35; H, 5.50; N, 4.59.
4.2.4. 3-Hydroxy-N-[(2S)-2-hydroxy-1,2,2-triphenylethyl]naph-
thalene-2-carboxamide 4
Amide 4 was prepared as described above for 1 starting from
3-hydroxy-2-naphthoic acid(1.00 g, 5.31 mmol), dry THF (5 mL),
N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride
(EDCI) (1.53 g, 7.965 mmol), HOBt (0.83 g, 5.416 mmol) and (S)-
(ꢁ)-2-amino-1,1,2-triphenylethanol (1.68 g, 5.84 mmol). The crude
product was recrystallized from ethyl acetate to give amide 4 as a
yellow solid (1.42 g, 59%) yield. Mp: 238.7–241.2 °C, [
(c 1, CHCl3), IR (KBr,
a
]
20 = ꢁ388.2
D
4.2.2. 3-Hydroxy-N-[(2S)-1-hydroxy-3-phenylpropan-2yl]naph-
thalene-2-carboxamide 2
m
max): 3444, 3321, 3289, 3086, 3005, 1655,
1616, 1550, 1448, 1354, 1227, 1150, 1079, 733, 697 cmꢁ1 1H
,
Amide 2 was prepared as described above for 1 starting from
3-hydroxy-2-naphthoic acid (1.00 g, 5.31 mmol), dry THF (5 mL),
N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride
(EDCI) (1.53 g, 7.965 mmol), HOBt (0.83 g, 5.416 mmol) and (2S)-
2-amino-3-phenyl-1-propanol (0.88 g, 5.841 mmol). The crude
product was purified by column chromatography through silica
gel, eluted with 1:1 hexane:ethyl acetate solvent mixture (TLC
Rf = 0.33), to give amide 2 as a white solid (1.15 g, 68%) yield.
NMR (DMSO-d6): d (ppm) 6.15 (d, J = 9.2 Hz, 1H, PhCH), 6.34 (s,
1H, OH), 7.05–7.86 (m, 20 H, ArAH), 8.34 (s, 1H, ArAH), 9.45 (d,
J = 9.2 Hz, 1H, NH), 11.34 (s, 1H, ArAOH). 13C NMR (DMSO-d6): d
(ppm) 59.68 (ArACH), 80.67 (aliphatic ipso C), 110.95 (ArAC),
121.19 (ArAC), 124.20 (ArAC), 126.12 (ArAC), 126.66 (ArAC),
126.70 (ArAC), 126.83 (ArAC), 126.98 (ArAC), 127.14 (ArAC),
127.23 (ArAC), 127.40 (ArAC), 127.83 (ArAC), 128.36 (ArAC),
128.55 (ArAC), 129.17 (ArAC), 129.79 (ArAC), 131.30 (ArAC),
136.06 (ArAC), 140.13 (ArAC), 145.61 (ArAC), 146.93 (ArAC),
154.27 (ArACAOH), 165.50 (C@O). Anal. Calcd for C31H25NO3
(Mw: 459 g/mol): C, 81.00; H, 5.44; N, 3.05. Found: C, 79.95; H,
5.50; N, 3.10.
Mp: 127–130 °C, [
a]
D
20 = ꢁ91.6 (c 1, CHCl3). IR (KBr,
mmax): 3552,
3488, 3368, 3325, 3053, 3023, 2925, 1653, 1618, 1548, 1466,
,
1300, 1227, 1171, 1037, 869, 744, 699 cmꢁ1 1H NMR (DMSO-d6):
d (ppm) A part of AB spin system: 2.88 (dd, J = 8.0 and 13.6 Hz,