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N. A. Cortez et al. / Tetrahedron: Asymmetry 24 (2013) 1297–1302
Table 1
Asymmetric transfer hydrogenation of ketones with Ru(arene)-5a
L*=
O2
S
O
OH
R
H
NH
NH2
[RuCl2(p-cymene)]2, L*
iPrOH, KOH
Ar
R
Ar
5
Ketone
t (h)
eeb (%)
>99
Yield (%)
95
Abs. Conf.c
O
O
H
N
16
(R)20
O
O
H3CO
H3CO
H
N
16
16
>99
>99
90
85
(R)20
O
O
ND
N
H
a
b
c
25 °C using a mixture of isopropanol/KOH.
Measured by HPLC analysis of the alcohol with chiral capillary column Whelk-01, (250 mm ꢁ 4.6 mm ꢁ 5
lm).
Absolute configurations were assigned by comparing the specific rotations with the literature values.
extracted with dichloromethane (3 ꢁ 10 mL). The dichloromethane
layers were combined, dried over anhydrous MgSO4, filtered, con-
centrated under reduced pressure, and then passed through a short
silica gel path. The residue containing the alcohol was acetylated
using acetic anhydride.
O
H
N
O
H3CO
For the ATH of ketones in water, a mixture of the metal precur-
sor [RhCl2(Cp⁄)]2 (0.0039 mmol) and the chiral ligand
(0.00075 mmol) was heated in water (2mL) at 40 °C for 1 h in air.
HCOONa (5.7 mmol) and the substrate were subsequently added
(1.14 mmol). The reaction mixture was stirred at 40 °C in air for
the time indicated in Table 2 for each individual reaction. The reac-
tion mixture was extracted with ether (3 ꢁ 10 mL). The ether lay-
ers were combined, dried over anhydrous MgSO4, filtered and
concentrated under reduced pressure. The residue containing the
alcohol was acetylated using acetic anhydride.
4.4. N-[2-(4-Methoxyphenyl)-2-keto-ethyl)]-cinnamamide 7
White solid; (0.40 g, 85%); mp 141–143 °C. IR (KBr) 3326, 3052,
2928, 2832, 1657, 1613, 1514, 1363, 1242, 1173, 1027 cmꢀ1 1H
.
NMR (200 MHz, CDCl3)
d 8.0 (d, J = 8.8 Hz, 2H), 7.68 (d,
J = 16.0 Hz, 1H), 7.56–7.51 (m, 1H), 7.39–7.36 (m, 3H), 6.97 (d,
J = 9.0 Hz, 2H), 6.57 (d, J = 14.2 Hz, 1H), 4.85 (d, J = 4.4 Hz, 2H),
3.89 (s, 3H). 13C NMR (50 MHz, CDCl3) d 192.6, 165.9, 164.4,
141.5, 134.8, 130.4, 129.8, 128.6, 127.9, 127.4, 120.3, 114.2, 55.6,
46.3. EIMS m/z (rel intensity) 295 [M]+ (11), 278 (1), 267 (1), 250
(1), 223 (1), 207(1), 192 (1), 164 (1), 146 (5), 135 (100), 107 (12),
103 (22), 77 (34), 51 (5). Anal. Calcd for C18H17NO3: C, 73.20; H,
5.80. Found: C, 73.25; H, 5.81.
4.6. Tembamide. (R)-(-)-N-(2-Hydroxy-2-(4-methoxyphenyl) ethyl)
benzamide 13
White crystals; mp 155–157 °C; ½a D20
¼ ꢀ58:4 (c 0.5, CH3Cl). IR
ꢂ
(KBr) 3365, 3064, 2935, 2848, 1636, 1600, 1525, 1364, 1254,
1159, 1092 cmꢀ1 1H NMR (500 MHz, CDCl3) d 7.78 (d, J = 8.4 Hz,
.
O
H
N
2H), 7.52 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 7.32 (d,
J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 6.64 (sa, 1H), 4.86 (dd,
J = 3.3 and J = 7.2 Hz, 1H), 3.9–3.82 (m, 1H), 3.8 (s, 3H), 3.56–3.44
(m, 1H), 3.28 (d, J = 3.3 Hz, 1H). 13C NMR (125 MHz, CDCl3) d
168.6, 159.4, 134.2, 134.0, 131.2, 128.6, 127.1, 127.0, 114.0, 77.3,
55.3, 47.8. EIMS m/z (rel intensity) 269 [M]+ (11), 252 (1), 241
(1), 224 (1), 211 (1), 181 (1), 164 (1), 148 (1), 105 (28), 92 (13),
77 (41), 51 (11). Calcd for C16H17NO3: C, 70.83; H, 6.32. Found: C,
70.88; H, 6.37.
O
H3CO
4.5. General procedure for the ATH
A mixture of the metal precursor [(arene)RuCl2]2 (0.0039 mmol)
and the chiral ligand (0.0075 mmol) in freshly distilled 2-propanol
was stirred at 80 °C for 30 min under an argon atmosphere. A
solution of potassium hydroxide in 2-propanol was then stirred
at 50 °C for 30 min. Next, the prochiral ketone in 2-propanol was
added to the catalyst solution followed by KOH solution and stirred
at room temperature for the time indicated in Table 1 for each indi-
vidual reaction. Water was then added to the reaction mixture and
H
N
HO
H
O
H3CO