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D. Zerla et al. / Tetrahedron: Asymmetry 25 (2014) 1031–1037
4.2.3. (R)-(À)-N-2-Dimethyl-5,6,7,8-tetrahydroquinolin-8-amine
((R)-NHMe-Me-CAMPY) L4
4.4. Synthesis of the substrates
To a solution of (R)-Me-CAMPY L2 (121 mg, 0.75 mmol) in THF
(5 mL), aqueous K2CO3 (1.5 mL, 1 M) and ethyl chloroformate
(0.11 mL, 1.1 mmol) were added at 0 °C. The solution was warmed
to room temperature and stirred for 2.5 h. The organic phase was
dried and the solvent was removed in vacuo. The crude oil
obtained was dissolved in anhydrous THF (5 mL) and added drop-
wise into a suspension of LiAlH4 (46 mg, 1.2 mmol) in anhydrous
THF (5 mL) at 0 °C, stirred at room temperature for 1 h and refluxed
for 2 h. The reaction mixture was quenched by adding THF, aque-
ous KOH and extracted with diethyl ether (3 Â 10 mL). The crude
product was purified by Kugelrohr distillation to obtain a pale yel-
low oil (99 mg, 0.56 mmol; 56% yield). 1H NMR (CDCl3, 300 MHz,
25 °C): d = 1.56–1.74 (m, 1H), 1.81–1.95 (m, 2H), 2.08 (s, 3H),
2.52 (s, 3H), 2.55–2.68 (m, 1H), 2.77 (t, J = 6.5 Hz, 2H), 4.76 (dd,
J = 9.6, 4.9 Hz, 1H), 6.70 (br, 1H), 7.00 (d, J = 7.9 Hz, 1H), 7.33 (d,
J = 7.9 Hz, 1H) ppm; 13C NMR (CDCl3, 75 MHz, 25 °C): d = 20.29,
24.13, 24.35, 28.14, 29.56, 51.64, 122.49, 130.15, 137.96, 154.62,
4.4.1. Enzymatic synthesis of rac-2-benzoylbutanenitrile 4
Commercial Baker’s yeast (50 g/L) was suspended in a phos-
phate buffer (200 mL, 0.1 M, pH 7) containing 50 g/L of glucose
and 5 g/L of the substrate 1 was added. The biotransformation sys-
tem was shaken with a mechanical stirrer at 28 °C. When total con-
version was achieved, the cells were separated by centrifugation.
Both the aqueous phases and the cell mixture were extracted with
diethyl ether (3 Â 50 mL), dried over Na2SO4 and the solvent was
removed in vacuo. The crude product was purified by flash chro-
matography (CH2Cl2/hexane/ethyl acetate = 4:1:1) to give 860 mg
of 4 (86% yield). 1H NMR (CDCl3, 300 MHz, 25 °C): d = 1.16 (t,
J = 7.7 Hz, 3 H), 2.02–2.15 (m, 2H), 4.30 (dd, J = 6.2, 4.3 Hz, 1H),
7.49–7.56 (m, 2H), 7.65 (d, J = 7.6 Hz, 1H) 7.95 (d, J = 6.7 Hz, 2H)
ppm; 13C NMR (CDCl3, 75 MHz, 25 °C): d = 11.71, 23.77, 41.69,
117.41, 128.92–134.63, 170.91, 190.97 ppm. FTIR
m = 3467, 2975,
2936, 2249, 1694, 1597, 1449, 1265, 1233, 1208, 1000, 696 cmÀ1
.
MS (ESI) of C11H11NO (m/z): calcd 173.2, found 196.1 [M+Na+].
155.75 ppm. FTIR
m
= 3330, 2940, 2860, 2785, 1707, 1596, 1574,
Compound 4a: 1H NMR (CDCl3, 300 MHz, 25 °C): d = 1.09 (t,
J = 7.7 Hz, 3H, anti), d = 1.17 (t, J = 7.6 Hz, 3H, syn), 1.51–1.69 (m,
2H), 2.76–2.83 (m, 2H, anti), 2.87–2.95 (m, 2H, syn), 4.79 (d,
J = 6.2 Hz, 1H, anti), 4.83 (d, J = 6.6 Hz, 1H, syn), 7.33–7.56 (m, 5H)
ppm; 13C NMR (CDCl3, 75 MHz, 25 °C): d = 9.84 (syn), 10.38 (anti),
24.86 (anti), 25.87 (syn), 76.86 (syn), 77.46 (anti), 127.04, 128.05
(anti), 128.22 (syn), 128.55 (anti), 128.69 (syn), 140.61 (anti)
1471, 1444, 1258, 1147, 1119, 1105, 1035, 850, 813, 783 cmÀ1
.
MS (ESI) of C11H16N2 (m/z): calcd 176.1, found 177.2 [M+1]+.
[a
]
D
20 = À52.5 (c 1, CH2Cl2).
4.3. General procedure for the synthesis of [Cp⁄Ir(H2O)(L)]SO4
141.42 (syn) ppm. FTIR
m = 3390, 2964, 1494, 1453, 160, 1103,
The complexes were prepared according to
procedure.18
a literature
1038, 702 cmÀ1. MS (ESI) of C11H11NO (m/z): calcd 175.1, found
198.3 [M+Na+]. Yield was evaluated by 1H NMR analysis. HPLC
data: OD-H Chiralcel, eluent: hexane: 2-propanol = 95:5,
flow = 0.8 mL/min, k = 216 nm. rt: (R, S) = 25.6 min, (S, S) = 26.5
min, (S, R) = 34.6 min, (R, R) = 36.0 min.
4.3.1. [Cp⁄Ir(H2O)(L1)]SO4
1H NMR (D2O, 300 MHz, 25 °C): d = 1.63 (m, 2H), 1.72 (s, 15H),
2.04–2.06 (m, 1H), 2.45–2.48 (m, 1H), 2.85–2.99 (m, 2 H), 4.02–
4.13 (m, 1H), 7.58 (dd, J = 5.9 Hz,1 H), 7.80 (d, J = 7.9 Hz,1 H),
8.70 (d, J = 5.5 Hz, 1H) ppm; 13C NMR (D2O, 75 MHz, 25 °C):
d = 10.24, 20.11, 29.39, 37.57, 51.79, 122.34, 132.17, 137.28,
147.39, 155.12 ppm. MS (ESI) of C17H27IrN2 [MÀSO4ÀH2OÀH] (m/
z): calcd 475.7, found 475.4.
4.4.2. Ethyl-2-(benzamidomethyl)-3-oxo-phenylpropanoate 10
The substrate was prepared according to a literature proce-
dure.26 1H NMR (CDCl3, 300 MHz, 25 °C): d = 1.18 (t, J = 6.9 Hz,
3H), 3.93–3.97 (m, 2H), 4.09–4.16 (m, 2H), 4.19 (q, J = 6.9 Hz,
2H), 4.87 (dd, J = 5.5, 3.7 Hz, 1H), 6.73 (br, 1H), 7.42–7.62 (m,
2H), 7.71 (dd, J = 8.0, 1.5 Hz, 4H), 8.10 (dd, J = 5.1, 2.2 Hz, 4H)
ppm; 13C NMR (CDCl3, 75 MHz, 25 °C): d = 14.1, 39.2, 53.7, 62.03,
127.1–135.9, 167.9 (isomer), 169.2 (isomer), 194.8 ppm. FTIR
4.3.2. [Cp⁄Ir(H2O)(L2)]SO4
1H NMR (D2O, 300 MHz, 25 °C): d = 1.52 (s, 15H), 1.62–1.66 (m,
2H), 1.74–1.85 (m, 2H), 2.28–2.32 (m, 2H), 2.70 (s, 3H), 4.58–4.66
(m, 1H), 7.35 (d, J = 7.7 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H) ppm; 13C
NMR (D2O, 75 MHz, 25 °C): d = 8.76, 20.12, 26.61, 26.83, 31.74,
62.37, 87.85, 126.62, 133.89, 141.28, 157.86, 158.02 ppm. MS (ESI)
of C20H29IrN2 [MÀSO4ÀH2OÀH] (m/z): calcd 489.7, found 489.6.
m
= 3334, 1961, 1734, 1679, 1637, 1534, 1311, 1250, 1211, 1198,
1078, 694 cmÀ1. MS (ESI) of C19H19NO4 (m/z): calcd 325.1, found
348.5 [M+Na+].
Compound 10a: 1H NMR (CDCl3, 300 MHz, 25 °C): d = 1.01 (t,
J = 7.0 Hz, 3H), 2.93–3.01 (m, 1H, syn), 3.15–3.24 (m, 1H, anti),
3.61–3.69 (m, 2H), 3.98 (q, J = 7.0 Hz, 2H), 4.12–4.19 (m, 2H),
4.95 (d, J = 7.3 Hz, 1H, anti), 4.96 (d, J = 7.3 Hz, 1H, syn), 6.72 (br,
1H), 7.29–7.53 (m, 4H), 7.77 (dd, J = 8.0, 1.5 Hz, 4H) ppm; 13C
NMR (CDCl3, 75 MHz, 25 °C): d = 14.0, 37.9 (syn), 38.0 (anti), 53.0,
4.3.3. [Cp⁄Ir(H2O)(L3)]SO4
1H NMR (D2O, 300 MHz, 25 °C): d = 1.54 (s, 15H), 1.66–1.69 (m,
2H), 1.75–1.78 (m, 2H), 2.54–2.69 (m, 2H), 3.10 (d, J = 6.1 Hz, 3H),
3.93–4.2 (m, 1H), 7.38 (dd, J = 7.7 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H),
8.51 (d, J = 5.5 Hz, 1H) ppm; 13C NMR (D2O, 75 MHz, 25 °C):
d = 8.46, 14.07, 22.35, 23.38, 28.79, 54.09, 116.39, 126.99, 131.42,
141.39, 151.76 ppm. MS (ESI) of C20H29IrN2 [MÀSO4ÀH2OÀH] (m/
z): calcd 489.7, found 489.5.
61.1, 72.6, 126.4–132.0, 164.31, 173.5 ppm. FTIR
m = 3364, 1948,
1724, 1649, 1607, 1535, 1301, 1246, 1111, 828 cmÀ1. MS (ESI) of
C
19H21NO4 (m/z): calcd 327.1, found 350.4 [M+Na+]. (2R,3R)
[a
]
20 = +33.2 (c 0.15, CHCl3); (2S,3S) [
a
]
D
20 = À11.0 (c 0.18, CHCl3);
D
(2R,3S) [
a
]
D
20 = À11.3 (c 0.12, CHCl3); Yield was evaluated by 1H
NMR analysis. HPLC data: AD Chiralpak, eluent hexane/2-propa-
nol = 90:10, flow = 0.6 mL/min, k = 230 nm. rt: (R, R) = 35.1 min,
(S, S) = 37.1 min, (S, R) = 49.8 min, (R, S) = 68.8 min.
4.3.4. [Cp⁄Ir(H2O)(L4)]SO4
1H NMR (D2O, 300 MHz, 25 °C): d = 1.68 (s, 15H), 1.94–1.97 (m,
2H), 2.48–2.50 (m, 2H), 2.62–2.65 (m, 2H), 2.70 (s, 3H), 3.14 (d,
J = 5.9 Hz, 3H), 3.99–4.04 (m, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.60 (d,
J = 8.1 Hz, 1H) ppm; 13C NMR (D2O, 75 MHz, 25 °C): d = 8.81,
19.78, 26.58, 38.77, 69.15, 88.43, 126.87, 134.00, 141.43, 156.67,
158.30 ppm. MS (ESI) of C21H31IrN2 [MÀSO4ÀH2OÀH] (m/z): calcd
503.7, found 503.4.
4.4.3. Ethyl 2-(benzamidomethyl)-3-(4-methoxyphenyl)-3-oxo-
propanoate 11
The substrate was prepared according to the literature by start-
ing from ethyl 3-(4-methoxyphenyl)-3-oxopropanoate.26 1H NMR
(CDCl3, 300 MHz, 25 °C) d = 1.22 (t, J = 7.3 Hz, 3H); 3.78 (s, 3H);
3.86–4.93 (m, 1H); 4.01–4.13 (m, 1H); 4.15 (q, J = 5.9 Hz, 2H);
4.88 (dd, J = 5.9, 3.8 Hz, 1H); 6.88 (d, J = 8.8 Hz, 2H); 7.37–7.67