Ooka et al.
386.3 mg, 96% yield, 92% ee. The enantiomeric excess of 8c was
determined by HPLC analysis. Column, CHIRALCEL OB-H;
eluent, hexane:2-propanol ) 98:2; flow, 0.5 mL min-1; column
temp, 40 °C; tR of (R)-8c, 11.3 min (96%); tR of (S)-8c, 14.0 min
Hydrogenation of 2,2-Diethoxy-2′-acetonaphthone (7g). Condi-
tions: (S,R)-6 (1.0 mg, 1.0 µmol), 7g (239.9 mg, 0.929 mmol),
t-C4H9OK (4.4 mg, 0.039 mmol), 2-propanol (3 mL), 8 atm H2, 30
°C, 24 h. (R)-2,2-Diethoxy-1-(2′-naphthyl)ethanol [(R)-8g]: 218.9
mg, 91% yield, 97% ee. The enantiomeric excess of 8g was
determined by HPLC analysis. Column, SUMICHIRAL OA-4400;
eluent, hexane:2-propanol ) 95:5; flow, 0.5 mL min-1; column
temp, 40 °C; tR of (R)-8g, 23.4 min (98.7%); tR of (S)-8g, 26.2 min
(1.3%). [R]24D -209.8 (c 1.01, CHCl3). IR (NaCl, neat) 3457, 2976,
2895, 1370, 1122, 1065, 1014, 820, 748 cm-1. 1H NMR (400 MHz,
CDCl3) δ 1.04 (t, 3H, J ) 7.0 Hz), 1.28 (t, 3H, J ) 7.0 Hz), 3.03
(br s, 1H), 3.19-3.27 (m, 1H), 3.54-3.64 (m, 2H), 3.80-3.88 (m,
1H), 4.49 (d, 1H, J ) 6.4 Hz), 4.79 (br dd, 1H), 7.46-7.51 (m,
2H), 7.58 (dd, 1H, J ) 8.5, 1.4 Hz), 7.83-7.87 (m, 3H), 7.93 (s,
1H). 13C NMR (100 MHz, CDCl3) δ 15.0, 15.2, 63.5, 64.5, 74.7,
105.9, 125.1, 125.7, 125.8, 126.0, 127.6, 128.0, 133.0, 133.1, 137.0.
HRMS(EI+), m/z (M+) calcd 260.1412, obsd 260.1414. Anal. Calcd
for C16H20O3: C, 73.82; H, 7.74. Found: C, 73.63; H, 7.78.
Hydrogenation of 2-Methoxy-1,2-diphenyl-1-ethanone (9a). Con-
ditions: (S,R)-6 (1.2 mg, 1.2 µmol), 9a (268.2 mg, 1.19 mmol),
t-C4H9OK (11.3 mg, 0.101 mmol), 2-propanol (3 mL), 8 atm H2,
30 °C, 18 h. (1R,2S)-2-Methoxy-1,2-diphenylethanol [(1R,2S)-10a]:
257.7 mg, 95% yield (syn:anti ) 97:3), 98% ee. The enantiomeric
excess of (1R*,2S*)-10a (anti) was determined by HPLC analysis.
Column, CHIRALCEL OD-H; eluent, hexane:2-propanol ) 98:2;
flow, 0.5 mL min-1; column temp, 40 °C; tR of (1S,2R)-10a, 27.0
min (1%); tR of (1R,2S)-10a, 33.1 min (99%). [R]23D +17.9 (c 0.939,
CHCl3), (lit.31 [R]D +23.4 (c 1.6, CHCl3), 1R,2S product). Analyti-
cal data are shown in the Supporting Information.
Hydrogenation of 2-Pivaloylamino-1-phenyl-1-propanone (9c).
Conditions: (S,R)-6 (1.3 mg, 1.3 µmol), 9c (279.1 mg, 1.28 mmol),
t-C4H9OK (11.3 mg, 0.101 mmol), 2-propanol (3 mL), 8 atm H2,
30 °C, 64 h. (1R,2R)-2-Pivaloylamino-1-phenylethanol [(1R,2R)-
10c]: 256.2 mg, 88% yield (syn:anti ) 96:4), 99% ee. The
enantiomeric excess of (1R*,2R*)-10c (syn) was determined by
HPLC analysis. Column, CHIRALCEL OD-H; eluent, hexane:2-
propanol ) 90:10; flow, 0.5 mL min-1; column temp, 40 °C; tR of
(1S,2S)-10c, 11.5 min (0.6%); tR of (1R,2R)-10c, 14.0 min (99.4%).
Mp 106-107 °C (hexane), [R]22D +12.3 (c 1.34, ethanol). IR (KBr-
disk) 3422, 2973, 1615, 1450, 1211, 766, 701 cm-1. 1H NMR (270
MHz, CDCl3) δ 1.12 (s, 9H), 1.14 (d, 3H, J ) 6.9 Hz), 3.82 (br s,
1H), 4.11-4.21 (m, 1H), 4.65 (distorted t, 1H, J ) 5 Hz), 5.87 (br
d, 1H), 7.22-7.36 (m, 5H). 13C NMR (67.5 MHz, CDCl3) δ 17.4,
27.4, 38.6, 51.2, 77.3, 126.2, 127.6, 128.2, 141.8, 179.2. HRM-
S(EI+), m/z (M + H+) calcd 236.1650, obsd 236.1649. Anal. Calcd
for C14H21NO2: C, 71.46; H, 8.99; N, 5.95. Found: C, 71.59; H,
9.15; N, 5.92.
(4%). [R]28 -38.3 (c 1.05, CHCl3). IR (NaCl, neat) 3465, 2976,
D
2929, 1372, 1120, 1065, 759 cm-1. 1H NMR (400 MHz, CDCl3) δ
0.99 (t, 3H, J ) 7.0 Hz), 1.27 (t, 3H, J ) 7.0 Hz), 2.39 (s, 3H),
2.70 (d, 1H, J ) 2.2 Hz), 3.12-3.20 (m, 1H), 3.52-3.59 (m, 2H),
3.80-3.87 (m, 1H), 4.42 (d, 1H, J ) 6.6 Hz), 4.89 (dd, 1H, J )
6.6, 2.2 Hz), 7.12-7.23 (m, 3H), 7.50 (m, 2H). 13C NMR (100
MHz, CDCl3) δ 15.1, 15.3, 19.7, 63.8, 65.2, 70.7, 106.9, 125.9,
126.5, 127.5, 130.1, 136.5, 137.9. HRMS(ESI+), m/z (M + Na+)
calcd 247.1310, obsd 247.1300. Anal. Calcd for C13H20O3: C, 69.61;
H, 8.99. Found: C, 69.15; H, 9.34.
Hydrogenation of 2,2-Diethoxy-4′-methylacetophenone (7d).
Conditions: (S,R)-6 (1.6 mg, 1.6 µmol), 7d (357.9 mg, 1.61 mmol),
t-C4H9OK (10.4 mg, 0.0927 mmol), 2-propanol (4 mL), 8 atm H2,
30 °C, 4 h. (R)-2,2-Diethoxy-1-(4-methylphenyl)ethanol [(R)-8d]:
343.7 mg, 95% yield, 96% ee. The enantiomeric excess of 8d was
determined by HPLC analysis. Column, CHIRALCEL OD-H;
eluent, hexane:2-propanol ) 98:2; flow, 0.5 mL min-1; column
temp, 40 °C; tR of (S)-8d, 13.9 min (2%); tR of (R)-8d, 14.9 min
(98%). [R]28D -19.0 (c 0.922, CHCl3). IR (NaCl, neat) 3454, 2976,
2890, 1517, 1120, 1065, 818 cm-1. 1H NMR (400 MHz, CDCl3) δ
1.05 (t, 3H, J ) 7.0 Hz), 1.25 (t, 3H, J ) 6.6 Hz), 2.34 (s, 3H),
2.71 (d, 1H, J ) 2.2 Hz), 3.21-3.29 (m, 1H), 3.51-3.62 (m, 2H),
3.77-3.85 (m, 1H), 4.37 (d, 1H, J ) 6.6 Hz), 4.56 (dd, 1H, J )
6.6, 2.2 Hz), 7.15 (d, 2H, J ) 8.1 Hz), 7.31 (d, 2H, J ) 8.1 Hz).
13C NMR (100 MHz, CDCl3) δ 15.0, 15.2, 21.1, 63.5, 64.3, 74.4,
105.9, 127.0, 128.7 (overlapping), 136.5, 137.3. HRMS(EI+), m/z
(M+) calcd 224.1412, obsd 224.1413. Anal. Calcd for C13H20O3:
C, 69.61; H, 8.99. Found: C, 69.23; H, 9.12.
Hydrogenation of 2,2-Diethoxy-4′-methoxyacetophenone (7e).
Conditions: (S,R)-6 (2.2 mg, 2.2 µmol), 7e (562.8 mg, 2.36 mmol),
t-C4H9OK (11.5 mg, 0.102 mmol), 2-propanol (5 mL), 8 atm H2,
30 °C, 5 h. (R)-2,2-Diethoxy-1-(4-methoxyphenyl)ethanol [(R)-8e]:
546.6 mg, 96% yield, 98% ee. The enantiomeric excess of 8e was
determined by HPLC analysis. Column, CHIRALCEL OD-H;
eluent, hexane:2-propanol ) 98:2; flow, 0.5 mL min-1; column
temp, 40 °C; tR of (S)-8e, 21.1 min (1%); tR of (R)-8e, 24.5 min
(99%). [R]26 -16.9 (c 1.05, CHCl3). IR (KBr, neat) 3475, 2976,
D
2898, 1614, 1515, 1250, 1119, 1065, 1034, 831 cm-1. H NMR
1
(400 MHz, CDCl3) δ 1.04 (distorted t, 3H, J ) 7 Hz), 1.26 (distorted
t, 3H, J ) 7 Hz), 2.73 (br s, 1H), 3.20-3.26 (m, 1H), 3.51-3.61
(m, 2H), 3.77-3.85 (m, 1H), 3.81 (s, 3H), 4.35 (d, 1H, J ) 6.6
Hz), 4.53 (br d, 1H), 6.88 (m, 2H), 7.34 (m, 2H). 13C NMR (100
MHz, CDCl3) δ 15.1, 15.3, 55.1, 63.5, 64.4, 74.2, 106.0, 113.4,
128.3, 131.6, 159.1. HRMS(EI+), m/z (M+) calcd 240.1361, obsd
240.1379. Anal. Calcd for C13H20O4: C, 64.96; H, 8.39. Found: C,
64.49; H, 8.07.
Hydrogenation of 2-(N-Benzoylmethylamino)-1-phenyl-1-pro-
panone (9d). Conditions: (S,R)-6 (1.1 mg, 1.1 µmol), 9d (144.4
mg, 0.542 mmol), t-C4H9OK (5.5 mg, 0.049 mmol), 2-propanol
(1.5 mL), 8 atm H2, 30 °C, 9 h. (1R,2R)-N-Benzoylpseudoephedrine
[(1R,2R)-10d]: 124.6 mg, 90% yield (syn:anti ) >99:1), 98% ee.
The enantiomeric excess of (1R*,2R*)-10d (syn) was determined
by HPLC analysis. Column, CHIRALCEL OJ-H; eluent, hexane:
ethanol ) 96:4; flow, 0.5 mL min-1; column temp, 40 °C; tR of
(1S,2S)-10d, 37.8 min (1%); tR of (1R,2R)-10d, 49.2 min (99%).
Mp 140 °C (hexane-ethyl acetate), [R]19D -139.7 (c 1.22, CHCl3).
Hydrogenation of 4′-Chloro-2,2-diethoxyacetophenone (7f). Con-
ditions: (S,R)-6 (1.2 mg, 1.2 µmol), 7f (323.0 mg, 1.33 mmol),
t-C4H9OK (10.6 mg, 0.0945 mmol), 2-propanol (4 mL), 8 atm H2,
30 °C, 4 h. (R)-1-(4-Chlorophenyl)-2,2-diethoxyethanol [(R)-8f]:
307.6 mg, 95% yield, 92% ee. The enantiomeric excess of 8f was
determined by HPLC analysis. Column, CHIRALCEL OB-H;
eluent, hexane:2-propanol ) 98:2; flow, 0.5 mL min-1; column
temp, 40 °C; tR of (R)-8f, 12.3 min (96%); tR of (S)-8f, 13.1 min
1
IR (KBr-disk) 3247, 2977, 1605, 1586, 774, 752, 698 cm-1. H
NMR (270 MHz, DMSO-d6 at 100 °C) δ 0.97 (d, 3H, J ) 6.6 Hz),
2.89 (s, 3H), 4.58 (br s, 1H), 5.19 (d, 1H, J ) 3.9 Hz), 7.23-7.39
(m, 10H). 13C NMR (100 MHz, DMSO-d6) δ 13.9 (minor), 15.0
(major), 26.8 (major), 32.3 (minor), 53.8 (minor), 59.2 (major),
73.6 (major), 73.7 (minor), 126.5, 126.7, 126.8, 127.2, 127.4, 128.0,
128.1, 128.2, 128.6, 129.0, 137.6 (minor), 137.7 (major), 143.4
(major), 143.5 (minor), 170.6 (minor), 171.4 (major). The terms
“major” and “minor” refer to the amide rotamers. Several signals
are overlapping. HRMS(EI+), m/z (M + H+) calcd 270.1494, obsd
270.1498. Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20.
Found: C, 75.60; H, 7.08; N, 5.16.
(4%). [R]27 -9.7 (c 1.07, CHCl3). IR (KBr, neat) 3460, 2977,
D
2896, 1492, 1120, 1065, 1014, 830 cm-1. H NMR (400 MHz,
1
CDCl3) δ 1.06 (t, 3H, J ) 7.0 Hz), 1.25 (t, 3H, J ) 7.0 Hz), 2.77
(d, 1H, J ) 2.2 Hz), 3.22-3.29 (m, 1H), 3.52-3.65 (m, 2H),
3.77-3.85 (m, 1H), 4.32 (d, 1H, J ) 6.2 Hz), 4.56 (dd, 1H, J )
6.2, 2.2 Hz), 7.30-7.33 (m, 2H), 7.36-7.39 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ 15.1, 15.3, 63.7, 64.7, 74.0, 105.8, 128.2,
128.5, 133.4, 138.0. HRMS(ESI+), m/z (M + Na+ (35Cl)) calcd
267.0763, obsd 267.0771. Anal. Calcd for C12H17O3Cl: C, 58.90;
H, 7.00. Found: C, 58.63; H, 6.76.
9092 J. Org. Chem. Vol. 73, No. 22, 2008