H. Naka, Y. Kondo et al.
16.8, 8.8 Hz, 1H), 3.51 (s, 3H), 3.55 (dd, J=16.8, 5.2 Hz, 1H), 3.73 (s,
3H), 3.86 (d, J=9.6 Hz, 1H), 4.19 (dt, J=9.2, 5.2 Hz, 1H), 7.14–7.29 (m,
5H), 7.42 (t, J=7.6 Hz, 2H), 7.53 (tt, J=7.6, 1.6 Hz, 1H), 7.87–7.92 ppm
(m, 2H); IR (neat): n˜ =2954, 2844, 1727, 1681, 1432, 1233, 1158, 1025,
747, 687 cmꢀ1; LRMS(EI): m/z: 340 [M+]; HRMS: m/z: calcd for
C20H20O5: 340.1311; found: 340.1307; elemental analysis calcd (%) for
C20H20O5: C 70.57, H 5.92; found: C 70.45, H 5.97; HPLC (Daicel Chiral-
pak AD, isopropanol/hexane 10:90, flow rate 1.0 mLminꢀ1, l=254 nm):
tR =28.4 min (minor enantiomer), tR =35.2 min (major enantiomer).
274.1099; elemental analysis calcd (%) for C18H14N2O: C 78.81, H 5.14, N
10.21; found: C 78.81, H 5.34, N 10.07; HPLC (Daicel Chiralpak AD, iso-
, l=254 nm): tR =
20.10 min (major enantiomer), tR =27.67 min (minor enantiomer).
propanol/hexane 10:90, flow rate 1.0 mLminꢀ1
2-[3-Oxo-3-phenyl-1-(4-tolyl)-propyl]-malonic acid dimethyl ester (4g):[17]
Recrystallized from Et2O/hexane, colorless needles; m.p. 75–768C;
1H NMR (400 MHz, CDCl3/TMS): d=2.26 (s, 3H), 3.40–3.57 (m, 5H),
3.72 (s, 3H), 3.83 (d, J=9.5 Hz, 1H), 4.15 (dt, J=9.1, 5.1 Hz, 1H), 7.04
(d, J=8.3 Hz, 2H), 7.13 (d, J=8.3 Hz, 2H), 7.39–7.46 (m, 2H), 7.50–7.56
(m, 1H), 7.88–7.93 ppm (m, 2H); IR (neat): n˜ =2954, 1729, 1681, 1233,
1208, 1194, 1160, 1025, 820, 688 cmꢀ1; LRMS(EI): m/z: 354 [M+];
HRMS: m/z: calcd for C21H22O5: 354.1467; found: 354.1478; elemental
analysis calcd (%) for C21H22O5: C 71.17, H 6.26; found: C 70.71, H 6.10;
HPLC (Daicel Chiralpak AD, isopropanol/hexane 10:90, flow rate
1.0 mLminꢀ1, l=254 nm): tR =24.0 min (minor enantiomer), tR =31.6 min
(major enantiomer).
2-(3-Oxo-1,3-diphenyl-propyl)-malonic acid diethyl ester (4b):[13b,14] Re-
crystallized from Et2O/hexane, colorless needles; m.p. 73–748C; [a]D31
=
+22.50 (c=1.01 in CHCl3) (lit.:[14] [a]D25 =+17.5 (c=0.8 in CHCl3));
1H NMR (400 MHz, CDCl3/TMS): d=1.01 (t, J=7.1 Hz, 3H), 1.24 (t, J=
7.1 Hz, 3H), 3.45 (dd, J=16.6, 9.0 Hz, 1H), 3.54 (dd, J=16.6, 4.6 Hz,
1H), 3.82 (d, J=9.8 Hz, 1H), 3.95 (q, J=7.1 Hz, 2H), 4.13–4.24 (m, 3H),
7.13–7.30 (m, 5H), 7.38–7.55 (m, 3H), 7.86–7.92 ppm (m, 2H); IR (neat):
n˜ =2983, 1721, 1679, 1293, 1239, 1167, 1030, 745, 700, 687 cmꢀ1; LRMS
(EI): m/z: 368 [M+]; HRMS: m/z: calcd for C22H24O5: 368.1624; found:
368.1612; elemental analysis calcd (%) for C22H24O5: C 71.72, H 6.57;
found: C 71.72, H 6.42; HPLC (Daicel Chiralpak AD, isopropanol/
hexane 10:90, flow rate 1.0 mLminꢀ1, l=254 nm): tR =22.4 min (minor
enantiomer), tR =39.1 min (major enantiomer).
2-[1-(4-Methoxyphenyl)-3-oxo-3-phenylpropyl]-malonic acid dimethyl
ester (4h):[17,18] Recrystallized from Et2O/hexane, colorless needles; m.p.
1
81–828C; H NMR (400 MHz, CDCl3/TMS): d=3.43 (dd, J=16.6, 8.9 Hz,
1H), 3.52 (dd, J=16.6, 4.8 Hz, 1H), 3.52 (s, 3H), 3.73 (s, 3H), 3.74 (s,
3H), 3.82 (d, J=9.4 Hz, 1H), 4.10–4.18 (m, 1H), 6.75–6.81 (m, 2H),
7.14–7.20 (m, 2H), 7.40–7.46 (m, 2H), 7.50–7.56 (m, 1H), 7.88–7.92 ppm
(m, 2H); IR (neat): n˜ =2954, 1729, 1681, 1515, 1231, 1179, 1158, 1025,
754, 729, 686 cmꢀ1; LRMS(EI): m/z: 370 [M+]; HRMS: m/z: calcd for
C21H22O6: 370.1416; found: 370.1413; elemental analysis calcd (%) for
C21H22O6: C 68.10, H 5.99; found: C 67.63, H 6.00; HPLC (Daicel Chiral-
pak AD, isopropanol/hexane 10:90, flow rate 1.0 mLminꢀ1, l=254 nm):
tR =51.76 min (minor enantiomer), tR =75.66 min (major enantiomer).
2-(3-Oxo-1,3-diphenyl-propyl)-malonic acid diisopropyl ester (4c):[13b,14]
Recrystallized from Et2O/hexane, colorless needles; m.p. 88–898C;
[a]3D1 =+15.80 (c=1.01 in CHCl3) (lit.:[14] [a]2D5 =+21.3 (c=0.7 in
CHCl3)); 1H NMR (400 MHz, CDCl3/TMS): d=0.97 (d, J=6.3 Hz, 3H),
1.04 (d, J=6.3 Hz, 3H), 1.24 (d, J=6.3 Hz, 6H), 3.43 (dd, J=16.5,
9.5 Hz, 1H), 3.53 (dd, J=16.5, 4.1 Hz, 1H), 4.15 (dt, J=9.7, 4.1 Hz, 1H),
4.79 (sept, J=6.3 Hz, 1H), 5.07 (sept, J=6.3 Hz, 1H), 7.12–7.28 (m, 5H),
7.38–7.44 (m, 2H), 7.49–7.54 (m, 1H), 7.86–7.91 ppm (m, 2H); IR (neat):
n˜ =2983, 2935, 1721, 1683, 1281, 1235, 1104, 750, 702, 691 cmꢀ1; LRMS
(EI): m/z: 396 [M+]; HRMS: m/z: calcd for C24H28O5: 396.1937; found:
396.1928; elemental analysis calcd (%) for C24H28O5: C 72.70, H 7.12;
found: C 72.58, H 7.09; HPLC (Daicel Chiralpak AD, isopropanol/
hexane 10:90, flow rate 1.0 mLminꢀ1, l=254 nm): tR =12.88 min (minor
enantiomer), tR =24.82 min (major enantiomer).
2-[1-(4-Chlorophenyl)-3-oxo-3-phenylpropyl]-malonic acid dimethyl ester
(4i): Recrystallized from Et2O/hexane, colorless needles; m.p. 87–888C;
1H NMR (400 MHz, CDCl3/TMS): d=3.45 (dd, J=17.0, 8.9 Hz, 1H),
3.53 (dd, J=17.0, 4.8 Hz, 1H), 3.53 (s, 3H), 3.74 (s, 3H), 3.82 (d, J=
9.2 Hz, 1H), 4.17 (dt, J=9.2, 4.8 Hz, 1H), 7.18–7.26 (m, 4H), 7.40–7.47
(m, 2H), 7.52–7.58 (m, 1H), 7.87–7.92 ppm (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3/TMS): d=40.1, 42.1, 52.5, 52.7, 57.0, 128.0, 128.6,
128.6, 129.5, 133.0, 133.2, 136.6, 139.0, 168.0, 168.5, 197.2 ppm; IR (neat):
n˜ =2956, 1729, 1681, 1235, 1162, 1023, 827, 752, 685, 665 cmꢀ1; LRMS
(EI): m/z: 374 [M+]; HRMS: m/z: calcd for C20H19O5Cl: 374.0921; found:
374.0904; elemental analysis calcd (%) for C20H19O5Cl: C 64.09, H 5.11;
found: C 63.97, H 5.11; HPLC (Daicel Chiralpak AD, isopropanol/
hexane 10:90, flow rate 1.0 mLminꢀ1, l=254 nm): tR =32.86 min (minor
enantiomer), tR =52.03 min (major enantiomer).
2-(3-Oxo-1,3-diphenyl-propyl)-malonic acid dibenzyl ester (4d):[13b,14] Re-
crystallized from Et2O/hexane, colorless needles; m.p. 106–1078C; [a]D31
=
+16.20 (c=1.01 in CHCl3) (lit.:[14] [a]D25 =+18.4 (c=1.0 in CHCl3));
1H NMR (400 MHz, CDCl3/TMS): d=3.49 (d, J=6.4 Hz, 2H), 3.94 (d,
J=9.5 Hz, 1H), 4.18–4.25 (m, 1H), 4.90 (s, 2H), 5.11 (d, J=12.2 Hz,
1H), 5.16 (d, J=12.2 Hz, 1H), 7.04–7.42 (m, 17H), 7.48–7.53 (m, 1H),
7.77–7.82 ppm (m, 2H); IR (neat): n˜ =3346, 3031, 1733, 1681, 1229, 1152,
1011, 965, 741, 699 cmꢀ1; LRMS(EI): m/z: 492 [M+]; HRMS: m/z: calcd
for C32H28O5: 492.1937; found: 492.1957; elemental analysis calcd (%) for
C32H28O5: C 78.03, H 5.73; found: C 77.99, H 5.86; HPLC (Daicel Chiral-
pak AD, isopropanol/hexane 10:90, flow rate 1.0 mLminꢀ1, l=254 nm):
tR =38.86 min (minor enantiomer), tR =73.36 min (major enantiomer).
2-[1-(4-Fluorophenyl)-3-oxo-3-phenylpropyl]-malonic acid dimethyl ester
(4j): Recrystallized from Et2O/hexane, colorless needles; m.p. 85–868C;
1H NMR (400 MHz, CDCl3/TMS): d=3.44 (dd, J=16.9, 8.9 Hz, 1H),
3.40–3.57 (m, 5H), 3.72 (s, 3H), 3.83 (d, J=9.5 Hz, 1H), 4.15 (dt, J=9.1,
5.1 Hz, 1H), 7.04 (d, J=8.3 Hz, 2H), 7.13 (d, J=8.3 Hz, 2H), 7.39–7.46
(m, 2H), 7.50–7.56 (m, 1H), 7.88–7.93 ppm (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3/TMS): d=40.1, 42.3, 52.4, 52.7, 57.2, 115.3 (d, J=
21.3 Hz), 128.1, 128.6, 129.7 (d, J=7.8 Hz), 129.8, 133.1 (d, J=3.3 Hz),
136.7, 161.8 (d, J=245.8 Hz), 168.0, 168.6, 197.3 ppm; IR (neat): n˜ =2954,
1729, 1681, 1233, 1208, 1194, 1160, 1025, 820, 688 cmꢀ1; LRMS(EI): m/z:
354 [M+]; HRMS: m/z: calcd for C21H22O5: 354.1467; found: 354.1478;
elemental analysis calcd (%) for C21H22O5: C 67.03, H 5.34; found: C
66.74, H 5.37; HPLC (Daicel Chiralpak AD, isopropanol/hexane 10:90,
flow rate 1.0 mLminꢀ1, l=254 nm): tR =24.0 min (minor enantiomer),
tR =31.6 min (major enantiomer).
2-(3-Oxo-1,3-diphenylpropyl)-malonic acid di-tert-butyl ester (4e):[16] Re-
crystallized from Et2O/hexane, colorless needles; m.p. 117–1188C; [a]D31
=
+8.57 (c=0.75 in CHCl3); 1H NMR (400 MHz, CDCl3/TMS): d=1.19 (s,
9H), 1.46 (s, 9H), 3.39 (dd, J=16.4, 9.9 Hz, 1H), 3.51 (dd, J=16.4,
3.9 Hz, 1H), 3.64 (d, J=10.1 Hz, 1H), 4.07 (dt, J=10.0, 3.9 Hz, 1H),
7.11–7.17 (m, 1H), 7.19–7.27 (m, 4H), 7.38–7.44 (m, 2H), 7.49–7.54 (m,
1H), 7.87–7.91 ppm (m, 2H); IR (neat): n˜ =2979, 1735, 1719, 1683, 1368,
1246, 1138, 741, 700, 687 cmꢀ1; LRMS(EI): m/z: 368 [Mꢀ56]+; HRMS:
m/z: calcd for C26H32O5: 368.1624; found: 368.1635; elemental analysis
calcd (%) for C26H32O5: C 73.56, H 7.60; found: C 73.57, H 7.57; HPLC
2-[1-(4-Nitrophenyl)-3-oxo-3-phenylpropyl]-malonic acid dimethyl ester
(4k):[18] Recrystallized from Et2O/hexane, colorless needles; m.p. 77–
788C; 1H NMR (400 MHz, CDCl3/TMS): d=3.50–3.63 (m, 5H), 3.75 (s,
3H), 3.89 (d, J=9.1 Hz, 1H), 4.31 (dt, J=8.9, 5.1 Hz, 1H), 7.41–7.50 (m,
4H), 7.53–7.79 (m, 1H), 7.86–7.92 (m, 2H), 8.10–8.16 ppm (m, 2H); IR
(Daicel Chiralpak AD, isopropanol/hexane 5:95, flow rate 1.0 mLminꢀ1
,
l=254 nm): tR =12.15 min (minor enantiomer), tR =41.15 min (major en-
antiomer).
2-(3-Oxo-1,3-diphenylpropyl)-malononitrile (4 f):[13b,14] Recrystallized
from CH2Cl2/hexane, colorless needles; m.p. 125–1268C; 1H NMR
(400 MHz, CDCl3/TMS): d=3.65 (dd, J=18.6, 5.3 Hz, 1H), 3.72 (d, J=
18.6, 8.5 Hz, 1H), 3.96 (dt, J=8.5, 5.1 Hz, 1H), 4.66 (d, J=5.1 Hz, 1H),
7.35–7.54 (m, 7H), 7.60–7.66 (m, 1H), 7.96–8.00 ppm (m, 2H); IR (neat):
n˜ =2919, 2900, 2256, 1681, 1449, 1233, 762, 748, 700, 690 cmꢀ1; LRMS
(EI): m/z: 274 [M+]; HRMS: m/z: calcd for C18H14N2O: 274.1106; found:
(neat): n˜ =2954, 1731, 1684, 1517, 1345, 1256, 1152, 856, 748, 688 cmꢀ1
;
LRMS(EI): m/z: 385 [M+]; HRMS: m/z: calcd for C20H19NO7: 385.1162;
found: 385.1154; elemental analysis calcd (%) for C20H19NO7: C 62.33, H
4.97, N 3.63; found: C 62.08, H 5.05, N 3.40; HPLC (Daicel Chiralpak
AD, isopropanol/hexane 30:70, flow rate 1.0 mLminꢀ1, l=254 nm): tR =
29.3 min (minor enantiomer), tR =59.7 min (major enantiomer).
5272
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 5267 – 5274