2280
R. Haraguchi, S. Matsubara
FEATURE ARTICLE
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 20:1, flow rate =
2.0 mL/min, λ = 254 nm, 40 °C): tR (major) = 19.3 min, tR (minor) =
23.3 min.
IR (KBr): 3297.5, 1679.1, 1663.7, 1607.7, 1599.1, 1554.7, 1498.8,
1444.8, 1319.4, 1254.8, 1236.4, 1086.0, 1046.4, 758.1, 700.2, 689.6
cm–1.
IR (KBr): 3298.4, 2961.8, 1669.5, 1603.9, 1554.7, 1499.7, 1442.8,
1312.6, 1060.9, 819.8, 754.2, 690.6, 581.6 cm–1.
1H NMR (CDCl3): δ = 7.80 (s, 1 H), 7.50 (d, J = 8.5 Hz, 2 H), 7.40
(d, J = 8.5 Hz, 2 H), 7.33 (m, 4 H), 7.13 (t, J = 7.5 Hz, 1 H), 5.20
(m, 1 H), 3.35 (d, J = 2.5 Hz, 1 H), 2.83 (dd, J = 15.5, 9.5 Hz, 1 H),
2.71 (dd, J = 15.0, 3.0 Hz, 1 H), 1.32 (s, 9 H).
1H NMR (CDCl3): δ = 7.64 (s, 1 H), 7.50 (d, J = 4.0 Hz, 2 H), 7.34
(t, J = 8.0 Hz, 2 H), 7.28 (d, J = 3.0 Hz, 1 H), 7.14 (t, J = 8.0 Hz, 1
H), 7.03 (d, J = 2.0 Hz, 1 H), 6.98 (t, J = 2.5 Hz, 1 H), 5.49 (m, 1
H), 3.79 (d, J = 3.5 Hz, 1 H), 2.90 (m, 2 H).
13C NMR (CDCl3): δ = 169.3, 146.3, 137.2, 129.1, 126.8, 125.0,
124.7, 123.8, 120.1, 67.2, 45.8.
13C NMR (CDCl3): δ = 169.8, 151.0, 139.7, 137.5, 129.0, 125.6,
125.3, 124.5, 120.0, 70.9, 46.0, 34.6, 31.3.
HRMS (ESI): m/z [M + Cl]– calcd for C13H13NO2SCl: 282.0350;
found: 282.0367.
HRMS (ESI): m/z [M + Cl]– calcd for C19H23NO2Cl: 332.1412;
found: 332.1425.
(S)-3-(2-Furyl)-3-hydroxy-N-phenylpropanamide (6bl)
Yield: 21.2 mg (92%); 76% ee; white solid; mp 133.0–134.0 °C.
[α]D20 –31.3 (c 0.24, CH2Cl2).
(S)-3-Hydroxy-3-mesityl-N-phenylpropanamide (6bi)
Yield: 17.9 mg (63%); 84% ee; white solid; mp 110.0–111.0 °C.
TLC: Rf = 0.43 (hexane–EtOAc, 1:1).
[α]D20 –16.9 (c 0.74, CH2Cl2).
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 20:1, flow rate =
2.0 mL/min, λ = 254 nm, 40 °C): tR (minor) = 19.6 min, tR (major) =
22.8 min.
TLC: Rf = 0.29 (hexane–EtOAc, 3:1).
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 20:1, flow rate =
2.0 mL/min, λ = 254 nm, 40 °C): tR (major) = 8.5 min, tR (minor) =
15.0 min.
IR (KBr): 3284.9, 1669.5, 1608.7, 1559.5, 1491.0, 1445.7, 1314.5,
1168.0, 1060.9, 1018.5, 759.0, 744.6, 693.4, 598.0 cm–1.
IR (KBr): 3431.5, 3269.5, 2921.3, 1628.0, 1600.0, 1545.1, 1498.8,
1444.8, 1312.6, 1253.8, 1172.8, 1071.5, 850.6, 752.3, 690.6, 351.1
cm–1.
1H NMR (CDCl3): δ = 8.05 (s, 1 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.33
(t, J = 8.5 Hz, 2 H), 7.12 (t, J = 7.0 Hz, 1 H), 6.83 (s, 2 H), 5.65 (d,
J =10.5 Hz, 1 H), 3.14 (dd, J = 15.5, 5.5 Hz, 1 H), 3.10 (s, 1 H), 2.49
(dd, J = 15.5, 2.0 Hz, 1 H), 2.43 (s, 6 H), 2.26 (s, 3 H).
13C NMR (CDCl3): δ = 170.0, 137.7, 137.2, 136.0, 134.8, 130.3,
129.0, 124.4, 120.0, 68.2, 42.7, 20.7, 20.7.
HRMS (ESI): m/z [M – H]– calcd for C18H20NO2: 282.1500; found:
1H NMR (CDCl3): δ = 7.71 (s, 1 H), 7.50 (d, J = 8.5 Hz, 2 H), 7.40
(m, 1 H), 7.34 (t, J = 7.0 Hz, 2 H), 7.13 (t, J = 7.5 Hz, 1 H), 6.35 (m,
1 H), 6.33 (d, J = 3.0 Hz, 1 H), 5.24 (m, 1 H), 3.62 (d, J = 4.5 Hz, 1
H), 2.96 (dd, J = 16.0, 8.5 Hz, 1 H), 2.87 (dd, J = 15.5, 3.5 Hz, 1 H).
13C NMR (CDCl3): δ = 169.4, 154.6, 142.3, 137.3, 129.0, 124.7,
120.1, 110.4, 106.5, 64.7, 42.0.
HRMS (ESI): m/z [M – H]– calcd for C13H12NO3: 230.0823; found:
230.0812.
(R)-3-Hydroxy-N-phenylbutanamide (6bm)
Yield: 8.06 mg (45%); 76% ee; white solid; mp 102.8–103.5 °C.
[α]D20 –21.2 (c 0.70, CHCl3).
282.1487.
(S)-3-Hydroxy-3-(2-naphthyl)-N-phenylpropanamide (6bj)
Yield: 25.9 mg (89%); 88% ee; white solid; mp 173.0–174.0 °C.
TLC: Rf = 0.28 (hexane–EtOAc, 1:2).
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 33:1, flow rate =
1.0 mL/min, λ = 254 nm, 40 °C): tR (major) = 34.7 min, tR (minor) =
38.8 min.
[α]D20 –250.0 (c 0.02, CH2Cl2).
TLC: Rf = 0.44 (hexane–EtOAc, 1:1).
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 20:1, flow rate =
2.0 mL/min, λ = 254 nm, 40 °C): tR (major) = 30.7 min, tR (minor) =
39.2 min.
IR (KBr): 3250.2, 1662.7, 1601.0, 1553.7, 1500.7, 1445.7, 1338.7,
1319.4, 1128.4, 1064.8, 753.2, 694.4 cm–1.
1H NMR (CDCl3): δ = 7.72 (s, 1 H), 7.50 (d, J = 9.0 Hz, 2 H), 7.33
(t, J = 8.0 Hz, 2 H), 7.12 (t, J = 7.5 Hz, 1 H), 4.32 (m, 1 H), 3.17 (d,
J = 3.0 Hz, 1 H), 2.55 (dd, J = 3.0, 15.5 Hz, 1 H), 2.48 (dd, J = 9.0,
15.5 Hz, 1 H), 1.30 (d, J = 6.5 Hz, 3 H).
13C NMR (CDCl3): δ = 170.3, 137.5, 129.0, 124.5, 120.0, 65.0,
45.2, 23.0.
HRMS (ESI): m/z [M + Cl]– calcd for C10H13NO2Cl: 214.0629;
IR (KBr): 3299.4, 1664.6, 1602.0, 1549.9, 1499.7, 1488.2, 1445.7,
1363.7, 1314.5, 1068.6, 761.0, 744.6 cm–1.
1H NMR (CDCl3): δ = 8.71 (s, 1 H), 7.87 (s, 1 H), 7.81 (m, 3 H),
7.52 (t, J = 8.5 Hz, 3 H), 7.45 (t, J = 7.5 Hz, 2 H), 7.29 (t, J = 7.0
Hz, 2 H), 7.07 (t, J = 7.5 Hz, 1 H), 5.33 (d, J = 9.5 Hz, 1 H), 4.79 (s,
1 H), 2.85 (dd, J = 16.0, 8.0 Hz, 1 H), 2.78 (dd, J = 15.5, 3.0 Hz, 1
H).
13C NMR (CDCl3): δ = 170.1, 140.8, 133.2, 132.9, 128.8, 128.3,
127.9, 127.6, 126.1, 125.8, 124.3, 124.1, 123.8, 121.1, 120.0, 70.9,
45.9.
found: 214.0643.
(S)-3-Hydroxy-4,4-dimethyl-N-phenylpentanamide (6bn)
Yield: 8.8 mg (49%); 83% ee; yellow solid; mp 110.0–111.0 °C.
[α]D20 –27.8 (c 0.27, CH2Cl2).
HRMS (ESI): m/z [M + Cl]– calcd for C19H17NO2Cl: 326.0942;
found: 326.0954.
TLC: Rf = 0.61 (hexane–EtOAc, 1:1).
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 33:1, flow rate =
2.0 mL/min, λ = 254 nm, 40 °C): tR (minor) = 13.0 min, tR (major) =
18.3 min.
(S)-3-Hydroxy-N-phenyl-3-(2-thienyl)propanamide (6bk)
Yield: 18.1 mg (73%); 94% ee; white solid; mp 159.5–160.2 °C.
[α]D20 –41.7 (c 0.12, CH2Cl2).
IR (KBr): 3293.6, 2958.9, 1659.3, 1603.9, 1552.8, 1501.7, 1445.7,
1337.7, 1149.6, 1070.5, 754.2, 702.1, 419.5 cm–1.
TLC: Rf = 0.50 (hexane–EtOAc, 1:1).
HPLC (Daicel Chiralcel AD-H, hexane–i-PrOH, 20:1, flow rate =
2.0 mL/min, λ = 254 nm, 40 °C): tR (minor) = 18.9 min, tR (major) =
21.4 min.
1H NMR (CDCl3): δ = 7.86 (s, 1 H), 7.50 (d, J = 7.5 Hz, 2 H), 7.32
(t, J = 7.0 Hz, 2 H), 7.11 (t, J = 7.5 Hz, 1 H), 3.79 (d, J = 5.0 Hz, 1
H), 3.01 (s, 1 H), 2.54 (dd, J = 2.0, 15.5 Hz, 1 H), 2.43 (dd, J = 10.5,
15.5 Hz, 1 H), 0.96 (s, 9 H).
Synthesis 2014, 46, 2272–2282
© Georg Thieme Verlag Stuttgart · New York