Y. Zhou, Z. Shan / Tetrahedron 62 (2006) 5692–5696
5695
d (ppm): 1.28–1.33 (m, 6H, CH3), 1.89–1.97 (m, 2H,
NCH2CH2), 2.20–2.28 (m, 2H, CHCH2), 3.16–3.24 (m,
1H, NCHH), 3.90–3.92 (m, 1H, NCHH), 4.23 (d,
J¼8.0 Hz, 4H, CH3CH2), 4.54 (d, J¼5.7 Hz, 2H, OCH),
4.68 (d, J¼8.3 Hz, 1H, NCH), 6.55 (s, 1H, NH); IR (KBr):
n 3230 (s, NH), 2991 (s, CH), 1764, 1748 (COOR), 1371
(ms, B–O), 1211 (vs, N/B), 1233 (s, C–O), 1069 (vs, B–O).
5.26 (s, 1H, CH), 3.63 (d, J¼3.3 Hz, 1H, OH), 2.89 (d,
J¼5.7 Hz, 2H, CH2), 2.23 (s, 3H, CH3); 13C NMR
(CDCl3, 300 MHz) d (ppm): 208.7, 148.6, 145.0, 132.0,
129.7, 122.8, 121.0, 69.1, 51.8, 31.0; IR (KBr): n 3417 (s,
OH), 3090 (w, Ph–H), 2917 (w, CH), 1709 (vs, C]O),
1618 (w, Ph–H), 1529, 1351 (s, NO2). Enantiomeric excess:
>99%, determined by HPLC (Daicel chiralpak OJ-H,
i-PrOH/hexane 20:80), UV 254 nm, flow rate: 1 ml/min.
(R)-Isomer, tR¼18.7 min and (S)-isomer, tR¼21.3 min.
4.2.2. General procedure for direct aldol reaction. In
a Schlenk test tube fitted with a magnetic bar, catalyst
(R,S)-4 (0.61 g 1.5 mmol) was charged, and followed by in-
jection of acetone (5 ml), after stirring for 15 min in ice bath,
an aromatic aldehyde (5 mmol) was added and continued to
stir at 0 ꢀC for 50 h. The reaction was quenched with satu-
rated aqueous ammonium chloride and extracted with ethyl
acetate (3ꢂ10 ml). The combined organic phase was dried
over anhydrous Na2SO4. After concentration, white solid
isolated upon standing (recovered catalyst), filtered and the
liquor was worked up through flash column chromatography
on a silica gel (200–300 mesh, eluent: petroether/acetate 2:1)
to give the desired product.
4.2.7. (4R)-Hydroxy-4-(40-nitrophenyl)-butan-2-one (9e).
1
Yield: 65%; [a]1D6 +51.03 (c 0.28, in CHCl3); H NMR
(CDCl3, 300 MHz) d (ppm): 8.23–7.53 (m, 4H, Ph–H),
5.27 (s, 1H, CH), 3.64 (s, 1H, OH), 2.86 (t, J¼4.5 Hz, 2H,
CH2), 2.23 (s, 3H, CH3); 13C NMR (CDCl3, 300 MHz)
d (ppm): 208.5, 150.2, 147.4, 129.0, 126.6, 124.4, 123.9,
69.2, 51.9, 31.1; IR (KBr): n 3436 (s, OH), 3081 (w, Ph–
H), 2902 (w, CH), 1707 (vs, C]O), 1602 (w, Ph–H),
1517, 1347 (s, NO2). Enantiomeric excess: 75%, determined
by HPLC (Daicel chiralpak AS-H, i-PrOH/hexane 30:70),
UV 254 nm, flow rate: 1 ml/min. (R)-Isomer, tR¼10.5 min
and (S)-isomer, tR¼13.5 min.
4.2.8. (4R)-Hydroxy-4-(40-chlorophenyl)-butan-2-one
(9f). Yield: 55%; [a]2D7 +46.36 (c 0.48, in CHCl3); 1H
NMR (CDCl3, 300 MHz) d (ppm): 7.33–7.26 (m, 4H, Ph–
H), 5.11 (q, J¼4.7 Hz, 1H, CH), 3.44 (s, 1H, OH), 2.83–
2.79 (m, 2H, CH2), 2.19 (s, 3H, CH3); 13C NMR (CDCl3,
300 MHz) d (ppm): 209.0, 141.4, 133.5, 128.9, 127.2,
69.5, 52.1, 31.1; IR (KBr): n 3426 (s, OH), 3001 (w,
Ph–H), 2902 (w, CH), 1711 (vs, C]O), 1597 (w, Ph–H).
Enantiomeric excess: 90%, determined by HPLC (Daicel
chiralpak AS-H, i-PrOH/hexane 10:90), UV 254 nm, flow
rate: 1 ml/min. (R)-Isomer, tR¼10.9 min and (S)-isomer,
tR¼12.6 min.
4.2.3. (4R)-Hydroxy-4-(10-naphthyl)-butan-2-one (9a).
1
Yield: 34%; [a]2D5 +56.30 (c 0.08, in CHCl3); H NMR
(CDCl3, 300 MHz) d (ppm): 8.02–7.46 (m, 7H, Naph–H),
5.94 (m, 1H, CH), 3.38 (s, 1H, OH), 3.02–2.99 (m, 2H,
CH2), 2.23 (s, 3H, CH3); 13C NMR (CDCl3, 300 MHz)
d (ppm): 207.8, 137.0, 132.5, 128.6, 127.8, 126.8, 125.0,
124.3, 121.7, 121.5, 65.5, 50.2, 29.7; IR (KBr): n 3421 (s,
OH), 3050 (w, Ph–H), 2923 (w, CH), 1687 (vs, C]O),
1614 (w, Ph–H). Enantiomeric excess: 96%, determined
by HPLC (Daicel chiralpak AS-H, i-PrOH/hexane 15:85),
UV 254 nm, flow rate: 1 ml/min. (R)-Isomer, tR¼8.7 min
and (S)-isomer, tR¼10.7 min.
4.2.4. (4R)-Hydroxy-4-phenyl-butan-2-one (9b). Yield:
1
44%; [a]2D0 +58.58 (c 0.39, in CHCl3); H NMR (CDCl3,
4.2.9. (4R)-Hydroxy-4-(30,50-dichlorophenyl)-butan-2-
1
300 MHz) d (ppm): 7.34–7.26 (m, 5H, Ph–H), 5.15–5.11
(m, 1H, CH), 3.50 (s, 1H, OH), 2.92–2.75 (m, 2H, CH2),
2.17 (s, 3H, CH3); 13C NMR (CDCl3, 300 MHz) d (ppm):
209.1, 143.0, 129.2, 128.7, 128.5, 127.9, 125.8, 70.1, 52.3,
31.1; IR (KBr): n 3420 (s, OH), 3031 (w, Ph–H), 2902 (w,
CH), 1708 (vs, C]O), 1602 (w, Ph–H). Enantiomeric ex-
cess: 96%, determined by HPLC (Daicel chiralpak AS-H,
i-PrOH/hexane 15:85), UV 254 nm, flow rate: 1 ml/min.
(R)-Isomer, tR¼8.1 min and (S)-isomer, tR¼8.9 min.
one (9g). Yield: 23%; [a]1D6 +39.22 (c 0.26, in CHCl3); H
NMR (CDCl3, 300 MHz) d (ppm): 7.25, 7.24 (s, 3H, Ph–
H), 5.09 (s, 1H, CH), 3.58 (s, 1H, OH), 2.81 (d, J¼6.7 Hz,
2H, CH2), 2.21 (s, 3H, CH3); 13C NMR (CDCl3,
300 MHz) d (ppm): 208.6, 146.3, 135.3, 127.9, 124.4,
68.9, 51.8, 31.1; IR (KBr): n 3430 (s, OH), 3078 (w, Ph–
H), 2925 (w, CH), 1711 (vs, C]O), 1594 (w, Ph–H), 689
(s, C–Cl). Enantiomeric excess: 74%, determined by
HPLC (Daicel chiralpak AS-H, i-PrOH/hexane 30:70), UV
254 nm, flow rate: 1 ml/min. (R)-Isomer, tR¼5.1 min and
(S)-isomer, tR¼6.1 min.
4.2.10. (4R)-Hydroxy-4-(20-methoxyphenyl)-butan-2-one
(9h). Yield: 26%; [a]2D5 +61.02 (c 0.15, in CHCl3); 1H
NMR (CDCl3, 300 MHz) d (ppm): 7.44–6.84 (m, 4H, Ph–
H), 5.40 (t, J¼10.3 Hz, 1H, CH), 3.83 (s, 1H, OCH3), 3.43
(d, J¼4.3 Hz, 1H, OH), 2.96–2.74 (m, 2H, CH2), 2.19 (s,
3H, CH3); 13C NMR (CDCl3, 300 MHz) d (ppm): 209.7,
156.0, 131.1, 128.6, 126.6, 121.1, 110.5, 65.8, 55.5, 50.6,
30.8; IR (KBr): n 3442 (s, OH), 3003 (w, Ph–H), 2939
(w, CH), 1708 (vs, C]O), 1600 (w, Ph–H), 1240, 1068 (s,
O–CH3).
4.2.5. (4R)-Hydroxy-4-(20-nitrophenyl)-butan-2-one (9c).
1
Yield: 65%; [a]2D7 ꢁ107.91 (c 1.11, in CHCl3); H NMR
(CDCl3, 300 MHz) d (ppm): 7.95–7.39 (m, 4H, Ph–H),
5.66 (d, J¼10.7 Hz, 1H, CH), 3.67 (s, 1H, OH), 3.13–2.68
(m, 2H, CH2), 2.12 (s, 3H, CH3); 13C NMR (CDCl3,
300 MHz) d (ppm): 208.8, 147.2, 138.7, 134.0, 128.5,
128.4, 124.6, 65.9, 51.4, 30.8; IR (KBr): n 3418 (s, OH),
3077 (w, Ph–H), 2920 (w, CH), 1712 (vs, C]O), 1609 (w,
Ph–H), 1524, 1348 (s, NO2). Enantiomeric excess: 96%, de-
termined by HPLC (Daicel chiralpak AS-H, i-PrOH/hexane
30:70), UV 254 nm, flow rate: 1 ml/min. (R)-Isomer,
tR¼9.0 min and (S)-isomer, tR¼3.8 min.
4.2.6. (4R)-Hydroxy-4-(30-nitrophenyl)-butan-2-one (9d).
4.2.11. (4R)-Hydroxy-4-(30-methoxyphenyl)-butan-2-one
(9i). Yield: 39%; [a]2D5 +38.45 (c 0.53, in CHCl3);
1H NMR (CDCl3, 300 MHz) d (ppm): 7.27–6.79 (m, 4H,
1
Yield: 92%; [a]2D7 +58.88 (c 0.45, in CHCl3); H NMR
(CDCl3, 300 MHz) d (ppm): 8.24–7.50 (m, 4H, Ph–H),