S. S. Chimni, D. Mahajan / Tetrahedron 61 (2005) 5019–5025
5023
(neat): 1664, 1595 cmK1; 1H NMR (CDCl3): d 2.34 (s, 3H,
CH3), 6.53 (d, 1H, JZ16.0 Hz, CH), 7.05–7.11 (m, 1H,
ArH), 7.23–7.30 (m, 1H, ArH), 7.40 (d, 1H, JZ5.1 Hz,
ArH), 7.63 (d, 1H, JZ16.0 Hz, CH,); 13C DEPT NMR
(CDCl3): d 27.7 (Cve), 125.7 (Cve), 128.2 (Cve), 128.8
(Ar-C), 131.4 (Cve), 135.6 (Ar-C), 139.7, 197.6.
(Kve), 45.1 (Kve), 49.9 (Kve), 120.5 (Cve), 122.6 (Cve),
126.1 (Cve), 128.2 (Cve), 128.44 (Cve), 128.7 (Cve),
128.9 (Cve), 137.1 (Cve), 140.74, 148.2 (Cve), 161.1,
200.1.
4.3.4. 2-[Hydroxy(20-pyridyl)methyl]cyclopentanone
(2f). Yield, 62% (119 mg); colourless crystalline solid, mp
118–120 8C, as inseparable mixture of syn and anti
diastereomers in 4:1; MS (m/z) 214 (MCNa)C. Anal.
Calcd for C11H13NO2: C, 69.10; H, 6.80; N, 7.32. Found: C,
4.2.8. 4-(Pyrrol-2-yl)but-3-en-2-one (8m). Yield, 62%
(84 mg); colourless crystalline solid, mp: 115–117 8C
(lit.17 mp: 117–120 8C); MS (m/z) EI: 135 (MC). Spectro-
scopic data consistent with literature.14b,d
69.20; H, 6.64; N, 7.49; IR (neat): 3221, 1708, 1592 cmK1
;
1H NMR (CDCl3): d 1.57–2.30 (m, 6H, CH2), 2.54–2.59 (m,
1H, CH), 4.98 (d, 1H, JZ6.3 Hz, CH anti/threo), 5.29 (d,
1H, JZ2.5 Hz, CH syn/erythro), 7.16–7.23 (m, 1H, PyH),
7.32 (d, 1H, JZ7.7 Hz, PyH), 7.66 (dt, 1H, JZ7.7, 1.8 Hz,
PyH) and 8.52 (d, 1H, JZ4.4 Hz, PyH). 13C DEPT NMR:
(CDCl3) d 20.5 (Kve), 22.1 (Kve), 38.9 (Kve), 54.8 (C
ve), 70.7 (Cve), 120.1 (Cve), 122.2 (Cve), 136.8 (Cve),
147.9 (Cve), 160.43, 219.53.
4.3. General procedure of aldol reaction of 1 with
different donor ketones
To a stirring mixture of 1 (107 mg, 1 mmol), methyl ketone
(5 mmol) and water (5 mL), pyrrolidine (30 mol%) was
added as catalyst. The monitoring of the reaction with TLC
showed that reaction was completed in 5 min. The reaction
was worked up by extraction with CH2Cl2 and washing the
CH2Cl2 layer with water. The organic layer was dried over
anhydrous Na2SO4 and distilled to obtain crude product.
Column chromatography of the crude on silica gel (60–120)
using mixture of ethyl acetate and hexane in varying
proportions as eluent, gave pure product.
4.3.5. 2-[Hydroxy(20-pyridyl)methyl]cyclohexanone (2g).
Yield, 86% (176 mg); colourless crystalline solid, mp: 120–
122 8C, as inseparable mixture of syn and anti dia-
stereomers18 in of 1:2; MS: (m/z) 228 (MCNa)C. Anal.
Calcd for C12H13NO2: C, 70.24; H, 7.31; N, 6.62. Found: C,
70.40; H, 7.09; N, 7.42; IR (neat): 3215, 1707, 1592 cmK1
;
4.3.1. 1-Hydroxy-1-(20-pyridyl)pentan-3-one (2b). Yield,
72% (129 mg); pale yellow liquid; HRMS (CI): exact mass
calcd for C10H13NO2: 179.0946. Found: 180.1024 (MC1);
1H NMR (CDCl3): d 1.52–1.93 (m, 4H, CH2), 2.01–2.19 (m,
2H, CH2), 2.25–2.41 (m, 2H, CH2), 3.02–3.11 (m, 1H, CH),
4.88 (d, 1H, JZ5.5 Hz, CH anti/threo), 5.36 (d, 1H, JZ
2.45 Hz, CH syn/erythro), 7.15–7.20 (m, 1H, PyH), 7.48 (d,
1H, JZ7.9 Hz, PyH), 7.68 (dt, 1H, JZ7.9, 1.5 Hz, PyH),
8.51 (d, 1H, JZ4.4 Hz, PyH); 13C DEPT NMR (CDCl3):
d 24.6 (Kve), 26.2 (Kve), 27.6 (Kve), 42.4 (Kve), 55.9
(Cve), 70.9 (Cve), 120.8 (Cve), 121.9 (Cve), 136.5
(Cve), 148.3 (Cve), 160.9, 213.8.
1
IR (neat): 3389, 1711, 1594 cmK1; H NMR (CDCl3): d
1.07 (t, 3H, JZ7.3 Hz, CH3,), 2.49 (q, 2H, JZ7.3 Hz, CH2),
2.84 (dd, 1H, JZ16.9, 8.2 Hz, CH of CH2), 3.04 (dd, 1H,
JZ16.9, 3.8 Hz, CH of CH2), 4.36 (br s, 1H, OH), 5.16
(dd, 1H, JZ8.2, 3.8 Hz, CH), 7.16–7.22 (m, 1H, PyH), 7.48
(d, 1H, JZ7.8 Hz, PyH), 7.70 (dt, 1H, JZ7.8, 1.6 Hz, PyH)
and 8.50 (d, 1H, JZ4.7 Hz, PyH,); 13C DEPT NMR
(CDCl3): d 7.7 (Cve), 36.5 (Kve), 49.3 (Kve), 69.8 (Cve),
120.2 (Cve), 122.2 (Cve), 136.5 (Cve), 148.5 (Cve),
161.42 and 208.0.
4.3.6. 4-Hydroxy-1,1-dimethoxy-4-(20-pyridyl)butan-2-
one (2h). Yield, 87% (196 mg); yellow thick liquid;
HRMS (CI): exact mass calcd for C11H15NO4: 225.1001.
1
Found: 226.1074 (MC1); IR (neat): 3442, 1732 cmK1; H
4.3.2. 1-Hydroxy-2-methyl-1-(20-pyridyl)butan-3-one
(2c). Yield, 11% (20 mg); yellow thick liquid, as insepar-
able mixture of syn and anti diastereomers in 1:1; MS (m/z)
NMR (CDCl3): d 3.07–3.15 (m, 2H, CH2), 3.40 (s, 3H,
OCH3), 3.41 (s, 3H, OCH3), 4.54 (s, 1H, CH), 5.23–5.27 (m,
1H, CH), 7.18–7.27 (m, 1H, Py-H), 7.43 (d, 1H, JZ8.1 Hz,
Py-H), 7.70 (dt, 1H, JZ7.8, 1.8 Hz, Py-H), 8.51–8.54
(m, 1H, Py-H). 13C DEPT NMR (CDCl3): 45.5 (Kve), 54.5
(Cve), 69.2 (Cve), 103.6 (Cve), 120.3 (Cve), 122.3
(Cve), 136.8 (Cve), 148.2 (Cve), 161.1, and 209.1.
ESI: 202 (MCNa)C; IR (neat): 3384, 1708, 1594 cmK1
;
1H NMR (CDCl3): d 0.99 (d, 3H, JZ7.0 Hz, CH3) and 1.10
(d, 3H, JZ7.0 Hz, CH3), 2.18 (s, 3H, CH3) and 2.24 (s, 3H,
CH3), 3.05–3.19 (m, 1H, CH of two diastereomers), 4.18 (d,
1H, JZ6.3 Hz, CH anti/threo), 5.17 (d, 1H, JZ3.3 Hz, CH
syn/erythro), 7.19–7.23 (m, 1H, PyH of two diastereomers),
7.34–7.42 (m, 1H, PyH of two diastereomers), 7.66–7.72
(m, 1H, PyH of two diastereomers) and 8.52 (d, 1H, JZ
3.9 Hz, PyH,). 13C DEPT NMR: (CDCl3) d 9.7 (Cve), 13.5
(Cve), 29.6 (Cve), 75.7 (Cve), 121.0 (Cve), 122.7 (Cve),
136.9 (Cve), 148.6 (Cve), 160.5 and 213.5.
4.4. Typical procedure for the aldol reaction of acetone
and pyridine-2-carboxaldehyde using NaOH as base
To a stirring mixture of acetone (0.37 ml, 5 mmol) and
water (5 mL) in a round bottom flask prefitted with a pH
meter, a solution of 1 N NaOH was added dropwise to make
the pH of the solution 11.75. At this constant pH of 11.75
pyridine-2-carboxaldehyde 1 (107 mg, 1 mmol) was added.
The reaction mixture was stirred for another 30 min, diluted
with 50 mL water and extracted with dichloromethane.
The organic layer was dried over anhydrous Na2SO4 and
distilled to get crude 4-hydroxy-4-(20-pyridyl)butan-2-one
(2a). Column chromatography of the crude on silica gel
(60–120) using mixture of ethyl acetate and hexane in
4.3.3. 5-Hydroxy-1-phenyl-5-(20-pyridyl)pentan-3-one
(2d). Yield, 76% (194 mg); dark yellow liquid; HRMS
(EI): exact mass calcd for C16H17NO2: 255.1259. Found:
255.1249; IR (neat): 3395, 1711, 1593 cmK1 1H NMR
;
(CDCl3): d 2.76–3.02 (m, 6H, CH2), 5.14 (dd, 1H, JZ7.8,
3.8 Hz, CH), 7.10–7.21 (m, 6H, ArH), 7.40 (d, 1H, JZ
7.8 Hz, PyH), 7.65 (dt, 1H, JZ7.6, 1.25 Hz, PyH), 8.46
(d, 1H, JZ4.7 Hz, PyH); 13C DEPT NMR (CDCl3): d 29.3