Y. Kawai et al. / Tetrahedron: Asymmetry 12 (2001) 3007–3013
3011
4.7. 4-(2-Hydroxyphenyl)-3-methyl-3-buten-2-one 1g
4.8.3. 3-Methyl-3-(4-pyridyl)-2-butanone 2c. 72% yield;
1
7
7% e.e. (S)-enantiomer; H NMR (CDCl , TMS) l
3
In a three-necked flask, (1-methyl-2-oxopropyl)tri-
phenylphosphonium bromide (4.69 g, 11.3 mmol)
in dry THF (100 mL) was cooled at 0°C under
an argon atmosphere. While stirring, a solution of
butyllithium in hexane (1.5 M, 18 mL, 27 mmol) was
added to the mixture, the color of the solution changed
to dark red. After 1 h, a solution of salicylaldehyde
1.13 (3H, d, J=7.0 Hz), 2.13 (3H, s), 2.55 (1H, dd,
J=7.1, 13.1 Hz), 2.85 (1H, sextet, J=6.9 Hz), 3.02 (1H,
dd, J=7.0, 13.2 Hz), 7.07–7.11 (2H, m), 8.48–8.52 (2H,
−
1
26
m); IR (neat) 1713 cm ; [h] +2.04 (c 1.56, EtOH).
D
Found: C, 73.58; H, 8.01; N, 8.41%. Calcd for
C H NO: C, 73.59; H, 8.03; N, 8.58%.
10
13
(
1.38 g, 11.3 mmol) in dry THF (5 mL) was added to
4.8.4. 3-(2-Pyridylmethyl)-2-pentanone 2h. 72% yield;
1
the solution, and the temperature was raised to room
temperature. The solution was neutralized with
aqueous saturated ammonium chloride and the
aqueous solution was extracted with ethyl acetate. The
combined extracts were washed with brine, dried over
anhydrous magnesium sulfate, and filtered. Removal of
the solvent gave the crude product. The residue was
chromatographed on silica gel and eluted with hexane/
ethyl acetate (4/1) to obtain the mixture of 4-(2-hydroxy-
phenyl)-3-methyl-3-buten-2-one and 1-(2-hydroxy-
phenyl)-1-buten-3-pentanone. The mixture was recrys-
tallized from ether to afford 4-(2-hydroxyphenyl)-3-
>99% e.e. (S)-enantiomer; H NMR (CDCl , TMS) l
3
0.92 (3H, t, J=7.4 Hz), 1.40–1.81 (2H, m), 2.11 (3H, s),
2.78–2.95 (1H, m), 3.04–3.19 (2H, m), 7.07–7.15 (2H,
m), 7.52–7.63 (1H, m), 8.49–8.54 (1H, m); IR (neat)
−
1
24
1711 cm ; [h] +13.0 (c 2.05, EtOH). Found: C, 74.43;
D
H, 8.58; N, 7.85%. Calcd for C H NO: C, 74.54; H,
11
15
8.53; N, 7.90%.
4.8.5. 3-(3-Pyridylmethyl)-2-pentanone 2i. 81% yield;
1
96% e.e. (S)-enantiomer; H NMR (CDCl , TMS) l
3
0.92 (3H, t, J=7.3 Hz), 1.45–1.80 (2H, m), 2.06 (3H, s),
2.61–3.02 (3H, m), 7.19–7.30 (1H. m), 7.40–7.48 (1H,
−
1
23
methyl-3-buten-2-one (0.84 g, 42%). Mp 124.6–126.0°C,
m), 8.43–8.56 (2H, m); IR (neat) 1711 cm ; [h] +11.1
D
1
H NMR (CDCl , TMS) l 1.99 (3H, d, J=1.4 Hz),
(c 5.39, EtOH). Found: C, 74.36; H, 8.61; N, 7.75%.
3
2
.49 (3H, s), 5.68 (1H, s), 6.87–7.01 (2H, m), 7.21–7.32
Calcd for C H NO: C, 74.54; H, 8.53; N, 7.90%.
11
15
−
1
(
2H, m), 7.69 (1H, br); IR (KBr) 1637 cm . Found: C,
7
6
4.81; H, 6.93%. Calcd for C H O : C, 74.98; H,
.86%.
4.8.6. 3-(4-Pyridylmethyl)-2-pentanone 2j. 82% yield;
11
12
2
1
>99% e.e. (S)-enantiomer; H NMR (CDCl , TMS) l
3
0
2
.92 (3H, t, J=7.4 Hz), 1.45–1.80 (2H, m), 2.06 (3H, s),
.61–2.98 (3H, m), 7.06–7.10 (2H, m), 8.48–8.51 (2H,
4
.8. General procedure for baker’s yeast reduction of
enones
−1
23
m); IR (neat) 1711 cm ; [h]D +4.21 (c 2.44, EtOH).
Found: C, 74.26; H, 8.56; N, 7.89%. Calcd for
C H NO: C, 74.54; H, 8.53; N, 7.90%.
The substrate (0.5 mmol) in tap water (20 mL) was
stirred vigorously at 35°C and dry baker’s yeast (5.0 g)
was added. The reaction was monitored by gas chro-
matography analysis. After an appropriate reaction
time, acetone (20 mL) was added and the yeast was
removed by suction filtration. After evaporation of the
acetone under reduced pressure, the residue was
extracted with dichloromethane. The combined extracts
were dried over anhydrous magnesium sulfate and the
solvent was removed under reduced pressure. The
residue was purified by column chromatography on
silica gel to obtain the corresponding ketones. The
enantiomeric excess (e.e.) of each chiral ketone was
determined by GLC except for 2c. The e.e. of 2c was
determined by HPLC. The yields of the isolated prod-
ucts, their e.e. and spectral and physical data are listed
below.
11
15
4
6
.8.7. 3-Methyl-3-(2-pyridyl)-2-butanone N-oxide 2d.
1
9% yield; 71% e.e. (R)-enantiomer; H NMR (CDCl ,
3
TMS) l 1.18 (3H, d, J=7.1 Hz), 2.16 (3H, s), 2.85 (1H,
dd, J=6.1, 13.1 Hz), 3.19–3.48 (2H, m), 7.11–7.32 (3H,
−1
24
m), 8.20–8.26 (1H, m); IR (neat) 1710 cm ; [h] −4.5
D
(
c 1.68, EtOH); HRMS m/z found: 179.0945; calcd for
C H NO : 179.0946.
10
13
2
4
8
.8.8. 3-Methyl-3-(3-pyridyl)-2-butanone N-oxide 2e.
1
7% yield; >95% e.e. (S)-enantiomer; H NMR (CDCl ,
3
TMS) l 1.13 (3H, d, J=7.0 Hz), 2.13 (3H, s), 2.57 (1H,
dd, J=7.0, 13.5 Hz), 2.83 (1H, sextet, J=7.0 Hz), 3.02
(
(
1H, dd, J=7.0, 13.5 Hz), 7.08–7.18 (2H, m), 7.47–7.55
−1 24
1H, m), 8.42–8.51 (1H, m); IR (neat) 1708 cm ; [h]
D
−
16.2 (c 1.29, EtOH); HRMS m/z found: 179.0940;
calcd for C H NO : 179.0946.
10
13
2
4
6
.8.1. 3-Methyl-3-(2-pyridyl)-2-butanone 2a. 59% yield;
30
D
5% e.e. (S)-enantiomer; [h] +6.5 (c 1.77, EtOH, 49%
4
.8.9. 3-Methyl-3-(4-pyridyl)-2-butanone N-oxide 2f.
e.e.). Spectroscopic data agreed with the previous
report.
1
2
8
64% yield; 72% e.e. (S)-enantiomer; H NMR (CDCl ,
3
TMS) l 1.17 (3H, d, J=7.0 Hz), 2.14 (3H, s), 2.56 (1H,
dd, J=6.4, 13.4 Hz), 2.82 (1H, sextet, J=6.9 Hz), 3.01
(1H, dd, J=7.6, 13.4 Hz), 7.08–7.12 (2H, m), 8.11–8.15
4
.8.2. 3-Methyl-3-(3-pyridyl)-2-butanone 2b. 76% yield;
1
>
95% e.e. (S)-enantiomer; H NMR (CDCl , TMS) l
3
−
1
24
1.13 (3H, d, J=7.0 Hz), 2.13 (3H, s), 2.57 (1H, dd,
(2H, m); IR (neat) 1709 cm ; [h] −2.2 (c 1.92, EtOH);
D
J=7.1, 13.4 Hz), 2.83 (1H, sextet, J=7.1 Hz), 3.02 (1H,
dd, J=6.9, 13.3 Hz), 7.17–7.25 (1H, m), 7.45–7.53 (1H,
HRMS m/z found: 179.0938; calcd for C H NO :
10
13
2
179.0946.
−
1
24
D
m), 8.42–8.48 (2H, m); IR (neat) 1712 cm ; [h] +2.3
(
c 0.61, EtOH, 14% e.e.). Found: C, 73.47; H, 8.11; N,
4.8.10. 3-(2-Pyridylmethyl)-2-pentanone N-oxide 2k.
1
8
8
.34%. Calcd for C H NO: C, 73.59; H, 8.03; N,
93% yield; >99% e.e. (S)-enantiomer; H NMR (CDCl ,
10
13
3
.58%.
TMS) l 0.95 (3H, t, J=7.5 Hz), 1.50–1.86 (2H, m),