K. Ahmad et al. / Tetrahedron 63 (2007) 445–450
449
on silica gel to give a semi-solid (1S,2R,3S)-2-methyl-1-
phenyl-1,3-butanediol 3 (149 mg, 83% yield), [a]2D5 ꢁ35.2
(c 1.0, CHCl3) (97% ee, 95% de).
with solvent ether (3ꢃ70 mL). The combined organic layer
was washed with water, dried over anhydrous sodium sulfate
and concentrated under reduced pressure to furnish a crude
product, which on purification by column chromatography
on silica gel and elution with hexane/ethyl acetate (85:15)
afforded (2R,3S)-3-hydroxy-2-methyl-1-phenylbutanone 6
as a semi-solid (85 mg, 85% yield); [a]2D5 ꢁ16.3 (c 1.0,
CHCl3) (99% ee); IR (KBr): 3442, 2974, 1677, 1448,
4.1.5. DIBAL-H reduction of 7: preparation of 4. THF
solution of (2S,3S)-3-hydroxy-2-methyl-1-phenylbutanone
7 (178 mg, 1 mmol) was reduced with DIBAL-H (3 mmol,
1 mol/L THF solution) at ꢁ78 ꢂC as described above. After
the completion of the reaction (3.5 h) and processing, purifi-
cation of the crude product by column chromatography on
silica gel gave (1R,2S,3S)-2-methyl-1-phenyl-1,3-butane-
diol 4 as a white solid, mp 82 ꢂC (153 mg, 85% yield),
[a]2D5 +37.5 (c 1.0, CHCl3) (97% ee, 93% de).
1
1215, 972, 910, 707 cmꢁ1; H NMR (200 MHz, CDCl3):
d 7.94 (2H, d, J¼8.1 Hz, Ar-H), 7.50–7.56 (3H, m, Ar-H),
4.24 (1H, qd, J¼6.0, 3.1 Hz, CH3CHOH), 3.42 (1H, qd,
J¼7.5, 3.1 Hz, CHC(2)), 1.26 (3H, d, J¼7.4 Hz,
CH3CHOH), 1.18 (3H, d, J¼6.4 Hz, CH3C(2)); 13C NMR
(50 MHz):
d
205.8(C1), 135.9, 133.4, 128.7(2C),
128.4(2C), 67.5(C3), 45.8(C2), 20.3(C4), 11.2(CH3); MS
m/z (%): 179 (0.7), 178 (0.2), 160 (11), 133 (30), 123 (34),
106 (10), 105 (100); Anal. Calcd for C11H14O2: C, 74.13;
H, 7.92. Found: C, 74.19; H, 7.79.
4.1.6. NaBH4 reduction of 7: preparation of 4 and 5. In a
methanolic solution of 7 (125 mg, 0.70 mmol, 50 mL),
NaBH4 (19 mg, 0.5 mmol) was added slowly at 0 ꢂC and the
reaction monitored by TLC. After the completion of the re-
action and usual processing, the products were separated by
chromatography over silica gel to give (1R,2S,3S)-2-methyl-
1-phenyl-1,3-butanediol 4 as a white solid, mp 83 ꢂC
(36 mg, 29% yield), [a]2D5 +36.8 (ee 97%) and (1S,2S,3S)-
2-methyl-1-phenyl-1,3-butanediol 5 as a white solid, mp
86 ꢂC (27 mg, 21% yield); [a]D25 ꢁ29.8 (c 1.0, CHCl3) (97%
ee); IR (KBr): 3356, 3057, 2974, 2933, 1490, 1453, 1416,
4.1.8.2. Preparation of (2S,3S)-3-hydroxy-2-methyl-1-
phenylbutanone 7. To a suspension of Z. rouxii (wet pellet,
4.5 g) in distilled water (55 mL) containing glucose (3 g), an
ethanolic solution of compound (ꢀ)-1 (100 mg, 0.57 mmol
in 1 mL) was added and the contents shaken at 28 ꢂC using
a bubbler. Reaction was monitored by TLC. After the com-
pletion of the reaction (48 h) and processing, purification by
column chromatography over silica gel gave a white solid
(2S,3S)-3-hydroxy-2-methyl-1-phenylbutanone 7, mp 43–
45 ꢂC (83 mg, 83% yield); [a]D25 +67.5 (c 1.0, CHCl3)
(98% ee); IR (KBr): 3441, 2973, 1678, 1448, 1376, 1112,
1
1126, 1020, 759, 705 cmꢁ1; H NMR (200 MHz, CDCl3):
d 7.21–7.30 (5H, m, Ar-H), 4.48 (1H, d, J¼9.2 Hz,
PhCHOH), 3.91 (1H, qd, J¼8.2, 6.1 Hz, CH3CHOH), 1.83
(1H, m, CHC(2)), 1.24 (3H, d, J¼6.1 Hz, CH3CHOH), 0.68
(3H, d, J¼7.1 Hz, CH3C(2)); 13C NMR (50 MHz): d 142.2,
128.7, 127.8, 127.0, 126.0, 125.5, 77.1(C1), 71.2(C3),
46.1(C2), 21.7(C4), 13.0(CH3); MS m/z (%): 181 (1), 162
(5), 133 (4), 125 (7), 107 (100), 105 (5), 91 (3), 79 (30),
57 (50), 43 (10); Anal. Calcd for C11H16O2: C, 73.30;
H, 8.95. Found: C, 73.39; H, 9.08.
1
911, cmꢁ1; H NMR (200 MHz, CDCl3): d 7.99 (2H, d,
J¼7.3 Hz, Ar-H), 7.52–7.58 (3H, m, Ar-H), 4.14 (1H, quin-
tet, J¼6.4 Hz, CH3CHOH), 3.51 (1H, quintet, J¼7.0 Hz,
CHC(2)), 1.31 (3H, d, J¼6.4 Hz, CH3CHOH), 1.26 (3H, d,
J¼7.3 Hz, CH3C(2)); 13C NMR (50 MHz): d 205.2(C1),
136.4, 133.2, 128.6(2C), 128.3(2C), 69.7(C3), 47.6(C2),
20.7(C4), 15.2(CH3); MS m/z (%): 179 (0.3), 178 (0.3),
164 (0.5), 163 (1), 160 (5), 145 (1), 133 (27), 123 (34),
105 (100), 91 (2); Anal. Calcd for C11H14O2: C, 74.13; H,
7.92. Found: C, 74.21; H, 7.84.
4.1.7. Preparation of racemic 3-hydroxy-2-methyl-1-phe-
nylbutanone. Racemic 2-methyl-1-phenyl-1,3-butanediol
(900 mg, 5 mmol), obtained as a result of NaBH4 reduction
of diketone (ꢀ)-1, was reacted with pyridinium dichromate
(1.880 g, 5 mmol) in dimethyl formamide (10 mL), the con-
tents stirred at 0 ꢂC for 2.5 h and the reaction monitored by
TLC. After completion of the reaction, the mixture diluted
with solvent ether (150 mL), filtered and the solid washed
with solvent ether (2ꢃ50 mL). The combined organic layer
was concentrated under reduced pressure. The crude product
was purified by column chromatography on silica gel to give
a mixture of syn- and anti-3-hydroxy-2-methyl-1-phenyl-
butanone as an oil (360 mg, 40% yield) in the ratio of
40:60 as analyzed from 1H NMR.
Acknowledgements
One of the authors (K.A.) is thankful to DBT for financial
support in the form of SRF.
References and notes
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P. I. Tetrahedron Lett. 2001, 42, 5005–5007; (c) Ireland, T.;
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Chimni, S. S.; Mahajan, D.; Babu, S. V. V. Tetrahedron Lett.
4.1.8. Biocatalytic reduction of 2-methyl-1-phenyl-1,3-
butanedione 1.
4.1.8.1. Preparation of (2R,3S)-3-hydroxy-2-methyl-1-
phenylbutanone 6. In a typical experiment, to a suspension
of S. marcescens (wet pellet, 4.5 g) in distilled water
(55 mL) containing glucose (3.0 g), an ethanolic solution
of compound (ꢀ)-1 (100 mg, 0.57 mmol in 1 mL) was added
and the contents shaken at 28 ꢂC using a bubbler. The
progress of the reaction was monitored by TLC. After the
completion of the reaction (54 h), the contents were centri-
fuged and the supernatant and cell pellet extracted separately