On the baker's yeast mediated transformation of α-bromoenones. Synthesis of (1S,2R)-2-bromoindan-1-ol and (2s,3s)-3-bromo-4-phenylbutan-2- ol

Article abstract of DOI:10.1016/S0957-4166(98)00128-1

Fermenting baker's yeast converts α-bromo substituted enones 7 and 10 into enantiomerically pure (1S,2R)2-bromoindan-1-ol 3 and (2S,3S)-3-bromo-4- phenylbutan-2-ol 11, respectively, through the intermediacy of the corresponding saturated ketones. Structurally related 16 provides the (2R)- allylic alcohol 17 prevalently.

Full text of DOI:10.1016/S0957-4166(98)00128-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1589–1596
On the baker’s yeast mediated transformation of α-bromoenones.
Synthesis of (1S,2R)-2-bromoindan-1-ol and (2S,3S)-3-bromo-
4-phenylbutan-2-ol
Josephina Aleu, Giovanni Fronza, Claudio Fuganti, Valentina Perozzo and Stefano Serra∗
Dipartimento di Chimica del Politecnico, Centro CNR per lo Studio delle Sostanze Organiche Naturali, Via Mancinelli 7,
I-20131 Milano, Italy
Received 11 March 1998; accepted 26 March 1998
Abstract
Fermenting baker’s yeast converts α-bromo substituted enones 7 and 10 into enantiomerically pure (1S,2R)-
2-bromoindan-1-ol 3 and (2S,3S)-3-bromo-4-phenylbutan-2-ol 11, respectively, through the intermediacy of the
corresponding saturated ketones. Structurally related 16 provides the (2R)-allylic alcohol 17 prevalently. © 1998
Elsevier Science Ltd. All rights reserved.
1. Introduction
The preparation of optically active forms of 1-aminoindan-2-ol has recently received interest mainly
because of the utility of the (1S,2R)-enantiomer 1 (Fig. 1) in the synthesis of the HIV protease in-
hibitor indinavir.1 To this end, the methodologies applied include the asymmetric epoxidation of indene
followed by ammonia treatment,2,3 the chemical resolution of the racemic material,4 and the use of
biological methods leading to a variety of enantiomerically pure forms of advanced intermediates.5–9
These also include the two enantiomeric forms of both diastereoisomers of indene bromohydrin. Accord-
ingly, (1S,2R)-3 is accessible by enzymic benzylic hydroxylation of prochiral 2-bromoindane6 whereas
the (1S,2S)-diastereoisomer 2 can be obtained by kinetic resolution in the enzymic acylation of the
racemic modification9 or by microbial reduction of 2-bromoindan-1-one 5 (Fig. 2) with Cryptococcus
macerans.10 The latter method seems of limited preparative significance because of the reported seven
days incubation period. The 55% isolated yield suggests, however, at least partial racemization in the
culture medium of the enantiomeric form of the ketone not accepted by the reducing enzyme(s).
∗
Corresponding author.
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00128-1

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Fig. 1.
Fig. 2.
2. Results and discussion
In light of the known ability of fermenting baker’s yeast to reductively transform a variety of
cyclic carbonyl compounds into optically active carbinols,11 we decided to study a baker’s yeast
mediated approach to optically active indene bromohydrin, using prochiral 2-bromo-2-inden-1-one 7 as
a substrate instead of the racemic ketone 5. The mode of baker’s yeast transformation of α,β-unsaturated
ketones is not fully predictable.12 Depending upon the nature of the substituents at relevant positions
in the molecule, α-enones provide enantiomerically pure allylic alcohols, saturated ketones, saturated
carbinols or mixtures thereof.13 Accordingly, a set of structurally related products to 7 was submitted to
baker’s yeast reduction which provided highly functionalized enantiomerically pure products of potential
synthetic interest and we outline the results here.
Thus, the unsaturated bromoketone 7 was prepared from 2,2-dibromoindan-1-one 614 upon treatment
with triethylamine at room temperature. The product, obtained as an amorphous solid, is rather unstable,
but can be kept for weeks when cooled. From the incubation of 7 (3 g) in fermenting baker’s yeast (250
g in 1 L tap water) after 24 h, a crystalline bromohydrin was isolated as the only transformation product
m.p. 106–109°C (from hexane), [α]D20=−59 (c 4.5, CHCl3) in 75% yields, 99% ee by HPLC analysis
on Chiracel OD. This material was shown to be (1S,2R)-3 by comparison with an authentic sample.6 The
analysis of samples withdrawn from the incubation mixture at different time intervals indicates that 7 is
transformed into 3 via the intermediacy of the ketone 5. The allylic alcohol derived from the reduction of
the carbonyl group of 7 was not detected. We were unable to determine the enantiomeric composition of
intermediate 5 produced by reduction of 7, because attempts at separation of the two enantiomeric forms
of the bromoketone by HPLC on Chiracel OD failed. Accordingly, the production of (1S,2R)-3 might be
a consequence of the direct reduction by baker’s yeast of enantiomerically pure (2R)-5, produced in the
enzymic double bond saturation, or of the kinetic preference for the (2R)-enantiomer of a ketone which
rapidly racemizes in the transformation medium.
Indeed, direct incubation of 5 with baker’s yeast provided enantiomerically pure 3 in over 85% isolated
yield, thus supporting the latter view. In an experiment in which the incubation of 5 was interrupted
at ca. 50% conversion, the recovered material, separated from 3 by SiO2 column chromatography,
1
was shown by H NMR studies in the presence of tris[3-(heptafluoropropylhydroxymethylene)-(+)-
camphorato]europium (III) to contain ca. 20% excess of a single enantiomer, conceivably corresponding
to the (S)-material. In ethanolic solution, the latter material showed a negative optical rotation, which,
however, decreased on standing. Product 5 is a better substrate for baker’s yeast than 7. It provided
enantiomerically pure 3 in 16 h incubation at 6 g/L in the presence of 250 g of baker’s yeast.

J. Aleu et al. / Tetrahedron: Asymmetry 9 (1998) 1589–1596
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Thus, in C. macerans and baker’s yeast, the reduction of 2-bromoindanone occurs with formal hydride
delivery onto the re-face of the carbonyl group to produce the (1S)-configured carbinol, but the preferred
absolute configuration of the substrate changes from (S) to (R), respectively, leading eventually to the
enantiomerically pure diastereoisomeric materials 2 and 3.
The dibromoketone 6 was also submitted to the action of baker’s yeast. The substrate was incubated at
1 g/L, due to the low solubility, and provided enantiomerically pure 3 in 30% yield. From the incubation
mixture unreacted 6 was also recovered (35%). At present, no indications are available on the mechanism
of the formal removal of one bromine atom from the framework of 6 during the yeast treatment. However,
it is also worth mentioning the conversion of 1-bromoindan-2-one 8, treated with baker’s yeast (3 g/L),
as above, within 4 h into indan-2-one 9 and indan-2-ol, in ca. 4:1 ratio.
Interestingly enough, baker’s yeast operates on indan-1-one derivatives structurally related to the above
materials in a different way. Thus, 2-benzylideneindan-1-one3 is rapidly reduced to the saturated ketone.
Only at long incubation time is there the formation of minute amounts of a carbinol, m.p. 98–100°C,
[α]D20=+12.6 (c 1, CHCl3), enantiomerically pure on the basis of HPLC analysis. The material was
assigned the anti relative configuration depicted in structural formula 4, while the absolute configuration
remains undefined. The relative stereochemistry of 4 was determined from the comparison of the 13C
NMR spectra of the two diastereoisomers obtained by NaBH4 reduction of the 2-benzylideneindan-1-
one. On going from the syn to the anti configuration, the carbons C-1 and C-2 are shifted downfield by
4.6 and 5.4 ppm respectively; similar chemical shift variations were observed between the syn and anti
2-methyl-1-cyclopentanols, thus allowing by comparison the assignment of the relative configuration of
4. The saturated ketone isolated from the incubation mixture was devoid of optical activity. Moreover, 3-
aryl substituted inden-1-ones are converted by baker’s yeast into the corresponding (S)-allylic alcohols, as
recently reported in the context of a synthetic study of enantiomerically pure antihypertensive therapeutic
agents.15
The study on the mode of yeast reduction of α-enones was subsequently extended to acyclic 10.16 The
latter product (Fig. 3) bears, as compound 7, α-bromo and β-phenyl substituents, but at opposite sites of
the double bond, in an acyclic framework. The bromoenone 10 proved to be a good substrate for baker’s
yeast. It is transformed at 8 g/L in the presence of 400 g of yeast into the saturated carbinol 11, oil,
[α]D20=−13.6 (c 2.2, CHCl3), in 80% isolated yields. The (2S,3S)-configuration depicted in structural
formula 11 and the substantial enantiomeric purity are assigned on the basis of the following evidence.
The bromoalcohol 11 was first converted by LiAlH4 treatment in refluxing THF into enantiomerically
pure (2S)-4-phenylbutan-2-ol 12, [α]D20=+13.8 (c 3.8, CHCl3), identical with the material obtained
from (−)-betuligenol17,18 by removal of the phenolic hydroxyl group.19,20 Subsequently, product 11,
upon basic treatment, was converted into an epoxide, [α]D20=−16.7 (c 8.2, CHCl3), which upon LiAlH4
treatment in refluxing THF provides (2S)-1-phenylbutan-2-ol 14, [α]D20=+18.5 (c 5.3, AcOEt) and +22
(c 1.5, Et2O) (lit.21 for the (R)-enantiomer, −21.7, Et2O), shown to be enantiomerically pure by HPLC
analysis, containing a minute amount of (2S)-12. With the expectation that epoxide formation took place
with inversion of configuration at the carbon atom from which the bromine atom is displaced, the present
results support the (2S,3S)-configuration for 11, the bromoalcohol, and structure 13 for the epoxide
derived from the latter upon basic treatment.
In the yeast reduction of 10, the only detectable species present in the incubation mixture were the
starting material and the saturated carbinol 11, with no trace of the allylic carbinol. This observation
suggests that the rate limiting process is the saturation of the double bond of the α-enone. The saturated
ketone, once formed, is rapidly reduced to the bromoalcohol actually isolated. The activating function
of the carbonyl group towards the enzymic double bond saturation is further supported by the following
experiments. The synthesis of 10 proceeds by sodium acetate induced dehydrobromination of the crude

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Fig. 3.
Fig. 4.
dibromoketone obtained by treatment with 1 mol. equiv. of bromine benzalacetone in CHCl3 solution.16
In our hands, the process provided, as well as 10, substantial quantities of 16 (Fig. 4), conceivably
formed by the action of acetate on 15, formed by α-bromination of benzalacetone. Baker’s yeast
incubation of 16 provides a ca. 3:1 mixture of the unsaturated and saturated (2R)-carbinols 17 and
19. The stereochemical assignment was made by converting the mixture, by catalytic hydrogenation
followed by basic hydrolysis, into (2R)-4-phenylbutan-1,2-diol 20, identical in every respect, including
specific rotation, to the product obtained from commercial (2R)-ethyl-2-hydroxy-4-phenylbutyrate22 by
LiAlH4 reduction. The enantiomerically pure allylic (2R)-diol 18 can be separated from 20 by fractional
crystallization from hexane.
The enone 16 in baker’s yeast undergoes carbonyl reduction to provide the allylic alcohol 17 or
saturation of the double bond, followed by carbonyl reduction, to yield eventually the saturated alcohol
19. Once the transformation took place, the ratio 17/19 is not altered over time, and, as the incubation
proceeds further, the only noticeable operation is the hydrolysis of the acetate ester to provide 18 and
20, respectively. Moreover, the synthetic carbinol 17, prepared from 16 by NaBH4 reduction at low
temperature and neutral pH in order to avoid acetate hydrolysis, on prolonged yeast incubation undergoes
only ester hydrolysis to racemic 18. Seen together, these results thus show that baker’s yeast, although
on the chemical scene for many years, still exhibits unpredictable behaviour towards structurally related
substrates, as here indicated by the different mode of transformation of 7, 10 and 16. However, these
processes make available highly functionalized enantiomerically pure products of synthetic potential,
such as the bromoalcohol 3, useful in the synthesis of (1S,2R)-1-aminoindan-2-ol, 11, 13 and the allylic
α-acetoxy carbinol 17.

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3. Experimental
3.1. General procedure for the baker’s yeast transformation
In a 2 L three-necked round-bottomed flask, a mixture is made up composed of 250 g baker’s yeast,
100 g of D-glucose and 1 L of tap water at 38–40°C. After 10 min stirring, the substrate dissolved in the
minimum amount of ethanol is added dropwise. The stirring is continued at the above temperature and
at the end of the process the mixture is poured into 2 L of acetone:ethyl acetate (1:1). After stirring for
2 h, the mixture is filtered through a large Buchner funnel on a Celite pad, which is later washed with
the same solvent. The aqueous phase is extracted twice with 0.5 L of ethyl acetate. The residue obtained
upon evaporation of the dried combined organic extracts is purified by column chromatography.
HPLC analyses were performed on a chiral column (Chiracel OD, Daicel, Japan): 254 nm, 0.6 mL/min,
hexane:isopropanol (9:1), (1S,2R)-3 Rt=13.96 min; (1R,2S)-3 Rt=14.56 min; (+)-4 Rt=12 min, (−)-4
Rt=26 min; (2S,3S)-11 Rt=10.78 min; (R)-12 Rt=11.00 min; (S)-12 Rt=15.44 min; (2S)-17 Rt=10.65;
(2R)-17 Rt=11.4 min (flux: 1 mL/min); (2S)-19 Rt=14.32 min; (2R)-19 Rt=15.7 min (flux: 1 mL/min);
(2S)-18 Rt=12.8; (2R)-18 Rt=17.45 min (flux: 1 mL/min); (2S)-20 Rt=14.62 min; (2R)-20 Rt=19.57 min
(flux: 1 mL/min).
3.2. 2-Bromoinden-1-one 7
2,2-Dibromoindan-1-one 614 (15 g, 52 mmol) in THF (100 mL) was treated with triethylamine (40
mL) at room temperature for 24 h. The mixture was diluted with ethyl acetate (150 mL) and washed with
cold water, 5% HCl and 1% NaHCO3. The dried organic phase was concentrated under reduced pressure
and the residue purified by SiO2 column chromatography with increasing amounts of ethyl acetate in
hexane to give 7, an amorphous solid, in 63% yield (7 g, 33 mmol). 1H NMR (250 MHz, CDCl3): δ 7.01
(1H, d, J=7.5 Hz), 7.15–7.25 (1H, m), 7.30–7.38 (1H, m), 7.45 (1H, d, J=7.5 Hz), 7.61 (1H, s); m/z (EI):
210 (M++2, 27), 208 (M+, 30), 182 (M++2−CO, 32), 180 (M+−CO, 35), 129 (M+−Br, 78), 101 (100),
98 (36), 74 (48).
3.3. (1S,2R)-2-Bromoindan-1-ol 3 from 5 and 7
Baker’s yeast reduction of 7 (3 g/L) and 5 (6 g/L) provided 3, m.p. 107–109°C and 108°C, respectively
(from hexane), [α]D20=−59 (c 4.5, CHCl3) and −60, respectively (lit6 [α]D20=−61). H NMR (250
1
MHz, CDCl3): δ 3.41 (2H, m), 4.95 (2H, m), 7.20–7.35 (4H, m); m/z (EI): 214 (M++2, 10), 212 (M+,
15), 197 (M++2−OH, 12), 195 (M+−OH, 10), 133 (M+−Br, 100), 116 (22), 103 (7), 77 (10). The two
materials were shown by the above HPLC analysis to possess 0.99 ee.
3.4. (2S)-2-Bromoindan-1-one 5 from baker’s yeast reduction of rac-5
Baker’s yeast reduction of 5 (6 g/L) was interrupted at ca. 50% conversion. The unchanged product
was separated from carbinol 3 by column chromatography (10% AcOEt in hexane) and submitted to 1H
NMR studies in the presence of tris[3-(heptafluoropropylhydroxymethylene)-(+)camphorato]europium
(III): 1H NMR of remaining 5 (CDCl3): δ 3.43 (1H, dd, J=3.0 and 17.9 Hz), 3.85 (1H, dd, J=7.4 and 17.9
Hz), 4.68 (1H, d, J=3.0 and 7.4 Hz), 7.46 (2H, m), 7.67 (1H, m), 7.85 (1H, d, J=7.7 Hz). Upon addition
of the Eu(III) complex to the solution, many signals are doubled, the best separation occurring for the
aromatic hydrogen peri to the carbonyl group (originally at 7.85 ppm) which gives rise to two signals at
8.29 (minor enantiomer) and 8.19 (major enantiomer) ppm. The two signals were integrated giving ca.
20% excess of a single enantiomer.

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3.5. anti-2-Benzylindan-1-ol 4 from benzylideneindan-1-one
2-Benzylideneindan-1-one3 was submitted (1 g/L) to the action of fermenting baker’s yeast. The usual
work-up, after 62 h incubation, provided, after separation on a SiO2 column with hexane:AcOEt (9:1),
2-benzylindan-1-one, devoid of optical activity in chloroform solution, and the crystalline carbinol 4,
1
m.p. 98–100°C (from hexane), [α]D20=+12.6 (c 1, CHCl3). H NMR (250 MHz, CDCl3): δ 2.43–2.62
(2H, m), 2.70–2.85 (1H, m), 2.90–3.14 (2H, m), 4.94 (1H, d, J=5.6 Hz), 7.10–7.40 (9H, m); 13C NMR
(CDCl3): δ 35.80 (CH2), 39.31 (CH2), 52.21 (CH), 80.84 (CHOH), 123.97 (1C), 124.78 (1C), 126.17
(1C), 126.78 (1C), 128.16 (1C), 128.55 (2C), 128.92 (2C), 140.64 (1C), 141.55 (1C), 144.56 (1C);
m/z (EI): 224 (M+, 20), 206 (M+−H20, 40), 132 (41), 115 (31), 91 (100), 77 (30). Found: C, 85.79;
H, 7.13; C16H16O requires C, 85.68; H, 7.19. syn-2-Benzylindan-1-ol (obtained by NaBH4 reduction
1
of benzylideneindan-1-one followed by separation of the two diastereoisomers), H NMR (400 MHz,
CDCl3): δ 1.80 (1H, s br), 2.51–2.79 (4H, m), 3.02 (1H, dd, J=5.5 and 13.2 Hz), 4.88 (1H, d, J=5.3 Hz),
7.10–7.30 (9H, m); 13C NMR (CDCl3): δ 34.92 (CH2), 35.84 (CH2), 46.84 (CH), 76.23 (CHOH), 124.75
(1C), 124.92 (1C), 125.84 (1C), 126.66 (1C),128.35 (2C), 128.43 (1C), 128.87 (2C), 141.30 (1C), 143.38
(1C) 144.75 (1C).
3.6. Baker’s yeast incubation of 2,2-dibromoindan-1-one 6
Product 614 (1 g/L) on yeast treatment provides, after usual work-up and chromatographic separation
of the crude extract, unreacted material (35%) and product 3 (30%), [α]D20=−60 (c 1, CHCl3). The
material was shown by HPLC analysis to possess 99% ee.
3.7. (2S,3S)-3-Bromo-4-phenylbutan-2-ol 11
Baker’s yeast reduction of 1016 (8 g/1 L, 0.4 kg baker’s yeast) provided 11 (6.5 g, 80%) as a colourless
1
oil, [α]D20=−13.6 (c 2.2, CHCl3). H NMR (250 MHz, CDCl3): δ 1.30 (3H, d, J=6.5 Hz), 3.10–3.45
(2H, m), 3.70 (1H, m), 4.12–4.25 (1H, m), 7.15–7.45 (5H, m); m/z (EI): 230 (M++2, 1), 228 (M+, 1), 148
(M+−Br, 25), 131 (77), 105 (58), 91 (100), 78 (38); IR (cm−1) 3422, 2976, 1496, 1455, 1376, 751, 700.
Found: C, 52.29; H, 5.80; Br, 34.99; C10H13BrO requires C, 52.42; H, 5.72; Br, 34.87.
3.8. Conversion of (2S,3S)-11 into (2S)-12
Compound 11 (1 g, 4.4 mmol) in diethyl ether (10 mL) was added to LiAlH4 (0.2 g, 5.3 mmol)
in refluxing diethyl ether (60 mL). After 2 h, ethyl acetate was added to the cooled reaction mixture,
followed by cold 5% HCl. The dried organic phase was evaporated and the residue was purified by
column chromatography to give carbinol 12 (0.6 g, 4.0 mmol) in 90% yield, purified by bulb-to-bulb
vacuum distillation at the water pump (oven temp.: 140°C), 0.98 ee by HPLC, [α]D20=+13.8 (c 3.8,
1
CHCl3). H NMR (250 MHz, CDCl3): δ 1.21 (3H, d, J=6.5 Hz), 1.70–1.83 (2H, m), 2.57–2.88 (2H,
m), 3.82 (1H, m), 4.83 (1H, s, OH), 7.15–7.33 (5H, m); m/z (EI): 150 (M+, 32), 132 (M+−OH, 64), 117
(100), 92 (39), 91 (65), 78 (15); IR (cm−1): 3357, 2928, 1497, 1454, 1375, 746.
3.9. Conversion of 11 into the epoxide 13
Product 11 (2 g, 8.8 mmol) in methanol (60 mL) was treated with Na2CO3 (5 g, 47 mmol) at room
temperature for 30 min. Water was then added and the mixture was extracted with diethyl ether (3×100
mL). The dried organic phase was evaporated under reduced pressure and the residue purified by column
chromatography to give the epoxide 13 (1.1 g, 7.4 mmol) in 84% yield, purified by bulb-to-bulb vacuum

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1595
distillation at 1 mmHg (oven temperature: 90°C), [α]D20=−16.7 (c 8.2, CHCl3). H NMR (250 MHz,
CDCl3): δ 1.04 (3H, d, J=6 Hz), 2.47 (1H, dd, J=14 Hz, J=6 Hz), 2.74 (1H, dd, J=14 Hz, J=6 Hz), 2.77
(1H, m), 2.99 (1H, m), 7.05–7.21 (5H, m); m/z (EI): 148 (M+, 100), 132 (M+−O, 24), 119 (92), 104 (42),
91 (14), 78 (20); IR (cm−1): 2997, 1497, 1455, 1389, 784. Found: C, 81.21; H, 8.12; C10H12O requires
C, 81.04; H, 8.16.
1
3.10. Conversion of the epoxide 13 into carbinols 14 and 12
Compound 13 (0.5 g, 3.4 mmol) in diethyl ether (30 mL) was treated with LiAlH4 (0.2 g, 5.3 mmol) at
reflux for 4 h to give, after the usual work-up, a mixture of carbinols 14 and 12 in ca. 8:1 ratio (by GLC).
Accurate column chromatography allows the separation of alcohol 14 (0.3 g, 2.0 mmol) in pure form, in
58% yield, [α]D20=+18.5 (c 5.3, AcOEt), +22 (c 1.5, Et2O) (lit.21 for the (R)-enantiomer, −21.7, Et2O).
1H NMR (250 MHz, CDCl3): δ 1.00 (3H, t, J=7.5 Hz), 1.49–1.66 (2H, m), 2.64 (1H, dd, J=9, 14.5 Hz),
2.82 (1H, dd, J=5, 14.5 Hz), 3.73 (1H, m), 7.17–7.39 (5H, m); m/z (EI): 150 (M+, 72), 133 (M+−OH,
18), 92 (100); IR (cm−1) 3370, 2933, 1455, 742, 700.
3.11. Acetoxy ketone 16
Column chromatography of the crude reaction mixture containing 10,16 produced by the action of
ethanolic sodium acetate from the crude mixture obtained treating benzalacetone with 1 mol. equiv. of
bromine in CHCl3, provides, with increasing amounts of ethyl acetate in hexane, in ca. 4:1 ratio, product
10 and the acetoxy derivative 16, oil. 1H NMR (250 MHz, CDCl3): δ 2.21 (3H, s), 4.96 (2H, s), 6.79 (1H,
d, J=15 Hz), 7.41 (3H, m), 7.56 (2H, m), 7.68 (1H, d, J=15 Hz). Found: C, 70.71; H, 6.01; C12H12O3
requires C, 70.58; H, 5.92.
3.12. 1-Acetoxycarbinols 17 and 19 and 1,2-diols 18 and 20
Baker’s yeast reduction of 16 (6 g/L) provided after 3 h incubation 17 and 19 in ca. 3:1 ratio, in
80% yield. Continuing the incubation, the ratio of unsaturated to saturated materials was not altered, but
1
there was hydrolysis of the acetate ester to give 18 and 20. H NMR of 17 in the mixture (250 MHz,
CDCl3): δ 2.10 (3H, s), 4.10–4.30 (2H, m), 4.56 (1H, m), 6.18 (1H, dd, J=7, 16 Hz), 6.70 (1H, d, J=16
Hz), 7.15–7.45 (5H, m); of 19 (250 MHz, CDCl3): δ 1.71–1.89 (2H, m), 2.09 (3H, s), 2.57–2.90 (2H,
m), 3.54–3.92 (2H, m), 7.10–7.31 (5H, m). The crude incubation mixture, containing 17–20, 5 g, in 30
ml MeOH was treated overnight at room temperature with 0.2 g of sodium methoxide. After that time,
the hydrolysis of the acetate group was complete (TLC: hexane:AcOEt=1:1). The reaction mixture was
concentrated under vacuum and diluted with water. Two extractions with AcOEt provided an oil, from
which diol 18 (50%) separated from hexane, m.p. 134°C, [α]D20=−78 (c 1, CHCl3). H NMR (250
1
MHz, CDCl3): δ 1.60–2.05 (2H, m), 4,43 (1H, m), 6.20 (1H, dd, J=5.5, 16.5 Hz), 6.69 (1H, d, J=16.5
Hz), 7.18–7.46 (5H, m). Found: C, 73.29; H, 7.31; C10H12O2 requires C, 73.15; H, 7.37. The material was
shown to possess 0.98 ee by HPLC analysis and comparison with the racemic material produced from
16 by NaBH4 reduction, followed by ester hydrolysis under basic conditions. Compounds 17, 18 and 19
have been also characterized by GC–MS: m/z (EI) (17): 146 (M+−CH3COOH, 50), 133 (M+−CH2OAc,
100), 115 (47), 105 (24), 91 (20); m/z (EI) (18): 149 (M+−OAc, 10), 130 (40), 117 (20), 104 (30), 91
(100); m/z (EI) (19): 164 (M+, 6), 146 (M+−H2O, 5), 133 (100), 115 (58), 103 (21), 91 (23).

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3.13. (2R)-4-Phenylbutan-1,2-diol 20
The mixture of the compounds 18 and 20 from baker’s yeast incubation (0.3 g) in AcOEt (50 mL)
was hydrogenated at normal pressure in the presence of 10% Pd/C (0.1 g) to give 20, colourless oil,
1
[α]D20=−13.2 (c 4.5, CHCl3). H NMR (250 MHz, CDCl3): δ 1.55–1.90 (2H, m), 2.60–2.90 (2H, m),
3.40–3.55 (2H, m), 3.56–3.75 (1H, m), 7.10–7.35 (5H, m); m/z (EI): 166 (M+, 2), 148 (M+−H2O, 23),
130 (8), 117 (30), 104 (10), 91 (100); IR (cm−1): 3358, 2931, 1497, 1455, 1389, 700. Found: C, 72.35;
H, 8.45; C10H14O2 requires C, 72.26; H, 8.49. 0.99 ee by HPLC analysis. This material was identical in
every respect to the product obtained when (2R)-ethyl-2-hydroxy-4-phenylbutyrate (Fluka) was reduced
with LiAlH4 in refluxing THF, followed by the usual work-up.
Acknowledgements
The financial support of Progetto Finalizzato CNR Biotecnologie is acknowledged.
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