Preparation of the four stereoisomers of 3-bromo-2-butanol or their acetates via lipase-catalysed resolutions of the racemates derived from dl- or meso-2,3-butanediol

Article abstract of DOI:10.1016/j.tetasy.2005.06.028

The four stereoisomeric 3-bromo-2-butanols and/or their acetates were prepared via lipase-catalysed kinetic resolution by hydrolyses of the acetates of the (±)-syn- and (±)-anti-3-bromo-2-butanols, or via esterifications of the alcohols. The diastereomeric bromoacetates were obtained by syntheses from the dl- and meso-2,3-butanediols, respectively. On a preparative scale, the four stereoisomers, either as the free alcohols or as their acetates, were obtained in >95% ee, and in 35-40% yield (based on the starting racemates).

Full text of DOI:10.1016/j.tetasy.2005.06.028

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2607–2611
Preparation of the four stereoisomers of 3-bromo-2-butanol or
their acetates via lipase-catalysed resolutions of the
racemates derived from dl- or meso-2,3-butanediol
Rong Liu,a,b Per Berglunda and Hans-Erik Hogbergb,*
¨
aSchool of Biotechnology, Department of Biochemistry, Royal Institute of Technology (KTH), AlbaNova University Center,
SE-106 91 Stockholm, Sweden
bDepartment of Natural Sciences, Mid Sweden University, SE-851 70 Sundsvall, Sweden
Received 25 May 2005; accepted 21 June 2005
Abstract—The four stereoisomeric 3-bromo-2-butanols and/or their acetates were prepared via lipase-catalysed kinetic resolution by
hydrolyses of the acetates of the ( )-syn- and ( )-anti-3-bromo-2-butanols, or via esterifications of the alcohols. The diastereomeric
bromoacetates were obtained by syntheses from the dl- and meso-2,3-butanediols, respectively. On a preparative scale, the four ste-
reoisomers, either as the free alcohols or as their acetates, were obtained in >95% ee, and in 35–40% yield (based on the starting
racemates).
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
be prepared by asymmetric chemical syntheses,2 by
microbial asymmetric reduction of haloketones,3 and
by lipase-catalysed resolution of haloalcohols and/or
esters.1,4 The pure enantiomers of anti- and syn-3-bromo-
2-butanol (R,S)-5 and (R,R)-6, respectively (Scheme 1)
and their esters (S,R)-3 and (S,S)-4 have, however,
Enantiomerically pure halohydrins are important as
convenient precursors of non-racemic chiral epoxides,
which are useful building blocks in enantioselective syn-
theses.1 Various enantiomerically pure halohydrins can
Br
Br
Br
a
b
b
+
2R
2S
3S
3R
HO
OH
AcO
AcO
HO
anti-2-acetoxy-
3-bromobutane
3
dl-2,3-
butanediol
1
(S,R)-3
(R,S)-5
Br
Br
3S
Br
3R
a
+
2R
2S
HO
OH
AcO
AcO
HO
syn-2-acetoxy-
3-bromobutane
4
meso-2,3-
butanediol
2
(S,S)-4
(R,R)-6
Scheme 1. Pure stereoisomers of 3-bromo-2-butanols (R,S)-5 and (R,R)-6 and 2-acetoxy-3-bromobutane (S,R)-3 and (S,S)-4 obtained by lipase
catalysed hydrolysis of racemic anti- or syn-2-acetoxy-3-bromobutanes 3 and 4 obtained from dl- or meso-2,3-butanediol, 1 and 2, respectively.
Reagents and conditions: (a) HBr in acetic acid, 0 °C, 30 min, 45 °C, 1 h (75–90%) and (b) CALB, Amano PS, or CRL, hexane–water, 1/1, 0.8–12 h.
*
Corresponding author. Tel.: +46 60 148704; fax: +46 60 148802; e-mail: hans-erik.hogberg@miun.se
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.06.028

2608
R. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 2607–2611
Br
Br
Br
3R
Br
3S
a
c
+
2R
2S
AcO
HO
HO
RCO2
anti-2-acetoxy-
3-bromobutane
3
anti-3-bromo-
2-butanol
5
(S,R)-5 (R,S)-7 (R = n-C3H7)
Br
Br
Br
3S
Br
3R
b or c
a
+
2R
2S
AcO
HO
HO
RCO2
syn-2-acetoxy-
3-bromobutane
4
syn-3-bromo-
2-butanol
6
(R,R)-4 (R = CH3)
(R,R)-8 (R = n-C3H7)
(S,S)-6
Scheme 2. Pure stereoisomers of 3-bromo-2-butanols (S,R)-5 and (S,S)-6 and either 2-acetoxy-3-bromobutane (S,S)-4 or 2-butanoyloxy-3-
bromobutanes (R,S)-7 and (R,R)-8 obtained by lipase catalysed acylation of racemic anti- or syn-3-bromo-2-butanols 5 and 6 obtained by chemical
hydrolysis of racemic anti- or syn-2-acetoxy-3-bromobutane 3 or 4. Reagents and conditions: (a) HCl (aq, 8 M), 24 h, 75%, (b) CALB, vinyl acetate,
CH2Cl2, rt, 22 h and (c) CALB, vinyl propionate, CH2Cl2, rt, 72 h.
attracted limited attention.5 Although the enantiomers
of the anti-esters 3 are easily accessible from the pure
d- and l-enantiomers of the 2,3-butanediol 1,5e the enan-
tiomers of the syn-esters 4 are not readily available. The
enantiomers of the anti-esters 3 are useful precursors of
enantiomerically pure (S,S)- or (R,R)-2,3-dimethyloxi-
rane,5e which, due to their C2-symmetry, are useful
building blocks. As a result they react with nucleophiles
to give a single product, whereas meso- or unsymmetri-
cal epoxides tend to give mixtures of products.6 The aim
of this work was to efficiently resolve either the ( )-anti-
and ( )-syn-2-acetoxy-3-bromobutanes, 3 and 4, respec-
tively, or the corresponding alcohols, ( )-anti- and
( )-syn-3-bromo-2-butanol, 5 and 6, by enzyme-cataly-
sed hydrolysis (Scheme 1) or esterification (Scheme 2).
mide in acetic acid (4.1 M) at 0 °C for 30 min and then
at 45 °C for 1 h, which furnished both anti- and syn-2-
acetoxy-3-bromobutanes 3 and 4 in 75–90% yield.
According to the known mechanism of the reaction,7
complete Walden inversion should take place at the
carbon atom bearing the bromine. Thus, the dl-diol 1
gave ( )-anti-2-acetoxy-3-bromobutane 3, whereas the
meso-diol 2 furnished ( )-syn-2-acetoxy-3-bromobutane
4. In the latter case, however, we observed a slight
decrease in the diastereomeric ratio. Thus a sample of
meso-diol 2 with 99/1 dr, gave syn-ester 4 with 95/5 dr.
In contrast, samples of dl-diol 1 (99.5/0.5 and 91/9 dr)
provided the anti-ester 3 with preserved diastereomeric
ratios.
2.2. Candida antarctica lipase B-catalysed hydrolysis
The racemic bromoacetates 3 and 4 are easily prepared
from the appropriate 2,3-butanediol diastereomers 1
and 2, respectively.5e,7 Both dl- and meso-2,3-butanediol
1 and 2 are accessible in high diastereomeric purity using
previously published procedures.8 Thus, commercially
available 2,3-butanediol as a meso-/dl-mixture [dr (dia-
stereomeric ratio) = 85/15] gives meso-2,3-butanediol 2
(dr = 99/1) after crystallisation while the dl-form 1
(dr ꢀ 95/5) is obtained from commercially available
dl-/meso-mixtures after epimerisation.8 The two racemic
diastereomers of the anti- and syn-bromoacetates 3 and
4 are then prepared from the respective diol diastereo-
mers 1 and 2 by treatment with hydrogen bromide in
acetic acid.7
The diastereomeric anti- and syn-2-acetoxy-3-bromo-
butanes 3 and 4 were only slightly soluble in water.
The partition coefficient between identical volumes of
hexane and the aqueous buffer solution used below
was found to be 97/3 for both of the bromoesters 3
and 4 (Scheme 1), while the partition coefficients of
the anti- and syn-3-bromo-2-butanols 5 and 6 (Scheme
2) were approximately 30/70. Thus, in an enzyme-catal-
ysed hydrolysis reaction in a hexane–water system, the
substrate, either the anti- or syn-2-acetoxy-3-bromo-
butane 3 or 4 was almost completely dissolved in the
hexane phase, whereas the main part of the product,
3-bromo-2-butanol, was found in the water phase.
The lipase-catalysed kinetic resolution by hydrolysis of
the two diastereomeric racemic acetates 3 and 4 of the
3-bromo-2-butanols 5 and 6 was then studied (Scheme 1).
Of the enzymes screened, lipase B from Candida antarc-
tica (CALB, see Table 1, footnote a) was found to be
best both in terms of rate and enantiomeric ratio (E)
in the resolution of both of the acetates 3 and 4.
2. Enzyme catalysed kinetic resolution of racemic
2-acetoxy-3-bromobutanes
The kinetic resolutions of the two syn- and anti-2-acet-
oxy-3-bromobutanes 4 and 3 were carried out by
lipase-catalysed hydrolyses in biphasic systems
consisting of hexane (1.5–2.0 mL/mmol of ester 4 or 3)
and 0.2 M sodium or potassium phosphate buffer solu-
tion (aq, pH 7.5, 1.5 mL/mmol of 4 or 3) at ambient
temperature. After equilibration of the reaction mixture
2.1. Preparation of the racemic anti- and syn-2-acetoxy-3-
bromobutanes
Both dl- and meso-2,3-butanediol8 1 and 2 (Scheme 1)
were treated with a saturated solution of hydrogen bro-

Table 1. Hydrolysis of the racemic 2-acetoxy-2-bromobutanes 3 and 4 catalysed by various lipasesa
Entry
Substrate (2-acetoxy-
3-bromobutane)
drb
Enzymea
Reaction
time (h)
Conversion
(%)b
Product (3-bromo-2-butanol)
Remaining substrate
(2-acetoxy-3-bromobutane)
E c SD
20
25
b
Prod drb (conf.)
½aꢁD
eesb (%)
drb (conf.)
½aꢁD
b
b
eep (%)
1
2
3
4
5
6
7
4
4
3
3
3
3
3
syn/anti
95/5
syn/anti
95/5
anti/syn
99.5/0.5
anti/syn
99.5/0.5
anti/syn
91/9
CALB
CALB
CALB
CALB
CALB
PS
0.75
4
43
54
44
54
55
55
87
97
84
95
84
79
78
—
(R,R)-6 100/0
(2R,3R)
(R,R)-6 97/3
(2R,3R)
ꢂ20.2 (c 2, CHCl3)d
75
94/6
(2S,3S)
94/6
(2S,3S)
>99.5/0.5
(2S,3R)
>99.5/0.5
(2S,3R)
92/8
(2S,3R)
91/9
(2S,3R)
91/9
99.5
75
ꢂ2.2 (neat)d
ꢂ16.6 (neat)e
110 10
2
(R,S)-5 ꢀ 99.5/0.5
+13.2 (neat)e
(2R,3S)
11
7
(R,S)-5 ꢀ 99.5/0.5
(2R,3S)
(R,S)-5 90/10
(2R,3S)
(R,S)-5 93/7
(2R,3S)
—
99
65
41 11
37
8
96
anti/syn
91/9
anti/syn
91/9
120
240
96
6
CRL
89
3
(2S,3R)
a Candida antarctica lipase B (commercial product ChirazymeÒ lipase L-2, c.-f., C3, lyo Roche) Pseudomonas cepacia lipase (commercial product Amano PS). Candida rugosa lipase (commercial product
ChirazymeÒ lipase L-3, Roche).
b Conversions were determined by using dodecane as the internal standard present in the reaction mixtures. Conversion, diastereomeric ratio (dr) and ee were determined by GC-analysis using an HP 5890
chromatograph with a b-DEX 120 capillary chiral column (id = 0.32 mm, 30 m, df = 0.25 lm) or a Cyclosilb capillary chiral column (id = 0.32 mm, 30 m, df = 0.25 lm) with He as the carrier gas. Optical
rotation was determined with a Perkin Elmer 341LC polarimeter.
c E = ln[(1 ꢂ ees)/(1 + ees/eep)]/ln[(1 + ees)/(1 + ees/eep)]. E was also determined from several experimental data points from ee as a function of conversion using the software Simfit.10 SD = standard
deviation.
23
d Literature values for syn-compounds: (2R,3R)-3-Bromobutan-2-ol (R,R)-6: [a]D = ꢂ1.1,5a,14 ½aꢁD ¼ ꢂ3.4 (c 5, CHCl3) for a sample of 61% ee.5b (2S,3S)-2-Acetoxy-3-bromobutane (S,S)-4:
[a]D = ꢂ0.31.5a,14
25
e Literature values for anti-compounds: (2R,3S)-3-Bromobutan-2-ol (R,S)-5: ½aꢁD ¼ þ13.9 (neat),5d [a]D = + 18 (c 30, CHCl3)5f {for the enantiomer (S,R)-5 = ꢂ13.2 (c 10, Et2O)5g}. (2S,3R)-2-Acetoxy-3-
25
25
bromobutane (S,R)-4: ½aꢁD ¼ ꢂ3.0.5a,14 Following the recipe described in Ref. 7, we transformed enantiopure (2R,3R)-2,3-butanediol into pure (R,S)-4 {½aꢁD ¼ þ18.8 (neat, after chromatography and
distillation)}.

2610
R. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 2607–2611
by stirring without the enzyme for 1 h, the hydrolytic
reactions were started by the addition of 50–80 mg of
the lipase powder per mmol of the acetate 4 or 3. In reac-
tions on a preparative scale (2–5 g of substrate), instead
of using the buffer solution, the pH was monitored by a
pH-meter and maintained at 7.2–7.7 by the addition of
0.2–1 M NaOH solution.
rugosa) were tested (Table 1, entries 6 and 7), but unfor-
tunately, only lipase Amano PS displayed a satisfactory
enantioselectivity (E = 37), similar to that of CALB.
Moreover, under the same general conditions (except
for the enzyme used), the Amano PS-reaction required
120 h to reach 55% conversion, compared with only
7 h when CALB was used. CRL gave poor results both
in terms of enantioselectivity (E = 3) and reaction time
(more than 200 h).
2.3. Results and discussion
The results of our CALB-catalysed hydrolysis reactions
are shown in Table 1. According to previous studies, the
(R)-enantiomer of 2-acetoxy-1-bromopropane is the
preferred substrate with this lipase.9 We found that both
the two racemic 2-acetoxy-3-bromobutanes 3 and 4
reacted with the same (R)-enantiopreference. This was
confirmed by comparison of the specific rotation of
the alcohols produced with the values reported in the lit-
erature5 (Table 1).
In our hands, CALB-catalysed hydrolysis reactions on a
preparative scale usually gave a lower E-value than that
obtained in small-scale reactions. This was probably due
to mass transfer limitations caused by the scale-up.12 The
reaction times were virtually unchanged; 4 h for the syn-
isomer 4 and 11 h for the anti-isomer 3 were required to
reach 54% conversion in large-scale reactions (Table 1,
entries 2 and 4). Slightly longer reaction times were, how-
ever, observed for the small-scale reactions with buffer
solution. In these reactions, not only could the presence
of the phosphates in the buffer affect the rate but also the
lack of continuous pH control might cause a lowering of
the rate if the buffering capacity is low. Such pH control
is important, because it can influence not only the rate
but also the enantioselectivity. A low pH might not only
make the equilibrium of the hydrolysis shift towards the
substrates, but also cause a non-selective acid-catalysed
hydrolysis. Conversely, a higher pH might result in an
alkaline ester hydrolysis, followed by the formation of
epoxides. Despite these expected effects of the lack of
continuous pH-control, the enantioselectivity in the
small-scale reactions was, as mentioned above, higher
than in preparative scale reactions.
The anti- and syn-acetates 3 and 4 were both hydrolysed
with good enantioselectivity with E-values of 65 and
110, respectively, on a preparative scale while in small-
scale reactions (6100 mg substrate) the E-values were
higher (>100 for 3 and >200 for 4). Thus, on a prepara-
tive scale, for the syn-acetate 4 and for a reaction inter-
rupted at 43% conversion, the hydrolysis product,
(2R,3R)-3-bromo-2-butanol (R,R)-6, was obtained
highly enantiomerically pure (97% ee, Table 1, entry
1). On the other hand, the remaining substrate
(2S,3S)-2-acetoxy-3-bromobutane (S,S)-4 (99.5% ee,
entry 2) could be isolated in reactions interrupted at a
higher conversion (54%). Similarly, but with a lower
enantioselectivity, (2R,3S)-3-bromo-2-butanol (R,S)-5
(95% ee, entry 3) was obtained at 44% conversion, while
the remaining (2S,3R)-2-acetoxy-3-bromobutane (S,R)-
3 (99% ee, entry 4) was recovered at 54% conversion.
3. Enzyme catalysed resolution of the rac-3-bromo-
2-butanols by esterification
The activity of C. antarctica lipase B working on the two
racemic diastereomeric acetates 3 and 4 was notably dif-
ferent. With the syn-ester 4 and the anti-one 3, the reac-
tions required on average 0.8 and 2 h, respectively, to
reach a conversion of 44% with the same enzyme concen-
tration. Consequently, the diastereomeric ratio (dr) of
both the syn-ester 4 and the anti-ester 3 changed with time
in both cases but in opposite directions (Table 1). The dr
of the remaining substrate (ꢂ)-syn-2-acetoxy-3-bromo-
butane (S,S)-4 decreased from 95/5 to 94/6 (entries 1
and 2) while that of (ꢂ)-anti-2-acetoxy-3-bromobutane
(S,R)-5 increased slightly (entries 3–5). In addition, the
diastereomeric purity of the substrate seemed to play an
important role in these enzyme-catalysed resolutions.
As shown in entry 5, the enantioselectivity appeared to
drop (from E = 65 to 41), when the experiment started
with anti-2-acetoxy-3-bromobutane 3 containing 9% of
its syn-isomer 4. This result could be explained by the
syn-isomer 4 acting as a competitive inhibitor.11
3.1. Candida antarctica lipase B-catalysed trans-
esterifications of vinyl esters
We also investigated the scope of the enzyme-catalysed
resolution reactions of secondary vicinal bromoalcohols
and their esters by studying some CALB-catalysed este-
rifications of the anti- and syn-3-bromo-2-butanols 5
and 6 on a small scale (Scheme 2). These alcohols were
obtained by acid-catalysed chemical hydrolyses of the
anti- or syn-acetates 3 or 4 by means of an aqueous solu-
tion containing 75% concentrated HCl.13
The mixture of a racemic anti- or syn-3-bromo-2-buta-
nol either 5 or 6 (0.3 mmol) and vinyl acetate or vinyl
butanoate (0.3 mmol) in dichloromethane (1.2 mL) was
incubated for 30 min at ambient temperature. The
lipase-catalysed transesterification reaction of the vinyl
ester was then initiated by the addition of 15–30 mg of
CALB (see footnote a, Table 1).
We investigated other lipases under the same reaction
conditions, in order to study if higher enantioselectivity
could be obtained in the resolution of the anti-enantio-
mers. Amano PS (Pseudomonas cepacia lipase) and
CRL (ChirazymeÒ lipase L-3, lyophilised, from Candida
3.2. Results and discussion
As shown in Table 2, syn-3-bromo-2-butanol 6 showed
excellent enantioselectivity in CALB-catalysed acyla-
tions: E = 180 for formation of (R,R)-4 from vinyl acetate

R. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 2607–2611
2611
Table 2. Transesterifications of vinyl esters with anti- or syn-bromobutanols 5 and 6 catalysed by Candida antarctica lipase Ba
drb
Reaction
time (h)
Acyl donor
Conv. (%)b
Product ester eep
(conf.) (%)
Remaining alcohol eesb
(conf.) (%)
Eb SD
b
Substrate
(3-bromo-2-butanol)
6
6
5
5
syn/anti
95/5
syn/anti
95/5
anti/syn
99.5/0.5
anti/syn
99.5/0.5
22
22
72
—
Vinyl butanoate
Vinyl acetate
47
96 (2R,3R)
96 (2R,3R)
92 (2R,3S)
—
86.5 (2S,3S)
93 (2S,3S)
76 (2S,3R)
—
160 15
170 15
49
Vinyl butanoate
Vinyl acetate
45
53
6
No rx
—
a The reaction conditions were similar to those described in Ref. 9a.
b See footnotes b and c in Table 1.
M. P.; Guerrero, A. Tetrahedron: Asymmetry 2000, 11,
2705–2717; (d) Anand, N.; Kapoor, M.; Koul, S.; Taneja,
S. C.; Sharma, R. L.; Qazi, G. N. Tetrahedron: Asymmetry
2004, 15, 3131–3138.
and E = 160 for formation of (R,R)-8 from vinyl butano-
ate. In contrast, the anti-isomer reacted with vinyl butano-
ate to give (R,S)-7 with a much lower enantioselectivity,
E = 53. The syn-isomer 6 showed higher activity (22 h
to give 49% conversion) than the anti-isomer (72 h for
45% conversion). Interestingly, anti-3-bromo-2-butanol
5 reacted very slowly with vinyl acetate as the acyl donor.
2. Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48,
10515–10530.
3. (a) Utaka, M.; Konishi, S.; Takeda, A. Tetrahedron Lett.
1986, 4737–4740; (b) Tsuboi, S.; Yamafuji, N.; Utaka, M.
Tetrahedron: Asymmetry 1997, 8, 375–379.
´
4. (a) Conde, S.; Fierros, M.; Rodrıguez-Franco, M. I.; Puig,
4. Conclusions
C. Tetrahedron: Asymmetry 1998, 9, 2229–2232; (b)
´
Izquierdo, I.; Plaza, M. T.; Rodrıguez, M.; Tamayo, J.
Tetrahedron: Asymmetry 2000, 11, 1749–1756; (c) Kapoor,
M.; Anand, N.; Ahmad, K.; Koul, S.; Chimni, S. S.;
Tanejaa, S. C.; Qazia, G. N. Tetrahedron: Asymmetry
2005, 16, 717–725.
Our results show that enantiomerically enriched 3-bro-
mo-2-butanols 5 and 6 and their esters 3 and 4 can
indeed be prepared by chemical conversion of either
pure meso- or pure dl-2,3-butanediol, 2 or 1, and using
the products, rac-2-acetoxy-3-bromobutane (4 or 3) or
rac-3-bromo-2-butanol (6 or 5) in a lipase-catalysed
resolution by hydrolysis or acylation. CALB was the
best enzyme of those tested and provided excellent
enantioselectivity and activity towards both syn-acetate
4 and the syn-alcohol 6. A more modest enantioselectiv-
ity was observed with the corresponding anti-com-
pounds, 3 and 5. Although Amano PS revealed a
similar trend and magnitude of enantioselectivity
towards the diastereomers, it required much longer reac-
tion times in the resolutions.
5. (a) Winstein, S.; Lucas, H. J. J. Am. Chem. Soc. 1939, 61,
2845–2848; (b) Joshi, N. N.; Srebnik, M.; Brown, H. C. J.
Am. Chem. Soc. 1988, 110, 6246–6248; (c) Lucas, H. J.;
Gould, C. W. J. Am. Chem. Soc. 1941, 63, 2541; (d) Lucas,
H. J.; Garner, H. K. J. Am. Chem. Soc. 1950, 72, 2145–
2150; (e) Bystro¨m, S.; Ho¨gberg, H.-E.; Norin, T. Tetra-
hedron 1981, 37, 2249–2254; (f) Gerdil, R.; Barchietto, G.
Tetrahedron Lett. 1989, 30, 6677–6678; (g) Konopelski,
J. P.; Boehler, M. A.; Tarasow, T. M. J. Org. Chem. 1989,
54, 4966–4970.
6. Whitesell, J. K. Chem. Rev. 1989, 89, 1581–1590.
7. Golding, B. T.; Hall, D. R.; Sakrikar, S. J. Chem. Soc.,
Perkin Trans. 1 1973, 1214–1220.
8. Liu, R.; Ho¨gberg, H.-E. Tetrahedron: Asymmetry 2001,
12, 771–778.
9. (a) Rotticci, D.; Orrenius, C.; Hult, K.; Norin, T.
Tetrahedron: Asymmetry 1997, 8, 359–362; (b) Takano,
S.; Setoh, M.; Ogasawara, K. Heterocycles 1992, 34, 173–
180.
10. van Tol, J. B. A.; Jongejan, J. A.; Geerlof, A.; Duine, J. A.
Recl. Trav. Chim. Pays-Bas 1991, 110, 255–262, The
software Simfit was generously supplied by van Tol et al.
11. Fersht, A. Structure and Mechanism in Protein Science: A
Guide to Enzyme Catalysis and Protein Folding; W. H.
Freeman and Company: New York, 1997, pp 112.
12. Rotticci, D.; Norin, T.; Hult, K. Org. Lett. 2000, 2, 1373–
1376.
Acknowledgements
We thank Professor Karl Hult and the Biocatalysis group,
KTH, for their enthusiastic help and advice. We also
thank Boehringer Mannheim and Amano Pharmaceuti-
cal Company for the generous gifts of lipases. Financial
support from Mid Sweden University, from the Swedish
Research Council for Environment, Agricultural Sciences
and Spatial Planning and from the Swedish Research
Council is also gratefully acknowledged.
13. Rac-anti-2-acetoxy-3-bromobutane (3.9 g, 20 mmol) and
HCl (aq. 8 M, 40 mL) were stirred for 24 h. Extractive
work-up and distillation provided anti-3-bromo-2-butanol
(2.3 g, 15 mmol, 75%) with unchanged dr.
14. The rotation values given in Ref. 5a are, as the authors
state, probably too low due to the low enantiomeric excess
of the samples.
References
1. (a) Igarashi, Y.; Otsutomo, S.; Harada, M.; Nakano, S.
Tetrahedron: Asymmetry 1997, 8, 2833–2837; (b) Adam,
W.; Blancafort, L.; Saha-Mo¨ller, C. R. Tetrahedron:
Asymmetry 1997, 8, 3189–3192; (c) Campos, F.; Bosch,