Tandem enzyme/gold-catalysis: from racemic α-allenic acetates to enantiomerically enriched 2,5-dihydrofurans in one pot

Article abstract of DOI:10.1002/adsc.200900434

We report the first example of a tandem kinetic resolution/ cycloisomerization of racemic alieme acetates in the presence of Burkholderia cepacia lipase (PS Amano SD) and catalytic amounts of chloroauric acid (HAuCl₄) which affords 2,5-dihydrof

Full text of DOI:10.1002/adsc.200900434

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DOI: 10.1002/adsc.200900434
Tandem Enzyme/Gold-Catalysis: From Racemic a-Allenic
Acetates to Enantiomerically Enriched 2,5-Dihydrofurans in
One Pot
Martta Asikainena and Norbert Krausea,*
a
Dortmund University of Technology, Organic Chemistry, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany
Fax : (+49)-231-755-3884; e-mail: norbert.krause@tu-dortmund.de
Received: June 23, 2009; Published online: October 1, 2009
Abstract: We report the first example of a tandem
kinetic resolution/cycloisomerization of racemic al-
lenic acetates in the presence of Burkholderia cepa-
cia lipase (PS Amano SD) and catalytic amounts of
chloroauric acid (HAuCl4) which affords 2,5-dihy-
drofurans, as well as unreacted starting material, in
one pot with high enantiomeric excess and moder-
ate to good yield.
We started our investigation with substrates of the
type 1 which bear a stereogenic center in the a-posi-
tion, but no axis of chirality. Screening of various en-
zymes in aqueous phosphate buffer showed a high hy-
drolytic activity of lipases from Pseudomonas fluores-
cens, Pseudomonas cepacia and Burkholderia cepacia
towards substrate 1a whereas bulkier allenic acetates
(e.g., 1b) were effectively resolved only with lipase
from Burkholderia cepacia (PS Amano SD). In con-
trast to this, all attempts for a lipase-catalyzed alco-
holysis of the racemic acetate 1a failed due to ex-
tremely slow conversions. Consequently, the gold-cat-
alyzed cycloisomerization of the allenic alcohol 2 had
to be carried out in aqueous medium in order to es-
tablish the desired tandem process. Recently, we have
shown that chloroauric acid (HAuCl4) is an efficient
Keywords: allenes; cycloisomerization; enzyme cat-
alysis; gold catalysis; kinetic resolution; tandem re-
actions
The combination of two or more catalytic transforma- precatalyst for the cyclization of various functional-
tions in a tandem or one-pot process[1] is one of the ized allenes in water.[9] Thus, we optimized the condi-
most powerful tools in sustainable chemistry.[2] tions for the tandem hydrolysis/cycloisomerization of
Among various catalytic methodologies, the combina- model substrate 1a using the lipase from Burkholderia
tion of enzyme and transition metal catalysis seems to cepacia and HAuCl4 (Table 1).
have received little attention so far.[3] For example,
Since reactions in pure aqueous buffer resulted in
the lipase-catalyzed kinetic resolution of secondary al- very low conversions, we performed the optimization
cohols, which is a widely used method for the genera- in the presence of 2.5 vol% of THF as cosolvent
tion of enantiomerically enriched or pure com- which improves the solubility of the substrate in the
pounds,[4,5] has so far only been combined with transi- phosphate buffer.[9] In the presence of 10 mg of the
tion metal catalysts which were designed to racemize lipase and 1 mol% of HAuCl4, substrate 1a (10 mg)
the substrate.[3,6] There seems to be no precedent for afforded 2,5-dihydrofuran 3a[10] with high enantiomer-
tandem enzyme/transition metal-catalyzed transfor- ic excess (>90%), but the conversion reached only
À
À
mations that involves C C or C heteroatom bond 25–30% after 48 h at room temperature (Table 1,
formation, resulting in products with increased molec-
ular complexity. A possible reason might be the pro-
pensity of enzymes and transition metals to deactivate
each other. Based on our interest in homogeneous
gold catalysis,[7] we now report a novel approach to
tandem enzyme/transition metal catalysis by combin-
ing the lipase-catalyzed kinetic resolution of racemic
a-allenic acetates 1 with the gold-catalyzed cycloiso-
merization of the resulting enantiomerically enriched
a-hydroxyallenes 2 to the corresponding 2,5-dihydro-
furans 3[7,8] in one pot (Scheme 1).
Scheme 1. Tandem lipase-catalyzed kinetic resolution/gold-
catalyzed cycloisomerization of racemic allenic acetates 1.
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Martta Asikainen and Norbert Krause
Table 1. Optimization of the tandem hydrolysis/cycloisomerization of allenic acetates 1a/b.[a]
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Entry
1
Lipase [mg]
HAuCl4 [mol%]
t [h]
(R)-3
% Conversion.
% ee
1
1a
1a
1a
1a
1a
1a
1a
1b
10
10
100
10
10
50
100
100
1
1
1
10
0.5
0.5
0.5
0.5
48
24
24
24
24
24
24
48
25–30
25–30
45–50
0
27
35
90–95
90–95
55–60
2[b]
3
4
5
6
7
96
87
63
94
46
45
8
[a]
Reaction conditions: 1 (10 mg) of in 2 mL of phosphate buffer (pH 7) and 50 mL of THF was treated with PS Amano SD
(30000 U) and aqueous HAuCl4 solution at room temperature.
Reaction temperature: 508C.
[b]
entry 1). Increasing the temperature to 508C gave the lower ees (entries 6 and 7). However, this normal be-
same result after 24 h, albeit with formation of un- haviour for a kinetic resolution[11] was not observed
identified by-products (entry 2). Increasing the for the somewhat bulkier propyl-substituted allenic
amount of the lipase to 100 mg resulted in improved acetate 1b which gave a high enantioselectivity of
conversion, but lower stereoselectivity (entry 3), 94% ee for cyclization product (R)-3b at a high con-
whereas no reaction took place with 10 mol% of version of 45% (entry 8).
HAuCl4 (entry 4). Thus, not only the conversion but
Having established that the activities of the lipase
also the ratio of enzyme to gold precatalyst strongly and the gold catalyst do not compromise each other
affects the tandem transformation. This observation as long as low amounts of the gold precatalyst are
was confirmed in subsequent reactions of 1a with dif- used, we examined the tandem lipase/gold-catalyzed
ferent amounts of the lipase and 0.5 mol% of hydrolysis/cycloisomerization of various allenic ace-
HAuCl4: we could obtain a satisfactory ee of 96% for tates 1 (Table 2).
(R)-3a only at rather low conversion of 27%
Whereas the tandem reaction works very well for
(entry 5), whereas higher conversions resulted in substrates with a straight alkyl chain at the acetate
Table 2. Tandem hydrolysis/cycloisomerization of allenic acetates 1.[a]
Entry
1
R1
R2
Lipase [mg]
(R)-3
% Conversion
% ee
1
1a
1b
1c
1d
1e
1f
1g
1h
N
Me
50
35
45
0
0
4
30
46
44
87
94
2[b]
3
n-Pr
c-Hex
i-Bu
100
100
100
100
50
4
5[c]
6
A
nd
94
99
86
n-Pr
n-Pr
n-Oct
7
8
50
50
[a]
Reaction conditions: 1 (10 mg) of in 2 mL of phosphate buffer (pH 7) and 50 mL of THF was treated with PS Amano SD
(30000 U) and aqueous HAuCl4 solution (0.5 mol%) at room temperature for 24 h.
Reaction time: 48 h.
Reaction time: 40 h.
[b]
[c]
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Tandem Enzyme/Gold-Catalysis: From Racemic a-Allenic Acetates
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Table 3. Tandem hydrolysis/cycloisomerization of allenic acetates 1 on preparative scale.[a]
Entry
1
R1
R2
(R)-3
(S)-1
% Yield
ee
% Yield
ee
1
2
3
4
1a
1b
1f
1h
N
Me
28
45
38
50
86
95
88
98
31
40
33
36
93
n-Pr
n-Pr
n-Oct
>95
>95
95
[a]
Reaction conditions: 1 (0.5 mmol) of in 15 mL of phosphate buffer (pH 7) and 0.1 mL of THF was treated with PS
Amano SD (30000 U) and aqueous HAuCl4 solution (0.5 mol%) at room temperature for 48 h.
dried glassware. Tandem reactions were performed in vials
(entries 1, 2, 6–8), bulkier groups R2 bearing either a
under air. Lipase PS Amano SD (30000 U) was obtained
from Amano Europe Ltd. and used as received. Aldehydes
phenyl substituent or a branch at the a- or b-carbon
atom give low or no conversion (entries 3–5). Thus,
the lipase is very sensitive to any steric hindrance at
this position. In contrast to this, both five- (entry 6)
and six-membered rings at the allene (entries 1 and 2)
are tolerated, as well as acyclic allenic acetates 1g and
h (entries 7 and 8). The latter substrates show the
highest reactivity and afford the corresponding 2,5-di-
hydrofurans with good to excellent ee at high conver-
sion.
After these small-scale experiments, the tandem hy-
drolysis/cycloisomerization was performed on prepa-
rative scale with 0.5 mmol of the allenic acetates 1a,
1b, 1f, and 1h (Table 3). Both the 2,5-dihydrofurans
(R)-3 and the unreacted allenic acetates (S)-1 were
obtained with moderate to good isolated yields (28–
50%) and good to excellent enantioselectivities (86–
98% ee). In some cases (e.g., 3a), the yield was com-
promised by the high volatility of the product.
were distilled prior to use. All other chemicals were pur-
chased from commercial sources and used as received.
Column chromatography was carried out with Acros silica
1
gel 60. H and 13C NMR spectra were recorded with Bruker
DRX 400 or DRX 500 spectrometers at room temperature
in CDCl3 as solvent. Chemical shifts were determined rela-
tive to the residual solvent peaks (CHCl3: d=7.26 for pro-
tons, d=77.1 for carbon atoms). GC analysis was carried
out with a CE Instruments GC 8000 on a octakis-(2,3-di-O-
pentyl-6-O-methyl)-g-cyclodextrin capillary column with hy-
drogen as carrier gas.
General Procedure for the Synthesis of a-Allenic
Acetates 1
Racemic a-hydroxyallenes were prepared according to a
known procedure[12] using p-TsOH (1 mol%) instead of HCl
gas. These were converted into the racemic acetates 1 ac-
cording to a known procedure[12] using DMAP (20 mol%)
and Et3N (2 equiv.) instead of pyridine.
In conclusion, we have developed the first example
for a tandem lipase/gold-catalyzed transformation by
treating racemic allenic acetates 1 with Burkholderia
cepacia lipase (PS Amano SD) and catalytic amounts
of chloroauric acid (HAuCl4). The one-pot kinetic
resolution/cycloisomerization affords 2,5-dihydrofur-
ans (R)-3, as well as unreacted starting material (S)-1,
with 28–50% isolated yield and 86–98% ee. Our re-
sults indicate a high mutual tolerance of the lipase
and gold catalyst which opens intriguing possibilities
for further tandem processes involving biocatalysts
and transition metals.
General Procedure for the Tandem Gold/Enzyme-
Catalyzed Hydrolysis/Cyclization on an Analytical
Scale
Racemic acetate 1 (10 mg) was dissolved in 2 mL of phos-
phate buffer (pH 7) and 50 mL of THF. Lipase from
Burkholderia cepacia (PS Amano SD; 10–100 mg) was
added, followed by HAuCl4 solution (0.012M in water,
20 mL, 0.5 mol%). The reaction mixture was stirred at room
temperature for 24–48 h, and the conversion and ee were de-
termined by GC analysis.
General Procedure for the Tandem Gold/Enzyme-
Catalyzed Hydrolysis/Cyclization on a Preparative
Scale
Experimental Section
Racemic acetate 1 (0.5 mmol) was dissolved in 15 mL of
phosphate buffer (pH 7) and 0.1 mL of THF. Lipase from
Burkholdia cepacia (PS Amano SD; 160–800 mg) and
HAuCl4 solution (0.012M in water, 0.2 mL, 0.5 mol%) were
General Remarks
The syntheses of racemic alcohols, acetates and 2,5-dihydro-
furans were performed under an inert atmosphere in oven-
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Martta Asikainen and Norbert Krause
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added. The reaction mixture was stirred at room tempera-
ture for 48 h, and the conversion was controlled by GC anal-
ysis. The reaction mixture was then extracted 5 times with
Et2O, and the combined organic extracts were washed with
satd. NaCl solution and dried with Na2SO4. After removal
of the solvent under vacuum, the crude product was purified
by flash column chromatography (pentane/Et2O, 30:1).
4-Cyclohexylidenebut-3-en-2-yl acetate (1a): Colorless oil.
Rf =0.65 (cyclohexane/EtOAc, 4:1). 1H NMR (400 MHz,
CDCl3): d=5.35–5.29 (m, 1H), 5.11–5.09 (m, 1H), 2.15–2.09
(m, 4H), 2.04 (s, 3H), 1.62–1.52 (m, 6H), 1.31 (d, J=6.5 Hz,
3H); 13C NMR (400 MHz, CDCl3): d=198.3, 170.6, 105.7,
90.6, 69.4, 31.4, 27.5, 26.2, 21.6, 19.9; IR: n=3055, 2983,
2932, 2891, 2855, 1731, 1447, 1370, 1265, 1245, 1038,
738 cmÀ1; HR-MS: m/z=194.1301, calcd. for C12H18O2 [M+]:
194.1307. (S)-1a (93% ee); [a]D: À117.4 (c 0.45, CH2Cl2).
1-Cyclohexylidenehex-1-en-3-yl acetate (1b): Colorless
m/z=209.1448, calcd. for C13H20O2 [M+]: 208.1463. (S)-1f
(>95% ee); [a]D: À113.2 (c 0.70, CH2Cl2).
7-Methylocta-5,6-dien-4-yl acetate (1g): Colorless oil. Rf =
0.55 (cyclohexane/EtOAc, 4:1). 1H NMR (400 MHz,
CDCl3): d=5.17 (q, J=6.5 Hz, 1H,), 5.00–4–97 (m, 1H),
2.03 (s, 3H), 1.70–1.68 (m, 6H), 1.64–1.53 (m, 2H), 1.42–
1.30 (m, 2H), 0.91 (t, J=7.5 Hz, 3H); 13C NMR (400 MHz,
CDCl3): d=202.0, 170.6, 97.8, 89.4, 72.9, 36.4, 21.5, 20.4,
18.8, 14.0; IR: n=3054, 2962, 2912, 2874, 1728, 1371, 1265,
1248, 738, 704 cmÀ1; HR-MS: m/z=182.1301, calcd. for
C11H18O2 [M+]: 182.1307.
2-Methyltrideca-2, 3-dien-5-yl acetate (1h): Colorless oil.
1H NMR (400 MHz, CDCl3): d=5.18–5.13 (q, J=6.5 Hz,
1H), 5.00–4.97 (m, 1H), 2.04 (s, 3H), 1.70–1.68 (m, 6H),
1.64–1.50 (m, 2H), 1.33–1.26 (m, 12H), 0.89–0.86 (m, 3H);
13C NMR (400 MHz, CDCl3): d=202.0, 170.6, 97.8, 89.5,
77.5, 73.2, 34.3, 32.0, 29.7, 29.5, 25.5, 22.8, 20.4, 14.3; IR: n=
3154, 2928, 2856, 2253, 1971, 1726, 1250, 912, 735, 650 cmÀ1
;
1
oil. Rf =0.66 (cyclohexane/EtOAc, 4:1). H NMR (400 MHz,
HR-MS: m/z=252.2084, calcd. for C16H28O2 [M+]: 252.2089.
(S)-1h (95% ee); [a]D: À76.0 (c 0.65, CH2Cl2).
CDCl3): d=5.21–5.16 (m, 1H), 5.02–5.00 (m, 1H), 2.14–2.11
(m, 4H), 2.04 (s, 3H), 1.65–1.33 (m, 10H), 0.92 (t, J=
8.0 Hz, 3H); 13C NMR (400 MHz, CDCl3): d=198.6, 89.3,
73.0, 36.3, 31.4, 27.5, 26.2, 21.6, 18.8, 14.0; IR: n=2957,
2932, 2855, 1968, 1732, 1371, 1239, 1017, 738 cmÀ1; HR-MS:
m/z=222.1614, calcd. for C14H22O2 [M+]: 222.1620. (S)-1b
(>95% ee); [a]D: À99.6 (c 1.40, CH2Cl2).
2-Methyl-1-oxaspiroACHTUNTRGNENUG[4.5]dec-3-ene (3a): Rf =0.74 (cyclo-
hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): d=5.87
(dd, J=6.0/2.5 Hz, 1H), 5.70 (d, J=6.0 Hz, 1H), 4.90 (dd,
J=6.5/2.0 Hz, 1H), 1.63–1.73 (m, 2H), 1.53–1.61 (m, 4H),
1.37–1.50 (m, 4H), 1.25 (d, J=6.5 Hz, 3H); 13C NMR
(400 MHz, CDCl3): d=133.4, 130.4, 89.6, 80.5, 39.6, 37.6,
25.6, 23.5; IR: n=2972, 2934, 2858, 2253, 1087 (cyclic ether),
1-Cyclohexyl-3-cyclohexylideneallyl acetate (1c): Color-
less viscous oil. Rf =0.57 (cyclohexane/EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): d=5.00–4.92 (m, 2H), 2.14–
2.08 (m, 4H), 2.05 (s, 3H), 1.78–1.72 (m, 4H), 1.64–1.49 (m,
8H), 1.26–0.99 (m, 5H); 13C NMR (400 MHz, CDCl3): d=
199.0, 170.6, 104.5, 87.6, 41.8, 31.4, 31.3, 28.9, 28.6, 27.4, 26.6,
26.2, 26.1, 26.1; IR: n=2930, 2854, 2253, 1725, 1248, 909,
733 cmÀ1; HR-MS: m/z=262.1927, calcd. for C17H26O2 [M+]:
262.1933.
907, 734, 650 cmÀ1
; HR-MS: m/z=152.1196, calcd. for
C10H16O [M+]: 152.1201. (R)-3a (86% ee); [a]D: À90.4 (c
0.38, CH2Cl2).
2-Propyl-1-oxaspiroACHTUNTRGNENUG[4.5]dec-3-ene (3b): Rf =0.67 (cyclo-
hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): d=5.09
(dd, J=6.0/2.0 Hz, 1H), 5.72 (dd, J=5.5/1.0 Hz, 1H), 4.81–
4.78 (m, 1H), 1.76–1.64 (m, 4H), 1.60–1.49 (m, 9H), 1.48–
1.37 (m, 1H), 0.93 (t, J=7.3 Hz, 3H); 13C NMR (400 MHz,
CDCl3): d=129.0, 89.2, 84.5, 39.6, 39.1, 37.7, 25.7, 23.8, 18.8,
14.4; IR: n=3053, 2933, 1448, 1265, 1109, 705 cmÀ1; HR-
MS: m/z=180.1509, calcd. for C12H20O [M+]: 180.1514. (R)-
3b (95% ee); [a]D: À100.6 (c 0.74, CH2Cl2).
1-Cyclohexylidene-5-methylhex-1-en-3-yl acetate (1d):
Yellow oil. Rf =0.64 (cyclohexane/EtOAc, 10:1). 1H NMR
(400 MHz, CDCl3): d=5.28–5.23 (m, 1H), 5.02–4.99 (m,
1H), 2.14–2.06 (m, 4H), 2.04 (s, 3H), 1.69–1.42 (m, 9H),
0.91 (dd, J=6.5/3.0 Hz, 6H); 13C NMR (400 MHz, CDCl3):
d=198.6, 170.6, 105.1, 89.4, 71.8, 43.2, 31.4, 31.3, 27.5, 27.4,
26.2, 24.9, 22.8, 22.7, 21.6. IR: n=3054, 2934, 2305, 1726,
1421, 1265, 896, 739, 705 cmÀ1; HR-MS: m/z= 236.1772,
calcd. for C15H24O2 [M+]: 236.1776.
2-Propyl-1-oxaspiroACHTUNTRGNENUG[4.4]non-3-ene (3f): Rf =0.60 (cyclo-
hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): d=5.70
(s, 2H), 4.77 (t, J=5.8 Hz, 1H), 1.80–1.70 (m, 4H), 1.62–
1.59 (m, 4H), 1.52–1.49 (m, 2H), 1.41–1.33 (m, 2H), 0.92 (t,
J=7.3 Hz, 3H); 13C NMR (400 MHz, CDCl3): d=133.4,
128.8, 84.8, 40.2, 39.2, 38.8, 27.1, 24.8, 24.7, 18.6, 14.5; IR:
n=2959, 2253, 1466, 1383, 912, 742, 650 cmÀ1; HR-MS:
m/z=166.1354, calcd. for C11H18O [M+]: 166.1358. (R)-3f
(88% ee); [a]D: À94.4 (c 0.64, CH2Cl2).
1-Cyclohexylidene-5-phenylpent-1-en-3-yl acetate (1e):
1
Colorless oil. Rf =0.59 (cyclohexane/EtOAc, 4:1). H NMR
(400 MHz, CDCl3): d=7.31–7.18 (m, 5H), 5.23 (q, J=
6.2 Hz, 1H,), 5.09–5.07 (m, 1H), 2.73–2.65 (m, 2H), 2.21–
2.10 (m, 4H), 2.06 (s, 3H), 1.68–1.49 (m, 8H); 13C NMR
(400 MHz, CDCl3): d=198.7, 170.5, 141.6, 128.5, 128.5,
126.0, 105.3, 89.1, 72.5, 35.8, 31.8, 31.4, 31.3, 27.4, 27.0, 26.1,
21.4; IR: n=3027, 2928, 2852, 2253, 1967, 1735, 1448, 1371,
1245, 1020, 911, 738, 650 cmÀ1; HR-MS: m/z=284.1776,
calcd. for C19H24O2 [M+]: 284.1776.
2,2-Dimethyl-5-propyl-2,5-dihydrofuran (3g): Rf =0.59 (cy-
clohexane/EtOAc, 4:1). Due to solvent residues in this very
volatile product, not all NMR peaks could be resolved.
1H NMR (400 MHz, CDCl3): d=5.68 (dd, J=6.0/2.0 Hz,
1H), 5.64 (dd, J=6.0/1.0 Hz, 1H), 1.49 (s, 6H), 1.40–0.95
(m, 4H), 0.92 (t, J=7.6 Hz, 3H); 13C NMR (400 MHz,
CDCl3): d=135.4, 128.4, 87.1, 85.0, 39.4, 29.3, 28.0, 27.1,
1-Cyclopentylidenehex-1-en-3-yl acetate (1f): Colorless
1
26.0, 18.8; IR: n=2977, 2873, 2253, 1110, 907, 732, 650 cmÀ1
HRMS: m/z=140.1195, calcd. for C9H16O [M+]: 140.1201.
;
oil. Rf =0.58 (cyclohexane/EtOAc, 4:1). H NMR (400 MHz,
CDCl3): d=5.19 (q, J=6.5 Hz, 1H), 5.10–5.05 (m, 1H),
2.38–2.31 (m, 4H), 2.03 (s, 3H), 1.70–1.64 (m, 4H), 1.62–
1.51 (m, 2H), 1.38–1.29 (m, 2H), 0.90 (t, J=7.5 Hz, 3H);
13C NMR (400 MHz, CDCl3): d=197.4, 170.6, 106.3, 91.8,
73.0, 36.3, 31.33, 31.25, 27.2, 27.0, 21.5, 18.8, 14.0; IR: n=
2960, 2253, 1727, 1372, 1248, 911, 741, 650 cmÀ1; HR-MS:
2,2-Dimethyl-5-octyl-2,5-dihydrofuran (3h): Rf =0.62 (cy-
clohexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): d=
5.70 (dd, J=6.0/2.5 Hz, 1H), 5.65 (dd, J=6.0/1.5 Hz, 1H),
4.81–4.78 (m, 1H), 1.55–1.49 (m, 2H), 1.32 (s, 6H), 1.29–
1.25 (m, 12H), 0.87 (t, J=8.0 Hz, 3H); 13C NMR (400 MHz,
2308
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Tandem Enzyme/Gold-Catalysis: From Racemic a-Allenic Acetates
COMMUNICATIONS
CDCl3): d=135.4, 128.4, 87.1, 85.2, 37.1, 32.0, 30.00, 29.4,
28.1, 22.8, 14.3; IR: n=2927, 2855, 2253, 1097, 911,
734 cmÀ1; HR-MS: m/z=210.1978, calcd. for C14H26O [M+]:
210.1984. (R)-3h (98% ee); [a]D: À78.2 (c 1.37, CH2Cl2).
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[10] The configuration of 1 and 3 was assigned based on the
known enantiopreference of the lipase from Burkhol-
deria cepacia: Q. Jing, R. J. Kazlauskas, Chirality 2008,
20, 724–735.
Financial support by the European Community (Marie-Curie
Early Stage Researcher Training), (MEST-CT-2005–019780)
is gratefully acknowledged. We thank Mr. Kim A. Vogt
(Dortmund University of Tchnology) for acetate 1d and
Amano Europe Ltd. for a gift of PS Amano SD lipase.
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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