A new and efficient chemoenzymatic route to both enantiomers of α′-acetoxy-α-methyl and γ-hydroxy-α-methyl cyclic enones

Article abstract of DOI:10.1016/j.tetasy.2003.12.006

A chemoenzymatic synthesis of both enantiomers of the pharmacologically interesting α′-acetoxy-α-methyl and γ-hydroxy-α- methyl cyclic enones starting from α-methyl-β-methoxy cyclic enones is reported. Manganese(III) acetate-mediated acetoxylation followe

Full text of DOI:10.1016/j.tetasy.2003.12.006

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 777–781
A new and efficient chemoenzymatic route to both enantiomers
of a0-acetoxy-a-methyl and c-hydroxy-a-methyl cyclic enones
*
€
Ayhan S. Demir, Hamide Fındık and Elif Kose
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 10 November 2003; accepted 2 December 2003
Abstract—A chemoenzymatic synthesis of both enantiomers of the pharmacologically interesting a0-acetoxy-a-methyl and c-hy-
droxy-a-methyl cyclic enones starting from a-methyl-b-methoxy cyclic enones is reported. Manganese(III) acetate-mediated acet-
oxylation followed by the enzyme-mediated hydrolysis of a0-acetoxy enone provides acetoxy enones 1a and 2a and hydroxy enones
1b and 2b with high enantiomeric excesses in good yields. The reduction of the acetoxy and hydroxy enones furnished both
enantiomers of c-hydroxy-a-methyl cyclic enones 3 and 4 in a high enantiomeric excess.
Ó 2003 Elsevier Ltd. All rights reserved.
1. Introduction
ee) together with the (R)-butyrate. (R)-Butyrate, isolated
by column chromatography, was cleaved to the (R)-
alcohol (78%, 46% ee) and the stereocenter inverted via
a Mitsunobu protocol, furnishing an additional quantity
of the (S)-alcohol (52%, 46% ee). The combined (S)-4
(60% ee) batches were exposed again to b,b,b-trifluoro-
ethyl butyrate and PPL in ether to provide (S)-4 in a
52% isolated yield and >98% ee.6
Chiral cyclic polyoxo-ketones 1–4 are important struc-
tural units in many biologically active compounds and
are important synthons for the asymmetric synthesis of
natural products.1 It is therefore of considerable interest
to develop efficient methods for the preparation of these
compounds in enantiomerically pure forms.
In our ongoing investigations, we have published several
papers concerning the Mn(OAc)3-mediated direct acet-
oxylation and acyloxylation of enones and aromatic
ketones followed by the enzymatic- and fungus-
mediated resolution of acyloxy enones to obtain
enantiomerically pure a-hydroxy ketones.7 Due to the
multi-functional nature of chiral a0-hydroxy-a-methyl,
a0-acetoxy-a-methyl, and c-hydroxy-a-methyl cyclic
enones 1–4, they can take part in several stereoselective
transformations, which led us to explore a chemoenzy-
matic method for obtaining them in their enantiomeri-
cally pure forms. We describe herein an efficient
chemoenzymatic route to the three-step synthesis of
both enantiomers of 1–4 starting from 3-methoxy-2-
methyl-cyclic enones 5 and 6, which are a representative
example for the simple enantioselective synthesis of
cyclic 2-substituted 4-hydroxy enones.
O
O
O
O
RO
RO
OCH3
*
*
*
*
OCH3
HO
OH
3
1a R=Ac
1b R=H
2a R=Ac
2b R=H
4
Several preparations of racemic 1, 22, 3,3 and 44 have
been published, but few examples have reported the
asymmetric synthesis of 3 and 4. The synthesis of (R)-3
has been described by Schultz et al.5 Fragmentation
reactions of 2-alkyl- and 2,4-dialkyl-3-iodo-1-oxocyclo-
hexan-2,4-carbolactones furnished (R)-3 in a 72% yield
together with the corresponding butenolide carboxylic
acid. (S)-4 was synthesized via enzymatic kinetic reso-
lution of rac-4 and converted to ())-fastigilin C. A PPL
mediated resolution of rac-4 with b,b,b-trifluoroethyl
butyrate in ether furnished the (S)-alcohol (43%, 68%
2. Result and discussion
Commercially available 1,3-diones 2-methylcyclopen-
tan-1,3-dione and 2-methylcyclohexan-1,3-dione were
* Corresponding author. Fax: +90-3122103242; e-mail: asdemir@
metu.edu.tr
0957-4166/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.12.006

778
A. S. Demir et al. / Tetrahedron: Asymmetry 15 (2004) 777–781
converted to the 3-methoxy-2-methyl cyclic enones 5
and 6 using a procedure previously reported in litera-
ture.8 As an initial reaction (Scheme 1), oxidation of the
enone 5 and 6 with four equivalents of manganese(III)
acetate in benzene was performed to obtain the desired
a0-acetoxy enones, rac-1 and 2, in 85-88% yield after
purification by column chromatography. Direct syn-
thesis of acyloxy enones rac-1 and 2 under mild condi-
tions from enones 5 and 6 using manganese(III) acetate
is an attractive alternative to the other (multi-step)
procedures for a0-oxidation.
holderia Graduloi) showed activity via the hydrolysis of
rac-1a. For the kinetic resolution step, the following
conditions provided the optimal results.
In a typical experiment for enzymatic hydrolysis, the
racemic 4-methoxy-3-methyl-2-oxocyclohex-3-en-1-yl
acetate, rac-1a, was dissolved in DMSO, a phosphate
buffer (pH 7.0) then added and the mixture stirred at
room temperature in the presence of the enzyme. The
reaction was monitored by TLC analysis and LC–MS
with a chiral column using rac-1a, and rac-6-hydroxy-3-
methoxy-2-methylcyclohex-2-en-1-one, rac-1b, (synthe-
sized from rac-1a with K2CO3/MeOH)7c;d as references.
When an approximately 50% conversion was attained,
the crude product was separated by flash column
chromatography to provide (S)-4-methoxy-3-methyl-2-
oxocyclohex-3-en-1-yl acetate, (S)-1a, and (R)-6-hydroxy-
3-methoxy-2-methylcyclohex-2-en-1-one, (R)-1b. All
enzymes affected the hydrolysis and preferentially rec-
ognized the (R)-enantiomer of rac-1a. Careful moni-
toring of the reactions with TLC and LC–MS provided
the acetoxy enone (S)-1a (50 to >98% ee, 41–51% yields)
and hydroxy enone (R)-1b (55 to >96% ee, 37–48%
yields). PLE, Amano PS and PPL exhibited high
enantioselectivity for the remaining acetoxy enone
(>98% ee) while PLE, PPL, TL, SL exhibited high
enantioselectivity for the hydroxyl enone (94–96% ee)
Lipase type enzymes are used extensively for the syn-
thesis of enantiomerically pure compounds via the res-
olution of racemic mixtures. The high stereoselectivity in
organic media and their low cost make them very useful
catalysts for enantioselective resolution.9
Based on the preliminary information available to us
from our previous work with biocatalyst-mediated
reactions,7c;d we tested a series of enzymes for screening
the enantioselective hydrolysis of acetoxy enone rac-1a.
As shown in Table 1, seven enzymes: PLE (Pig Liver
esterase), Amano PS, CCL (Candida Cylindracea lipase),
PPL (Porcine Pancreatic lipase), Lipase TL (Pseudo-
monas Stutzeri PL-836), Lipase SL (Pseudomonas
(Burkholderia) cepacia SL-25), and Lipase QLM (Burk-
O
O
Mn(OAc)3,
benzene, reflux
O
O
O
enzyme
O
HO
n( )
+
n( )
O
OCH3
n( )
n( )
O
OCH3
rac-1a
rac-2a
OCH3
OCH3
n= 2
n= 1
5
6
(R)-1a
(S)-1a
(S)-1b
(R)-1b
O
(S)-2b
(R)-2b
HO
(R)-2a
(S)-2a
n( )
OCH3
rac-1b
rac-2b
Scheme 1.
Table 1. Enzymatic hydrolysis of 4-methoxy-3-methyl-2-oxocyclohex-3-en-1-yl acetate rac-1a
No
Enzyme
Reaction
time (h)
Conversion
ca (%)
Acetate
Yieldc (%)
Alcohol
Ed
Eeb (%)
Eeb (%)
Yieldc (%)
1
2
3
4
5
6
7
PLE
24
22
24
23
8 d
52
12
51
47
58
51
35
48
48
>98
>98
60
45
41
50
49
49
47
51
96
88
55
95
94
95
82
47
45
43
37
41
38
48
>200
>200
5
Amano PS
CCL
PPL
TLe
SLe
QLMe
>98
50
180
53
86
77
108
23
a c ¼ ees=ðees þ eep).
b Determined by HPLC using the chiral column (Chiralcell OB column, UV detection at 254 nm, eluent: hexane/2-propanol ¼ 75:25, flow
0.80 mL minꢀ1 20 °C, using racemic compounds as references; Rf : for (S)-1a: 20 min; (R)-1a: 27 min; Rf : for (R)-1b: 10 min; (S)-1b: 8 min).
c Isolated yield after flash column chromatography.
d See Ref. 13. E values are calculated using the program ÔSelectivityÕ by K. Faber and H. Hoenig, http://www.cis.TUGraz.at/orgc/.
e MEITO SANGYO Co., Ltd., Tokyo, Japan.

A. S. Demir et al. / Tetrahedron: Asymmetry 15 (2004) 777–781
779
(Table 1). Among the organic solvents used (toluene,
xylene, THF, dioxane, acetonitrile, benzene, and ether)
DMSO provided the optimal results.
O
reduction
RO
HO
*
*
n( )
n( )
OCH3
O
Under the above mentioned conditions, the enantio-
selective hydrolysis of 4-methoxy-3-methyl-2-oxocyclo-
pent-3-en-1-yl acetate rac-2a was investigated with four
readily available enzymes: PLE (Pig Liver esterase),
Amano PS, CCL (Candida Cylindracea lipase) and PPL
(Porcine Pancreatic lipase). Careful monitoring of the
reactions with TLC and LC–MS provided the acetoxy
enone (R)-2a (28–98% ee, 41–54% yields) and hydroxy
enone (S)-2b (32–95% ee, 37–47% yields). PLE and
Amano PS exhibited high enantioselectivity for both
acetoxy enone (97–98% ee), and hydroxyl enone (93–
95% ee) (Table 1). The enzymes PLE (Pig Liver ester-
ase), Amano PS, and CCL (Candida Cylindracea lipase)
preferentially recognized the (S)-enantiomer of rac-2a,
while PPL preferentially recognized the (R)-enantiomer
of rac-2a (Table 2, Scheme 1).
3, 4
1a,b
2a,b
Scheme 2.
3. Conclusion
The results show that manganese(III) acetate-mediated
acetoxylation of an enone followed by enzyme-mediated
hydrolysis of the acetoxy group provides hydroxy
enones 1b and 2b and acetoxy enone 1a and 1b with high
enantiomeric excesses (95 to >98%) in good chemical
yields. In these conversion reactions, the enzymes favor
the (R)-enantiomer with six-member ring compound 1a
while most of the enzymes shows reverse selectivity with
five-member ring compound 2a. The reduction of the
acetoxy and hydroxy enone followed by acid hydrolysis
provided both enantiomers of 4-hydroxy-2-methyl
cyclohex-2-en-1-one 3 and 4-hydroxy-2-methyl cyclo-
pent-2-en-1-one 4 in a high enantiomeric excess. This
method provides a simple new entry to the synthesis of
cyclic 4-hydroxy enones, which are important precursors
for pharmacologically interesting compounds.
The absolute configuration of products 1 and 2 was
based on the absolute configuration of the known final
products 35 and 4.6 As we reported earlier for related
systems, racemization free interconversion of acetate to
alcohol and vice versa gives additional flexibility to this
method.7c;d;10;11 Since the reduction of a0-acetoxy or
a0-hydroxy-a,b-unsaturated enone 1 and 2 provide
access to c-hydroxy-a,b-unsaturated enone,7c;d the
reaction of 1 and 2 with LiAlH4 followed by acid cata-
lyzed hydrolysis and elimination furnished the desired
products 3 and 4 in 79–81% yields after separation of the
crude product by column chromatography. The abso-
lute configuration of the product was assessed by com-
parison of its specific rotation and HPLC data with data
from the literature.5;6 The chiroptical comparison and
HPLC analysis of the products 3 and 4 with racemic
reference compounds using a chiral column showed that
no isomerization occurred during this reaction. For the
high yield formation of 3 and 4 we suggest that either
the reduction works with high selectivity or acid or base
catalyzed isomerization at the a-position occurs during
the elimination. Until now it has not been possible to
isolate the reduction products before elimination;
therefore we cannot give an exact mechanism for this
step. The reason for this behavior is still under investi-
gation (Scheme 2).
4. Experimental
4.1. Materials and methods
NMR spectra were recorded on a Bruker DPX 400.
Column chromatography was conducted on silica gel 60
(mesh size 40–63 lm). Optical rotations were measured
with a Bellingham–Stanley P20 polarimeter or Autopol
IV automatic polarimeter. Enantiomeric excesses were
determined by HPLC analysis using a Thermo Quest
(TSP) GCLCMS equipped with an appropriate optically
active column.
4.2. General procedures
4.2.1. General procedure for Mn(OAc)3 oxidation. A
solution of 5 and 6 (22.3 mmol), Mn(OAc)3 (17.2 g,
Table 2. Enzymatic hydrolysis of 4-methoxy-3-methyl-2-oxocyclopent-3-en-1-yl acetate (rac-1b)
No
Enzyme
Reaction
time (h)
Conversion
ca (%)
Acetate
Yieldc (%)
Alcohol
Yieldc (%)
Ed
Eeb (%)
Eeb (%)
1
2
3
4
PLE
16
22
51
51
44
53
98
97
68
28
45
41
51
54
95
93
87
32
47
45
43
37
180
115
29
Amano PS
CCL
PPL
28 d
23 d
3
a c ¼ ees=ðees þ eepÞ.
b Determined by HPLC using chiral column (Chiralpak OB column, UV detection at 254 nm, eluent: hexane/2-propanol ¼ 75:25, flow 0.80 mL minꢀ1
20 °C, using racemic compounds as references; Rf : for (S)-2a: 50 min; (R)-2a: 22 min; Rf : for (R)-2b: 15 min; (S)-2b: 10 min).
c Isolated yield after flash column chromatography.
d See Ref. 13. E values are calculated using the program ÔSelectivityÕ by K. Faber and H. Hoenig, http://www.cis.TUGraz.at/orgc/.

780
A. S. Demir et al. / Tetrahedron: Asymmetry 15 (2004) 777–781
66.9 mmol) and benzene (200 mL) were heated under
reflux for 30–54 h. After cooling, the reaction mixture
was first filtered and then washed with satd NaHCO3
solution. The mixture was then dried over MgSO4,
concentrated and purified by flash column chromato-
graphy (2:1 EtOAc/hexane) to yield rac-1a and rac-2a.
4.2.3. General procedure for reductions. To a suspension
of LiAlH4 (66.8 mg, 1.8 mmol) in anhydrous Et2O
(50 mL) was added acetoxy enone (1 mmol) or hydroxy
enone (1 mmol) at rt over 15 min. The mixture was re-
fluxed for 30–50 min, cooled to rt and quenched with
water and 10% H2SO4. The organic phase was washed
with satd NaHCO3 solution and brine and then dried
over MgSO4. After evaporation of the solvent flash
column chromatography (EtOAc) was performed to
obtain 4-hydroxy cyclic enones 3 and 4 in 79–81% yield.
4.2.2. General procedure for the lipase-catalyzed asym-
metric hydrolysis of rac-1a and rac-2a. Lipase (200–
300 mg) was dissolved in a potassium phosphate buffer
(20 mM, pH 7, 30 mL) and added to a solution of the
pure substrate 1a and 2a (1 mmol) in DMSO (3 mL) and
the reaction mixture left to stir at rt. The reaction was
monitored by TLC and HPLC and when maximum
conversion was reached, the reaction was terminated by
filtration. The unreacted acetate and product were sep-
arated by flash chromatography over silica (n-hexane/
ethyl acetate, 4:1).
4.2.3.1. (R)-4-Hydroxy-2-methyl-2-cyclohexen-1-one,
(R)-3.3;5 Light yellow semi-solid. (100 mg, 79%);
20
½aꢁ ¼ +46.7 (c 0.1, CHCl3); IR (CHCl3): m ¼ 3300,
D
1715, 1635 cmꢀ1. 1H NMR (400 MHz, CDCl3) d 1.73 (t,
J ¼ 1:3 Hz, 3H, Me-2), 1.88 (m, 1H, H-5), 2.27 (m, 2H,
H-5 + H-6), 2.53 (m, 1H, H-6), 4.44 (m, 1H, H-4), 6.60
(m, 1H, H-3); 13C NMR (100 MHz, CDCl3) d 15.6, 32.7,
35.3, 66.4, 135.6, 147.7, 199.1.
4.2.3.2. (S)-4-Hydroxy-2-methylcyclopent-2-en-1-one,
4.2.2.1.
(S)-6-Acetoxy-3-methoxy-2-methyl-2-cyclo-
20
D
(S)-4.6 Yellow oil (91 mg). ½aꢁ ¼ )33.5 (c 1.1, CHCl3)
hexen-1-one, (S)-1a.2d Yellow semi-solid. (97 mg);
20
{lit.6 ½aꢁ ¼ )30.0 (c 1.2, CHCI3)}; IR (CHCI3):
20
½aꢁ ¼ )87.9 (c 0.6, CHCl3); IR (CHCl3): m ¼ 1735,
D
D
m ¼ 3400, 1710, 1640 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d 1.74 (s, 3H, CH3), 2.07 (br s, 1H, OH), 2.2 (dd,
J ¼ 18:5, 1.8 Hz, 1H, CH2), 2.71 (dd, J ¼ 18:5, 6.07 Hz,
1H, CH2), 4.85 (m, 1H, CHOH), 7.09 (m, 1H, @CH);
13C NMR (100 MHz, CDCI3) d 206.2, 156.7, 144.0, 68.8,
44.8, 10.3.
1640, 1610 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 1.61 (s,
3H, CH3), 1.99 (ddd, J ¼ 24:0, 12.5, 5.7 Hz, 1H, H-5),
2.09 (s, 3H, COCH3), 2.19 (m, 1H, H-5), 2.60 (m, 1H, H-
4), 2.70 (m, 1H, H-4), 3.77 (s, 3H, OCH3), 5.15 (dd,
J ¼ 12:9, 5.1 Hz, 1H, H-6); 13C NMR (100 MHz,
CDCl3) d 8.0, 21.2, 23.9, 26.7, 55.5, 72.3, 114.2, 170.2,
170.3, 192.5.
Acknowledgements
4.2.2.2. (R)-6-Hydroxy-3-methoxy-2-methyl-2-cyclo-
hexen-1-one, (R)-1b. Colorless semi-solid. (73 mg).
20
Financial support was funded by the Middle East
Technical University (BAP-2003), the Scientific and
Technical Research Council of Turkey (TUBITAK), the
Turkish Academy of Sciences (TUBA), and the Turkish
State Planning Organization (DPT) and is gratefully
acknowledged. We would like to thank MEITO SAN-
GYO Co., Ltd., Tokyo, Japan for the enzymes TL, SL,
and QLM.
½aꢁ ¼ +167.3 (c 0.3, CHCl3); IR (CHCl3): m ¼ 3250,
D
1650, 1620 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 1.64 (s,
3H, CH3), 1.69 (ddd, J ¼ 5:4, 12.4, 25.5 Hz, 1H, H-5),
2.34 (m, 1H, H-5), 2.54 (m, 1H, H-4), 2.68 (m, 1H, H-4),
3.79 (s, 3H, OCH3), 3.88 (dd, J ¼ 5:4, 13.3 Hz, 1H, H-
6); 13C NMR (100 MHz, CDCl3) d 8.0, 24.0, 29.4, 55.4,
71.0, 112.4, 171.5, 198.8. Anal. Calcd for C8H12O3
(156.18): C, 61.52; H, 7.74. Found: C, 61.21; H, 7.98.
4.2.2.3.
(R)-4-Methoxy-3-methyl-2-oxocyclopent-3-
en-1-yl acetate, (R)-2a.2d;e Yellow oil (83 mg).
20
References and notes
½aꢁ ¼ +32.1 (c 0.01, CHCI3); IR (CHCl3): m ¼ 1750,
D
1710, 1630 cmꢀ1. 1H NMR (400 MHz, CDCl3) d 1.58 (s,
3H, CH3), 2.05 (s, 3H, COCH3), 2.43 (dd, J ¼ 17:4,
1.5 Hz, 1H, CH2), 3.14 (ddd, J ¼ 17:4, 6.8, 1.5 Hz, 1H,
CH2), 3.9 (s, 3H, OCH3), 5.03 (dd, J ¼ 6:8, 2.5 Hz, 1H,
CH); 13C NMR (100 MHz, CDCI3) d 197.5, 179.9,
169.2, 114.4, 69.9, 55.7, 31.9, 19.6, 4.9.
1. (a) Noyori, R.; Suzuki, M. Angew. Chem., Int. Ed. Engl.
1984, 23, 847, and references cited therein; (b) Collins,
P. W.; Djuric, S. W. Chem. Rev. 1993, 93, 1533; (c) Dols,
P. P. M. A.; Klunder, A. J. H.; Zwanenburg, B. Tetra-
hedron 1994, 50, 8515; (d) Coppola, G. M.; Schuster, H. F.
a-Hydroxy Acids in Enantioselective Synthesis; VCH:
Weinheim, 1997; (e) Davies, F. A.; Chen, B. C. Chem.
Rev. 1992, 92, 919; (f) Mabuchi, H.; Haba, T.; Tatami, R.;
Miyamoto, S.; Sakai, Y.; Wakasugi, T.; Watanabe, A.;
Koizumi, J.; Takeda, R.. New Engl. J. Med. 1981, 305,
478.
2. (a) Matoba, K.; Maeda, T.; Nagase, K.; Yamazaki, T.
Chem. Pharm. Bull. 1976, 24, 165; (b) Katsube, J.; Matsui,
M. Agric. Biol. Chem. 1971, 353, 401; (c) Canonica, L.;
Corbella, A.; Jommi, G.; Pelizzoni, F.; Scolastico, C.
Tetrahedron Lett. 1966, 26, 3031; (d) Demir, A. S.; Sayrac,
T.; Watt, D. S. Synthesis 1990, 1119; (e) Kitamoto, M.;
4.2.2.4. (S)-5-Hydroxy-3-methoxy-2-methylcyclopent-
2-en-1-one, (S)-2b.12 Colorless solid (47 mg). Mp 155–
20
157 (lit.12 158–161 °C). ½aꢁ ¼ +78.8 (c 0.1, CHCl3); IR
D
(CHCl3): m ¼ 3450, 1710, 1640 cmꢀ1
.
1H NMR
(400 MHz, CDCl3) d 1.58 (t, 3H, J ¼ 1:9, CH3), 2.48 (dt,
J ¼ 17:0, 1.9 Hz, 1H, CH2), 2.96 (ddd, J ¼ 17:0, 6.5,
1.9 Hz, 1H, CH2), 3.33 (br s, OH), 3.92 (s, 3H, OCH3),
4.17 (d, J ¼ 6:5 Hz,1H, CH); 13C NMR (100 MHz,
CDCI3) d 205.0, 182.2, 115.2, 70.9, 57.1, 34.3, 6.2.

A. S. Demir et al. / Tetrahedron: Asymmetry 15 (2004) 777–781
781
Terashima, S.; Yamada, S. Chem. Pharm. Bull. 1977, 25,
41.
3. Ochoa, M. E.; Arias, M. S.; Aguilar, R.; Delgado, F.;
Tamariz, J. Tetrahedron 1999, 55, 14535.
4. (a) Csaky, A. G.; Contreras, C.; Mba, M.; Plumet, J.
Synlett 2002, 1451; (b) Csakym, A. G.; Contreras, C.;
Mba, M.; Plumet, J. J. Org. Chem. 2001, 66, 9026; (c)
Lola, D.; Belakovs, S.; Gavars, M.; Turovskis, I.; Kemme,
A. Tetrahedron 1998, 54, 1589; (d) Baraldi, P. G.; Pollini,
G. P.; Simoni, D.; Zanirato, V.; Barco, A.; Benetti, S.
Synthesis 1986, 781; (e) Scettri, A.; Piancatelli, G.;
DÕAuria, M.; David, G. Tetrahedron 1979, 35, 135; (f)
Piancatelli, G.; Scettri, A. Synthesis 1977, 116.
20, 2279; (c) Demir, A. S.; Sesenoglu, O. Org. Lett. 2002,
4, 2021; (d) Demir, A. S.; Sesenoglu, O. Tetrahedron:
Asymmetry 2002, 13, 667; (e) Demir, A. S.; Hamamci, H.;
Sesenoglu, O.; Aydogan, F.; Capanoglu, D.; Neslihano-
glu, R. Tetrahedron: Asymmetry 2001, 12, 1953.
8. (a) Quesada, M. L.; Schlessinger, R. H.; Parsons, W. H. J.
Org. Chem. 1978, 43, 3968; (b) Clerici, A.; Pastori, N.;
Porta, O. Tetrahedron 2001, 57, 217.
9. (a) Bornscheuer, U. T.; Kazlauskas, R. J. Hydrolases in
Organic Synthesis––Regio- and Stereoselective Biotransfor-
mations; Wiley-VCH: Weinheim, 1999; (b) Liese, A.;
Seelbach, K.; Wandrey, C. Industrial Biotransformations;
Wiley-VCH: Weinheim, 2000; (c) Faber, K. Biotransfor-
mations in Organic Chemistry, 4th ed.; Springer: Berlin, 2000.
10. Chandra, K. L.; Saravanan, P.; Singh, R. K.; Singh, V. K.
Tetrahedron 2002, 58, 1369.
5. (a) Schultz, A. G.; Zhang, X. Chem. Commun. 2000, 399;
(b) Schultz, A. G.; Dai, M.; Khim, S.-K.; Pettus, L.;
Thakkar, K. Tetrahedron Lett. 1998, 39, 4203.
6. Tanis, S. P.; Robinson, E. D.; McMills, M. C.; Watt, W.
J. Am. Chem. Soc. 1992, 114, 8349.
11. (a) Kajiro, H.; Mitamura, S.; Mori, A.; Hiyama, T. Synlett
1998, 51; (b) Kobayashi, S. Synlett 1994, 689.
7. (a) Demir, A. S.; Camkerten, N.; Gercek, Z.; Duygu, N.;
Reis, O.; Arikan, E. Tetrahedron 1999, 55, 2441; (b)
12. Cimarusti, C. M.; Wolinsky, J. J. Org. Chem. 1966, 31,
4118.
€
Demir, A. S.; Cßamkerten, N.; Akgun, H.; Tanyeli, C.;
13. Chen, C.-S.; Fujimoto, Y.; Girdaukas, G.; Sih, C. J.
J. Am. Chem. Soc. 1982, 104, 7294.
Mahasneh, A. S.; Watt, D. S. Synth. Commun. 1990,