Chemo- And stereoselective reduction of β-keto-α-oximino nitriles by using baker's yeast

Article abstract of DOI:10.1002/ejoc.201403393

The baker's yeast mediated reduction of β-keto-α-oximino nitriles 3 at 20 ° C gave β-hydroxy-α-oximino nitriles 4 in high yields with high enantiomeric purity [enantiomeric excess (ee) values >99%]. At room temperature, the same reaction afforded the product in a slightly lower yield. The β-hydroxy-α-oximino nitriles 4 were obtained as single stereoisomers according to chiral GC-MS analyses and the 1H and 19F NMR spectra of the corresponding Mosher esters. The abso-lute stereochemistry of alcohol 4a was determined by hydrolysis of its oximino nitrile group followed by conversion into its corresponding α-hydroxy ester. The β-hydroxy-α-oximino nitrile products were further submitted to oxime- and nitrileselective transformations. This chemo- and stereoselective reduction can be used to generate important chiral building blocks.

Full text of DOI:10.1002/ejoc.201403393

FULL PAPER
DOI: 10.1002/ejoc.201403393
Chemo- and Stereoselective Reduction of β-Keto-α-oximino Nitriles by Using
Baker’s Yeast
Kilwoong Mo,[a,b] Soon Bang Kang,[a] Youseung Kim,[a] Yong Sup Lee,[b] Jae Wook Lee,*[c,d]
and Gyochang Keum*[a,d]
Keywords: Synthetic methods / Biotransformations / Reduction / Chemoselectivity / Enantioselectivity
The baker’s yeast mediated reduction of β-keto-α-oximino
nitriles 3 at 20 °C gave β-hydroxy-α-oximino nitriles 4 in high
yields with high enantiomeric purity [enantiomeric excess
(ee) values Ͼ99%]. At room temperature, the same reaction
afforded the product in a slightly lower yield. The β-hydroxy-
α-oximino nitriles 4 were obtained as single stereoisomers
according to chiral GC–MS analyses and the 1H and 19F
NMR spectra of the corresponding Mosher esters. The abso-
lute stereochemistry of alcohol 4a was determined by hydrol-
ysis of its oximino nitrile group followed by conversion into
its corresponding α-hydroxy ester. The β-hydroxy-α-oximino
nitrile products were further submitted to oxime- and nitrile-
selective transformations. This chemo- and stereoselective
reduction can be used to generate important chiral building
blocks.
and the environment. Furthermore, biocatalysts such as en-
zymes or whole cell systems have been used to generate new
chirality in a broad range of transformations, including re-
duction,[3] ligation,[4] and oxidation[5] reactions as well as
many others.[6] Recently, the scope of biocatalysis has been
expanded to the generation of chemically unfavorable syn-
thetic structures.[7] Compared to purified enzymes, enzymes
in whole cell biocatalytic systems are inherently more stable,
as they are retained in their natural surroundings.[8] In ad-
dition, whole cell systems can regenerate various cofactors
such as nicotinamide adenine dinucleotide (NADH) and
nicotinamide adenine dinucleotide phosphate (NADPH),
which are required for enzymatic reduction.[9]
Introduction
Microbial transformations by using fungi and bacteria
have been known for thousands of years, ever since the
fermentation of yeast was carried out to brew alcohol. In
particular, Saccharomyces cerevisiae, also known as baker’s
yeast, has been widely applied to biocatalytic processes.[1]
Such processes have been used to produce chiral com-
pounds for employment as important building blocks in the
chemical and pharmaceutical industries.[2] Although enan-
tiomerically pure compounds can be extracted from avail-
able natural sources, biocatalytic syntheses of structurally
divergent chiral building blocks have the advantage of scal-
ability. Relative to conventional chemical syntheses, biocat-
alytic syntheses are less hazardous to the health of humans
β-Hydroxy nitriles are versatile building blocks in many
chemical syntheses and especially in the preparation of nat-
ural products and pharmaceutically important scaffolds.[10]
[a] Center for Neuro-medicine, KIST,
Hwarang-ro 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Chiral β-hydroxy nitriles have been generated from asym-
Korea
metric aldol-type reactions with acetonitrile, the β-boration
E-mail: gkeum@kist.re.kr
of α,β-unsaturated nitriles followed by an oxidation reac-
tion, borane reductions, and the hydrogenation of β-keto
nitriles with an organometallic catalyst.[11] In addition, an
asymmetric synthesis of β-hydroxy nitriles has been devel-
oped by using chemo-enzymatic transformations with iso-
lated enzymes or microorganisms. For example, the enan-
tioselective synthesis of a β-hydroxy nitrile was achieved by
lipase-catalyzed dynamic kinetic resolution of the corre-
sponding racemate with a maximum 50% conversion.[12]
The asymmetric reductions of β-keto nitriles by using whole
cell biocatalytic systems such as baker’s yeast (S. cerevisiae)
and Curvularia lunata have been hampered by low isolated
yields and competing α-alkylation reactions.[13] The amount
of ethylated byproduct could be reduced by lowering the
reaction temperature or using methanol as a cosolvent.[14]
http://eng.kist.re.kr/kist_eng
[b] Department of Pharmacy, College of Pharmacy & Department
of Life and Nanopharmaceutical Sciences, Kyung Hee
University,
1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of
Korea
http://pharm.khu.ac.kr/english/e_intro_03.htm
[c] Natural Product Research Center, Korea Institute of Science
and Technology (KIST),
Saimdang-ro 679, Gangneung, Gangwon-do, Republic of
Korea
E-mail: jwlee5@kist.re.kr
http://gn.kist.re.kr/handler/gen/Index
[d] Department of Biological Chemistry, University of Science and
Technology,
217 Gajeong-ro Yuseong-gu, Daejeon 305-350, Republic of
Korea
http://www.ust.ac.kr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403393.
Eur. J. Org. Chem. 2015, 1137–1143
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1137

K. Mo, S. B. Kang, Y. Kim, Y. S. Lee, J. W. Lee, G. Keum
FULL PAPER
Byproducts in the reduction of β-keto nitriles can also be Table 1. The reduction of β-keto-α-oximino nitriles with baker’s
yeast.
avoided by using isolated carbonyl reductase from various
strains of yeast combined with an NADPH cofactor and/
or a d-glucose dehydrogenase (GDH) cofactor regeneration
system.[10,15] In particular, each enantiomer can be selec-
tively synthesized by selecting an appropriate baker’s yeast
reductase that offers high stereospecificity.
We designed β-keto-α-oximino nitriles as the substrate
Entry
R
H
Yeast type Temp. [°C] Time [h] % Yield 4a[a] % ee[b]
for a baker’s yeast-mediated reduction (see Figure 1). This
strategy largely eliminates the α-ethylated byproducts, and
therefore the β-hydroxy nitriles can be practically used as
chiral building blocks. It has been hypothesized that an op-
tically pure β-hydroxy-α-oximino nitrile could be used as an
intermediate in syntheses of chemically and pharmaceuti-
cally important building blocks through appropriate con-
versions of the α-oximino nitrile unit.[16]
1
2
3
4
5
6
7
8
2
Sigma II
r.t.
r.t.
20
20
r.t.
20
20
r.t.
–
NR
66
–
3a CH3 Sigma II
3a CH3 Sigma II
3a CH3 IMBY[c]
3a CH3 Sigma I
3a CH3 Sigma I
3a CH3 Oriental
36
16
24
31
39
39
–
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
–
74
61
51
73
36
NR
3b Bn
Sigma II
[a] Reactions were performed on a 0.4 mmol scale with baker’s
yeast (2 g), saccharose (3 g), ethanol (1.5 mL), and tap water
(60 mL). Isolated yields are provided (NR = no reaction). [b] Enan-
tiomeric excess (ee) values were determined by GC analysis on a
Supelco-DEX 225 chiral column (20 mm, 0.25 mm ID, 0.25 μm
film) at 170 °C under isothermal conditions. Optical rotation:
[α]2D3 = +1.53 (c = 1.0, CHCl3). [c] Sigma type II yeast was immobi-
lized on montmorillonite K10.[18] IMBY: immobilized baker’s ye-
ast.
The oxime unit was not reduced in these reactions, which
indicates that baker’s yeast chemoselectively reduces the
ketone moiety of the β-keto-α-methyloximino nitrile.[19] The
yield of β-hydroxy-α-methyloximino nitrile 4a improved to
74% (see Table 1, Entry 3) by using Sigma type II baker’s
yeast at 20 °C. The immobilization of Sigma type II baker’s
yeast on montmorillonite K10[18] did not increase the yield
of 4a (see Table 1, Entry 4). Thus, the reaction was influ-
enced primarily by the type of baker’s yeast that was em-
ployed, with Sigma type II yeast providing the highest
yields. The effect of the reaction temperature was also
evaluated. The reduction of 3a with baker’s yeast was per-
formed at room temperature and 20 °C, to yield product 4a
in isolated yields of 51 and 73% (see Table 1, Entries 5 and
6), respectively. Thus, decreasing the reaction temperature
resulted in a significant improvement in isolated yield.
Interestingly, the reduction of 3 with Oriental baker’s yeast
at 20 °C gave product 4a in a low yield of 36% (see Table 1,
Entry 7). Product 4a was obtained with Ͼ99% enantio-
meric purity, which was determined by the chiral GC–MS
analysis of 4a relative to the corresponding racemate ob-
tained by the NaBH4 reduction of 3a. Compound 4a was
Figure 1. Baker’s yeast (BY)-mediated reduction and subsequent
conversion of β-keto-α-oximino nitrile.
Results and Discussion
A series of β-keto-α-oximino nitriles 3 were prepared by
the nitrosylation of β-keto nitrile 1 and subsequent O-alkyl-
ation of the resulting α-hydroxyimino-β-keto nitrile 2 in
high yields (see Scheme 1).[17]
Scheme 1. The synthetic route for the preparation of compounds
3a and 3b. Reagents and conditions: (i) NaNO2/H2O, AcOH, 75%;
(ii) Me2SO4, K2CO3, acetone, 91%; (iii) BnBr, K2CO3, acetone,
94%.
1
obtained as a single isomer according to the H and 19F
We evaluated the reactivity of α-hydroxyimino-β-keto NMR analysis of the corresponding Mosher ester. In the
nitrile 2 and 2-oximino-3-oxo-3-phenylpropionitriles 3a and baker’s yeast reduction, the enantiomeric purity of 4a was
3b with different strains of baker’s yeast under a variety not affected by the type of baker’s yeast or the reaction
of reaction conditions. Only commercially available baker’s temperature. The absolute stereochemistry of alcohol 4a
yeasts were used. Table 1 shows that oxime 2 and benzylox- was determined by converting it into mandelic acid methyl
ime 3b were not reduced to the alcohol under these condi- ester 6a, which was performed by the acidic hydrolysis of
tions. β-Keto-α-methyloximino nitrile 3a afforded alcohol the oximino nitrile moiety to give acid 5a followed by esteri-
4a in 66% yield after isolation by a keto-selective reduction fication to give the ester in 50% yield over the two steps
using Sigma type II yeast at room temperature (23–28 °C) (see Scheme 2). The absolute configuration of the chiral
fr 36 h (see Table 1, Entry 2).
center of mandelic acid methyl ester 6a {[α]2D4 = –166 (c =
1138
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 1137–1143

Chemo- and Stereoselective Reduction by Using Baker’s Yeast
1.0, MeOH)} was confirmed as R by comparing experimen- Table 2. Reduction of β-keto-α-oximino nitriles with baker’s yeast.
tal data with reported optical rotation data {[α]2D0 = –144 (c
= 1.0, MeOH)}.[20]
R
Yeast type Time [d]
[α]D23
% Yield[a] % ee[b]
3c
3c
3c
3d
3d
3d
3e
3e
3e
3f
2-ClC6H4
2-ClC6H4
2-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
2,4-Cl2C6H3 Sigma I
2,4-Cl2C6H3 Sigma II
2,4-Cl2C6H3 Oriental
4-MeOC6H4 Sigma I
4-MeOC6H4 Sigma II
4-MeOC6H4 Oriental
3-MeOC6H4 Sigma I
3-MeOC6H4 Sigma II
3-MeOC6H4 Oriental
Sigma I
Sigma II
Oriental
Sigma I
Sigma II
Oriental
3
3
3
6
4
5
3
5
4.5
5.5
5.5
4
3
3
4
2
2
3
–
39
62
43
71
37
35
58
54
40
22
6
13
84
66
50
76
95
24
–
Ͼ99
–
Ͼ99
–
–
–
Ͼ99
–
Ͼ99
–
–
Ͼ99
–
–
–
–14.79
–
+18.62
–
–
–
+2.45
–
–2.38
–
Scheme 2. The synthesis of methyl mandelate 6a. Reagents and
conditions: (i) HCl (6 n), reflux, 2 h, 80% (for 5a); (ii) Amberlyst-
15, CH3OH, room temp., 21 h, 63% (for 6a); [α]2D4 = –166 (c = 1.0,
MeOH); ref.[20] [α]2D0 = –144 (c = 1.0, MeOH).
The effects of different substitution patterns were also
investigated with regard to this baker’s yeast-mediated
stereoselective reduction reaction. β-Keto-α-methyloximino
nitriles that contained either a substituted aromatic (i.e., 3c–
3g) or a cyclohexyl (i.e., 3h) group at the β-position were
prepared from the appropriate β-keto nitriles by using the
same method for the preparation of 3a (see Scheme 3).
3f
3f
–
3g
3g
3g
3h
3h
3h
+18.89
–
–
–
–4.97
–
cyclohexyl
cyclohexyl
cyclohexyl
Sigma I
Sigma II
Oriental
Ͼ99
–
[a] Reactions were carried out on a 0.4 mmol scale with baker’s
yeast (2 g), saccharose (3 g), ethanol (1.5 mL), and tap water
(60 mL) at 20 °C. Isolated yields are provided. [b] The ee values
were determined by chiral GC–MS analysis and the 1H and 19F
NMR spectra of the corresponding Mosher esters.
α-hydroxy ester 6h {[α]2D4 = –0.26 (c = 1.0, CHCl3)} and
then comparing the experimental optical rotation data with
that reported for its enantiomer.[21]
In addition to the conversion of optically active β-
hydroxy-α-methyloximino nitriles into β-hydroxy acetic acid
derivatives, nitrile- and oxime-selective conversions of meth-
yloximino nitrile product 4a were performed as shown in
the Scheme 4. Product 4a was converted into carboxamide
7a in a 91% yield by using a nitrile-selective hydrolysis. Af-
ter O-benzyl protection, the oxime of 4a was selectively re-
Scheme 3. The synthesis of β-keto-α-oximino nitriles 3c–3h. Rea-
gents and conditions: (i) NaH/toluene, p-toluenesulfonic acid
(TsOH), room temp., overnight; (ii) NaNO2/H2O, AcOH, r.t.,
30 min; (iii) Me2SO4, r.t.
The reduction of β-keto nitriles 3c–3g was performed
with three different types of baker’s yeasts under the pre-
viously optimized conditions. As shown in Table 2, most of
the substrates, with the exception of 3f, were reduced to the
alcohol products (i.e., 4c–4e, 4g, and 4h) in high yields. β-
Keto nitrile 3f, which contained an electron-donating group
at the para position of the aromatic group, gave relatively
low yields of the product. In contrast, β-cyclohexyl-substi-
tuted keto nitrile 3h was reduced to alcohol 4h in 95% yield.
As discussed above, the type of baker’s yeast was important.
The reduction of 3c and 3h by using Sigma type II baker’s
yeast resulted in high yields. For the reduction of com-
pounds 3d–3g, Sigma type I baker’s yeast gave the highest
yields. Interestingly, the Oriental-type baker’s yeast gave low
yields in general. All of the products 4c–4h were obtained
as a single isomer according to chiral GC–MS analysis and
the 1H and 19F NMR spectra of the corresponding Mosher
esters (see Supporting Information). The optical rotation
data of products 4c–4g, which have substituted aromatic
rings, are reported in the Table 2. The absolute stereochem-
istry of aliphatic alcohol 4h was also confirmed as the R
Scheme 4. The chemoselective transformation of 4a. Reagents and
conditions: (i) 30% NaOH, reflux, 7 d, 91%; (ii) BnBr, Ag2O,
CH2Cl2, room temp., 48 h, 96%; (iii) Zn, AcOH/Ac2O, r.t., 27 h,
70%; (iv) NaN3, ZnBr2, H2O/iPrOH, reflux, 48 h, 92%;
(v) NH2OH·HCl, K2CO3, EtOH, reflux, 8 h; NaH, EtOAc, tetra-
configuration. This was determined by converting 4h into hydrofuran (THF), reflux, 1 h, 50%.
Eur. J. Org. Chem. 2015, 1137–1143
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1139

K. Mo, S. B. Kang, Y. Kim, Y. S. Lee, J. W. Lee, G. Keum
FULL PAPER
[M]+, 129, 105 (100), 77, 51. 1H NMR (300 MHz, CDCl3): δ =
duced to an amine by a zinc-mediated reduction. A subse-
quent acetylation reaction gave cyanoacetamide 8, albeit
with low diastereoselectivity. The nitrile group of 8 was fur-
ther converted into tetrazole 9 and oxadiazole 10 heterocy-
cles.
8.01–7.47 (m, 5 H), 4.33 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ
= 184.04, 134.67, 134.53, 132.23, 130.90, 128.99, 108.37,
66.50 ppm. IR (KBr): ν = 2362 (O=C–C=N), 1648 (C=O) cm–1.
˜
3-(2-Chlorophenyl)-2-methoxyimino-3-oxopropionitrile (3c): MS
1
(70 eV): m/z (%) = 222 [M]+, 187, 139 (100), 111, 75, 51. H NMR
(300 MHz, CDCl3): δ = 7.47–7.37 (m, 4 H), 4.24 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 185.62, 135.17, 132.65, 131.87,
130.98, 130.16, 129.86, 126.72, 107.29, 66.33 ppm. IR (KBr): ν =
˜
Conclusions
2364 (O=C–C=N), 1700 (C=O) cm–1.
In summary, the baker’s yeast mediated asymmetric re-
3-(4-Chlorophenyl)-2-methoxyimino-3-oxopropionitrile (3d): MS
1
duction of β-keto-α-methoxyimino nitriles was successfully (70 eV): m/z (%) = 222 [M]+, 139 (100), 111, 85, 75, 51. H NMR
(300 MHz, CDCl3): δ = 7.98–7.46 (m, 4 H), 4.34 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 182.33, 140.94, 132.38, 131.83,
achieved in high yields and with high enantioselectivities.
Sigma type II baker’s yeast afforded the products in the
129.78, 128.93, 107.66, 66.13 ppm. IR (KBr): ν = 2364 (O=C–
˜
highest yields. The β-keto-α-methyloximino nitriles that
contained a substituted aromatic (i.e., 3c–3g) or cyclohexyl
(i.e., 3h) group at the β-position were reduced in this baker’s
yeast mediated reaction to give the corresponding β-
hydroxy-α-oximino nitrile. The products were exclusively
obtained as single stereoisomers, the configurations of
which were confirmed as R by their conversion into the
corresponding β-hydroxy carboxylic acid derivatives. As
shown in Scheme 4, methyloximino nitrile 4a can be further
transformed by using an oxime-selective reduction and a
nitrile-selective conversion. Additional procedures to con-
vert the functionality of compounds 4 are needed to de-
velop useful chiral building blocks. This new baker’s yeast
mediated reduction of β-keto-α-oximino nitriles that is de-
scribed herein is an effective chemo- and stereoselective re-
action. In addition, the method makes use of a whole cell
system, which is an environmentally benign means to pre-
pare β-hydroxy-α-oximino nitriles with high stereoselecti-
vity.
C=N), 1700 (C=O) cm–1.
3-(2,4-Dichlorophenyl)-2-methoxyimino-3-oxopropionitrile (3e): MS
(70 eV): m/z (%) = 256 [M]+, 221, 173 (100), 145, 109, 74. 1H NMR
(300 MHz, CDCl3): δ = 7.48–7.36 (m, 3 H), 4.25 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 184.64, 138.46, 133.61, 133.07,
132.45, 130.90, 130.26, 127.24, 107.14, 64.04 ppm. IR (KBr): ν =
˜
2365 (O=C–C=N), 1702 (C=O) cm–1.
2-Methoxyimino-3-(4-methoxyphenyl)-3-oxopropionitrile (3f): MS
(70 eV): m/z (%) = 218 [M]+, 187, 159, 135 (100), 107, 92, 77, 64.
1H NMR (300 MHz, CDCl3): δ = 8.07–6.94 (m, 4 H), 4.33 (s, 3
H), 3.90 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 133.29,
132.29, 132.48, 131.78, 114.98, 114.20, 113.83, 66.02, 55.85 ppm.
IR (KBr): ν = 2360 (O=C–C=N), 1693 (C=O) cm–1.
˜
2-Methoxyimino-3-(3-methoxyphenyl)-3-oxopropionitrile (3g): MS
1
(70 eV): m/z (%) = 218 [M]+, 135 (100), 107, 92, 77, 64. H NMR
(300 MHz, CDCl3): δ = 7.61–7.17 (m, 4 H), 4.33 (s, 3), 3.86 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 183.26, 159.58, 135.24,
131.79, 129.50, 123.23, 120.70, 114.58, 107.89, 65.97, 55.48 ppm.
IR (KBr): ν = 2359 (O=C–C=N), 1692 (C=O) cm–1.
˜
3-Cyclohexyl-2-methoxyimino-3-oxopropionitrile (3h): The pro-
cedure for the preparation of 3a was followed by starting from the
corresponding oxime, which was obtained by nitrosylation of 3-
cyclohexyl-3-oxopropanenitrile, to afford 3h (69%). MS (70 eV):
Experimental Section
1
m/z (%) = 194 [M]+, 179, 163, 136, 111, 83 (100), 67, 55. H NMR
2-Hydroxyimino-3-oxo-3-phenylpropionitrile (2): To a solution of
benzoylacetonitrile (5.0 g, 34.4 mmol) in acetic acid (10 mL) was
added dropwise a solution of sodium nitrite (2.49 g, 36.1 mmol) in
water (5 mL) at 0 °C. The reaction mixture was stirred at room
temperature for 30 min. Upon completion, the reaction mixture
was poured into brine (50 mL), and the resulting solution was ex-
tracted with EtOAc (3ϫ 30 mL). The combined organic layers were
washed with brine and dried with Na2SO4. The solvent was re-
moved under reduced pressure to give a residue, which was purified
by flash chromatography on silica gel (hexane/EtOAc, 4:1) to afford
compound 2 (3.60 g, 60%). MS (70 eV): m/z (%) = 174 [M]+, 131,
(300 MHz, CDCl3): δ = 4.31 (s, 3 H), 1.83–1.20 (m, 10 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 195.71, 131.59, 107.94, 66.37,
45.66, 28.93, 25.99, 25.76 ppm. IR (CCl ): ν = 2362 (O=C–C=N),
˜
4
1696 (C=O) cm–1.
Synthesis of 3-Hydroxy-2-methoxyimino-3-phenylpropionitrile (4a):
2-Methoxyimino-3-oxo-3-phenylpropionitrile (3a, 0.4 mmol) was
dissolved in ethanol (1.5 mL), and the solution was added to a
suspension of baker’s yeast (2 g) and saccharose (3 g) in tap water
(60 mL) with shaking at 20 °C. The reaction mixture was shaken
for the specified time (see Table 1) and then saturated with sodium
chloride. The resulting mixture was filtered through Celite, which
was rinsed with chloroform. The filtrate was then extracted with
chloroform (3ϫ), and the combined organic layers were dried with
Na2SO4 and concentrated under reduced pressure. The residue was
purified by flash chromatography on silica gel (hexane/EtOAc, 7:1)
to give compound 4a (55.9 mg, 74%) as an oil. MS (70 eV): m/z (%)
= 190 [M]+, 161, 170 (100), 79, 51. 1H NMR (300 MHz, CDCl3): δ
= 7.46–7.39 (m, 5 H), 5.53 (s, 1 H), 4.10 (s, 3 H), 2.78 (s, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 137.36, 134.28, 129.20, 129.04,
126.27, 108.52, 72.65, 64.08 ppm. HRMS (FAB): calcd. for
C10H10N2O2Na+ [M + Na]+ 213.0640; found 213.0645. IR (CCl4):
1
105 (100), 77, 51. H NMR (300 MHz, CDCl3): δ = 7.28–8.00 (m,
5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 185.39, 134.77, 134.46,
133.47, 130.89, 128.83, 108.68 ppm. IR (KBr): ν = 3300 (OH), 2362
˜
(O=C–C=N), 1646 (C=O) cm–1.
2-Methoxyimino-3-oxo-3-phenylpropionitrile (3a): To a stirred solu-
tion of
2 (1.0 g, 5.7 mmol) and dimethyl sulfate (0.82 mL,
1.5 equiv.) in acetone (10 mL) was added K2CO3 (1.19 g, 1.5 equiv.)
portionwise at 0 °C. The reaction mixture was stirred at room tem-
perature for 5 h. The reaction mixture was then filtered, and the
filtrate was concentrated under reduced pressure. The residue was
purified by flash chromatography on silica gel (hexane/EtOAc, 7:1)
to give compound 3a (0.98 g, 91%). MS (70 eV): m/z (%) = 188 ν = 3742 (OH) cm–1.
˜
1140
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 1137–1143

Chemo- and Stereoselective Reduction by Using Baker’s Yeast
3-(2-Chlorophenyl)-3-hydroxy-2-methoxyiminopropionitrile (4c): MS
(70 eV): m/z (%) = 224 [M]+, 189 (100), 162, 141, 113, 105, 77, 51.
1H NMR (300 MHz, CDCl3): δ = 7.73–7.28 (m, 4 H), 5.95 (s, 1
EtOAc, 4:1) to give compound 6a (22 mg, 63%). MS (70 eV): m/z
1
(%) = 166 [M]+, 107, 79 (100), 51. H NMR (300 MHz, CDCl3): δ
= 7.45–7.34 (m, 4 H), 5.19 (d, J = 6 Hz, 1 H), 3.77 (s, 3 H), 3.51
H), 4.11 (s, 3 H), 2.96 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): (d, J = 6 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 174.50,
δ = 135.15, 133.17, 132.95, 130.69, 130.21, 128.54, 127.94, 108.93, 138.70, 129.00, 128.90, 127.00, 73.30, 53.40 ppm. HRMS (FAB):
69.62, 64.66 ppm. HRMS (FAB): calcd. for C10H9ClN2O2Na+ [M calcd. for C9H10O3Na+ [M + Na]+ 189.0522; found 189.0524. IR
+ Na]+ 247.0250; found 247.0251. IR (CCl ): ν = 3744 (OH) cm–1.
(CCl ): ν = 3440 (OH), 1740 cm–1.
˜
˜
4
4
3-(4-Chlorophenyl)-3-hydroxy-2-methoxyiminopropionitrile (4d): MS
Methyl (R)-2-Cyclohexyl-2-hydroxyacetate (6h): The title com-
1
(70 eV): m/z (%) = 224 [M]+, 195, 141 (100), 113, 77, 51. H NMR pound was obtained from 4h by following the procedure for the
(300 MHz, CDCl3): δ = 7.40 (s, 4 H), 5.53 (s, 1 H), 4.11 (s, 3 H),
2.88 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 136.18, 135.53, (hexane/EtOAc, 8:1) afforded 6h (48%). [α]2D4 = –0.26 (c = 1.0,
134.34, 129.63, 128.08, 108.78, 72.03, 64.62 ppm. HRMS (FAB):
CHCl3); for enantiomer, ref.[21] [α]2D0 = +0.33 (CHCl3). MS (70 eV):
preparation of 6a. In this case, flash chromatography on silica gel
calcd. for C10H9ClN2O2Na+ [M + Na]+ 247.0250; found 247.0250. m/z (%) = 172 [M]+, 113, 83, 67, 55 (100). 1H NMR (300 MHz,
IR (CCl ): ν = 3743 (OH) cm–1.
CDCl3): δ = 4.03 (d, J = 6.3 Hz, 1 H), 3.79 (s, 3 H), 2.63 (d, J =
6.0 Hz, 1 H), 1.76–1.10 (m, 11 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 185.70, 76.40, 52.64, 42.56, 28.30, 26.64, 26.30 ppm.
HRMS (FAB): calcd. for C9H16O3Na+ [M + Na]+ 195.0992; found
195.0995.
˜
4
3-(2,4-Dichlorophenyl)-3-hydroxy-2-methoxyiminopropionitrile (4e):
MS (70 eV): m/z (%) = 258 [M]+, 231, 223, 196, 175 (100), 147,
111, 75. 1H NMR (300 MHz, CDCl3): δ = 7.66–7.35 (m, 3 H), 5.89
(s, 1 H), 4.09 (s, 3 H), 2.94 (s, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 135.59, 133.33, 133.11, 132.35, 129.56, 129.07, 127.87,
108.40, 68.77, 64.33 ppm. HRMS (FAB): calcd. for
C10H8Cl2N2O2Na+ [M + Na]+ 280.9855; found 280.9857. IR
3-Hydroxy-2-(methoxyimino)-3-phenylpropanamide (7a): A suspen-
sion of compound 4a (49 mg, 0.26 mmol) in 30% NaOH (5 mL)
was heated at reflux and stirred for 7 d. The mixture was extracted
with ethyl acetate (10 mL), and the organic layer was dried with
MgSO4 and concentrated. The residue was purified by chromatog-
raphy on a silica gel column (n-hexane/EtOAc, 2:1) to give com-
(CCl ): ν = 3746 (OH) cm–1.
˜
4
3-Hydroxy-2-methoxyimino-3-(4-methoxyphenyl)propionitrile (4f):
MS (70 eV): m/z (%) = 220 [M]+, 191, 137 (100), 109, 94, 77, 66,
1
pound 7a (49 mg, 91%). H NMR (300 MHz, CDCl3): δ = 7.42–
1
51. H NMR (300 MHz, CDCl3): δ = 7.40–6.92 (m, 4 H), 5.48 (s,
7.23 (m, 5 H), 6.69 (s, 1 H), 6.08 (d, J = 11.1 Hz, 1 H), 5.74 (s, 1
H), 5.45 (d, J = 11.1 Hz, 1 H), 4.03 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 165.70, 150.62, 140.32, 128.49, 127.71,
125.73, 68.45, 63.63 ppm. Data for O-TBS protected 7a (TBS =
tert-butyldimethylsilyl): 1H NMR (300 MHz, CDCl3): δ = 7.41–
7.23 (m, 5 H), 6.88 (s, 1 H), 6.40 (s, 1 H), 5.39 (s, 1 H), 4.08 (s, 3
H), 0.95 (s, 9 H), 0.12 (s, 6 H) ppm.
1 H), 4.09 (s, 3 H), 3.82 (s, 3 H), 2.69 (s, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 160.68, 134.85, 129.91, 128.13, 114.87,
109.05, 72.78, 64.44, 55.76 ppm. HRMS (FAB): calcd. for
C11H12N2O3Na+ [M + Na]+ 243.0740; found 243.0745. IR (CCl4):
ν = 3738 cm–1.
˜
3-Hydroxy-2-methoxyimino-3-(3-methoxyphenyl)propionitrile (4g):
MS (70 eV): m/z (%) = 220 [M]+, 191, 162, 135, 109 (100), 94, 77,
O-Benzyl Protection of 4a: To a solution of 3-hydroxy-2-meth-
oxyimino-3-phenylpropionitrile (120 mg, 0.63 mmol) and silver ox-
ide (219 mg, 1.5 equiv.) in dichloromethane (6.3 mL), was added
benzyl bromide (0.2 mL, 162 mg, 1.5 equiv.) at room temperature.
The reaction mixture was stirred at room temperature for 48 h.
Upon completion, the reaction mixture was filtered, and the filtrate
was evaporated under reduced pressure. The residue was purified
by flash chromatography on a silica gel column (n-hexane/EtOAc,
10:1) to afford O-benzyl protected 4a (170 mg, 96%). 1H NMR
(300 MHz, CDCl3): δ = 7.45–7.26 (m, 10 H), 5.19 (s, 1 H), 4.65,
4.61 (ABq, J = 11.7 Hz, 2 H), 4.09 (s, 3 H) ppm.
1
66, 51. H NMR (300 MHz, CDCl3): δ = 7.36–6.90 (m, 4 H), 5.49
(s, 1 H), 4.10 (s, 3 H), 3.83 (s, 3 H), 2.07 (s, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 160.44, 139.39, 134.66, 130.53, 118.90,
115.90, 112.09, 108.97, 72.85, 64.49, 55.76 ppm. HRMS (FAB):
calcd. for C11H12N2O3Na+ [M + Na]+ 243.0740; found 243.0741.
IR (CCl ): ν = 3738 cm–1.
˜
4
3-Cyclohexyl-3-hydroxy-2-methoxyiminopropionitrile (4h): MS
(70 eV): m/z (%) = 195 [M]+, 165, 114, 83 (100), 67, 55. H NMR
1
(300 MHz, CDCl3): δ = 4.11 (d, J = 9 Hz, 1 H), 4.06 (s, 3 H), 2.84
(s, 1 H), 1.93–1.02 (m, 11 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 134.89, 109.40, 75.20, 64.27, 41.76 28.50, 26.46, 26.01 ppm.
HRMS (FAB): calcd. for C10H16N2O2 [M]+ 196.1212; found
N-[2-(Benzyloxy)-1-cyano-2-phenylethyl]acetamide (8): To a solu-
tion of 3-benzyloxy-2-methoxyimino-3-phenylpropionitrile (100 mg,
0.36 mmol) in a mixture of acetic acid/acetic anhydride (1:1,
3.6 mL) was added a solution of activated zinc dust (466.3 mg,
20.0 equiv.) in AcOH/Ac2O (1:1, 1.4 mL) at room temperature. The
reaction mixture was stirred at 40 °C for 27 h. The zinc dust was
removed by filtration and washed with dichloromethane. The fil-
trate was concentrated under reduced pressure, and the residue was
purified by flash chromatography on silica gel (n-hexane/EtOAc,
3:1) to afford diastereomeric upper (36.1 mg) and lower (36.9 mg)
spots of compound 8 (total 70% yield). Data for upper spot of 8:
197.1290. IR (CCl ): ν = 3742 (OH) cm–1.
˜
4
Methyl (R)-Mandelate (6a): A solution of compound 4a (50 mg,
0.26 mmol) in HCl (6 n solution, 3 mL) was heated at reflux and
stirred for 2 h. The reaction mixture was then cooled and extracted
with diethyl ether (3ϫ 10 mL). The combined organic fractions
were concentrated in vacuo, and the resulting residue was dissolved
in a 10% sodium hydrogen carbonate solution. This aqueous solu-
tion was washed with diethyl ether (10 mL) and then acidified to
pH = 2 by the addition of HCl (1 n solution). This aqueous solu-
tion was then extracted with diethyl ether (3ϫ 10 mL). The com-
bined organic layers were washed with brine, dried with MgSO4,
filtered, and concentrated under reduced pressure to yield mandelic
acid 5a (32 mg, 80%). Amberlyst-15 resin (50 mg) was added to a
solution of 5a in methanol (3 mL). The reaction mixture was stirred
at room temperature for 21 h and then filtered through Celite. The
filtrate was concentrated under reduced pressure to give a residue,
which was purified by flash chromatography on silica gel (n-hexane/
1
MS (70 eV): m/z (%) = 294 [M]+, 197, 105, 91 (100), 77, 65, 51. H
NMR (300 MHz, CDCl3): δ = 7.46–7.26 (m, 10 H), 5.91 (d, J =
8.7 Hz, 1 H), 5.18 (dd, J = 8.7, 3.9 Hz, 1 H), 4.71 (d, J = 3.9 Hz,
1 H), 4.64 (d, J = 11.4 Hz, 1 H), 4.43 (d, J = 11.4 Hz, 1 H), 1.88
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.30, 136.60,
135.14, 129.30, 128.89, 128.55, 128.23, 128.09, 127.07, 117.04,
78.70, 71.39, 45.78, 22.54 ppm. HRMS (FAB): calcd. for
C H N O [M + H+] 295.1447; found 295.1446. IR (CCl ): ν =
˜
18 19
2
2
4
Eur. J. Org. Chem. 2015, 1137–1143
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1141

K. Mo, S. B. Kang, Y. Kim, Y. S. Lee, J. W. Lee, G. Keum
FULL PAPER
3215 (NH), 1518, 1658 (C=O) cm–1. Data for lower spot of 8: H
NMR (300 MHz, CDCl3): δ = 7.66–7.32 (m, 10 H), 6.19 (d, J =
9.0 Hz, 1 H), 5.07 (dd, J = 9.3, 3.9 Hz, 1 H), 4.72 (d, J = 12.0 Hz,
1 H), 4.54 (d, J = 3.9 Hz, 1 H), 4.29 (d, J = 12.0 Hz, 1 H), 1.93 (s,
3 H) ppm.
1
Stürmer, T. Zelinski, Angew. Chem. Int. Ed. 2004, 43, 788–824;
Angew. Chem. 2004, 116, 806.
[2]
[3]
a) T. Daußmann, H. G. Hennemann, T. C. Rosen, Chem. Ing.
Tech. 2006, 78, 249–255; b) B. Cornils, W. A. Herrmann, Ap-
plied Homogeneous Catalysis with Organometallic Compounds,
Wiley-VCH, Weinheim, Germany, 2002; c) R. A. Sheldon, Chi-
rotechnology, Marcel Dekker, New York, 1993; d) M. Beller, C.
Bolm, Transition Metals for Organic Synthesis: Building Blocks
and Fine Chemicals, Wiley-VCH, Weinheim, Germany, 1998; e)
R. E. Deasy, A. R. Maquire, Eur. J. Org. Chem. 2014, 3737–
3756.
a) N. K. Modukuru, J. Sukumaran, S. J. Collier, A. S. Chan,
A. Gohel, G. W. Huisman, R. Keledjian, K. Narayanaswamy,
S. J. Novick, S. M. Palanivel, D. Smith, Z. Wei, B. Wong, W. L.
Yeo, D. A. Entwistle, Org. Process Res. Dev. 2014, 18, 810–815;
b) C. P. Marocco, E. V. Davis, J. E. Finnell, P.-H. Nguyen, S. C.
Mateer, I. Ghiviriga, C. W. B. D. Feske, Tetrahedron: Asym-
metry 2011, 22, 1784–1789.
N-[2-(Benzyloxy)-2-phenyl-1-(2H-tetrazol-5-yl)ethyl]acetamide (9):
To a solution of the upper isomer of 8 (36 mg, 0.12 mmol) in water/
2-propanol (2:1, 3 mL) were added sodium azide (15.9 mg,
2.0 equiv.) and zinc bromide (ZnBr2, 3.8 mg, 0.5 equiv.) at room
temperature. The reaction mixture was heated at reflux and stirred
for 48 h. Upon completion, HCl (1 n solution) and ethyl acetate
were added, and the resulting mixture was stirred until the solid
was entirely dissolved. The organic layer was separated, and the
aqueous layer was extracted with ethyl acetate (2ϫ). The combined
organic layers were washed with brine, dried with MgSO4, filtered,
and concentrated under reduced pressure. The residue was purified
by chromatography on a silica gel column (CH2Cl2/MeOH, 30:1–
1:1) to give tetrazole 9 (38 mg, 92%). MS (70 eV): m/z (%) = 338
[4]
[5]
N. Wehofsky, S. Thust, J. Burmeister, S. Klussmann, F. Bor-
dusa, Angew. Chem. Int. Ed. 2003, 42, 677–679; Angew. Chem.
2003, 115, 701.
[M]+, 197, 99, 91 (100), 77, 65, 51. H NMR (300 MHz, CD3OD):
1
a) V. Uppada, S. Bhaduri, S. B. Noronha, Curr. Sci. 2014, 106,
946–957; b) A. Schallmey, P. Dominguez de Maria, P. Bracco,
in: Stereoselective Synthesis of Drugs and Natural Products
(Eds.: V. Andrushko, N. Andrushko), Wiley-Blackwell, Ho-
boken, 2013, vol. 2, p. 1089–1114; c) L. Pollegioni, P. Motta,
G. Molla, Appl. Microbiol. Biotechnol. 2013, 97, 9323–9341.
N. J. Turner, E. O’Reilly, Nat. Chem. Biol. 2013, 9, 285–288.
K. M. Blazewska, T. Gajda, Tetrahedron: Asymmetry 2009, 20,
1337–1361.
δ = 7.38–6.96 (m, 10 H), 5.54 (d, J = 9.0 Hz, 1 H), 4.72 (d, J =
9.0 Hz, 1 H), 4.43 (d, J = 12.0 Hz, 1 H), 4.18 (d, J = 11.4 Hz, 1
H), 1.71 (s, 3 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 172.53,
157.07, 138.62, 129.91, 129.63, 129.34, 128.99, 128.85, 128.55,
128.23, 82.04, 71.73, 50.76, 22.08 ppm. HRMS (FAB): calcd. for
C18H20N5O2 [M + H]+ 338.1617; found 338.1616. IR (KBr): ν =
[6]
[7]
˜
3220 (NH), 1516, 1648 (C=O) cm–1.
N-[2-(Benzyloxy)-1-(5-methyl-1,2,4-oxadiazol-3-yl)-2-phenylethyl]- [8]
acetamide (10): A suspension of nitrile 8 (90 mg, 0.31 mmol), hy-
droxylamine hydrochloride (64 mg, 3.0 equiv.), and potassium
E. Brenna, Synthetic Methods for Biologically Active Molecules,
Wiley-VCH, Weinheim, Germany, 2013.
B. R. Riebel, P. R. Gibbs, W. B. Wellborn, A. S. Bommarius,
[9]
Adv. Synth. Catal. 2003, 345, 707–712.
carbonate (253 mg, 6.0 equiv.) in absolute ethanol (5 mL) was
[10]
a) H. Ankati, D. Zhu, Y. Yang, E. R. Biehl, L. Hua, J. Org.
Chem. 2009, 74, 1658–1662; b) C.-C. Xu, H.-L. Yu, Z.-J.
Zhang, J.-H. Xu, Org. Lett. 2013, 15, 5408–5411; c) R. J. Ham-
mond, B. W. Poston, I. Ghiviriga, B. D. Feske, Tetrahedron
Lett. 2007, 48, 1217–1219.
heated at reflux for 8 h. The reaction mixture was cooled to room
temperature and filtered, and the filtrate was concentrated under
reduced pressure. The resulting amide oxime was dissolved in anhy-
drous tetrahydrofuran (5 mL) that contained powdered molecular
sieves (4 Å, 120 mg), and the mixture was stirred for 30 min. So-
dium hydride (60% dispersion in oil, 18.5 mg prewashed with hex-
ane, 1.5 equiv.) was added, and the mixture was heated at 60 °C for
30 min and then was cooled to room temperature. Ethyl acetate
(60 mL, 2.0 equiv.) was added, and the reaction mixture was heated
at reflux for 1 h and then cooled to room temperature. The mixture
was filtered, and the filtrate was concentrated under reduced pres-
sure to give a residue, which was purified by flash chromatography
on a silica gel column (n-hexane/EtOAc, 4:1) to afford compound
10 (54 mg, 50%). MS (70 eV): m/z (%) = 352 [M]+, 197, 112, 91
[11]
a) Y. Suto, R. Tsuji, M. Kanai, M. Shibasaki, Org. Lett. 2005,
7, 3757–3760; b) S. Mun, J. E. Lee, J. Yun, Org. Lett. 2006, 8,
4887–4889; c) V. Lillo, A. Bonet, E. Fernández, Dalton Trans.
2009, 2899–2908; d) G.-y. Wang, X.-y. Liu, G. Zhao, Synlett
2006, 1150–1154; e) H. Vázquez-Villa, S. Reber, M. A. Ariger,
E. M. Carreira, Angew. Chem. Int. Ed. 2011, 50, 8979–8981;
Angew. Chem. 2011, 123, 9141; f) W. Xiao, R. Jin, T. Cheng,
D. Xia, H. Yao, F. Gao, B. Deng, G. Liu, Chem. Commun.
2012, 48, 11898–11900; g) B. Deng, T. Cheng, M. Wu, J. Wang,
G. Liu, ChemCatChem 2013, 5, 2856–2860; h) T. Hamada, T.
Torii, K. Izawa, T. Ikariya, Tetrahedron 2004, 60, 7411–7417;
i) T. Touge, T. Hakamata, H. Nara, T. Kobayashi, N. Sayo, T.
Saito, Y. Kayaki, T. Ikariya, J. Am. Chem. Soc. 2011, 133,
14960–14963; j) M. Watanabe, K. Murata, T. Ikariya, J. Org.
Chem. 2002, 67, 1712–1715.
a) M. Sakamoto, M. Hamada, T. Higashi, M. Shoji, T. Sugai,
J. Mol. Catal. B: Enzym. 2010, 64, 96–100; b) O. Pàmies, J.-E.
Bäckvall, Adv. Synth. Catal. 2002, 344, 947–952; c) A. Kamal,
G. B. R. Khanna, Tetrahedron: Asymmetry 2002, 13, 2039–
2051.
a) A. J. Smallridge, A. Ten, M. A. Trewhella, Tetrahedron Lett.
1998, 39, 5121–5124; b) V. Gotor, J. R. Dehli, F. Rebolledo, J.
Chem. Soc. Perkin Trans. 1 2000, 307–309; c) J. R. Dehli, V.
Gotor, Tetrahedron: Asymmetry 2001, 12, 1485–1492.
a) P. Florey, A. J. Smallridge, A. Ten, M. A. Trewhella, Org.
Lett. 1999, 1, 1879–1880; b) J. R. Dehli, V. Gotor, Tetrahedron:
Asymmetry 2000, 11, 3693–3700.
1
(100), 77, 65, 51. H NMR (300 MHz, CDCl3): δ = 7.39–7.09 (m,
10 H), 6.41 (d, J = 9.0 Hz, 1 H), 5.40 (dd, J = 9.3, 2.7 Hz, 1 H),
4.97 (d, J = 2.7 Hz, 1 H), 4.59 (d, J = 11.4 Hz, 1 H), 4.22 (d, J =
12.0 Hz, 1 H), 2.52 (s, 3 H), 1.95 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 176.57, 169.77, 169.30, 137.27, 128.57, 128.41, 128.24,
127.90, 127.83, 126.72, 79.82, 71.11, 52.29, 29.65, 22.92, 12.31 ppm.
HRMS (FAB): calcd. for C20H22N3O3 [M + H]+ 352.1661; found
[12]
[13]
352.1656. IR (CCl ): ν = 3227 (NH), 1514, 1650 (C=O) cm–1.
˜
4
Acknowledgments
This work was supported by the Korea Institute of Science and
Technology Institutional Program (grant numbers 2E25023,
2Z03983).
[14]
[15]
a) D. Zhu, H. Ankati, C. Mukherjee, Y. Yang, E. R. Biehl, L.
Hua, Org. Lett. 2007, 9, 2561–2563; b) A. S. Rowan, T. S.
Moody, R. M. Howard, T. J. Underwood, I. R. Miskelly, Y. He,
B. Wang, Tetrahedron: Asymmetry 2013, 24, 1369–1381.
[1] a) R. Csuk, B. I. Glaenzer, Chem. Rev. 1991, 91, 49–97; b) M.
Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Keßeler, R.
1142
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 1137–1143

Chemo- and Stereoselective Reduction by Using Baker’s Yeast
[16]
[19] a) D. E. Gibbs, D. Barnes, Tetrahedron Lett. 1990, 31, 5555–
5558; b) S. S. Chimni, R. J. Singh, World J. Microbiol. Biotech-
nol. 1997, 14, 247–250; c) A. Kamal, M. V. Rao, H. M. Mesh-
ram, J. Chem. Soc. Perkin Trans. 1 1991, 2056–2057.
[20] E. Reyes, L. Carrillo, J. L. Vicario, D. Badia, Lett. Org. Chem.
2004, 1, 331–334.
a) H. Wamhoff, R. Berressem, M. Nieger, J. Org. Chem. 1993,
58, 5181–5185; b) H. Szczepanski, M. Zeller, H. Ziegler, Norv-
artis AG, PCT International Patent Appl. WO 2000003974 A1,
2000.
[17] a) M. J. Fray, D. J. Bull, M. Kinns, J. Chem. Res. Synop. 1992,
1, 10–11; b) C. Scolastico, E. Conca, L. Prati, G. Guanti, L.
Banfi, A. Berti, P. Farina, U. Valcavi, Synthesis 1985, 850–855.
[18] O. C. Kreutz, P. J. S. Moran, J. A. R. Rodrigues, Tetrahedron:
Asymmetry 1997, 8, 2649–2653.
[21] A. I. Meyers, J. D. Brown, Tetrahedron Lett. 1988, 29, 5617–
5620.
Received: October 25, 2014
Published Online: December 22, 2014
Eur. J. Org. Chem. 2015, 1137–1143
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1143