Exploration of chiral induction on epoxides in lipase-catalyzed epoxidation of alkenes using (2R,3S,4R,5S)-(-)-2,3:4,6-di-O-isopropylidiene-2-keto-l-gulonic acid monohydrate

Article abstract of DOI:10.1016/j.tetasy.2009.05.001

Epoxidation of alkenes by peracid, generated in situ from (2R,3S,4R,5S)-(-)-2,3:4,6-di-O-isopropylidiene-2-keto-l-gulonic acid monohydrate [(-)-DIKGA] and hydrogen peroxide by lipase catalysis induces chirality on the product epoxides with moderate to good enantioselectivity (35-71%). Alkoxy/aralkyloxy styrenes however did not undergo any epoxidation. (R)-(+)-4-Hydroxy styrene-7,8-oxide was formed and isolated with moderate enantiomeric excess (57%) but was found to have poor stability.

Full text of DOI:10.1016/j.tetasy.2009.05.001

Tetrahedron: Asymmetry 20 (2009) 1295–1300
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Exploration of chiral induction on epoxides in lipase-catalyzed epoxidation
of alkenes using (2R,3S,4R,5S)-(–)-2,3:4,6-di-O-isopropylidiene-2-keto-L-gulonic
acid monohydrate
b
Kuladip Sarma a, Amrit Goswami a, , Bhabesh C. Goswami
*
a Synthetic Organic Chemistry Division, North-East Institute of Science and Technology (A Constituent Establishment of CSIR, Govt of India), Jorhat 785 006, Assam, India
b Department of Chemistry, Gauhati University, Guwahati 781 014, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Epoxidation of alkenes by peracid, generated in situ from (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-
Received 2 April 2009
Accepted 1 May 2009
Available online 3 June 2009
2-keto-
L
-gulonic acid monohydrate [(ꢀ)-DIKGA] and hydrogen peroxide by lipase catalysis induces chi-
rality on the product epoxides with moderate to good enantioselectivity (35–71%). Alkoxy/aralkyloxy sty-
renes however did not undergo any epoxidation. (R)-(+)-4-Hydroxy styrene-7,8-oxide was formed and
isolated with moderate enantiomeric excess (57%) but was found to have poor stability.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
oured chiral acid with the products detracted our interest to look
for an alternative in order to prepare a few chirally pure epoxide
Epoxides are very important synthetic intermediates for a
variety of biologically active and synthetic molecules such as
b-amino alcohols1 used as b-blockers, antibiotics,2 neuroprotec-
tive agents,3 antidepressents,4 as well as other natural and clin-
ical products. Chiral epoxides whether produced from alkenes or
other sources have the same advantages as electrophilic inter-
mediates for stereochemical synthesis involving reactions with
nucleophiles.
With regard to the stereoselectivity, although the problem
has been solved by the formation of enantiomerically pure epox-
ides from achiral alkenes using various metal catalyst,5 the more
environmentally desirable organic molecule that catalyzed the
formation of epoxides is not as abundant.6 Following the pio-
neering work of Bjorkling et al.,7 the use of a lipase in epoxida-
tion reactions of alkenes by peracid generating in situ from a
suitable acid and a peroxide, has become a valuable addition
to the synthetic repertoire. Also this method is one of the
chalked out area for further exploration in the Round table of
the ACS and several leading global pharmaceutical industries
meet held during 2005.8
intermediates of pharmaceutical value.
Chiral ketones, in particular the carbocyclic analogues of fruc-
tose10 2 (Fig. 1) have been reported to be effective organocatalysts
for the asymmetric epoxidation of cis- and trans-alkenes through
formation peroxo ketone 4 with oxone (Scheme 1).
COOH
NO2
O
O
O
N
O
O
O
O
O
O
O
O
H2O
HO
O
NO2
1
2
3
Figure 1. N-2,4-Dinitrophenyl-
thro-2,3-hexodiulo-2,6-pyranose 2 and (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylid-
iene-2-keto-
-gulonic acid monohydrate [(ꢀ)-DIKGA] 3.
L-proline 1, 1,2:4,5-di-O-isopropylidene-b-D-ery-
L
A major disadvantage of this expensive organocatalyst is its
simultaneous decomposition through the Baeyer–Villiger oxida-
tion in the reaction with oxone. A similar molecule in the natural
chiral pool is the carbohydrate (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-iso-
In our original protocol,9 the use of a chirality inducer N-2,4-
dinitrophenyl-L-proline 1 (Fig. 1) to prepare chiral epoxides with
70–81% enantiomeric excess through lipase-catalyzed formation
was reported. The approach can be used in the efficient synthesis
of members of a large family of chiral intermediates without the
need to design custom chiral synthesis for each new compound.
However, the highly associative nature of this intensely yellow col-
propylidiene-2-keto-
L
-gulonic acid monohydrate [(ꢀ)-DIKGA)] 3
and has been reported11 for use in the resolution of various impor-
tant racemic amines. The molecule is less expensive than 2 and un-
til now, the catalytic activity of it as an oxygen carrier from
different oxygen sources via peracid formation to alkenes in the
epoxidation reactions and its ability for chiral induction in prod-
ucts have not yet been explored.
* Corresponding author.
E-mail address: amritg_2007@rediffmail.com (A. Goswami).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.05.001

1296
K. Sarma et al. / Tetrahedron: Asymmetry 20 (2009) 1295–1300
that has the potential to release the oxidant in a controlled
manner.12
As proposed, three alternative styrene derivatives, 4-acetoxy
2. Results and discussion
This molecule was chosen11 as a chiral oxygen transferring agent
to alkenes through lipase-based peracid formation using Candida
antarctica B in its immobilized form (Novozyme [435]) in order to
prepare three industrially very important intermediates, (R)-4-
alkoxystyrene-7,8-oxide 5 for (R)-(ꢀ)-denopamine- a selective b1-
adrenoreceptor agonist, effective against refractory vasospastic
angina pectoris, (2R,3R)-epoxybut-1-ol 6b, an intermediate for a
macrolide antibiotic erythromycin, 2S,3S-epoxy-2-methylpentan-
1-ol 8, another intermediate for a macrolide antibiotic methymycin
(Fig. 2).
The main reason for the synthetic importance of epoxide inter-
mediates for these drugs is the economic and environmental
requirement of reducing the number of steps during synthesis.
The necessity of the gradual addition of aqueous hydrogen per-
oxide to the reaction mixture over several hours in the original
protocol, in order to avoid enzyme deactivation, has been over-
come by using the adduct of urea and hydrogen peroxide (UHP)
styrene, 4-benzyloxy styrene and 4-methoxy styrene, were taken
as substrates initially to synthesize the configurationally desired
styrene oxide for (R)-(ꢀ)-denopamine. The peracid of (ꢀ)-DIKGA
was generated in situ by treatment with UHP in the presence of li-
pase at 0ꢀ5 °C in a dichloromethane and tetrahydrofuran mixture
in a 4:1 ratio and then after about 1 h, 4-acetoxy styrene was
added. A problem was however encountered with the substrate
due to parallel lipase-catalyzed hydrolysis of it to 4-hydroxy sty-
rene 2a. 4-Methoxy styrene and 4-benzyloxy styrene did not turn
up to give any product under the reaction conditions.
Taking the 4-hydroxy styrene obtained by the lipase hydrolysis
(using Pseudomonas cepacia for better yield) of 4-acetoxy styrene,
the reaction was carried out for about 20 h, whereby (R)-(ꢀ)-4-
hydroxystyrene-7,8-oxide 2b was furnished in good yield (Scheme
2). It could also be isolated immediately by filtration under cold
condition and thus characterized after purification from its NMR
(1H and 13C), IR and mass spectroscopic data. The product isolated
was found to undergo rapid decomposition at room temperature.
From the specific rotation data and HPLC analysis of 4-hydroxy sty-
rene-7,8-oxide on a chiral column, the configuration has been
found to be (R) with an enantiomeric excess of 57% (Table 1).
Under identical reaction condition, the reaction of 2-methyl-
pent-2-en-1-ol, however, gave (2R,3R)-epoxy-2-methylpent-1-ol
7b instead of (2S,3S)-epoxy-2-methylpent-1-ol 8 with 71% ee. On
the other hand, but-2-en-1-ol obtained by the reduction of but-
2-en-diethylacetal by a novel bimetal redox system13 under li-
pase-catalyzed epoxidation with UHP and (ꢀ)-DIKGA yielded
(2R,3R)-epoxy but-1-ol in 35% enantiomeric excess as determined
from its specific rotation data and HPLC chiral column analysis.
The other epoxides from the corresponding styrene derivatives
were prepared in an analogous manner.
O
O
O
O
O
O
O
H2SO5
O
O
O
O
O
O
4
2
O
O
O
O
O
UHP, Lipase
Urea + H2O
O
O
O
O
H2O
O
O
O
HO
O
OH
H2O
3
2.1. Solvent effect
Scheme 1.
The catalytic epoxidation of the styrene derivative was also
studied in various solvents for better yield and selectivity (Table
2); dichloromethane (DCM), dry tetrahydrofuran (THF), a mixture
of dry dichloromethane and tetrahydrofuran in a 4:1 ratio, ionic li-
quid 1-butyl-3-methyl imidazolium bromide ([bmim]Br) and flu-
orous solvent 1,1,1,3,3,3-hexafluoropropan-2-ol. Among all these
solvents used, the solvent system consisting of dry DCM and THF
in 4:1 proved to be the best system in the epoxidation of all of
the alkenes in terms of both yield and enantiomeric excess. This
indicates that although lipases perform well in ionic liquids in
O
O
O
O
OH
OH
OH
RO
6b
7b
8
5
Figure 2.
78% Yield
HO
O
DCM, RT, 10 h
AcO
HO
< 5% Yield
Pseudomonas
cepacia,
THF:H2O (2:1),
10 h, RT
UHP + Lipase
(-) DIKGA 2
Peracid of DIKGA
O
Urea + H2O
DCM:THF (4:1), RT, 20 h
HO
HO
90% Yield
75% Yield
Scheme 2.

K. Sarma et al. / Tetrahedron: Asymmetry 20 (2009) 1295–1300
1297
Table 1
Epoxidation of the styrene derivatives using UHP in the presence of chiral acid (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-L-gulonic acid monohydrate 3 and Novozyme
[435] in dry dichloromethane solvent unless otherwise stated
Entry
1
Substrates 1a–7a
Productsa 1b–7b
Time (h)
20
Yieldb (%)
70
eec (%)
46
O
O
O
2d
20
48
20
20
20
20
75
20
78
74
65
70
57
46
63
68
35
71
HO
HO
3
Cl
Cl
O
O2N
O2N
4
NO2
NO2
O
5
6
O
OH
OH
OH
7
O
OH
a
The products were characterized from their respective IR, NMR and mass spectroscopic data and by comparison with the literature data.
Isolated yields of products.
Determined from specific rotation data, HPLC and GC analysis.
b
c
d
The reaction was carried out in the solvent system DCM/THF, 4:1.
Table 2
Effect of solvents in the epoxidation of 4-hydroxy styrene 2a using UHP in presence of (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-L-gulonic acid monohydrate and
Novozyme [435]a
Entry
Solvent
Time (h)
Conversionb (%)
eec (%)
1
2
3
4
5
Dry dichloromethane (DCM)
Dry tetrahydrofuran (THF)
Dry DCM/dry THF = 4:1
1-Butyl-3-methylimidazolium bromide ([bmim]Br)
1,1,1,3,3,3-Hexafluoropropan-2-ol
30
30
20
30
30
65
48
75
45
40
55
53
57
50
51
a
Reaction conditions: 4-Hydroxystyrene: 1 g (8.3 mmol), urea hydrogen peroxide: 3 g (32 mmol), immobilized lipase: 100 mg, 2R,3S,4R,5S-(ꢀ)-2,3:4,6-di-O-isopropy-
-gulonic acid monohydrate 3: 0.3 g (1.03 mmol), solvent (total): 15 mL.
Conversions were determined by GC analysis as well as from crude NMR spectra.
Determined from specific rotation data, HPLC and GC analysis.
lidiene-2-keto-
L
b
c
ammonolysis, alcoholysis, perhydrolysis, etc. reactions, the peracid
formation is poor in such solvents as well as in water miscible or-
ganic solvents. This is in agreement with the earlier findings of
Bjorkling et al.7
3. Conclusion
We have presented a novel chemoenzymatic method for the
preparation of enantiomerically pure epoxides via chirality induc-
tion from the oxygen carrier chiral acid. The chiral inducing prop-
erty of the acid (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-
2.2. Recycling of chiral acid [(–)-DIKGA] and lipase catalyst
keto-
L
-gulonic acid monohydrate [(ꢀ)-DIKGA] has been unveiled
The epoxidation reaction of 4-hydroxy styrene 2a was repeat-
edly carried out with the recovered amount of the chiral acid and
the enzyme to study their recyclability. It was found that there
was no significant loss in the activity of the chiral acid and the en-
zyme with respect to the isolated yield of the corresponding prod-
uct (Fig. 3).
for the first time and the yields of the resulting epoxides obtained
are good; this was achieved by using stoichiometric amounts of
UHP and catalytic amount of the chiral acid and lipase enzyme.
Although the enantioselectivity of the products is low at this
stage, this method has opened up a new route for further
improvement.

1298
K. Sarma et al. / Tetrahedron: Asymmetry 20 (2009) 1295–1300
90
80
70
60
50
40
30
4.4. Preparation of (R)-(+)-phenyloxirane 1b
75
To a mixture of urea hydrogen peroxide (UHP) adduct (3 g,
73
71
70
68
66
32 mmol) with (2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-
keto-L-gulonic acid monohydrate (0.3 g, 1.03 mmol) in dry dichlo-
romethane (15 mL) was added, Novozyme [435] (100 mg) at 0ꢀ5 °C
and the mixture stirred for about 1 h. Styrene (1 g, 9.6 mmol) was
then added dropwise and the reaction continued at room temper-
ature for 20 h. The reaction was monitored by TLC. The mixture
was filtered and the residue washed with dichloromethane after
which the filtrate was reduced under pressure using a vacuum
flash evaporator. The reaction mixture was washed with 10% NaH-
CO3 solution (2 ꢁ 20 mL) to remove any trace amount of the acid
present in it. The organic layer was then washed again with fresh
water (2 ꢁ 10 mL) and dried over anhydrous Na2SO4. The product
was purified by preparative TLC with 40% CH2Cl2/hexane. Yield:
70%; oil (C8H8O requires C, 79.97; H, 6.71. Found: C, 79.91; H,
6.65); Rf (40% CH2Cl2/hexane) 0.55. The enantiomeric excess was
determined by HPLC analysis using a Chiralcel OD column [iPrOH/
1
2
3
4
5
6
Reaction Runs using the same batch of the
acid and lipase
Figure 3. Variation of the yields of the epoxides in six different epoxidation
reactions of 4-hydroxy styrene using the same batch of chiral acid (2R,3S,4R,5S)-
(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid monohydrate 3 and lipase
keeping the other reaction condition identical.
4. Experimental
hexane = 0.2:99.8, flow rate 0.2 cm3 minꢀ1], ½a D22
¼ þ21:5 (c 0.8,
ꢂ
4.1. General methods
PhH) 46% ee, (R); {lit.,15
½
a 2D2
ꢂ
¼ þ44:5 (c 1.05, PhH) 95% ee (R)}. mmax
All the IR, 1H NMR, 13C NMR and mass spectra were recorded on
an FT IR System-2000 PERKIN–ELMER, AVANCE-DPX-300 MHz FT-
NMR BRUKER standard and WATERS Micro-mass ZQ 4000 (ESI
Probe) spectrometers, respectively. The chemical shifts are re-
ported in ppm relative to CHCl3 (d = 7.26) for 1H and relative to
the central CDCl3 resonance (d = 77.0) for 13C NMR. GC analyses
were carried out using Chemito GC 1000 spectrometers. Optical
rotations were measured on a Jasco Digital P-1020 polarimeter.
The enantiomeric excess (ee) of the products was determined by
chiral HPLC using Chiralcel OD, Chiralcel OJ, Chiralpak AD, Chiralcel
OD-R, columns with hexane-2-propanol and methanol–water as
eluent.
(neat/cmꢀ1) 1496, 1476, 1452, 1390; dH (300 MHz; CDCl3) 2.81 (1H,
dd, J 2.6 and 5.5, HCOCHH), 3.15 (1H, dd, J 4.1 and 5.5, HCOCHH), 3.87
(1H, dd, J 2.6 and 4.0, PhCHOCH2), 7.26–7.36 (5H, m, 5 ꢁ CH, arom.);
dC (75 MHz; CDCl3) 51.2 (CH2), 52.4 (CH), 125.5, 128.2, 128.4 and
137.6 (6 ꢁ C-Ph). MS m/z (rel. intensity %): 122 (M+2, 15), 121
(M+1, 43), 120 (M+, 20), 105 (100), 91 (68), 77 (88).
4.5. Preparation of (R)-(+)-4-hydroxyphenyloxirane 2b
4.5.1. In a DCM/THF system (4:1)
The same procedure was followed as given in Section 4.4. using a
4-hydroxy styrene (1 g, 8.3 mmol), Novozyme [435] (100 mg), (2R,
3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid
4.2. Materials
monohydrate (0.3 g, 1.03 mmol) and UHP (3 g, 32 mmol) in dry
dichloromethane/tetrahydrofuran solvent mixture (4:1) (15 mL).
The product was purified by preparative TLC in dry DCM/THF in a
4:1 ratio. Yield: 75%; oil (C8H8O2 requires C, 70.58; H, 5.88. Found:
C, 70.70; H, 5.91); Rf (90% CH2Cl2/EtOAc) 0.55. The enantiomeric ex-
cess was determined by HPLC analysis using a Chiralcel OD-R col-
All the starting materials (alkenes), chiral acid (2R,3S,4R,5S)-
(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid monohy-
drate [(ꢀ)-DIKGA] and UHP were purchased commercially from Al-
drich Chemicals. The lipases Novozyme [435] and P. cepacia were
purchased from Fluka Chemicals. The dry solvents were purchased
from Across Organics. Silica gel G for thin layer chromatography
and silica gel 100–200 mesh for column chromatography were
purchased from RANKEM, India.
umn [MeOH, flow rate 0.2 cm3 minꢀ1], ee 57%, (R); ½a 2D5
¼ þ4:95 (c
ꢂ
0.8, CHCl3); m
max (neat/cmꢀ1) 3406, 2961, 2924, 2856, 1513, 1457;
dH (300 MHz; CDCl3) 2.0 (1H, b, HCOCHH), 2.2 (1H, br s, HCOCHH),
3.4 (1H, br s, CHOCH2), 5.1 (1H, br s, OH), 6.7–7.0 (4H, m, 4 ꢁ CH,
arom.); dC (300 MHz; CDCl3) 26.4 (CH2), 48.13 (CH), 115.5, 128.2,
137.3, 154.2 (6 ꢁ C-Ph). MS m/z: 136 [M+].
4.3. Preparation of 4-hydroxy styrene 1a from 4-acetoxy
styrene
The residue obtained by filtration of the above reaction mixture
in the epoxidation of 4-hydroxystyrene contains Novozyme [435]
4-Acetoxy styrene (3 g, 18.5 mmol) and P. cepacia lipase (30 mg)
were taken in a round-bottomed flask in 15 mL THF/H2O (2:1) and
the mixture was stirred for 10 h at room temperature. The crude
mixture was then filtered to remove the lipase to reuse it again
and the major THF layer was distilled out from the filtrate under
reduced pressure. The remaining aqueous layer was then extracted
again with ethyl acetate (3 ꢁ 15 mL) and then dried over anhy-
drous Na2SO4. After that the organic solvent was distilled out un-
der reduced pressure and the hydrolyzed product was purified
with column chromatography to give the pure product 4-hydroxy
styrene as a solid (1.99 g, 16.65 mmol, 90% yield), mp 71–72 °C
(lit.14 mp 73 °C). C8H8O requires C, 79.97; H, 6.71. Found: C,
79.91; H, 6.77); Rf (in CH2Cl2) 0.55. mmax (neat/cmꢀ1) 3405, 2960,
2925, 2855, 1611; dH (300 MHz; CDCl3) 4.7 (1H, b, HHCCHPh),
4.9 (1H, b, HHCCHPh), 5.1 (1H, b, OH), 5.6 (1H, b, H2CCHPh), 6.8–
7.3 (4H, m, 4 ꢁ CH, arom.); dC (75 MHz; CDCl3) 110.1 (CH2CHPh),
136.0 (CH2CHPh), 114.8, 125.5, 127.0, 154.2 (6 ꢁ C-Ph). MS m/z:
120 [M+].
and (2R, 3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulo-
nic acid monohydrate. The residue was then dried and recycled for
the next five successive reactions.
4.5.2. In dry DCM
The same procedure was followed as given in Section 4.4. using
4-hydroxystyrene (1 g, 8.3 mmol), Novozyme [435] (100 mg), (2R,
3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid
monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry
dichloromethane (15 mL). Reaction time: 30 h, yield: 60%,
½
a 2D5
ꢂ
¼ þ4:8 (c 0.9, CHCl3); ee 55%, (R).
4.5.3. In dry THF
The same procedure was followed as given in Section 4.4. using 4-
hydroxy styrene (1 g, 8.3 mmol), Novozyme [435] (100 mg), (2R,3S,
4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid mo-
nohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry tetrahy-

K. Sarma et al. / Tetrahedron: Asymmetry 20 (2009) 1295–1300
1299
drofuran (15 mL). Reaction time: 30 h, yield: 48%, ½a D25
ꢂ
¼ þ4:6 (c 0.6,
5S-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L
-gulonic acid mono-
CHCl3); ee 53%, (R).
hydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry dichloro-
methane (15 mL). Reaction time: 20 h. The product was purified by
preparative TLC with 40% CH2Cl2/hexane. Yield: 74%; light yellow
solid; mp 51–52 °C; (C8H7NO3 requires C, 58.18; H, 4.27; N, 8.48.
Found: C, 58.20; H, 4.28; N, 8.51); Rf (25% EtOAc/hexane) 0.52;
4.5.4. In fluorous solvent 1,1,1,3,3,3-hexafluoropropan-2-ol
The same procedure was followed as given in Section 4.4. using
4-hydroxy styrene (1 g, 8.3 mmol), Novozyme [435] (100 mg),
2R,3S,4R,5S-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid
½
a 1D9:5
ꢂ
¼ ꢀ72:9 (c 1.20, CHCl3), (R); {lit.,17
½
a 1D9:5
ꢂ
¼ ꢀ107:2 (c 1.65,
monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and
1,1,1,3,3,3-hexafluoropropan-2-ol (15 mL). Reaction time: 30 h,
CHCl3), (R)}; The enantiomeric excess was determined by HPLC anal-
ysis using Chiralcel OD column and showed it to be 68% ee (eluent at
yield: 45%, ½a 2D5
ꢂ
¼ þ4:3 (c 0.6, CHCl3); ee 50%, (R).
V = 0.8 mL minꢀ1 hexane/2-propanol = 9: 1). mmax (neat/cmꢀ1
, )
3150, 2997, 1532, 1353, 1254, 899, 859, 809, 737, 684; dH
(300 MHz; CDCl3) 2.67 (1H, dd, J 2.5 and 5.4, HCOCHH), 3.30 (1H,
dd, J 4.2 and 5.4, HCOCHH), 4.48 (1H, dd, J 2.5 and 4.2, PhCHOCH2),
7.41–7.56 (1H, m, 1 ꢁ CH, arom.), 7.57–7.77 (2H, m, 2 ꢁ CH, arom.)
and 8.14 (1H, dd, J 1.21 and 8.13, 1 ꢁ CH, arom.). dC (75 MHz; CDCl3)
50.5 (CH2), 51.6 (CH), 124.6, 128.5, 128.8, 131.7, 133.5, 149.1
(6 ꢁ C-Ph); MS m/z (rel. intensity %): 165(M+, 0.3), 149(2), 135(21),
105(10), 104(10), 91(79), 89(21), 79(71), 77(100).
4.5.5. In ionic liquid 1-butyl-3-methylimidazolium bromide
([bmim]Br)
The same procedure was followed as given in Section 4.4. using 4-
hydroxy styrene (1 g, 8.3 mmol), Novozyme [435] (100 mg), (2R,
3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid
monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and 1-butyl-
3-methylimidazolium bromide ([bmim]Br) (15 mL). Reaction time:
30 h, yield: 40%, ½a D25
¼ þ4:4 (c 0.6, CHCl3); ee 51%, (R).
ꢂ
4.9. Preparation of (2R,3R)-epoxybutan-1-ol 6b
4.6. Preparation of (R)-(–)-(4-chlorophenyl) oxirane 3b
The same procedure was followed as given in Section 4.4. using
The same procedure was followed as given in Section 4.4. using
but-2-en-1-ol (1 g, 13.9 mmol), Novozyme [435] (100 mg),
4-chlorostyrene (1 g, 6.41 mmol), Novozyme [435] (100 mg),
2R,3S,4R,5S-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid
2R,3S,4R,5S-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L
-gulonic acid
monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry
dichloromethane (15 mL). Reaction time: 20 h. The product was
purified by preparative TLC with 70% EtOAc/hexane. Yield: 65%;
oil (C4H8O2 requires C, 54.5; H, 9.09. Found: C, 54.2; H, 9.2); Rf
(70% EtOAc/hexane) 0.45. The enantiomeric excess was determined
by HPLC analysis using a Chiralcel OD-R column [MeOH/water (9:1),
monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry
dichloromethane (15 mL). Reaction time: 48 h. The product was
purified by preparative TLC with 40% CH2Cl2/hexane. Yield: 36%;
oil (C8H7OCl requires C, 62.09; H, 4.53. Found: C, 62.11; H, 4.51);
Rf (40% EtOAc/hexane) 0.51; ½a D22
ꢂ
¼ ꢀ11:5 (c 0.65, CHCl3); {lit.,16
½
a 2D0
ꢂ
¼ ꢀ24:0 (c 1.08, CHCl3), 97% ee, (R)}; HPLC analysis using a
flow rate 0.5 cm3 minꢀ1], ½a D25
ꢂ
¼ þ19:3 (c 0.05, CHCl3) 35% ee; {lit.,2
Chiralcel OJ column showed it to be 46% ee [hexane/2-propa-
nol = 9:1, flow rate 0.8 cm3 minꢀ1]. mmax (neat/cmꢀ1) 3054, 2992,
2920, 1602, 1496, 1478, 1417, 1381, 1199, 1090, 1015, 987, 879,
831, 769; dH (300 MHz; CDCl3) 2.68–2.69 (1H, dd, J 2.6 and 5.4,
HCOCHH), 3.08 (1H, dd, J 4.0 and 5.4, HCOCHH), 3.77 (1H, dd, J
2.6 and 4.0, PhCHOCH2), 7.13–7.26 (4H, m, 4 ꢁ CH, arom.); dC
(75 MHz; CDCl3) 51.2 (CH2), 51.8 (CH), 126.7, 126.6, 133.9 and
136.1 (6 ꢁ C-Ph). MS m/z (rel. intensity %): 157, 155, 153 (M+, 3,
7), 138(3), 125(40), 119(39), 91(29), 89(100), 63(34), 50(17).
½
a 2D4
ꢂ
¼ þ55:0 (c 0.36, CHCL3), 95% ee};
m
max (neat/cm-1) 3399, 2957,
2924, 2853, 1464, 1378; dH (300 MHz; CDCl3) 1.2 (3H, d, CH3CHO),
2.1 (1H, b, CH2OH), 2.6 (1H, m, HOCH2CHO), 2.7 (1H, m, CH3CHO),
3.7 (2H, m, OCHCH2OH); dC (75 MHz; CDCl3) 16.2 (CH3CHO), 46.5
(CH3CHO), 62.0 (HOCH2CHO), 64.3 (CH2OH). MS m/z: 88 [M+].
4.10. Preparation of (2R,3R)-epoxy-2-methylpentan-1-ol 7b
The same procedure was followed as given in Section 4.4. taking
2-methyl-penten-2-ol (1 g, 10 mmol), Novozyme [435] (100 mg),
4.7. Preparation of (R)-(–)-(3-nitrophenyl) oxirane 4b
(2R,3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic
acid monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry
dichloromethane (15 mL). Reaction time: 20 h. The product was
purified by preparative TLC with 30% EtOAc/hexane. Yield: 70%;
oil (C6H12O2 requires C, 62.07; H, 10.34. Found: C, 62.01; H,
10.65); Rf (30% EtOAc/hexane) 0.65. The enantiomeric excess was
determined by HPLC analysis using a Chiralcel OD-R column
The same procedure was followed as given in Section 4.4. using
3-nitrostyrene (1 g, 6.06 mmol), Novozyme [435] (100 mg), (2R,
3S,4R,5S)-(ꢀ)-2,3:4,6-di-O-isopropylidiene-2-keto-
L-gulonic acid
monohydrate (0.3 g, 1.03 mmol), UHP (3 g, 32 mmol) and dry
dichloromethane (15 mL). Reaction time: 20 h. The product was
purified by preparative TLC with 40% CH2Cl2/hexane. Yield: 78%;
yellow oil (C8H7NO3 requires C, 58.18; H, 4.27; N 8.48. Found: C,
[MeOH, flow rate 0.5 cm3 minꢀ1], ½a D25
¼ þ4:3 (c 0.03, CHCl3) 71%
ꢂ
ee; {lit.,2
½
a 2D4
ꢂ
¼ ꢀ5:8 (c 0.36, CHCL3), 95% ee}; mmax (neat/cmꢀ1
)
58.22; H, 4.28; N, 8.50); Rf (25% EtOAc/hexane) 0.50; ½a D20
ꢂ
¼ ꢀ1:6
3407, 2963, 2932, 2875, 1457, 1376; dH (300 MHz; CDCl3) 0.96
(3H, t, CH2CH3), 1.31 (3H, s, OCCH3), 1.46 (2H, m, OCHCH2CH3),
2.0 (1H, b, OH), 2.51 (1H, t, OCHCH2), 3.5–3.7 (2H, m, CCH2OH);
dC (300 MHz; CDCl3) 11.0 (CH3CH2), 14.5 (CH3CO), 21.6 (CH2CH2),
61.7 (CH2CHO), 62.8 (CH3CO), 70.3 (CH2OH). MS m/z: 116 [M+].
(c 2.1, CHCl3), (R); {lit.,17
½
a 1D8
ꢂ
¼ þ2:5 (c 2.8, CHCl3, (S)}; HPLC anal-
ysis using a Chiralpak AD column showed it to be 63% ee [hexane/
2-propanol = 9:1, flow rate 0.8 cm3 minꢀ1]. max (neat/cmꢀ1) 3113,
m
2995, 1517, 1343, 1301, 1042, 983, 888, 788, 740; dH (300 MHz;
CDCl3) 2.80 (1H, dd, J 2.5 and 4.8, HCOCHH), 3.21 (1H, dd, J 3.9
and 4.8, HCOCHH), 3.97 (1H, dd, J 2.5 and 3.9, PhCHOCH2), 7.40–
7.75 (2H, m, 2 ꢁ CH, arom.) and 8.01–8.24 (2H, m, 2 ꢁ CH, arom.);
dC (75 MHz; CDCl3) 51.7 (CH2), 51.9 (CH), 126.0, 126.4, 145.4 and
148.6 (6 ꢁ C-Ph); MS m/z (rel. intensity %): 165(M+, 18), 150(32),
136(68), 120(25), 105(17), 90(100), 77(22), 74(12), 65(52), 63(59).
Acknowledgements
The authors gratefully acknowledge the Department of Science
& Technology, New Delhi for financial support and Dr. P. G. Rao,
Director, NEIST, Jorhat for providing the facility. They also grate-
fully acknowledge Dr. J. C. S. Kataky, Head, Synthetic Organic
Chemistry Division and the Analytical Chemistry Division of this
Institute for their help to carry out the work. One of the authors
(K.S.) also thanks CSIR, New Delhi for the award of senior research
fellowship.
4.8. Preparation of (R)-(–)-(2-nitrophenyl) oxirane 5b
The same procedure was followed as given in Section 4.4. taking
2-nitrostyrene (1 g, 6.06 mmol), Novozyme [435] (100 mg), 2R,3S,4R,

1300
K. Sarma et al. / Tetrahedron: Asymmetry 20 (2009) 1295–1300
T. B.; Zhuang, W.; Jorgensen, K. A. J. Am. Chem. Soc. 2005, 127, 6964; (e)
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