A rapid 1,2-dihydroxylation of alkenes using a lipase and hydrogen peroxide under microwave conditions

Article abstract of DOI:10.1016/j.tetlet.2007.07.087

The combined advantages of using an enzyme immobilized lipase from Pseudomonas sp [PSLG6], hydrogen peroxide, ethyl acetate and microwave irradiation for the dihydroxylation of olefins are reported.

Full text of DOI:10.1016/j.tetlet.2007.07.087

Tetrahedron Letters 48 (2007) 6776–6778
A rapid 1,2-dihydroxylation of alkenes using a lipase and
hydrogen peroxide under microwave conditions
Kuladip Sarma, Naleen Borthakur and Amrit Goswami*
Synthetic Organic Chemistry Division, Regional Research Laboratory, Jorhat 785 006, Assam, India
Received 8 June 2007; revised 3 July 2007; accepted 12 July 2007
Available online 21 July 2007
Abstract—The combined advantages of using an enzyme immobilized lipase from Pseudomonas sp [PSLG6], hydrogen peroxide,
ethyl acetate and microwave irradiation for the dihydroxylation of olefins are reported.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1,2-Dihydroxy compounds are important intermediates
for the preparation of different pharmaceuticals such
as antagonists of central and peripheral dopamine
OH
50% H2O2, EtOAc, MW
receptors,1 fragrants,2 cosmetics,3 photographic plates4
and lubricants5 and also as additives6 in various syn-
thetic reactions. Generally 1,2-diols are prepared either
by acid7 catalyzed hydrolysis of epoxides in the presence
of metal oxides, transition metal complexes8 or epoxide
hydrolases,1,9 dihydroxylation of olefins with potassium
permanganate,10 osmium tetroxide,11 zeolite catalysts,12
or by reduction of a-hydroxy ketones and diketones.13
However, from the point of view of atom efficiency,
the performance of these reagents is very poor. Further,
over-oxidation with consequent cleavage of C–C bonds
in certain cases, poor selectivity, long reaction times14
and use of toxic solvents are some of the associated
problems. Hence, the controlled use of hydrogen perox-
ide for 1,2-dihydroxylation of olefins under specific con-
ditions provides a better solution.15
Lipase [PSLG6]
OH
1b-16b
1a-16a
Scheme 1. Lipase catalyzed dihydroxylation of olefins under micro-
wave irradiation.
The yields of the 1,2-diols ranged from 70% to 90% (Table
1). The advantages of our method are: (i) it is metal free;
(ii) is rapid; (iii) gives high yields; (iv) the catalyst can be
recycled four times and; (v) the method is simple and safe.
A control experiment was carried out to check the
requirement for lipase in the reaction. In the absence
of lipase, no diol formation occured.
The reaction proceeds through formation of an epoxide
(Scheme 2),19 however, no intermediate epoxide could
be isolated from the olefins 1a–16a. In the cases of
cholesterol and stigmasterol 17a and 18a, the reaction
is noteworthy. The isolated double bond in stigmasterol
18a at C-22 remained unaffected under the reaction
conditions, whilst the sterically hindered double bonds
at C-5,6 in both cholesterol 17a and stigmasterol 18a
were epoxidized to give 5a,6a-epoxides 17b and 18b
(Scheme 3). The hydroxyl at C-3 of cholesterol 17a
and stigmasterol 18a probably facilitated epoxide
formation. Epoxides 17b and 18b were stable and did
not undergo ring opening to the diols.
Lipase assisted epoxidations using peroxides and acids
or esters is an attractive reaction in clean chemistry
research areas.16 In continuation of our recent work17
on epoxidation using such methodologies, we report
here a rapid method for direct 1,2-dihydroxylation of
various alkenes using immobilized lipase from Pseudo-
monas [PSLG6], 50% hydrogen peroxide and ethyl ace-
tate in a microwave in a single step (Scheme 1).18
Keywords: Alkene; Dihydroxylation; Hydrogen peroxide; Lipase;
Microwave.
*
The dihydroxylation of cyclohexene and 1-phenylcyclo-
hexene 12a and 13a under the above conditions
Corresponding author. Tel.: +91 376 2372948; fax: +91 376
2370011; e-mail: amritg_2007@rediffmail.com
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.087

K. Sarma et al. / Tetrahedron Letters 48 (2007) 6776–6778
6777
Table 1. 1,2-Dihydroxylation of olefins with 50% H2O2 and ethyl acetate in the presence of [PSLG6] under microwave irradiationa
Entry
Substrates 1a–18a
Productsb 1b–18b
Time (min)
Yieldc (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Styrene
1-Phenyl-1,2-ethanediol
6
5
5
6
5
5
6
7
7
7
10
8
10
10
10
10
10
10
76
90
85
80
83
81
79
85
83
80
77
87
80
70
72
83
85
83
4-Cl–styrene
3-Cl–styrene
2-Cl–styrene
4-Br–styrene
3-Br–styrene
2-Br–styrene
4-Nitrostyrene
3-Nitrostyrene
2-Nitrostyrene
4-MeO–styrene
Cyclohexene
1-C6H4-1-Cyclohexene
a-Me–styrene
1-Hexene
4-Cl–phenyl-1,2-ethanediol
3-Cl–phenyl-1,2-ethanediol
2-Cl–phenyl-1,2-ethanediol
4-Br–phenyl-1,2-ethanediol
3-Br–phenyl-1,2-ethanediol
2-Br–phenyl-1,2-ethanediol
4-Nitrophenyl-1,2-ethanediol
3-Nitrophenyl-1,2-ethanediol
2-Nitrophenyl-1,2-ethanediol
4-MeO–phenyl-1,2-ethanediol
trans-Cyclohexane-1,2-diol
trans-1-Phenylcyclohexane-1,2-diol
1-Me-1-phenyl-1,2-ethanediol
1,2-Hexanediol
trans-2-Hexene
Cholesterol
Stigmasterol
trans-2,3-Hexanediol
Cholest-5a,6a-epoxy-3b-ol18,20I
Stigmast-5a,6a-epoxy-3b-ol18,20K
a The reactions were run with olefin (8–10 mmol), 50% H2O2 (2.5 mL, 36 mmol), ethyl acetate (5 mL) and lipase PSLG6 (20 mg) under microwave
irradiation for 5–10 min.
b The products were characterized from their respective IR, NMR and mass spectroscopic data and by comparison with the literature data.20
c Isolated yields of products.
produced trans-1,2-cyclohexanediol 12b and trans-1-
phenylcyclohexanediol 13b in 87% and 80% yields,
respectively. Interestingly, under microwave irradiation
(150 W) the immobilized lipase [PSLG6] was not dena-
tured and could be recycled in subsequent runs which
is in agreement with the earlier observations.15 The con-
version was found to occur best on exposure to MW
irradiation (150 W) for 5–10 min whereby the reaction
temperature was about 60 ꢁC (measured in a conven-
tional manner by stopping the exposure). The micro-
wave irradiation increases the reaction rate and
decreases inactivation of the enzyme during the reac-
tion.15 When the reaction was carried out under conven-
tional conditions at reflux, it required more than 20 h for
completion and the yield of the diols obtained were
found to be lower in comparison. The product diols in
all the cases were accompanied by 5–8% of the 2-acetyl-
oxy derivatives formed through transesterification with
ethyl acetate in the presence of lipase. Similar results
OH
O
OH
O
O
O
OH
OOH
OEt
EtOH
+
H2O
H2O2
Lipase
Scheme 2. Lipase catalyzed dihydroxylation of olefins under micro-
wave irradiation.
50% H O , EtOAc, MW
2
2
Lipase [PSLG6]
HO
HO
O
17a
17b
50% H O , EtOAc, MW
2
2
Lipase [PSLG6]
HO
HO
O
18a
18b
Scheme 3. Lipase catalyzed epoxidation of sterol substrates under microwave irradiation.

6778
K. Sarma et al. / Tetrahedron Letters 48 (2007) 6776–6778
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benign method for the direct 1,2-dihydroxylation of
olefins was developed that could be carried out within
a few minutes.
Acknowledgements
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We gratefully acknowledge the DST, New Delhi, for a
research grant and Dr. P. G. Rao, Director, North-East
Institute of Science and Technology, Jorhat, for provid-
ing the facilities to carry out the work.
17. Sarma, K.; Bhati, N.; Borthakur, N.; Goswami, A.
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18. Typical procedure: A 50 mL conical flask was charged with
styrene 1a (1.04 g, 10 mmol), aqueous hydrogen peroxide
(50%, 2.5 mL, 36 mmol), ethyl acetate (5 mL) and lipase
[PSLG6] (20 mg). The mixture was irradiated at 150 W in
a microwave oven (EMS-820 Precision Pulsed Laboratory
Microwave Oven) for 5 min. Air was purged through the
reaction mixture in order to ensure thorough mixing of the
reactants inside the MW chamber. The mixture was then
allowed to cool and ethyl acetate (10 mL) was added. The
mixture was then filtered and the residual solid immobi-
lized lipase was washed with 8:2 acetonitrile–water mix-
ture and dried for subsequent use. The filtrate containing
both the aqueous and organic layer was separated. The
organic layer was washed with Na2SO3 solution (20%,
10 mL), NaHCO3 solution (5%, 20 mL · 2) and then with
water (20 mL · 2), and dried over anhydrous Na2SO4. The
solvent was removed under reduced pressure to afford 1-
phenyl-1,2-ethanediol (1.24 g, 9 mmol) as a white solid;
mp 67 ꢁC (lit.,20b 66–67 ꢁC). The same reaction was carried
out with various alkenes in a similar manner to give the
corresponding diols 1b–16b and epoxides 17b and 18b.
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