Table 2 CMO catalysed oxidation of sulfides to the corresponding
conclusions: (i), both enzymes exibit high enantioselectivity in
the oxidation of cycloalkyl methyl and alkyl methyl sulfides
with limited steric requirements; (ii), the two enzymatic systems
are enantiocomplementary for pentyl methyl sulfide and for
octyl methyl sulfide, leading in all other cases to the
(R)-sulfoxides; (iii) chloroperoxidase is more convenient than
cyclohexanone monooxygenase since it is commercially avail-
able, uses hydrogen peroxide as oxidant and does not require the
regeneration of the cofactor, as in the case with CMO.
sulfoxides a
Conver-
sion (%) Ee (%)
Configura-
tion
Sulfide
1 Cyclopentyl methyl sulfide
2 Cyclohexyl methyl sulfide
3 Allyl methyl sulfide
4 Pentyl methyl sulfide
5 Octyl methyl sulfide
6 Isopropyl methyl sulfide
7 tert-Butyl methyl sulfide
8 tert-Butyl ethyl sulfide
10 tert-Butyl vinyl sulfide
11 Cyclohexyl ethyl sulfide
12 4-Hydroxyethyl methyl sulfide
80
86
82
58
50
75
85
30
78
8
!98
!98
!98
60
Rb
R
R
S
50
S
This work was partially supported by EEC Human Capital
and Mobility Programme and by COST Programme.
!98
!98
35
!98
47
R
R
R
R
R
R
References
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80
33
a The sulfide (0.1 mmol) was magnetically stirred in 4 ml of 0.05 mol dm23
Tris–HCl buffer, pH 8.6, containing 2 mmol NADPH, 0.4 mmol glucose-
6-phosphate, 5 units of CMO and 10 units of glucose-6-phosphate
dehydrogenase. After overnight reaction, the solution was extracted with 4
portions (4 ml each) of diethyl ether and the organic extract was dried and
evaporated. The enantiomeric excesses of sulfoxides were determined by
chiral HPLC on a Chiralcel OB column (Daicel), using the proper mixture
of hexane and propan-2-ol as the mobile phase. The absolute configuration
of sulfoxides was determined by comparison with authentic samples
b
prepared by Sharpless oxidation and using chiral HPLC. The absolute
configuration of cyclopentyl methyl sulfoxide was determined by analysis
of its 1H NMR spectrum in the presence of the chiral shift reagent (S)-(+)-a-
methoxy-a-phenylacetic acid.17
dialkyl sulfides affords predominantly or exclusively the
corresponding (R)-sulfoxide.
For CMO promoted sulfoxidation, high enantioselectivity is
observed for cycloalkyl methyl sulfoxides (1, 2), and methyl
sulfoxides with a linear or branched alkyl chain of up to four
carbon atoms (3, 6, 7). In all these cases the absolute
configuration of the prevailing enantiomer is R. A longer alkyl
chain not only causes a drastic drop in the chemical and optical
yield 4, 5, but also changes the stereochemical course of the
sulfoxidation, since the resulting enantiomer now has the S
absolute configuration.
The predictive active site model for the cyclohexanone
monooxygenase catalysed oxidation of sulfides to sulfoxides,
already proposed by us,16 is compatible with these results but
does not offer conclusive evidence due to the high conforma-
tional freedoms of dialkyl sulfides.
A comparison of the results obtained in the oxidation of
dialkyl sulfides with CPO and CMO leads to the following
Received, 12th December 1996; Com. 6/08352H
440
Chem. Commun., 1997