New ligands for manganese catalysed selective oxidation of sulfides to sulfoxides with hydrogen peroxide

Article abstract of DOI:10.1016/S0040-4039(01)00626-8

In situ prepared manganese complexes with ligands 1-5 have been used in the catalytic oxidation of sulfides to sulfoxides using hydrogen peroxide at 0°C in acetone. Using ligand 4, methyl phenyl sulfoxide is obtained in 55% yield and turnover numbers up t

Full text of DOI:10.1016/S0040-4039(01)00626-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4049–4052
New ligands for manganese catalysed selective oxidation of
sulfides to sulfoxides with hydrogen peroxide
Jelle Brinksma,a Rene´ La Crois,a Ben L. Feringa,a,* Maria Irene Donnolib and Carlo Rosinib,*
aLaboratory of Organic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4,
9747 AG Groningen, The Netherlands
bDipartimento di Chimica, Universita` della Basilicata, via N. Sauro 85, 85100 Potenza, Italy
Received 8 February 2001; accepted 11 April 2001
Abstract—In situ prepared manganese complexes with ligands 1–5 have been used in the catalytic oxidation of sulfides to
sulfoxides using hydrogen peroxide at 0°C in acetone. Using ligand 4, methyl phenyl sulfoxide is obtained in 55% yield and
turnover numbers up to 250, while the formation of sulfone is almost suppressed. © 2001 Elsevier Science Ltd. All rights reserved.
The selective catalytic oxidation of sulfides to sulfoxides
has been a challenge for many years, owing to the
importance of sulfoxides as intermediates in organic
synthesis.1 The use of H2O2 as an oxidant has been
extensively studied. Compared to catalytic methods
that require oxidants such as NaOCl and ammonium
periodates, the use of aqueous H2O2 offers the advan-
tage that it is a cheap, environmentally benign and a
readily available reagent.2 Since water is the only
expected side product, catalytic oxidation methods
using this reagent are undoubtedly appealing, providing
efficient catalysis is accomplished. The undesired sul-
fone is a common by-product in sulfide oxidation with
H2O2 and its formation has to be suppressed. Much
effort has also been devoted to the development of
catalytic methods for the preparation of optically active
sulfoxides owing to their importance as chiral ligands,3
and bioactive products.4 Since the first reports of
Kagan5 and Modena,6 who used diethyltartrate, Ti(Oi-
Pr)4 and hydroperoxides as oxidants yielding e.e.s
higher than 90%, a number of publications related to
this research followed.7 Hydrogen peroxide has been
Figure 1.
Keywords: hydrogen peroxide; sulfoxides; manganese; oxidation.
* Corresponding authors.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00626-8

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J. Brinksma et al. / Tetrahedron Letters 42 (2001) 4049–4052
investigated as a terminal oxidant in the oxidation
reactions with titanium derivatives supported on silica,8
but only low enantioselectivities (13%) were obtained.9
The use of the Jacobsen (salen) Mn(III) complexes
provided good chemical yields and enantiomeric
excesses in the range of 34–68% with a reaction system
consisting of hydrogen peroxide, acetonitrile as solvent
and 2–3 mol% of the salen complex.10
Next the dinuclear manganese(IV) complex 1 based on
the N,N%,N¦-1,4,7-trimethyl-1,4,7-triazacyclononane
(MeTACN) ligand13 (used as catalyst in the selective
oxidation of sulfides to sulfones with periodic acid in
pyridine14) was used as catalyst for the oxidation of
methyl phenyl sulfide with H2O2. Furthermore, the in
situ-formed complexes with dinucleating ligands
N,N,N%,N% - tetrakis(2 - pyridylmethyl) - 1,3 - propanedia-
mine (2, TPTN) and N,N,N%,N%-tetrakis(2-pyridyl-
methyl)-1,2-ethanediamine (3, TPEN) both featuring
the three N-donor set for each Mn site, were used (Fig.
1). The ligands 2 and 3 contain a three- and two-carbon
spacer, respectively, between the three N-donor sets.12
Considering that one could expect that a good epoxida-
tion catalyst can also work as a promoter of the
oxidation of thioethers, we report here the use of
complex 1 and some in situ formed complexes with
ligands 2–4 (Fig. 1) that were highly active in the
oxidation of benzylic alcohols to aldehydes11 and of
olefins to epoxides12 with H2O2. In addition, we report
some preliminary results on the possibility of inducing
enantioselectivity using the optically active Mn complex
with ligand (S)-5 (Fig. 1).
Typical catalytic reactions were performed15 at 0°C
under a nitrogen atmosphere using 1 equiv. of catalyst,
1000 equiv. of substrate and 8 equiv. of H2O2 with
respect to substrate. The complexes and in situ-formed
catalysts turned out to be very active in sulfide oxida-
tion. For instance, the dinuclear manganese complex
based on 1 performs very efficiently in the oxidation of
methyl phenyl sulfide and generally resulted in full
conversion in 1 h (Table 2). Unfortunately, besides the
desired sulfoxide, overoxidation to sulfone was
observed. Manganese complexes based on TPTN-2 and
TPEN-3 were also found to be very active. However,
overoxidation was also found. Based on the oxidation
results with complex 1 and Mn complexes derived from
ligands 2 and 3 (all featuring three N-donor sets) and
because of the successful Jacobsen salen oxidation cata-
lysts containing two N-donor and two O-donor sets,10
we decided to use the new ligand 2-{[[di(2-
Since we found that several manganese salts catalyse
oxidation reactions with H2O2, we first examined the
oxidation of methyl phenyl sulfide with H2O2 in the
presence of only Mn(OAc)3·2H2O. Different solvents,
the effect of temperature and the amount of oxidant
were investigated, and the results are collected in Table
1. The oxidation of methyl phenyl sulfide is almost
completely suppressed in acetone and acetonitrile at
0°C using 2 equiv. of H2O2. Only 6% of methyl phenyl
sulfide was converted to sulfoxide after 6 h in both
solvents. When, under the same conditions, an excess (8
equiv.) of oxidant was used, 30% (in acetone) and 68%
(in acetonitrile) of sulfide was converted.
pyridinyl)methyl](methyl)amino]methyl}phenol16
(4,
Table 1. Oxidation of methyl phenyl sulfide with hydrogen peroxide (30% in water) in the presence of 0.2 mol%
Mn(OAc)3·2H2O at 0°C
Entry
Solvent
Oxidant equiv.a
T.O.N.b 2 h sulfoxidec T.O.N.b 4 h sulfoxidec
T.O.N.b 6 h sulfoxidec
(sulfonec)
Sulfide not
reacted (%)
(sulfonec)
(sulfonec)
1
2
3
Acetone
Acetone
Acetonitrile
Acetonitrile
Dichloromethane 8
2
8
2
8
14 (0)
56 (53)
20 (5)
98 (51)
21 (19)
15 (0)
61 (62)
20 (5)
115 (149)
27 (36)
16 (0)
73 (78)
20 (5)
126 (181)
35 (70)
94
70
94
32
75
4
5d
a H2O2 with respect to substrate.
b T.O.N.=turnover number=mol product/mol catalyst.
c All products were identical to independent samples and identified by GC (HP 6890, column HP1 15×0.3 mm×2.65 mm, polydimethylsiloxane).
d Room temperature.
Table 2. Oxidation of methyl phenyl sulfide with 8 equiv. of hydrogen peroxide (30% in water) in the presence of 0.2 mol%
Mn(OAc)3·2H2O and 0.2 mol% of ligand at 0°C
Complex liganda
T.O.N.b 2 h sulfoxide (sulfone)
T.O.N.b 4 h sulfoxide (sulfone)
T.O.N.c 6 h sulfoxide (sulfone)
1
574 (395)c
349 (222)
330 (220)
247 (58)
N.d.
N.d.
N.d.
357 (464)
255 (74)
2
563 (342)
342 (343)
248 (69)
3d
4
a See Fig. 1.
b T.O.N.=turnover number=mol product/ mol catalyst.
c T.O.N. result after 1 h.
d Room temperature.

J. Brinksma et al. / Tetrahedron Letters 42 (2001) 4049–4052
Table 3. Oxidation of sulfides using Mn-catalysts based and (S)-5a
4051
Entry
Ar
R
Sulfoxide (%)b
eec
Absolute configurationd
1
2
3
4
5
6
Ph
Me
Me
Me
CH2Ph
Me
55
50
48
50
52
52
18
8
5
5
6
R
R
R
R
R
R
p-MeC6H4
p-MeOC6H4
Ph
2-Naphthyl
1-Naphthyl
Me
7
a Acetone, T=0°C under a N2 atmosphere, reaction time 2 h, 8 equiv. of 30% H2O2 in water as oxidant.
b Isolated yield after column chromatography (SiO2, EtOAc).
c Determined by HPLC on a Daicel Chiralcel OB-H column.
d Determined by Daicel Chiralcel OJ column; determined by comparison with literature values.7b
gen peroxide as a terminal oxidant. Studies to enhance
the enantioselectivity in this new catalytic system are in
progress.
Fig. 1), featuring a three N-donor and one O-donor
ligand. Using the complex formed in situ from ligand 4
with Mn(OAc)3·2H2O and methyl phenyl sulfide as a
test compound, high selectivity was observed, while
only slight overoxidation was found. After 4 h, 248
turnover numbers to sulfoxide and only 69 turnover
numbers to sulfone were detected (Table 2). After
column chromatography a 55% isolated yield of pure
sulfoxide was obtained.
Acknowledgements
M.I.D. and C.R. wish to thank MURST (Roma) and
Universita` della Basilicata for financial support. Finan-
cial support from the Dutch Foundation for Scientific
Research (NWO-CW) (J.B., B.L.F.) and the Ministry
of Economic Affairs through IOP Catalysis program
(R.L.C., B.L.F.) is gratefully acknowledged.
Even in the case of slow oxidant addition (over a 1 h
period), only a negligible effect in increasing the conver-
sion was found. Using Mn(ClO4)2·6H2O instead of
Mn(OAc)3·2H2O caused an increase in overoxidation to
sulfone, whereas switching from acetone to acetonitrile
or dichloromethane as solvent resulted in a dramatic
decrease in conversion. It turned out that the best
conditions for ligand 4 are acetone as the solvent, and
performing the oxidation at 0°C and 8 equiv. of hydro-
gen peroxide. In summary, the Mn complex with ligand
4 is a promising catalyst in the selective oxidation of
methyl phenyl sulfide using hydrogen peroxide: with a
very low amount of catalyst (0.2 mol%) we obtained the
corresponding sulfoxide with 55% chemical yield, with-
out formation of sulfone. We decided to test ligand
(S)-5,16 a chiral version of ligand 4, reasoning that we
should obtain sulfoxides with conversion comparable
with those obtained using ligand 4, but in optically
active form. The results of oxidation of several sub-
strates using this new ligand are presented in Table 3.
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