Stereochemistry of organic sulfur compounds: More than 100?years of history, current state and further challenges

Article abstract of DOI:10.1080/10426507.2016.1252366

In the paper presented are the author's subjective views on the most important achievements in the stereochemistry of organic sulfur compounds, which, as an object of research, has more than 100-year history. Prospects for further development are also men

Full text of DOI:10.1080/10426507.2016.1252366

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Stereochemistry of organic sulfur compounds:more than 100 years of history, current state and
further challenges
1
,2
Józef Drabowicz
1
Center of Molecular and Macromolecular Studies PAS, 90-363 Lodz,, Sienkiewicza 112,
Poland
2
Jan Dlugosz University in Czestochowa, Institute of Chemistry, Environmental Protection and
Biotechnology, Armii Krajowej 13/15, 42-201 Czestochowa, Poland
Corresponding author Email: draj@cbmm.lodz.pl
Abstract.
In the paper presented are the author’s subjective views on the most important achievements in
the stereochemistry of organic sulfur compounds, which, as an object of research, has more than
1
00-year history. Prospects for further development are also mentioned.
Keywords
organosulfur derivatives; stereochemistry; optical activity; asymmetric synthesis, chiral
auxiliaries
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INTRODUCTION
Research on the stereochemistry of organic sulfur compounds comprises more than a hundred
1
,2
years of history . Its course can be easily divided into two periods. The first one, which lasted
until the end of the seventies of the twentieth century, was associated with methodological
studies, which were focused on the synthesis of optically active compounds with a stereogenic
sulfur atom having various valency and/or coordination number, determination of their optical
and chemical stability and reactivity, stereochemistry of the basic functional group
interconversions and basic structural parameters including their chiraloptical properties. The
second period, lasting until now, has been focused on research aimed at the use of the optically
active derivatives with a stereogenic sulfur atom as chiral auxiliaries or catalysts in asymmetric
synthesis and chiral substrates useful in the synthesis of new materials. At the same time,
thorough research has been conducted on the biological activity of these types of organic sulfur
compounds with the hope of discovering new pharmaceutically applicable ingredients.
RESULTS AND DISCUSSION
Methodological studies focused on the synthesis of optically active compounds with a
stereogenic sulfur atom having various valency and/or coordination number
The first period of research devoted into the stereochemistry of organic sulfur compounds,
3
which opened in 1900 and lasted roughly until the end of the seventies of the twentieth century,
was focused above all on:
a) synthesis of model optically active compounds with a stereogenic sulfur and
determination of their optical stability
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b) determination of the absolute configurations and enantiomeric excesses of substrates and
products of examined conversions
c) description of the mechanisms of nucleophilic substitution at a stereogenic sulfur,
including the determination of stereochemical consequences of nucleophilic substitution
at the sulfur (similarities and differences in comparison with the reactions of nucleophilic
substitution at the stereogenic carbon atom)
3
The pioneering report on successful optical resolution of sulfonium ion 2 (Scheme 1) was of
great contemporary importance in the development of the theory of optical activity based on the
tetrhedral model (the role of a fourth substituent is played by the unshared pair of electronson the
sulfur atom). It should be noted here that the isolation of the diasteromerically pure sulfonim salt
2
a or the diasteromerically pure sulfonim salt 2b were possible only after very tedious fractional
crystallization of starting salt 2 from a mixture of absolute alcohol and ether (some 40 to 50
3
times) .
4
-6
In recent years, enantiomeric sulfonium salts 3 have been frequently used as precursors
of the optically active sulfonium ylides 4, useful chiral auxiliaries in the asymmetric synthesis of
epoxides 5 formed according to Scheme 2.
The fundamental importance in stereochemistry of organosulfur compounds plays
diastereomerically pure O-menthyl p-toluenesulfinate 8 obtained for the first time in 1926 by the
7
reaction of p-toluenesulfinyl chloride 7 with (-) -- (1R, 2S, 5R)- menthol- 7 (Scheme 3).
Considering details of this procedure it is evident that it constitutes the first example of the
8
reaction that now have been termed as dynamic kinetic resolution (DKR) process . It should also
9
-10
be noted that recent modifications of this procedure , including a base and solvent free reaction
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1
1
of p-toluenesulfinyl chloride with menthol , allows the convenient isolation of (S )-8
S
diastereomer in a very high yield. This sulfinate was also used as a substrate in the first
stereospecyfic synthesis of enantiomerically pure aryl alkyl and nonsymmetric diaryl sulfoxides.
This procedurę, now known as the Andersen’s method, is ilustrated on Scheme 4 by the original
1
-2,12
reaction which afforded enantiomerically pure ethyl p-tolyl sufoxide 9 (Scheme 4)
.
After this seminal paper of Andersen a number of diasteromerically pure sufinates have been
prepared and used as precursors of enantomerically pure, nonfunctionalized and differently
1
-2, 13-14
functionalized aryl alkyl, diaryl and dialkyl sulfoxides
.
The second methods for the preparation of enantiopure sulfoxides is asymmetric sulfide
oxidation. Developing a novel oxidation method that involves reacting a sulfide 10 with an chiral
oxidising agent (COA-11) to form the enantiopure (or enriched) sulfoxide 12 (Scheme 5) has
1
3-15
been, and still is, a very hot research topic
. Key advances in this field are related to the use as
1
6
17-19
oxidation reagents: a) Davis oxaziridines b) oxidants based on an organometallic core
c)
2
0-21
biological oxidants
The fundamental importance in stereochemistry of organosulfur compounds plays also
.
1
-2,22
23
1-2,24
sulfoximines 13
(which show a very interesting biological activity) , sulfinamides 14
1
-2,25
and N-alkylidenesulfinamides 15
. All three classes of compounds are very useful as chiral
2
6
auxiliaries and / or precursors of other optically active sulfinyl derivatives .
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Determination of optical stability and chiraloptical properties.
An advantage of using optically active compound with a stereogenic sulfur atom as chiral species
in asymmetric reactions lies in their relatively high optical stability. This is especially evident for
1
,2
the sulfoxides, sulfoximines, sulfinamides and sulfonium salts . Classic works of Mislow’s
team showed that for the majority of sulfoxides racemisation only occurs via pyramidal inversion
2
7
with measurable speed at around 200 C. Exceptions constitute benzyl sulfoxides, which
racemise via a homolitic scission mechanism at 130--150 C, and allyl sulfoxides where [2,3]-
2
8-29
sigmatropic rearrangements occur before pyramidal inversion at temperatures of 50--70 C.
In this context it should be noted that sulfoxides with a proton in the β-position may undergo
3
0
elimination to generate olefins at temperatures of around 80 C the majority of sulfonium salts
31
racemisation via pyramidal inversion with measurable speed at around 70 C.
Considering the possibilities of determination of the absolute configuration of compounds with
stereogenic sulfur atom the importance of chiroptical properties should be stressed. The first
empirical correlations between electronic circular dichroism (CD) and optical rotatory dispersion
(
ORD) spectra (210-265 nm) of several nonracemic sulfoxides and sulfinates and their absolute
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3
2
configurations were also reported by Mislow’s team. The detailed discussions of experimental
3
3
ORD and CD spectra of chiral sulfur compounds is given by Laur whereas nonempirical
3
4
35
interpretations of CD spectra for several aryl alkyl sufoxides aryl benzyl sufoxides are
discussed by Rosini et al. The first nonempirical circular dichroism determination of the absolute
configuration of N-phthalimidosulfoximines based on excition coupling mechanism was found to
3
6
allow simultaneous determination of the absolute configuration of parent sulfoxides.
Simultaneously, the nonempirical determination of the absolute configuration of chiral
sulfoxides was found to be possible based on the comparison of experimental and ab initio
3
7-38
predicted absorption and VCD spectra.
Further challenges
a) Synthesis of optically active sulfurous acid derivatives 16 derived from achiral, unstable
sulfurous acid 17 and optically active sulfoimidoyl derivatives 18
b) Synthesis of optically active hypervalent derivatives 19 and 20
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c) studies devoted to stereochemical aspects of the flow process (for reactions carried out in
microreactors)
d) studies devoted to stereochemical aspects of the reaction carried out under high pressure
e) studies devoted to the use optically active compounds containing a stereogenic sulfur
atom in the chemistry of „new materials”
1
. Synthesis of polymers functionalized with substituents containing
a stereogenic sulfur atom
. Funtionalization of nanaocarbon materials with substituents containing
2
a stereogenic sulfur atom
f) studies devoted to the use of optically active compounds containing a stereogenic sulfur
matom as chiral auxiliaries in asymmetric synthesis including a search for greener and
reusable analogues
g) suplamolecular chemistry of optically active compounds containing a stereogenic sulfur
atom
h) search for optically active compounds containing a stereogenic sulfur atom as
pharmaceutically useful substances
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Acknowledgments
The author thanks for the support from the fund of the National Science Center awarded on the
basis of the decisions UMO-2012/06/A/ST5/00227 and UMO-2014/15/B/ST5/05329
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Scheme 1 Optical resolution of sulfonium ion 2
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Scheme 2 Asymmetric synthesis of optically active epoxides 5 based on sulfonium ylide 4 as a
chiral auxiliary
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Scheme 3 The first protocol for the preparation of diastereomerically pure O-menthyl p-
toluenesulfinate 8
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Scheme 4. The first preparation of enantiomerically pure ethyl p-tolyl sulfoxide 9
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Scheme 5 Asymmetric oxidation of sulfides 10 to the corresponding sulfoxides 12
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