Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5493_Библиотеки_им_академика_М_И_Перельмана.pdf
2 1 Synthesis of Sulfoximines and Cyclic Sulfoximines
There are various methods available for synthesizing sulfoximines, ranging from
traditional to state-of-the-art approaches. Some early methods involved oxidizing
thioamides or reducing sulfoxides. But as technology has improved, new methods
have come along that are more efficient and highly atom economic. Rhodium-
catalyzed reactions and other transition metal-catalyzed methods have become more
popular because they offer better selectivity and scalability. Asymmetric synthesis
methods have also grown in popularity, which makes it possible to make enantioen-
riched sulfoximines, which is important for medicinal uses where stereochemistry is
very important.
Sulfoximines have interesting features and reactions because they have a lot of
different structural types. Their special mix of S=O and S=N double bonds gives them
unique electronic and steric properties. The sulfur–oxygen double bond, which is one
of their most important features, gives them polarization and affects how they interact
with other molecules. The stereochemistry around the sulfur atom makes them even
more complicated, which makes stereocontrolled synthesis possible. Understanding
the small details of sulfoximine structures is crucial for tailoring their qualities to
specific uses in medicinal chemistry, materials science, or catalysis. The physical
properties of these substances include the following: Stability: Sulfoximines are
usually stable chemicals, especially when it comes to how well they handle a wide
range of chemical conditions and how stable they are at high temperatures. Response:
Their response is shown by their ability to go through different chemical changes.
This makes them useful building blocks in the process of organic synthesis. Sulfox-
imines can undergo changes in their electronic structures through the application of
electricity. Researchers can fine-tune the compounds’ features to fit specific needs.
Sulfoximines have a bright future ahead because researchers are still working on
developing new drugs [
9] and learning more about how they can be used to treat
new diseases and make current treatments better. Researchers are making agrochem-
icals faster to solve world agricultural problems while also improving their environ-
mental impact and effectiveness. Researchers are studying materials and developing
improved ones for use in electronics, optoelectronics, and other emerging technolo-
gies. To sum up, sulfoximines will continue to make important contributions to fields
like medicine, agriculture, and materials science in the future, thanks to their long
history and wide range of uses. Researchers are conducting more studies to discover
additional uses and potential for these compounds.
Sulfoximines have the potential to be used in medical chemistry. Researchers
are increasingly using sulfoximines in drug discovery due to their good pharmacoki-
netic qualities and unique ways of interacting with biological targets. These chemicals
have been especially useful for making enzyme inhibitors, such as protease inhibitors
and kinase modulators. Because sulfoximines can behave like peptide bonds, they
are more useful for designing bioactive molecules. This makes it possible to create
medicines that can treat a wide range of illnesses. Researchers in the field of medic-
inal chemistry have conducted extensive investigations into the characteristics of
sulfoximines. However, a significant number of specialists continue to be interested
in researching them. Good physicochemical properties, great metabolic stability, and
the capacity to accept and donate hydrogen bonds are some of the characteristics that
1.1 Synthesis of Sulfoximines 3
have been observed in this substance [10–12]. In addition, they play a role in directing
the process of C–H functionalization, which are also facilitated by transition metals
[
13]. In addition, NH-sulfoximines are capable of undergoing a variety of chemical
transformations, including arylation, alkylation, vinylation, alkynylation, and other
reactions [
14–17].
Sulfoximines are useful for more than just medicine. Furthermore, sulfoximines
serve as versatile building blocks in chemical synthesis. Their wide range of reactions
makes it possible to build complicated molecular structures, which makes it easier
to make natural products and bioactive compounds. Sulfoximines can be used in a
wide range of synthetic situations thanks to their ability to change functional groups,
cycles, and cross-couple processes [
18
]. As synthetic scientists keep looking for new
ways to change things, sulfoximines are still one of the most important tools they
have. They provide new and effective ways to get to complex molecular structures.
Although sulfoximines have definitely made their place in the scientific world,
there are still problems to solve. Researchers are still trying to figure out how to
make synthesis processes more scalable and less harmful to the environment. Under-
standing the full range of sulfoximine reactions and finding new uses for them are also
ongoing projects. There could be more breakthroughs in catalysis, materials science,
and drug research in the future, which is very exciting. Collaboration between indi-
viduals from different fields is likely to uncover new aspects of sulfoximine chem-
istry. This will push the field to new heights of discovery. This research aims to
provide evidence of the most recent developments in manufacturing and modifying
sulfoximines. This work aims to provide individuals with a more comprehensive
understanding of the origins of sulfoximine.
Overall, studying sulfoximines is like taking a fast-paced trip through the areas of
production, structure, and use. This group of compounds used to be less important,
but now it is at the top of chemical study, opening up a lot of new scientific possi-
bilities and technological advances. As scientists learn more about the complexities
of sulfoximine chemistry, they keep finding new and useful things that could change
the world. This makes sulfoximines an interesting topic at the point where science
and innovation meet.
1.1.1 Synthesis of NH-sulfoximines
One very useful group of synthetic intermediates is sulfoximines. They play an impor-
tant role in the field of chemical synthesis [
19
]. There is a multi-step process that
is involved in the synthesis of NH-sulfoximines. This process involves converting
amines into sulfoximine compounds. This method is used to add the sulfoximine
group, which is known for being flexible, to organic compounds. Sometimes, the
first step in the process is for amines to combine with sulfur sources that are elec-
trophilic. This is followed by an oxidation phase that creates the final NH-sulfoximine
product. Making NH-sulfoximines, a unique group of sulfoximine compounds, is an
4 1 Synthesis of Sulfoximines and Cyclic Sulfoximines
interesting way to learn about the complicated world of organic chemistry. NH-
sulfoximines are defined by the addition of a nitrogen atom to the imine functional
group instead of a hydrogen atom. This makes their structure and reactions even more
complicated. This introduction aims to give a thorough look at the different ways that
NH-sulfoximines are made, with a focus on how important these compounds are in
pharmaceutical chemistry, the differences in their structures, and how the methods
used to make them have changed over time.
The addition of nitrogen to the imine moiety changes the qualities and uses of
sulfoximines in new ways. This strategic change has a big effect on their elec-
tronic properties and how they connect with biological targets. NH-sulfoximines
have gotten a lot of attention for their possible use in drug discovery. This is because
they have special pharmacophoric properties that make compounds more likely to
bind and change how biologically active the compounds are. Therefore, making
NH-sulfoximines is very important because it opens up new ways to build and create
bioactive molecules with specific properties.
There have been huge strides made in the synthesis of NH-sulfoximines, with
different methods being used to deal with the problems that come up when nitrogen
is added to the imine structure. In the old ways, sulfinamides are mixed with nitrogen
sources that work well, like amines or amides, and then the reaction is carefully
managed. Newer methods look into transition metal-catalyzed methods, which give
better control over stereochemistry and make it possible to work with a wider range
of substrates.
Synthesis with Transition Metals: Strategies that use transition metals have
become very useful for making NH-sulfoximines. Some of the catalysts that have
been used to speed up key changes are palladium, rhodium, and copper. One example
is using a palladium catalyst to connect sulfinamides with amines in a way that only
delivers NH-sulfoximines. Not only do these ways increase yields, they also make
it possible to add different nitrogen sources, which increases the structural diversity
of the compounds that are made.
To get the most out of NH-sulfoximines, it’s important to keep the stereochem-
istry around the new nitrogen atom under control. To get enantioenriched NH-
sulfoximines, asymmetric synthesis methods have been created. Chiral catalysts are
very important for getting high amounts of stereocontrol. This skill is very important
in medical chemistry, because the way atoms are arranged in three dimensions can
have a big effect on how biologically active a molecule is. Adding nitrogen changes
the overall shape and electronic qualities of NH-sulfoximines in unique ways. It
is very important to understand these details in order to change how they respond
in certain situations. The nitrogen atom not only gives the imine nitrogen different
electronic properties, but it also makes it more basic, which could change how it
reacts with acidic protons in enzyme reactions. By studying how NH-sulfoximines
respond, we can change them in many ways, such as by changing their functional
groups or adding other chemicals to them. This makes them very useful in organic
synthesis.
1.1 Synthesis of Sulfoximines 5
These ways of synthesizing of sulfoximines are helpful in medicinal chemistry,
agrochemicals, and materials science because they let scientists make compounds
with a lot of different biological activities and qualities that can be changed to
fit different needs. There is freedom in the process of creating synthetic pathways
because the reagents and conditions that are used can be changed depending on the
final product that is needed. Researchers have written about a number of different
ways to make NH-sulfoximines. The nitrene transfer process, the amination of
sulfoxides, and the oxidation of sulfoximine are a few of these ways [
20, 21].
Making NH-sulfoximines is still hard, even though we’ve made a lot of progress.
Researchers are still working on making the process more scalable, finding more
environmentally friendly ways to make manufactured materials, and adding more
substrates to the mix. In the future, scientists may look into new catalytic systems,
more nitrogen sources, and better ways to control the stereochemistry of these
molecules. Because organic synthesis is changing and people want new drug options
more than ever, NH-sulfoximines are likely to be studied more as useful building
blocks in medicinal chemistry.
Finding new ways to make NH-sulfoximines is an active and growing area of
organic chemistry. Researchers are always pushing the limits of synthetic methods
to get to these interesting compounds, from old-fashioned methods to cutting-edge
transition metal-catalyzed techniques. Because of their complicated structures and
unique reactions, NH-sulfoximines are essential tools for designing and developing
bioactive molecules. This means that their contributions to medicinal chemistry will
continue to grow in the years to come.
1.1.2 Synthesis of Sulfoximines from Sulfoxides
The process of synthesizing sulfoximines from sulfoxides is both appealing and
valuable in organic chemistry. It gives us a flexible and quick way to get to this
interesting group of compounds. A sulfur–oxygen double bond is present in the
imine functional group, which is what makes sulfoximines stand out. They have
gotten a lot of attention for their many uses in fields like medical chemistry and
materials science. In this introduction, we will talk about all the different ways that
sulfoxides can be turned into sulfoximines. We will look at the basic ideas behind
these methods, the main ways that reactions happen, and what these methods mean
in the bigger picture of organic synthesis.
Sulfoxides are a group of molecules that have a sulfur atom double-bonded to an
oxygen atom. They have been useful in organic synthesis for a long time. To change
sulfoxides into sulfoximines, this functional group is changed strategically so that
the oxygen atom is replaced with a nitrogen atom. This gives the new sulfoximine
molecules their own unique properties. This change is not only interesting from
a synthetic point of view, but it is also very important because sulfoximines have
special properties and respond in very specific ways.
6 1 Synthesis of Sulfoximines and Cyclic Sulfoximines
The goal of making sulfoximines from sulfoxides is to use the different quali-
ties of sulfoximines in different ways. Scientists have found that sulfoximines are
very useful building blocks for making organic compounds because they are very
reactive and can be changed in many ways. By switching oxygen for nitrogen, the
molecule works better generally, which changes its electronic and steric properties.
In medicinal chemistry, small changes in molecular structure can have big effects on
how well a molecule works in living things. This change is especially important in
this case. To change sulfoxides into sulfoximines, different synthetic strategies have
been created, and each has its own benefits based on the goal and the needs of the
target molecule. In one of the oldest ways, sulfoxides are treated with amines while
they are oxidizing. This method, which is often sped up by transition metals like
copper or iron, makes it easier to add nitrogen while effectively oxidizing the sulfur
atom. Electrophilic nitrogen sources, like nitrosyl chloride or nitrosoarenes, are used
in another important way to convert substances in mild conditions.
In recent years, transition metal-catalyzed methods have become more popular
because they are good at changing sulfoxide to sulfoximine and are selective. Palla-
dium, rhodium, and copper catalysts have been used to speed up these processes. This
makes the reaction conditions more stable and lets scientists better control the stere-
ochemistry. These catalytic systems have added to the synthetic toolbox by letting
scientists get to a wider range of sulfoximines more precisely. One of the oldest
ways of synthesizing sulfoximines is to use sulfoxides to make sulfoximines. There
are hundreds of other ways to do this as well. Several metal or non-metal catalyzed
methods are used to make N-substituted or NH-sulfoximines, and a lot of research
has been done on them. Most of the time, a transition metal catalyst is used to make
sulfoximines in order to carry out the nitrene transfer process to the sulfoxides (As
shown in Scheme
1.1)[22]. The mechanistic processes that change sulfoxides into
sulfoximines are very interesting because they show how complicated these changes
are. The metal catalyst is very important in oxidative processes because it helps
move oxygen to nitrogen. A nitrogen-sulfur bond is made when the amine attacks
the intermediate sulfoxide with its nucleophilic force. The change to the sulfoximine
is finished by oxidation, which often involves the metal catalyst. It is important to
understand these processes in order to improve reaction conditions and add more
sulfoxide and amine substrates to the synthetic repertoire.
In 2002, Tye’s group synthesized N-protected sulfoximines by using iminoiodine
or mesitylene sulfonyl hydroxylamine as nitrene transfer agents. These reagents
were reactive with a range of sulfoxides that possessed functionalized side chains.
Deprotection of the sulfoximine adducts with thiophenol (when R
3
= Ns and p-nosyl)
Scheme 1.1 Synthesis of
N-protected sulfoximines via
transition metal catalyzed
nitrene transfer reaction
R'
S
O
R''
R'
S
O
N
R''
R
PhI = N-R
Cu, Rh, Ag
or Fe catalysts
R = SO
2
Ar, COCF
3
, CO
2
R
1.1 Synthesis of Sulfoximines 7
R'
S
O
R''
R'
S
O
N
R''
R'''
imination
PhSH, Cs
2
CO
3
CH
3
CN or DMF, rt
R'
S
O
NH
R''
TBAF, THF, 50
o
C
30-95% yield
R''' = Ns, 59% yield
R''' = Ses, 86% yield
Scheme 1.2 The synthetic method of Tye’s team
R'
S
O
R''
R'
S
O
N
R''
X-NH
2
(2.0 mmol),
PhI(OAc)
2
(1.5 mmol)
X
R'
S
O
NH
R''
MgO, [Rh
2
(OAc)
4
] (2.5 mol %)
CH
2
Cl
2
, rt
K
2
CO
3
, MeOH
X = Ns, Ms, COCF
3
66-88% yield
Scheme 1.3 The Rh-catalyzed synthesis of sulfoximines developed by the Bolm’s team
or TBAF (when R
3
= Ses) resulted in the formation of NH-sulfoximines, as shown
in Scheme
1.2 [23].
Using [Rh
2
(OAc)
4
] as a catalyst and iodobenzenediacetate as an oxidant, the group
led by Bolm reported in 2004 that both sulfoxides and sulfides can be converted into
N-protected sulfoximines. This transformation can be easily deprotected, as shown
in Scheme
1.3 [24].
Furthermore, in 2005, this research team led by Bolm discovered that silver
salts, when combined with chelating ligands, were able to successfully catalyze the
stereospecific amination of sulfoxides and sulfides with sulfonamides, PhI(OAc)
2
,
resulting in a high yield (as shown in Scheme 1.4, Eq. a) [25].
It was in the same year that his group investigated the reaction of Fe(III) catalyzed
amination of sulfoxides and sulfides in the presence of (diacetoxyiodo)benzene. The
most positive results were achieved by using Fe(acac)
3
as a catalyst when mixed with
iodobenzene (Scheme
1.4, Eq. b) [26
]. It was believed that iron (II) trifluoromethane-
sulfonate was a powerful and effective catalyst for the sulfuration reaction. At room
temperature, sulfonylimidoiodine (PhI = NSO
2
R) was able to successfully imidize
a variety of sulfoxides and thioethers. As a result, the matching sulfoximines were
synthesized with high yields in just a short period of time (Scheme
1.4, Eq. c) [27
].
The above methods to synthesize sulfoximines that were reported by Bolm’s group
are somewhat difficult because they use two steps to get NH-sulfoximines, but they
gave us a new idea for the next step in the process of synthesis. Magnier and his
colleagues described a two-step process to synthesize NH-sulfoximines. Sulfoxides
that are perfluoroalkylated reacted with nitriles and trifluoromethanesulfonic anhy-
dride to produce N-acyl sulfilimines. These are then deaylated and oxidized with
KMnO
4
(Scheme 1.5)[28
].
In 2013, The team led by Bolm was able to convert sulfoxides into N-
alkoxycarbonyl sulfilimines. This was made possible by using chemicals of the
Burgess type [
29]. After that, the N-alkoxycarbonyl sulfilimines are oxidized to
produce N-alkoxycarbonyl sulfoximines. These were then broken down in water
8 1 Synthesis of Sulfoximines and Cyclic Sulfoximines
R
1
S
O
N
R
2
X
R
2
HN
O
S
R
1
X = Ns, Ts, Ses
Cs
2
CO
3
, PhSH
MeCN,
rt
R
1
S
O
N
R
2
Fe(acac)
3
(10 mol %)
X-NH
2
PhI(OAc)
2
=O
X
Cs
2
CO
3
, PhSH
R
1
S
O
NH
R
2
MeCN, rt
X = Ns, Ts, Ses, etc.
R
1
S
O
N
R
2
X
Cs
2
CO
3
, PhSH
R
1
S
O
NH
R
2
MeCN, rt
R
1
S
O
R
2
(a)
(b)
(c)
MeCN, rt
X = Ns, SO
2
R,
73-98% yield
72-96% yield
45-96% yield
R
1
S
O
R
2
R
1
S
O
R
2
AgNO
3
(8 mol %)
4, 4',4''-t-Bu
3
tpy (8 mol %)
X-NH
2
PhI(OAc)
2
MeCN, rt or reflux
Fe(OTf)
2
(2.5-15 mol %)
PhI=NX, MS 4Å, MeCN, rt
Scheme 1.4 a Ag-catalyzed synthesis of sulfoximines. b The Fe-catalyzed synthesis of sulfox-
imines. c Fe(OTf)
2
-catalyzed synthesis of sulfoximines. All developed by Bolm’s group
R
1
S
O
R
2
1) R
3
-CN, Tf
2
O
2) H
2
O
R
1
S
N
R
2
O
R
3
R
1
S
O
NH
R
2
R
2
= CF
3
, C
4
F
9
KMnO
4
NaOH, H
2
O
22-74% yield
36-72% yield
Scheme 1.5 The synthetic method of Magnier’s group
(hydrolyzed) to make NH-sulfoximines in aqueous H2SO4. For reaction to happen,
you need a three-step process. NH-sulfoximines of synthetic value have been synthe-
sized from sulfoxides by means of N-protected thionimides (Scheme
1.6). This was
accomplished by utilizing this technique in conjunction with the applicable reagent
variations [
29].
In 2014, Richard and his colleagues published the research that described the
direct synthesis of NH-sulfoximines using O-(2,4-dinitrophenyl) hydroxylamine as
the nitrogen source and rhodium complex as the catalyst. This was achieved in
conditions that were not protected (Scheme
1.7)[30
].
In the year 2017, Bolm came up with a new method for the synthesis of NH-
sulfoximines. This method involved the direct preparation of sulfoxides through the
use of iron catalysis. When it came to the amine source, they used hydroxylamine; but
they also used the easily available and shelf-stable hydroxylamine triflate in order to
achieve synthesis. This method does not require the addition of an extra oxidant, and
the substrate range is very wide, which includes a number of heterocyclic compounds
(As shown in Scheme
1.8).
Another method for the synthesis of NH-sulfoximines was proposed by Luisi,
Bull, and their coauthors rest of their team. This method involved the use
1.1 Synthesis of Sulfoximines 9
R
1
S
R
2
O
N
S
N
O
O
O
O
CF
3
THF, reflux, 2 h
R
1
S
R
2
N
O
O
CF
3
NaIO
4
, RuCl
3.
H
2
O
MeOH:H
2
O (1:2), rt, 1 h
R
1
S
R
2
N
O
O
CF
3
O
aq. H
2
SO
4
(50%)
110
o
C, 2 h
76-99% yield
R
1
S
R
2
O
NH
37-81% yield
54-99% yield
Scheme 1.6 Bolm’s three-step method for synthesis of NH-sulfoximines
Scheme 1.7 Synthesis of
sulfoximines with O-(2,4-
dinitrophenyl)hydroxylamine
R
1
S
O
R
2
R
1
S
O
NH
R
2
O
O
2
N
NO
2
H
2
N
[Rh
2
(esp)
2
]
58-94% yield
R
1
S
R
2
O
FeSO
4
(20 mol%)
1,10-Phen (40 mol%)
MeCN, 30
o
C, Ar, 48h
21-98% yield
R
1
S
R
2
O
NH
+
O
2
N
O
O
NH
3
OTf
Scheme 1.8 FeSO
4
-catalyzed synthesis of sulfoximides from hydroxylamine triflate
of ammonium salts as a source of nitrogen and diacetoxyiodobenzene as an
oxidant. Additionally, the ammonium carbamate could be substituted by O-
mesitylenesulfonylhydroxylamine with base [
31
]. It was found that thioethers
and sulfoxides were sufficient sources of organosulfur for this particular protocol
(Scheme
1.9)[32
].
In addition, NH-sulfoximines can be synthesized by reacting sulfoxides with
NaN
3
(Scheme 1.10). There are two ways to achieve this process [33–35
]. However,
this method has a number of limitations, and it is suggested to not use it again because
of the explosive nature of NaN
3
, which is extremely dangerous.
The way that sulfoxides are made into sulfoximines is very important in medic-
inal chemistry. The sulfoximines that are made have special structural traits that
Scheme 1.9 Synthesis of
sulfoximines with
ammonium salt and
diacetoxyiodobenzene
R
1
S
O
NH
R
2
H
2
NCO
2
NH
4
, PhI(OAc)
2
R
1
, R
2
= alkyl, aryl, vinyl, cyclic, acyclic
R
1
S
R
2
O
or
R
1
S
R
2
9-90% yield
10 1 Synthesis of Sulfoximines and Cyclic Sulfoximines
Scheme 1.10 Synthesis of
sulfoximines with sulfoxides
and NaN
3
R
S
O
R'
R
S
O
NH
R'
NaN
3
, catalyst
affect how they work in the body and how they affect other substances. By using
this synthetic route, we can finetune the structure of sulfoximines. This makes it
possible to create new bioactive molecules. Because sulfoximines are more stable
and reactive, they are good options for use in drug development. Adding them can
give drugs desirable properties like better binding affinity and metabolic stability.
Making sulfoximines from sulfoxides has come a long way, but there are still prob-
lems that need to be solved. Ongoing study is needed to solve problems with the
regioselectivity, stereoselectivity, and scalability of some reactions. The goal is still
on making methods that are more sustainable and atom-economical, which fits with
the growing need for synthetic processes that are better for the environment.
In conclusion, making sulfoximines from sulfoxides is an active and growing area
of organic chemistry. This change, which is important for organic synthesis because of
how well it works and how it changes the qualities of the sulfoximines that are made,
is very attractive. Researchers are always improving and adding to the tools they use
to get to these useful compounds, ranging from traditional oxidative methods to state-
of-the-art transition metal-catalyzed approaches. The creation of sulfoximines from
sulfoxides will be very important in the future for making new materials, bioactive
chemicals, and other uses. This shows how important this synthetic journey will be
for a long time.
1.1.3 Synthesis of Sulfoximines from Thioethers
Thioethers are useful starting materials in organic synthesis because they have a sulfur
atom linked to two organic groups. When thioethers are changed into sulfoximines,
the sulfur atom is oxidized, which adds a nitrogen atom to the imine molecule.
The sulfoximines that are made after this structural change have special qualities
that make them very useful in many chemical situations. The process of making
sulfoximines from thioethers is tactically important because it gives us access to
compounds that are more reactive and can be used in a wide range of ways. The
synthesis of sulfoximines from thioethers is an interesting journey in the field of
organic chemistry. It provides a strategic way to get to a special group of chemicals
that have gotten a lot of attention for the many uses they have. Sulfoximines are
interesting chemicals because they have interesting features and reactions that make
them useful in many areas, from medicinal chemistry to materials science. They are
identified by a sulfur–oxygen double bond within the imine functional group. It is the
goal of this introduction to give a full look at the synthetic methods used to change
thioethers into sulfoximines, explaining important ideas, how reactions work, and
what these methods mean in the bigger picture of organic synthesis.
1.1 Synthesis of Sulfoximines 11
Making sulfoximines from thioethers is done because scientists want to use the
unique qualities that the sulfur–oxygen double bond in the imine group gives it. This
change adds a nitrogen atom, which changes the electronic and steric properties of
the sulfoximines that are made. Understanding how important this change is can be
seen in the many things it can be used for, from creating new bioactive molecules to
building complex organic structures.
To change thioethers into sulfoximines, different synthetic strategies have been
created, and each has its own benefits based on the end goal and the needs of the target
molecule. Oxidative methods, which use oxidants like peroxides or metal catalysts,
are the most common way to make this change. Modern methods that use transition
metals as catalysts have also become very useful. They make reaction conditions
softer and give us better control over regioselectivity and stereoselectivity. Alternative
Methods: In oxidative methods, molecular oxidants are used to change thioethers into
sulfoximines. Peracids, peroxides, or metal-based catalysts that make it easier for
oxygen to move to sulfur are all common oxidizing agents. To avoid over-oxidation
to sulfones and get high selectivity toward the desired sulfoximine product, these
reactions often need careful control of the reaction conditions. By using classical
oxidation methods, we have learned a lot about how thioethers change, which has
led to further progress in this area.
In recent years, transition metal-catalyzed methods have become more popular
because they are quick and flexible ways to make sulfoximine from thioethers. Cata-
lysts like palladium, copper, or iron are very important for the oxidative coupling
between thioethers and molecules that contain nitrogen. These methods have bene-
fits like mild reaction conditions, better functional group tolerance, and the ability
to get to a wide range of sulfoximines. Using a catalytic method has opened up new
ways to make chemicals, making it easier to change different thioether substrates
into sulfoximines. The change from thioethers to sulfoximines can be explained in
terms of a set of oxidation–reduction steps. In oxidative processes, the metal cata-
lyst often helps molecular oxygen or other oxidants get going, which speeds up the
oxidation of the sulfur atom in the thioether. Then, molecules that contain nitrogen
attack and form a nucleophilic bond with the sulfur, which leads to the formation
of the sulfoximine product. It is important to study the details of these processes in
order to improve reaction conditions, create new catalytic systems, and make more
substrates usable.
There are other methods that can be used in order to synthesize sulfoximines from
thioethers. A number of synthetic procedures will be described in the sections that
follow, in addition to the different methods that were discussed earlier (shown in
Schemes
1.3, 1.4, and 1.8). With the help of thioethers, Bolm was able to synthesize
sulfoximines in three steps in the year 2007. The synthesis of N-cyanosulfoximines
was carried out by reacting the appropriate sulfides with cyanamide in the presence of
an alkali and either NBS or I
2
as a halogenating agent. Following further elimination
of cyano groups, NH-sulfoximines are produced (Scheme
1.11)[36]. With the help
of oxidation and the subsequent breaking of the C–N bond, synthetically NH-free
sulfoximines are produced.