Iodine(III)-Mediated Preparations of Nitrogen-Containing Sulfur Derivatives: Dramatic Influence of the Sulfur Oxidation State

Article abstract of DOI:10.1002/chem.200305525

Reaction of sulfonamides with iodosobenzene leads to phenyliodinanes. A new catalysis reaction of the decomposition of these products in the presence of sulfoxides that allows the smooth synthesis of sulfoximines has been evidenced and studied: copper(n) salts were used to prepare compounds 4a-j and 5b, d, f, j, k from the corresponding, easily prepared, sulfoxides. The reactions proceed with retention of configuration at the sulfur center, and copper(II) triflate is the best candidate for the catalyst for the imination. Switching from sulfonamides to sulfinamides in the preparation of the starting iodinanes completely alters the reaction pathway: iodinanes are no longer accessible, and sulfonimidates 7a-j are obtained instead. This behavior can be rationalized by the increase in pK_a brought about by the removal of one oxygen atom from the sulfur center. Sulfonimidates are interesting molecules with varied applications. Optimization of their one-pot synthesis has been achieved by carrying out the reaction in acetonitrile. The stereochemical study has shown that the transformation proceeds with global retention of the configuration at the sulfur center, albeit with erosion of the enantiomeric purity. A model accounting for this outcome is proposed. In addition, the presence of oxidized sulfonamide by-products has been explained, and this latter pathway becomes the sole one when alcohol is replaced by water. Good yields of the oxidized products are obtained.

Full text of DOI:10.1002/chem.200305525

FULL PAPER
Iodine(iii)-Mediated Preparations of Nitrogen-Containing Sulfur Derivatives:
Dramatic Influence of the Sulfur Oxidation State
Dominique Leca, Kai Song, Muriel Amatore, Louis Fensterbank, Emmanuel LacÙte, and
Max Malacria*[a]
Dedicated to Prof. Pierre Gouzerh on the occasion of his 60th birthday
Abstract: Reaction of sulfonamides
with iodosobenzene leads to phenylio-
dinanes. A new catalysis reaction of
the decomposition of these products in
the presence of sulfoxides that allows
the smooth synthesis of sulfoximines
has been evidenced and studied: cop-
per(ii) salts were used to prepare com-
pounds 4a j and 5b, d, f, j, k from the
corresponding, easily prepared, sulfox-
ides. The reactions proceed with reten-
tion of configuration at the sulfur
center, and copper(ii) triflate is the
best candidate for the catalyst for the
imination. Switching from sulfonamides
to sulfinamides in the preparation of
the starting iodinanes completely alters
the reaction pathway: iodinanes are no
longer accessible, and sulfonimidates
7a j are obtained instead. This behav-
ior can be rationalized by the increase
in pKa brought about by the removal
of one oxygen atom from the sulfur
center. Sulfonimidates are interesting
molecules with varied applications. Op-
timization of their one-pot synthesis
has been achieved by carrying out the
reaction in acetonitrile. The stereo-
chemical study has shown that the
transformation proceeds with global re-
tention of the configuration at the
sulfur center, albeit with erosion of the
enantiomeric purity. A model account-
ing for this outcome is proposed. In ad-
dition, the presence of oxidized sulfo-
namide by-products has been ex-
plained, and this latter pathway be-
comes the sole one when alcohol is re-
placed by water. Good yields of the
oxidized products are obtained.
Keywords: iodine
¥
oxidation
¥
¥
sulfonimidates
sulfur
¥
sulfoximines
Introduction
such compounds, and, more generally, most chiral nitrogen-
containing sulfur moieties.
Nitrogen-containing sulfur derivatives are highly important
compounds that have found a wide range of applications, for
example, as partners for asymmetric synthesis, ligands, bio-
active molecules, and bricks for new materials. In particular,
sulfonamides,[1] sulfinamides,[2] and sulfoximines[3,4] are
among the most prominent members of this family. Thus,
the quest for new routes for their preparations is a never-
ending challenge that needs to be approached with new per-
spectives. Some time ago, we reported on our work devoted
to asymmetric radical reactions involving chiral sulfox-
ides.[5,6] Because sulfoximines can be prepared from sulfox-
ides, we looked for new ways to stereoselectively access to
When we initiated our work, one of the best syntheses of
sulfoximines used phenyliodinane, a hypervalent iodine(iii)
derivative, as the nitrogen source (Scheme 1). This does not
Scheme 1. General preparation of sulfoximines from sulfoxides.
come as a big surprise because the chemistry of hypervalent
iodine compounds has experienced a tremendous develop-
ment during the last decade.[7,8]
This surging interest is mainly due to their useful mild oxi-
dizing properties and their low toxicity (especially compared
to heavy-metal derived oxidizing agents).[7] Among all iodi-
ne(iii) reagents, iodinanes are very convenient nitrene pre-
cursors, whose metal-mediated decomposition is a very pow-
erful tool. Mansuy and co-workers first described the aziridi-
[a] D. Leca, Dr. K. Song, M. Amatore, Dr. L. Fensterbank,
Dr. E. LacÙte, Prof. M. Malacria
Universitÿ Pierre et Marie Curie
Laboratoire de chimie organique, UMR CNRS 7611
B. 229, 4 place Jussieu, 75005 Paris (France)
Fax : (+33)1-44-27-73-60
E-mail: malacria@ccr.jussieu.fr
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DOI: 10.1002/chem.200305525
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906 916
nation of alkenes with phenyliodinane in the presence of
iron or manganese porphyrins.[9] The mechanism involves a
porphyrin metal nitrene complex.[10] Evans and co-workers
have further investigated the aziridination of alkenes and
have made copper salts the catalysts of choice for this reac-
tion.[11] Generally, copper(i) is used. The reaction has been
extended to sulfides and sulfoxides as nitrene traps to yield
sulfimides[12] and sulfoximines, respectively, by Vogt and
In all the latter cases, the iodinanes have been first isolat-
ed and subsequently decomposed to yield the desired imi-
nated products. This process has been converted into very
26]
elegant one-pot procedures.[23
Chiral ligands were used for asymmetric aziridination[11]
and sulfimidation,[12,27] but the ee values obtained in the
copper-mediated sulfimide synthesis are not satisfactory.
Carreira and Tomooka have nicely improved the asymmet-
ric preparation of chiral sulfinimines by using nitridoman-
ganeses complexes.[28] However, a full equivalent of the
metal is required to reach high ee values. We decided to ex-
amine the preparation of chiral iodinanes, in which a sulfinyl
group replaced the sulfonyl one, and thus to prepare C
(Scheme 3). We reasoned that since one oxygen atom of the
sulfonyl group always plays no role in the stabilization, sulfi-
nyl moieties could be valid chiral surrogates for the secon-
dary interactions. Precursor C
Muller[13] and by Bolm and co-workers.[14,15]
18]
Different phenyliodinanes have been prepared[16
by
coupling the corresponding sulfonamide with iodosobenzene
derivatives in KOH/methanol. The initial step is presumably
the solvolysis of the initial iodine reagent.[19] Sulfonamides
react by nucleophilic substitution on the iodine atom, possi-
bly giving birth to a dissociated intermediate, that would
eventually be deprotonated (Scheme 2).
could be prepared by a stan-
dard procedure starting from a
chiral sulfinamide rather than a
sulfonamide. We report below
the findings we gathered along
this path.
Results and Discussion
Scheme 2. Possible mechanism for the formation of phenyliodinanes.
Catalytic system: Prior to our
study, we decided to have a
The iodinanes are highly polarized molecules. Thorough
studies of their structure and solid-state aggregation have
shown that these molecules are best described as possessing
closer look at the catalytic
system we would end up using. Several metallic systems can
decompose phenyliodinane. Most of them fall into two dis-
tinct categories. Porphyrins were the first reported systems:
by analogy to the biomimetic oxidations, Mansuy and co-
workers reported the aziridination of different aryl-substi-
tuted alkenes by iron(iii) and manganese(iii) porphyrins.[9] It
is assumed that these reactions occur via terminal imidoir-
on(v) and manganese(v) intermediates, as can be inferred
from the isolation of an elusive terminal (imido)mangane-
se(v) corrole complex.[10] The second main category contains
copper complexes. For aziridination reactions, the oxidation
state of the active species has not been clearly identified
and a debate is still going on. While Deeth, Scott and co-
workers[29] and Norrby and co-workers[30] favor a route in-
volving a copper(i) intermediate, Evans and co-workers re-
ported in their seminal article that UV-monitoring of the
aziridination of double bonds showed that ™it is reasonable
to conclude that these reactions are being catalyzed through
CuII rather than CuI as originally presumed∫.[11] The reac-
tions are very likely substrate dependent.
À
I N single bonds with substantial amounts of charge on the
I and N atoms.[20] This can lead to varied polymeric assem-
blies, which can be stabilized through secondary interactions
with the oxygen atoms of the sulfonyl moiety.[21] Thus, iodi-
nanes generally are poorly soluble and the catalytic reac-
tions that employ them are heterogeneous and rather slow.
This problem can be overcome by the preparation of iodi-
nane B in which an additional sulfonyl group is put on the
aryl group attached to the iodine center (Scheme 3).[22] Dis-
ruption of the electrostatic intermolecular forces on B is
achieved by the introduction of intramolecular secondary
bonds. The reactivity is thus much better.
Sulfimides can be obtained from sulfides with both cop-
per(i) and copper(ii) salts.[12] However copper(ii) derivatives
were inferior to copper(i) triflate for asymmetric sulfimida-
tion. The authors attribute this loss to the competition be-
tween acetonitrile and the chiral ligand for the ligand sites
on copper and/or to the poorer solubility of copper(ii) tri-
flate. Formation of sulfoximines was even less examined.[4]
To the best of our knowledge, only two groups had focused
on the preparation of sulfoximines from sulfoxides and phe-
Scheme 3. Routes to modified phenyliodinanes.
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M. Malacria et al.
FULL PAPER
nyliodinane. Both chose to rely on copper(i) catalysts to do
demanding sulfoxides. Entries 9 and 10 in Table 1 show that
acetylenic sulfoximines can also be prepared by this
method. To the best of our knowledge, this was the first
preparation of such compounds, whose reactivity looks
promising.[32] Chiral HPLC analysis of 3i and 3j showed
that the reaction was stereoselective, no loss in ee being ob-
served. This is consistent with the earlier studies with cop-
per(i) triflate by Muller and Vogt,[13] who reported complete
retention of configuration at the sulfur center. Attack of the
sulfur lone pair leads to the formation of the S=N bond.
When submitted to our conditions, (R)-methyl-p-tolyl sulf-
oxide (ee>98%) yielded the corresponding known (À) sulf-
oximine (97%, ee>98%), implying an R absolute configu-
ration at the sulfur center[33] (we obtained the same specific
rotation as the authors. This de-
15,31]
the work.[13
After reviewing the available literature and
taking advantage of what was described for alkenes and sul-
fides, we were confident sulfoximines could be prepared by
using copper(ii) salts. There are two advantages for such an
approach: beyond the economic aspects (copper(ii) is gener-
ally much less expensive), the practicality of the reaction
would be improved, since copper(i) triflate is air-sensitive
and must be handled in a glovebox.
The synthesis of sulfoximines was achieved by treatment
of suitably substituted sulfoxides with one equivalent of phe-
nyliodinane in acetonitrile, in the presence of 10 mol% of
copper(ii) triflate.[46] Representative results are summarized
in Table 1.
livers additional evidence for a
good ee). The reaction thus pro-
Table 1. Catalytic synthesis of sulfoximines with copper(ii) triflate.
ceeds with retention of configu-
ration.
We next turned our attention
to the nature of the copper salt
(Table 2). We decided to carry
out our tests with sulfoxide 1c,
because of the average chal-
lenges it poses (one double
bond, but no additional poten-
tially problematic functionality,
and not too reactive).
Entry
1
Sulfoxide
Sulfoximine Yield [%] Entry
Sulfoxide
Sulfoximine Yield [%]
3a
3b
4a
4b
96
91
6
7
3 f
3g
4 f
4g
91
89
2
Copper(ii) triflate appears to
be the reagent of choice, both
in terms of yields and rates
(Table 2, entry 1). Catalyst load
could be reduced to 3 mol%
without problems (Table 2,
entry 2), while further decrease
resulted in an important reduc-
tion of the rate of the reaction.
3
4
3c
3d
4c
4d
96
53
8
9
3h
3i
4h
4i
75
89
5
3e
4e
7210
3j
4j
89
Table 2. Optimization of the catalyst.
Sulfoximines 4a j were obtained in good to excellent
yields. We developed our method first with alkylaryl- and di-
alkyl sulfoxides 3a,b, which led to their imine counterparts
in 96% and 91%, respectively (Table 1, entries 1 and 2).
The reaction was almost instantaneous. When stirring is pro-
longed, a precipitate appears, probably an iodinated by-
product. Versatile vinyl sulfoxides (Table 1, entries 3 5) and
allylic bromides (Table 1, entries 6 8) were easily trans-
formed even when reactions were carried out in an open
flask with acetonitrile from the bottle. The yield for phenyl
vinyl sulfoxide is lower than for all the other derivatives.
Phenyl vinyl sulfoxide is prone to anionic polymerization,
which is maybe what happens during the imidation. An ad-
ditional hint for such a behavior is given by entry 5 in
Table 1: The triisopropylphenyl derivative 3e is particularly
hindered because of the bulky aromatic ring. This could
have prevented or hindered reactions at or near the sulfur
atom. Sulfoximine 4e was obtained in higher yield than its
parent compound (72%, entry 5). More interestingly, the
imidation occurred as quickly and easily as the sterically less
Entry
Catalyst
Yield [%]
1
Cu(OTf)2
96
87
2Cu(OTf)
2, 3 mol%
3
4
5
6
CuCl2
CuSO4¥5H2O
Cu(acac)2
43 (20% sm)[a]
no reaction
86
Cu(OAc)2¥H2O
77 (7% sm)
[a] PhINTs (1 equiv) and CuCl2 (10 mol%) were added after 1 h. acac=
acetylacetonate; sm=starting material.
Copper(ii) chloride does not work well (Table 2, entry 3).
Copper sulfate gave no reaction at all (Table 2, entry 4),
whereas Cu(acac)2 worked well, although it was slightly less
active than copper triflate (compare entries 1 and 5,
Table 2). Copper(ii) acetate monohydrate is also an accepta-
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Iodine(iii)-Mediated Preparations of Nitrogen-Containing Sulfur Derivatives
906 916
ble catalyst, thus demonstrating that our method is not only
compatible with oxygen but also with water (Table 2,
entry 6). This quick survey showed that copper(ii) triflate is
the best catalyst. This has not been further examined but
from this point on we have continued with the triflate.
The next step was to examine the nature of the iodinane.
In order to know whether the reaction was limited to aryl-
sulfonyliodinane, we introduced the corresponding methyl-
sulfonyl iodinane (Table 3).[18]
iodobenzene moiety at the nitrogen center on D rather than
deprotonate it, thus leading to sulfinyl hydroxylamines
(Scheme 4).
Maricich and co-workers evidenced in 1973 that, in some
cases, sulfinylhydroxylamines underwent spontaneous rear-
rangement to sulfonimidates, with migration of the alkoxy
Table 3. Catalytic synthesis of N-methanesulfonyl sulfoximines with cop-
per(ii) triflate.
Entry
1
Sulfoxide
Sulfoximine
Yield [%]
Scheme 4. Possible mechanism for the formation of sulfonimidates.
3b
5b
95
70
group from the nitrogen to the sulfur atom.[36] In any case,
this alternative route would be of great interest, since sulfo-
nimidates are very interesting chiral and nitrogen-containing
compounds. They have also applications in material sciences,
as monomers of ™inorganic polymers∫,[37,38] and biochemis-
try, where they may act as inhibitors of human carbonic an-
hydrase II.[39] In addition, Johnson and coworkers have
shown that they can be used in asymmetric synthesis as
chiral enantiopure sulfoximine precursors.[40] Reggelin and
co-workers developed these precursors with high levels of
sophistication by introducing cyclic sulfonimidates.[41,42]
When submitted to potassium hydroxide in methanol at
room temperature, tosylsulfinamide led to the correspond-
ing sulfonimidate after just a few minutes. This not only
showed that our assumption was correct, but also that we
could prepare sulfonimidates by a one-pot procedure, in
contrast to the known reported methods which were multi-
step procedures.[43,44] Next, we optimized the reaction condi-
tions: it is unnecessary to use a base if PhI=O is used as the
starting iodine reagent. This avoids having to work under
overly basic conditions. With the optimized procedure in
hand, we studied the scope and limitations of this reaction
(Table 4).
2
3
3 f
5 f
3k
5k
98
4
5
3d
3j
5d
5j
70
40
We tested the sulfoximination with an assay of our sulfox-
ides. All sulfoximines were obtained in yields similar to
those obtained with p-toluenesulfonyliodinane except for 5j,
thus demonstrating that the reaction was not limited to the
aryl derivatives. This is quite interesting because these new
sulfoximines are electronically different from the previous
ones and their properties may thus be tuned by the choice
of the substituent on the iodinane. In the case of acetylenic
sulfoxides 3j, we did not observe any other by-product than
iodobenzene. Since the triple bond is a good ligand for
metals, it is possible that it starts interfering with the imina-
tion at the sulfur center.
Table 4. Preparation of sulfonimidates (1): Alcohol as solvent.
Access to sulfonimidates: With our system in hand, we
turned our attention to the preparation of sulfinyl-derived
iodinanes. In doing so, we kept in mind that another reac-
tion path was possible. To produce imidoiodinanes, iodoso-
benzene and iodosobenzene diacetate react with sulfona-
mides.[9,34] As mentioned before, the initial step is presuma-
bly the solvolysis of the initial iodine reagent.[19] Sulfona-
mides react by nucleophilic substitution on the iodine atom,
possibly giving birth to a dissociated intermediate arising
Entry
R
Sulfonimidate
Yield [%]
1
2Et
3
Me
7a
7b
7c
91
94
iPr
73[a]
4
5
6
7d
7e
7 f
71
92
85
[b]
[c]
À
from the I O bond cleavage on A. Deprotonation eventual-
7
8
Bn
tBu
ly delivers the iminoiodinanes (Scheme 2). Now, switching
to sulfinamides implies a strong reduction of the amide
function acidity.[35] A methoxide group could substitute the
[a] Reaction took 1 h. [b] Tosylbenzylamine (17%) was isolated. [c] Sul-
fonamide (90%) was obtained.
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M. Malacria et al.
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Entries 1, 2, and 4 7 in Table 4 show that the reaction
works well with primary alcohols, with the exception of
benzyl alcohol. The only isolated product was tosylbenzyl-
amine in low yield. This product arises from the known rear-
rangement of sulfonimidates.[45] The reaction proved very
sensitive to steric hindrance: while the rate diminished with
2-propanol (Table 4, entry 3), no reaction took place in tert-
butyl alcohol (Table 4, entry 8). This could be explained by
the impossible solvolysis of iodosobenzene, which is an in-
soluble polymeric material: when alcohols are too sterically
demanding, dialkoxyiodosobenzene could not be formed
and the reaction could not proceed.
The main limitation was, of course, the amount of alcohol
needed for the transformation. While this posed no problem
when methanol or ethanol were used, it became more trou-
blesome when a more expensive alcohol was targeted. We
reasoned that if the limiting step was the solvolysis of the
starting material, we should be able to reduce the number
of equivalents of alcohol used, ideally lowering it to two.
Therefore we switched to acetonitrile, anticipating that its
polarity could allow the formation of the dialkoxy adducts.
Indeed we observed the formation of the desired sulfonimi-
dates, albeit in slightly lower yields. Sulfonamide–arising
from the standard oxidation of sulfinamides–was also iso-
lated, and this accounts for the loss in yield (Table 5).
would not allow them to be used as solvents (e.g. Table 5,
entry 7). Propanediol led to a crystalline compound which
was unambiguously proven to be the sulfonimidate by X-ray
diffraction (Table 5, entry 8). The ethyl compound was also
prepared according to the Roy method; both reactions gave
the same product. As stated before, the only observed by-
products were sulfonamides. Lowering the amount of alco-
hol below three equivalents leads to an increase of oxidation
at the expense of the desired product. This result is still in-
teresting, since–to the best of our knowledge–no such oxi-
dation involving iodine(iii) derivatives has been reported.
The scope of the oxidation is presented below. Aromatic al-
cohols are not suitable: degradation occurs presumably
through electrophilic aromatic substitution (Table 5,
entry 11).[7,8]
We then turned our attention to the asymmetric version
of this reaction (Table 6). Before that, we made sure our re-
action was working with other substituents on sulfur and,
most importantly, on nitrogen. The reactions work well in
both cases and are versatile (Table 6, entries 1, 3 and 5). For
better comparison of the stereochemical outcomes, we car-
ried out the reactions in methanol as solvent. As before, re-
actions work in acetonitrile, but are slower and accompanied
by various amounts of oxidized by-products: 9 yielded 52%
of 10 and 22% of 26, while 13 yielded 71% of 14 and 7%
of 27. However, the reaction failed with N-acylsulfinamide
21 (see Table 7 for formula). In this case, only oxidation
took place (see below). Sulfinamides are chiral compounds.
Our first step was to prepare them enantiomerically pure
and check the fate of the stereogenic sulfur atom. The pro-
posed mechanism of the rearrangement of sulfinyl hydroxyl-
amines by Maricich and co-workers involves a dissociative
step to give a nitrenium cation.[36] One could thus have an-
ticipated a loss of stereochemical information during the re-
arrangement (Scheme 5).
Table 5. Preparation of sulfonimidates (2): Acetonitrile as solvent.
Entry
R
Sulfonimidate Yield [%] 8, Yield [%]
1
2Et
3
Me
7a
7b
7c
85
5
23
30
67
iPr
39[a]
4
5
6
7d
7e
7 f
60
76
71
36
21
13
7
7 g
57
27
8
9
7h
7i
60
95
1
3
10
11
7j
6211
[b]
Scheme 5. Proposed mechanism for the rearrangement of N-alkoxy-
benzenesulfinamides.
[b]
Ph
[a] Molecular sieves 3 ä were also used. [b] Immediate degradation was
observed.
We were rather pleased to observe that, when carried out
starting from (S)-9 [or (S)-11], the reaction led to the corre-
sponding sulfonimidates with 62% ee [72% ee, Table 6, en-
tries 2and 4, respectively). Products ( R)-10 and (R)-12 were
resubmitted to the reaction conditions: they neither isomer-
ize nor react in the reaction vessel or on silica for periods of
time much longer than the reaction time (but eventually
slowly tautomerize into sulfonamides[45]). Thus, maybe the
mechanism is slightly different than the one inspired from
the literature. To gain more information, we diastereoselec-
tively prepared sulfinamides 15, 17, and 19, which bear
The reaction was smooth except in the case of secondary
alcohols (Table 5, entry 3), which led to a dramatic drop in
yield of the desired product. We imagined that the water re-
leased during the formation of the dialkoxyiodosobenzene
was accountable for this loss, but the addition of molecular
sieves in the reaction mixture was not entirely conclusive. It
may sometimes slightly improve yields, but not as a general
rule.
Nonetheless, the result was quite satisfactory for expen-
sive primary alcohols or for those, whose physical properties
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Iodine(iii)-Mediated Preparations of Nitrogen-Containing Sulfur Derivatives
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between A
(Scheme 2) and D, the latter
would not lead to deprotona-
tion, but rather rearrange via a
six-electron transition state to
afford sulfonimidates with re-
Table 6. Stereochemical issues associated with the sulfonimidate synthesis.
pKa
values
Entry
Sulfinamide
Sulfonimidate[a]
Yield [%][b]
74
1
9
10
2
3
4
5
(S)-9[c]
11
(R)-10
12
96, 62% ee[d]
tention
of
configuration
(path a). Sulfinamides are easily
oxidized by electrophilic oxi-
dants, which make their lone
pair relatively nucleophilic.[47]
Alternatively, D could undergo
a competitive three-atom rear-
rangement similar to the one
evidenced by Reggelin and co-
workers (path b).[61] In Regge-
lin×s case, the oxidation of sulfi-
namides by tert-butyl hypo-
chlorite leads to a sulfonimidoyl
chloride by initial N-halogena-
tion, which is subsequently sub-
stituted by the alcohol with in-
version.[42] In our case, the in-
termediate sulfonimidoyl iodo-
nium derivative would probably
be configurationnally labile
(contrary to chlorides, bromides
72
(S)-11[c]
13
(R)-12
14
71, 72% ee[d]
100[e]
6
7
8
15
17
19
16
18
20
89, 81:19 ds[f]
90, 88:12ds [f]
73, 73:22 ds[f]
[a] Only the major product is shown. [b] All reactions were run in methanol. [c] 100% ee, determined by
chiral HPLC. [d] Determined by chiral HPLC. [e] Enantiomers could not be separated. [f] Determined by
are
not
configurationnally
1
400 MHz H NMR spectroscopy.
chiral auxiliaries on the nitrogen center (Table 6, entries 6
8). Amazingly, the chiral auxiliaries have no effect on the se-
lectivity: sulfonimidates 16, 18, and 20 are cleanly isolated
with essentially the same selectivities as before. Once again,
those products do not isomerize or tautomerize during the
reaction. We were able to isolate a crystal of 16, whose
structure determined by X-ray crystallography indicated
that the reaction mainly occurred with retention of configu-
ration (Figure 1).
Scheme 6. Revised mechanism for the preparation of sulfonimidates.
stable), and racemize before trapping by methanol, presum-
ably with inversion too. Thus, if some of the material fol-
lowed this reaction path, there would be a loss in ee. Anoth-
er possibility is that some competitive reaction occurs fol-
lowing the dissociative pathway proposed by Maricich and
co-workers, contributing to the drop in the ee value.
Figure 1. X-ray structure of sulfonimidate 16.
Oxidation of sulfinamides: When the reactions were run in
acetonitrile, the sole by-product was that from the oxidation.
To the best of our knowledge, hypervalent iodine reagents
had never been used for such a transformation in spite of
the discrete reducing power of sulfinamides. Traditionally,
This prompted us to propose a revised mechanism and a
model accounting for the overall retention of configuration
(Scheme 6). The reaction would proceed as proposed earlier
through intermediate D. Because of the difference in the
911
Chem. Eur. J. 2004, 10, 906 916
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. Malacria et al.
FULL PAPER
meta-chloroperoxybenzoic acid (MCPBA) is the reagent of
choice.[47] However, since it is important to diversify the ar-
senal available to the chemist, our previous observation
prompted us to examine this mild oxidation (Table 7).
important variation of reactivity between sulfinamides and
sulfonamides, which can be explained by their difference in
pKa value. While sulfonamides lead to the corresponding
iminoiodinanes, the parent sulfinamides have a very differ-
ent behavior and yield sulfonimidates. The preparation has
a fair degree of retention, which is independent of the sub-
stituents on nitrogen. We have proposed a mechanism ac-
counting for these findings. Work to further investigate this
model is underway (such as the influence of the solvent, al-
cohols and aromatic group on the iodine) and will be report-
ed in due course.
Table 7. PhI=O-mediated oxidation of sulfinamides to sulfonamides.
Entry
Sulfinamide
Sulfonamide
Yield [%]
1
6
8
84
2
3
21
22
24
82
81
23
15
Experimental Section
General remarks: Reactions were carried out under an inert gas, with
magnetic stirring and degassed solvents when necessary. HPLC grade al-
cohols were purchased from various manufacturers and were used with-
out further purification. MeCN was dried and distilled from CaH2. Thin-
layer chromatography (TLC) was performed on Merck 60 F254 silica gel.
Merck Geduran SI 60 A silica gel (35 70 mm) was used for column chro-
matography. The melting points reported were measured with a Reichert
hot-stage apparatus and are uncorrected. IR spectra were recorded with
a Perkin-Elmer 1420 and a Bruker Tensor 27 ATR diamant PIKE spec-
trometer. 1H NMR [13C NMR] spectra were recorded at room tempera-
ture with 200 MHz [50 MHz] Bruker AC 200 and ARX 200 spectrome-
ters, 250 MHz [62.5 MHz] Bruker ARX 250 and 400 MHz [100 MHz]
Bruker ARX 400 and AVANCE 400 spectrometers. Chemical shifts are
given in ppm, referenced to the residual proton resonances of the sol-
vents (d=7.26 or 77.0, respectively, for CDCl3). Coupling constants (J)
are given in Hertz (Hz). Elemental analyses were performed by the Serv-
ice Rÿgional de Microanalyse de L’Universitÿ Pierre et Marie Curie and
Exact Mass were recorded at ICSN (CNRS, Gif) on a LCT micromass
apparatus (Electrospray source). Optical rotatory powers were recorded
on a Perkin Elmer 343 device. The enantiomeric excess (ee) values were
measured by chiral HPLC (Waters 1525 binary with a Waters 2487 detec-
tor) using a CHIRALPAK AD-H stationary phase. The X-ray diffraction
study was carried out at the Laboratoire de chimie inorganique et matÿri-
aux molÿculaires (UMR 7071 CNRS, UPMC). CCDC-219334 contains
the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.can.ac.uk/conts/retrieving.html (or
from the Cambridge Crystallographic Center, 12Union Road, Cambridge
CB21EZ, UK; Fax: (+44)1223-336033; or deposit@ccdc.cam.ac.uk). The
starting sulfinamides were either commercially available and used with-
out further purification or were prepared following reported proce-
dures.[50, 51]
4
25
78
5
6
7
9
26
27
28
82
80
81
13
11
The best yields were attained when water was added to
the mixture of iodosobenzene and sulfinamide in acetoni-
trile. The reaction proved to be very general: the sulfon-
amides were isolated in good yields (typically ꢀ80%) with
a broad range of substituents. Their structures were assessed
by comparison with published data. Both aryl and alkylsulfi-
namides work (compare Table 7, entries 1 6). Many differ-
ent groups can be attached on the nitrogen center, even acyl
groups (Table 7, entry 2), and the reaction does not seem
sensitive to steric hindrance (compare, for example, Table 7,
entries 9 and 11). This contrasts with the sulfonimidates
preparation, and this explains the by-products: the oxidation
would have a fairly constant rate, so whenever the sulfoni-
midate formation is quick enough, no oxidation is observed,
while it becomes appreciable as soon as the former rate de-
creases.
We next looked for other oxidizing agents. The Koser re-
agent PhI(OMe)OTs[48] also does the job with comparable
yields (100% and 69% for the oxidation of 6 and 15, respec-
tively). It was previously used to oxidize sulfides. Sulfoxides
are usually deemed not to be nucleophilic enough to react
with this type of reagents.[49] Sulfinamides seem to be in be-
tween. We did not pursue the study further because the
yields are similar, but the reagent is more difficult to obtain
and leads to the formation of an additional by-product
(methyl p-toluenesulfonate), which has to be removed from
the reaction mixture.
General procedure 1 (GP1): Preparation of N-Tosyl sulfoximines: Sulfox-
ides 3a j (0.5 mmol; 1 equiv) were added to a solution of Cu(OTf)2
(0.05 mmol; 10 mol%; 18 mg) in acetonitrile (3 mL) at room tempera-
ture. PhI=NTs (0.55 mmol; 1.1 equiv; 205 mg) was then added dropwise
in one batch. The reaction was monitored by the rapid disappearance of
the yellowish powder from the reaction mixture, which turned homoge-
neous and green generally after two minutes. Acetonitrile was removed
in vacuo and the crude material was purified by flash chromatography on
silica gel to yield sulfoximines 4a j.
General procedure 2 (GP2): Preparation of N-Mesyl sulfoximines: Sulf-
oxides
3 b,d,f,j,k (0.5 mmol; 1 equiv) were added to a solution of
Cu(OTf)2 (0.05 mmol; 10 mol%; 18 mg) in acetonitrile (3 mL) at room
temperature. PhI=NMs (0.65 mmol; 1.3 equiv; 193 mg) was then added
dropwise in one batch. MeCN was removed in vacuo and the crude mate-
rial was purified by flash chromatography on silica gel to yield sulfoxi-
mines 5b,d,f,j,k.
General procedure 3 (GP3): Preparation of sulfonimidates (alcohol as
solvent): PhI=O[52] (0.75 mmol; 1 equiv; 165 mg) was added at room tem-
perature to a solution of sulfinamide (0.75 mmol; 1 equiv; 116 mg) in al-
cohol (2mL). After completion (ranging from 15 min to overnight), the
excess alcohol was removed in vacuo. The crude mixture was purified by
flash chromatography.
Conclusion
Hypervalent iodine derivatives are good reagents for prepar-
ing nitrogen-containing sulfur(vi) products. We evidenced an
912
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 906 916

Iodine(iii)-Mediated Preparations of Nitrogen-Containing Sulfur Derivatives
906 916
General procedure 4 (GP4): Preparation of sulfonimidates in acetonitrile:
Alcohol (2.25 mmol, 3 equiv) and PhI=O (0.75 mmol; 1 equiv; 165 mg)
AB, J=12Hz, 1H; =CCHH), 4.76 (B of AB, J=12Hz, 1H; =CCHH),
7.24 (d, J=8.1 Hz, 2H; arom.), 7.51 7.55 (m, 2H; arom.), 7.60 7.63 (m,
1H; arom.), 7.83 (d, J=8.2Hz, 2H; arom.), 8.10 ppm (d, J=8.1 Hz, 2H;
arom.); 13C NMR (100 MHz, CDCl3): d=21.6 (Tol), 23.3 (=CMe), 25.0 (=
CMe), 27.0 (=CCH2), 126.7 (CH arom.), 127.9 (CH arom.), 129.3 (CH
arom.), 129.4 (CH arom.), 134.0 (CH arom.), 139.0, 140.7, 142.9, and
145.2(4 C arom. and =CCH3), 157.6 ppm (=CCH2); C18H2OBrNO3S2
(442.4): cacld. C 48.87, H 4.56, N 3.17; found: C 48.89, H 4.64, N 3.15.
were added at room temperature to
a solution of sulfinamide
(0.75 mmol; 1 equiv; 116 mg) in MeCN (2mL). After completion (gener-
ally 1 h), the solvent was evaporated. The crude mixture was purified by
flash chromatography. When diols were used, the evaporated mixture
was diluted in CH2Cl2 and washed with water to get rid of excess alcohol
before chromatography.
General procedure 5 (GP): Oxidation of sulfinamides: PhI=O (0.5 mmol;
1 equiv; 110 mg) was added at room temperature to a solution of sulfin-
amide (0.5 mmol) and water (5.0 mmol; 10 equiv; 90 mL) in acetonitrile
(1.5 mL). After completion, the solvent was removed in vacuo. The crude
mixture was purified by flash chromatography.
4 g: Following GP1, sulfoximine 4 g was isolated (petroleum ether/ethyl
acetate 70:30; 203 mg; 89%) as a white solid. M.p. 117 1198C; [a]D25
=
1
156.8 (c=1, CHCl3); IR (neat): n˜ =3030, 1620, 1600, 1070 cmÀ1; H NMR
(200 MHz, CDCl3): d=1.87 (s, 3H; =CCH3), 2,03 (s, 3H; =CCH3), 2.37
(s, 3H; Tol), 2.40 (s, 3H; Tol), 4.47 (B of AB, J=12.3 Hz, 1H; =CCHH),
4.73 (A of AB, J=12.3 Hz, 1H; =CCHH), 7.21 7.32 (m, 4H arom.,
S(O)Tol), 7.81 (d, J=8.4 Hz, 2H arom. SO 2Tol), 7.95 ppm (d, J=8.4 Hz,
2H arom. SO 2Tol); 13C NMR (50 MHz, CDCl3): d=21.6 (CH3), 21.7
(CH3), 23.3 (CH3), 25.0 (CH3), 27.1 (=CCH2), 126.7 (CH, arom.), 128.0
(CH, arom.), 129.3 (CH, arom.), 130.0 (CH, arom.), 133.8 (C), 136.0 (C),
140.9 (C), 142.8 (C), 145.2 (C), 157.1 ppm (C); elemental analysis (%)
for C19H22BrNO3S2 (456.42): calcd: C 50.00, H 4.86, N 3.07; found: C
49.76, H 4.99, N 3.38.
4a: Following GP1, sulfoximine 4a was isolated (petroleum ether/ethyl
acetate 50:50; 163 mg; 96%) as a white solid. M.p. 79 818C; IR (neat):
n˜ =3000, 2940, 2220, 1575 cmÀ1 1H NMR (400 MHz, CDCl3): d=1.28 (t,
;
J=7.4 Hz, 3H; CH2Me), 2.41 (s, 3H; Tol), 2.48 (s, 3H; Tol), 3.53 (q, J=
7.4 Hz, 2H; CH2Me), 7.27 (d, J=8.1 Hz, 2H arom.), 7.41 (d, J=8.1 Hz,
2H arom.), 7.86 ppm (d, J=7.9 Hz, 4H arom.); 13C NMR (50 MHz,
CDCl3): d=7.2(CH Me), 21.3 (Tol), 21.5 (Tol), 52.7 (CH2Me), 126.4 (CH
2
arom.), 128.2 (CH arom.), 129.0 (CH arom.), 130.0 (CH arom.), 132.3 (C
arom.), 140.7 (C arom.), 142.4 (C arom.), 145.4 ppm (C arom.); elemental
analysis (%) for C16H19O3S2 (337.45): calcd: C 56.95, H 5.67, N 4.15,
found: C 56.79, H 5.82, 4.27.
4h: Following GP1, sulfoximine 4h was isolated (petroleum ether/ethyl
acetate 70:30; 188 mg; 75%) as a white solid. M.p. 628C; [a]2D5 =À49.9
(c=0.73, CHCl3); IR (neat): n˜ =3040, 2350, 1600, 1080 cmÀ1 1H NMR
;
(200 MHz, CDCl3): d=2.37 (s, 3H; CH3), 2.44 (s, 3H; CH3), 4.18 (B of
AB, J=12.3 Hz, 1H; =CCHH), 4.44 (A of AB, J=12.3 Hz, 1H; =
CCHH), 7.22 7.67 (m, 9 H arom., Ph+S(O)Tol), 7.83 7.98 ppm (m, 5H;
arom. SO2Tol + =CH); 13C NMR (62.5 MHz, CDCl3): d=22.0 (CH3),
22.1 (CH3), 24.0 (=CCH2), 127.1 (CH, arom.), 129.2 (CH, arom.), 129.6
(CH, arom.), 129.7 (CH, arom.), 130.6 (CH, arom.), 130.9 (CH, arom.),
131.5 (CH, arom.), 132.7 (C), 134.9 (C), 136.7 (C), 141.1 (C), 143.4 (C),
144.1 (CHPh), 146.2ppm (C); elemental analysis (%) for C 23H22BrNO3S2
(504.47): calcd: C 54.76, H 4.40, N 2.78; found: C 54.72, H 4.44, N 2.59.
4b: Following GP1, sulfoximine 4b was isolated (124 mg; 91%). Analy-
ses were similar to those described by Horner et al.[53] 1H NMR
(400 MHz, CDCl3): d=2.33 (m, 4H; SCH2CH2), 2.41 (s, 3H; Tol), 3.29
(m, 2H; SCH2), 3.79 (m, 2H; SCH2), 7.28 (d, J=8.4 Hz, 2H; arom.),
7.87 ppm (d, J=8.4 Hz, 2H; arom.).
4c: Following GP1, sulfoximine 4c was isolated (petroleum ether/ethyl
acetate 70:30; 194 mg; 96%) as a colorless oil. IR (neat): n˜ =3348, 3262,
3061, 2934, 2858, 1616, 1597 cmÀ1 1H NMR (200 MHz, CDCl3): d=1.32
;
1.91 (m, 6H; CH2(CH2)3CH2), 2.45 (s, 3H; Tol), 2.50 (s, 3H; Tol), 2.12
2.82 (m, 4H; =CCH2), 7.29 (d, J=8.5 Hz, 2H; arom.), 7.39 (d, J=8.5 Hz,
2H; arom.), 7.66 7.92ppm (m, 4H; arom.); 13C NMR (50 MHz, CDCl3):
d=21.6 (Tol), 21.7 (Tol), 25.4 (CH2), 26.9 (CH2), 28.2 (CH2), 29.7 (CH2),
37.6 (CH2), 122.8 (=CH), 126.7 (CH arom.), 127.5 (CH arom.), 129.2
(CH arom.), 130.0 (CH arom.), 137.8 (C), 141.1 (C), 142.6 (C), 144.6 (C),
164.6 ppm (C); C21H25NO3S2 (337.45): HRMS calcd. for C21H25NNaO3S2
[M+Na]+ 426.1174; found 426.1138.
4i: Following GP1, sulfoximine 4i was isolated (petroleum ether/ethyl
acetate 75:25; 173 mg; 89%) as a colorless oil. IR (neat): n˜ =3064, 2959,
2930, 2197, 1595 cmÀ1 1H NMR (400 MHz, CDCl3) : d=0.84 (t, J=
;
7.1 Hz, 3H; CH2CH3), 1.24 1.53 (m, 4H; CH2CH2Me), 2.32 (t, J=7.4 Hz,
2H; ꢁCCH2), 2.36 (s, 3H; Tol), 2.39 (s, 3H; Tol), 7.25 (d, J=7.9 Hz, 2H;
arom.), 7.33 (d, J=8.4 Hz, 2H; arom.), 7.87 (d, J=7.9 Hz, 2H; arom),
7.87 ppm (d, J=8.4 Hz, 2H; arom); 13C NMR (100 MHz, CDCl3): d=
13.4 (CH2CH3) 19.1 (CH2), 21.6 (CH2), 21.7 (Tol), 22.0 (Tol), 28.8 (ꢁ
CCH2), 75.5 (CꢁCS), 103.2(C ꢁCS), 127.0 (CH arom.), 127.3 (CH arom.),
129.3 (CH arom.), 130.2 (CH arom.), 136.7 (C arom.), 140.3 (C arom.),
143.0 (C arom.), 146.0 ppm (C arom.); elemental analysis (%) for
C20H23NO3S2 (389.53): calcd: C 61.67, H 5.95, N 3.60; found: C 61.57, H
6.08, N 3.50.4j: Sulfoximine 4j is identical to 4i. [a]2D5 78.3 (c=1.1,
CHCl3).
4d: Following GP1, sulfoximine 4d was isolated (petroleum ether/ethyl
acetate 50:50; 85 mg; 53%) as a white solid. M.p. 1368C; IR (neat): n˜ =
3200, 1580, 1150 cmÀ1 1H NMR (400 MHz, CDCl3): d=2.40 (s, 3H;
;
CH3), 6.20 (br d, J=9.7 Hz, 1H; =CHH), 6.48 (br d, J=16.3 Hz, 1H; =
CHH), 6.84 (dd, J=16.3, 9.7 Hz, 1H; =CHS), 7.26 (d, J=8.1 Hz, 2H;
arom.), 7.56 7.69 (m, 3H; arom.), 7.86 (d, J=8.1 Hz, 2H; arom.), 7.96
7.98 ppm (m, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=21.9 (CH3),
127.0 (CH arom.), 128.4 (CH arom.), 129.7 (CH arom.+CH2), 130.1 (CH
arom.), 134.7 (CH arom. or CH=CH2), 137.7 (C arom.), 137.9 (CH arom.
or CH=CH2), 141.1 (C arom.), 143.3 ppm (C arom.); elemental analysis
(%) for C15H15NO3S2 (321.42): calcd: C 56.05, H 4.70, N 4.36; found: C
55.88, H 4.75, N 4.37.
5b: Following GP2, sulfoximine 5b was isolated (petroleum ether/ethyl
acetate 20:80; 94 mg; 95%) as a white solid. M.p.: 93 958C; IR (neat):
n˜ =3010, 2700, 2340, 1055 cmÀ1 1H NMR (400 MHz, CDCl3): d=2.17
;
2.23 (m, 4H; CH2CH2S), 2.97 (s, 3H; Me), 3.20 3.25 (m, 2H; CH2S),
3.58 3.61 ppm (m, 2H; CH2S); 13C NMR (100 MHz, CDCl3): d=23.2
(CH2CH2S), 45.0 (Me), 54.2ppm (CH 2S); elemental analysis (%) for
C5H11NO3S2 (197.28): calcd: C 30.44, H 5.62, N 7.10; found: C 30.46, H
5.73, N 7.16.
4e: Following GP1, sulfoximine 4e was isolated (petroleum ether/ethyl
acetate 80:20; 161 mg; 72%) as a white solid. M.p. 116 1188C; [a]2D5 =77
(c=1.1, CHCl3); IR (neat): n˜ =1598, 1230, 1075, 1051 cmÀ1 1H NMR
.
5d: Following GP2, sulfoximine 5d was isolated (petroleum ether/ethyl
acetate 60:40; 86 mg; 70%) as a white solid. M.p.: 97 988C; IR (neat):
(400 MHz, CDCl3): d 1.31 1.36 (m, 18H; Me2CH), 2.47 (s, 3H; Tol), 2.98
(sept., J=7.1 Hz, 1H; p-CHMe2), 4.21 (sept., J=7.1 Hz, 2H; m-CHMe2),
6.23 (d, J=9.7 Hz, 1H; =CHH), 6.36 (d, J=16.3 Hz, 1H; =CHH), 7.28
(s, 2H; H arom.), 7.28 7.35 (m, 1H; =CH), 7.35 (d, J=8.7 Hz, 2H; arom.
Tol), 7.95 ppm (d, J=8.7 Hz, 2H; arom. Tol); 13C NMR (100 MHz,
CDCl3): d=21.6 (Tol), 23.6 (Me), 24.3 (Me), 24.9 (Me), 29.5 (CHMe2),
34.3 (CHMe2), 124.8 (CH arom.), 126.8 (CH arom.), 127.4 (=CH2), 129.3
(CH arom.+C arom.), 140.7 (CHS), 141.4 (C arom.), 142.7 (C arom.),
151.3 (C arom.), 154.6 ppm (C arom.); elemental analysis (%) for
C24H33NO3S2 (447.66): calcd: C 64.39, H 7.43, N 3.13; found: C 64.15, H
7.68, N 3.11.
n˜ =3020, 2700, 2350, 1085 cmÀ1 1H NMR (400 MHz, CDCl3): d=3.09 (s,
;
3H; Me), 6.19 (dd, J=9.7, 1.5 Hz, 1H; CHH=CH), 6.45 (dd, J=16.3,
1.5 Hz, 1H; CHH=CH), 6.81 (dd, J=16.3, 9.7 Hz, 1H; CH2=CH), 7.54
7.67 (m, 3H; arom.), 7.92 7.95 ppm (m, 3H; arom.); 13C NMR
(100 MHz, CDCl3): d=45.5 (Me), 128.0 (CH arom.), 129.8 (=CH2), 129.9
(CH arom.), 134.6 (CH arom. or CH=CH2), 137.1 (C arom.), 137.3 ppm
(CH arom. or CH=CH2); elemental analysis (%) for C9H11NO3S2
(245.32): calcd: C 44.06, H 4.52, N 5.71; found: C 44.07, H 4.68, N 5.74.
5 f: Following GP2, sulfoximine 5 f was isolated (petroleum ether/ethyl
acetate 60:40; 128 mg; 70%) as a yellowish solid. M.p.: 97 998C; IR
4 f: Following GP1, sulfoximine 4 f was isolated (petroleum ether/ethyl
acetate 60:40; 201 mg; 91%) as a white solid. M.p. 107 1098C; IR (neat):
1
(neat): n˜ =3050, 1610, 1090 cmÀ1; H NMR (400 MHz, CDCl3): d=2.00 (s,
n˜ =1598, 1226, 1150, 1086, 1018 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=
3H; =CMe), 2.10 (s, 3H; =CMe), 3.18 (s, 3H; MeSO2), 4.49 (A of AB,
J=12.2 Hz, 1H; =CCHH), 4.76 (B of AB, J=12.2 Hz, 1H; =CCHH),
1.89 (s, 3H; =CMe), 2.06 (s, 3H; =CMe), 2.39 (s, 3H; Tol), 4.49 (A of
913
Chem. Eur. J. 2004, 10, 906 916
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. Malacria et al.
FULL PAPER
7.59 7.70 (m, 3H; arom.) 8.16 8.19 ppm (m, 2H; arom.); 13C NMR
(100 MHz, CDCl3): d=23.7 (=CMe), 25.4 (=CMe), 27.2 (CH2), 45.9
(CH3SO2), 128.2 (CH arom.), 129.8 (CH arom.), 133.7 (C arom. or =
CMe), 134.5 (CH arom.), 139.4 (=CMe or C arom.), 157.9 ppm (=CCH2);
HRMS calcd for C12H14BrNO3S2 [M+Na, 79Br]+ 387.9653; found
387.9633, [M+Na, 81Br]+ 389.9571; found 389.9600.
21.5 (Tol), 69.9 (OCH2), 119.3 (=CH2), 127.6 (CH arom.), 129.6 (CH
arom.), 131.2( =CH), 135.0 (C arom.), 143.6 ppm (C arom.); elemental
analysis (%) for C10H13NO2S (211.28): calcd: C 56.85, H 6.20, N 6.63;
found: C 56.92, H 6.19, N 6.58.
7e: Following GP3 [or GP4], sulfonimidate 7e was isolated (petroleum
ether/ethyl acetate 70:30; 145 mg [110 mg]; 92% [70%]) as a pale yellow
oil. Following GP4, sulfonamide 8 (5 mg; 4%) was also obtained. IR
5j: Following GP2, sulfoximine 5j was isolated (petroleum ether/ethyl
acetate 80:20; 63 mg; 40%) as
a
colorless oil. [a]2D5 =63.6 (c=1.2,
(neat): n˜ =3280, 2220, 1590, 920 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
CHCl3); IR (neat): n˜ =2700, 2360, 2200, 1110 cmÀ1
;
1H NMR (400 MHz,
2.40 (s, 3H; Tol), 2.42 (t, J=2.1 Hz, 1H; ꢁCH), 3.43 (s, 1H; NH), 4 .51
(d, J=2.1 Hz, 2H; OCH2), 7.29 (d, J=8.3 Hz, 2H; arom.), 7.87 ppm (d,
J=8.3 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=21.7 (Tol), 56.7
(CH2), 76.5 (ꢁCH), 76.7 (CꢁCH), 128.0 (CH arom.), 129.8 (CH arom.),
134.5 (C arom.), 144.5 ppm (C arom.); elemental analysis (%) for
C10H11NO2S (209.27): calcd: C 57.39, H 5.30, N 6.69; found: C 57.38, H
5.28, N 6.71.
CDCl3): d=0.84 (t, J=7.6 Hz, 3H; CH2Me), 1.31 1.36 (m, 2H;
MeCH2CH2), 1.49 1.52(m, 2H; Me CH2CH2), 2.41 (t, J=7.1 Hz, 2H;
CH2Cꢁ), 2.44 (s, 3H; Tol), 3.14 (s, 3H; MeS), 7.38 (d, J=8.1 Hz, 2H;
arom.), 7.93 ppm (J=8.1 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3):
d=13.4 (CH2Me), 19.1 (MeCH2CH2), 21.8 (Tol), 22.0 (MeCH2CH2), 28.8
(CH2Cꢁ), 45.0 (MeS), 75.6 (CH2Cꢁ), 103.7 (ꢁCS), 127.3 (CH arom.),
130.4 (CH arom.), 136.5 (C arom.), 146.2ppm (C arom.); elemental anal-
ysis (%) for C14H19NO3S2 (313.44): calcd: C 53.65, H 6.11, N 4.47; found:
C 54.11, H 6.42, N 4.30.
7 f: Following GP3 [or GP4], sulfonimidate 7 f was isolated (petroleum
ether/ethyl acetate 80:20; 143 mg [91 mg]; 85% [53%]) as a colorless oil.
Following GP4, sulfonamide 8 (50 mg; 39%) was also obtained. IR
5k: Following GP2, sulfoximine 5k was isolated (petroleum ether/ethyl
acetate 70:30; 185 mg; 98%) as a white solid. M.p.: 154 1578C; IR
(neat): n˜ =3300, 2960, 1600, 730 cmÀ1 1H NMR (400 MHz, CDCl3): d=
;
2.31 (m, 2H; OCH2CH2), 2.39 (s, 3H; Tol), 3.30 (s, 1H; NH), 3.90
(m, 2H; OCH2), 4.09 (m, 2H; =CH2), 5.63 (m, 1H; =CH), 7.28 (d,
J=8.0 Hz, 2H; arom.), 7.85 ppm (d, J=8.0 Hz, 2H; arom.); 13C NMR
(100 MHz, CDCl3): d=21.6 (Tol), 33.3 (OCH2CH2), 68.5 (OCH2),
117.8 (=CH2), 127.7 (CH arom.), 129.6 (CH arom.), 133.1 (=CH), 135.1
(C arom.), 143.9 ppm (C arom.); elemental analysis (%) for C11H15NO2S
(neat): n˜ =3010, 1615, 1095 cmÀ1 1H NMR (400 MHz, CDCl3): d=0.96
.
0.99 (m, 2H; CH2 of c-Pr), 1.25 1.29 (m, 2H; CH2 of c-Pr), 1.81 1.84 (m,
1H; CH of c-Pr), 3.17 (s, 3H; MeSO2), 4.33 (A of AB, J=12.2 Hz, 1H; =
CCHH), 4.43 (B of AB, J=12.2 Hz, 1H; =CCHH), 6.64 (d, J=11.2Hz,
1H; =CH), 7.60 7.70 (m, 3H; arom.), 8.00 8.03 ppm (m, 2H; arom.);
13C NMR (100 MHz, CDCl3): d=10.8 (CH2 of c-Pr), 10.9 (CH2 of c-Pr),
14.0 (CH of c-Pr), 22.3 (=CCH2), 45.8 (MeSO2), 128.7 (CH arom.), 129.9
(CH arom.), 133.0 (C arom. or =CCH2), 134.7 (CH arom.), 138.0 (C
arom. or =CCH2), 155.9 ppm (=CH); elemental analysis (%) for
C13H16BrNO3S2 (378.31): calcd: C 41.27, H 4.26, N 3.70; found: C 41.19,
H 4.42, N 3.69.
(225.31): calcd:
N 6.04.
C 58.64, H 6.71, N 6.22; found: C 58.72, H 6.81,
7g: Following GP4, sulfonimidate 7 g was isolated (petroleum ether/ethyl
acetate 60:40; 130 mg; 57%) as a white oil, along with sulfonamide 8
(35 mg; 27%). IR (neat): n˜ =3300, 3040, 2950, 1600 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=1.59 1.63 (m, 4H; -(CH2)2-), 2.40 (s, 3H; Tol),
2.53 (t, J=6.9 Hz, 2H; CH2Ph), 3.19 (s, 1H; NH), 3.88 (m, 2H; OCH2),
7.09 (d, J=7.1 Hz, 2H; arom.), 7.16 (t, J=7.1 Hz, 1H; arom.), 7.24 (t,
J=7.1 Hz, 2H; arom.), 7.28 (d, J=8.1 Hz, 2H; arom.), 7.87 ppm (d, J=
8.1 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=21.6 (Tol), 27.3
(OCH2CH2), 28.6 (CH2CH2Ph), 35.3 (OCH2), 69.4 (CH2Ph), 125.9 (CH
arom.), 127.7 (CH arom.), 128.4 (CH arom.), 129.6 (CH arom.), 135.2 (C
arom.), 141.8 (C arom.), 143.9 ppm (C arom.); elemental analysis (%) for
C17H21NO2S (303.42): calcd: C 67.29, H 6.98, N 4.62; found: C 67.44, H
7.06, N 4.53.
7a: Following GP3 [or GP4], sulfonimidate 7a was isolated (petroleum
ether/ethyl acetate 70:30; 126 mg [118 mg]; 91% [85%]) as a white solid.
Following GP4, sulfonamide 8 (8 mg; 5%) was also obtained. M.p. 45
478C; IR (neat): n˜ =3300, 3020, 2905, 1180, 1040 cmÀ1
;
1H NMR
(400 MHz, CDCl3): d=2.35 (s, 3H; Tol), 3.36 (s, 1H; NH), 3.35 (s, 3H;
OMe), 7.25 (d, J=8.1 Hz, 2H; arom.), 7.81 ppm (d, J=8.1 Hz, 2H;
arom.); 13C NMR (100 MHz, CDCl3): d=21.3 (Tol), 55.3 (OMe), 127.6
(CH arom.), 129.4 (CH arom.), 133.9 (C arom.), 143.8 ppm (C arom.); el-
emental analysis (%) for C8H11NO2S (185.24): calcd: C 51.87, H 5.99, N
7.56; found: C 51.84, H 6.17, N 7.45.
7h: Following GP4, sulfonimidate 7h was isolated (petroleum ether/ethyl
acetate 20:80; 116 mg; 68%) as white crystals, along with sulfonamide 8
(3 mg; 1%). M.p. 52 548C; IR (neat): n˜ =3300, 2960, 2950, 1600,
7b: Following GP3 [or GP4], sulfonimidate 7b was isolated (petroleum
ether/ethyl acetate 70:30; 140 mg [100 mg]; 94% [67%]) as a pale yellow
oil. Following GP4, sulfonamide 8 (30 mg; 23%) was also obtained. IR
1
820 cmÀ1; H NMR (400 MHz, CDCl3): d=1.82(m, 2H; OCH 2CH2), 2.42
1
(neat): n˜ =3280, 2960, 1590 cmÀ1; H NMR (400 MHz, CDCl3): d=1.22 (t,
(s, 3H; Tol), 2.48 (t, J=5.6 Hz, OH), 3.34 (s, 1H; NH), 3.61 (m, 2H;
CH2OH), 4.08 (m, 2H; SOCH2), 7.31 (d, J=7.6 Hz, 2H; arom.),
7.86 ppm (d, J=7.6 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=
21.4 (Tol), 31.6 (OCH2CH2), 57.8 (CH2OH), 66.3 (SOCH2), 127.4 (CH
arom.), 129.5 (CH arom.), 134.8 (C arom.), 143.9 ppm (C arom.); elemen-
tal analysis (%) for C10H15NO3S (229.30): calcd: C 52.38, H 6.59, N 6.11;
found: C 52.51, H 6.57, N 6.18.
J=7.1 Hz, 3H; CH2Me), 2.41 (s, 3H; Tol), 3.20 (s, 1H; NH), 3.95 (m,
2H; OCH2), 7.29 (d, J=8.2Hz, 2H; arom.), 7.86 ppm (d, J=8.4 Hz, 2H;
arom.); 13C NMR (100 MHz, CDCl3): d=14.9 (CH2Me), 21.6 (Tol), 65.7
(OCH2), 127.7 (CH arom.), 129.6 (CH arom.), 135.3 (C arom.),
143.9 ppm (C arom.); NH3-CIMS m/z (%): 200 ([M+1]+, 14), 189 (100);
elemental analysis (%) for C9H13NO2S (199.27): calcd: C 54.25, H 6.58, N
7.03; found: C 54.17, H 6.87, N 6.75.
7i: Following modified GP4 (5 equiv alcohol), sulfonimidate 7i was iso-
lated (petroleum ether/ethyl acetate 70:30; 184 mg; 95%) as a colorless
oil, along with sulfonamide 8 (4 mg; 3%). IR (neat): n˜ =3250, 2900, 2840,
7c: Following GP3 [or GP4], sulfonimidate 7c was isolated (petroleum
ether/ethyl acetate 70:30; 115 mg [28 mg]; 73% [18%]) as a colorless oil.
Following GP4, sulfonamide 8 (84 mg; 74%) was also obtained. IR
1580 cmÀ1
;
1H NMR
(400 MHz,
CDCl3):
d=1.28
(m,
2H;
(neat): n˜ =3280, 2960, 2920, 1590, 740 cmÀ1 1H NMR (400 MHz, CDCl3:
;
CH2(CH2)3CH2), 1.40 (m, 2H; CH2(CH2)3CH2), 1.52(m, H2;
d=1.03 (d, J=6.2Hz, 3H; CH Me), 1.07 (d, J=6.2Hz, 3H; CH Me), 2.28
(s, 3H; Tol), 3.09 (s, 1H; NH), 4.46 (hept, J=6.2Hz, 2H; OCH), 7.16 (d,
J=8.2Hz, 2H; arom.), 7.74 ppm (d, J=8.2Hz, 2H; arom.); 13C NMR
(100 MHz, CDCl3): d=21.6 (Tol), 22.9 (CHMe), 23.9 (CHMe), 75.1
(OCH), 127.4 (CH arom.), 129.5 (CH arom.), 136.5 (C arom.), 143.6 ppm
(C arom.); elemental analysis (%) for C10H15NO2S (213.30): calcd: C
56.31, H 7.09, N 6.57; found: C 56.02, H 7.37, N 6.31.
CH2(CH2)3CH2), 2.34 (s, 3H; Tol), 3.09 (s, 1H; NH), 3.45 (t, J=6.4 Hz,
2H; CH2OH), 3.82(m, 2H; SO CH2), 7.24 (d, J=8.1 Hz, 2H; arom.),
7.78 ppm (d, J=8.1 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=
21.4 (Tol), 21.7 (CH2(CH2)3CH2), 28.5 (CH2(CH2)3CH2), 31.8
(CH2(CH2)3CH2), 61.9 (HOCH2), 69.3 (SOCH2), 127.4 (CH arom.), 129.5
(CH arom.), 134.9 (C arom.), 143.9 ppm (C arom.); elemental analysis
(%) for C12H19NO3S (257.35): calcd. C 56.00, H 7.44, N 5.44; found: C
55.58, H 7.58, N 5.31.
7d: Following GP3 [or GP4], sulfonimidate 7d was isolated (petroleum
ether/ethyl acetate 80:20; 112 mg [95 mg]; 71% [60%]) as a colorless oil.
Following GP4, sulfonamide 8 (47 mg; 36%) was also obtained. IR
7j: Following GP4, sulfonimidate 7j was isolated (petroleum ether/ethyl
acetate 70:30; 129 mg; 62%) as a colorless oil, along with sulfonamide 8
1
(neat): n˜ =3300, 2920, 1650, 1600, 780 cmÀ1; H NMR (400 MHz, CDCl3):
(14 mg; 11%). IR (neat): n˜ =3280, 1590 cmÀ1 1H NMR (400 MHz,
;
d=2.41 (s, 3H; Tol), 3.28 (s, 1H; NH), 4.39 (m, 2H; OCH2), 5.24 (m,
2H; =CH2), 5.79 (m, 1H; =CH), 7.30 (d, J=8.1 Hz, 2H; arom.),
7.87 ppm (d, J=8.1 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=
CDCl3): d=2.42 (s, 3H; Tol), 3.41 (t, J=6.1 Hz, 2H; CH2Br), 3.41 (s,
1H; NH), 4.14 (t, J=6.1 Hz, 2H; OCH2), 7.31 (d, J=8.6 Hz, 2H; arom.),
7.88 ppm (d, J=8.6 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=
914
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 906 916

Iodine(iii)-Mediated Preparations of Nitrogen-Containing Sulfur Derivatives
906 916
21.7 (Tol), 28.2 (CH2Br), 68.1 (OCH2), 127.7 (CH arom.), 129.8 (CH
arom.), 134.4 (C arom.), 144.4 ppm (C arom.).
(NCH), 123.9 (CH arom.), 124.4 (CH arom.), 125.5 (CH arom.), 125.8
(CH arom.), 126.3 (CH arom.), 128.4 (CH arom.), 129.1 (CH arom.),
129.6 (CH arom), 130.8 (C arom.), 134.1 (C arom), 138.9 (C arom.),
141.4 (C arom.), 142.7 ppm (C arom.); elemental analysis (%) for
C19H19NOS (339.43): calcd: C 73.75, H 6.19, N 4.53; found: C 73.74, H
6.16, N 4.46.
(R)-10: Following GP3 starting from sulfinamide (S)-9,[54] sulfonimidate
(R)-10 was isolated (petroleum ether/ethyl acetate 90:10; 164 mg; 96%)
as a colorless oil. [a]2D5 =À37 (c=1, CHCl3); IR (neat): n˜ =2920, 2850,
1450, 980, 810, 700 cmÀ1 1H NMR (400 MHz, CDCl3): d=0.92, (t, J=
;
7.4 Hz, 3H; CH2Me), 1.41 (m, 2H; CH2CH2Me), 1.60 (m, 2H;
CH2CH2Me), 2.40 (s, 3H; Tol), 3.19 (m, 1H; NCHH), 3.29 (m, 1H;
NCHH), 3.54 (s, 3H; OMe), 7.28 (d, J=8.1 Hz, 2H; arom.), 7.83 ppm (d,
J=8.1 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=13.9 (CH2Me),
20.4 (CH2CH2Me), 21.6 (Tol), 34.7 (CH2CH2Me), 42.5 (NCH2), 55.4
(OMe), 127.9 (CH, arom.), 129.2 (CH, arom.), 134.2 (C, arom.),
143.6 ppm (C, arom.); elemental analysis (%) for C10H15NO3S (229.30):
calcd: C 59.72, H 7.93, N 5.80; found: C 59.71, H 7.89, N 5.78.
20: Following GP3 starting from sulfinamide 19, sulfonimidate 20 was
isolated (petroleum ether/ethyl acetate 80:20; 186 mg; 73%) as a mixture
of two diastereomers in a 78:22 ratio (determined by 1H NMR spectros-
copy). The major diastereomer crystallized out but the minor diastereom-
er could not be obtained pure. Major diastereomer: colorless crystals.
M.p. 115 1178C; [a]2D5 =À96 (c=0.95, CHCl3). IR (neat): n˜ =3050, 2971,
1
2927, 1160, 983 cmÀ1; H NMR (400 MHz, CDCl3): d=1.73 (d, J=6.6 Hz,
3H; CHMe), 2.46 (s, 3H; Tol), 3.28 (s, 3H; OMe), 5.67 (q, J=6.6 Hz,
1H; CHMe), 7.34 (d, J=8.6 Hz, 2H; arom.), 7.49 7.58 (m, 3H; arom.),
7.78 (d, J=8.1 Hz, 1H; arom.), 7.90 (t, J=6.6 Hz, 2H; arom.), 7.96 (d,
J=8.2Hz, 2H; arom.), 8.35 ppm (d, J=8.6 Hz, 1H; arom.); 13C NMR
(100 MHz, CDCl3): d=21.7 (Tol), 27.0 (CHMe), 49.7 (NCH), 55.5
(OMe), 123.7 (CH arom.), 123.9 (CH arom.), 125.4 (CH arom.), 125.8
(CH arom.), 127.3 (CH arom.), 128.1 (CH arom.), 129.0 (CH arom),
129.7 (CH arom.), 130.5 (C arom), 134.1 (C arom), 134.4 (C arom.),
142.6 (C arom.), 143.8 ppm (C arom.); elemental analysis (%) for
C20H21NO2S (339.45): calcd: C 70.77, H 6.24, N 4.13; found: C 70.80, H
6.24, N 3.99. Minor diastereomer: 1H NMR (400 MHz, CDCl3): d=1.74
(d, J=6.6 Hz, CHMe), 2.41 (s, 3H; Tol), 3.63 (s, 3H; OMe), 5.67 (q, J=
6.6 Hz, 1H; CHMe), 7.28 (d, J=8.6 Hz, 2H; arom.), 7.49 7.58 (m, 3H;
arom.), 7.74 (d, J=8.1 Hz, 1H; arom.), 7.85 7.97 (m, 4H; arom.),
8.26 ppm (d, J=8.6 Hz, 1H; arom.); 13C NMR (100 MHz, CDCl3): d=
21.7 (Tol), 26.3 (CHMe), 49.9 (NCH), 55.5 (OMe), 123.4 (CH arom.),
123.8 (CH arom.), 125.3 (CH arom.), 125.7 (CH arom.), 127.4 (CH
arom.), 127.9 (CH arom.), 128.9 (CH arom), 129.6 (CH arom.), 130.6 (C
arom), 134.1 (C arom), 134.6 (C arom.), 142.4 (C arom.), 143.7 ppm (C
arom.).
(R)-12: Following GP3 starting from sulfinamide (S)-11,[55] sulfonimidate
(R)-12 was isolated (petroleum ether/ethyl acetate 90:10; 130 mg; 72%)
as a colorless oil. [a]2D5 =0 (c=1, CHCl3). IR (neat): n˜ =2970, 2870, 2360,
1
984 cmÀ1; H NMR (400 MHz, CDCl3): d=1.43 (s, 9H; tBu), 2.41 (s, 3H;
Tol), 3.52(s, 3H; OMe), 7.27 (d, J=8.6 Hz, 2H; arom.), 7.83 ppm (d, J=
8.6 Hz, 2H; arom.); 13C NMR (100 MHz, CDCl3): d=21.5 (Tol), 32.8
(CMe3), 55.3 (CMe3), 55.5 (OMe), 127.8 (CH, arom.), 129.4 (CH, arom.),
143.0 (C, arom.), 145.6 ppm (C, arom.); elemental analysis (%) for
C12H19NO2S (141.35): calcd: C 59.72, H 7.93, N 5.80; found: C 59.70, H
8.06, N 5.73.
14: Following GP3 starting from commercially available sulfinamide 13,
sulfonimidate 14 was isolated (petroleum ether/ethyl acetate 90:10;
113 mg; 100%) as
a
colorless oil. IR (neat): n˜ =3295, 2981, 2952,
1152cm À1
;
1H NMR (400 MHz, CDCl3): d=1.44 (s, 9H; tBu), 2.70 (s,
1H; NH), 3.75 ppm (s, 3H; OMe); 13C NMR (100 MHz, CDCl3): d=24.7
(CMe3), 52.3 (OMe), 52.7 ppm (CMe3); elemental analysis (%) for
C5H13NO2S (151.23): calcd: C 39.71, H 8.66, N 9.26; found: C 39.48, H
8.88, N 9.35.
16: Following GP3 starting from sulfinamide 15,[50] sulfonimidate 16 was
isolated (petroleum ether/ethyl acetate 90:10; 193 mg; 89%) as a mixture
of two diastereomers in a 81:19 ratio (determined by 1H NMR spectros-
copy). The major diastereomer crystallized out (it corresponds to the
enantiomer of the minor diastereomer of 18). M.p. 55 568C. [a]2D5 =À56
21: Sulfinamide 21[56] was prepared from sulfinamide 6 and trimethyl
acetic anhydride according to the literature (41% yield).[51] White solid.
M. p. 110 1128C; IR (neat): n˜ =3380, 3054, 2986, 1098 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=1.18 (s, 9H; tBu), 2.38 (s, 3H; Tol), 7.26 (d, J=
7.9 Hz, 2H; arom.), 7.47 (d, J=7.9 Hz, 2H; arom.), 8.40 ppm (bs, 1H;
NH); 13C NMR (100 MHz, CDCl3): d=21.41(Tol), 26.9 (Me of tBu), 39.6
(C of tBu), 124.8 (CH arom.), 129.9 (CH arom.), 132.6 (C arom.), 142.3
(C arom.), 179.1 ppm (C=O); elemental analysis (%) for C12H17NO2S
(239.33): calcd: C 60.22, H 7.16, N 5.85; found: C 60.10, H 7.26, N 6.00.
(c=0.99, CHCl3). IR (neat): n˜ =3054, 2986, 896 cmÀ1
;
1H NMR
(400 MHz, CDCl3): d=1.60 (d, J=6.6 Hz, 3H; CHMe), 2.45 (s, 3H; Tol),
3.32(s, 3H; OMe), 4.91 (q, J=6.6 Hz, 1H; CHMe), 7.27 (m, 4H; arom.),
7.53 (d, J=7.6 Hz, 2H; arom.), 7.93 ppm (d, J=8.1 Hz, 1H; arom.);
13C NMR (100 MHz, CDCl3): d=21.6 (Tol), 27.3 (CHMe), 52.6 (NCH),
55.3 (OMe), 126.3 (CH arom.), 126.7 (C arom.), 128.0 (CH arom.),
128.3 (CH arom.), 129.6 (CH arom.), 134.3 (C arom.), 143.6 (C
arom.), 146.7 ppm (C arom.); elemental analysis (%) for C16H19NO2S
22: Following GP5 starting from sulfinamide 21, sulfonamide 22 was iso-
lated (petroleum ether/ethyl acetate 90:10; 105 mg; 82%). Data corre-
sponded to those described in the literature.[57]
(289.39): calcd:
N 5.01.
C 66.40, H 6.62, N 4.84; found: C 66.22, H 6.70,
23: Sulfinamide 23 was synthesized from (À)-menthyl sulfinate and 2-
(tert-butyldimethylsilanyloxy)-1-phenyl-ethylamine according to the
above-mentioned reference (68% yield). White solid. M.p. 77 798C; IR
18: Following GP3 starting from sulfinamide 17,[50] sulfonimidate 18 was
isolated (petroleum ether/ethyl acetate 90:10; 198 mg; 90%) as a mixture
of two diastereomers in a 88:12ratio (determined by 1H NMR). The
major diastereomer was separated (it corresponds to the enantiomer of
the minor diastereomer of 16). Colorless oil. [a]2D5 =À60 (c=0.98,
(neat): n˜ =3209, 2954, 2928, 2856, 1088 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=À0.09 (s, 3H; SiMeMe), À0.05 (s, 3H; SiMeMe), 0.84 (s, 9H;
tBu), 2.30 (s, 3H; Tol), 3.78 (A of ABX, J=9.9, 5.1 Hz, 1H; CHHOSi),
3.91 (B of ABX, J=9.9, 4.6 Hz, 1H; CHHOSi), 4.45 (m, 1H; NCH), 5.05
(bs, 1H; NH), 7.08 7.26 (m, 7H; arom.), 7.46 ppm (d, J=8.6 Hz, 2H;
arom.); 13C NMR (100 MHz, CDCl3): d= À5.5 (SiMe), 18.3 (SiC), 21.3
(Tol), 25.9 (Me of t-Bu), 56.3 (CH2), 68.0 (NCH), 126.0 (CH arom.),
127.2 (CH arom.), 127.4 (CH arom.), 128.0 (CH arom.), 129.2 (CH
arom.), 140.4 (C arom.), 141.0 (C arom.), 141.2ppm (C arom.); elemental
analysis (%) for C21H31NO2SSi (389.63): calcd: C 64.73, H 8.02, N 3.59;
found: C 64.61, H 8.12, N 3.69.
CHCl3). IR (neat): n˜ =3062, 3027, 2971, 814 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d=1.58 (d, J=6.6 Hz, 3H; CHMe), 2.42 (s, 3H; Tol), 3.60 (s,
3H; OMe), 4.88 (q, J=6.6 Hz, 1H; CHMe), 7.21 7.33 (m, 5H; arom.),
7.46 (d, J=7.1 Hz, 2H; arom.), 7.87 ppm (d, J=8.1 Hz, 1H; arom.);
13C NMR (100 MHz, CDCl3): d=21.6 (Tol), 26.7 (CHMe), 52.9 (NCH),
55.3 (OMe), 126.3 (CH arom.), 126.6 (C arom.), 128.0 (CH arom.), 128.3
(CH arom.), 129.6 (CH arom.), 143.6 (C arom.), 146.7 ppm (C arom.); el-
emental analysis (%) for C16H19NO2S (289.39): calcd: C 66.40, H 6.62, N
4.84; found: C 66.22, H 6.70, N 5.01.
24: Following GP5 starting from substituted sulfinamide 23, sulfonamide
24 was isolated (petroleum ether/ethyl acetate 90:10; 164 mg, 81%) as a
colorless oil. IR (neat): n˜ =3278, 2929, 2857, 2361, 1090 cmÀ1 1H NMR
;
19: Sulfinamide 19 was prepared from (À)-menthyl sulfinate and (R)-
(+)-1-naphthyl-1-ethylamine according to the abovementioned procedure
(2.3 mmol scale; 217 mg; 28%). Colorless crystals. M.p. 141 1438C;
[a]2D5 =À2 6 c(=1, CHCl3); IR (neat): n˜ =3179, 3080, 2974, 2925,
(400 MHz, CDCl3): d=À0.10 (s, 3H; SiMeMe), À0.09 (s, 3H; SiMeMe),
0.81 (s, 9H; tBu), 2.73 (s, 3H; Tol), 3.57 (A of ABX, J=10.2, 6.8 Hz, 1H;
CHHOSi), 3.67 (B of ABX, J=10.2, 4.4 Hz, 1H; CHHOSi), 4.29 (m, 1H;
NCH), 5.33 (bs, NH), 7.15 7.21 (m, 7H; arom.), 7.58 ppm (d, J=8.0 Hz,
2H; arom.); 13C NMR (100 MHz, CDCl3): d=À5.5(SiMe), 18.3 (C), 21.6
(Tol), 25.9 (Me of tBu), 59.4 (CH2), 66.7 (NCH), 127.3 (CH arom.), 127.4
(CH arom.), 127.8 (CH arom.), 128.3 (CH arom.), 129.5 (CH arom.),
137.2(C arom.), 138.2(C arom.), 143.3 ppm (C arom.); elemental analy-
1087 cmÀ1 1H NMR (400 MHz, CDCl3): d=1.68 (d, J=6.6 Hz, 3H;
;
CHMe), 2.40 (s, 3H; Tol), 4.21 (s, 1H; NH), 5.52 (m, 1H; CHMe), 7.28
(d, J=8.1 Hz, 2H; arom.), 7.48 7.66 (m, 6H; arom.), 7.82 (d, J=8.1 Hz,
1H; arom.), 7.86 (d, J=7.6 Hz, 1H; arom.), 8.27 ppm (d, J=8.1 Hz, 1H;
arom.); 13C NMR (100 MHz, CDCl3): d=21.4 (Tol), 24.7 (CHMe), 50.7
915
Chem. Eur. J. 2004, 10, 906 916
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. Malacria et al.
FULL PAPER
sis (%) for C21H31NO3SSi (405.63): calcd: C 62.18, H 7.70, N 3.45; found:
C 62.04, H 7.85, N 3.60.
[25] J.-L. Liang, S.-X. Yuan, J.-S. Huang, W.-Y. Yu, C.-M. Che, , Angew.
Chem. 2002, 114, 3615 3618; Angew. Chem. Int. Ed. 2002, 41,
3465 3468.
[26] J. J. Fleming, K. W. Fiori, J. Du Bois, J. Am. Chem. Soc. 2003, 125,
2028 2029.
[27] Y. Tamura, T. Uchida, T. Katsuki, Tetrahedron Lett. 2003, 44, 3301
3303.
[28] C. S. Tomooka, E. M. Carreira, Helv. Chim. Acta 2002, 85, 3773
3784.
[29] K. M. Gillespie, E. J. Crust, R. J. Deeth, P. Scott, Chem. Commun.
2001, 785 786.
[30] P. Brandt, M. J. Soedergren, P. G. Andersson, P.-O. Norrby, J. Am.
Chem. Soc. 2000, 122, 8013 8020.
25: Following GP5 starting from substituted sulfinamide 15, sulfonamide
25 was isolated (petroleum ether/ethyl acetate 90:10; 107 mg; 78%).
Data corresponded to those described in the literature.[58,59]
26: Following GP5 starting from substituted sulfinamide 9, sulfonamide
26 was isolated (petroleum ether/ethyl acetate 90:10; 93 mg; 82%). Data
corresponded to those of an authentic sampled which could be purchased
from Aldrich.
27: Following GP5 starting from commercially available sulfinamide 13,
sulfonamide 27 was isolated (petroleum ether/ethyl acetate 90:10; 55 mg;
80%). Data corresponded to those described in the literature.[60]
28: Following GP5 starting from substituted sulfinamide 11, sulfonamide
28 was isolated (petroleum ether/ethyl acetate 90:10; 92mg; 81%). Data
corresponded to those described in the literature.[57]
[31] For a related approach using Boc-azide, see: T. Bach, C. Kˆrber,
Eur. J. Org. Chem. 1999, 1033 1039.
[32] During the publishing process, Craig×s group reported another ex-
ample of acetylenic sulfoximines and their use in intramolecular
Diels Alder reactions: D. Craig, V. G. De la Rosa, Synlett 2001,
761 764.
[33] C. R. Johnson, C. W. Schroeck, J. Am. Chem. Soc. 1973, 95, 7418
7423.
Acknowledgement
[34] R. A. Abramovitch, T. D. Bailey, T. Takaya, V. Uma, J. Org. Chem.
1974, 39, 340 345.
[35] To our knowledge, the pKa values of the two intermediates have not
been measured, but there is usually a four units gap between sulfo-
nyl and sulfinyl derivatives.
We thank Bernard Malÿzieux (UPMC) for the chiral HPLC measure-
ments, and Patrick Herson (UPMC) for the X-ray determinations. CNRS
and UPMC are gratefully acknowledged for financial support. D.L. and
K.S. thank the Ministõre de la Recherche for grants.
[36] T. J. Maricich, R. A. Jourdenais, T. A. Albright, J. Am. Chem. Soc.
1973, 95, 5831 5832.
[37] Roy, A. K. U.S. Patent 5233019, 1993.
[1] The Chemistry of Sulphonic Acids, Esters, and their Derivatives
(Eds.: S. Patai, Z. Rappoport), Wiley, Chichester, New York, 1991.
[2] The Chemistry of Sulphinic Acids, Esters and their Derivatives
(Ed. S. Patai), Wiley, New York, 1990.
[3] C. R. Johnson, Aldrichimica Acta 1985, 18, 3 10.
[4] M. Reggelin, C. Zur, Synthesis 2000, 1 64.
[38] A. K. Roy, G. T. Burns, G. C. Lie, S. Grigoras, J. Am. Chem. Soc.
1993, 115, 2604 2612.
[39] J. Y. Liang, W. N. Lipscomb, Substrate and inhibitor binding to
human carbonic anhydrase II: a theoretical study (Carbonic Anhy-
drase, Proc. Int. Workshop); (Eds.: F. Botre, G. Gros, B. T. Storey)
VCH, Weinheim, 1991, 50 64.
[5] B. Delouvriÿ, L. Fensterbank, E. LacÙte, M. Malacria, J. Am. Chem.
Soc. 1999, 121, 11395 11401.
[40] C. R. Johnson, E. U. Jonsson, A. Wambsgans, J. Org. Chem. 1979,
44, 2061 2065.
[6] V. Mouriõs, B. Delouvriÿ, E. LacÙte, L. Fensterbank, M. Malacria,
Eur. J. Org. Chem. 2002, 1776 1787.
[7] P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123 1178.
[8] V. V. Zhdankin, P. J. Stang, Chem. Rev. 2002, 102, 2523 2584.
[9] D. Mansuy, J. P. Mahy, A. Dureault, G. Bedi, P. Battioni, J. Chem.
Soc. Chem. Commun. 1984, 1161 1163.
[41] M. Reggelin, R. Welcker, Tetrahedron Lett. 1995, 36, 5885 5886.
[42] M. Reggelin, B. Junker, Chem. Eur. J. 2001, 7, 1232 1239.
[43] E. S. Levchenko, N. Y. Derkach, A. V. Kirsanov, Zh. Obshch. Khim.
1960, 30, 1971 1975.
[44] E. S. Levchenko, L. N. Markovskii, A. V. Kirsanov, Zh. Org. Khim.
1967, 3, 1273 1282.
[10] R. A. Eikey, S. I. Khan, M. M. Abu-Omar, Angew. Chem. 2002, 114,
3744 3747; Angew. Chem. Int. Ed. 2002, 41, 3592 3595.
[11] D. A. Evans, M. T. Bilodeau, M. M. Faul, J. Am. Chem. Soc. 1994,
116, 2742 2753.
[12] H. Takada, Y. Nishibayashi, K. Ohe, S. Uemura, C. P. Baird, T. J.
Sparey, P. C. Taylor, J. Org. Chem. 1997, 62, 6512 6518.
[13] J. F. K. Muller, P. Vogt, Tetrahedron Lett. 1998, 39, 4805 4806.
[14] C. Bolm, K. Muniz, N. Aguilar, M. Kesselgruber, G. Raabe, Synthe-
sis 1999, 1251 1260.
[45] B. C. Challis, J. N. Iley, J. Chem. Soc. Perkin Trans. 2 1985, 699 703.
[46] E. LacÙte, M. Amatore, L. Fensterbank, M. Malacria, Synlett 2002,
116 118.
[47] F. A. Davis, P. Zhou, G. V. Reddy, J. Org. Chem. 1994, 59, 3243
3245.
[48] G. F. Koser, P. B. Kokil, M. Shah, Tetrahedron Lett. 1987, 28, 5431
5434.
[49] K. R. Roh, K. S. Kim, Y. H. Kim, Tetrahedron Lett. 1991, 32, 793
796.
[15] C. Bolm, M. Kesselgruber, K. Muniz, G. Raabe, Organometallics
2000, 19, 1648 1651.
[50] R. Kluge, H. Hocke, M. Schulz, F. Schilke, Phosphorus, Sulfur and
Silicon 1999, 149, 179 206.
[16] M. J. Sodergren, D. A. Alonso, A. V. Bedekar, P. G. Andersson, Tet-
rahedron Lett. 1997, 38, 6897 6900.
[17] P. Dauban, R. H. Dodd, J. Org. Chem. 1999, 64, 5304 5307.
[18] S. Taylor, J. Gullick, P. McMorn, D. Bethell, P. C. B. Page, F. E. Han-
cock, F. King, G. J. Hutchings, J. Chem. Soc. Perkin Trans. 2 2001,
1714 1723.
[19] B. C. Schardt, C. L. Hill, Inorg. Chem. 1983, 22, 1563 1565.
[20] A. K. Mishra, M. M. Olmstead, J. J. Ellison, P. P. Power, Inorg.
Chem. 1995, 34, 3210 3214.
[51] Sulfinamide 21 was prepared according to B. J. Backes, D. R. Drago-
li, J. A. Ellman, J. Org. Chem. 1999, 64, 5472 5478.
[52] Organic Syntheses Collect. Vol. V, Wiley, New York, 1973, p. 658.
[53] L. Horner, A. Christmann, Chem. Ber. 1963, 96, 388 398.
[54] T. J. Maricich, C. N. Angeletakis, J. Org. Chem. 1984, 49, 1931 1934.
[55] J. L. Garcia-Ruano, R. Alonso, M. M. Zarzuelo, P. Noheda, Tetrahe-
dron: Asymmetry 1995, 6, 1133 1142.
[56] F. A. Davis, Y. Zhang, Y. Andemichael, T. Fang, D. L. Fanelli, H.
Zhang, J. Org. Chem. 1999, 64, 1403 1406.
[21] M. Boucher, D. Macikenas, T. Ren, J. D. Protasiewicz, J. Am. Chem.
Soc. 1997, 119, 9366 9376.
[22] D. Macikenas, E. Skrzypczak-Jankun, J. D. Protasiewicz, J. Am.
Chem. Soc. 1999, 121, 7164 7165.
[57] J. Wrobel, A. Dietrich, Heterocycles 1994, 38, 1823 1837.
[58] M. Raban, S. K. Lauderback, J. Org. Chem. 1980, 45, 2636 2641.
[59] B. M. Chanda, R. Vyas, A. V. Bedekar, J. Org. Chem. 2001, 66, 30
34.
[23] P. Dauban, L. Saniere, A. Tarrade, R. H. Dodd, J. Am. Chem. Soc.
2001, 123, 7707 7708.
[60] K. Hovius, J. B. F. N. Engberts, Tetrahedron Lett. 1972, 181 182.
[61] We thank our manuscript×s referees for their fruitful suggestions.
[24] C. G. Espino, J. Du Bois, Angew. Chem. 2001, 113, 618 620; Angew.
Chem. Int. Ed. 2001, 40, 598 600.
Received: September 8, 2003 [F5525]
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