Angewandte
Chemie
4a, which we hoped to convert into sulfondiimine 5a by
treatment with aniline. Because all attempts to isolate 4a
failed, a one-pot reaction sequence was envisaged. Thus, 1a
was first treated with the oxidizing agent (Selectfluor) in
acetonitrile in the presence of a base (Na2CO3), and aniline
was added after five hours. As hypothesized, this protocol led
indeed to the formation of sulfondiimine 5a, albeit with
varying amounts of sulfoximine 6 and sulfoxide 7 as by-
products [Eq. (4)]. After significant optimization of the
reaction conditions (solvent, base, reaction time, etc.)[15]
sulfondiimine 5a could finally be isolated in 42% yield.
Scheme 2. Amine substrate scope. Yields after column chromatogra-
phy. [a] Use of the corresponding sodium salt (RNHNa) of the amine.
[b] Use of the HCl salt of the corresponding amine and 4.2 equiv of
Na2CO3. [c] Use of hexamethyldisilylamine (HMDS) as amino source
and 4.2 equiv of Na2CO3. Bn=benzyl, DMF=N,N-dimethylformamide,
Mes=2,4,6-trimethylphenylsulfonyl, Ns=4-nitrobenzenesulfonyl,
PMB=p-methoxybenzyl, Ts=4-toluenesulfonyl.
Considering the role of Selectfluor as oxidant and F+
source, other Hal+ transfer agents were tested next. Whereas
N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS)
were less effective or even ineffective,[15] the use of
N-chlorosuccinimide (NCS) significantly improved the yield
of sulfondiimine 5a, and the amounts of by-products were
reduced. In this case, halogenated intermediates, such as 3b or
4b, could not be isolated. Compared to the reaction sequence
with Selectfluor, the halogenation step with NCS appeared to
be much faster (15 min versus 5 h), whereas the amine
substitution needed more time (12 h versus 1 h). Further-
more, the amount of both Na2CO3 and Hal+ transfer agents
could be reduced to 1.2 equivalents by using NCS (compared
to 5 and 2 equivalents, respectively, with Selectfluor). Now,
sulfondiimine 5a was obtained in 75% yield from the reaction
in DMF and by using Na2CO3 as base, even on multigram
scale.
With enantiopure a-methylbenzylamine, the reaction
gave a separable 1:1 mixture of diastereomers of 5n in 35%
yield. The high functional-group tolerance in reactions with
aliphatic amines (5o–s) is noteworthy; products with a free
hydroxy, a carboxy, and an alkynyl moiety were obtained.
Finally, N,N’-nonsubstituted sulfondiimine 5t was prepared in
31% yield by using HMDS as a masked source of ammonia.
Considering the initially mentioned sulfone–sulfoximine–
sulfondiimine analogy, the straightforward access to this
product might be of relevance for subsequent developments
in medicinal and crop-protection chemistry.
Application of the optimized conditions to reactions
between 1a and various primary amines (including sulfon-
amides) led to an array of N-monosubstituted sulfondiimines
(Scheme 2). To our delight, the functional-group tolerance
was excellent, and most products were formed in satisfying
yields (31–80%), in particular considering the complexity and
substrate sensitivity of the one-pot reaction. Aniline deriva-
tives that bear either electron-donating or electron-with-
drawing groups generally gave the corresponding sulfon-
diimines (5b–h) in good yields (47–71%).
Noteworthy, in these reactions, both iodo and acetyl
substituents on the aniline core were tolerated (5g and 5h).
Also, less nucleophilic amino derivatives, such as cyanamide,
nosyl or tosyl amide, reacted well, although in these cases the
corresponding sodium salts had to be used (5i–k). N-Benzyl
derivatives were obtained in moderate yields (5l–n).
Next, the sulfiliminium salt was varied by using aniline as
nucleophile in the imination step (Scheme 3). Awide range of
synthetically challenging S-alkyl-S-aryl sulfondiimines (8–14)
was obtained in good yields (up to 74%). Various substituents
on the aryl group were tolerated, and electron-rich substrates
gave the best results (11 and 12). Sulfiliminium salts derived
from benzyl phenyl sulfide and cyclopropyl phenyl sulfide
afforded the corresponding products in 66 and 70% yield,
respectively. As representatives for dialkyl and diaryl deriv-
atives, 15 and 16 were prepared starting from tetrahydrothio-
phene and diphenyl sulfide, respectively. Although in these
cases the yields were low (46 and 27%), the results confirmed
that substrates with those substitution patterns were also
suitable starting materials in the newly devised protocol.
In order to evaluate the reactivity of the N-monosubsti-
tuted sulfondiimines, several transformations were studied by
Angew. Chem. Int. Ed. 2012, 51, 4440 –4443
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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