Efficient copper-mediated reactions of nitrenes derived from sulfonimidamides

Article abstract of DOI:10.1021/ol0485520

(Chemical Equation Presented) Sulfonimidamides lead efficiently to nitrenes and have been converted to sulfimides, sulfoximines, and aziridines in good yields, through a copper-mediated multicomponent reaction. The stereogenic sulfur atom and the trivalent nitrogen atom present in the molecules open the way to asymmetric synthesis, whose first results are presented.

Full text of DOI:10.1021/ol0485520

ORGANIC
LETTERS
2004
Vol. 6, No. 20
3573-3575
Efficient Copper-Mediated Reactions of
Nitrenes Derived from Sulfonimidamides
Dominique Leca, Aure´lie Toussaint, Camille Mareau, Louis Fensterbank,*
Emmanuel Lacoˆte,* and Max Malacria*
UniVersite´ Pierre et Marie Curie, Laboratoire de Chimie Organique,
UMR CNRS 7611, 4 place Jussieu, C. 229, 75005 Paris, France
fensterb@ccr.jussieu.fr; lacote@ccr.jussieu.fr; malacria@ccr.jussieu.fr
Received July 26, 2004
ABSTRACT
Sulfonimidamides lead efficiently to nitrenes and have been converted to sulfimides, sulfoximines, and aziridines in good yields, through a
copper-mediated multicomponent reaction. The stereogenic sulfur atom and the trivalent nitrogen atom present in the molecules open the way
to asymmetric synthesis, whose first results are presented.
Because nitrogen-containing molecules are ubiquitous, selec-
tive nitrogen atom insertions into organic substrates are
essential tools that can be used by synthetic chemists.1
Among all the available methods, metal-mediated aminations
and nitrene-derived reactions are of great interest. The latter
method allows the formation of C-N and SdN2 bonds via
insertion or transfer. In particular, olefin aziridination can
be achieved from both nitrido-metal and imido-metal
complexes. The former has been pioneered by Groves3 and
Carreira.4 Nitrogen sources for the latter are diverse, but the
most widely used are chloramine-T5 and iminoiodanes,6
which are more convenient and versatile. Thus, a variety of
catalytic systems are suitable for the decomposition of the
hypervalent iodine derivatives: metal porphyrins,7 salen8 and
terpyridine9 complexes, non-heme iron compounds,10 rhod-
ium11 and copper salts,12 etc. Yet, the range of iodanes
allowed is very narrow (basically limited to compounds
originating from a few sulfonamides). DuBois’ announce-
ment that in situ-generated iminoiodanes obtained from
carbamates and sulfamate esters could be used in rhodium-
catalyzed multicomponent C-H insertions13 and aziridina-
tion14 triggered several reports focusing on the development
of one-pot processes.15 In addition, contrary to the case with
carbenes, the enantioselective versions of those processes
are much less efficient, notably because they are highly
substrate-dependent.16 As a consequence, this aspect remains
(7) Mansuy, D.; Mahy, J. P.; Dure´ault, A.; Bedi, G.; Battioni, P. J. Chem.
Soc., Chem. Commun. 1984, 1161-1163.
(1) Modern Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim,
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J. F. K.; Vogt, P. Tetrahedron Lett. 1998, 39, 4805-4806. (c) Bolm, C.;
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1260.
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2074.
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10.1021/ol0485520 CCC: $27.50
© 2004 American Chemical Society
Published on Web 08/27/2004

a challenge worth investigating, and there is a real need for
new systems. Because of our previous work on chiral sulfur
functions,17 we decided to replace the sulfonamide/sulfamate
moiety of the nitrene with a stereogenic sulfur-containing
one. To the best of our knowledge, this approach to chiral
nitrenes had never been reported, and our first choice was
to use a sulfinamide. Such compounds led to oxidation when
treated with iodosobenzene, the standard method for prepar-
ing iminoiodanes.18 We thus decided to switch to a more
oxidized function. We report herein the results we gathered
using sulfonimidamides (1).
imidoyl sulfoximines. Reaction with tetrahydrothiophene
oxide proceeded smoothly and yielded 80% of the corre-
sponding sulfoximine (Table 1, entry 1). This outcome
validated our approach. Upon starting from a chiral enan-
tiopure sulfoxide, we could isolate two diastereomers of the
Table 1. Reactions of Sulfonimidamide-Derived Cu-Nitrenes
The first problem we faced was the known interconversion
between the two nitrogen atoms of sulfonimidamides (Scheme
1).19 We anticipated that this tautomerization should be
Scheme 1. Proton Exchange on Sulfonimidamides
hampered by the presence of an additional carbonyl group
on the imido nitrogen. The equilibrium would be presumably
displaced toward 1, with the required free amino group.20
When submitted to iodosobenzene diacetate in the presence
of a base, 1 gave a yellowish precipitate, which decomposed
upon drying. We assumed that the iodinane could indeed be
formed but was too sensitive to be isolated easily. Dauban
and Dodd reported similar problems with some of their
substrates and introduced one of the above-mentioned
multicomponent procedures.15a
We thus adopted the same procedure, using the less
expensive and less sensitive copper(II) salt instead of the
copper(I) one. Sulfonimidate 1 was added together with
iodosobenzene in five small lots (one every 15 min) to a
slurry of a nitrene trap (sulfur function or olefin), 3 Å MS,
and copper(II) triflate (10 mol %) at room temperature
(Scheme 2).
Scheme 2. Nitrene Formation from Sulfonimidamides
As we were more familiar with sulfur chemistry, we started
our study by preparing the previously unknown N-sulfon-
aAll reactions were run at room temperature in MeCN in the presence
of 3 Å MS, 1 equiv of 1, and 10 mol % Cu(OTf)2. PhIO was added in five
different lots over 2 h. b Unless otherwise noted, diastereoselection was
measured by NMR and HPLC. c p-Tolyl benzoyl sulfonimidamide was used.
d Corresponding sulfoxide was also observed (5%). e Corresponding sul-
foxide was also observed (3%). f Performed with 5 equiv of olefin.
g Diastereomers could not be separated.
(15) (a) Dauban, P.; Sanie`re, L.; Tarrade, A.; Dodd, R. H. J. Am. Chem.
Soc. 2001, 123, 7707-7708. (b) Duran, F.; Leman, L.; Ghini, A.; Burton,
G.; Dauban, P.; Dodd, R. H. Org. Lett. 2002, 4, 2481-2483. (c) Liang,
J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu, W.-Y.; Che, C.-M. Angew. Chem.
Int. Ed. 2002, 41, 3465-3468. (d) Okamura, H.; Bolm, C. Org. Lett. 2004,
6, 1305-1307.
(16) Mu¨ller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905-2919.
3574
Org. Lett., Vol. 6, No. 20, 2004

sulfoximine (entry 2). The reaction proceeded with retention
of optical purity of the sulfoxide’s sulfur atom (both isolated
products were enantiopure; they were racemic upon starting
from the same racemic sulfoxide).21 As it is customary with
such imination,2b,c we assumed that the nitrene attacked the
sulfur lone pair.
an aromatic ring was attached to the double bond, the
aziridines were obtained in higher yields and from only 1
equiv of the styrene derivatives (entries 9-12). The best yield
was reached with styrene (78%, entry 9). The diastereo-
selectivities were also much better, nearing 50% de, which
is acceptable for aziridinations. Our best result so far has
been with trans-â-methylstyrene (3:1 ds, entry 12). Reduction
of the catalyst loading to 5% led to diminished yields (40%),
without loss of stereoselection. Copper(II) triflate is probably
not the most active system to allow low loadings.
In conclusion, we have introduced a new class of nitrenes,
which are more reactive than their parent sulfonamide-
derived ones. In some cases, we could lower the amount of
trapping agents used to only 1 equiv, thus broadening the
scope of those intermediates. Besides, we have shown that
the reactions proceed with some diastereoselectivity. Since
the diastereoselectivities are very promising and seem to be
a function of both steric and electronic effects, we can take
advantage of the versatility provided by the presence of an
additional group on the SdN nitrogen atom. Work toward
the optimization of the selectivities, by fine-tuning the
starting sulfonimidamide, trying different metals, and/or
looking for potential matched pairs for double induction, as
well as the extension of the reactivity to insertions is under
way and will be reported in due course.
Sulfides are interesting targets for iminations, since the
latter lead to chiral sulfimides. Here, methyl (respectively,
ethyl) phenyl sulfide gave the corresponding sulfimides in
acceptable yields (entries 3 and 4). Those products were
accompanied by traces of sulfoxides arising from the direct
oxidation of the sulfides by iodosobenzene.22 The diastereo-
selectivities were low. Yet, it seems that the substitution
pattern of the sulfide does bring some modifications.
For the aziridinations, we initially decided to use 5 equiv
of the olefins. With aliphatic alkenes, we were able to isolate
the corresponding aziridines in acceptable yields (entries
5-7). 2-Methyl-2-butene failed to give any selectivity (entry
6). Since some sulfonimidamides are bioactive,23 we have
an access to a new class of compounds, whose activity is
under investigation. Nitrenes are electrophilic and generally
less reactive toward electron-poor alkenes. This explains the
loss in yield when an acrylate was used (entry 8).
A second class of olefins was much more promising: when
(17) (a) Delouvrie´, B.; Fensterbank, L.; Lacoˆte, E.; Malacria, M. J. Am.
Chem. Soc. 1999, 121, 11395-11401. (b) Brebion, F.; Delouvrie´, B.; Na`jera,
F.; Fensterbank, L.; Malacria, M.; Vaissermann, J. Angew. Chem. Int. Ed.
2003, 42, 5342-5345.
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2002, 4, 4093-4095. (b) Leca, D.; Song, K.; Amatore, M.; Fensterbank,
L.; Lacoˆte, E.; Malacria, M. Chem. Eur. J. 2004, 10, 906-916.
(19) Johnson, C. R.; Jonsson, E. U.; Bacon, C. C. J. Org. Chem. 1979,
44, 2055-2061.
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3472.
(21) See Supporting Information for the HPLC spectra.
(22) Roh, K. R.; Kim, K. S.; Kim, Y. H. Tetrahedron Lett. 1991, 32,
793-796.
(23) Toth, J. E.; Grindey, G. B.; Ehlhardt, W. J.; Ray, J. E.; Boder, G.
B.; Bewley, J. R.; Klingerman, K. K.; Gates, S. B.; Rinzel, S. M.; Schultz,
R. M.; Weir, L. C.; Worzalla, J. F. J. Med. Chem. 1997, 40, 1018-1025.
Acknowledgment. The authors thank CNRS, Universite´
Pierre et Marie Curie, and the Institut Universitaire de France,
of which M.M. is a member, for generous financial support
of this work. D.L. thanks the Ministe`re de la Recherche for
a grant.
Supporting Information Available: Experimental pro-
cedures and spectral data for all new compounds, evidence
for purity, and proof of retention related to entry 2 of Table
1. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL0485520
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