Sulfonimidamides: Efficient chiral iminoiodane precursors for diastereoselective copper-catalyzed aziridination of olefins

Article abstract of DOI:10.1021/ol048167a

(Chemical equation presented) N-(p-Toluenesulfonyl)-p- toluenesulfonimidamide reacts with iodosylbenzene to afford in situ a chiral iminoiodane. The latter gives, in the presence of a copper(I) catalyst, a nitrene that is very efficiently transferred unde

Full text of DOI:10.1021/ol048167a

ORGANIC
LETTERS
2004
Vol. 6, No. 24
4503-4505
Sulfonimidamides: Efficient Chiral
Iminoiodane Precursors for
Diastereoselective Copper-Catalyzed
Aziridination of Olefins
Pablo H. Di Chenna, Fabien Robert-Peillard, Philippe Dauban,* and
Robert H. Dodd*
Institut de Chimie des Substances Naturelles, CNRS, aVenue de la terrasse, F-91198
Gif-sur-YVette, France
philippe.dauban@icsn.cnrs-gif.fr; robert.dodd@icsn.cnrs-gif.fr
Received September 10, 2004
ABSTRACT
N-(p-Toluenesulfonyl)-p-toluenesulfonimidamide reacts with iodosylbenzene to afford in situ a chiral iminoiodane. The latter gives, in the
presence of a copper(I) catalyst, a nitrene that is very efficiently transferred under stoichiometric conditions to a variety of alkenes with
diastereoselectivities up to 60%.
The past decade has witnessed a growing interest in carbon-
nitrogen bond formation via functionalization of alkanes and
alkenes by nitrene insertion or addition.1 Considering the high
number of nitrogen-containing natural and/or biologically
active compounds, these methodologies display a promising
potential in total synthesis. As a result, several methods are
now available for the generation of highly reactive nitrene
intermediates starting from N-aminoheterocycles,2 azides,3
haloamines,4 or iminoiodanes.5 Among these nitrene precur-
sors, the latter have gained popularity since their use in
copper-catalyzed aziridination of olefins6 and rhodium-
catalyzed C-H amidation7 has found applications in total
synthesis.5,8 Moreover, enantioselective nitrene transfer9 has
been developed from iminoiodanes in conjunction with chiral
transition metal catalysts.
It has been recently demonstrated that iminoiodanes can
be efficiently generated in situ using iodosylbenzene10 or
iodosylbenzene(diacetate).7,11 These processes greatly sim-
plify the troublesome handling of iminoiodanes but more
importantly enhance the variety of nitrogenous compounds
(6) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc. 1994,
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Yudin, A. K. J. Am. Chem. Soc. 2002, 124, 530-531.
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R.; Bedekar, A. V. J. Org. Chem. 2001, 66, 30-34.
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2000, 2, 2233-2236.
(5) Dauban, P.; Dodd, R. H. Synlett 2003, 1571-1586.
10.1021/ol048167a CCC: $27.50
© 2004 American Chemical Society
Published on Web 11/03/2004

Scheme 1. Diastereoselective Aziridination with a Chiral
Scheme 2. Preparation of
Sulfur(VI) Reagent
N-(p-Toluenesulfonyl)-p-toluenesulfonimidamide 1
likely to be transformed into these hypervalent iodine(III)
reagents. Thus, while formerly, only iminoiodanes derived
from sulfonamides were available,5,12 carbamates7a,13 and
sulfamates7b,13b,14 can now be used as practical and syntheti-
cally useful precursors.
2) via the corresponding sulfonimidoyl chloride obtained by
action of anhydrous chloramine-T.19
Despite these improvements, the intermolecular copper-
catalyzed aziridination of olefins still suffers from low to
moderate yields when stoichiometric conditions are employed
in the case of simple aliphatic or electron-deficient alkenes.
Moreover, although a large number of ligands have been
described for asymmetric aziridination,15 their application
remains limited to styrene-type substrates.
It was therefore with the intention of enhancing the scope
of this process that we felt it interesting to apply our one-
pot methodology to generate chiral iminoiodanes in situ. As
has been previously noted,5 this strategy has not been
explored so far. To this end, we aimed to prepare a chiral
sulfur(VI) reagent since it was expected that the stereogenic
information could be transmitted to the targeted carbon atom
of the aziridine (Scheme 1).16
We therefore turned our attention to sulfonimidamides first
described by Levchenko17 more than 40 years ago but which
have received little attention so far, particularly those with
an unsubstituted amido nitrogen.18 Since initial experiments
with N-(alkyl)arylsulfonimidamides did not lead to satisfac-
tory results (less than 20% aziridination), we decided to use
the more robust N-(p-toluenesulfonyl)-p-toluenesulfonimi-
damide 1. The latter is easily prepared in three steps from
commercially available sodium p-toluenesulfinate (Scheme
The first investigations of the copper-catalyzed aziridina-
tion with 1 were performed on methyl acrylate. It has been
previously observed that this olefinic substrate displays poor
reactivity with sulfonamide-derived iminoiodanes under these
conditions,20 a frustrating result since the corresponding
aziridine-2-carboxylate is a useful precursor of R- or â-amino
acids.21 In contrast, we have now found that methyl acrylate
is an excellent aziridination substrate for 1. Thus, after
extensive screening of the reaction parameters, treatment of
5 equiv of methyl acrylate with 1 at -20 °C in acetonitrile
in the presence of 10 mol % Cu(MeCN)4PF6 led to compound
2a in 93% yield and 55% de. However, more interestingly,
the sulfonimidamide-derived iminoiodane appeared to be
highly reactive since the same procedure gave aziridine 2a
in 81% yield and 50% de using methyl acrylate as the
limiting component (Table 1, entry 1). Similar results were
obtained with other R,â-unsaturated esters. Reactions with
methyl methacrylate and tiglate are nearly quantitative (96
and 92%, respectively, entries 2 and 4) but occur with a
slightly lower de (41 and 38%, respectively), while the
highest diastereoselectivity has been obtained by using 5
equiv of the less reactive methyl crotonate (63% yield, 60%
de, entry 3).
Application of these conditions to simple aliphatic alkenes
of moderate reactivity6,22 also demonstrates the high reactivity
of sulfonimidamide 1 in the copper-catalyzed aziridination.
The monosubstituted terminal olefin 1-heptene was trans-
formed to aziridine 2e in 60% yield under stoichiometric
conditions (entry 5), while cyclic systems such as cyclohex-
(12) (a) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975,
361-362. (b) So¨dergren, M. J.; Alonso, D. A.; Bedekar, A. V.; Andersson,
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Org. Lett. 2002, 4, 863-865. (b) Cui, Y.; He, C. Angew. Chem., Int. Ed.
2004, 43, 4210-4212. (c) Padwa, A.; Flick, A. C.; Leverett, C. A.; Stengel,
T. J. Org. Chem. 2004, 69, 6377-6386.
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R. H. Org. Lett. 2002, 4, 2481-2483. (b) Guthikonda, K.; Du Bois, J. J.
Am. Chem. Soc. 2002, 124, 13672-13673. (c) Wehn, P. M.; Lee, J.; Du
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Tetrahedron: Asymmetry 2004, 15, 1019-1026. (e) Fruit, C.; Mu¨ller, P.
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J. S.; Che, C. M. J. Org. Chem. 2004, 69, 3610-3619.
(15) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
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3450-3458.
(16) Initial experiments with chiral sulfinamides failed since these sulfur-
(IV) reagents did not survive the oxidizing conditions of the PhIdO-
mediated aziridination. See also: Leca, D.; Song, K.; Amatore, M.;
Fensterbank, L.; Lacoˆte, E.; Malacria, M. Chem. Eur. J. 2004, 10, 906-
916.
(17) Levchenko, E. S.; Derkach, N. Y.; Kirsanov, A. V. Zh. Obshch.
Khim. 1962, 32, 1208-1212.
(18) (a) Takei, H.; Watanabe, I.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
1965, 38, 1989-1993. (b) Jones, M. R.; Cram, D. J. J. Am. Chem. Soc.
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Org. Chem. 1988, 53, 4190-4193. (e) Tsushima, S.; Yamada, Y.; Onami,
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Chem. Soc. Jpn. 1989, 62, 1167-1178. (f) Toth, J. E.; Grindey, G. B.;
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4504
Org. Lett., Vol. 6, No. 24, 2004

Scheme 3. Aziridine Ring-Opening
Table 1. Copper-Catalyzed Aziridination of Olefins with
Sulfonimidamide 1
(S)-bis((t-Bu)oxazoline) ligand affords aziridine 2j in 77%
yield and 60% de under stoichiometric conditions.
The synthetic value of aziridines is directly related to their
ability to undergo nucleophilic ring-opening.24 Such reactions
are facilitated by the introduction on the nitrogen atom of
the aziridine of an electron-withdrawing group, which is
clearly the case of the N-(p-toluenesulfonyl)-p-toluenesulfon-
imidoyl group. This was indeed confirmed by the efficient
and regioselective ring-opening of aziridines 2b and 2j with
methanol under mild conditions (Scheme 3).
In conclusion, we have demonstrated that use of a chiral
sulfur(VI) reagent, i.e., sulfonimidamide 1, has allowed the
generation in situ of the first chiral iminoiodane. The latter
is a highly efficient nitrene precursor that reacts with a wide
range of olefins in the presence of a catalytic copper(I) salt
to afford the corresponding aziridines 2 in good to excellent
yields, particularly in the case of the poorly reactive R,â-
unsaturated esters.25 Diastereoselectivities of up to 60% have
been obtained, results that pave the way for the development
of an efficient methodology for the stereoselective synthesis
of amino acids.26 To this end, screening of sulfonimidamides
is in progress in order to optimize their reactivities and
diastereoselectivities.
a Isolated yield after flash chromatography. Diastereoisomers could not
be separated on silica gel. Value in parentheses for yield obtained with 5
equiv of olefins. b Diastereomeric excess was measured by NMR. Value in
parentheses for de was obtained with 5.0 equiv of olefins. c trans-Aziridine.
d cis-Aziridine
Acknowledgment. We thank the Institut de Chimie des
Substances Naturelles for fellowships (P.H.D.C. and F.R.P.).
The support and sponsorship concerted by COST Action D24
“Sustainable Chemical Processes: Stereoselective Transition
Metal-Catalyzed Reactions” are kindly acknowledged.
ene or cyclopentene gave 62 and 59% of the corresponding
aziridines 2h and 2i, respectively (entries 8 and 9). The trans-
and cis-aziridines 2f and 2g, respectively, were also obtained
stereospecifically in good yield (entries 6 and 7). However,
these alkenes did not afford appreciable diastereoselectivities.
In the cases of styrene and of 1,2-dihydronaphthalene, the
reaction with an excess of olefin still occurred with very
high efficiency (96 and 88%, respectively), while the
procedure applied to 1.0 equiv of substrate gave a good yield
of 63% for each compound (entries 10 and 11). Surprisingly,
only very modest diastereomeric excesses of 20 and 25%,
respectively, were observed. These rather disappointing
results are, however, likely to be improved by using
sulfonimidamides in conjunction with one of the several
chiral ligands described for the asymmetric copper-catalyzed
aziridination of styrene-type olefins.9,15 Initial experiments
have shown that such higher diastereoselectivities could
indeed be observed. Thus, a combination of (-)-123 with
Supporting Information Available: General experimen-
tal procedures and characterization for compounds 2a-k,
3, and 4. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL048167A
(23) Both enantiomers of sulfonimidamide 1 are accessible by resolution
using (S)- or (R)-R-methylbenzylamine. See ref 18e.
(24) Hu, X. E. Tetrahedron 2004, 60, 2701-2743.
(25) During the submission of this manuscript, a paper has appeared
where the use of N-(benzoyl)sulfonimidamides for copper-mediated nitrene
transfer is described. See: Leca, D.; Toussaint, A.; Mareau, C.; Fensterbank,
L.; Lacoˆte, E.; Malacria, M. Org. Lett. 2004, 6, 3573-3575.
(26) In this context, it should be mentioned that the N-(p-toluenesulfonyl)-
p-toluenesulfonimidoyl group may be cleaved under reductive conditions,
i.e., by using sodium naphthanelide. See ref 18e.
Org. Lett., Vol. 6, No. 24, 2004
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