Intramolecular Phl=O mediated copper-catalyzed aziridination of unsaturated sulfamates: A new direct access to polysubstituted amines from simple homoallylic alcohols

Article abstract of DOI:10.1021/ol0200899

(Matrix presented) Olefinic sulfamates derived from primary and secondary alcohols undergo intramolecular copper-catalyzed aziridination in the presence of iodosylbenzene to afford novel bicyclic fused aziridines. The latter were opened by various nucleop

Full text of DOI:10.1021/ol0200899

ORGANIC
LETTERS
2002
Vol. 4, No. 15
2481-2483
Intramolecular PhIdO Mediated
Copper-Catalyzed Aziridination of
Unsaturated Sulfamates: A New Direct
Access to Polysubstituted Amines from
Simple Homoallylic Alcohols
Fernando Duran,† Lo1ıc Leman,‡ Alberto Ghini,† Gerardo Burton,†
,‡
,‡
Philippe Dauban,* and Robert H. Dodd*
Departamento de Quimica Organica, Facultad de Ciencias Exactas y Naturales,
UniVersidad de Buenos Aires, Argentina, and Institut de Chimie des Substances
Naturelles, C. N. R. S., F-91198 Gif-sur-YVette, France
philippe.dauban@icsn.cnrs-gif.fr; robert.dodd@icsn.cnrs-gif.fr
Received April 29, 2002
ABSTRACT
Olefinic sulfamates derived from primary and secondary alcohols undergo intramolecular copper-catalyzed aziridination in the presence of
iodosylbenzene to afford novel bicyclic fused aziridines. The latter were opened by various nucleophiles to give the corresponding substituted
cyclic sulfamates, which in turn reacted, after nitrogen activation, with a second nucleophile at the carbon atom bearing the oxygen atom.
Concomitant removal of the sulfonyloxy moiety thus gave access to polysubstituted amines.
Since its discovery in the early 1990s,1 the copper-catalyzed
aziridination of olefins has been applied to the total synthesis
of natural and/or biologically active compounds, albeit in a
restricted number of cases.2 Given the simplicity of this
nitrene transfer onto olefins, such a limited interest could
appear paradoxical. In this context and in order to increase
the scope of this reaction, we have recently found new
iminoiodinanes useful for this process,3 and in particular,
we have developed an intramolecular version of the copper-
catalyzed aziridination.3c The efficiency of the latter was
improved by the discovery of a one-pot procedure mediated
by iodosylbenzene,4 allowing access to substituted cyclic
sulfonamides with potential biological activity. However,
since the SO2-N moiety is only rarely found in nature,5 this
intramolecular process appears to be of very limited useful-
ness for the total synthesis of natural products.
* Fax: + (1) 69077247.
† Universidad de Buenos Aires.
‡ Institut de Chimie des Substances Naturelles.
(1) (a) Initial report: Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Org.
Chem. 1991, 56, 6744. (b) For a full account: Evans, D. A.; Faul, M. M.;
Bilodeau, M. T. J. Am. Chem. Soc. 1994, 116, 2742.
(2) (a) Hudlicky, T.; Tian, X.; Ko¨nigsberger, K.; Maurya, R.; Rouden,
J.; Fan, B. J. Am. Chem. Soc. 1996, 118, 10752. (b) Masse, C. E.; Knight,
B. S.; Stavropoulos, P.; Panek, J. S. J. Am. Chem. Soc. 1997, 119, 6040.
(c) Overman, L. E.; Tomasi, A. L. J. Am. Chem. Soc. 1998, 120, 4039. (d)
Sudau, A.; Mu¨nch, W.; Bats, J. W.; Nubbemeyer, U. Chem. Eur. J. 2001,
7, 611. (e) White, R. D.; Wood, J. L. Org. Lett. 2001, 3, 1825. (f) Ahmadian,
M.; Khare, N. K.; Riordan, J. M.; Klon, A. E.; Borhani, D. W. Tetrahedron
2001, 57, 9899. (g) Baron, E.; O’Brien, P.; Towers, T. D. Tetrahedron
Lett. 2002, 43, 723.
(3) (a) Dauban, P.; Dodd, R. H. J. Org. Chem. 1999, 64, 5304. (b) Di
Chenna, P. H.; Dauban, P.; Ghini, A.; Burton, G.; Dodd, R. H. Tetrahedron
Lett. 2000, 41, 7041. (c) Dauban, P.; Dodd, R. H. Org. Lett. 2000, 2, 2327.
(4) Dauban, P.; Sanie`re, L.; Tarrade, A.; Dodd, R. H. J. Am. Chem. Soc.
2001, 123, 7707.
(5) (a) For a brief discussion: Dauban, P.; Dodd, R. H. Tetrahedron Lett.
2001, 42, 1037. (b) Banwell, M. G.; Crasto, C. F.; Easton, C. J.; Karoli, T.;
March, D. R.; Nairn, M. R.; O’Hanlon, P. J.; Oldham, M. D.; Willis, A.
C.; Yue, W. Chem. Commun. 2001, 2210.
10.1021/ol0200899 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/25/2002

Accordingly, we felt it necessary to find a procedure which
would permit removal of the undesired sulfonyl moiety. To
this end, the application of the intramolecular copper-
catalyzed aziridination to unsaturated sulfamates was con-
sidered (Scheme 1). Thus, in addition to both electrophilic
Table 1. Intramolecular Copper-Catalyzed Reactions
Scheme 1
carbon atoms of the expected aziridines, a third center, i.e.,
the carbon atom bearing the oxygen functionality, could
theoretically react with a nucleophile. The resulting displace-
ment would then lead to formation of a sulfamate salt, which
could be easily removed by acidic hydrolysis. Therefore,
starting from unsaturated alcohols, the preparation of polysub-
stituted amines could be envisaged.
During the course of our investigations, several publica-
tions appeared in which the use of cyclic sulfamidates for
the preparation of modified amino acids was described.6
These studies all rely on a single regioselective nucleophilic
ring opening of the cyclic sulfamidates. By comparison, our
strategy should in principle pave the way to the development
of a more versatile methodology. In this context, we describe
our preliminary results in this field and, in particular, report
the selectiVe introduction of nucleophiles onto these new
ambident synthons.
The starting unsaturated sulfamates 1a-f were prepared
from the corresponding primary or secondary alcohols by
reaction with an in situ generated sulfamoyl chloride7 using
a recently described sulfamoylation reaction.8 Yields were
generally very good, typically in the 80-95% range. These
unsaturated sulfamates are stable at room temperature and
were stored for several weeks at 4 °C without notable
decomposition. Compounds 1a-f were then engaged in a
direct intramolecular copper-catalyzed aziridination mediated
by iodosylbenzene.4 Results are summarized in Table 1.9
a Isolated yield after flash chromatography.
The one-pot procedure appeared to be more efficient than
the classical two-step procedure involving isolation of the
intermediate iminoiodinane. In this case, the sulfamates 1a,b
gave the corresponding aziridines 2a,b in yields that never
exceeded 40% compared to 69 and 53% yields, respectively,
for the one-pot procedure. The reaction was best run under
moderately dilute conditions (concn ) 0.2 M), and the
aziridines were isolated in acceptable to very good yields in
all cases.10 Interestingly, the product isolated from substrate
1e stands in sharp contrast to the C-H insertion product
obtained from the analogous sulfonamide.3c The reaction is
also stereospecific with respect to the alkene geometry; trans-
and cis-aziridines 2c,d were prepared respectively from trans-
and cis-sulfamates 1c,d. However, no diastereoselectivity was
observed in the case of compound 1f since the reaction
afforded the corresponding aziridine 2f in a 1:1 cis/trans ratio
(C-4/C-6 relative stereochemistry).
(6) (a) Wei, L.; Lubell, W. D. Can. J. Chem. 2001, 79, 94 and references
therein. (b) Atfani, M.; Wei, L.; Lubell, W. D. Org. Lett. 2001, 3, 2965.
(c) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois, J. J. Am. Chem. Soc.
2001, 123, 6935. (d) Cohen, S. B.; Halcomb, R. L. J. Am. Chem. Soc. 2002,
124, 2534. (e) Nicolaou, K. C.; Huang, X.; Snyder, S. A.; Bheema Rao, P.;
Bella, M.; Reddy, M. V. Angew. Chem., Int. Ed. 2002, 41, 834. (f) Pound,
M. K.; Davies, D. L.; Pilkington, M.; de Pina Vaz Sousa, M. M.; Wallis,
J. D. Tetrahedron Lett. 2002, 43, 1915.
We next turned our attention to the study of the electro-
philic reactivity of these new types of heterocyclic structures
particularly with respect to any possible regioselectivity of
(9) See Supporting Information for typical aziridination procedures.
(10) Application of the intramolecular aziridination to the stable sulfamate
derived from an allyl alcohol surprisingly did not give any traces of product.
This could be related to the high strain of the expected bicyclic compound.
(7) Appel, R.; Berger, G. Chem. Ber. 1958, 91, 1339.
(8) Okada, M.; Iwashita, S.; Koizumi, N. Tetrahedron Lett. 2000, 41,
7047.
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Org. Lett., Vol. 4, No. 15, 2002

ring-opening. As previously observed with the aziridines
derived from sulfonamides, we were pleased to find that
reaction of 2a with different types of nucleophiles (methanol,
thiophenol, morpholine, benzylamine, trimethylsilyl azide,
and piperidine) afforded in good yields the seven-membered
ring products 3-8 resulting from opening of the aziridine
at the more substituted site (Scheme 2). The structure of the
been reported, there are apparently no examples of such
reactions of seven-membered cyclic sulfamidates. We pre-
sumed that the reactivity of the latter should be weaker than
that of their lower homologues. On this basis, we decided
to increase the electrophilic character of the sulfamidate by
introducing an electron-withdrawing group on the nitrogen
atom. Inspired by the report from Du Bois,6c compound 8
was transformed into its N-Cbz analogue 10, which in turn
was reacted with thiophenol under basic conditions. Acidic
workup of the reaction mixture gave the expected diamino
product 11 in an unoptimized 42% yield over two steps
(Scheme 3).
Scheme 2
Scheme 3
In conclusion, intramolecular copper-catalyzed aziridina-
tion applied to unsaturated sulfamates derived from primary
and secondary alcohols allows access to new types of
heterocycles. Their electrophilic reactivity can be controlled
such that two different nucleophiles can be introduced
selectively and consecutively, while the sulfonyloxy moiety
is easily removed at the end of the reaction sequence.
Application of this strategy to the total synthesis of natural
products is currently under investigation.
Acknowledgment. We thank ECOS-France (Grant
A97E06) for financial support.
Supporting Information Available: Experimental details
and characterization for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
seven-membered ring sulfamates was unambiguously deter-
mined by 2D NMR experiments. No other products could
be detected by TLC or H NMR analyses of the crude
1
OL0200899
reaction mixture. More interestingly, only monosubstituted
compounds were isolated even in the presence of excess
nucleophile as was the case with methanol, thiophenol, and
morpholine. The same result and, particularly, regioselectivity
were observed when aziridine 2c reacted with benzylamine.
Nucleophilic attack occurred at the same position as before
as indicated by the HMBC spectrum of product 9.
This regioselective aziridine ring-opening reaction then
afforded the opportunity to introduce a second nucleophile
by reaction at the carbon atom bearing the sulfamate function.
While nucleophilic ring openings of five-membered6a,11 and,
more rarely, six-membered6b,c,12 cyclic sulfamidates have
(11) (a) Boulton, L. T.; Stock, H. T.; Raphy, J.; Horwell, D. C. J. Chem.
Soc., Perkin Trans. 1 1999, 1421. (b) White, G. J.; Garst, M. E. J. Org.
Chem. 1991, 56, 3177. (c) Alker, D.; Doyle, K. J.; Harwood, L. M.;
McGregor, A. Tetrahedron: Asymmetry 1990, 1, 877. (d) Baldwin, J. E.;
Spivey, A. C.; Schofield, C. J. Tetrahedron: Asymmetry 1990, 1, 881.
(12) (a) Lyle, T. A.; Magill, C. A.; Pitzenberger, S. M. J. Am. Chem.
Soc. 1987, 109, 7890. (b) Thompson, W. J.; Anderson, P. S.; Britcher, S.
F.; Lyle, T. A.; Thies, J. E.; Magill, C. A.; Varga, S. L.; Schwering, J. E.;
Lyle, P. A.; Christy, M. E.; Evans, B. E.; Colton, C. D.; Holloway, M. K.;
Springer, J. P.; Hirshfield, J. M.; Ball, R. G.; Amato, J. S.; Larsen, R. D.;
Wong, E. H. F.; Kemp, J. A.; Tricklebank, M. D.; Singh, L.; Oles, R.;
Priestly, T.; Marshall, G. R.; Knight, A. R.; Middlemiss, D. N.; Woodruff,
G. N.; Iversen, L. L. J. Med. Chem. 1990, 33, 789. (c) Lowe, G.; Reed, M.
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