Copper-catalyzed nitrogen transfer mediated by iodosylbenzene PhI=O [2]

Full text of DOI:10.1021/ja010968a

J. Am. Chem. Soc. 2001, 123, 7707-7708
7707
of this reaction lies in the preparation and isolation of these
iminoiodinanes which can be sometimes difficult to reproduce.
Since aziridines are useful intermediates in total synthesis,11
their direct preparation from sulfonamides would enhance the
scope and the synthetic value of the reaction. In this regard we
have discovered that an unusual copper-catalyzed nitrogen
transfer to olefins can be mediated by the primary oxygen atom
source iodosylbenzene 1 [eq 1].
Copper-Catalyzed Nitrogen Transfer Mediated by
Iodosylbenzene PhIdO
Philippe Dauban,* Laurent Sanie`re, Aure´lie Tarrade, and
Robert H. Dodd*
Institut de Chimie des Substances Naturelles
C.N.R.S., F-91198 Gif-sur-YVette, France
ReceiVed April 16, 2001
Transition metal-catalyzed functionalization of hydrocarbons
is a fundamental process of paramount importance in organic
synthesis. Among the numerous existing methodologies, catalyzed
atom transfer to olefins plays a pivotal role since it allows access
to aziridines,1amino alcohols,2 diols,2,3 and epoxides.1,4 In the latter
case, iodosylbenzene5 (PhIdO) 1 has been extensively used as a
primary oxygen atom source in combination with manganese, iron,
ruthenium or chromium catalysts.1,6 In a theoretical study, even
copper complexes were found to transfer oxygen from 1 to
cyclohexene.7
Copper complexes formed from the aza-analogue of 1, that is
[N-(p-toluenesulfonyl)imino]phenyliodinane (PhIdNTs) display
a high capacity to catalyze aziridination of olefins.8 Among the
many known metal-catalyzed nitrene-transfer reactions,1 this
process represents the method of choice and has been successfully
applied to the total synthesis of natural or biologically active
products.9 The commercial availability of easy-to-handle copper-
(I) and particularly -(II) complexes makes this reaction highly
practical. Moreover, a wide array of olefins reacts to give
N-(sulfonylated)aziridines in moderate to excellent yields. Finally,
several iminoiodinanes, differing in the substituents attached to
the sulfonyl group, have been developed as sources of nitrene
for synthetic applications.10 However, one of the major drawbacks
Initial experiments investigated the use of iodosobenzene-
(diacetate) [PhI(OAc)2] alone or in the presence of bases such as
t-BuOK, CaO, i-PrNEt2 for the copper-catalyzed aziridination of
olefins starting from sulfonamides. Since all attempts were
unsatisfactory, we decided to explore other hypervalent iodine
-(III) reagents. Inspired by the papers of White12 and Simandi,13
we supposed that such a direct copper-catalyzed aziridination
could be performed starting from iodobenzene dimethoxide [PhI-
(OMe)2]. Indeed, sequential addition to this reagent, in acetonitrile
and in the presence of 3 Å molecular sieves, of p-toluenesulfona-
mide and after 3 h,14 of tetrakis(acetonitrile)copper(I) hexa-
fluorophosphate and methyl methacrylate15 gave rise to aziridine
2a in 37% yield. Since preparation of PhI(OMe)2 from 1 is rather
tedious,16 the reaction was attempted directly with PhIdO which
is easily accessible in large quantity and with high purity by base
treatment of commercially available PhI(OAc)2.17 Application of
the same procedure then led to the expected product 2a in 56%
yield. Finally, because the course of formation of the intermediate
iminoiodinanes is difficult to monitor, we decided to introduce
all of the reagents at once at the beginning of the reaction. To
our surprise, aziridine 2a was isolated with nearly the same yield
of 54%, while no epoxide was detected. This result prompted us
to study the aziridination of various olefins under these “one-
pot” conditions.
(1) Mu¨ller, P. Transition Metal-Catalyzed Nitrene Transfer. In AdVances
in Catalytic Processes; Doyle, M. P., Ed.; JAI Press Inc.: Greenwich, CT,
1997; vol. 2, pp 113-151. (b) Katsuki, T. Asymmetric Epoxidation of
Unfunctionalized Olefins and Related Reactions. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 287-325.
(2) Bolm, C.; Hildebrand, J. P.; Muniz, K. Recent Advances in Asymmetric
Dihydroxylation and Aminohydroxylation. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 399-428.
Typical experiments18 were run with olefins as the stoichio-
metrically limiting component (except in entries 4 and 6, Table
1) in the presence of a catalytic amount of copper(I) salt and a
slight excess of 1 and the sulfonamide. For the purpose of this
study, we chose p-toluenesulfonamide, the precursor of the
standard and easily prepared reagent PhIdNTs, as well as
p-methoxybenzenesulfonamide and 2-(trimethylsilyl)ethanesulfon-
amide whose parent iminoiodinanes are not easily isolated. Results
are shown in Table 1. Generally, yields are comparable to those
obtained in the aziridinations using iminoiodinanes. Therefore,
in addition to its practical interest, this new direct nitrene transfer
appears to be at least as efficient as the classical procedure since
preparation of PhIdNSO2R is far from being quantitative. This
is also apparent in the intramolecular version of the reaction,10e
the results of which are summarized in Table 2. Moreover, it is
(3) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric Dihydroxylation
- Discovery and Development. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; Wiley-VCH: New York, 2000; pp 357-398.
(4) Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric Epoxidation of
Allylic Alcohols. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-
VCH: New York, 2000; pp 231-285.
(5) Willgerodt, C. Chem. Ber. 1892, 25, 3494.
(6) For some representative examples: (a) Lichtenberger, F.; Nastainczyk,
W.; Ullrich, V. Biochem. Biophys. Res. Commun. 1976, 70, 939. (b) Groves,
J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105, 5786. (c) Srinivasan, K.;
Michaud, P.; Kochi, J. K. J. Am. Chem. Soc. 1986, 108, 2309. (d) Zhang, W.;
Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112,
2801. (e) Yang, Y.; Diederich, F.; Valentine, J. S. J. Am. Chem. Soc. 1991,
113, 7195. (f) Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman,
J. I. Science 1993, 261, 1404.
(7) Franklin, C. C.; VanAtta, R. B.; Fan Tai, A.; Valentine, J. S. J. Am.
Chem. Soc. 1984, 106, 814. (b) Nam, W.; Valentine, J. S. J. Am. Chem. Soc.
1990, 112, 4977. (c) Nam, W.; Valentine, J. S. J. Am. Chem. Soc. 1991, 113,
7449.
(8) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Org. Chem. 1991, 56,
6744. (b) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.; Barnes,
D. M. J. Am. Chem. Soc. 1993, 115, 5328. (c) Evans, D. A.; Faul, M. M.;
Bilodeau, M. T. J. Am. Chem. Soc. 1994, 116, 2742.
(9) 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.
(10) So¨dergren, M. J.; Alonso, D. A.; Bedekar, A. V.; Andersson, P. G.
Tetrahedron Lett. 1997, 38, 6897. (b) Macikenas, D.; Skrzypczak-Jankun, E.;
Protasiewicz, J. D. J. Am. Chem. Soc. 1999, 121, 7164. (c) Meprathu, B. V.;
Diltz, S.; Walsh, P. J.; Protasiewicz, J. D. Tetrahedron Lett. 1999, 40, 5459.
(d) Dauban, P.; Dodd, R. H. J. Org. Chem. 1999, 64, 5304. (e) Dauban, P.;
Dodd, R. H. Org. Lett. 2000, 2, 2327.
(11) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599. (b) Osborn,
H. M. I.; Sweeney, J. Tetrahedron: Asymmetry 1997, 8, 1693. (c) McCoull,
W.; Davis, F. A. Synthesis 2000, 1347.
(12) White, R. E. Inorg. Chem. 1987, 26, 3916.
(13) Besenyei, G.; Nemeth, S.; Simandi, L. I. Tetrahedron Lett. 1993, 34,
6105.
(14) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975, 361.
(15) We chose to explore and optimize the conditions of the reaction on
methyl methacrylate since this substrate has higher synthetic value than styrene.
For an example of its application to the preparation of amino acids, see:
Dauban, P.; Dodd, R. H. Tetrahedron Lett. 1998, 39, 5739.
(16) Schardt, B. C.; Hill, C. L. Inorg. Chem. 1983, 22, 1563.
(17) Saltzman, H.; Sharefkin, J. G. In Organic Syntheses; Baumgarten, H.
C., Ed.; John Wiley & Sons: New York, 1973; Vol. 5, pp 658-659.
(18) See Supporting Information for typical aziridination procedures with
each sulfonamide.
10.1021/ja010968a CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/14/2001

7708 J. Am. Chem. Soc., Vol. 123, No. 31, 2001
Communications to the Editor
Table 1. Copper-Catalyzed Aziridination of Representative Olefins
Mediated by PhIdO
Table 2. Intramolecular Copper-Catalyzed Reactions Mediated by
PhIdO
a Isolated yield after flash chromatography. b Value in parentheses
for yield reported using classical methodology.10e
Scheme 1
a Isolated yield after flash chromatography. b Value in parentheses
for yield reported in the literature starting from PhIdNSO2R under
comparable conditions. c 5 equiv of olefin and 1 equiv of (PhIdO +
RSO2NH2) were used.
The most striking feature of this process is the nitrogen-transfer
mediated by an oxo donor. Control experiments run on methyl
methacrylate, styrene, and cyclohexene in the absence of sul-
fonamide did not allow isolation of epoxides in significative
amounts (less than 10%), confirming that these reactions are
sluggish,7,21 while aziridination was found to occur even with
copper(II) salts. Since copper complexes do not significantly
catalyze oxygen transfer, it seemed worthwhile to test the
generality of the pathway depicted in Scheme 1, starting from
acidic hydrogen-containing products. We thus decided to attempt
cyclopropanation of styrene directly from dimethyl malonate.22
To our satisfaction, a copper-catalyzed carbene transfer was
observed under stoichiometric conditions starting from 1 leading
to cyclopropane 14 in 55% yield [eq 3].
noteworthy that portionwise addition of 1 and the sulfonamide
to the olefin allowed isolation of aziridines in better yields,
particularly in the case of the highly reactive intermediate
iminoiodinanes.
Because the reaction was also found to occur in dichloro-
methane or benzene, asymmetric copper-catalyzed aziridination
was performed. By applying the experimental procedure described
by Evans to styrene,8b aziridine 3a was obtained with an ee of
59% comparable to that obtained previously [eq 2].
In conclusion, we have developed a direct copper-catalyzed
nitrogen transfer mediated by the powerful oxygen atom donor
PhIdO. This unique reaction greatly simplifies the procedure for
copper-catalyzed aziridination of olefins and enhances its ef-
ficiency.
From a mechanistic point of view, this nitrene-transfer reaction
contradicts the previous assumption which postulated that copper-
catalyzed aziridination could be hampered by metal-catalyzed
hydrolysis of iminoiodinanes to sulfonamides and 1. Indeed, PhId
O-mediated aziridination occurred even in the presence of water.19
Therefore, we propose that metal-catalyzed degradation of imi-
noiodinanes leads to iodobenzene and, via nitrenoid 13, the
starting sulfonamide. This hypothesis led us to suppose, according
to the mechanistic pathway in Scheme 1,20 that an excess of the
sulfonamide was not necessary to perform the reaction. Indeed,
use of an equimolar amount of methyl methacrylate and TsNH2
in the presence of a slight excess (1.4 equiv) of 1 led to aziridine
2a with the same yield of 56%.
Supporting Information Available: Experimental details and char-
acterization for all new compounds (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
JA010968A
(20) Brandt, P.; So¨dergren, M. J.; Andersson, P. G.; Norrby, P.-O. J. Am.
Chem. Soc. 2000, 122, 8013.
(21) A test experiment conducted on stilbene, which was the most reactive
substrate towards copper-mediated epoxidation of olefins by 1, confirmed this
assumption since an NMR study of the crude reaction revealed a 10:1 ratio
of aziridine and epoxide.
(19) Aziridination of styrene in the presence of 3 equiv of water without
molecular sieves led to approximatively a 50% yield of aziridine.
(22) Mu¨ller, P.; Fernandez, D. HelV. Chim. Acta 1995 78, 947.