C O M M U N I C A T I O N S
Table 3. Synthesis of Aziridines from Allylic
N-Tosyloxycarbamates
3). The aziridination reaction is stereospecific, as only one
diastereomer was observed. The aziridination reaction proceeded
equally well with disubstituted (entries 1-2) and trisubstituted
alkenes (entries 3-5).20
In conclusion, we have devised a new general process to convert
N-tosyloxycarbamates into metal nitrene species which can undergo
aziridination and C-H insertion reactions efficiently using rhodium
catalysts. This very practical transition-metal-catalyzed process does
not require the use of hypervalent iodine reagents and led to the
desired products with high yields.
Acknowledgment. The authors thank Michel Couturier (Pfizer
Inc., Groton) for helpful discussions. This research was supported
by Pfizer Inc., NSERC (Canada), Merck Frosst Canada, the CFI
and the Universite´ de Montre´al. K.H. thanks NSERC (Canada) for
a graduate scholarship. We thank the Charette group (Universite´
de Montre´al) for the use of chiral columns. We thank Francine
Be´langer-Garie´py for resolution of the X-ray crystal structure.
Supporting Information Available: Characterization data for new
compounds and experimental procedures. This material is available free
References
(1) Recent examples: (a) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed.
2001, 40, 598-600. (b) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois,
J. J. Am. Chem. Soc. 2001, 123, 6935-6936. (c) Espino, C. G.; Fiori, K.
W.; Kim, M.; Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378-15379.
(d) Cui, Y.; He, C. Angew. Chem., Int. Ed. 2004, 43, 4210-4212.
(2) (a) Doyle, M. P.; Forbes, D. C. Chem. ReV. 1998, 98, 911-935. (b) Merlic,
C. A.; Zechman, A. L. Synthesis 2003, 1137-1156.
(3) (a) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919-7946.
(b) Lebel, H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem. ReV.
2003, 103, 977-1050. (c) Maas, G. Chem. Soc. ReV. 2004, 33, 183-
190.
(4) (a) Davies, H. M. L.; Beckwith, R. E. J. Chem. ReV. 2003, 103, 2861-
2903. (b) Davies, H. M. L.; Loe, O. Synthesis 2004, 2595-2608.
(5) Kuhn, F. E.; Santos, A. M. Mini-ReV. Org. Chem. 2004, 1, 55-64.
(6) A notable exception is the activation of BocN3; see, for example: (a)
Bach, T.; Korber, C. Eur. J. Org. Chem. 1999, 1033-1039. (b) Tamura,
Y.; Uchida, T.; Katsuki, T. Tetrahedron Lett. 2003, 44, 3301-3303. See
also: (c) Bach, T.; Schlummer, B.; Harms, K. Chem.sEur. J. 2001, 7,
2581-2594. (d) Ragaini, F.; Penoni, A.; Gallo, E.; Tollari, S.; Gotti, C.
L.; Lapadula, M.; Mangioni, E.; Cenini, S. Chem.sEur. J. 2003, 9, 249-
259.
C-H bond, was isolated in 64% yield. The C-N bond formation
was stereospecific, as the rhodium-catalyzed insertion of chiral enan-
tioenriched N-tosyloxycarbamate 8 occurred with retention of con-
figuration, providing oxazolidinone 9 without racemization (eq 2).
(7) (a) Abramovitch, R. A.; Davis, B. A. Chem. ReV. 1964, 64, 149-185.
(b) Moody, C. J. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 7, p 21.
(8) (a) Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1965, 87, 3630-
3637. (b) Methcohn, O. Acc. Chem. Res. 1987, 20, 18-27.
(9) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656-3665.
(10) Recent examples: (a) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc.
2002, 124, 13672-13673. (b) Padwa, A.; Stengel, T. Org. Lett. 2002, 4,
2137-2139. (c) Cui, Y.; He, C. J. Am. Chem. Soc. 2003, 125, 16202-
16203. (d) Di Chenna, P. H.; Robert-Peillard, F.; Dauban, P.; Dodd, R.
H. Org. Lett. 2004, 6, 4503-4505. (e) Leca, D.; Toussaint, A.; Mareau,
C.; Fensterbank, L.; Lacote, E.; Malacria, M. Org. Lett. 2004, 6, 3573-
3575. (f) Padwa, A.; Flick, A. C.; Leverett, C. A.; Stengel, T. J. Org.
Chem. 2004, 69, 6377-6386.
Nitrene species are also known to perform aziridination reactions,
thus substrates derived from homoallylic alcohols may lead to both
allylic C-H insertion or aziridination products.9 However, only
traces of the aziridination product was observed from 10, and
oxazolidinone 11 was isolated in 60% yield (eq 3). In contrast, the
decomposition of Nopol-derived N-tosyloxycarbamate 12 (contain-
ing a more electron-rich double bond) led to 45% of C-H insertion
product 13 as a mixture of diastereomers and 40% of aziridination
product 14 as a single diastereomer (eq 4).19 Conversely, the reaction
of allylic N-tosyloxycarbamates is chemoselective and leads to
aziridination products exclusively in the presence of 5 mol % of
Rh2(OAc)4, an excess of K2CO3 in acetone.
(11) Review: Davies, H. M. L.; Long, M. S. Angew. Chem., Int. Ed. 2005, 44,
3518-3520.
(12) (a) Muller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905-2919. (b) Dauban,
P.; Dodd, R. H. Synlett 2003, 1571-1586. (c) Halfen, J. A. Curr. Org.
Chem. 2005, 9, 657-669.
(13) For N-arenesulfonyloxycarbamates in other amination processes, see: (a)
Greck, C.; Genet, J. P. Synlett 1997, 741-748. (b) Erdik, E. Tetrahedron
2004, 60, 8747-8782. (c) Fioravanti, S.; Morreale, A.; Pellacani, L.;
Tardella, P. A. Eur. J. Org. Chem. 2003, 4549-4552 and references
therein.
(14) (a) Lebel, H. Leogane, O. Org. Lett. 2005, 7, 4107-4110. (b) Lebel, H.;
Paquet, V. Organometallics 2004, 23, 1187-1190. (c) Lebel, H.; Paquet,
V. J. Am. Chem. Soc. 2004, 126, 320-328.
(15) Albone, D. P.; Challenger, S.; Derrick, A. M.; Fillery, S. M.; Irwin, J. L.;
Parsons, C. M.; Takada, H.; Taylor, P. C.; Wilson, J. Org. Biomol. Chem.
2005, 3, 107-111.
(16) N-tosyloxycarbamates are very easily prepared via tosylation of N-
hydroxycarbamates (see Supporting Information for details).
(17) Lower catalyst loading led to lower yields (5 mol %:83% yield of 2).
(18) Low conversion was observed with Na2CO3, NaHCO3, and MgO.
(19) For X-ray crystal structure, see Supporting Information.
(20) Both C-H insertion and aziridination reactions are not sensitive to water,
and spectrograde solvent may be used.
A variety of aziridines, resulting from the intramolecular reaction
of nitrene species generated from N-tosyloxycarbamates, were
obtained under these reaction conditions with good yields (Table
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