ORGANIC
LETTERS
2009
Vol. 11, No. 9
1895-1898
Ketonitrones via Cope-Type
Hydroamination of Allenes
Joseph Moran, Jennifer Y. Pfeiffer, Serge I. Gorelsky, and Andre´ M. Beauchemin*
Centre for Catalysis Research and InnoVation, Department of Chemistry, UniVersity of
Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Received February 11, 2009
ABSTRACT
The synthesis of ketonitrones from N-alkylhydroxylamines and monosubstituted allenes is accomplished via a Cope-type hydroamination
reaction in moderate to good yields. Allenes also undergo a similar reaction with aqueous hydroxylamine to give oximes in excellent yield.
DFT calculations support a proposed concerted, five-membered hydroamination process, and calculated transition state energies are in excellent
agreement with experimental observations.
Nitrones are highly useful intermediates in organic synthesis,
and their reactivity has been studied extensively, particularly
in the context of 1,3-dipolar cycloaddition chemistry.1,2 The
large bulk of this work focuses on aldonitrones, largely due
to their ease of preparation via the condensation of an
N-alkyhydroxylamine with an aldehyde. In contrast, the
preparation of ketonitrones may not always be accomplished
by simple condensation with a ketone, and occasional reports
of synthetic routes to these compounds are typically of
narrow scope and are rare for linear ketonitrones.3 As such,
the applications of ketonitrones as 1,3-dipoles and radical
traps have been much less extensive than for their aldonitrone
cousins.2-4 Herein, we report a direct preparation of keto-
nitrones via an intermolecular Cope-type hydroamination
reaction of N-alkylhydroxyalmines with allenes.5
The hydroamination reaction is a direct and atom-
economical approach to the synthesis of nitrogen-containing
molecules from unsaturated precursors.6 The addition of
amines to allenes has been particularly well studied because
of the activated nature of their double bonds and their ability
to give either imines or allylamines depending on the
regiochemistry of the reaction.7,8
(5) For intramolecular hydroaminations of N-allenylhydroxylamines, see:
(a) Dumez, E.; Dulce`re, J.-P. Chem. Commun. 1998, 479. (b) Dumez, E.;
Faure, R.; Dulce`re, J.-P. Eur. J. Org. Chem. 2001, 2577. (c) Schade, W.;
Reissig, H.-U. Synlett 1999, 632.
(1) (a) Grigor’ev, I. A. In Nitrile Oxides, Nitrones, and Nitronates in
Organic Synthesis; Feuer, H., Ed.; Wiley: Hoboken, 2008; Chapter 2. (b)
Tufaniello, J. J. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.;
VCH: New York, 1988; Vol. 2, pp 83-168.
(6) For selected reviews including allene substrates, see: (a) Mu¨ller, T. E.;
Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. ReV. 2008, 108,
3795. (b) Aillaud, I.; Collin, J.; Hannedouche, J.; Schulz, E. Dalton Trans.
2007, 5105. (c) Hunt, P. A. Dalton Trans. 2007, 1743. (d) Hultzsch, K. C.
AdV. Synth. Catal. 2005, 347, 367–391. (e) Mu¨ller, T. E.; Beller, M. Chem.
ReV. 1998, 98, 675.
(2) Hamer, J.; Macaluso, A. Chem. ReV. 1964, 64, 473
.
(3) (a) Fischer, R.; Hyrgova, E.; Fisera, L.; Hametner, C.; Cyranski, M.
Chem. Pap. 2005, 59, 275. (b) Tomioka, Y.; Nagahiro, C.; Nomura, Y.;
Maruoka, H. J. Heterocycl. Chem. 2003, 40, 121. (c) Torrente, S.; Noya,
B.; Branchadell, V.; Alonso, R. J. Org. Chem. 2003, 68, 4772. (d) Hulsbos,
E.; Marcus, J.; Brussee, J.; van der Gen, A. Tetrahedron: Asymmetry 1997,
8, 1061. (e) Franco, S.; Mercha´n, F. L.; Merino, P.; Tejero, T. Synth.
Commun. 1995, 25, 2275. (f) Black, D. St. C.; Johnson, L. M. Aust. J. Chem.
1984, 37, 117. (g) Exner, O. Collect. Czech. Chem. Commun. 1951, 16,
258.
(7) For recent examples of intramolecular hydroaminations of allenes,
see: (a) Zhang, Z.; Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc.
2007, 129, 14148. (b) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007,
129, 4253. (c) Lalonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F. D.
J. Am. Chem. Soc. 2007, 129, 2452. (d) Bender, C. F.; Widenhoefer, R. A.
Chem. Commun. 2008, 2741
.
(8) For recent examples of intermolecular hydroamination of allenes,
see: (a) Lavallo, V.; Frey, G. D.; Donnadieu, B.; Soleilhavoup, M.; Bertrand,
G. Angew. Chem., Int. Ed. 2008, 47, 5224. (b) Nishina, N.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2006, 45, 3314. (c) Kinder, R. E.; Zhang, Z.;
(4) (a) Hassan, I. E.; Charles, L.; Lauricella, R.; Tuccio, B. New J. Chem.
2008, 32, 680. (b) Hassan, I. E.; Lauricella, R.; Tuccio, B. Cent. Eur.
J. Chem. 2006, 4, 338
.
Widenhoefer, R. A. Org. Lett. 2008, 10, 3157.
10.1021/ol900292r CCC: $40.75
Published on Web 03/30/2009
2009 American Chemical Society