ORGANIC
LETTERS
2002
Vol. 4, No. 9
1471-1474
Brønsted Acid-Catalyzed Intramolecular
Hydroamination of Protected
Alkenylamines. Synthesis of Pyrrolidines
and Piperidines
Bjo1rn Schlummer and John F. Hartwig*
Department of Chemistry, Yale UniVersity, P.O. Box 208107,
New HaVen, Connecticut 06520-8107
Received February 3, 2002
ABSTRACT
The cyclization of aminoalkenes bearing an electron-withdrawing group on the nitrogen atom was catalyzed by triflic or sulfuric acid in
toluene. Pyrrolidines and piperidines were formed in excellent yields. N-Phenylanilides also underwent cyclization to form γ-lactams.
Nitrogen-containing saturated heterocyclic systems are im-
portant core structures in organic chemistry because of their
presence in many natural products. For this reason simple
procedures for the formation of pyrrolidines and piperidines
are highly desirable.1 One of the most appealing approaches
to these heterocycles is hydroamination, in which the nitrogen
carbon bond is formed by the addition of an amine to an
olefin.2 Although several transition metal-promoted processes
based on early2b,3 and late4 transition metals are known, it
seemed that an acid-catalyzed route could be developed.
Related methods for C-O bond formation using acid
catalysis have been studied in great detail. Alkenes undergo
hydration in moderately concentrated aqueous sulfuric acid
to generate saturated alcohols.5 However, the focus for the
addition of electronically similar tosylamides has been on
Hg(II)-mediated cyclizations of N-tosyl-4-pentenamines and
use of â-silicon effect for acid-catalyzed cyclizations of
sulfonamides tethered to allylsilanes.6 During studies on
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1999, 18, 2568-2570. Kim, Y. K.; Livinghouse, T.; Bercaw, J. E.
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1999, 64, 4570-4571. Su, R. Q.; Mueller, T. E. Tetrahedron 2001, 57,
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654. Willi, A. V. HelV. Chim. Acta 1964, 47, 655-661. Levy, J. B.; Taft,
R. W.; Hammett, L. P. J. Am. Chem. Soc. 1953, 75, 1253-1254.
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Org. Chem. 1992, 57, 4401-4404. Takahata, H.; Bandoh, H.; Momose, T.
Heterocycles 1993, 36, 2777-2782. Harding, K. E.; Burks, S. R. J. Org.
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10.1021/ol025659j CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/27/2002