ORGANIC
LETTERS
2002
Vol. 4, No. 9
1475-1478
A Highly Reactive Titanium Precatalyst
for Intramolecular Hydroamination
Reactions
Lutz Ackermann and Robert G. Bergman*
Department of Chemistry and Center for New Directions in Organic Synthesis,
UniVersity of California, Berkeley, California 94720-1460
Received February 5, 2002
ABSTRACT
Tetrakisamido titanium complexes are significantly more active than Cp2TiMe2 (1) in the intramolecular hydroamination of aminoalkynes and
aminoallenes. In the latter case, the regioselectivity of the transformation depends on the nature of the precatalyst, yielding the most selective
and reactive catalysis with the bis(sulfonamido) complex 11.
The direct addition of an N-H bond across a carbon-carbon
multiple bond, the hydroamination reaction, is the most atom
economical way to synthesize substituted amines.1 Although
appreciable progress has been made,2 a general procedure
for this transformation remains elusive.
precatalyst.5 Detailed mechanistic investigations of this
reaction in our group revealed that the catalytically active
species is generated via a Cp/amide ligand exchange. This
conversion of the titanocene species (Cp2TiL2) into a
monocyclopentadienyl titanium amido complex (CpTi(N-
RH)Ln)6 led to the development of a titanium complex with
enhanced catalytic activity in the hydroamination of alkynes
and allenes.7 Therefore, we became interested in studying
the catalytic reactivity of noncyclopentadienyl-supported
titanium precursors. The recent report by Odom and co-
workers8 that Ti(NMe2)4 (2) catalyzes the hydroamination
of alkynes prompted us to disclose our preliminary results
In the early 1990s, we reported the catalytic activity of
zirconocene amido complexes in the hydroamination of
alkynes.3 Doye subsequently disclosed the intermolecular
4
hydroamination of alkynes using Cp2TiMe2 (1) as the
(1) (a) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675. (b) Nobis,
M.; Driessen-Ho¨lscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983.
(2) (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546.
(b) Kawatsura, M.; Hartwig, J. F. Organometallics 2001, 20, 1960. (c) Lo¨ber,
O.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 4366. (d)
Ryu, J.-S.; Marks, T. J.; McDonald, F. E. Org. Lett. 2001, 3, 3091. (e)
Straub, T.; Haskel, A.; Neyroud, T. G.; Kapon, M.; Botoshansky, M.; Eisen,
M. S. Organometallics 2001, 20, 5017. (f) Yamamoto, Y.; Radhakrishnan,
U. Chem. Soc. ReV. 1999, 28, 199. (g) Senn, H. M.; Blo¨chel, P. E.; Togni,
A. J. Am. Chem. Soc. 2000, 112, 4098. (h) Mu¨ller, T. E.; Berger, M.;
Grosche, M.; Herdtweck, E.; Schmidtchen, F. P. Organometallics 2001,
20, 4384. (i) Minami, T.; Okamoto, H.; Ikeda, S.; Tanaka, R.; Ozawa, F.;
Yoshifuji, M. Angew. Chem., Int. Ed. 2001, 40, 4501. (j) Hartung, C. G.;
Tillack, A.; Trautwein, H.; Beller, M. J. Org. Chem. 2001, 66, 6339. (k)
Hartung, C. G.; Breindl, C.; Tillack, A.; Beller, M. Tetrahedron 2000, 56,
5157.
(3) (a) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J. Am. Chem.
Soc. 1992, 114, 1708. (b) Baranger, A. M.; Walsh, P. J.; Bergman, R. G.
J. Am. Chem. Soc. 1993, 115, 2753.
(4) Siebenreicher, H.; Doye, S. J. Prakt. Chem. 2000, 342, 102.
(5) (a) Haak, E.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 1999,
38, 3389. (b) Bytschkov, I.; Doye, S. Eur. J. Org. Chem. 2001, 4411.
(6) McGrane, P. L.; Jensen, M.; Livinghouse, T. J. Am. Chem. Soc. 1992,
114, 5459.
(7) Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 2923.
(8) Shi, Y.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001, 20,
3967.
10.1021/ol0256724 CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/30/2002