Imidotitanium complexes as hydroamination catalysts: Substantially enhanced reactivity from an unexpected cyclopentadienide/amide ligand exchange

Full text of DOI:10.1021/ja005685h

J. Am. Chem. Soc. 2001, 123, 2923-2924
2923
species that hydroaminated 1,2-propadiene in good yields (eq 2).
Aryl and alkylamines are both tolerated, as are hydrazines; bulky
amines appear to react with greater facility than those with
lessened steric demand.
Imidotitanium Complexes as Hydroamination
Catalysts: Substantially Enhanced Reactivity from
an Unexpected Cyclopentadienide/Amide Ligand
Exchange
Jeffrey S. Johnson and Robert G. Bergman*
Department of Chemistry and Center for
New Directions in Organic Synthesis
UniVersity of California, Berkeley, California 94720
ReceiVed October 10, 2000
The addition of an N-H bond across a carbon-carbon double
or triple bond is potentially one of the most direct and efficient
methods of alkylating an amine. Considerable effort has been
expended in the search for transition metal complexes that will
catalyze this desirable transformation, and while notable successes
have been realized, general solutions to the problem have proven
elusive.1 As a consequence, the discovery and development of
hydroamination reactions remain important goals.
Relatively few early transition metal complexes have been
shown to be hydroamination catalyst precursors. Among these
are the class of bis(cyclopentadienyl)zirconium and titanium
alkyne hydroamination catalysts studied earlier by our group2 and
by Doye’s3,4 (eq 1). In both systems it has been assumed that the
critical intermediates are the 16-electron imido complexes Cp2Md
NR. The purpose of this communication is to report titanium-
based imido complexes5,6 that function as catalyst precursors for
both allene and alkyne hydroamination reactions.7-9 A detailed
mechanistic investigation has revealed an unexpected cyclopen-
tadienide/amide ligand exchange reaction that transforms the bis-
cyclopentadienyltitanium precursors (Cp2TiLn) into a monocy-
clopentadienyl titanium(amido) complex (Cp(ArNH)TiLn)10
exhibiting substantially higher reactivity than the Cp2TiLn precur-
sor.
Monitoring these hydroamination reactions by 1H NMR
spectroscopy revealed the liberation of cyclopentadiene in amounts
that varied with the particular amine being employed.13 In an effort
to determine the identity of the true catalyst, stoichiometric
reactions of Cp2TiMe2 with 2,6-dimethylaniline (2.0 equiv) were
carried out (C6D6, 75 °C, 24 h). This revealed the decomposition
of the starting complex, and the formation of four different Cp-
containing compounds plus free cyclopentadiene. Thermolysis of
this mixture in the presence of added pyridine (1.5 equiv, 75 °C)
resulted in formation of the single cyclopentadienyl(amido)-
titanium imido complex 6‚py in 62% yield versus internal standard
(eq 3). We have not established the identity of the products formed
prior to pyridine trapping, but it seems likely that pyridine
effectively intercepts (or promotes formation of) a monomeric
imido species14 from a monomer-dimer equilibrium. Imido
complex 6‚py, a titanium analogue of a similar imidozirconium
complex previously prepared from (η5-C5Me5)ZrCl3, LiNH(2,6-
i-Pr2C6H3), and pyridine,15 could be isolated as a brown solid in
∼55-60% yield, contaminated with 2,6-dimethylaniline. The
difficulties associated with removing amine contaminants from
early transition metal imido complexes have been previously
noted.16,17 Complex 6‚py underwent facile dative ligand exchange
with trimethylphosphine oxide to afford complex 6‚OPMe3, which
was independently prepared from CpTiCl3, LiNH(2,6-Me2C6H3),
and Me3PO. An X-ray diffraction study of 6‚OPMe3 confirmed
the presence of the TidN linkage and the bent nature of the amide
ligand.
We became interested in catalytic allene hydroamination with
the discovery that enantiopure (ebthi)zirconium imido complexes
kinetically resolve chiral racemic allenes under stoichiometric
conditions (ebthi ) ethylene bis(tetrahydroindenyl)).11 Experi-
ments to explore the feasibility of metal-catalyzed allene hy-
droamination were undertaken with the eventual goal of devel-
oping a catalytic variant of this kinetic resolution. A brief screen
of catalysts revealed that titanium complexes were more reactive
12
than their zirconium counterparts, and that Cp2TiMe2 was a
convenient precursor to an undefined, but competent, catalyst
(1) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675.
(2) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J. Am. Chem. Soc. 1992,
114, 1708.
(3) Haak, E.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 1999, 38,
3389.
(4) Haak, E.; Siebeneicher, H.; Doye, S. Org. Lett. 2000, 2, 1935.
(5) Mountford, P. Chem. Commun. 1997, 2127.
(6) Wigley, D. E. Prog. Inorg. Chem. 1994, 42, 239.
(7) Besson, L.; Gore´, J.; Cazes, B. Tetrahedron Lett. 1995, 36, 3857.
(8) Al-Masum, M.; Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1997,
38, 6071.
Mono(Cp) complex 6‚py catalyzed allene hydroamination at
an unusally low temperature (eq 4, 45 °C, t1/2 < 30 min, [allene]0
) 0.40 M, [6‚py] ) 0.02 M). The mildness of these conditions
prompted us to carry out a detailed kinetic analysis of the reaction.
Our initial attempts were frustrated by erratic rates presumably
caused by the presence of trace amounts of water and oxygen.
(9) Arredondo, V. M.; McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc.
1998, 120, 4871.
(10) McGrane, P. L.; Jensen, M.; Livinghouse, T. J. Am. Chem. Soc. 1992,
114, 5459.
(11) Sweeney, Z. K.; Salsman, J. L.; Andersen, R. A.; Bergman, R. G.
Angew. Chem., Int. Ed. 2000, 39, 2339.
(12) Sieibeneicher, H.; Doye, S. J. Prakt. Chem. 2000, 342, 102.
10.1021/ja005685h CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/02/2001

2924 J. Am. Chem. Soc., Vol. 123, No. 12, 2001
Communications to the Editor
Scheme 1
the addition of 2,6-dimethylaniline to diphenylacetylene (75 °C,
t1/2 < 15 min, [alkyne]0 ) 0.43 M, [6‚py] ) 0.01 M), while
complex 2, under identical conditions, yielded no enamine product
after 12 h. In accord with Doye’s observations,3 hydroamination
using 2 was achieved only after 3 d at 105 °C; similarly, the use
of Cp2Zr(NHAr)2 (1) required 13 d at 120 °C.2
However, the addition of small quantities of Cp2ZrMe2, a powerful
desiccant we have used previously to solve such problems,18
eliminated this difficulty and gave clean pseudo-first-order
disappearance of allene in the presence of excess amine.19
Repeating these rate studies in the presence of varying concentra-
tions of catalyst, pyridine, and excess amine revealed that the
reaction is zero-order in [amine], inverse first-order in [pyridine],
and first-order in [6‚py] (eq 5).20 This contrasts the previously
studied Cp2Zr(NHR)2 system2 which exhibited an inverse first-
order dependence on [amine]. The rate law for the catalysis by
6‚py, coupled with the fact that complex 6‚py is the only Ti-
containing species observed during the catalytic reaction (1H NMR
spectroscopy), indicates that addition of ArNH2 to the TidN
linkage to form CpTi(NHAr)3 is not thermodynamically favored
in the titanium system, behavior that also differs from the Cp2-
Zr(NHR)2 system.
In preliminary experiments we have also utilized imido
complex 6‚py in the more challenging task of hydroaminating
substituted allenes. The catalyzed additions of 2,6-dimethylaniline
to 1-phenyl-1,2-propadiene (12), 1,2-nonadiene (13), and 1,2-
cyclononadiene (14) proceed to give imines 15-17 in good
isolated yields (eq 7).22 Complete regiocontrol is observed in
hydroamination of substituted allenes, a direct consequence of
the regiochemistry of the [2 + 2] cycloaddition that places the
exocyclic olefin â to the metal center in the product metallacycle
(8). This regiochemistry is complementary to palladium-catalyzed
intermolecular allene hydroamination reactions that afford allylic
amine products.7,8
In summary, we have found that Cp2TiMe2 functions as a
catalyst precursor for allene hydroamination. However, mecha-
nistic studies establish that an unusual ligand exchange reaction
results in loss of a cyclopentadienyl ligand to generate the highly
active monocyclopentadienyltitanium catalyst precursor 6‚py. We
assume that the same mono-Cp complex is formed in alkyne
hydroamination, but its presence in low concentration requires
the use of higher temperatures. Accordingly, more rapid alkyne
hydroamination is also achieved by directly charging the system
with 6‚py. Future work will focus on understanding the cause of
this Cp-amido ligand exchange and developing highly active,
general hydroamination catalysts, as well as asymmetric variants.
A mechanism consistent with the observed rate law is outlined
in Scheme 1. Reversible pyridine dissociation from 6‚py generates
the Lewis base-free imido complex 7. Formal [2 + 2] cycload-
dition with allene21 leads to an azametallacyclobutane (8) that is
rapidly protonated by amine to generate tris(amido)Ti complex
9. Elimination expels the enamine product 10 (which tautomerizes
to the thermodynamically stable imine 11) and regenerates the
catalyst 7.
The generally enhanced reactivity of 6‚py was apparent when
it was compared to that of Cp2TiMe2 (2) in the alkyne hydroami-
nation reaction (eq 6). Complex 6‚py (3 mol %) rapidly catalyzed
Acknowledgment. This paper is dedicated to Professor David Evans
on the occasion of his 60th birthday. This research was supported by the
National Institutes of Health (Grant no. GM-25459 to R.G.B. and a NRSA
postdoctoral fellowship to J.S.J.). The structural study of 6‚OPMe3 was
carried out by Drs. A. G. Oliver and F. J. Hollander of the U.C. Berkeley
College of Chemistry X-ray Diffraction Facility (CHEXRAY). We thank
Professor R. A. Anderson, Professor J. Arnold, D. M. Tellers, and J. S.
Yeston for helpful discussions and experimental assistance. The Center
for New Directions in Organic Synthesis is supported by Bristol-Myers
Squibb as Sponsoring Member.
(13) Fuhrhop, J. H. Tetrahedron Lett. 1969, 3205.
(14) Bennett, J. L.; Wolczanski, P. T. J. Am. Chem. Soc. 1994, 116, 2179.
(15) Bai, Y. N.; Roesky, H. W.; Noltemeyer, M.; Witt, M. Chem. Ber.
1992, 125, 825.
(16) Arney, D. J.; Bruck, M. A.; Huber, S. R.; Wigley, D. E. Inorg. Chem.
1992, 31, 3749.
(17) Blake, A. J.; Collier, P. E.; Dunn, S. C.; Li, W. S.; Mountford, P.;
Shishkin, O. V. J. Chem. Soc., Dalton Trans. 1997, 1549.
(18) Proulx, G.; Bergman, R. G. Organometallics 1996, 15, 684.
(19) Control experiments demonstrate that Cp2ZrMe2 is not catalytically
competent under the reaction conditions employed.
Supporting Information Available: Details of kinetic analysis with
relevant plots, experimental procedures, characterization data for new
compounds, and X-ray diffraction data for 6‚OPMe3 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
(20) Details of the reaction kinetics may be found in the Supporting
Information.
(21) Bashall, A.; Collier, P. E.; Gade, L. H.; McPartlin, M.; Mountford,
P.; Tro¨sch, D. J. M. Chem. Commun. 1998, 2555.
(22) Attempts to hydroaminate acyclic 1,3-disubstituted allenes, heteroatom-
substituted allenes, or unfunctionalized alkenes have to date been unsuccessful.
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