Catalytic hydroamination of alkynes and norbornene with neutral and cationic tantalum imido complexes

Article abstract of DOI:10.1021/ol0492851

(Matrix Presented) Several tantalum imido complexes have been synthesized and shown to efficiently catalyze the hydroamination of internal and terminal alkynes. An unusual hydroamination/hydroarylation reaction of norbornene catalyzed by a highly electrop

Full text of DOI:10.1021/ol0492851

ORGANIC
LETTERS
2004
Vol. 6, No. 15
2519-2522
Catalytic Hydroamination of Alkynes
and Norbornene with Neutral and
Cationic Tantalum Imido Complexes
Laura L. Anderson, John Arnold,* and Robert G. Bergman*
Department of Chemistry, UniVersity of California, Berkeley, California 94720
bergman@cchem.berkeley.edu; arnold@socrates.berkeley.edu
Received April 19, 2004
ABSTRACT
Several tantalum imido complexes have been synthesized and shown to efficiently catalyze the hydroamination of internal and terminal alkynes.
An unusual hydroamination/hydroarylation reaction of norbornene catalyzed by a highly electrophilic cationic tantalum imido complex is also
reported. Factors affecting catalyst activity and selectivity are discussed along with mechanistic insights gained from stoichiometric reactions.
Catalytic hydroamination is a potentially powerful synthetic
method by which valuable nitrogen-containing products (e.g.,
amines, imines, and enamines) may be obtained in a single
step from readily available unsaturated hydrocarbons. Several
recent reviews have highlighted the considerable current
interest in this transformation.1 Catalysts derived from both
early and late transition metals as well as lanthanides have
shown significant activity for the addition of N-H bonds
across a variety of alkynyl and activated alkenyl moieties;2-7
however, a general and selective protocol for the hydroami-
nation of unactivated alkenes remains unknown.
in contrast to the extensive application of group 4 metals to
hydroamination catalysis, no examples existed of catalysis
(2) (a) Ryu, J.-S.; Marks, T. J.; McDonald, F. E. J. Org. Chem. 2004,
69, 1038-1052. (b) Hong, S.; Kawaoka, A. M.; Marks, T. J. J. Am. Chem.
Soc. 2003, 125, 15878-15892. (c) Kim, Y. K.; Livinghouse, T. Angew.
Chem., Int. Ed. 2002, 41, 3645-3647. (d) Utsunomiya, M. Hartwig, J. F.
J. Am. Chem. Soc. 2004, 126, 2702-2703. (e) Yamashita, M., Vicario J.
V. C., Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 16347-16360. (f)
Kanzelberger, M.; Zhang, X.; Emge, T. J.; Goldman, A. S.; Zhao, J.;
Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 13644-13645.
(g) Fadini, L.; Togni, A. Chem. Commun. 2003, 30-31. (h) Dorta, R.; Egli,
P.; Zurcher, F.; Togni, A. J. Am. Chem. Soc. 1997, 119, 10857-10858. (i)
Brunet, J.-J.; Cadena, M.; Chu, N. C.; Diallo, O.; Jacob, K.; Mothes, E.
Organometallics 2004, 23, 1264-1268. (j) Lauterwasser, F.; Hayes, P. G.;
Brase, S.; Piers, W. E.; Schafer, L. L. Organometallics 2004, 23, 2234-
2237. (k) Hultzsch, K. C.; Hampel, F.; Wagner, T. Organometallics 2004,
23, 2601-2612.
(3) (a) Baranger, A. M.; Walsh, P. J.; Bergman, R. G. J. Am. Chem.
Soc. 1993, 115, 2753-2763. (b) Walsh, P. J.; Baranger, A. M.; Bergman,
R. G. J. Am. Chem. Soc. 1992, 114, 1708-1719. (c) Johnson, J. S.; Bergman,
R. G. J. Am. Chem. Soc. 2001, 123, 2923-2924. (d) Straub, B. F.; Bergman,
R. G. Angew. Chem., Int. Ed. 2001, 40, 4632-4635. (e) Ackermann, L.;
Bergman, R. G. Org. Lett. 2002, 4, 1475-1478. (f) Ackermann, L.;
Bergman, R. G.; Loy, R. N. J. Am. Chem. Soc. 2003, 125, 11956-11963.
(4) (a) Haak, E.; Siebeneicher, H.; Doye, S. Org. Lett. 2000, 2, 1935-
1937. (b) Haak, E.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 1999,
38, 8, 3389-3391. (c) Pohlki, F.; Doye, S. Angew. Chem., Int. Ed. 2001,
40, 2305-2308.
Hydroamination methods using complexes of the group 4
metals have been described by the Bergman group3 as well
as by Doye,1e,4 Odom,5 Beller,6 and others.7 In each of these
examples, metal-imido (MdNR) species have been proposed
as key intermediates in the catalytic cycle. We noticed that,
(1) (a) Muller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675-703. (b)
Beller, M.; Breindl, C.; Eichberger, M.; Hartung, C. G.; Seayad, J.; Thiel,
O. R.; Tillack, A.; Trauthwein, H. Synlett 2002, 10, 1579-1594. (c) Pohlki,
F.; Doye, S. Chem. Soc. ReV. 2003, 32, 104-114. (d) Bytschkov, I.; Doye,
S. Eur. J. Org. Chem. 2003, 935-946. (e) Yamamoto, Y.; Radhakrishnan,
U. Chem. Soc. ReV. 1999, 28, 199-207. (f) Seayad, J.; Tillack, A.; Hartung,
C. G.; Beller, M. AdV. Synth. Catal. 2002, 344, 795-813. (e) For an
extensive list of references also see: Heutling, A.; Doye, S. J. Org. Chem.,
2002, 67, 1961-1964.
(5) (a) Shi, Y.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001,
20, 3967-3969. (b) Cao, C.; Ciszewski, J. T.; Odom, A. L. Organometallics
2001, 20, 5011-5013. (c) Li, Y.; Shi, Y.; Odom, A. L. J. Am. Chem. Soc.
2004, 126, 1794-1803.
10.1021/ol0492851 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/29/2004

Scheme 1. Synthesis of Neutral and Cationic Alkyl Tantalum
Table 1. Hydroamination of Diphenylacetylene with Aniline
Using Tantalum Imido Complexes
Imido Complexes
entry
[Ta]
time (h)
% yieldb
1
2
3
4
5
6
(PhCH2)3TadNCMe3, 1a
[(PhCH2)TadNCMe3]+, 2
Np3TadNCMe3, 1b
(Et2N)3TadNCMe3
Ta(NMe2)5
30
8
12
30
30
30
>95
>95
>95
>95
>95
NR
Cl3TadNCMe3
by group 5 analogues.8 Cationic group 5 imido complexes
seemed particularly promising as potential hydroamination
catalysts, since these compounds are isoelectronic to the
group 4 catalysts and the enhanced polarity of the metal
imide linkage of such compounds would likely result in
increased catalytic activity.
a Identical results were obtained when the reaction was run in C6D6 or
C7D8. b Yields are given as NMR yields.
>95% yield were achieved through in situ generation of 2
(Table 1, entry 2).10 All subsequent experiments with the
cationic complex were therefore performed by premixing 1a
and Ph3CB(C6F5)4 with the substrate-amine mixture.
Several neutral Ta complexes were also evaluated as
catalysts for the hydroamination of diphenylacetylene with
aniline. As shown in Table 1, compounds 1a, 1b, (Et2N)3-
TadNCMe3, and Ta(NMe2)511 were all competent catalysts,
affording the desired products as thermodynamic imine/
enamine mixtures. While all the catalysts screened provided
high yields, the enhanced reactivity associated with neutral
tris(neopentyl) complex 1b and cationic 2 made these
compounds attractive for further study.
We report herein the synthesis of new neutral and cationic
imidotantalum complexes and their application to the cata-
lytic hydroamination of alkynes. These tantalum imido
species also catalyze an unusual hydroamination/hydroary-
lation reaction between norbornene and aniline. The hy-
droamination of norbornene represents one of the first reports
of an intermolecular alkene hydroamination catalyzed by an
early transition metal.9 The scope of this method, a com-
parison between neutral and cationic tantalum catalysts, and
mechanistic insights gained from stoichiometric reactions are
discussed below.
Several alkynes were treated with aniline in the presence
of 1b and 2 in order to determine the scope of this method
with respect to the alkyne component (Table 2). Both
complexes catalyze the hydroamination of all substrates
investigated; dialkylacetylenes react more slowly than diphe-
nylacetylene (entries 1 and 2), while terminal alkynes are
converted significantly faster (entries 3 and 4). The hy-
droamination of 2-hexyne (entry 2) proceeded with no
regioselectivity. High levels of Markovnikov selectivity are
observed with other substrates (entries 3 and 4), but may be
caused by selective decomposition of the anti-Markovnikov
product.12 Surprisingly, 1-phenylpropyne was a difficult
substrate for these catalytic systems (entry 5). However, the
hydroamination of 1-phenylpropyne with 2, while 1b fails
to react, suggests that 2 is the more potent catalyst. Although
2 exhibits greater activity toward 1-phenylpropyne, neutral
Neutral trialkyltantalum imido complexes 1a and 1b were
synthesized by treatment of the trichlorotantalum precursor
(py)2Cl3TadNCMe3 (py ) pyridine) with 3 equiv of the
corresponding Grignard reagent (Scheme 1). Benzyl anion
abstraction from 1a with Ph3CB(C6F5)4 produced an insoluble
orange solid that was tentatively assigned as an oligomer of
the 10e- cationic complex 2. This formulation was supported
by reaction of 2 with diphenylacetylene, which afforded the
fully characterized azametallacyclobutene complex 3.
In a preliminary experiment, a mixture of diphenylacety-
lene and aniline in the presence of 5 mol % of 2 at 135 °C
gave the products of hydroamination (imine/enamine ) 3:1)
in 26% yield (1H NMR). Under analogous conditions,
complex 3 gave similar results. Improved reactivity and
(6) (a) Tillack, A.; Castro, I. G.; Hartung, C. G.; Beller, M. Angew.
Chem., Int. Ed. 2002, 41, 2541-2543. (b) Khedkar, V.; Tillack, A.; Beller,
M. Org. Lett. 2003, 5, 4767-4770.
(10) The cause of higher activity in the in situ generated complex is
presently unknown; unfortunately, neither the cationic complex nor any
subsequent intermediates can be observed using NMR spectroscopy due to
constraints of instantaneous reactivity and insolubility, respectively.
(11) This compound has already been shown to catalyze the hydroami-
nation of 1-hexyne. See ref 8.
(12) When this reaction is performed at 75 °C, production of the anti-
Markovnikov enamine can be observed by 1H NMR but decomposes before
the reaction goes to completion. Low yields of product caused by
oligomerization of phenylacetylene have also been observed by Odom and
co-workers (see ref 5a). Low yields and Markovnikov selectivity were also
observed by Vendier and co-workers (see ref 8).
(7) (a) Ong, T. G.; Yap, G. P. A.; Richeson, D. S. Organometallics 2002,
21, 2839-2841. (b) Li, C.; Thomson, R. K.; Gillon, B.; Patrick, B. O.;
Schafer, L. L. Chem. Commun. 2003, 2462-2463. (c) Zhang, Z.; Schafer,
L. L. Org. Lett. 2003, 5, 4733-4736. (d) Knight, P. D.; Munslow, I.;
O’Shaughnessy, P. N.; Scott, P. Chem. Commun. 2004, 894-895.
(8) During the course of this work, a V(IV) hydroaminationcatalyst was
reported: Lorber, C.; Choukroun, R.; Vendier, L. Organometallics 2004,
23, 1845-1850.
(9) See the accompanying paper in this issue for independent work on a
Ti-catalyzed system for the hydroamination of norbornene: Ackermann,
L.; Kaspar, L. T.; Gschrei, C. J. Org. Lett. 2004, 6, 2515-2518.
2520
Org. Lett., Vol. 6, No. 15, 2004

Scheme 2. Hydroamination of Allene and Cyclononadiene
Table 2. Hydroamination of Various Alkynes with Aniline
% yieldb
entry
R1, R2
6/7
NA
time (h)
1b
2
1
2
3
4
5
Et, Et
n-Pr, Me
Ph, H
n-Pr, H
Ph, Me
24
24
2
2
24
>95 (83c)
>95
77 (65c)
70
>95
71
66
62
19
1:1
only 6
only 6
only 7
products of catalyst decomposition were obtained in reactions
with benzylamine and n-butylamine. Sterically demanding
tert-butylamine was unreactive in the presence of both
catalysts.
NR
a Identical results were obtained when the reaction was run in C6D6 or
C7H8. b Yields are given as NMR yields. Hydrolysis to the corresponding
ketone was used to confirm these assignments. c Isolated yield of imine
reduction product.
In an attempt to extend the scope of Ta-catalyzed hy-
droaminations beyond alkynes, both 1b and 2 were examined
as catalysts for the addition of anilines to allenes and olefins.
Catalyst 1b failed to exhibit any activity toward allenes;
however, 2 catalyzed the hydroamination of both propadiene
and cyclonona-1,2-diene (Scheme 2).
Treatment of a mixture of norbornene and aniline with a
catalytic amount of 2 afforded products both of olefin
hydroamination (10) and hydroarylation (11) in a ratio of
1:2 (Scheme 3).9,14,15 This is one of the first examples of
catalyst 1b appears to provide reaction products for this
survey of alkynes in consistently higher yields.
Several substituted anilines were examined in the reaction
with diphenylacetylene to determine the tolerance of the two
catalysts for the amine component (Table 3). Both 1b and 2
were efficient catalysts for the reaction with para-substituted
anilines. Ortho-substituted anilines proved to be more
challenging substrates, showing little or no reaction with 1b
and giving moderate yields with 2. The rate of catalyst
Scheme 3. Addition of Aniline to Norbornene
Table 3. Addition of Substituted Anilines to Diphenylacetylene
intermolecular alkene hydroamination with an early transition
metal catalyst. Unoptimized, this reaction only provides 32%
yield of the desired amines. A significant amount of polymer
and other higher molecular weight byproducts were observed
in this reaction and are thought to be responsible for the
overall low yields of the desired products. An interesting
aspect of this transformation is the possibility of selectively
activating N-H bonds versus C-H bonds. Variation of the
ratio of aniline to norbornene failed to alter the 1:2 ratio of
products; however, preliminary studies with substituted
anilines have shown promising results.16
% yieldb
entry
X
8/9
3:1
4:1
7:1
4:1
only 8
1b
98
79
31
>95
7
2
1
2
3
4
5
H
96 (75c)
74
72 (83c)
>95 (66c)
69
4-Me
4-OMe
4-Cl
2,6-Me2
a Identical results were obtained when the reaction was run in C6D6 or
C7D8. b Yields are given as NMR yields. Hydrolysis to the corresponding
ketone was used to confirm these assignments. c Isolated yield of the ketone
hydrolysis product.
Two key steps in the catalytic cycles proposed for
hydroamination with group 4 complexes are the formation
of an intermediate azametallacycle and its subsequent pro-
decomposition in these cases appears to be competitive with
the rate of hydroamination.13 The reaction in entry 5 can be
driven to completion if additional 2 is introduced after 24 h.
Very low yields of hydroaminated products along with
(14) Compound 1b showed no reactivity when treated with a mixture of
norbornene and aniline.
(15) This reaction has previously been observed with a Rh catalyst.
Brunet, J.-J.; Commenges, G.; Neibecker, D.; Philippot, K. J. Organomet.
Chem. 1994, 469, 221-228.
(16) Preliminary GC-MS results indicate that electron-withdrawing
substituents on aniline favor formation of 10 while electron-donating
substituents favor formation of 11.
(13) Preliminary results indicate that the catalyst decomposes to a
tantalum imido cluster within 24 h.
Org. Lett., Vol. 6, No. 15, 2004
2521

In summary, several neutral and cationic tantalum imido
complexes have been identified as effective catalysts for the
hydroamination of alkynes, allenes, and norbornene. Cationic
tantalum complex 2 has shown enhanced reactivity toward
more challenging substrates such as ortho-substituted anilines
and allenes, in agreement with our original hypothesis.
Interestingly, the cationic complex is also one of the first
two early metal complexes shown to catalyze the intermo-
lecular hydroamination of norbornene. Stoichiometric reac-
tions have indicated that the cationic tantalum catalyzed
processes are occurring through a mechanism similar to that
known for group 4 catalysts. Work is currently in progress
to increase the lifetimes, activities, and substrate scope of
these and related catalysts.
Scheme 4. Treatment of 3 with 2,6-Dimethylaniline
tonation by amine.3a,c,d,4b To assess whether similar steps
could be involved in cationic Ta-catalyzed hydroaminations,
a study was carried out using stoichiometric amounts of
isolable azametallacyclobutene complex 3 and 2,6-dimethyl-
aniline (Scheme 4). Upon mixing at room temperature, the
amine immediately coordinates to the electrophilic tantalum
center of 3, as indicated by the appearance of two distinctive
diastereotopic N-H resonances (δ ) -1.05, -1.23) in the
1H NMR spectrum of the reaction mixture (12).17 Interest-
ingly, this complex is stable at room temperature for
approximately 24 h before the Ta-C bond of the metalla-
cycle is protonated and the diastereotopic N-H resonances
disappear. Furthermore, metallacycle 3 catalyzes the addition
of aniline to diphenylacetylene with efficiency identical to
that of 2. Overall, these results suggest that cationic tantalum-
catalyzed hydroaminations proceed through a catalytic cycle
similar to that proposed for group 4 analogues.
Acknowledgment. We would like to thank Dr. Lutz
Ackermann for sharing information about his titanium
hydroamination system and for publishing concurrently. This
work was supported by the National Institutes of Health
(Grant No. GM-25459 to R.G.B.) and the National Science
Foundation (Grant No. CHE-0072819 to J.A.).
Supporting Information Available: Experimental pro-
cedures, relevant NMR spectra, and characterization data for
new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
(17) An analogous experiment with 2,6-dimethylaniline-N-d2 confirmed
the assignment of the protons in question.
OL0492851
2522
Org. Lett., Vol. 6, No. 15, 2004