Use of group 4 Bis(sulfonamido) complexes in the intramolecular hydroamination of alkynes and allenes

Article abstract of DOI:10.1021/ja0361547

Titanium tetrakis(amido) complexes catalyze the intramolecular hydroamination of alkynes and allenes more efficiently than Cp-based species. We report here that electron-withdrawing and sterically demanding bis(sulfonamido) ligands lead to enhanced catalytic activity. Zirconium analogues have also been prepared, and the tosyl-substituted complex 20 has been structurally characterized. As in the titanium series, bis(sulfonamido) zirconium catalysts are more efficient in the intramolecular hydroamination of allenes than bis(cyclopentadienyl) complex Cp₂ZrMe₂ (23). Furthermore, these compounds transform 1,3-disubstituted aminoallenes with high stereoselectivity to the Z-allylamines and allow the hydroamination of a trisubstituted allene. Titanium bis(sulfonamido) imido complex 27 was synthesized. It converts aminoallene 10 to cylic imine 11 with a rate comparable to that of tetrakis(amide) 15, supporting the hypothesis of a catalytically active titanium imido intermediate.

Full text of DOI:10.1021/ja0361547

Published on Web 09/09/2003
Use of Group 4 Bis(sulfonamido) Complexes in the
Intramolecular Hydroamination of Alkynes and Allenes
Lutz Ackermann,† Robert G. Bergman,* and Rebecca N. Loy
Contribution from the Department of Chemistry and Center for New Directions in
Organic Synthesis, UniVersity of California, Berkeley, California 94720-1460
Received May 14, 2003; E-mail: bergman@cchem.berkeley.edu
Abstract: Titanium tetrakis(amido) complexes catalyze the intramolecular hydroamination of alkynes and
allenes more efficiently than Cp-based species. We report here that electron-withdrawing and sterically
demanding bis(sulfonamido) ligands lead to enhanced catalytic activity. Zirconium analogues have also
been prepared, and the tosyl-substituted complex 20 has been structurally characterized. As in the titanium
series, bis(sulfonamido) zirconium catalysts are more efficient in the intramolecular hydroamination of allenes
than bis(cyclopentadienyl) complex Cp2ZrMe2 (23). Furthermore, these compounds transform 1,3-
disubstituted aminoallenes with high stereoselectivity to the Z-allylamines and allow the hydroamination of
a trisubstituted allene. Titanium bis(sulfonamido) imido complex 27 was synthesized. It converts aminoallene
10 to cylic imine 11 with a rate comparable to that of tetrakis(amide) 15, supporting the hypothesis of a
catalytically active titanium imido intermediate.
Introduction
former and the high costs of the latter compounds are significant
drawbacks to these procedures.
The direct addition of a N-H bond across a carbon-carbon
multiple bond, the hydroamination reaction, constitutes an atom-
economical method for the synthesis of substituted amines.1,2
While a general procedure for the hydroamination of unactivated
alkenes remains elusive,3,4 appreciable progress has been made
in developing analogous transformations of alkynes.5,6 The first
catalytic intermolecular hydroamination of alkynes used highly
toxic mercury and thallium compounds.7,8 More recently,
reactions relying on alkali metal bases,9 organolanthanides10,11
and -actinides12 as well as late transition metals, such as
palladium,13 rhodium,14 and ruthenium,15,16 have been devel-
oped. However, the extreme air- and water-sensitivity of the
In contrast to many other potential catalysts, titanium and
zirconium complexes are readily available and inexpensive. In
the early 1990s, we reported the catalytic activity of zirconocene
amido complexes in the hydroamination of alkynes.17,18 Sub-
sequently, Doye disclosed the intermolecular hydroamination
of alkynes using Cp2TiMe219 (1) as the precatalyst.20-24 Detailed
mechanistic investigations of this reaction in our group revealed
that the catalytically active species is generated via an unex-
pected Cp/amido ligand exchange.25,26 The isolated monocy-
clopentadienyl titanium amido complex Cp(ArNH)(py)TidNAr
(Ar ) 2,6-(Me)2C6H3) (2)27 exhibits enhanced catalytic activity
in the hydroamination of alkynes and allenes.25 Therefore, we
wondered if the efficiency could be further increased by the
replacement of the remaining Cp ligand in 2 by another amide.28
A report from Odom’s group29 revealed that hydroamination
reactions can be mediated by commercially available Ti(NMe2)4
† Present address: Department of Chemistry, Ludwig-Maximilians-
Universitaet, D-81377 Muenchen, Germany.
(1) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675.
(2) Nobis, M.; Driessen-Ho¨lscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983.
(3) As early as 1993, the catalytic anti-Markovnikov addition of amines to
olefins was mentioned as one of the top 10 challenges for catalysis: Haggin,
J. Chem. Eng. News 1993, 71, 6.
(4) For leading references for the hydroamination of activated alkenes, see:
(a) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem. Soc.
1988, 110, 6738. (b) Dorta, R.; Egli, P.; Zu¨rchner, F.; Togni, A. J. Am.
Chem. Soc. 1997, 119, 10857. (c) Beller, M.; Eichberger, M.; Trauthwein,
H. Angew. Chem., Int. Ed. Engl. 1997, 36, 2225. (d) Kawatsura, M.;
Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546. (e) Kawatsura, M.;
Hartwig, J. F. Organometallics 2001, 20, 1960. (f) Fadini, L.; Togni, A.
Chem. Commun. 2003, 30.
(16) Tokunaga, M.; Eckert, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1999,
38, 3222.
(17) Baranger, A. M.; Walsh, P. J.; Bergman, R. G. J. Am. Chem. Soc. 1993,
115, 2753.
(18) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. J. Am. Chem. Soc. 1992,
114, 1708.
(19) Siebenreicher, H.; Doye, S. J. Prakt. Chem. 2000, 342, 102.
(20) Haak, E.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 1999, 38, 3389.
(21) Bytschkov, I.; Doye, S. Eur. J. Org. Chem. 2001, 4411.
(22) Pohlki, F.; Heutling, A.; Bytschkov, I.; Hotopp, T.; Doye, S. Synlett 2002,
799.
(23) Siebenreicher, H.; Doye, S. Eur. J. Org. Chem. 2002, 1213.
(24) For titanium-based hydroamination catalysts, see also: (a) Tillack, A.;
Castro, I. G.; Hartung, C. G.; Beller, M. Angew. Chem., Int. Ed. 2002, 41,
2541. (b) Ong, T.-G.; Yap, G. P. A.; Richeson, D. S. Organometallics 2002,
21, 2839.
(25) Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 2923.
(26) Straub, B. F.; Bergman, R. G. Angew. Chem., Int. Ed. 2001, 40, 4632.
(27) McGrane, P. L.; Livinghouse, T. J. Org. Chem. 1992, 57, 1323.
(28) Ackermann, L.; Bergman, R. G. Org. Lett. 2002, 4, 1475.
(29) Shi, Y.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001, 20, 3967.
(5) Shimada, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12670.
(6) For a review, see: Pohlki, F.; Doye, S. Chem. Soc. ReV. 2003, 32, 104.
(7) Barluenga, J.; Aznar, F. Synthesis 1977, 195.
(8) Barluenga, J.; Aznar, F.; Liz, R.; Rodes, R. J. Chem. Soc., Perkin Trans.
1 1980, 2732.
(9) Seayad, J.; Tillack, A.; Hartung, C. G.; Beller, M. AdV. Synth. Catal. 2002,
344, 795.
(10) Li, Y.; Marks, T. J. Organometallics 1996, 15, 3770.
(11) Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1998, 120, 1757.
(12) Haskel, A.; Straub, T.; Eisen, M. S. Organometallics 1996, 15, 3773.
(13) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. ReV. 1999, 28, 199.
(14) Hartung, C. G.; Tillack, A.; Trautwein, H.; Beller, M. J. Org. Chem. 2001,
66, 6339.
(15) Uchimaru, Y. Chem. Commun. 1999, 1133.
9
11956
J. AM. CHEM. SOC. 2003, 125, 11956-11963
10.1021/ja0361547 CCC: $25.00 © 2003 American Chemical Society

Bis(sulfonamido) Complexes in Hydroamination
A R T I C L E S
Figure 1. Titanium alkoxo complexes.
Table 1. Hydroamination of Aminoalkyne 4
(3) and, hence, confirmed our hypothesis. On the basis of these
results, Odom and co-workers developed efficient titanium
dipyrrolylmethane catalysts for the hydroamination of alkynes.30-33
We, however, were intrigued by the potential of using titanium
bis(sulfonamido) complexes34 to accomplish regioselective
hydroamination reactions. Herein, we (a) disclose a compre-
hensive investigation of titanium- and zirconium-catalyzed
intramolecular hydroamination reactions of alkynes and allenes,
(b) show that the reactivity and regioselectivity of these
cyclization reactions strongly depend on the transition metal as
well as the ligand set, and (c) provide evidence for a titanium
imido intermediate in the catalytic cycle.
entry
cat.
T/°C
t/h
yield (NMR, %)
1
2
3
4
5
6
7
105
105
75
75
25
16
2
3
16
30
-
-
45
35
85
8
9a
3
a Prepared in situ from 3 and the corresponding diol.
Scheme 1
Results and Discussion
Hydroamination of Alkynes. At the outset of our studies,
we evaluated the catalytic activity of various titanium complexes
in the intramolecular hydroamination of alkyne 4 to cyclic imine
5 (eq 1).
hydroamination of aminoallenes can result in two different
regioisomers (Scheme 1). Whereas Ag-, Hg-, and Pd-based
precatalysts exclusively provide allylamines via pathway a,39-43
lanthanide complexes convert monosubstituted aminoallenes into
mixtures of the two regioisomers (pathways a and b). However,
it is noteworthy that lanthanide catalysts convert 1,3-disubsti-
tuted aminoallenes exclusively to the corresponding allyl-
amine.44-46
We studied the conversion of aminoallene 10 using 5 mol %
of various titanium catalyst precursors (eq 2). The Cp-based
complexes Cp2TiMe2 (1) and CpTi(NHAr)(NAr)py (Ar: 2,6-
dimethylphenyl) (2) have been applied successfully in numerous
intermolecular hydroamination reactions of allenes.25 Unexpect-
edly, the intramolecular transformation proceeded relatively
slowly at 75 °C, and harsher reaction conditions were necessary
to guarantee a quantitative conversion of substrate 10 (Table 2,
entries 1 and 2). On the other hand, tetrakis(amide) 3 ac-
complishes the formation of imine 11 selectively at room
temperature, although a temperature of 75 °C is necessary to
achieve a practical reaction rate (entry 3). Since titanium bis-
(sulfonamides) such as 13 are readily available following
Walsh’s procedure,34 we also explored the use of tosyl-
substituted complex 13 in the hydroamination of aminoallene
10. The chelating bis(sulfonamido) ligand resulted in a signifi-
cantly increased reactivity, leading to selective and quantitative
Titanium tetrakis(alkoxide) complexes, such as TADDOL-
compound 635 or salen-complex 736 (Figure 1), afforded no
product even at elevated temperature (Table 1, entries 1 and
2). Replacing two alkoxides with dimethylamides, as in BINOL-
or TADDOL-complexes 8 and 9, gave rise to catalytic activity,
but the conversion was rather slow even at 75 °C (entries 3
and 4).37,38 Commercially available Ti(NMe2)4 (3) efficiently
converted aminoalkyne 4 to imine 5 even at room temperature
(entry 5).
Hydroamination of Allenes. Since the hydroamination of
alkynes is easily effected by titanium tetrakis(amide) 3,28,37 these
substrates are of limited value for probing the reactivity of
potentially more powerful catalysts. The hydroamination of
allenes, however, is more challenging25 and hence constitutes
a more stringent assay of catalytic activity. Additionally, the
(30) Shi, Y.; Hall, C.; Ciszewski, J. T.; Cao, C.; Odom, A. L. Chem. Commun.
2003, 586.
(31) Harris, S. A.; Ciszewski, J. T.; Odom, A. L. Inorg. Chem. 2001, 40, 1987.
(32) Li, Y.; Turnas, A.; Ciszewski, J. T.; Odom, A. L. Inorg. Chem. 2002, 41,
6298.
(33) Cao, C.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001, 20, 5011.
(34) Pritchett, S.; Gantzel, P.; Walsh, P. J. Organometallics 1999, 18, 823.
(35) Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.; Hunziker, D.;
Petter, W. HelV. Chim. Acta 1992, 75, 2171.
(36) Flores-Lope´z, L. Z.; Parra-Hake, M.; Somanathan, R.; Walsh, P. J.
Organometallics 2000, 19, 2153.
(37) Duncan, D.; Livinghouse, T. Organometallics 1999, 18, 4421.
(38) For the catalytic activity of isolated alkoxo(imido) titanium complexes,
see: Hill, J. E.; Profilet, R. D.; Fanwick, P. E.; Rothwell, I. P. Angew.
Chem., Int. Ed. Engl. 1990, 29, 664.
(39) Arseniyadis, S.; Gore, J. Tetrahedron Lett. 1983, 24, 3997.
(40) Kinsman, R.; Lathbury, D.; Vernon, P.; Gallagher, T. J. Chem. Soc., Chem.
Commun. 1987, 243.
(41) Fox, D. N. A.; Gallagher, T. Tetrahedron 1990, 46, 4697.
(42) Al-Masum, M.; Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1997, 38,
6071.
(43) Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421.
(44) Arredondo, V. M.; McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc. 1998,
120, 4871.
(45) Arredondo, V. M.; Tian, S.; McDonald, F. E.; Marks, T. J. J. Am. Chem.
Soc. 1999, 121, 3633.
(46) Arredondo, V. M.; McDonald, F. E.; Marks, T. J. Organometallics 1999,
18, 1949.
9
J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003 11957

A R T I C L E S
Ackermann et al.
Table 2. Hydroamination of Aminoallene 10
a Ar ) 2,6-(CH3)2-C6H3; b Prepared in situ from 3 and the corresponding bis(amine).
product formation even at room temperature (entry 4). The
chelating N,N′-dimethyl-substituted complex 14, however,
exhibits a reactivity profile similar to that of Ti(NMe2)4 (3)
(entry 5). Therefore, the bidentate nature of the ligand is not
the sole source of enhanced reactivity. The improved perfor-
mance of 13 might instead be a consequence of a weak
coordination of the sulfur-bound oxygen atoms to the metal
center34 or of the different electronic properties of the bis-
(sulfonamido) ligand (vide infra). Furthermore, the six-
membered ring product is formed exclusively using titanium
tetrakis(amide) complexes.
we studied the substrate scope provided by 13 in intramolecular
hydroamination reactions of allenes. Differently substituted
aminoallenes were synthesized following the general sequence
depicted in Scheme 2.
When the R-position of a monosubstituted aminoallene bore
an aromatic group, the regioselectivity of the cyclization
depended upon the nature of the amido ligands (Table 3). While
3 generated a mixture of regioisomers (5-10% allylamine), the
chelated titanium complex 13 formed the cyclic imines as the
sole products, thereby allowing the isolation of these compounds
by simple filtration through K2CO3. The examples listed in Table
3 demonstrate the superior activity of 13, which led to
completion at significantly reduced reaction times. This system
tolerates a range of substituents on the aromatic ring and
provides the respective products in good yields, thus offering
the possibility for further transformations (entries 5-8). More
important, the scope of this procedure is not limited to the
generation of relatively strain-free six-membered rings, but can
also be extended to the formation of seven-membered ring
systems (entry 9).47
Having discovered the increased reactivity as well as the
improved regioselectivity of bis(sulfonamide)-based catalyst 13,
(47) Note that the synthesis of seven-membered rings was not achieved using
Cp2TiMe2: Bytschkov, I.; Doye, S. Tetrahedron Lett. 2002, 43, 3715.
9
11958 J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003

Bis(sulfonamido) Complexes in Hydroamination
A R T I C L E S
Scheme 2
(sulfonamido) ligand on the catalytic activity, we synthesized
the methyl- and trifluoromethyl-substituted analogues 16 and
17 from Ti(NMe2)4 (3) and the corresponding bis(amide)
(eq 3).
While bis(triflamide) 17 converted aminoalkyne 4 to imine
5 selectively and efficiently even at room temperature (47%
conversion after 15 min), no transformation of 4 was achieved
by the methyl-substituted complex 16 at this temperature (90
min, 1H NMR). These experiments illustrate the importance of
the electron-withdrawing nature of the sulfonamido ligands on
the catalytic activity. Furthermore, bis(triflamido) complex 17
converts aminoallenes selectively to the corresponding cyclic
imines (Table 5). The transformation of 1,3-disubstituted allene
18 demonstrates the increased efficacy of bis(triflamide) 17,
yielding 87% of imine 19 at 75 °C after 20 h. Note that complex
13 affords only 12% of 19 under the same reaction conditions.
Zirconium Analogues. Previously we have carried out
nitrogen-carbon bond-forming reactions using zirconium imido
complexes.17,18,49 Therefore, we were interested in comparing
the synthesis and catalytic activity of titanium complexes 13
and 15 with their zirconium analogues. The corresponding tosyl-
and mesitylsulfonyl-substituted complexes 20 and 21 (Figure
3) were obtained starting from Zr(NMe2)4 (22) as outlined for
the respective titanium complexes.
Steric Influence of the Bis(sulfonamido) Ligand. The
influence of steric congestion around the metal center of the
bis(sulfonamido) catalyst was studied by comparing the reactiv-
ity of p-tolyl-substituted precursor 13 with that of mesityl-
substituted complex 1534 (Figure 2). Both precatalysts efficiently
Whereas mesitylsulfonyl complex 21 showed the expected
NMR features, tosyl-substituted compound 20 exhibited reso-
nances for two separate sets of p-tolyl groups. In addition, 1
equiv of HNMe2 was detected. A crystal structure analysis was
performed and unambiguously confirmed the structure of 20
shown in Figure 4. This confirms that coordination of the sulfur-
bound oxygen atoms to the metal center has occurred.
Initially, we explored the catalytic reactivity of a variety of
different zirconium species in the hydroamination of parent
aminoallene 10 (eq 2). The cyclopentadienyl-based complex 23
converted the aminoallene to products 11 and 12 slowly even
at a temperature of 135 °C (Table 6, entry 1). Abstraction of a
methyl group with B(C6F5)3 prior to the addition of the substrate
led to an acceleration of the reaction at 135 °C. The cationic
zirconium complex gave an inverted regioselectivity, yielding
the allylamine as the major product (entry 2). In analogy to the
titanium series, a more pronounced effect was observed upon
switching from a Cp to an amido ligand set, illustrated by a
lower reaction temperature of 75 °C (entry 3). The reaction was
even faster using bis(sulfonamido) complexes (entries 4 and 5).
While the tosyl-substituted sulfonamide complex 20 exhibited
a catalytic activity comparable to that of Zr(NMe2)4 (22) (entry
4), mesitylsulfonyl-substituted compound 21 was a precursor
to a significantly more efficient catalyst (entry 5). This improved
Figure 2. Titanium bis(sulfonamido) complexes.
convert aminoalkynes and monosubstituted aminoallenes regio-
selectively to six-membered cyclic imines (Table 4, entries
1-4). They are also capable of affecting the more demanding
hydroamination of 1,3-disubstituted allenes,48 yielding exclu-
sively the corresponding cyclic imines (entries 5-8). The data
obtained thus far suggest that the efficacy of the sterically more
hindered catalyst 15 exceeds that of tosyl-substituted complex
13 (entry 1 versus 2 and 5 versus 6).
Electronic Influence of the Bis(sulfonamido) Ligand. To
study the influence of the electronic nature of the bis-
(48) All attempts to convert acyclic disubstituted allenes using cyclopentadienyl-
based titanium catalysts have met with no success.25
(49) Sweeney, Z. K.; Salsman, J. L.; Andersen, R. A.; Bergman, R. G. Angew.
Chem., Int. Ed. 2000, 39, 2339.
9
J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003 11959

A R T I C L E S
Ackermann et al.
Table 3. Hydroamination of Aryl-Substituted Aminoallenes (5 Mol % of Catalyst in C6D6, 75 °C)
a Yields in parentheses refer to ratio of imine/allylamine by NMR after complete and selective conversion of the starting material (versus internal standard);
b 10 mol %.
performance can be rationalized by the increased steric hin-
drance around the metal center, as observed in the titanium
series. In contrast to the analogous titanium species, the use of
zirconium complexes yields significant amounts of allylamine
12. The introduction of substituents at the terminal position of
the allene moiety inverts the regioselectivity of the cyclization
reaction (eq 4). Several examples demonstrate that the regio-
selectivity changes from 1:16 (Table 6, entry 5) for the parent
substrate to 4:1 and 7:1 (Table 7, entries 1 and 2) in the case of
1,3-disubstituted aminoallenes. Furthermore, the diastereose-
lectivity is excellent for the conversion of 1,3-disubstituted
substrates, yielding the corresponding Z-isomers 24 and 25
exclusively. The scope of this transformation is further high-
lighted by the hydroamination of a trisubstituted allene (Table
7, entry 3). In this case, a good regioselectivity of 11:1 favoring
allylamine 26 is obtained.
Mechanistic Considerations. The mechanism of the Cp2-
TiMe2-catalyzed hydroamination reaction has been investigated
experimentally25,50 and theoretically.26 These studies suggest that
the catalytically active species is a titanium imido complex. To
gain insight into the mechanism of the reaction mediated by
tetrakis(amido) precursors, we performed the stoichiometric
reaction between titanium catalyst 15 and a primary amine (eq
5). To avoid a potential dimerization of the imido species,25,26
we chose the sterically hindered 2,6-dimethylaniline. Monitoring
(50) Pohlki, F.; Doye, S. Angew. Chem., Int. Ed. 2001, 40, 2305.
9
11960 J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003

Bis(sulfonamido) Complexes in Hydroamination
A R T I C L E S
Table 4. Hydroamination of Substituted Aminoallenes with 13 and 15 (5 Mol % of Catalyst in C6D6)
a 93% isolated yield.
the reaction by 1H NMR revealed the formation of imido
complex 27 accompanied by liberation of HNMe2. Pyridine was
added to stabilize the imido compound, and the resulting adduct
was isolated in 61% yield, contaminated with free amine. All
attempts to remove the remaining impurities met with no
success, which prevented satisfactory elemental analysis. Dif-
ficulties associated with removing amine contaminants from
early transition metal imido species have been reported previ-
ously.25,51,52 Imido complex 27 (5 mol %) converts aminoallene
10 quantitatively to imine 11 after 3 h at room temperature and,
hence, leads to a reaction with a rate comparable to that observed
using precatalyst 15.
Knochel and co-workers have shown that intramolecular
hydroamination reactions of alkynes can be mediated by
bases.9,53,54 However, catalytic amounts of LiNMe2 (10 mol %)
isomerized aminoallene 10 quantitatively in 1 h at ambient
1
temperature to internal alkyne 28 (observed by H and 13C
NMR). Alkyne 28 was subsequently converted to the five-
membered cyclization product 29 (eq 6). Imine 29 was observed
neither in the titanium- nor in the zirconium-catalyzed reactions.
Therefore, it seems unlikely that the catalytic activity originates
from traces of free amide.
On the basis of our results, we propose the catalytic cycle
depicted in Scheme 3 for the hydroamination reactions discussed
in this work (illustrated for titanium and an allene). In the crucial
steps of this mechanism, a formal [2 + 2] cycloaddition of the
imido species with the allene is followed by a stepwise
protonation of the azametallacyclobutane to regenerate the actual
catalysts as well as to release the hydroamination product.
(51) Arney, D. J.; Bruck, M. A.; Huber, S. R.; Wigley, D. E. Inorg. Chem.
1992, 31, 3749.
(52) Blake, A. J.; Collier, P. E.; Dunn, S. C.; Li, W. S.; Mountford, P.; Shishkin,
O. V. J. Chem. Soc., Dalton Trans. 1997, 1549.
(53) Koradin, C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P.
Tetrahedron 2003, 59, 1571.
(54) Rodriguez, A. L.; Koradin, C.; Dohle, W.; Knochel, P. Angew. Chem., Int.
Ed. 2000, 39, 2488.
9
J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003 11961

A R T I C L E S
Ackermann et al.
Table 5. Hydroamination Reactions of Allenes Using Catalyst 17 (5 Mol % of Catalyst in C6D6)
Table 7. Synthesis of Allylamines Using Zirconium Catalysts 21
Figure 3. Zirconium bis(sulfonamido) complexes.
1
a Isolated as the trifluoroacetamide derivative. b By H NMR. c 10 mol
% 21.
through the use of electron-withdrawing or sterically demanding
bis(sulfonamido) ligands. Analogous zirconium complexes have
been synthesized, and one of them has been structurally
characterized. These complexes catalyze the intramolecular
hydroamination of allenes more efficiently than Cp2ZrMe2 (23).
More importantly, these compounds convert 1,3-disubstituted
aminoallenes with good stereoselectivity to the Z-allylamines
and allow the hydroamination of a trisubstituted allene moiety.
Finally, titanium bis(sulfonamido) imido complex 27 cyclizes
aminoallene 10 at a rate comparable to that observed using
tetrakis(amide) 15, supporting the hypothesis that in the catalytic
cycle a titanium imido species is an important intermediate.
Figure 4. ORTEP diagram of complex 20.
Table 6. Hydroamination of Allene 10 Using Zirconium
Complexes (5 Mol % of Catalyst in C6D6)
yield (NMR, %)
entry
cat.
T/°C
t/h
11
12
Experimental Section
1
2
3
Cp2ZrMe2 (23)
Cp2ZrMe2 (23)/B(C6F5)3
Zr(NMe2)4 (22)
20
135
135
75
75
135
75
18
18
24
3
3
4
16
34
35
10
84
94
3
66
2
-
12
6
General. All syntheses were carried out under N2 using predried
glassware. All hydroamination reactions and complex synthesis were
performed in a N2-filled Vacuum Atmospheres inert atmosphere box.
Et2O, pyridine, THF, and d6-benzene were dried by distillation over
Na and transferred under N2. CH2Cl2, benzene, n-pentane, and toluene
were dried by passing through a single column of activated alumina.55,56
Flash chromatography: Merck silica gel 60 (230-400 mesh). NMR:
4
5
21
Conclusion
Titanium tetrakis(amido) complexes catalyze the intramo-
lecular hydroamination of alkynes and allenes more efficiently
than do Cp-based species. The catalytic activity can be increased
(55) Alaimo, P. J.; Peters, D. W.; Arnold, J.; Bergman, R. G. J. Chem. Educ.
2001, 78, 64.
(56) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers,
F. J. Organometallics 1996, 15, 1518.
9
11962 J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003

Bis(sulfonamido) Complexes in Hydroamination
A R T I C L E S
Scheme 3
solved ligand remained, stirring was discontinued and the solution was
cooled to -35 °C. The solution was decanted, washed with cold Et2O
(1 mL, -35 °C), and the product was dried in vacuo.
Following the general procedure, 20 was obtained as white crystals
in 46% yield.
1H NMR (C6D6, 400 MHz): δ 8.03 (2H, d, J ) 8.2 Hz), 7.96 (2H,
d, J ) 8.2 Hz), 6.87 (2H, d, J ) 7.9 Hz), 6.81 (2H, d, J ) 8.1 Hz),
3.45-3.35 (2H, m), 3.41 (6H, s), 3.23 (6H, s), 2.40 (6H, d, J ) 6.1
Hz), 2.20 (1H, m), 1.99 (1H, m), 1.88 (3H, s), 1.87 (3H, s), 1.70 (1H,
m), 1.34 (1H, m), 1.26 (1H, m), 1.20-0.85 (3H, m). 13C NMR (C6D6,
100 MHz): δ 142.7, 142.4, 129.8, 129.5, 128.1, 127.9, 126.8, 126.1,
65.2, 63.7, 47.6, 44.6, 42.8, 40.3, 32.8, 24.7, 21.1, 21.1. IR (CH2Cl2):
3363, 3284, 3065, 3054, 2938, 2859, 1599, 1451, 1428, 1337, 1262,
1162, 1093, 904 cm-1. C26H43N5O4S2Zr (645.01) Anal. Calcd: C, 48.42;
H, 6.72; N, 10.86. Found: C, 48.36; H, 6.66; N, 10.51.
Typical Procedure for the Hydroamination/Cyclization Reaction.
A solution of 1-(4-fluoro-phenyl)-hexa-4,5-dienyl-1-amine (121 mg,
0.63 mmol) and 13 (18 mg, 0.03 mmol) in benzene (3 mL) was heated
for 10 h to 75 °C. The solution was cooled and treated with 20 drops
of methanolic NaOH (10%). The mixture was stirred for 0.5 h at room
temperature and concentrated in vacuo. The remaining residue was
extracted with n-hexane (30 mL) and filtered through K2CO3 to afford
2-(4-fluoro-phenyl)-6-methyl-2,3,4,5-tetrahydro-pyridine (112 mg, 93%)
as a pale yellow oil with a purity of >95% by NMR.
2-(4-Fluoro-phenyl)-6-methyl-2,3,4,5-tetrahydro-pyridine. 1H NMR
(CD2Cl2, 300 MHz): δ 7.23 (m, 2H), 7.01 (tm, 2H, J ) 8.9 Hz), 4.43
(m, 1H), 2.30-2.10 (m, 2H), 1.98 (d, 3H, J ) 2.0 Hz), 1.95-1.60 (m,
3H), 1.40-1.20 (m, 1H). 13C NMR (CD2Cl2, 100 MHz): δ 168.6, 128.4,
128.3, 114.8, 114.5, 60.8, 30.6, 29.9, 27.3, 19.0. MS (EI) m/z (relative
intensity): 191 (81) [M+], 163 (14), 162 (14), 148 (11), 121 (100),
109 (10). HRMS (EI) m/z: calcd for C12H14FN, 191.1110; found,
191.1109.
Spectra were recorded on Bruker AMX300 or AMX400 spectrometers
in the solvents indicated; chemical shifts (δ) are given in ppm relative
to TMS, coupling constants (J) in Hz. 1,3,5-Trimethoxybenzene
(Aldrich) was employed as an internal standard in NMR tube reactions.
IR: Mattson Galaxy FTIR 3000, wavenumbers in cm-1; only selected
data are reported. Mass spectra were performed by the University of
California, Berkeley Micro-Mass Facility.
Acknowledgment. This work was supported by the U.S.
National Institutes of Health (Grant No. GM-25459 to R.G.B.).
L.A. thanks the Deutscher Akademischer Austauschdienst
(DAAD) for a postdoctoral fellowship. The structural study of
20 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). The Center for New Directions in
Organic Synthesis is supported by Bristol-Myers Squibb as a
sponsoring member and Novartis as a supporting member.
Herein, selected representative procedures are reported. A fully
detailed account is provided in the Supporting Information.
General Procedure for the Synthesis of Titanium and Zirconium
Complexes.57 Under an N2 atmosphere, the appropriate ligand (1 mmol)
was stirred in Et2O (10 mL) at room temperature. To this mixture was
added Ti(NMe2)4 (1 mmol) as a solution in Et2O (1 mL) in one portion.
On addition of the titanium complex, the mixture turned red-brown,
and the ligand dissolved to give a clear solution. If necessary, the
solution was filtered after the ligand had dissolved. When no undis-
Supporting Information Available: Experimental procedures
and characterization data for new compounds (PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
(57) A general procedure for the synthesis of such titanium complexes has been
reported.34
JA0361547
9
J. AM. CHEM. SOC. VOL. 125, NO. 39, 2003 11963