TiIV-mediated reactions between primary amines and secondary carboxamides: Amidine formation versus transamidation

Article abstract of DOI:10.1021/ja0650293

Titanium(IV)-mediated reactions between primary amines and secondary carboxamides exhibit different outcomes, amidine formation versus transamidation, depending on the identity of the Ti^IV complex used and the reaction conditions employed. The present study probes the origin of this divergent behavior. We find that stoichiometric Ti^IV, either Cp*Ti^IV complexes or Ti(NMe₂)₄, promotes formation of amidine and oxotitanium products. Under catalytic conditions, however, the outcome depends on the identity of the Ti^IV complex. Competitive amidine formation and transamidation are observed with Cp*Ti^IV complexes, generally favoring amidine formation. In contrast, the use of catalytic Ti(NMe₂)₄ (≤20 mol %) results in highly selective transamidation. The ability of Ti^IV to avoid irreversible formation of oxotitanium products under the latter conditions has important implications for the use of Ti^IV in catalytic reactions.

Full text of DOI:10.1021/ja0650293

Published on Web 01/19/2007
TiIV-Mediated Reactions between Primary Amines and
Secondary Carboxamides: Amidine Formation Versus
Transamidation
Denis A. Kissounko, Justin M. Hoerter, Ilia A. Guzei, Qiang Cui,*
Samuel H. Gellman,* and Shannon S. Stahl*
Contribution from the Department of Chemistry, UniVersity of WisconsinsMadison,
1101 UniVersity AVenue, Madison, Wisconsin 53706
Received July 14, 2006; E-mail: cui@chem.wisc.edu; gellman@chem.wisc.edu; stahl@chem.wisc.edu
Abstract: Titanium(IV)-mediated reactions between primary amines and secondary carboxamides exhibit
different outcomes, amidine formation versus transamidation, depending on the identity of the TiIV complex
used and the reaction conditions employed. The present study probes the origin of this divergent behavior.
We find that stoichiometric TiIV, either Cp*TiIV complexes or Ti(NMe2)4, promotes formation of amidine and
oxotitanium products. Under catalytic conditions, however, the outcome depends on the identity of the TiIV
complex. Competitive amidine formation and transamidation are observed with Cp*TiIV complexes, generally
favoring amidine formation. In contrast, the use of catalytic Ti(NMe2)4 (e20 mol %) results in highly selective
transamidation. The ability of TiIV to avoid irreversible formation of oxotitanium products under the latter
conditions has important implications for the use of TiIV in catalytic reactions.
halides;3 however, thermodynamically controlled exchange
reactions involving carboxamides, including transamidation and
Introduction
Methods for facile, equilibrium-controlled exchange of
covalent bonds have gained widespread attention in recent years
because they enable product formation under thermodynamic,
rather than kinetic, control.1 Prominent functional groups
compatible with these transformations include esters, disulfides,
imines, acetals, and alkenes.2 Carboxamides are ubiquitous in
chemistry and biology, and numerous methods have been
developed to prepare carboxamides under kinetic control via
the condensation of amines with carboxylic acids, esters, or acid
amide metathesis, have very little precedent.4,5 In our initial
studies focused on this type of reactivity, we discovered that
homoleptic metal-amido complexes, Ti(NMe2)4 and Al2-
(NMe2)6, promote equilibration of simple primary amine/
secondary carboxamide pairs under moderate conditions (e.g.,
eq 1).6 In order to develop improved catalysts, we have been
investigating the mechanism of these reactions.7
(1) Equilibrium-controlled manipulation of other functional groups is the subject
of significant current interest. For reviews, see: (a) Lehn, J.-M. Chem.s
Eur. J. 1999, 5, 2455-2463. (b) Rowan, S. J.; Cantrill, S. J.; Cousins,
G. R. L.; Sanders, J. K. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2002,
41, 898-952.
Primary amines are known to react with Ti(NMe2)4 to form
imido ligands,8,9 and we recently postulated that imidotitanium
(2) For selected recent examples of DCC, see (a) Brady, P. A.; Bonar-Law,
R. P.; Rowan, S. J.; Suckling, C. J.; Sanders, J. K. M. Chem. Commun.
1996, 319-320. (b) Oh, K.; Jeong, K.-S.; Moore, J. S. Nature 2001, 414,
889-893. (c) Otto, S.; Furlan, R. L. E.; Sanders, J. K. M. Science 2002,
297, 590-593. (d) Kilbinger, A. F. M.; Cantrill, S. J.; Waltman, A. W.;
Day, M. W.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42, 3281-3285.
(e) Vignon, S. A.; Jarrosson, T.; Iijima, T.; Tseng, H.-R.; Sanders, J. K.
M.; Stoddart, J. F. J. Am. Chem. Soc. 2004, 126, 9884-9885. (f) Cantrill,
S. J.; Grubbs, R. H.; Lanari, D.; Leung, K. C.-F.; Nelson, A.; Poulin-
Kerstien, K. G.; Smidt, S. P.; Stoddart, J. F.; Tirrell, D. A. Org. Lett. 2005,
7, 4213-4216. (g) Cacciapaglia, R.; Di Stefano, S.; Mandolini, L. J. Am.
Chem. Soc. 2005, 127, 13666-13671.
(5) For intermolecular precedents, see: (a) Beste, L. F.; Houtz, R. C. J. Polym.
Sci. 1952, 8, 395-407. (b) Ogata, N. Makromol. Chem. 1959, 30, 212-
224. (c) Miller, I. K. J. Polym. Sci., Part A: Polym. Chem. 1976, 14, 1403-
1417. (d) McKinney, R. J. U.S. Patent 5,302,756, 1994. (e) McKinney,
R. J. U.S. Patent 5,395,974, 1995. (f) Bon, E.; Bigg, D. C. H.; Bertrand,
G. J. Org. Chem. 1994, 59, 4035-4036.
(6) Eldred, S. E.; Stone, D. A.; Gellman, S. H.; Stahl, S. S. J. Am. Chem. Soc.
2003, 125, 3422-3423.
(3) Beckwith, A. L. J. In The Chemistry of Amides; Zabicky, J., Ed.; Wiley:
New York, 1970; p 73-185.
(7) (a) Kissounko, D. A.; Guzei, I. A.; Gellman, S. H.; Stahl, S. S.
Organometallics 2005, 24, 5208-5210. (b) Hoerter, J. M.; Otte, K. M.;
Gellman, S. H.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 5177-5183.
(8) (a) Bradley, D. C.; Torrible, E. G. Can. J. Chem. 1963, 41, 134-138. (b)
Nugent, W. A.; Harlow, R. L. Inorg. Chem. 1979, 18, 2030-2032. (c)
Thorn, D. L.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1981, 103,
357-363.
(4) Most precedents consist of intramolecular reactions. See, for example: (a)
C¸ alimsiz, S.; Lipton, M. A. J. Org. Chem. 2005, 70, 6218-6221. (b)
Alajar´ın, M.; Vidal, A.; Tovar, F. Tetrahedron 2005, 61, 1531-1537. (c)
Klapars, A.; Parris, S.; Anderson, K. W.; Buchwald, S. L. J. Am. Chem.
Soc. 2004, 126, 3529-3533. (d) Lasri, J.; Gonza´lez-Rosende, M. E.;
Sepu´lveda-Arques, J. Org. Lett. 2003, 5, 3851-3853. (e) Langlois, N.
Tetrahedron Lett. 2002, 43, 9531-9533. (f) Gotor, V.; Brieva, R.; Gonza´lez,
C.; Rebolledo, F. Tetrahedron 1991, 47, 9207-9214. (g) Zaragoza-Do¨rwald,
F.; von Kiedrowski, G. Synthesis 1988, 11, 917-918. (h) Crombie, L.;
Jones, R. C. F.; Haigh, D. Tetrahedron Lett. 1986, 27, 5151-5154. (i)
Martin, R. B.; Parcell, A.; Hedrick, R. I. J. Am. Chem. Soc. 1964, 86, 2406-
2413.
(9) Ti(NMe2)4 catalyzes the hydroamination of alkynes and alkenes, reactions
that probably proceed via imidotitanium intermediates. For leading refer-
ences, see: (a) Shi, Y.; Ciszewski, J. T.; Odom, A. L. Organometallics
2001, 20, 3967-3969. (b) Ackermann, L.; Bergman, R. G.; Loy, R. N.
J. Am. Chem. Soc. 2003, 125, 11956-11963. (c) Lorber, C.; Choukroun,
R.; Vendier, L. Organometallics 2004, 23, 1845-1850. (d) Bexrud, J. A.;
Beard, J. D.; Leitch, D. C.; Schafer, L. L. Org. Lett. 2005, 7, 1959-1962.
9
1776
J. AM. CHEM. SOC. 2007, 129, 1776-1783
10.1021/ja0650293 CCC: $37.00 © 2007 American Chemical Society

TiIV-Mediated Reactions
A R T I C L E S
Scheme 1. Reactions of an Imido-TiIV Species with Secondary
Scheme 2. Preparation of Bis- and Trisamidate Complexes of TiIV
Carboxamides
intermediates might participate in the transamidation reaction.7a
To test this hypothesis, we investigated the reactivity of a well-
defined imido-TiIV complex, Cp*Ti(NtBu)(py)Cl (3, Cp* ) η5-
C5Me5),10 with secondary carboxamides; however, no trans-
amidation was observed. Secondary amides react with complex
3 at room temperature by displacing pyridine and tert-butyl-
amine together with the formation of bis(κ2-amidate)TiIV
complex 4 (Scheme 1). Subsequent treatment of 4 with aniline
derivatives at elevated temperatures (90 °C) results in formation
of 1 equiv of N,N′-diarylamidine and unidentified Ti byprod-
ucts.11
amido or amidate ligands. In addition, we probe the effect of
substrate/Ti loading under catalytic conditions. The results reveal
that amidine formation is relatively insenstitive to the ancillary
ligand environment and is the major reaction pathway when
the substrate/Ti ratio approaches 1:1. In contrast, transamidation
can be achieved only with a relatively high substrate/Ti ratio
and proceeds most effectively when the TiIV lacks the electron-
donating and sterically bulky Cp* ligand. The results of this
study potentially have general implications for avoiding the
formation of inert oxotitanium complexes in catalytic reactions.
This previous study highlighted the ability of TiIV to activate
intrinsically unreactive carboxamides toward a reaction with
simple primary amines; however, the formation of amidines in
these reactions raises fundamental questions concerning the
ability of TiIV to promote transamidation under catalytic
conditions. How do amido-, imido-, and/or amidatotitanium
adducts, which seem certain to exist under catalytic conditions,
avoid generating amidines and inert oxo-Ti products? What
factors dictate whether amines and carboxamides will undergo
transamidation or form amidines in the presence of TiIV?
In our consideration of these questions, we noted at least two
significant differences between the catalytic transamidation
reactions (eq 1) and the stoichiometric reactions of TiIV
complexes (Scheme 1). First, the ligands coordinated to TiIV
differ between the two classes of reactions. In the catalytic
reactions initiated by Ti(NMe2)4, only amine and carboxamide
substrates are available as ligands, whereas the stoichiometric
reactions feature TiIV bearing ancillary Cp* and chloride ligands.
Another important difference is the substrate/Ti ratio. Under
catalytic conditions, both the amine and carboxamide substrates
are present in a 20:1 ratio relative to Ti, whereas the mechanistic
studies feature a substrate/Ti ratio of approximately 1:1.12
The present study seeks to address whether either of these
differences underlies the divergence between transamidation and
amidine formation in Ti-promoted reactions between primary
amines and secondary carboxamides. We describe reactions of
TiIV-amidate complexes in which the ancillary chloride ligand
in 4 (Scheme 1) has been replaced by catalytically more relevant
Results and Discussion
Synthesis of Ti-Amidate Complexes. To probe the effect
of the TiIV coordination sphere on the outcome of Ti-mediated
reactions between primary amines and secondary carboxamides,
we sought an analogue of Cp*Ti(κ2-amidate)2Cl (4) in which
the chloride is replaced by an amido or a third amidate ligand.
The known Cp*Ti(NMe2)3 (5) complex13 reacts cleanly in the
presence of a 10-fold excess of iPrNH2 to provide the trisiso-
propylamido derivative 6 (Scheme 2). The amido ligands in 6
undergo facile exchange with secondary carboxamides. Addition
of 2 equiv of acetanilide to 6 in diethylether at ambient
temperature yields the bis(amidate)monoamidoTiIV complex, 7.
Three equiv of acetanilide react with 6 to form the tris(amidate)-
TiIV complex 8. Attempts to form the monoamidate complex,
however, were unsuccessful. The reaction of 6 with 1 equiv of
acetanilide provides 7 in reduced yield together with unreacted
6. These observations indicate a strong (albeit, not surprising)
preference of TiIV for amidate rather than amido ligands. This
preference can be explained, in part, by the ability of the
amidates to serve as chelating ligands; however, the facile
formation of 8 from 6 shows that even monodentate amidates
are favored over amido ligands. The oxophilicity of TiIV together
with the significantly higher acidity of amides relative to amines
undoubtedly contributes to these results. Comparable observa-
tions have been made recently in our study of amine and
carboxamide reactions with AlIII.7b
Complexes 6-8 were characterized by infrared, 1H, and 13C-
{1H} NMR spectroscopy and elemental analysis. The 1H NMR
signal of the amido N-H in 7 is shifted significantly downfield
relative to that in 6 (9.24 and 5.18 ppm, respectively; C6D6).
This shift presumably reflects the enhanced electrophilicity of
the Ti center in 7 relative to 6. We cannot exclude the possibility
of intramolecular hydrogen bonding in 7 between the N-H and
the oxygen of an amidate ligand; however, no evidence for such
(10) Dunn, S. C. Mountford, P.; Robson, D. A. J. Chem. Soc., Dalton Trans.
1997, 293-304.
(11) In light of these results, it is noteworthy that Schafer and co-workers recently
reported the first example of Ti and Zr imido complexes bearing ancillary
amidate ligands. The lack of amidine formation from these complexes, even
at elevated temperatures (up to 140 °C), presumably reflects the presence
of the extremely bulky 2,6-diisopropylphenyl substituents on the amidate
nitrogen atoms. See: Thomson, R. K.; Bexrud, J. A.; Schafer, L. L.
Organometallics 2006, 25, 4069-4071.
(12) As noted by a reviewer, we observed catalyst-dependent chemoselectivity
in our initial discovery of transamidation (ref 6)snamely, alkylamide
substrates are more reactive with Al catalysts, whereas arylamides are more
reactive with Ti complexes. The present study focuses exclusively on Ti
chemistry and, therefore, does not address the origin of transamidation
chemoselectivity. The latter issue will be the focus of future work.
(13) Mart´ın, A.; Mena, M.; Ye´lamos, C.; Serrano, R.; Raithby, P. R.
J. Organomet. Chem. 1994, 467, 79-84.
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A R T I C L E S
Kissounko et al.
Figure 2. Molecular structure of 8 (30% thermal ellipsoids). All hydrogen
atoms have been removed for clarity.
Figure 1. Molecular structure of 7 (30% thermal ellipsoids). All hydrogen
atoms have been removed for clarity.
an interaction is provided by the IR spectroscopic or X-ray
crystallographic data (see later).
Structural Analysis of Ti-Amidate Complexes. Only a few
examples of titanium amidate complexes have been reported
in the literature.7a,14 A particularly interesting class of com-
pounds has been described by Schafer and co-workers, who have
prepared and structurally characterized pseudo-octahedral TiIV(κ2-
amidate)2(NEt2)2 complexes for use as catalysts in the hy-
droamination of alkynes.14b-d Although the hydroamination
reactions are performed in the presence of excess primary amine,
no reaction of the ancillary κ2-amidate ligands (e.g., transami-
dation or amidine formation) has been noted. The relative
inertness of the amidate ligands in these reactions, which are
performed in benzene at 65 °C, probably has a steric origin.
The amidate ligands have large substituents on nitrogen (e.g.,
tert-butyl and 2,6-diisopropylphenyl) and an aryl group bonded
to the central carbon atom that orients perpendicular to the
amidate π-system.
X-ray crystal structures of 7 and 8 were obtained. As shown
in Figure 1, complex 7 exhibits a pseudo-octahedral geometry
with the Cp* ligand and an amidate nitrogen atom occupying
the apical positions. The two amidate ligands are distinguished
by different relative C-O and C-N bond lengths: the bond
lengths for the diequatorial amidate implicates more double-
bond character for the C-O bond [C(11)-O(1), 1.2848(19);
C(11)-N(1), 1.311(2) Å] relative to the equatorial/apical
amidate, in which the C-O and C-N bond lengths are identical
[C(19)-O(2), 1.300(2); C(19)-N(2), 1.300(2) Å]. Correspond-
ing differences are evident in the Ti-amidate bond lengths. For
the diequatorial amidate, the Ti-N bond is shorter than the
Ti-O bond [Ti-N(1), 2.1570(13); Ti-O(1), 2.2037(12) Å],
whereas for the equatorial/apical amidate, the Ti-O bond is
shorter than the Ti-N bond [Ti(1)-O(2), 2.0664(12); Ti(1)-
N(2), 2.2985(14) Å].
Figure 3. Molecular structure of compound 10 (30% thermal ellipsoids).
All hydrogen atoms have been removed for clarity.
are negligible, and for both ligands, the Ti-O bonds are shorter
than the Ti-N bonds [Diequatorial: C(11)-O(1), 1.298(5);
C(11)-N(1), 1.307(6); Ti-O(1), 2.070(3); Ti-N(1) 2.225(4)
Å. Equatorial/apical: C(19)-O(2), 1.316(5); C(19)-N(2),
1.299(5); Ti-O(2), 2.052(3); Ti-N(2) 2.231(4) Å]. The third
amidate in 8 coordinates in a monodentate fashion through the
oxygen atom, and the Ti-O bond [1.907(3) Å] is significantly
shorter than that of the κ2-amidate ligands. Furthermore, the
C-O and C-N bond lengths of this ligand [C(27)-N(3), 1.281-
(6); C(27)-O(3), 1.319(5) Å] are consistent with the CdN and
C-O formulation in Scheme 2.15 Other structural parameters
are available in the Supporting Information.
Reactivity of Ti-Amidate Complexes. We previously dem-
onstrated that exogenous amine reacts with the bis(amidate)-
TiIV complex 4 to yield an amidine product (Scheme 1).7a
Preparation of the bis(amidate)monoamidoTiIV complex 7
enabled us to test whether an amido ligand present within the
coordination sphere of Ti would undergo transamidation or form
an amidine product. Thermolysis of complex 7 at 50 °C in C6D6
resulted in exclusive formation of a 2:1 mixture of the secondary
amidine, MeC(dNiPr)NHPh (9), and the bis(µ-oxo)Ti dimer,
{Cp*Ti(µ-O)[κ2-OC(Me)NPh]}2 (10) (eq 2). The structure of
10 was confirmed by NMR spectroscopy and X-ray crystal-
The structure of trisamidate complex 8 is similar to that of
7, but an O-bound κ1-amidate occupies the position of the
isopropylamido ligand in 7 (Figure 2). More detailed analysis
of the structure of 8 reveals that bonding distinctions between
the diequatorial and equatorial/apical κ2-amidate ligands in 8
(14) (a) Giesbrecht, G. R.; Shafir, A.; Arnold, J. Inorg. Chem. 2001, 40, 6069-
6072. (b) Zhang, Z.; Schafer, L. L. Org. Lett. 2003, 5, 4733-4736. (c) Li,
C. Y.; Thomson, R. K.; Gillon, B.; Patrick, B. O.; Schafer, L. L. Chem.
Commun. 2003, 2462-2463. (d) Thomson, R. K.; Zahariev, F. E.; Zhang,
Z.; Patrick, B. O.; Wang, Y. A.; Schafer, L. L. Inorg. Chem. 2005, 44,
8680-8689.
(15) For similar structural parameters observed in κ1-amidate structures of
aluminum and lithium, see (a) Peng, Y.; Bai, G.; Fan, H.; Vidovic, D.;
Roesky, H. W.; Magull, J. Inorg. Chem. 2004, 43, 1217-1219. (b)
Davidson, M. G.; Davies, R. P.; Raithby, P. R.; Snaith, R. Chem. Commun.
1996, 1695-1696.
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TiIV-Mediated Reactions
A R T I C L E S
Figure 4. Kinetic data for the thermolysis of 7 at 50 °C in C6D6, which
yields amidine 9 and the bis(m-oxo)Ti dimer 10, [7] ) 0.11 M.
Figure 5. Kinetic data for the reaction of 8 with benzyl amine (10 equiv)
at 70 °C in C6D6, [8] ) 0.46 M.
lography (Figure 3). No evidence for transamidation was
obtained in this reaction.
Table 1. Composition of a Product Mixture from the Reaction
between 8 and Benzyl Amine in the Presence of Acetanilide at 70
°C and in C6D6 for 24 h
Kinetic studies of the conversion of 7 into 9 and 10 were
performed by monitoring the reaction by 1H NMR spectroscopy.
Clean exponential decay of 7 (k ) 2.97(3) × 10-4 s-1) (Figure
4) together with the fact that free amine (3-5 equiv iPrNH2)
does not affect the rate suggests that the reaction proceeds by
an intramolecular pathway. Thermolysis of the deuterated
analogue of 7, Cp*Ti(NDiPr)[κ2-OC(Me)NPh]2 (7-d1), revealed
that the reaction does not exhibit a kinetic isotope effect
(kH/kD ) 1.0((0.1)).
The reactivity of trisamidate complex 8 in the presence of
exogenous benzyl amine was examined (Figure 5). At elevated
temperatures, 8 reacts with 1 equiv of benzyl amine (PhCH2-
NH2) to afford the amidine MeC(dNPh)NHCH2Ph (11), the
bis(µ-oxo)Ti dimer 10, and acetanilide in 2:1:2 ratio, respectively
(eq 3). The same products are observed when the reaction is
performed in the presence of a 10- and 20-fold excess of benzyl
amine, and the rate approximately doubles when the benzyl
amine concentration is increased from 10 to 20 equiv (pseudo-
first-order rate constants ) 1.6(3) × 10-4 and 3.4(3) × 10-4
s-1, respectively, at 70 °C). No significant kinetic isotope effect
is observed when the reaction is performed with PhCH2ND2
(kH/kD ) 1.1((0.1)). As for thermolysis of 7, the reaction of 8
with benzyl amine provides no evidence for transamidation (e.g.,
formation of N-benzylacetamide or -amidate products).
transamidation
yield
amidine
yielda
(%)
PhCH2NH2
(equiv)
acetanilide
(equiv)
entry
[8] (M)
(%)a,b
1
2
3
4
5
6
7
8
0.26
0.26
0.26
0.26
0.26
0.26
0.26
0.02
1
10
20
1
0
0
0
0
0
0
0
0
8
24
0
g97
g97
g97
g97
g97
89
1
1
10
10
10
10
10
25
10
75
g97
a Transamidation product ) N-benzylacetamide. b Yields of N-benzy-
lacetamide and amidine 11 reported relative to the initial concentration of
complex 8.
a substrate/Ti ratio g 10).16 Even in these cases, however
(entries 6 and 7), the transamidation yield is substoichiometric
with respect to 8. Furthermore, the transamidation reactivity
disappears when the substrate and Ti concentration is reduced
(entry 8). Under the reaction conditions employed in this final
entry, exclusive transamidation is observed if 8 is replaced by
Ti(NMe2)4 (see later).
These results with Cp*-ligated Ti complexes reveal that the
Cp* ligand significantly reduces or eliminates the ability of TiIV
to promote transamidation. In nearly every case tested, the
formation of amidines and oxotitanium products is favored over
transamidation. For transamidation to be observed, a large excess
of amine and carboxamide substrate relative to Ti and a high
Ti concentration appear to be essential. These conclusions
provided a basis for further investigation of the origin of the
divergence between amidine formation and transamidation.
Reactivity of Primary Amine/Carboxamide Mixtures in
the Presence of Ti(NMe2)4. The transamidation reaction
between benzyl amine and N-phenylheptanamide (1), which
forms aniline and N-benzylheptanamide (2), is catalyzed ef-
Whereas transamidation was not observed under the condi-
tions of eqs 2 and 3, we previously reported that 5 mol % Cp*Ti-
(NtBu)(py)Cl (3) catalyzes transamidation between carboxamide
1 and benzyl amine (six turnovers after 20 h; cf. eq 1).7a This
evidence that Cp*-ligated Ti complexes can promote transami-
dation (albeit not as effectively as Ti(NMe2)4) prompted us to
test the possibility that transamidation could be observed with
complex 8 under alternate reaction conditions (Table 1). The
first three entries in Table 1 denote the results described above
wherein 1, 10, and 20 equiv of benzyl amine react with 8 in
toluene at 90 °C to produce the amidine 11 in nearly quantitative
yield. Addition of exogenous acetanilide to the reaction of 8
with 1 equiv of benzyl amine does not alter the outcome (entries
4 and 5). The only conditions identified that lead to transami-
dation with 8 feature the use of excess benzyl amine and
acetanilide (i.e., conditions simulating catalytic conditions with
(16) After these reactions were complete, a small amount of water was added
to quench the Ti catalyst, and the organic layer was analyzed by gas
chromatography. No evidence for the presence of free Cp*H ligand was
found. We conclude from this result that a [Cp*Ti]-based complex accounts
for the observed transamidation, not a small amount of a Cp*-free Ti
complex that forms under the reaction conditions.
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A R T I C L E S
Kissounko et al.
the substrate/Ti ratio and is not necessarily a function of the
identity of the titanium complex. Nevertheless, the ancillary
ligands play an important role because Cp*-ligated Ti complexes
are poor transamidation catalysts and promote amidine formation
even under conditions that lead to transamidation with
Ti(NMe2)4 as the catalyst. The size as well as the electron-rich
character of the Cp* ligand could contribute to diminished
transamidation activity of Cp*TiIV-based complexes.
Mechanistic Considerations Relevant to the Divergence
between Amidine Formation and Transamidation. The
results of this study reveal that primary amines react with
carboxamides to form amidines if a stoichiometric quantity of
TiIV is present. With a catalytic quantity of TiIV, either
transamidation or amidine formation can occur, depending on
the identity of the Ti complex.
Thermolysis of the Cp*Ti(κ2-amidate)2(amido) complex 7
(eq 2) is perhaps the simplest reaction among those investigated
in this study. The kinetics data reveal that the reaction proceeds
intramolecularly. The negligible kinetic isotope effect indicates
that proton transfer is not rate-limiting; however, pre-equilibrium
proton transfer cannot be excluded, particularly if the proton is
transferred between two atoms whose bonds to hydrogen have
similar force constants. In this context, a plausible reaction
sequence for amidine formation (Scheme 3) consists of (i) pre-
equilibrium proton transfer from the amido ligand to the κ2-
amidate ligand to produce a neutral O-bound carboxamide and
an imido ligand (B), (ii) [2+2]-cycloaddition to form metalla-
cycle C, (iii) retro-[2+2]-cycloaddition to produce a Ti complex
bearing a coordinated amidine and an oxo ligand (D), and (iv)
dissociation of the amidine together with aggregation of the
oxotitanium species.
The [2+2]-cycloaddition of group 4 imidometal fragments
with organic carbonyl groups has precedent with ketone and
aldehyde substrates,17 and we recently reported a similar reaction
involving a tertiary carboxamide (eq 6).7a N,N-Dimethylaceta-
mide adduct 14, which resembles intermediate B in Scheme 3,
reacts intramolecularly to produce amidine 15 and the oxotita-
nium trimer 16. The metallacyclic species 17 (cf. C, Scheme
3) is a probable intermediate in the reaction shown in eq 6, and
the formation of strong Ti-O bonds provides a thermodynamic
driving force for this process.
Figure 6. Dependence of the product distribution on the Ti(NMe2)4 loading
in the reaction between benzyl amine and the N-phenylheptanamide.
Reaction conditions: 1 (0.39 mmol), PhCH2NH2 (0.39 mmol), Ti(NMe2)4
(0.020-0.39 mmol), toluene (2 mL), 90 °C, 18 h.
fectively by Ti(NMe2)4 (5 mol %) (eq 1).6 On the basis of the
results with Cp*-ligated Ti complexes, we investigated the effect
of varying the Ti(NMe2)4 loading on the outcome of the reaction
between 1 and benzyl amine (eq 4, Figure 6).
When e20 mol % Ti(NMe2)4 is used, the only product
obtained from the reaction is 2, resulting from the transamidation
of 1. As the titanium loading is increased, however, the reaction
yields a mixture of 2 and amidine isomers, 12 and 13. With
50 mol % Ti(NMe2)4, both transamidation and amidine products
form; however, neither forms in good yield. When a stoichio-
metric quantity of Ti(NMe2)4 is present, amidine products form
almost exclusively in a ratio of ∼2:1 favoring 13. No diben-
zylamidine (i.e., the amidine arising from reaction of amide 2
and benzyl amine) is observed under any of these conditions.
The reaction progress under these stoichiometric conditions was
monitored to ascertain whether enhanced levels of transamida-
tion are evident at short reaction times (i.e., whether transami-
dation is kinetically favored, but amidine formation thermody-
namically favored); however, only trace amounts of the
transamidation product are observed throughout the course of
the reaction.
The amidine product ratio appears to be under kinetic control.
A different product ratio (12/13-10:1) is observed in the
reaction between N-benzylamide 2 and aniline in the presence
of 100 mol % Ti(NMe2)4 (eq 5), indicating that amidines 12
and 13 do not equilibrate, at least not rapidly, under the reaction
conditions. None of the transamidation product 1 is observed
under the conditions of eq 5. We note that the amidine product
that is favored in eqs 4 and 5 incorporates the amine substrate
into the “imine” site of the product. These observations are
consistent with a mechanism in which the primary amine reacts
to form an imido ligand prior to reaction with the carbonyl of
the amide substrate (see later).
In principle, transamidation, too, could proceed via a four-
membered metallacycle (i.e., C, Scheme 3). Such a transami-
dation pathway would require that the uncoordinated amine
fragment in C exchange with the amido ligand (C f C′, Scheme
4) followed by retro-[2+2] cycloaddition to regenerate an imido-
(17) (a) Walsh, P. J.; Hollander, F. J.; Bergman, R. G. Organometallics 1993,
12, 3705-3723. (b) Lee, S. Y.; Bergman, R. G. J. Am. Chem. Soc. 1996,
118, 6396-6406.
These collective results indicate that the divergence between
transamidation and amidine formation can be dictated by varying
9
1780 J. AM. CHEM. SOC. VOL. 129, NO. 6, 2007

TiIV-Mediated Reactions
A R T I C L E S
Scheme 3. Proposed Mechanism for Amidine Formation from the Bis(amidate)amidoTi Complex 7
Scheme 4. Hypothetical Mechanism for Transamidation
Proceding via Metallacyclic Intermediates
Scheme 5. Proposed Mechanism for TiIV-Mediated
Transamidation Involving Intramolecular Nucleophilic Attack of an
Amido Ligand on a Coordinated Neutral Carboxamide Ligand
rather than an oxotitanium species (C′ f B′, Scheme 4). The
retrocycloaddition of C′ to form B′ seems unlikely, however,
and preliminary density-functional theory (DFT) calculations
confirm this suspicion. The energy profile in Figure 7 reveals
that [2+2]-retrocycloaddition from C1 (a methyl-substituted
analogue of intermediate C) to form an oxotitanium fragment
with a coordinated amidine (D1) is both kinetically and
thermodynamically favored over formation of an imidotitanium
fragment and a coordinated carboxamide (B1). These results
imply that transamidation does not proceed via the metallacyclic
structure C because such a metallacycle should instead lead to
amidine formation.
Scheme 6. Proposed Mechanism for TiIV-Mediated
Transamidation Involving Nucleophilic Attack of an External Amine
on a Coordinated Amidate Ligand
We do not yet fully understand the mechanistic origin of
transamidation activity; however, several of our observations
establish important constraints for any mechanistic hypothesis.
Transamidation requires a high substrate/Ti ratio (cf. Table 1
and Figure 6). In addition, secondary carboxamides exchange
readily with amido and imido ligands at TiIV to form TiIV-
amidate species, and the amidate ligands may coordinate in a
κ1 or κ2 manner (cf. Schemes 1 and 2). These observations
suggest that Ti(NMe2)4 will form a tetrakis(amidate)TiIV species
in the presence of g4 equiv of carboxamide (e.g., under catalytic
conditions). A similar conclusion was reached in our recent
study of AlIII-catalyzed transamidation, which revealed the
formation of tris(amidate)AlIII species when Al2(NMe2)6 is
combined with g3 equiv of secondary carboxamide per Al
center.7b,18 In the Ti-mediated reactions, we propose that the
presence of excess carboxamide substrate under catalytic
conditions serves to prevent formation of imidotitanium species
(B, Scheme 4) and, thereby, inhibits the production of amidines.
In light of these considerations, we suggest two possible
mechanisms to explain the origin of transamidation activity. In
the first pathway (Scheme 5), a primary amine reacts with a
tetrakis(amidate)TiIV species F to form an amidotitanium species
G, which possesses a neutral, oxygen-bound carboxamide
ligand. Intramolecular nucleophilic attack of the amido ligand
on the carboxamide forms metallacycle H, which can undergo
dissociation of the amino fragment to yield the symmetrical
tetrahedral intermediate I. The latter species can revert to starting
materials or proceed to the transamidation product F′. The
second hypothetical mechanism (Scheme 6) is related to Scheme
5 but features a different C-N bond-forming step. An external
amine undergoes nucleophilic attack on a coordinated amidate
ligand to produce zwitterionic intermediate J, and intramolecular
proton transfer generates metallacycle H′, which appears also
in Scheme 5.
Both of these mechanisms avoid formation of metallacycle
C (Scheme 4, Figure 7), which appears to lead to amidine
formation. Although intermediates H and H′ resemble C, we
hypothesize that the presence of a proton on the coordinated
nitrogen atom of the metallacycles in H and H′ will weaken
the Ti-N bond, thereby facilitating exchange of the amino
fragments and enabling transamidation. Because amidines also
(18) Further support for (amidate)titanium species under catalytic conditions is
obtained from kinetic studies. Both Ti- and Al-catalyzed transamidation
reactions exhibit a zero-order rate dependence on [carboxamide], consistent
with the proposal that the amide substrate is complexed to the catalytic
metal center prior to the rate-determining step (ref. 7b for detailed
discussion).
Figure 7. Free energy profile for retrocycloaddition from a model
metallacycle C1 at 90 °C derived from DFT calculations optimized with a
double ú basis set. See Experimental Section for details.
9
J. AM. CHEM. SOC. VOL. 129, NO. 6, 2007 1781

A R T I C L E S
Kissounko et al.
1
product 6 as yellow crystals (0.219 g, 52.5%). H NMR (300 MHz,
benzene-d6): δ 1.11 (d, 18 H, J ) 7.2 Hz, CHMe2), 1.87 (s, 15 H,
C5Me5), 4.27 (sept, 3 H, J ) 7.2 Hz, CHMe2), 5.18 (br s, 3 H, NH).
13C{1H} NMR (75 MHz, benzene-d6): δ 11.7 (C5Me5), 27.8 (CHMe2),
54.8 (CHMe2), 116.8 (C5Me5). IR (CH2Cl2): νmax 2956 s, 2912 s, 2859
s (NH) cm-1. Anal. Calcd for C34H39N3O3Ti: C, 63.83; H, 11.02; N,
11.76. Found: C, 63.62; H, 10.95, N, 11.73.
can potentially form via intermediates H/H′ and I, further studies
will be needed test these proposals. Extensive DFT studies have
been initiated to probe the mechanisms in Schemes 5 and 6 in
an effort to identify the preferred C-N bond forming pathway
and to evaluate whether the intermediates in these mechanisms
face higher barriers for amidine formation relative to transa-
midation.
Cp*Ti(NDiPr)3 (6-d1). This complex was prepared in a similar way
as 6 from 5 (0.372 g, 1.18 mmol) and iPrND2 (0.56 g, 11.80 mmol) to
afford the product 6-d1 as yellow crystals (0.201 g, 49.2%). H NMR
Conclusion
1
The data reported here significantly advance our understand-
ing of Ti-mediated exchange processes involving carboxamides
and amines, particularly with respect to the ability of TiIV to
promote either transamidation or amidine formation depending
on the reaction conditions. We find that TiIV, when present in
approximately stoichiometric quantity with respect to the
substrates, promotes amidine formation rather than transami-
dation. This result is attributed to the formation of a four-
membered metallacycle that can undergo retrocycloaddition to
form amidine and a thermodynamically stable oxotitanium
product. The ability of TiIV to avoid irreversible formation of
oxotitanium products and promote transamidation under the
catalytic conditions is quite remarkable. Insights from the present
study suggest that exogenous substrates (both amine and
carboxamide) present under catalytic conditions prevent forma-
tion of a four-membered metallacycle, as in C, that leads to
amidine formation and Ti inactivation via formation of an oxo
complex. Avoidance of metallacycle C under catalytic reaction
conditions enables transamidation to occur. Substoichiometric
transamidation is observed in the presence of the Cp*TiIV-
(amidate)3 complex 8; however, the electron-donating and
sterically bulky Cp* ligand renders TiIV ineffective as a
transamidation catalyst. Thus, we find that the ability of TiIV
to promote transamidation depends upon both the substrate/Ti
ratio and the ancillary ligands coordinated to TiIV. Although
further work will be necessary to elucidate the mechanistic origin
of transamidation activity, the results of this study highlight an
unexpected dichotomy in the reactivity of TiIV with carboxa-
mides and amines.
(300 MHz, benzene-d6): δ 1.11 (d, 21 H, J ) 7.2 Hz, CHMe2), 1.88
(s, 15 H, C5Me5), 4.28 (sept, 3 H, J ) 7.2 Hz, CHMe2).
Cp*Ti(NHiPr)[κ2-OC(Me)NPh]2 (7). To a solution of 6 (0.047 g,
0.13 mmol) in 10 mL of Et2O, acetanilide (0.025 g, 0.19 mmol) was
added at ambient temperature. The reaction was stirred overnight,
whereupon all the volatiles were removed under vacuum, and the
residue was extracted with pentane, filtered through Celite, and
evaporated to dryness. The residue was crystallized from ca. 3 mL of
pentane at -30 °C to afford the product 7 as yellow crystals (0.032 g,
47.8%). 1H NMR (300 MHz, benzene-d6): δ 0.91 (d, 6 H, J ) 6.6 Hz,
CHMe2), 2.80 (s, 3 H, CMe[OC(Me)NPh]), 2.08 (s, 15 H, C5Me5), 4.86
(sept, 1 H, J ) 6.6 Hz, CHMe2), 6.94-7.21 (m, 10 H, Ph), 8.64 (br s,
1 H, NH). 13C{1H} NMR (75 MHz, benzene-d6): δ 14.2 (C5Me5), 21.7
(CMe[OC(Me)NPh]), 28.7 (CHMe2), 57.6 (CHMe2), 125.3 (C5Me5),
125.9, 128.2, 131.4, 150.8 (Ph), 178.6 (CMe[OC(Me)NPh]). IR (CH2-
Cl2): νmax 3044 m (NH) cm-1; 1588 s, 1546 m (sh) (amidate) cm-1
.
Anal. Calcd for C29H39N3O2Ti: C, 68.36; H, 7.73; N, 8.25. Found: C,
68.66; H, 7.90, N, 8.22.
Cp*Ti(NDiPr)[κ2-OC(Me)NPh]2 (7-d). This complex was prepared
in a similar way as 7-d1 from 6-d1 (0.047 g, 0.13 mmol) and acetanilide
(0.026 g, 0.19 mmol) to afford the product 7-d1 as yellow crystals (0.034
1
g, 51.2%). H NMR (300 MHz, benzene-d6): δ 0.87 (d, 6 H, J ) 6.6
Hz, CHMe2), 1.75 (s, 3 H, CMe[OC(Me)NPh]), 2.02 (s, 15 H, C5Me5),
4.80 (sept, 1 H, J ) 6.6 Hz, CHMe2), 6.90-7.15 (m, 10 H, Ph).
Cp*Ti[κ1-OC(Me)NPh][κ2-OC(Me)NPh]2 (8). To a solution of 6
(0.094 g, 0.26 mmol) in 15 mL of Et2O, acetanilide (0.107 g, 0.78
mmol) was added at ambient temperature. The reaction was stirred
overnight, whereupon all the volatiles were removed under vacuum,
the residue was extracted three times with 4 mL of 6:1 pentane/toluene
solvent mixture, filtered through Celite, and evaporated to dryness. The
residue was crystallized from ca. 5 mL of 6:1 pentane/toluene solvent
mixture at -30 °C to afford the product 8 as red crystals (0.107 g,
1
70.0%). H NMR (300 MHz, benzene-d6): δ 1.66 (s, 3 H, CMe[κ1-
Experimental Section
OC(Me)NPh]), 2,12 (s, 6 H, CMe[κ2-OC(Me)NPh]), 1.92, 1.93 (s, 15
H, C5Me5), 6.99-7.53 (m, 15 H, Ph). 13C{1H} NMR (75 MHz, benzene-
d6): δ 11.8, 12.0 (C5Me5), 19.1 (CMe[κ1-OC(Me)NPh]), 24.3 (CMe[κ2-
OC(Me)NPh]), 123.3, 124.2 (C5Me5), 121.6, 124.6, 128.6, 129.0, 129.9,
146.4, 147.3, 150.8 (Ph), 174.8 (CMe[κ1-OC(Me)NPh]), 175.3 (CMe-
[κ2-OC(Me)NPh]). IR (CH2Cl2): νmax 1604 m (sh), 1596 s, 1561 m
(sh) (amidate) cm-1. Anal. Calcd for C34H39N3O3Ti: C, 69.73; H, 6.73;
N, 7.18. Found: C, 69.65; H, 6.85, N, 7.63.
Thermolysis of 7 Leading to MeC(dNiPr)NHPh (9) and Cp*Ti(µ-
O)[κ2-OC(Me)NPh]}2 (10). A solution of 7 (0.058 g, 0.11 mmol) in 1
mL of C6D6 was heated at 50 °C for 3 h, whereupon 1H NMR spectrum
showed ∼100% conversion of the starting material into amidine 9 and
complex 10. Then all the volatiles were removed under vacuum, the
residue was dissolved in 1 mL of CH2Cl2, layered with 5 mL of pentane,
and stored at -30 °C for 2 days. The supernatant, decanted from yellow
crystals of 10 (0.042 g, 87.4%), which contained 9 and residual 10
was evaporated to dryness; the residue extracted with ca. 3 mL of 2:1
pentane/Et2O solvent mixture, filtered through Celite, and crystallized
at -30 °C to afford the amidine 9 as white crystals (0.014 g, 69.5%).
General Procedures. All manipulations were carried out under an
atmosphere of nitrogen using standard Schlenk or glove box techniques.
All solvents (diethyl ether, dichloromethane, toluene, and pentane) were
dried by passing over a column of activated alumina followed by a
column of Q-5 scavenger. Complex 5,13 PhCH2ND2, and iPrND219 were
synthesized according to literature procedures. All other reagents were
purchased from commercial sources and used as supplied.
Benzene-d6 and CD2Cl2 were dried over Na-K alloy/benzophenone
and CaH2, respectively, for 24 h and vacuum transferred prior to use.
1H and 13C{1H} NMR spectra were recorded on Bruker AC-300
spectrometers at 300 and 75 MHz, respectively. Elemental analyses
were performed by Midwest Microlab laboratory.
Cp*Ti(NHiPr)3 (6). To a solution of 5 (0.372 g, 1.18 mmol) in 10
mL of toluene, isopropyl amine (1.0 mL, 11.80 mmol) was added at
ambient temperature. The reaction was brought to reflux in a sealed
Schlenk tube at 110 °C overnight, whereupon all the volatiles were
removed under vacuum, and the residue was extracted with 10 mL of
pentane, filtered through Celite and evaporated to dryness. The residue
was crystallized from ca. 7 mL of pentane at -30 °C to afford the
(20) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1988, 37, 785-789. (c) Becke, A. D. J. Chem.
Phys. 1993, 98, 5648-5652.
(19) (a) Khanzada, A. W. K.; McDowell, C. A. J. Magn. Res. 1977, 27, 483-
496. (b) Ross, S. D.; Finkelstein, M.; Petersen, R. C. J. Am. Chem. Soc.
1959, 81, 5336-5342.
(21) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299-310.
9
1782 J. AM. CHEM. SOC. VOL. 129, NO. 6, 2007

TiIV-Mediated Reactions
A R T I C L E S
9: 1H NMR (300 MHz, benzene-d6): δ 1.19 (d, 6 H, J ) 6.6 Hz,
CHMe2), 3.54 (br s, 1 H, NH), 4.51 (sept, 1 H, J ) 6.6 Hz, CHMe2),
7.08-7.45 (m, 5 H, Ph). MS (EI) m/z: 176 (100, M+).
Reaction between N-Phenyl Heptanamide (1) and Benzyl Amine
in the Presence of Ti(NMe2)4. To a solution of 1 (0.080 g, 0.39 mmol)
and Ph3CH (3 mg, internal standard) in 2 mL of toluene, benzyl amine
(42 µL, 0.39 mmol) was added at ambient temperature followed by
the appropriate amount of Ti(NMe2)4 (0.02-0.39 mmol). The reaction
mixture was stirred for 5 min, whereupon it was stripped to dryness to
remove any HNMe2. Then the residue was redissolved in 2 mL of
toluene and brought to 90 °C in a sealed vial and heated for 18 h,
whereupon it was cooled to ambient temperature. Water (100 µL) was
added to the reaction mixture to hydrolyze Ti-based species. The toluene
solution was dried over Na2SO4 and analyzed by GC.
10: 1H NMR (300 MHz, CD2Cl2): δ 1.83 (s, 30 H, C5Me5), 2.25
(s, 6 H, CMe[OC(Me)NPh]), 7.09-7.36 (m, 10 H, Ph). 13C{1H} NMR
(75 MHz, CD2Cl2): δ 11.5 (C5Me5), 19.5 (CMe[OC(Me)NPh]), 123.3
(C5Me5), 123.8, 124.2, 128.5, 144.9 (Ph), 175.7 (CMe[OC(Me)NPh]).
Anal. Calcd for C36.125H46.28Cl0.25N2O4Ti2 (contains 1/8 CH2Cl2 solvent
molecule): C, 64.07; H, 6.90; N, 4.14. Found: C, 63.95; H, 6.97, N,
4.37.
Kinetic Studies of the Reaction between Trisamidate Complex
8 and Benzyl Amine. A solution of 8 (0.270 g, 0.46 mmol), benzyl
amine (0.5 mL, 4.60 mmol), and 1,3,5-trimethoxybenzene (internal
standard) in 0.5 mL of C6D6 was heated at 70 °C for 24 h, whereupon
the 1H NMR spectrum revealed ∼100% conversion of the starting
material into amidine 11 and complex 10.
Computational Methods. The geometries for all critical species
(reactants, intermediates, transition states, and products) were optimized
in the gas phase using the hybrid density-functional theory, B3LYP.20
To simplify calculations, the amide was replaced with acetamide. The
effective core potential (ECP) of Hay and Wadt21 and the corresponding
basis set (augmented by an f function22) were used for Ti; the 6-31G-
(d,p) basis23 was used for all other main group elements during geometry
optimizations and frequency calculations. Vibrational frequency cal-
culations were subsequently carried out to verify the character of the
optimized structures and to obtain zero-point energy corrections to
barrier heights. Single-point total energies were calculated for all atoms
with the all electron 6-311+G(d,p) basis set,24 and the thermal
corrections from the optimized structure was added to generate the free
energies. All calculations were performed with the Gaussian 03
program.25
Studies of the Thermal Reaction between Trisamidate Complex
8, Acetanilide, and Benzyl Amine. (a) A solution of 8 (0.077 g, 0.13
mmol), appropriate amounts of benzyl amine and acetanilide, and 1,3,5-
trimethoxybenzene (internal standard) in 0.5 mL of C6D6 was heated
at 70 °C for 24 h, whereupon the 1H NMR spectrum revealed ∼100%
conversion of the starting material into complex 10, amidine 11, and
benzylacetamide (transamidated carboxiamide). After that, water (100
µL) was added to the reaction mixture to hydrolyze Ti-based species.
The solution was dried over Na2SO4 and analyzed by GC.
(b) A solution of acetanilide (0.080 g, 0.39 mmol), 8 (0.022 g, 0.039
mmol) in 2 mL of toluene, benzyl amine (42 µL, 0.39 mmol), and
Ph3CH (3 mg, internal standard) was brought to 90 °C in a sealed tube
and heated for 18 h, whereupon it was cooled to ambient temperature.
Water (100 µL) was added to the reaction mixture to hydrolyze Ti-
based species. The toluene solution was dried over Na2SO4 and analyzed
by GC.
Acknowledgment. We are grateful to the NSF Collaborative
Research in Chemistry program (Grant CHE-0404704) for
financial support of this work. We thank Prof. L. L. Schafer
for sharing ref 11 with us prior to publication.
(22) Ehlers, A. W.; Bo¨hme, M.; Dapprich, S.; Gobbi, A.; Ho¨llwarth, A.; Jonas,
V.; Ko¨hler, K. F.; Stegmann, R.; Veldkamp, A.; Frenking, G. Chem. Phys.
Lett. 1993, 208, 111-114.
Supporting Information Available: Complete ref 25, crystal-
lographic data for 7, 8, and 10 (PDF, CIF), and computed
geometries for structures in Figure 7 (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
(23) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213-222.
(24) (a) Hay, P. J. J. Chem. Phys. 1977, 66, 4377-4384. (b) Krishnan, R.;
Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72, 650-654.
(c) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639-5648.
(d) Raghavachari, K.; Trucks, G. W. J. Chem. Phys. 1989, 91, 1062-
1065.
(25) Frisch, M. J.; et al. Gaussian 03, revision B.04; Gaussian, Inc.: Wallingford,
CT, 2004.
JA0650293
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