Ti(NMe2)4 and [HNMe2Ph][B(C 6F5)4]: A convenient blend for effective catalytic carboamination of alkynes

Article abstract of DOI:10.1021/om0602207

Ti(NMe₂)₄, when combined with [HNMe ₂Ph][B(C₆F₅)₄], catalyzes carboamination of alkynes with aldimines to form highly arylated α,β-unsaturated imines with exclusive (E,E)-configuration at the olefin and (mine residues. Complexes [Ti-(NHMe₂)(NMe ₂)₃][B(C₆F₅)₄] and [Ti=NAr(NHMe₂)₃(NMe₂)]-[B(C₆F ₅)₄] (Ar = 2,6-ⁱPr₂C ₆H₃), isolated from stoichiometric reactions involving Ti(NMe₂)₄/[HNMe₂Ph][B(C₆F ₅)₄] and Ti-(NMe₂)₄/[HNMe ₂Ph][B(C₆F₅)₄]/ArNH₂, respectively, also catalyze carboamination with activity comparable to that of the Ti(NMe₂)₄/[HNMe₂Ph][B(C₆F ₅)₄] system.

Full text of DOI:10.1021/om0602207

2402
Organometallics 2006, 25, 2402-2404
Ti(NMe2)4 and [HNMe2Ph][B(C6F5)4]: A Convenient Blend for
Effective Catalytic Carboamination of Alkynes
Halikhedkar Aneetha, Falguni Basuli, John Bollinger, John C. Huffman, and
Daniel J. Mindiola*
Department of Chemistry and Molecular Structure Center, Indiana UniVersity,
Bloomington, Indiana 47405
ReceiVed March 8, 2006
Scheme 1. Mechanism for the Catalytic Carboamination of
Alkynes with Imines
Summary: Ti(NMe2)4,whencombinedwith[HNMe2Ph][B(C6F5)4],
catalyzes carboamination of alkynes with aldimines to form
highly arylated R,â-unsaturated imines with exclusiVe (E,E)-
configuration at the olefin and imine residues. Complexes [Ti-
(NHMe2)(NMe2)3][B(C6F5)4] and [TidNAr(NHMe2)3(NMe2)]-
[B(C6F5)4] (Ar ) 2,6-iPr2C6H3), isolated from stoichiometric
reactions inVolVing Ti(NMe2)4/[HNMe2Ph][B(C6F5)4] and Ti-
(NMe2)4/[HNMe2Ph][B(C6F5)4]/ArNH2, respectiVely, also cata-
lyze carboamination with actiVity comparable to that of the
Ti(NMe2)4/[HNMe2Ph][B(C6F5)4] system.
The catalytic carboamination of alkynes with imines is an
emerging field in organotransition metal chemistry allowing
access to a new class of highly arylated organic archetypes.1-3
Recently, the Bergman group reported imidozirconocene-
catalyzed carboamination reactions involving aryl aldimines and
diaryl alkynes to generate R,â-unsaturated imines.1,2 Inspired
by this work, in which new CdC and CdN bonds are formed,
our group discovered that the latent low-coordinate titanium
imide [(nacnac)TidNAr(FC6H5)][B(C6F5)4] (nacnac- ) [ArNC(t-
Bu)]2CH, Ar ) 2,6-iPr2C6H3) can also engage, efficiently, in
catalytic carboamination reactions to produce R,â-unsaturated
imines as well as triaryl-substituted quinolines.3 In both titanium-
and zirconium-catalyzed reactions, the first step in the catalytic
cycle involves generation of an unsaturated metal imide [M]d
NR1. [2+2] Cycloaddition of the alkyne across the MdN
linkage and subsequent insertion of aldimine into the M-C bond
of the four-membered azametallacyclobutene forms a six-
membered metallacycle. The latter readily undergoes a retro-
[4+2] cycloaddition to extrude the R,â-unsaturated imine
product and regenerate the corresponding imide (Scheme 1).
In the catalytic reaction, the electron-deficient cation [(nacnac)-
TidNAr(FC6H5)]+ was a precatalyst since it readily underwent
imine metathesis in situ with the appropriate aldimine substrate
to afford a sterically less hindered imide, which would then
execute the catalytic cycle. Although the Ti(IV) fluorobenzene
precatalyst was effective in performing these reactions, the
exceedingly reactive nature of this complex limited our ability
to manipulate this system under traces of donors as well as
explore functional group tolerance.3 Consequently, these limita-
tions prompted us to seek other catalysts or precatalysts that
not only would be facile to prepare and manipulate but would
reduce reaction times and temperatures and expand the range
of substrates.
In this work, we wish to disclose that the combination of
Ti(NMe2)4 and [HNMe2Ph][B(C6F5)4]4 generates an efficient
catalyst system for the carboamination of alkynes with aldi-
mines. The commercial availability of the two reagents avoids
multistep ligand and metal complex syntheses, allowing for the
facile preparation of highly arylated R,â-unsaturated imines.
Additionally, this catalyst system also tolerates a variety of
functional groups and reduces both reaction times and temper-
atures. In the process of investigating the active species involved
in the catalytic carboamination cycle we discovered two titanium
salts, both of which appear to be precatalysts in the catalytic
carboamination reaction.
Previous studies by Odom5 and Schafer6 have demonstrated
that common reagents such as Ti(NMe2)4 can serve as competent
precatalysts for the hydroamination7,8 of alkynes and intramo-
lecular hydroamination of amino alkenes, respectively. Unfor-
tunately, Ti(NMe2)4 was not efficient in catalyzing carboami-
nation reactions using di-p-tolylaldimine and PhCCPh in the
presence or absence of p-toluidine (Table 1, entries 1, 2).
Realizing that the carboamination precatalyst [(nacnac)TidNAr-
(4) Tjaden, E. B.; Swenson, D. C.; Jordan, R. F.; Petersen, J. L.
Organometallics 1995, 14, 371-386.
(5) Shi, Y.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001, 20,
3967-3969.
(6) Bexrud, J. A.; Beard, J. D.; Leitch, D. C.; Schafer, L. L. Org. Lett.
2005, 7, 1959-1962.
* To whom correspondence should be addressed. E-mail: mindiola@
indiana.edu.
(7) Pohlki, F.; Doye, S. Chem. Soc. ReV. 2003, 32, 104-114.
(8) (a) Lorber, C.; Choukroun, R.; Vendier, L. Organometallics 2004,
23, 1845. The common reagent titanium tetrachloride has been demonstrated
to be an active hydroamination catalyst. (b) Kaspar, L. T.; Fingerhut, B.;
Ackermann, L. Angew. Chem. Int. Ed. 2005, 44, 5971-5974. (c) Acker-
mann, L.; Kaspar, L. T.; Gschrei, C. J. Org. Lett. 2004, 6, 2515-2518.
(1) Ruck, R. T.; Bergman, R. G. Organometallics 2004, 23, 2231-2233.
(2) Ruck, R. T.; Zuckermann, R. L.; Krska, S. W.; Bergman, R. G.
Angew. Chem., Int. Ed. 2004, 43, 5372-5374.
(3) Basuli, F.; Aneetha, H.; Huffman, J. C.; Mindiola, D. J. J. Am. Chem.
Soc. 2005, 127, 17992-17993.
10.1021/om0602207 CCC: $33.50 © 2006 American Chemical Society
Publication on Web 04/11/2006

Communications
Organometallics, Vol. 25, No. 10, 2006 2403
Table 1. Screening of Catalysts for the Carboamination
Reactiona
entry
catalyst
time (h)
yield (%)
1
2
Ti(NMe2)4 (20 mol %)
Ti(NMe2)4/4-CH3C6H4NH2
(20 mol % each)
120
120
traces
traces
Figure 1. Molecular structure of cationic components of complexes
1 (left) and 2 (right) depicting thermal ellipsoids at the 50%
probability level. Only R-hydrogens on the amines are depicted
for the purpose of clarity. Selected bond lengths (Å) and angles
(deg) for the cation of 1: Ti1-N2, 1.857(2); Ti1-N8, 1.870(2);
Ti1-N11, 1.876(2); Ti-N5, 2.188(2); N2-Ti1-N8, 108.96(5);
N2-Ti1-N11, 111.12(5); N2-Ti1-N5, 110.71(5); N5-Ti1-N8,
102.72(5); N5-Ti1-N11, 110.16(5); N8-Ti1-N11, 112.87(5). For
the cation of 2: Ti1-N2, 1.714(2); Ti1-N15, 1.908(2); Ti1-N18,
2.234(2); Ti1-N24, 2.259(3); Ti1-N21, 2.295(2); N15-Ti1-N18,
91.2(1); N18-Ti1-N21, 85.11(9); N21-Ti1-N24, 81.49(9);
N24-Ti1-N15, 93.1(1); N15-Ti1-N2, 105.9(1); N18-Ti1-N2,
99.2(1); N21-Ti1-N2, 109.1(1); N24-Ti1-N2, 96.2(1); Ti1-
N2-C3, 173.4(9).
3
4
Ti(NMe2)4/4-CH3C6H4NH2/
[HNMe2Ph][B(C6F5)4](10 mol % each)
Ti(NMe2)4/[HNMe2Ph][B(C6F5)4]
(10 mol % each)
16
16
80-90
80-90
a Reactions were carried out on a 0.25 mmol scale of aldimine using 10
mol % catalyst in C6D6 at 125 °C and % yield was assayed by H NMR.
1
(FC6H5)][B(C6F5)4] is a salt-like, latent low-coordinate titanium
imide reagent, we hypothesized whether acids such as [HNMe2-
Ph][B(C6F5)4] could activate Ti(NMe2)4.
Gratifyingly, 1:1:1 C6D6 solutions of 10 mol % Ti(NMe2)4,
[HNMe2Ph][B(C6F5)4], and p-toluidine catalyzed carboamination
reactions in considerably shorter reaction times (16 h) and lower
temperatures (125 °C) when compared to the Cp2Zr2 and
(nacnac)Ti-based3 catalysts previously reported in the literature
(Table 1, entry 3).9 To our surprise, the same carboamination
reaction also proceeded smoothly but in the absence of the
aniline (Table 1, entry 4).9 Since early transition metal imides
have been proposed to be active intermediates along the
carboamination cycle,1-3 the absence of aniline in the latter
reaction suggests that aldimine might be playing a role as an
imide-transfer reagent.10 The titanium reagent Ti(NMe2)4 is
critical in these reactions since 10-20 mol % of [HNMe2Ph]-
[B(C6F5)4] alone failed to show any conversion to the R,â-
unsaturated imine product.
On the basis of these preliminary experiments, reactions of
a series of aldimines and alkynes were carried out according to
the reaction conditions described in entry 4 of Table 1.
Aldimines bearing electron-donating groups such as methyl,
methoxy, and dimethylamino groups gave the corresponding
R,â-unsaturated imine derivatives in good yields (Table 2a,
entries 2-8), whereas aldimines bearing an electron-withdraw-
ing trifluoromethyl group did not afford the product. Alkynes
such as bis(p-methylphenyl)acetylene and bis(p-methoxyphe-
nyl)acetylene containing electron-donating groups also gave the
corresponding R,â-unsaturated imine derivatives in good yields
(Table 2a, entries 9-12). The carboamination of bis(p-bro-
mophenyl)acetylene afforded the corresponding dibromo-
substituted R,â-unsaturated imine in 32% yield (Table 2a, entry
13). Unsymmetrical alkynes such as PhCC(4-CH3C6H4) did not
exhibit regioselective carboamination. All the R,â-unsaturated
imines generated from these carboamination reactions have
exclusive (E,E)-configuration at the olefin and the imine residues
(Table 2a, entries 1-13).9 Most notably, the reaction times are
dramatically reduced from 24-96 h to 16-24 h using this
combination of ingredients.
lene, and p-tolylaldimine. Accordingly, reaction of Ti(NMe2)4
with 1 equiv of [HNMe2Ph][B(C6F5)4] generated the trisamide
monoamine salt [Ti(NHMe2)(NMe2)3][B(C6F5)4] in 85% yield.
1H, 13C, 19F, and 11B NMR spectra of 1 are consistent with cation
formation resulting from an amide being protonated, while the
single-crystal X-ray structure confirms the ionic and monomeric
nature of the four-coordinate titanium center (Figure 1).9,11 Our
hypothesis that aldimine might play a role as an imide transfer
reagent in the catalytic cycle proved reasonable inasmuch as
isolated samples of complex 1 catalyze carboamination reactions
of alkynes with aldimines with similar catalytic activity (Table
2b, entries 14-17) to the Ti(NMe2)4/[HNMe2Ph][B(C6F5)4]
system reported in entries 2, 4, 6, and 7 of Table 2a (vide
supra).9 Multiple attempts to isolate a complex from the
stoichiometric reaction mixtures containing Ti(NMe2)4, [HNMe2-
Ph][B(C6F5)4], and p-tolylaldimine in the presence and absence
of diphenylacetylene were unsuccessful.
The possibility of a titanium imide playing a role in these
carboamination reactions motivated us to prepare a terminal
imide using an alternative method. Treatment of 1 with the
hindered aniline H2NAr (Ar ) 2,6-iPr2C6H3) afforded the five-
coordinate titanium imide [TidNAr(NHMe2)3(NMe2)][B(C6F5)4]
(2) in excellent yield. NMR spectra, as well as the single-crystal
X-ray structure, confirmed a cationic, five-coordinate titanium
center possessing a terminal imide motif (Figure 1).9,12 More
specifically, the molecular structure of 2 clearly depicts a square
pyramidal Ti(IV) center containing a terminal arylimide func-
tionality in the axial position, while three pyramidalized
dimethylamines and one planar dimethylamide occupy the
equatorial sites. Complex 2 also catalyzes carboamination
reactions comparable to that of the in situ-generated catalyst
(11) Crystal data for 1: C32H25BF20N4Ti, 904.27 g/mol, triclinic, P1h,
yellow prism, a ) 14.4540(17) Å, b ) 17.392(2) Å, c ) 17.702(2) Å, R )
109.676(3)°, â ) 108.043(3)°, γ ) 106.675(3)°, V ) 3583.7(7) Å3, T )
127(2) K, Z ) 4, R(F, observed data) ) 0.0371, S ) 1.014. Data were
collected on a Bruker three-circle diffractometer with a SMART 6000
detector. The structure was solved by direct methods (SHELXS) and refined
via full-matrix least-squares (SHELXL). Hydrogen atoms were placed in
idealized positions and refined isotropically; non-hydrogen atoms were
refined anisotropically.
To isolate an active species involved in the carboamination
reactions, we studied the products generated by various com-
binations of Ti(NMe2)4, [HNMe2Ph][B(C6F5)4], diphenylacety-
(9) See Supporting Information for complete experimental details.
(10) Gomez-Sal, P.; Martin, A.; Mena, M.; Morales, M. C.; Santamaria,
C. Chem Commun. 1999, 1839-1840.

2404 Organometallics, Vol. 25, No. 10, 2006
Table 2a. Carboamination Reactions Catalyzed by a Ti(NMe2)4/[HNMe2Ph][B(C6F5)4] Mixturea
Communications
entry
aldimine
alkyne
product
yield (%)
1b
2b
3
3a; R1 ) R2 ) H
4a; Ar ) Ph
5a
5b
5c
5d
5e
5f
5g
5h
5i
71
69
70
68
70
68
75
72
72
76
62
64
32
3b; R1 ) R2 ) CH3
4a; Ar ) Ph
3c; R1 ) CH3, R2 ) OCH3
3d; R1 ) OCH3, R2 ) CH3
3e; R1 ) NMe2, R2 ) OCH3
3f; R1 ) R2 ) OCH3
4a; Ar ) Ph
4b
5
4a; Ar ) Ph
4a; Ar ) Ph
6
7
8
9
10
11
12
13c
4a; Ar ) Ph
3g; R1 ) OCH3, R2 ) NMe2
3h; R1 ) CH3, R2 ) NMe2
3g; R1 ) OCH3, R2 ) NMe2
3h; R1 ) CH3, R2 ) NMe2
3f; R1 ) R2 ) OCH3
4a; Ar ) Ph
4a; Ar ) Ph
4b; Ar ) 4-CH3C6H4
4c; Ar ) 4-OCH3C6H4
4b; Ar ) 4-CH3C6H4
4c; Ar ) 4-OCH3C6H4
4d; Ar ) 4-BrC6H4
5j
5k
5l
3d; R1 ) OCH3, R2 ) CH3
3h; R1 ) CH3, R2 ) NMe2
5m
a Reactions were carried out with 10 mol % Ti(NMe2)4/[HNMe2Ph][B(C6F5)4] in C6D6 at 125 °C for 24 h. Reaction times were not minimized. Yield of
the isolated product after column chromatography. b Reactions also proceeded to completion with 5 mol % catalyst mixture. c 15 mol % Ti(NMe2)4/
[HNMe2Ph][B(C6F5)4] was used.
Table 2b. Carboamination Reactions Catalyzed by Isolated Samples of Compound 1 or 2d
entry
catalyst
aldimine
alkyne
product
yield (%)
14
15
16
17
18
19
20
21
1
1
1
1
2
2
2
2
3b; R1 ) R2 ) CH3
4a; Ar ) Ph
4a; Ar ) Ph
4a; Ar ) Ph
4a; Ar ) Ph
4a; Ar ) Ph
4a; Ar ) Ph
4a; Ar ) Ph
4a; Ar ) Ph
5b
5d
5f
5g
5b
5d
5f
80-90e
64f
3d; R1 ) OCH3, R2 ) CH3
3f; R1 ) R2 ) OCH3
66f
3g; R1 ) OCH3, R2 ) NMe2
3b; R1 ) R2 ) CH3
71f
80-90e
65f
3d; R1 ) OCH3, R2 ) CH3
3f; R1 ) R2 ) OCH3
69f
3g; R1 ) OCH3, R2 ) NMe2
5g
73f
d Reactions were carried out on a 0.25 mmol scale of aldimine using 10 mol % of catalyst in C6D6 at 125 °C for 24 h. Reaction times were not minimized.
1
e The percent yield was assayed by H NMR spectroscopy. f The percent yield was obtained after column chromatography.
system (Table 2b, entries 18-21), thereby hinting that 2 might
also be a precatalyst.
in the absence of aniline suggests tantalizingly that aldimine
might be playing a role as an imide transfer reagent. We are
currently exploring the mechanism of this reaction and the role
of [HNMe2Ph][B(C6F5)4] with other common reagents of
titanium.
In conclusion, we have shown that [HNMe2Ph][B(C6F5)4] can
transform a commercially available starting material such as
Ti(NMe2)4 into an efficient catalyst for carboamination of
alkynes, therefore providing a facile protocol for the synthesis
of highly arylated R,â-unsaturated imines. The fact that complex
1 catalyzes carboamination reactions of alkynes with aldimines
Acknowledgment. D.J.M. thanks Indiana University-
Bloomington, the Dreyfus Foundation, the Sloan Foundation,
and the NSF (CHE-0348941, PECASE) for financial support
of this research. The authors also thank Prof. Todd B. Marder
for a gift of disubstituted alkyne.
(12) Crystal data for 2: C44H44BF20N5Ti, 1081.55 g/mol, triclinic, P1h,
yellow prism, a ) 11.516(2) Å, b ) 13.155(3) Å, c ) 16.474(3) Å, R )
88.869(5)°, â ) 73.304(5)°, γ ) 86.209(5)°, V ) 2385.4(8) Å3, T ) 124-
(2) K, Z ) 2, R(F, observed data) ) 0.0474, S ) 0.860. Data were collected
on a Bruker three-circle diffractometer with a SMART 6000 detector. The
structure was solved by direct methods (SHELXS) and refined via full-
matrix least-squares (SHELXL). Hydrogen atoms were placed in idealized
positions and refined isotropically; non-hydrogen atoms were refined
anisotropically.
Supporting Information Available: Complete experimental
preparation (1 and 2, and organic products 3-5) and crystal-
lographic data (1 and 2). This material is available free of charge
via the Internet at http://pubs.acs.org.
OM0602207