by this work, we described last year stable titanocene alkyne
complexes of the type [Cp2Ti(η2-Me3SiC2R)] for the selective
anti-Markovnikov hydroamination of terminal alkynes with
aliphatic amines.11
More recently, non-Cp-based titanium complexes were
studied for intermolecular hydroamination of alkynes. Odom
and co-workers described Ti(NMe2)4 212 and pyrrolyl tita-
nium complexes,13 and Richeson et al. reported a guanidinate-
supported titanium imido complex as precatalyst for these
reactions.14
Despite the aforementioned advantages, known titanocene
precatalysts exhibit in general high air and moisture sensitiv-
ity. Also mixtures of regioisomeric imines are often obtained
as products using nonsymmetrical alkynes as starting materi-
als. Thus, there exists a considerable interest in the improve-
ment of titanium-based hydroamination catalysts. We won-
dered whether it was possible to improve the performance
of Odom’s useful catalyst 2 by addition of sterically hindered
phenols as ligands. In general, free hydroxy groups are not
tolerated by titanium complexes and catalyst activity breaks
down. Nevertheless, sterically hindered phenols have been
used in a few titanium-catalyzed reactions as controlling
ligands.15 However, to the best of our knowledge, apart from
one example, phenols have not been applied as ligands in
intermolecular hydroamination reactions.16
Table 1. Hydroamination of 1-Octynea
catalyst
(mol %)
temp
(°C)
convb
(%)
yield (%)c
entry
R2
Ph
(5a :5b)
1
2
3
4
5
6
7
2 (5)
2 (5)/3 (10)
1 (5)
2 (10)
2 (10)/3 (20)
1 (10)
1 (5)
100
100
100
100
100
75
100
100
100
74
100
90
84
97
100
100
100
100
89 (60:40)
98 (93:7)
99 (93:7)
0
98 (87:13)
90 (63:37)d
84 (60:40)
90 (69:31)
98 (72:28)
99 (75:25)
99 (81:19)
96 (>99:1)
PhCH2
85
8
9
10
11
12
1 (10)
1 (5)
1 (10)
1 (5)
85
100
100
120
140
1 (5)
a Reaction conditions: 1-octyne (1.5 mmol), amine (1.8 mmol), time
(24 h), toluene (2.0 mL). b Conversion is based on 1-octyne. c Yield is
determined by GC analysis with dodecane or hexadecane as internal
d
standard. Time (48 h).
1). Simply adding 10 mol % of 3 improved the yield and
selectivity in a remarkable manner. Similarly, precatalyst 1
gave an excellent yield (99%) and high regioselectivity of
the Markovnikov imine (93:7) (Table 1, entry 3). Using
benzylamine in the presence of 10 mol % of 2 did not lead
to any imine product; however, oligomerization of 4 is
observed (Table 1, entry 4). Again, by simply adding 20 mol
% of 3 or by using complex 1 as catalyst, an excellent yield
of the corresponding imines (98-99%) (Table 1, entries 5
and 10) is obtained. The model reaction also proceeds at
lower temperature (75 °C) and with a lower amount of cat-
alyst (Table 1, entries 6-8). Interestingly, the best regiose-
lectivities (Markovnikov/anti-Markovnikov ) >99:1) are
achieved at 140 °C.
Here we report for the first time that bis(2,6-di-tert-butyl-
4-methylphenoxo)-bisdimethyl-amide titanium 1 is a highly
chemo- and regioselective hydroamination catalyst for ter-
minal and internal alkynes with primary and secondary ali-
phatic amines, benzylamines, and anilines.
In first experiments, the addition of aniline and benzyl-
amine to 1-octyne 4 was studied as a model reaction (Scheme
1). Initially the behaviors of complex 1, Ti(NMe2)4 2, and 2
Next, we were interested in the behavior of complex 1 in
the reaction of 1-octyne with other aromatic and aliphatic
amines. Despite the possibility of using an in situ-catalyst
(2/3) we decided to apply 1 as a catalyst due to the easier
handling and increased stability compared to 2. 1 is easily
synthesized from commercially available 2,6-di-tert-butyl-
4-methylphenol 3 and 2 in one step in good yield (72%).17
Advantageously, the bisaryloxotitanium complex 1 can be
handled without precautions for short time in air. Under ar-
gon at room temperature it is even stable for several months.
Scheme 1
in the presence of 2,6-di-tert-butyl-4-methylphenol 3 were
compared (Table 1).
The hydroamination of 1-octyne with aniline in the pres-
ence of 5 mol % of commercially available 2 gave the corre-
sponding imine in good yield (89%) but low regioselectivity
(Markovnikov/anti-Markovnikov ) 60:40) (Table 1, entry
(14) Ong, T. G.; Yap, G. P. A.; Richeson, D. S. Organometallics 2002,
21, 2839.
(15) Selected recent examples: (a) Himes, R. A.; Fanwick, P. E.;
Rothwell, I. P. Chem. Commun. 2003, 18. (b) Gonzalez-Maupoey, M.;
Cuenca, T.; Frutos, L. M.; Castano, O.; Herdtweck, E. Organometallics
2003, 22, 2694. (c) Sturla, S. J.; Buchwald, S. L. Organometallics 2002,
21, 739. (d) Michalczyk, L.; de Gala, S.; Bruno, J. W. Organometallics
2001, 20, 5547. (e) Sato, F.; Urabe, H.; Okamoto, S. Chem. ReV. 2000,
100, 2835. (f) Okamoto, S.; Livinghouse, T. J. Am. Chem. Soc. 2000, 122,
1223. (g) Thorn, M. G.; Etheridge, Z. C.; Fanwick, P. E.; Rothwell, I. P. J.
Organomet. Chem. 1999, 591, 148. (h) Waratuke, S. A.; Thorn, M. G.;
Fanwick, P. E.; Rothwell, A. P.; Rothwell, I. P. J. Am. Chem. Soc. 1999,
121, 9111.
(16) Rothwell and co-worker reported the synthesis of an aryloxo(imido)-
titanium complex and the hydroamination of the internal alkyne 3-hexyne:
Hill, J. E.; Profilet, R. D.; Fanwick, P. E.; Rothwell, I. P. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 664.
(17) Duff, A. W.; Kamarudin, R. A.; Lappert, M. F.; Norton, R. J. J.
Chem. Soc., Dalton Trans. 1986, 489.
(9) (a) Straub, B. F.; Bergman, R. G. Angew. Chem., Int. Ed. 2001, 40,
4632. See also ref 5 (e, i, j).
(10) (a) Pohlki, F.; Doye, S. Angew. Chem., Int. Ed. 2001, 40, 2305.
See also ref 5 (b-d, f-h).
(11) (a) Tillack, A.; Garcia Castro, I.; Hartung, C. G.; Beller, M. Angew.
Chem., Int. Ed. 2002, 41, 2541.
(12) Shi, Y.; Ciszewski, J. T.; Odom, A. L. Organometallics 2001, 20,
3967.
(13) (a) Shi, Y.; Hall, C.; Ciszewski, J. T.; Cao, C.; Odom, A. L. Chem.
Commun. 2003, 584. (b) Cao, C.; Shi, Y. H.; Odom, A. L. J. Am. Chem.
Soc. 2003, 125, 2880. (c) Cao, C.; Shi, Y.; Odom, A. L. Org. Lett. 2002,
4, 2853. (d) Cao, C.; Ciszewski, T.; Odom, A. L. Organometallics 2001,
20, 5011.
4768
Org. Lett., Vol. 5, No. 25, 2003