compounds required elevated temperatures. Consequently, only
the titanium complex of 3 was prepared. It was noted that the
amido ligand (either dimethyl or diethyl amido) did not impact
the observed progress of the reaction. This is consistent with the
bis(amidate)group 4-bis(amido) complexes being precatalysts
and the catalytically active intermediate being a Ti or Zr imido
species derived from the primary amine of the substrate, as has
been reported for group 4 hydroamination catalysis.12 Most
importantly, we observed that the incorporation of electron
withdrawing substituents on the carbonyl moiety of the amidate
ligand dramatically enhances catalytic activity. Thus, while the
alkyl substituted titanium amidate complex requires 14 h to go
to completion, the reaction time is reduced to less than 15
minutes with the pentafluorophenyl derivative (entry 5).
leads to the regioisomeric Markovnikov and anti-Markovnikov
products. All reactions were carried out on NMR tube scale with
10 mol% catalyst loading for 24 hours at 65 °C. These results
show that intermolecular hydroamination is efficient for
terminal alkyl alkynes for both alkyl (entry 1) and aryl amines
(entry 4). Interestingly, the regioselectivity of hydroamination
changes from a preference for anti-Markovnikov in the case of
alkyl amines to Markovnikov in the case of aryl amines. Thus,
this catalyst system addresses the synthetically challenging
regioselective intermolecular hydroamination of terminal al-
kynes with alkyl amines.3b In contrast, Cp2TiMe2 is ineffective
for this reaction12 and Ti(NMe2)4 is limited to hydroamination
using aryl amines.1g These preliminary results demonstrate that
the Ti complex of 3 is an effective precatalyst for the
intermolecular, anti-Markovnikov hydroamination of terminal
alkyl alkynes with alkyl amines.
In summary, we have developed a reliable protocol for the
facile preparation of a series of bis(amidate)group 4-bis(amido)
complexes. The easily modified amidate ligands allow for
significant flexibility in the ligand substituents. Most im-
portantly, they have been shown to be highly tunable pre-
catalysts for both the intra- and intermolecular hydroamination
of alkynes. Mechanistic investigations and further elaboration
of the amidate ligand to vary reactivity and selectivity in both
intra- and intermolecular hydroamination of C–C multiple
bonds is on-going, and results will be reported in due course.
The authors thank NSERC and UBC for financial support.
(2)
Further comparison of these results with those reported in the
literature for Cp2TiMe2 (entry 6) and the commercially
available Ti(NMe2)4 (entry 7) shows that our most active
catalyst (entry 5) is favourable. In order to directly compare our
catalyst with Ti(NMe2)4 we evaluated both precatalysts using
identical reaction conditions on the more challenging substrate
6 to form the six-membered ring product 7 [eqn. (3)]. This
experiment demonstrates the high activity of our newly
developed catalyst, as this reaction had gone to completion
within 3 hours at 40 °C while the Ti(NMe2)4 catalyst had only
gone to 30% completion.
Notes and references
‡ Crystal data: C30H38N4O2F10Ti, M = 724.54, monoclinic, a = 10.510(1),
b = 20.104(2), c = 15.820(1) Å, V = 3342.1(5) Å3, determined to be a
four-component twin with the unit cell parameters given, T = 173 K, space
group P21/a (#14), Z = 4, m(MoKa) = 0.35 cm21, 8086 reflections
measured, 4988 unique (Rint = 0.072) which were used in all calculations.
The final R(F2) was 0.140 (all data). CCDC 208892. See http://
other electronic format.
(3)
To demonstrate the scope of reactivity of this precatalyst, the
Ti complex of deprotonated 3 was used for the more challenging
intermolecular hydroamination of alkynes,12 as summarized in
Table 2. Intermolecular hydroamination of terminal alkynes
1 (a) T. E. Muller and M. Beller, Chem. Rev., 1998, 98, 675; (b) T.
Shimada and Y. Yamamoto, J. Am. Chem. Soc., 2002, 124, 12670; (c)
U. Nettekoven and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 1166;
(d) S. Burling, L. D. Field and B. A. Messerle, Organometallics, 2000,
19, 87; (e) M. Tokunaga, M. Eckert and Y. Wakatsuki, Angew. Chem.,
Int. Ed., 1999, 38, 3222; (f) Y. Shi, J. T. Ciszewski and A. L. Odom,
Organometallics, 2001, 20, 3967; (g) L. Fadini and A. Togni, Chem.
Commun., 2003, 30.
2 (a) S. Hong and T. J. Marks, J. Am. Chem. Soc., 2002, 124, 7886; (b) G.
A. Molander, E. D. Dowdy and S. K. Pack, J. Org. Chem., 2001, 66,
4344; (c) A. Haskel, T. Straub and M. S. Eisen, Organometallics, 1996,
15, 3773; (d) Y. K. Kim and T. Livinghouse, Angew. Chem., Int. Ed.,
2002, 41, 3645.
Table 1 Intramolecular hydroamination of alkyne 4 (5 mol% catalyst)
Entry
Proligand
Metal
T/°C
t/h
Yield (%)a
1
2
3
4
5
6
7
1
2
1
2
Zr
Zr
Ti
Ti
Ti
Ti
Ti
60
60
25
25
25
24
7
14
3.5
0.25
4
95
98
99
98
97
90b
Quant.6
3
CpH
HNMe2
110
25
0.5
a NMR conversion versus 1,3,5-trimethoxybenzene. b Reported yield for
the isolated amine product after reduction of imine 5.3c
3 (a) J. S. Johnson and R. G. Bergman, J. Am. Chem. Soc., 2001, 123,
2923; (b) A. Tillack, I. G. Castro, C. G. Hartung and M. Beller, Angew.
Chem., Int. Ed., 2002, 41, 2541; (c) T. Bytschkov and S. Doye,
Tetrahedron Lett., 2002, 43, 3715; (d) E. Haak, I. Bytschkov and S.
Doye, Angew. Chem., Int. Ed., 1999, 38, 3389.
Table 2 Intermolecular hydroamination of 1-hexyne with various amines
4 C. Cao, J. T. Ciszewski and A. T. Odom, Organometallics, 2001, 20,
5011.
5 T.-G. Ong, G. P. A. Yap and D. S. Richeson, Organometallics, 2002, 21,
2839.
6 L. Ackermann and R. G. Bergman, Org. Lett., 2002, 4, 1475.
7 (a) J. Duncan, T. P. Z. Malinski, Z. S. Hu, K. M. Kadis and J. L. Bear,
J. Am. Chem. Soc., 1982, 104, 5507; (b) A. Dolmella, F. P. Intini, C.
Pacifico, G. Padovano and G. Natile, Polyhedron, 2002, 21, 275.
8 G. R. Giesbrecht, A. Shafir and J. Arnold, Inorg. Chem., 2001, 40,
6069.
9 B.-H. Huang, T.-L. Yu, Y.-L. Huang, B.-T. Ko and C.-C. Lin, Inorg.
Chem., 2002, 41, 2987.
10 (a) N. De Kimpe, R. Verhe, L. De Buyck, J. Chys and N. Schamp, Org.
Prep. Proc. Int., 1978, 10, 149; (b) A. D. Nikolic, N. Perisic-Janjic, N.
L. Kobilarov and S. D. Petrovic, J. Mol. Struct., 1984, 114, 161.
11 See supporting information.
Entry
Amine
Yield (%) (anti-M : M)a
1
2
3
4
tBuNH2
iPrNH2
Ph2CHNH2
2,6-Dimethylaniline
93 (99 : 1)
78 (99 : 1)
50 (12 : 1)b
79 (1 : 99)
a Yields determined by NMR using 1,3,5-trimethoxybenzene as internal
standard, reaction conditions not optimized. b Product ratio confirmed by
GCMS.
12 F. Pohlki and S. Doye, Chem. Soc. Rev., 2003, 104.
CHEM. COMMUN., 2003, 2462–2463
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