Catalytic intermolecular hydroamination of methylenecyclopropanes

Article abstract of DOI:10.1021/om050518h

The octahedral titanium catalyst Ti(Ph₂-PN_py) ₂(NEt₂)₂ (1) was found to be an efficient catalyst for the hydroamination of methylenecyclopropane with either aromatic or aliphatic amines. For a symmetrical methylenecyclopropane, only one product is obtained in high yield. The reaction of complex 1 with ethylamine and aniline produces the dimeric titanium complexes Ti₂(Ph₂PN _py)₂(μ-NEt)₂ and Ti₂(Ph ₂PN_py)₂(μ-NPh)₂, respectively.

Full text of DOI:10.1021/om050518h

© Copyright 2005
Volume 24, Number 23, November 7, 2005
American Chemical Society
Communications
Catalytic Intermolecular Hydroamination of
Methylenecyclopropanes
Elena Smolensky, Moshe Kapon, and Moris S. Eisen*
Department of Chemistry and Institute of Catalysis Science and Technology,
TechnionsIsrael Institute of Technology, Haifa 32000, Israel
Received June 23, 2005
Summary: The octahedral titanium catalyst Ti(Ph2-
the hydroamination reaction, group IV metal com-
plexes2,3 have provoked widespread interest, due to their
general reactivity and ubiquitous availability compared
to toxic metals (Hg, Tl,4 U, and Th5), or more expensive
lanthanides6 and late-transition-metal complexes (Ru,
PNpy)2(NEt2)2 (1) was found to be an efficient catalyst
for the hydroamination of methylenecyclopropane with
either aromatic or aliphatic amines. For a symmetrical
methylenecyclopropane, only one product is obtained in
high yield. The reaction of complex 1 with ethylamine
and aniline produces the dimeric titanium complexes
Ti2(Ph2PNpy)2(µ-NEt)2 and Ti2(Ph2PNpy)2(µ-NPh)2, re-
spectively.
(2) For recent examples see: (a) Heutling, A.; Pohlki, F.; Bytschkov,
I.; Doye, S. Angew. Chem., Int. Ed. 2005, 44, 2951. (b) Petersen, J. R.;
Hoover, J. M.; Kassel, W. S.; Rheingold, A. L.; Johnson, A. R. Inorg.
Chim. Acta 2005, 358, 687. (c) Bexrud, J. A.; Beard, J. D.; Leitch, D.
C.; Schafer, L. L. Org. Lett. 2005, 7, 1959. (d) Rosenthal, U.; Burlakov,
V. V.; Arndt, P.; Baumann, W.; Spannenberg, A.; Shur, V. B. Eur. J.
Inorg. Chem. 2004, 4739. (e) Gribkov D. V.; Hultzsch, K. C. Angew.
Chem., Int. Ed. 2004, 43, 5542. (f) Tillack, A.; Khedkar, V.; Beller, M.
Tetrahedron Lett. 2004, 45, 8875. (g) Cao, C.; Li, Y.; Shi, Y.; Odom, A.
L. Chem. Commun. 2004, 2002. (h) Ramanathan, B.; Keith, A. J.;
Armstrong, D.; Odom, A. L. Org. Lett. 2004, 6, 2957. (i) Heutling, A.;
Pohlki, F.; Doye, S. Chem. Eur. J. 2004, 10, 3059. (j) Tillack, A.; Jiao,
H.; Castro, I. G.; Hartung, C. G.; Beller M. Chem. Eur. J. 2004, 10,
2409. (k) Pohlki, F.; Bytschkov, I.; Siebeneicher, H.; Heutling, A.;
Ko¨nig, W. A.; Doye S. Eur. J. Org. Chem. 2004, 1967. (l) Lorber, C.;
Choukroun, R.; Vendier, L. Organometallics 2004, 23, 1845. (m)
Knight, P. D.; Munslow, I.; O’Shaughnessy, P. N.; Scott, P. Chem.
Commun. 2004, 7, 894. (n) Ackermann, L.; Kaspar, L. T.; Gschrei, C.
Org. Lett. 2004, 6, 2515.
(3) For reviews see: (a) Odom, A. L. J. Chem. Soc., Dalton Trans.
2005, 2, 225. (b) Doye, S. Synlett 2004, 10, 1653. (c) Pohlki, F.; Doye,
S. Chem. Soc. Rev. 2003, 32, 104. (d) Bytschkv, I.; Doye, S. Eur. J.
Chem. 2003, 935. (e) Nobis, M.; Driessen-Ho¨lscher, B. Angew. Chem.,
Int. Ed. 2001, 40, 3983. (f) Mu¨ller, T. E.; Beller, M. Chem. Rev. 1998,
98, 675.
(4) (a) Barluenga, J.; Aznar, A.; Liz, R.; Rodes, R. J. Chem. Soc.,
Perkin Trans. 1 1980, 2732. (b) Barluenga, J.; Aznar, A. Synthesis
1977, 195. (c) Barluenga, J. Aznar, A. Synthesis 1975, 704.
(5) (a) Stubbert, B. D.; Stern, C. L.; Marks, T. J. Organometallics
2003, 22, 4836. (b) Wang, J.; Dash, A. K.; Kapon, M.; Berthet, J.-C.;
Ephritikhine, M.; Eisen, M. S. Chem. Eur. J. 2002, 8, 5384. (c) Straub,
T.; Haskel, A.; Neyroud, T. G.; Kapon, M.; Botoshansky, M.; Eisen, M.
S. Organometallics 2001, 20, 5017.
Addition of a nitrogen-hydrogen bond over an un-
saturated carbon-carbon bond is a highly desirable
transformation in organic chemistry, offering an ef-
ficient synthetic route to amines, enamines, and imines.
Amines especially play an outstanding role as products
and intermediates in the chemical industry.1 However,
such a transformation of unsaturated hydrocarbons does
not occur spontaneously in the presence of amines.
Catalytic hydroamination offers a very convenient solu-
tion for lowering the activation barrier for those reac-
tions. An efficient hydroamination process can offer
significant economical and environmental benefits com-
pared to classic methods for the synthesis of the same
target compounds. Over the years, a great deal of effort
went into finding the most efficient catalysts that will
promote this process. Among the different catalysts for
* To whom correspondence should be addressed. E-mail: chmoris@
tx.technion.ac.il.
(1) Heilen, G.; Mercker, H. J.; Frank, D.; Reck, R. A.; Ja¨ckh, R.
Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed.; VCH: Wein-
heim, Germany, 1985; Vol. A2, p 1.
10.1021/om050518h CCC: $30.25 © 2005 American Chemical Society
Publication on Web 10/12/2005

5496 Organometallics, Vol. 24, No. 23, 2005
Communications
Pd, Rh, Pt, and Ag).7 However, to date, the field of
intermolecular hydroamination reactions catalyzed by
group IV metal complexes remained limited to alkyne,
allene, and norbornene substrates.2 Therefore, one of
the main challenges in this field is with regard to the
expansion of the reaction scope.
Here we introduce a new titanium catalyst that
promotes the intermolecular hydroamination of a new
class of substrates, the methylenecyclopropanes (MCPs),
with aliphatic and aromatic amines. MCPs have been
tested in hydroamination reactions promoted by late
transition metals8 and lanthanides,9 producing allyl-
amines and imines correspondingly.
Table 1. MCPs Hydroamination Results with 1 as
a Precatalyst
isolated
%
time
A
B
conversn yield A Ntc
entry
R
R′
cat.a (h)
(%) (%)
(%)
(B)b
(h-1
)
1
Ph Et
Ph Et
Ph Ph
Ph Ph
Ph Bu
Ph iPr
5
5
5
5
5
5
5
5
2
2
2
2
2
4
40
4
17
20
96
120
100 0
100 0
87 13
87 13
100 0
84 16
100 0
38.5
1.93
0.50
3.65
2
100
95
3
73
100
94
80
24
4
83 (10) 1.15
90
63 (8)
5
6.25
0.41
0.04
0.01
1.08
1.05
1.29
0.83
1.12
6
7
Ph (o-iPr)2Ph
Ph (o-iPr)2Ph
8
2.5d 100 0
36
45
36
36
36
100
78
97
9
H
H
H
H
H
Ph
Ph
Et
100 e
100 e
100 e
100 e
100 e
10
11
12
13
95
90
90
56
76
93
The octahedral titanium catalyst Ti(Ph2PNpy)2(NEt2)2
(1) was synthesized in a one-step reaction between 2
equiv of the neutral ligand 2-((diphenylphosphanyl)-
amino)pyridine and 1 equiv of the homoleptic tetrakis-
(diethylamino)titanium (eq 1). The structure of 1 and
Bu
60
iPr
81
a All of the hydroamination reactions were performed in toluene-
d8 as a solvent at 110 °C. b Percent yield of the isolated products.
c Turnover frequencies (nproduct/(ncat h)) measured in toluene-d8.
d Reaction time in months. e R ) H; therefore, A ) B.
that 1,2-insertion of the MCP double bond into the TidN
bond results in the formation of the azatitanacyclobu-
tane complex 6.11,12 Complex 6 may undergo two dif-
ferent ring-opening transformations to form more stable
five-membered-ring complexes (7A and 7B). The cleav-
age of the C2-C3 bond (pathway a) will result in the
formation of 7A, whereas the cleavage of the C2-C4
bond (pathway b) will induce the formation of complex
7B. Complex 7A is more stable than 7B, since the metal
in the former complex is bonded to a benzylic carbon,
whereas in the latter complex the metal is bonded to a
primary carbon. Therefore, pathway a is expected to be
the preferential route, as observed from the product
distribution in Table 1. Protonolysis of complexes 7A
and 7B will form the corresponding bis(amido) com-
plexes (8A and 8B). As in the hydroamination of
alkynes, we suggest that the concomitant R-elimination
of the enamines will regenerate the imido complex 3.
Products A and B will most likely be obtained by the
tautomerization of 9A and 9B, correspondingly.
the dynamic behavior of the chelating ligands respon-
sible for the formation of elastomeric polypropylene
when complex 1 was activated with MAO (methylalu-
moxane) have been recently determined.10
The scope and chemo- and regioselectivity of the
intermolecular hydroamination of unsymmetrical and
symmetrical MCPs promoted by complex 1 are sum-
marized in eq 2 and Table 1. On the basis of the studied
In the intermolecular hydroamination of unsym-
metrical MCPs with aliphatic amines, a slightly de-
(7) For recent examples see: (a) Shimada, T.; Bajracharya, G. B.;
Yamamoto, Y. Eur. J. Org. Chem. 2005, 1, 59. (b) Bender, C. F.; Ross,
A.; Widenhoefer, R. A. J. Am. Chem. Soc. 2005, 127, 1070. (c)
Bajracharya, G. B.; Huo, Z.; Yamamoto, Y. J. Org. Chem. 2005, 70,
4883. (d) Brunet, J.-J.; Chu, N. C.; Diallo, O. Organometallics 2005,
24, 3104. (e) Yi, C. S.; Yun, S. Y. Org. Lett. 2005, 7, 2181. (f) Takaya,
J.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5756. (g) Qian, H.;
Widenhoefer, R. A. Org. Lett. 2005, 7, 2635. (h) Zotto, A. D.; Baratta,
W.; Felluga, Al.; Rigo, P. Inorg. Chim. Acta 2005, 358, 2749. (i)
Robinson, R. S.; Dovey, M. C.; Gravestock, D. Eur. J. Org. Chem. 2005,
3, 505. (j) Krogstad, D. A.; Owens, S. B.; Halfen, J. A.; Young, V. G.
Inorg. Chem. Commun. 2005, 8, 65.
(8) (a) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J. Org. Chem. 1998,
63, 6458. (b) Nakamura, I.; Itagaki, H.; Yamamoto, Y. Chem. Hetero-
cycl. Compd. 2001, 12, 1532.
mechanisms for the hydroamination of alkynes pro-
moted by titanium complexes,3a,b a plausible mechanism
for the intermolecular hydroamination of MCP’s with
amines is presented in Scheme 1. In the first step of
the mechanism, complex 1 reacts with primary amines,
yielding complex 2, which eliminates an amine to
produce the active imido complex 3. This complex exists
in equilibrium with its dimer form (4 and 5). We suggest
(9) Ryu, J.-S.; Li, G. Y.; Marks, T. J. J. Am. Chem. Soc. 2003, 125,
12584.
(10) (a) Smolensky, E.; Kapon, M.; Woollins, J. D.; Eisen, M. S.
Organometallics 2005, 24, 3255. (b) Xavier, K. O.; Smolensky, E.;
Kapon, M.; Aucott, S. M.; Woollins, J. D.; Eisen, M. S. Eur. J. Inorg.
Chem. 2004, 4795. (c) Volkis, V.; Smolensky, E.; Lisovskii, A. Eisen,
M. J. Polym. Sci., A: Polym. Chem. 2005, 43, 4505.
(11) Ward, B. D.; Maisse-Franc¸ois, A.; Mountford, P.; Gade, L. H.
Chem. Commun. 2004, 704.
(12) As followed by NMR, the reaction of 1 equiv of complex 1 with
2 equiv of aniline and 1 equiv of PhMCP shows after heating (110 °C)
for a short amount of time the disappearance of the signal (5.50 ppm,
doublet of quartets) associated with the exocyclic methylene group of
the PhMCP, and the appearance of new signals (5.446 and 5.455 ppm,
two doublets with 2JHH ) 4.5 Hz) associated with the -CH2- group of
the azatitanacyclobutane 6.
(6) For recent examples see: (a) Panda, T. K.; Zulys, A.; Gamer, M.
T.; Roesky, P. W. Organometallics 2005, 24, 2197. (b) Hong, S.; Marks,
T. J. Acc. Chem. Res. 2004, 37, 673. (c) Ryu, J.-S.; Marks, T. J.;
McDonald, F. E. J. Org. Chem. 2004, 69, 1038.

Communications
Organometallics, Vol. 24, No. 23, 2005 5497
Scheme 1. Proposed Catalytic Cycle for the Intermolecular Hydroamination of MCPs
creased trend in turnover frequencies (Nt) is observed
as compared to the aromatic amine (entries 2, 4, and 6
in addition to entry 5). This result may reflect the
increased nucleophilicity of the aliphatic amines, pro-
moting the formation of the bis(amido) species (2) out
of the catalytic cycle (Scheme 1). In comparison to
organolanthanide complexes, the opposite effect was
observed for similar substrates.9 However, the hydro-
amination of an ortho-substituted amine (entries 7 and
8) is extremely slow due to the steric hindrance between
the ortho substituent and the diphenylphosphino motif
of the ligands, precluding the formation of the active
imido complex 3. With regard to the regioselectivity, one
or two regioisomers are observed (A and B, eq 2). It is
most likely that both isomers are products via a 1,2-
addition of the TidN into the MCP exo methylene. For
the metallacyclic complex 6 two regioisomers can be
expected (6a and 6b).11 Complex 6a will be the preferred
isomer, due to the lack of steric hindrance between the
amine substituent (R′) and the diphenylphosphine
Figure 1. ORTEP plot of the structure of complex Ti2(Ph2PNpy)4(µ-NPh)2 (5). Thermal ellipsoids are given at the 50%
probability level.

5498 Organometallics, Vol. 24, No. 23, 2005
Communications
tion of complex 1 with an excess of ethylamine or aniline
produces rapidly the dimeric titanium complexes Ti2(Ph2-
PNpy)2(µ-NEt)2 (4)10a and Ti2(Ph2PNpy)2(µ-NPh)2 (5),
respectively. The ORTEP plot of complex 5 is shown in
Figure 1.
In complex 5 both titanium atoms exhibit an octahe-
dral environment, with N1 and N4 disposed in apical
positions. The four-membered ring Ti-N(3)-Ti-N(3)*
is totally planar (sum of internal angles 360.0°), al-
though both bridging nitrogens are placed asym-
metrically (Ti(1)-N(3) ) 2.0117(14) Å; Ti(1)-N(3)# )
1.8794(14) Å). Complex 4 was found to be isostructural
with complex 5.10a
In conclusion, although MCPs are highly strained
compounds, they are remarkably stable. These proper-
ties make them suitable as substrates for the hydroami-
nation reaction. We have shown here a new catalyst that
can promote MCPs hydroamination reaction in high
isolated yields and good stereoselectivity.
moiety. In addition, the latter group (-PPh2) will always
be expected to be transoid to the phenyl group of the
PhMCP.12
In all cases the linear imine A is observed as the
major product. For the less bulky amine, the reaction
is also chemoselective, producing 100% of the linear
imine A. The selectivity results are comparable to those
obtained for MCP hydroamination promoted by organ-
lanthanides.9
Acknowledgment. This research was supported by
the German Israel Foundation under Contract No.
I-621-27.5/1999.
In the case of the symmetrical MCP, only one product
is expected (R ) H in eq 2). In general, the PhMCP
reacts faster than the MCP (except in the reaction with
iPrNH2); however, the hydroaminations of MCP with
different types of amines (entries, 10, 11, and 13)
produce similar Nt values.
To shed some light on the fate of the precatalyst in
the hydroamination process, the reactivity of complex
1 with various primary amines was studied. The reac-
Supporting Information Available: Text, tables, and
figures giving details of the syntheses and NMR analyses of
compounds A, B, and 5, a representative diagram for the
formation of imine as a function of time, and the crystal-
lographic data for the crystal structure of complex 5; crystal-
lographic data are also available as a CIF file. This material
is available free of charge via the Internet at http://pubs.acs.org.
OM050518H