Titanium-Catalyzed Hydroaminoalkylation of Ethylene

Article abstract of DOI:10.1002/chem.201904502

The first examples of titanium-catalyzed hydroaminoalkylation reactions of ethylene with secondary amines are presented. The reactions can be achieved with various titanium catalysts and they do not require the use of high pressure equipment. In addition, the first solid-state structure of a titanapyrrolidine that is formed by insertion of an alkene into the Ti?C bond of a titanaaziridine is reported.

Full text of DOI:10.1002/chem.201904502

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Accepted Article
Title: Titanium-Catalyzed Hydroaminoalkylation of Ethylene
Authors: Michael Rosien, Iris Töben, Marc Schmidtmann, Rüdiger
Beckhaus, and Sven Doye
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Titanium-Catalyzed Hydroaminoalkylation of Ethylene
Michael Rosien,[a] Iris Töben,[a] Marc Schmidtmann,[a] Rüdiger Beckhaus,*[a] and Sven Doye*[a]
or pesticides.
Abstract:
The
first
examples
of
titanium-catalyzed
Interestingly, the mechanism of the titanium-catalyzed
hydroaminoalkylation reaction (Scheme 2),[4a,8] which includes
the insertion of the alkene substrate into the TiC bond of a
catalytically active titanaaziridine as the CC bond-forming key-
step, suggests that ethylene should react smoothly because in
comparison to larger 1-alkenes or styrenes, steric hindrance of
the insertion step is minimized in the case of ethylene. Based on
this assumption, we recently decided to investigate the
performance of a number of titanium catalysts developed in our
group in hydroaminoalkylation reactions of ethylene.
hydroaminoalkylation reactions of ethylene with secondary amines
are presented. The reactions can be achieved with various titanium
catalysts and they do not require the use of high pressure equipment.
In addition, the first solid state structure of a titanapyrrolidine that is
formed by insertion of an alkene into the TiC bond of
a
titanaaziridine is reported.
Amines are among the most important classes of organic
compounds and as a consequence, the development of efficient
and sustainable methods for their synthesis is of exceptional
interest in academic and industrial chemical research. While
traditional synthetic pathways for the synthesis of amines usually
rely on nucleophilic substitution, reductive amination, or cross-
coupling
processes,
the
transition
metal-catalyzed
hydroaminoalkylation of alkenes[1] (Scheme 1) allows the direct
addition of α-C(sp3)H bonds of amines across C-C double
bonds of alkenes. Because corresponding reactions take place
without the formation of any side products and inexpensive and
widely available starting materials can be used it is not
surprising that the development of hydroaminoalkylation
processes has raised significant attention in recent years.[2-5]
Although corresponding reactions can be achieved in the
presence of selected late transition metal[2] and group 3 metal
catalysts,[3] group 4[4] and group 5[5] metal catalysts offer the
broadest scope. Interestingly, in the latter cases, only liquid
alkenes such as 1-hexene, 1-octene, or styrene have
extensively been used as substrates while the simplest alkene,
ethylene, has largely been ignored. Only the first report on early
transition metal-catalyzed hydroaminoalkylation reactions which
was published in 1980 by Clerici and Maspero[6] already
describes two examples of [Nb(NMe2)5]- or [Nb(NEt2)5]-catalyzed
hydroaminoalkylation reactions of ethylene with dimethyl- or
diethylamine. Unfortunately, these reactions were performed at
elevated pressure (20 atm) and the hydroaminoalkylation
products were only obtained in low yields between 13 and 28 %.
In this context, it should be emphasized that in industry,
approximately 150 million tons of ethylene are produced per
year[7] and as a consequence, ethylene is not only the most
widely used alkene in industry, it must also be regarded as one
of the most important organic compounds. For that reason,
efficient catalytic procedures for the hydroaminoalkylation of
ethylene could offer immense economic benefits in the chemical
industry. The corresponding products, n-propylamines, could be
of interest as intermediates for the synthesis of pharmaceuticals
Scheme 1. Transition metal-catalyzed hydroaminoalkylation of alkenes.
Scheme
2.
Simplified
mechanism
of
the
titanium-catalyzed
hydroaminoalkylation of ethylene with secondary amines.
Initial experiments to achieve the hydroaminoalkylation of
ethylene using very simple experimental set-up were
a
performed with a selection of our recently developed titanium
catalysts shown in Figure 1 or mentioned in Table 1. For that
purpose, in each case, a Schlenk tube (V = 100 ± 5 mL)
containing a solution of N-methylaniline (1a, 2 mmol) and the
titanium catalyst (10 mol%) in toluene (1 mL) was first filled with
ethylene (1.4 atm,  5.7 mmol) and sealed. Then the obtained
mixture was stirred at temperatures between 105 °C and 160 °C
for 3-48 h and finally, the crude product mixture was purified by
[a]
M. Rosien, I. Töben, Dr. M. Schmidtmann, Prof. Dr. R. Beckhaus,
Prof. Dr. S. Doye
Institut für Chemie, Universität Oldenburg
Carl-von-Ossietzky-Straße 9-11, 26129 Oldenburg (Germany)
E-mail: ruediger.beckhaus@uni-oldenburg.de, doye@uni-
oldenburg.de
Supporting information for this article is available on the WWW
under http://_____.
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column chromatography. Consistent with the 1980’s
12
I
105
105
105
160
160
24
24
24
24
24
19
–
experiments,[6]
it
was
first
found
that
13
II
21
10
68
20
10
5
tetrakis(dimethylamino)titanium does not show any catalytic
activity up to temperatures of 140 °C (Table 1, entry 1). On the
other hand, [Ind2TiMe2] (Ind = η5-indenyl) does catalyze the
reaction at a temperature of 105 °C and delivers the expected
hydroaminoalkylation product N-propylaniline (2a) in 69 % yield
after a reaction time of 24 h (Table 1, entry 3). Surprisingly, from
this experiment, N-(pentan-3-yl)aniline (3a), which is formed by
alkylation of the initially formed product 2a with ethylene, could
also be isolated in 23 % yield. In this context, it should be
mentioned that N-alkylanilines possessing an alkyl substituent
larger than a methyl group usually react slowly in titanium-
catalyzed hydroaminoalkylation reactions[4] (vide infra) and
especially in the presence of the catalyst [Ind2TiMe2], they were
reported to lack any reactivity.[4b] Interestingly, formation of the
dialkylated product 3a could not be suppressed by a shorter
reaction time of 6 h and even in this case, 3a was obtained in
17 % yield (Table 1, entry 2).
14
III
15[d]
16
[Ta(NMe2)5]
[Nb(NMe2)5]
7
3
[a] Reaction conditions: 1) N-methylaniline (214 mg, 2.00 mmol), ethylene
(1.4 atm), catalyst (0.20 mmol, 10 mol%), toluene (1 mL), T, t, isolated
yields. [b] The reaction could also be achieved with reduced catalyst
loadings. 5 mol% III gave 2a in 77 % yield and 3a in 9 % yield; 2.5 mol%
III gave 2a in 68 % yield and 3a in 6 % yield; 1.25 mol% III gave 2a in
33 % yield and 3a in trace amounts. [c] The reaction could also be
achieved with reduced catalyst loadings. 5 mol% III gave 2a in 79 % yield
and 3a in 9 % yield; 2.5 mol% III gave 2a in 68 % yield and 3a in 4 %
yield; 1.25 mol% III gave 2a in 30 % yield and 3a in trace amounts. [d]
The reaction could also be achieved with a reduced catalyst loading. 5
mol% [Ta(NMe2)5] gave 2a in 41 % and 3a in trace amounts.
Subsequent experiments performed with the second generation
titanium catalysts I,[4d] II,[4f] and III[4e] (Figure 1) at temperatures
between 140 °C and 160 °C then revealed that in comparison to
[Ind2TiMe2], these catalysts favor the formation of the
monoalkylated product 2a with better selectivities (Table 1,
entries 4-11). In this context, the finding that the dialkylated
product 3a was not formed at all in the presence of the sterically
crowded trityl-substituted mono(aminopyridinato) catalyst II
deserves particular attention (Table 1, entry 5). In addition, it
Figure 1. Selected titanium catalysts for hydroaminoalkylation reactions.
was
also
found
that
among
the
catalysts
I-III,
Table 1. Catalyst screening for the hydroaminoalkylation of ethylene with N-
methylaniline (1a).[a]
mono(formamidinate) catalyst III is the most active one (Table 1,
compare entry 4 with 6 and entry 5 with 10). As a result,
reactions performed with catalyst III gave access to 2a in
improved isolated yields between 72 % and 78 % (Table 1,
entries 6-11) and even after a relatively short reaction time of 3 h
at 160 °C, it was possible to isolate 2a in 72 % yield (Table 1,
entry 7). Interestingly, the size of the Schlenk tube did not
dramatically affect the isolated yields and the selectivity of the
reaction. For example, a control experiment performed in a
smaller Schlenk tube (V = 75 ± 5 mL mL, 10 mol% III, 160 °C, 24
h) gave 2a and 3a still in 71 % and 17 % yield, respectively. On
the other hand, under ambient pressure of ethylene, the
formation of the dialkylated product 3a was significantly
suppressed and as a result, 3a was only isolated in 3 % yield
from a corresponding control experiment (V = 100 ± 5 mL, 10
mol% III, 160 °C, 24 h). Unfortunately, in this case, the yield of
2a also decreased to 64 %. Additional control experiments,
performed with the catalysts I-III at 105 °C (Table 1, entries 12-
14) revealed that at this temperature, I-III do not show sufficient
catalytic activity. On the other hand, at 160 °C, a reduction of the
catalyst loading is possible and as a consequence, with 5 or 2.5
mol% III, 2a could still be obtained in yields between 68 and
79 % (Table, 1, entries 9 and 10, footnotes [b] and [c]). For a
final direct comparison of our catalysts with the catalyst systems
published by Clerici and Maspero,[6] we also conducted
experiments with 10 or 5 mol% of [Nb(NMe2)5] or [Ta(NMe2)5]
under our reaction conditions. As can be seen from Table 1,
entries 15 and 16 and footnote [d], [Ta(NMe2)5] turned out to be
catalytically more active than [Nb(NMe2)5] while both catalysts
deliver the products 2a and 3a in lower yields than catalyst III.
Entry
1
Catalyst
T [°C]
140
105
105
140
160
140
160
160
160
160
160
t [t]
24
6
Yield 2a [%]
Yield 3a [%]
[Ti(NMe2)4]
–
–
2
[Ind2TiMe2]
66
69
48
67
72
72
75
78
76
78
17
23
4
3
[Ind2TiMe2]
24
24
24
24
3
4
I
5
II
–
6
III
III
III
III
III
III
17
9
7
8
6
17
16
17
19
9[b]
10[c]
11
12
24
48
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To further investigate the scope of the hydroaminoalkylation of
ethylene, we then turned our attention towards reactions of a
number of functionalized N-methylanilines (Table 2). Because it
was expected that some of the amines would react more slowly
than N-methylaniline (1a), these reactions were usually
performed under the conditions of entry 10 of Table 1 (10 mol%
III, 160 °C, 24 h). As can be seen from Table 2, under these
conditions, ethylene reacted smoothly with the N-methylanilines
1c-1p to give the desired mono-alkylated products 2c-2p in
good to very good yields of 69-91 % while the di-alkylated
products 3c-3p were only obtained in yields of 6-16 % (Table 2,
entries 3-16). Overall, it turned out that the reaction tolerates
alkyl, ether, thioether, and fluoro substitution as well as the
presence of chloro and bromo substituents which offer various
possibilities for further functionalization. As observed before in
titanium-catalyzed hydroaminoalkylation reactions, the reactivity
of the ortho-methyl-substituted substrate 1b was found to be
significantly reduced compared with the meta- and para-
substituted analogues 1c and 1d and as a consequence, in this
case, the reaction had to be stirred for 48 h at 160 °C to obtain
the product 2b in 55 % yield (Table 2, entry 2).
16
p-SCF3 (1p)
80 (2p)
13 (3p)
93
[a] Reaction conditions: 1) amine (2.00 mmol), ethylene (1.4 atm), III (109
mg, 0.20 mmol, 10 mol%), toluene (1 mL), 160 °C, 24 h, isolated yields.
[b] 160 °C, 48 h. [c] The product could not be isolated in pure form.
To further study the scope and especially the limitations of the
hydroaminoalkylation of ethylene, we next performed a number
of corresponding experiments with secondary amines, which are
all known to usually react sluggishly with sterically more
demanding 1-alkenes
or styrenes (Table 3).[4a,4b,4d-f]
Unfortunately, during this study, it was first found that reactions
of ethylene with the N-alkylanilines 2a and 4 possessing alkyl
substituents larger than a methyl group do not give better results
than reported for corresponding reactions of other alkenes
(Table 3, entries 1 and 2). However, interesting is the fact that
3a which had already been obtained in 17 % yield as the
dialkylation side product of the hydroaminoalkylation of ethylene
with N-methylaniline (1a, (Table 1, entry 9) was only isolated in
9 % yield when 2a was used as the starting material (Table 3,
entry 1). From a mechanistic point of view, this finding strongly
suggests that once 2a is formed under catalytic conditions from
ethylene and N-methylaniline (1a), it stays bonded or at least in
close proximity to the titanium center which facilitates the CH
activation that initiates the second alkylation step (Scheme 2).
The fact that N-benzylaniline (5) and N-methylbenzylamine (6)
gave the desired hydroaminoalklyation products 14 and 15[9] in
significantly better yields of 45 % and 69 % (Table 3, entries 3
and 4) can simply be explained by the increased reactivity of the
benzylic position which selectively undergoes CH activation
during the course of the reaction. However, it should be noted
that even in these cases, it was beneficial to expand the reaction
Table 2. Hydroaminoalkylation of ethylene with various N-methylanilines (1a-
1p).[a]
time
to
48
h.
Under
identical
conditions,
the
hydroaminoalkylation of N-methylcyclohexylamine (7) with
ethylene took place regioselectively at the sterically less
hindered methyl group to give the corresponding product 16[9] in
71 % yield (Table 3, entry 5). While this result suggests that
dialkylamines can in principal, be regarded as suitable
substrates for the titanium-catalyzed hydroaminoalkylation of
ethylene, nitrogen-containing heterocycles were found to be
problematic substrates. Among the heterocycles 8-12 (Table 3,
entries 6-10), only 1,2,3,4-tetrahydroquinoline (11) gave the
desired hydroaminoalkylation product 20 in acceptable yield
(61 %, Table 3, entry 9). In contrast, pyrrolidine (8) and indoline
(10) were found to be completely unreactive and piperidine (9)
could only be converted into product 18[9] in poor yield (7 %,
Table 3, entry 7). The fact that the hydroaminoalkylation of
ethylene with 1,2,3,4-tetrahydroisoquinoline (12) did deliver the
expected product 21[9] in 19 % yield (Table 3, entry 10) deserves
particular attention because to the best of our knowledge, this
reaction represents the first successful example of a titanium-
catalyzed alkene hydroaminoalkylation that involves 1,2,3,4-
tetrahydroisoquinoline (12) as a substrate. A simple explanation
for the observation that 12 reacts more sluggishly than 1,2,3,4-
tetrahydroquinoline (11) is the fact that 12 is not an aniline
derivative.[5a] In comparison to N-methylbenzylamine (6), 12
gives a significantly lower yield because the benzylic position in
which the reaction takes place is part of a piperidine ring and
piperidine (9) was found to be a poor substrate (Table 3, entry 7).
Entry
1
R (1)
Yield 2 [%]
76 (2a)
55 (2b)
81 (2c)
75 (2d)
77 (2e)
82 (2f)
Yield 3 [%]
17 (3a)
5[c] (3b)
14 (3c)
14 (3d)
11 (3e)
16 (3f)
15 (3g)
12 (3h)
12 (3i)
Yield 2+3 [%]
H (1a)
93
60
95
89
88
98
86
81
90
81
91
97
87
90
90
2[b]
3
o-Me (1b)
m-Me (1c)
p-Me (1d)
p-i-Pr (1e)
m-F (1f)
4
5
6
7
p-F (1g)
71 (2g)
69 (2h)
78 (2i)
8
m-Cl (1h)
p-Cl (1i)
9
10
11
12
13
14
15
m-Br (1j)
p-Br (1k)
p-OMe (1l)
p-OPh (1m)
p-SMe (1n)
p-OCF3 (1o)
72 (2j)
9 (3j)
79 (2k)
91 (2l)
12 (3k)
6[c] (3l)
11 (3m)
9 (3n)
76 (2m)
81 (2n)
77 (2o)
13 (3o)
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of dimethylamine in toluene[4g] was used and as reported
before,[4g] monoalkylation as well as dialkylation at both -
positions of 22 occurred at 160 °C. Subsequent toslyamide
formation delivered the corresponding products 23[9] and 24[9,11]
in 16 % and 29 % yield, respectively and in good agreement with
the observations made with N-methylaniline (1a, Table 1), the
trialkylated product 25[9] could also be isolated in 12 % yield.
Table 3. Hydroaminoalkylation of ethylene with various secondary amines.[a]
Entry
1
Starting Material
Product
t [h]
Yield
[%]
24
9
2
24
48
48
15
45
69
Scheme 3. Hydroaminoalkylation of ethylene with dimethylamine (22).
3
Although the insertion of an alkene into the TiC bond of a
catalytically active titanaaziridine is generally accepted to be the
CC bond-forming key-step of the hydroaminoalkylation
(Scheme 2),[4c,8] to the best of our knowledge, only one
corresponding insertion-product has already been isolated and
characterized by IR, NMR, and MS techniques[8] while no
information about its solid-state structure is available. To close
this gap in knowledge, we performed a couple of insertion
reactions between ethylene (1.4 atm) and the titanaaziridines
26a-26c[8] which smoothly gave access to the expected
titanapyrrolidines 27a-27c in 78-85 % yield (Scheme 4). In this
context, it should be mentioned that titanium complexes with
sterically demanding adamantyl-substituted cyclopentadiene
ligands like the titanaaziridines 26a-26c are known to lack any
catalytic activity in hydroaminoalkylation reactions of alkenes[12]
and for that reason, they are perfectly suited as model
compounds for the isolation and characterization of stable
intermediates of the catalytic cycle.[8,13] Slow evaporation of a
solution of 27b in n-hexane/C6D6 then delivered crystals suitable
for X-ray single crystal analysis. As can be seen from the
corresponding solid state structure (Figure 2), the
titanapyrrolidine ring of 27b adopts an open envelop
conformation that includes a trigonal planar geometry around the
nitrogen center. Finally, it should be mentioned that the
hydroaminoalkylation product 2a could easily be released from
titanapyrrolidine 27a by simple hydrolysis. On the other hand,
attempts to regenerate 26a from 27a by the addition of one
equivalent of N-methylaniline (1a) and heating to 90 °C failed.[14]
4[b]
5[b]
48
71
6[b]
24
48
–
7[b]
7
8
24
48
48
–
9
61
19
10[b]
[a] Reaction conditions: 1) amine (2.00 mmol), ethylene (1.4 atm), III (109
mg, 0.20 mmol, 10 mol%), toluene (1 mL), 160 °C, t, isolated yields. [b]
The product was tosylated after the hydraminoalkylation to simplify the
purification.
Because dimethylamine (22) is one of the most important
amines in the chemical industry,[10] we finally attempted to prove
that this amine can also be reacted with ethylene in the
presence of catalyst III (Scheme 3). For that purpose, a solution
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Forschungsgemeinschaft for financial support of our research
and Jessica Reimer for experimental assistance.
Keywords:
amination
•
amines
•
ethylene
•
hydroaminoalkylation • titanium
[1]
[2]
For reviews on hydroaminoalkylation reactions of alkenes, see: a) E.
Chong, P. Garcia, L. L. Schafer, Synthesis 2014, 46, 2884-2896; b) J.
Hannedouche, E. Schulz, Organometallics 2018, 37, 4313-4326; c) P.
M. Edwards, L. L. Schafer, Chem. Commun. 2018, 54, 12543-12560.
For selected examples of late transition metal-catalyzed
hydroaminoalkylation reactions of alkenes, see: a) A. T. Tran, J.-Q. Yu,
Angew. Chem. 2017, 129, 10666-10670; Angew. Chem. Int. Ed. 2017,
56, 10530-10534; b) M. Spettel, R. Pollice, M. Schnürch, Org. Lett.
2017, 19, 4287-4290; c) S. M. Thullen, T. Rovis, J. Am. Chem. Soc.
2017, 139, 15504-15508; d) G. Lahm, T. Opatz, Org. Lett. 2014, 16,
4201-4203; e) M. Schinkel, L. Wang, K. Bielefeld, L. Ackermann, Org.
Lett. 2014, 16, 1876-1879; f) A. A. Kulago, B. F. Van Steijvoort, E. A.
Mitchell, L. Meerpoel, B. U. W. Maes, Adv. Synth. Catal. 2014, 356,
1610-1618.
Scheme 4. Insertion of ethylene into the Ti-C bond of titanaaziridines 26a-26c
and subsequent hydrolysis of titanapyrrolidine 27a to 2a.
[3]
[4]
For selected examples of group 3 metal catalyzed hydroaminoalkylation
reactions of alkenes with tertiary amines, see: a) A. E. Nako, J.
Oyamada, M. Nishiura, Z. Hou, Chem. Sci. 2016, 7, 6429-6434; b) F.
Liu, G. Luo, Z. Hou, Y. Luo, Organometallics 2017, 36, 1557-1565; c) H.
Gao, J. Su, P. Xu, X. Xu, Org. Chem. Front. 2018, 5, 59-63.
For selected examples of group 4 metal catalyzed hydroaminoalkylation
reactions of alkenes, see: a) R. Kubiak, I. Prochnow, S. Doye, Angew.
Chem. 2009, 121, 1173-1176; Angew. Chem. Int. Ed. 2009, 48, 1153-
1156; b) R. Kubiak, I. Prochnow, S. Doye, Angew. Chem. 2010, 122,
2683-2686; Angew. Chem. Int. Ed. 2010, 49, 2626-2629; c) I.
Prochnow, P. Zark, T. Müller, S. Doye, Angew. Chem. 2011, 123, 6525-
6529; Angew. Chem. Int. Ed. 2011, 50, 6401-6405; d) J. Dörfler, T.
Preuß, A. Schischko, M. Schmidtmann, S. Doye, Angew. Chem. 2014,
126, 8052-8056; Angew. Chem. Int. Ed. 2014, 53, 7918-7922; e) J.
Dörfler, T. Preuß, C. Brahms, D. Scheuer, S. Doye, Dalton Trans. 2015,
44, 12149-12168; f) L. H. Lühning, C. Brahms, J. P. Nimoth, M.
Schmidtmann, S. Doye, Z. Anorg. Allg. Chem. 2015, 641, 2071-2082;
g) J. Bielefeld, S. Doye, Angew. Chem. 2017, 129, 15352-15355;
Angew. Chem. Int. Ed. 2017, 56, 15155-15158.
Figure 2. Molecular structure of 27b. Hydrogen atoms are omitted for clarity
except H6 and H21. Thermal ellipsoids are drawn at the 50% probability level.
Selected bond lenghts (Å) and angles (°): Ti1–N1 2.068(2), N1–C33 1.472(3),
C33–C32 1.515(4), C32–C31 1.523(3), C31–Ti1 2.192(2), C1–C6 1.516(3),
C16–C21 1.513(3), N1–Ti1–C31 82.29(9), Ct1–Ti1–Ct2 131.28 Definitions:
Ct1, centroid C1-C5; Ct2, centroid C16-C20.
[5]
For selected examples of group 5 metal catalyzed hydroaminoalkylation
reactions of alkenes, see: a) S. B. Herzon, J. F. Hartwig, J. Am. Chem.
Soc. 2007, 129, 6690-6691; b) A. L. Reznichenko, T. J. Emge, S.
Audörsch, E. G. Klauber, K. C. Hultzsch, B. Schmidt, Organometallics
2011, 30, 921-924; c) A. L. Reznichenko, K. C. Hultzsch, J. Am. Chem.
Soc. 2012, 134, 3300-3311; d) J. M. Lauzon, P. Eisenberger, S.-C.
Roşca, L. L. Schafer, ACS Catal. 2017, 7, 5921-5931; e) J. W. Brandt,
E. Chong, L. L. Schafer, ACS Catal. 2017, 7, 6323-6330; f) P. M.
Edwards, L. L. Schafer, Org. Lett. 2017, 19, 5720-5723; g) R. C.
DiPucchio, S.-C. Roşca, L. L. Schafer, Angew. Chem. 2018, 130, 3527-
3530; Angew. Chem. Int. Ed. 2018, 57, 3469-3472; h) R. C. DiPucchio,
S.-C. Roşca, G. Athavan, L. L. Schafer, ChemCatChem 2019, 11,
3871-3876; i) C. Braun, M. Nieger, S. Bräse, L. L. Schafer,
ChemCatChem 2019, 11, 5264-5268.
In summary, we have presented the first examples of titanium-
catalyzed hydroaminoalkylation reactions of ethylene with
secondary amines. The new reaction does not require the use of
high pressure equipment and it tolerates the presence of alkyl,
ether, thioether, fluoro, chloro, and bromo substitution in the
amine substrates. In addition, it was possible for the first time to
determine the solid state structure of a titanapyrrolidine that is
formed by insertion of an alkene into the TiC bond of a
titanaaziridine.
[6]
[7]
M. G. Clerici, F. Maspero, Synthesis 1980, 305-306.
Research and Markets, "The Ethylene Technology Report 2016", can
be found under: https://www.researchandmarkets.com.
[8]
[9]
M. Manßen, N. Lauterbach, J. Dörfler, M. Schmidtmann, W. Saak, S.
Doye, R. Beckhaus Angew. Chem. 2015, 127, 4458-4462; Angew.
Chem. Int. Ed. 2015, 54, 4383-4387.
The initially formed hydroaminoalkylation product was converted into
the corresponding tosylamide to simplify the work up procedure and the
final chromatographic purification.
Acknowledgements
[10] K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, 4th ed., Wiley-
VCH, Weinheim, 2003, 51-52.
We thank the Research Training Group "Chemical Bond
Activation"
(GRK
2226)
funded
by
the
Deutsche
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10.1002/chem.201904502
Chemistry - A European Journal
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[11] The initially formed product, di-n-propylamine, is an intermediate for the
industrial production of herbicides (e.g. oryzalin).
[12] In a control experiment, complex 26a (10 mol%) did not catalyze the
hydroaminoalkylation of ethylene with N-methylaniline (1a) at 140 °C.
[13] All attempts to isolate or at least to characterize intermediates of the
proposed catalytic cycle from catalytically active complexes such as
Ind2TiMe2 or III have failed so far.
[14] The experiment was performed in toluene-D8 and followed by 1H NMR.
At temperatures above 90 °C, slow decomposition of 27a was observed.
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10.1002/chem.201904502
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
M. Rosien, I. Töben, M. Schmidtmann,
R. Beckhaus,* S. Doye*
Page No. – Page No.
Titanium-Catalyzed
Hydroaminoalkylation of Ethylene
No high pressure equipment is required for achieving the hydroaminoalkylation of
ethylene with secondary amines in the presence of titanium catalysts. This finding is
in good agreement with the observation that the insertion of ethylene into the TiC
bond of titanaaziridines which are regarded to be the catalytically active species of
hydroaminoalkylation reactions takes place easily to give titanapyrrolidines.
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