Selective hydrosilylation of N-allylimines using a (3-iminophosphine)palladium precatalyst

Article abstract of DOI:10.1039/c5cy01859e

Hydrosilylation utilizing a (3-iminophosphine)palladium catalyst leads to the selective reduction of the imine unit of allylimines. Successful reduction of twenty-five different substituted aromatic and alkyl allylimines demonstrated the scope and selecti

Full text of DOI:10.1039/c5cy01859e

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DOI: 10.1039/C5CY01859E
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COMMUNICATION
Selective Hydrosilylation of N-Allylimines using a (3-
Iminophosphine)Palladium Precatalyst
Hosein Tafazoliana and Joseph A. R. Schmidta*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
substrate tolerance in the palladium-catalyzed reduction of imines.
Recently, we demonstrated that cationic complexes of the type
[(3-iminophosphine)Pd(allyl)]+ successfully catalyze the efficient
and regioselective hydrosilylation of allenes.14 We also postulated
that in this process, the catalyst activated primary and secondary
hydrosilanes to form a Pd-H intermediate, an assertion that was
further supported by an H/D crossover experiment.14 Since
allylamines have broad significance in synthetic chemistry, we
hoped to utilize the hydrosilane activation in our system to effect the
catalytic hydrosilylation of allylimines in order to reduce them to
allylamines following hydrolysis. Herein, we report palladium-
catalyzed selective hydrosilylation/reduction of various allylimines
under mild conditions (Scheme 1). All catalytic reactions were
Hydrosilylation utilizing a (3-iminophosphine)palladium
catalyst leads to the selective reduction of the imine unit of
allylimines. Successful reduction of twenty-five different
substituted aromatic and alkyl allylimines demonstrated the
scope and selectivity of this catalytic system.
Allylamines are fundamentally important organic building blocks,
especially as moieties within chiral amines because of their
occurrence in natural products and pharmaceuticals.1, 2 Many modern
efforts in the development of new synthetic strategies facilitating
amine synthesis have targeted catalytic hydroamination reactions for
the addition of primary and secondary amines to C-C unsaturated
bonds.2-9 Alternatively, catalytic hydrosilylation has been
extensively used to form new C-Si bonds10-14 with many examples
utilizing catalytic hydrosilylation or hydrogenation as a means to
form amines from imines or amides.15-21 Overall, successes in
functional group tolerance, chemoselectivity, and enantioselectivity
in imine hydrosilylation/reduction demonstrated by various research
groups have garnered much interest in this field.22-27 To date,
1
performed in NMR tubes with H NMR spectra observed frequently
to monitor reaction completion.
numerous
examples
of
metal
catalyzed
imine
hydrosilylation/reduction have been reported, often utilizing
titanium,28 iron,21, 27 zinc,20, 29 ruthenium,30 rhodium, or iridium.17, 18,
31, 32
Although highly active metal and even metal-free examples of
imine hydrosilylation have been reported, they often suffer from a
lack of selectivity for the imine in reduction reactions or very poor
33, 34
overall functional group tolerance.27,
Furthermore, there are
only a few examples of palladium-catalyzed hydrosilylation of
imines, and no comprehensive study of substrate scope with
palladium catalysts for this transformation has been undertaken.31, 35
With regard to palladium-catalyzed imine reduction, many recent
hydrogenation examples, especially those involving the asymmetric
hydrogenation of imines, require PMP or tosyl protected imines
while displaying a relatively limited substrate scope.36 This raises the
need for the development of useful new catalysts with broad
Scheme
1.
First
example
of
palladium-catalyzed
hydrosilylation/reduction of allylimines.
Preliminary results showed that the hydrosilylation of 1a at room
temperature was moderately slow, therefore the reaction temperature
was varied in order to find more optimal reaction conditions (Table
1). Acceptable reaction rates were observed with mild heating (40-50
oC), while higher temperatures resulted in the formation of a
complex mixture of products due to uncharacterized competing side
reactions.
a Department of Chemistry & Biochemistry, School of Green Chemistry and
Engineering, College of Natural Sciences and Mathematics, The University
of Toledo, 2801 W. Bancroft St. MS 602, Toledo, Ohio 43606-3390, USA
*
E-mail: Joseph.Schmidt@utoledo.edu. Tel: +1-419-530-1512. Fax: +1-
419-530-4033.
†
Electronic supplementary information is available containing experimental
details and spectroscopic data.
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Table 1. Effect of reaction temperature.a
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16 90
(2h)
8
9
DOI: 10.1039/C5CY01859E
(1h)
(1i)
4
84
(2i)
10
3
76
(2j)
(1j)
Completion timeb (h)
24
Temperature (oC)
11
2
91
78
(1k)
(1l)
(2k)
(2l)
rt
12
13
44
30
40
50
60
16
8
2
89
(2m)
(2n)
(2o)
(2p)
(1m)
(1n)
6
14
15
16
36
30
34
92
83
88
4c
a
Catalytic procedure: Reactions were carried out in NMR
tubes prepared in a glovebox using CDCl3 (800 µl), catalyst
(0.025 mmol), PhSiH3 (0.6 mmol, 1.2 equiv.), and allylimine
(0.5 mmol, 1 equiv.); Reaction completion was monitored
and recorded by H NMR spectroscopy by observation of the
(1o)
(1p)
b
1
d
17
-
-
-
diminishing allylimine peaks. Hydrosilylated product was
hydrolysed in 2 ml of H2O to yield the secondary allylamine; c
Formation of side-products was detected by 1H NMR.
(1q)
(1r)
18
19
20
3
6
4
79
81
89
(2r)
(1s)
(2s)
The best solvent was found to be CDCl3 (see supporting
information for more details). In an effort to further enhance the rate
of the reaction, a stronger σ-donating di-tert-butyl phosphine unit
was utilized on the 3IP ligand (3b) in place of the diphenylphosphine
in 3a. Using this improved ligand set reduced the completion time
(1t)
(2t)
21
22
6
87
84
(2u)
(1u)
o
for the hydrosilylation of 1a to 4 h at 40 C. Having determined the
18
better catalyst system and useful mild reaction conditions, we set out
to investigate the functional group tolerance for this transformation.
A variety of allylimines were synthesized via the Schiff base
condensation of aromatic aldehydes with allylamine, which were
then subsequently subjected to catalytic hydrosilylation (Table 2).
(1v)
(2v)
(2w)
(2x)
23
24
10
14
88
81
(1w)
(1x)
o
a Catalytic procedure: Reactions were carried out at 40 C in NMR
tubes prepared in a glovebox using CDCl3 (800 µl), catalyst (0.025
mmol), PhSiH3 (0.6 mmol, 1.2 equiv.), and allylimine (0.5 mmol, 1
Table 2. Pd-catalyzed reduction of allylimines.a
b
1
equiv.); Reaction completion was monitored and recorded by H
NMR spectroscopy by observation of the diminishing allylimine
peaks. Hydrosilylated product was hydrolysed in 2 ml of H2O to yield
the secondary allylamine; Isolated yield; Catalyst decomposition
occurred.
c
d
yieldc
(%)
Entry
1
Allylimine
Product
tb (h)
4
81
Previous reports have noted that a PdCl2/hydrosilane system can
result in the cleavage of C=N moieties,35 but this reaction was not
observed in our system. Instead, our system displayed clean
hydrosilylation of the imine moiety for a wide range of aromatic
imines, all of which underwent smooth hydrolysis in water. The
necessary reaction times were highly dependent on the substituents
on the aldimine aryl group with EDG requiring shorter reaction
times compared to substrates bearing EWG. Representative
secondary and tertiary alkyl N-allylimine substrates (1w and 1x)
showed that this hydrosilylation catalyst system also operated
efficiently for alkyl derivatives. It was found that acetonitrile and
benzonitrile did not react under these catalytic conditions, so this
process is benign to alkyl and aryl nitriles. Further investigations
revealed that ketimines were also relatively unreactive, with less
than 5% conversion detected after 8 hours at room temperature using
catalyst 3b. Longer reaction times with ketimines proved somewhat
(1a)
(1b)
(2a)
2
3
4
5
12
14
12
16
89
79
76
82
(2b)
(1c)
(1d)
(2c)
(2d)
(2e)
(1e)
(1f)
(1g)
6
7
12
12
84
92
(2f)
(2g)
2 | J. Name., 2012, 00, 1-3
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effective, although the crude product was contaminated with report is the only example of palladium-catalyzVeidew AarltlicyleliOmnilinnee
significant amounts of side-products (Table 3). Although the hydrosilylation/reduction to date.
electronic character of the allylimines adequately explains the This work was based on financial support by the National
DOI: 10.1039/C5CY01859E
different reaction rates for aldimines, it does not clarify the low Science Foundation under CHE-0841611.
reactivity of ketimines. In our previous study, it was found that
substrate sterics (in both the unsaturated substrate and the silane)
play a major role in the reactivity of the system due to the necessary
formation of a σ-complex within the catalytic mechanism in which
the hydrosilane must approach the palladium center. Thus, in the
hydrosilylation of ketimines, the presence of the second substituent
(methyl) on the imine significantly hinders formation of this required
σ-complex. Utilizing a ketimine bearing an electron-donating
methoxy group did not significantly influence the reactivity and
approximately the same reaction rate as the unsubstituted ketimine
was observed. Thus, it seems that for ketimines, steric hinderance in
the σ-complex formation step of the catalytic cycle is more
important than electronic effects in the imine aryl unit.
Table 3. Investigation of ketimines.a
yieldd
(%)
Entry
25
Allylimine
Product
tb (h)
72c
68
(2y)
(1y)
26
72c
53
(2z)
(1z)
Figure 1. Proposed catalytic cycle for hydrosilylation of allylimines
o
a Catalytic procedure: Reactions were carried out at 40 C in NMR
tubes prepared in a glovebox using CDCl3 (800 µl), catalyst (0.025
mmol), PhSiH3 (0.6 mmol, 1.2 equiv.), and allylimine (0.5 mmol, 1
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DOI: 10.1039/C5CY01859E
-
OTf
Pd
tBu2P
NtBu
R'
R'
H
5 mol%
N
N
PhSiH3
CDCl3
40 oC
H
R
R
R' = H or Me
1 equiv.
then H2O
selective reduction of C=N
twenty-three examples
reaction time: 2-44 h (aldimines)
72 h (ketimines)
1.2 equiv.