Cationic [(Iminophosphine)Nickel(Allyl)]+Complexes as the First Example of Nickel Catalysts for Direct Hydroamination of Allenes

Article abstract of DOI:10.1002/chem.201605611

The first example of nickel-catalyzed hydroamination of allenes is reported. The new cationic [(3-iminophosphine)nickel(allyl)]⁺catalysts have been fully characterized and act regioselectively in the catalytic hydroamination of allenes with sec

Full text of DOI:10.1002/chem.201605611

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Accepted Article
Title: Cationic [(Iminophosphine)nickel(allyl)]+ Complexes as the First
Example of Nickel Catalysts for Direct Hydroamination of Allenes
Authors: Hosein Tafazolian and Joseph A Schmidt
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Cationic [(Iminophosphine)nickel(allyl)]+ Complexes as the First
Example of Nickel Catalysts for Direct Hydroamination of Allenes
Hosein Tafazolian and Joseph A. R. Schmidt*
Abstract: The first example of nickel-catalyzed hydroamination of
allenes is reported. The new cationic [(3-
iminophosphine)nickel(allyl)]+ catalysts have been fully characterized
and act regioselectively in the catalytic hydroamination of allenes
with secondary amines at room temperature.
nickel-catalyzed transformations, as studied by Togni,[5]
Zargarian[6] and Garcia,[7] support a likely mechanism for nickel-
catalyzed hydroamination of activated C-C multiple bonds
(mainly acrylonitrile and related compounds) based on the
electrophilicity of the Ni center. In research moving beyond
these highly activated systems, Ackermann has described the
intramolecular hydroamination of alkynes to form indoles.[8]
Unfortunately, one drawback of Ackermann’s system is the high
temperature (120 oC) needed to obtain significant reactivity. The
only well-defined report of nickel-catalyzed intermolecular
hydroamination of unactivated C-C multiple bonds is a single
paper by Hartwig in which the intermolecular hydroamination of
1,3-dienes to form allylamine products is reported.[9]
Although nickel-catalyzed C-N bond formation has attracted
much interest, direct hydroamination catalyzed by nickel remains
an unsolved challenge.[10] It is clear that metal-catalyzed
hydroamination processes are dependent on both the metal
utilized and the effects of the ancillary ligands employed. Both
features impact the overall efficiency and operable mechanism
in known systems. In our recent work involving the mechanistic
study of palladium-catalyzed allene hydroamination, we showed
that electronic effects in the supporting 3-iminophosphine (3IP)
ligands often dictate the rate-limiting step in the mechanism for
this process.[2f] With this understanding of ligand effects, we felt
well poised to address the challenging reactivity of nickel
analogues based on our previously reported palladium catalysts,
especially as applied to allene hydroamination catalysis. Herein,
we describe the first example of nickel-based allene
Hydroamination, commonly noted as one of the most
challenging and interesting addition reactions, is defined as N-H
bond addition to a C-C multiple bond and is unobtainable without
a catalyst, except in rare cases where the unsaturated substrate
is highly activated. The distinctly negative entropy term coupled
with only modest exothermicity explains the difficult nature of
direct intermolecular hydroamination.[1] Despite its underlying
complexity, the significance of this process relies on the broad
potential utilization of the resulting products in pharmaceuticals
1c]
and specialty chemicals.[1a,
Although many early and late
transition metals can promote hydroamination of C-C multiple
bonds, due to issues involving substrate scope, cost, toxicity,
and oxophilicity, many known reactive metal complexes are
unsatisfactory for industrial utilization.[1a] These factors have led
to the extensive investigation of late transition metals such as
Ru, Rh, Pd, Ir, Pt and Au as some of the most promising
2]
candidates for broad application.[1a,
However, despite the
demonstration of excellent reactivity profiles, one remaining
unsolved problem is the cost of catalyst since these highly active
late transition metal catalysts for hydroamination are very
expensive. Thus, the development of a first row late transition
metal hydroamination catalyst derived from Ni or Cu would be
quite favorable. Recently, copper has shown promise in
catalysis of C-N bond forming reactions, although direct
hydroamination using copper has only recently emerged while
the overall atom economy is low in other copper-based
amination reactions due to the formation of byproducts.[3]
Curiously, nickel-based catalysts have not been the subject of
recent reports. With common accessible oxidation states of 0, +1,
+2, and +3, it seems likely that the rich chemistry of nickel would
include applications in hydroamination, since two unit oxidation
state toggles are common in direct metal-catalyzed
hydroamination.[1a, 4] However, surprisingly, virtually all reports of
nickel-catalyzed hydroamination to date are limited to highly
activated substrates or require very high temperatures. These
hydroamination
through
the
use
of
cationic
[(3-
iminophosphine)nickel(allyl)]+ complexes.
Overall, the synthesis of allylnickel complexes proceeded
similarly to our reported palladium analogues,[2q, 11] except for the
fact that usage of a non-polar solvent is crucial in some steps to
obtain the desired nickel complexes (Table 1).
Table 1. Cationic [(3IP)Ni(allyl)]+ complexes.
[*]
Dr. H. Tafazolian, Prof. Dr. J. A. R. Schmidt
Department of Chemistry and Biochemistry, School of Green
Chemistry and Engineering, College of Natural Sciences and
Mathematics
R’
R
N
1
1
1
2
Ni complex
Isolated yield (%)
tButyl
Phenyl
Phenyl
tButyl
1a
1b
1c
1d
87
85
82
91
The University of Toledo
2801 W. Bancroft St. MS 602, Toledo, Ohio, 43606-3390, USA
E-mail: joseph.schmidt@utoledo.edu
2,6-Xylyl
2,6-Xylyl
2,6-Xylyl
Phenyl
Supporting information for this article is given via a link at the end of
the document.
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The putative nickel hydride concurrently formed in this reaction
is unstable, decomposing in the absence of allene substrate and
eluding adequate characterization in our hands.
Attempts to use other solvents in the complexation reaction of
the allylnickelbromide dimer with the 3IP ligand, such as diethyl
ether, tetrahydrofuran, dichloromethane or acetonitrile, led to
intractable mixtures. As previously reported, allylnickelhalide
dimers are only stable in nonpolar solvents, undergoing ligand
redistribution/disproportionation reactions in more polar
environments.[12] Once the nickel complexes were synthesized,
they were characterized by NMR spectroscopy and elemental
analysis. Suitable crystals of 1b were grown from a saturated
solution of the complex in tetrahydrofuran layered with pentane.
Its structure was solved via direct methods (Figure 1).
Scheme 1. Reaction of 1b with secondary amines.
We previously observed a similar catalyst activation/first
turnover product in palladium analogues of these nickel
complexes, leading to their allene hydroamination activity.[2f]
Thus, we set out to examine the catalytic activity of these newly
synthesized nickel complexes in the hydroamination of mono-
substituted allenes. A comparison of the catalytic activity of 1a-
1d using the reaction of cyclohexylallene with morpholine as a
benchmark reaction showed that 1b was the best catalyst, while
1c had somewhat reduced reactivity (see SI for further details).
Catalysts 1a and 1d showed low conversion values by NMR
spectroscopy, with significant contamination by unidentified
products. Thus, 1b was chosen as the catalyst for utilization in a
study of substrate scope in this reaction. Cyclohexylallene
served as the allene precursor and was treated with a variety of
amines (Table 2). Excess amine (4 equiv.) was utilized to
increase the overall reaction rates, leading to moderate or better
conversion after 48 hours. Secondary amines functioned well in
this system, forming linear allylamine products in moderate to
good yields. The production of linear products was not surprising,
as this is the thermodynamically favored product in these
reactions.[2a] Primary amines of various types were invariably
found to be unreactive, as observed in many cases with our less
reactive Pd analogs.[11]
Figure 1. Crystal structure of 1b (50% thermal ellipsoids); hydrogen atoms,
triflate anion and cocrystallized solvent (THF) have been omitted for clarity;
Selected bond distances (Å) and bond angle (deg): Ni-P, 2.174; Ni-N, 1.920;
P-Ni-N, 99.3.
Once the desired allylnickel complexes were isolated, their
reactivity in the catalytic hydroamination of allenes was explored.
As
a means to investigate catalyst activation, equimolar
amounts of nickel complex 1b and thiomorpholine were added to
an NMR tube with C6D6 as solvent, and the reaction progress
was observed every 10 minutes.
Table 2. Hydroamination of cyclohexylallene catalyzed by 1b.a
Isolated yield
Entry
HNR1R2
Product
4a
(%)
1
67
Time/10 (min)
2
3
4
4b
4c
4d
52
71
91
Figure 2. Time-resolved 1H NMR spectra of equimolar reaction between 1b
and thiomorpholine (recorded every 10 minutes).
5
4e
87
This time-resolved 1H NMR data showed that after
coordination of the secondary amine to the nickel precatalyst, N-
allylthiomorpholine product peaks (the catalyst activation
product) steadily grow in, while the allyl ligand peaks
correspondingly diminished in tandem. At the final time point
(100 minutes), the reaction had reached 22% N-
allylthiomorpholine along with 78% unreacted catalyst (Figure 2).
A similar stoichiometric reaction between 1b and indoline led
smoothly to the analogous N-allylindoline product (Scheme 1).
6
7
4f
50
39
4g
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8
4h
92
5c (93%)
5d (90%)
9
4i
4j
53b
84
10
5e (80%)
6a (75%)
5f (91%)
6b (60%)
11
12
-
-
-
-
13
-
-
14
15
16
-
-
-
-
-
-
6c (82%)
6d (79%)
a Reactions were performed in small vials; toluene (2 ml) was added to 1b
(0.025 mmol, 5 mol%), followed by addition of amine (2 mmol, 4 eq.) and
b
cyclohexylallene (0.5 mmol, 1 eq.). Catalyst loading was increased to
6e (76%)
7a (91%)
6f (79%)
7b (83%)
0.05 mmol (10 mol%) and allowed to stir for 72 hours.
Although cyclooligomerization and polymerization of allenes is
well-known,[13] very little of such byproducts was detected after
48 hours. During reaction optimization, it was found that using
coordinating solvents (tetrahydrofuran, acetonitrile, or dioxane)
resulted in lower conversions, possibly due to coordinative
competition with the substrate amine. This was also examined
through an NMR scale catalytic reaction in which
cyclohexylallene, thiomorpholine and triethylamine (1 eq., 1 eq.,
and 2 eq., respectively) were allowed to react in the presence of
2.5 mol% of 1b. As observed by frequent 1H NMR spectra of the
mixture, only 10% conversion after 30 h was detected, while
25% conversion was obtained in only 12 hours without
triethylamine. Thus, it was concluded that coordination of the
substrate amine plays a key role in this catalytic process, which
is especially evident in comparison of entries 8 and 9 with
methylindoline having less reactivity than indoline due to steric
hinderance. Such effects were also observed in the related Pd
catalysts.[2q]
7c (81%)
7d (81%)
7e (79%)
7f (77%)
a Reactions were performed in small vials; toluene (2 ml) was added to 1b
(0.05 mmol, 10 mol%), followed by addition of amine (2 mmol, 4 eq.) and
allene (0.5 mmol, 1 eq.).
The substrate scope of this system was further investigated
via hydroamination of additional mono-substituted allenes (3b,
3c and 3d) with secondary amines (Table 3). As with
cyclohexylallene, all examples resulted in regioselective
hydroamination of the allene to form the linear allylamine
product as primarily the E isomer in moderate to good yields.
In one further effort to expand substrate scope, 1,1-
dimethylallene was subjected to hydroamination. Reaction
monitoring revealed that longer reaction times were required to
obtain good yields in the hydroamination of 1,1-dimethylallene at
room temperature (Table 4). Performing the reaction at higher
temperatures unfortunately led to the formation of complex
mixtures of products, rather than merely increasing reaction rate.
Table 3. Hydroamination of nhexyl-, nbutyl- and benzylallene catalyzed by 1b.a
Despite
a
commonly believed misconception, mono-
substituted allenes are readily available starting materials, easily
generated from commercially available mono-substituted
alkenes. One synthetic route to accomplish this is by treatment
of alkenes with
a
dibromocarbene reagent to yield
a
dibromocyclopropane intermediate, followed by reaction with a
Grignard reagent to open this three-membered ring, utilizing
these three carbon atoms as the allene core.[14] The allylamines
subsequently formed by hydroamination are then of great
interest in pharmaceuticals, while alternate synthetic methods to
obtain these products are often less efficient and lower
yielding.[15]
5a (63%)
5b (82%)
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Acknowledgements
This work was based on financial support by the National
Science Foundation under CHE-0841611.
Table 4. Hydroamination of 1,1-dimethylallene catalyzed by 1b.a
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and allene (0.5 mmol, 1 eq.).
Mechanistically, the preliminary results reported herein show
that cationic [(3IP)Ni(allyl)]+ complexes behave similarly to their
palladium analogues upon treatment with secondary amines.
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formation of a nickel-amido species constitutes a plausible
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allylamine followed by oxidative ligation of the iminium proton to
the nickel complex results in the active nickel hydride species,
producing the corresponding first turnover products 2a and 2b
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a
similar
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In summary, we have described the synthesis of novel cationic
[(3IP)Ni(allyl)]+ complexes and their reactivity in the
hydroamination of allenes with secondary amines, constituting
the first example of nickel-catalyzed hydroamination of
unactivated substrates. The resulting allylamines were isolated
in good yields and characterized by NMR spectroscopy and
mass spectrometry. These results revealed good efficiency and
selectivity with these new nickel complexes, although we expect
that higher reactivity can be achieved by further tuning the ligand
system. Further study of the mechanism and continued
expansion of the hydroamination substrate scope utilizing these
novel nickel catalysts is ongoing.
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Synthetic procedures and characterization data for nickel
complexes and hydroamination products are available in the
supporting information file. CCDC 1516985 contains the
supplementary crystallographic data for this paper. These data
are provided free of charge by The Cambridge Crystallographic
Data Centre.
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10.1002/chem.201605611
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10.1002/chem.201605611
Chemistry - A European Journal
COMMUNICATION
The first successful nickel-based catalysts for the hydroamination of allenes are reported.
These new base-metal cationic [(3-iminophosphine)nickel(allyl)]+ catalysts have been fully
characterized and act regioselectively in the catalytic hydroamination of allenes with
secondary amines to produce moderate to high yields of allylamines at room temperature.
Keywords:
Allyl ligands; Catalysis; Homogeneous catalysis; N,P ligands; Organometallic chemistry
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