Easily available nickel complexes as catalysts for the intermolecular hydroamination of alkenes and alkynes

Article abstract of DOI:10.1039/c3dt52648h

A series of nickel complexes of the type [(P-P)NiX₂] ((P-P) = bisphospines or bisphosphites, X = chloride, triflate) were used as catalysts for the hydroamination of both activated and unactivated alkenes and alkynes with pyrrolidine. In general, the use of activated unsaturations, such as acrylonitrile, required mild reaction conditions (e.g. 100 °C and 4 h) in comparison with other non-activated alkenes. Particularly with a series of alkynes, the use of nickel(ii) centers diminished or even inhibited the formation of otherwise undesired homocoupling and/or transfer hydrogenation by-products, such as the ones obtained in the presence of zerovalent nickel. When using less activated substrates, better selectivity was obtained, although harsher reaction conditions were needed. From a general perspective, the results of this report strongly support the potential use of nickel as a good candidate for further application in the hydroamination of organic unsaturations by means of screening of several π acceptor ligands. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3dt52648h

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PAPER
Easily available nickel complexes as catalysts for
the intermolecular hydroamination of alkenes and
alkynes†
Cite this: Dalton Trans., 2014, 43,
1762
Adán Reyes-Sánchez, Ilnett García-Ventura and Juventino J. García*
A series of nickel complexes of the type [(P–P)NiX2] ((P–P) = bisphospines or bisphosphites, X = chloride,
triflate) were used as catalysts for the hydroamination of both activated and unactivated alkenes and
alkynes with pyrrolidine. In general, the use of activated unsaturations, such as acrylonitrile, required mild
reaction conditions (e.g. 100 °C and 4 h) in comparison with other non-activated alkenes. Particularly
with a series of alkynes, the use of nickel(II) centers diminished or even inhibited the formation of other-
wise undesired homocoupling and/or transfer hydrogenation by-products, such as the ones obtained in
the presence of zerovalent nickel. When using less activated substrates, better selectivity was obtained,
although harsher reaction conditions were needed. From a general perspective, the results of this report
strongly support the potential use of nickel as a good candidate for further application in the hydroamina-
tion of organic unsaturations by means of screening of several π acceptor ligands.
Received 23rd September 2013,
Accepted 26th October 2013
DOI: 10.1039/c3dt52648h
www.rsc.org/dalton
alkenes mostly in an intramolecular fashion, and in this
regard, the extended use of samarium developed by Marks
1. Introduction
Alkynes and alkenes represent two of the most important et al.9–12 is noteworthy. Nevertheless, one of the main dis-
building blocks for the synthesis of target compounds with advantages of both early transition and rare earth metal com-
wide applications both in industry and fine chemistry.1 plexes is their high oxophilicity, which eventually limits their
Besides conventional reactions to functionalize these sub- use with some oxygen-containing substrates.3
strates, hydroamination, defined as the direct addition of
Regarding the use of late transition metals, palladium is, by
amines to alkynes and alkenes,2,3 represents a route to syn- far, the most widely employed metal in hydroamination and
thesize N-derivatives such as amines, imines and enamines in other well known relevant organic transformations.13 Particu-
one step and with high atom economy. In general, intramole- larly with palladium, there have been some interesting reports
cular hydroamination has been shown to be thermodynami- related to the effect of variables involving the electronic charac-
cally and kinetically more favored and easier to achieve than ter of the metal itself and its ligands, which eventually could
the intermolecular manner. In order to afford the hydroamina- be applied to neighboring elements. For instance, Hartwig
tion of C–C unsaturations, catalysts, mainly based on elements et al.14 have found that in the hydroamination of vinylarenes
of the d and f blocks of the periodic table, have been develo- and dienes, the use of ancillary phosphines bearing wide bite
ped.2 The found reactivity with such catalysts varies mostly by angles (e.g. xantphos) allows the formation of the corres-
means of their electronic properties conferred both by the ponding products more efficiently compared to other phos-
element and its ligands as is briefly described below.
phines with narrower angles. The same authors adduce this
Among the most efficient metal complexes used in the effect to a more favorable nucleophilic attack over the alkene
hydroamination stands the use of titanium4–6 and other early when this is coordinated to a metal center with a wider phos-
transition metals.7,8 In most of the reported examples, the phine. In another example, the Müller group has reported a
corresponding hydroamination products have been obtained study15 describing the enhancement of the rate of hydro-
in high yields. In the same way, complexes based on rare earth amination of aminoalkynes when the counter ion of a cationic
complexes have allowed the hydroamination of alkynes and palladium catalyst is a sulfonic acid derivative (e.g. triflate or
tosylate) because of the easiness of replacing them by an
alkyne or amine.
There have been some recent efforts to mimic the catalytic
activity of palladium, mainly because, when compared to this
Facultad de Química, Universidad Nacional Autónoma de México, Circuito Escolar,
Ciudad Universitaria, Mexico City 04510, Mexico. E-mail: juvent@servidor.unam.mx
†Electronic supplementary information (ESI) available: Selected NMR and
element, other alternate metals such as copper, nickel and
GC-MS spectra are available. See DOI: 10.1039/c3dt52648h
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iron offer lower costs and toxicities as well as a better bio- under 4 Å molecular sieves for 24 h before use. Complexes
compatibility. In this regard, some recent approaches involve the [(dippe)NiCl2], [(diphos)NiCl2], [(dippf)NiCl2] and [(dppf)-
intermolecular hydroamination of activated alkenes, such as NiCl2] were prepared from solutions of NiCl2·6H2O and the
derivatives of acrylonitrile, catalyzed by hydride and NHC com- corresponding chelating bisphosphine by adapting reported
plexes of copper,16,17 the use of silver in the intermolecular procedures.32 The nickel dimer [Ni(dippe)(μ-H)]2 was syn-
hydroamination of alkynes,18,19 and the iron-catalyzed inter- thesized from a stirred suspension of [(dippe)NiCl2] and Super-
and intramolecular hydroamination of styrenes20 and amino- Hydride® by the procedure reported in the literature.33 The
alkenes,21 respectively. For the particular case of nickel, its use complex [(diphos)Ni](OTf)2 was prepared according to reported
in hydroamination is still scarce, even though it holds great procedures.34,35 NMR spectra of complexes and organic pro-
potential as a cheap and biocompatible catalyst, for example, ducts were acquired at room temperature using a 300 MHz
in the hydroamination of activated alkenes,22–27 dienes,14 and Varian Unity Inova spectrometer. Samples and reactions moni-
alkynes.15,28–31 Recently, our group has reported the hydro- tored by NMR were manipulated under an inert atmosphere
amination and transfer semihydrogenation of alkynes catalyzed and charged in thin wall (0.33 mm) Wilmad NMR tubes,
by the complex [(dippe)NiH]2.31 In the mentioned work, the equipped with J. Young valves and heated in silicon oil baths
hydroamination products of diphenylacetylene and 2-ethynyl- at the desired temperature. Chemical shifts in 1H NMR spectra
aniline could be successfully obtained, although in moderate (δ, ppm) are reported according to the residual protio in the
yields (<40%) because of the competing prevalence of both the solvent. 31P{1H} NMR spectra are referred to the 0 ppm signal
hydroamination and hydrogenation in the media. Considering of external 85% H3PO4. 19F{1H} NMR spectra are referred to
these results and in order to avoid or diminish reactions other the −76.55 ppm signal of an external solution of CF3COOH.
than the hydroamination, we envisaged the use of a more
acidic nickel center to enhance and favor the nucleophilic
attack over the coordinated alkyne or alkene also aided by the
presence of activating substituents in the substrates. Herein,
we present the results of such investigations using different
nickel compounds as catalysts in the hydroamination of both
activated and unactivated alkynes and alkenes. The facile com-
mercial and/or synthetic availability of the ligands and nickel
precursors, as well as the easiness of the procedure, is
highlighted.
2.2 Hydroamination of acrylonitrile mediated by
[(diphos)Ni](OTf)2
In a vial, 40 mg (0.053 mmol) of the complex [(diphos)Ni]-
(OTf)2 were dissolved in 0.7 mL of CD2Cl2. Then, 2 equiv.
(7 μL, 5.8 mg, 0.11 mmol) of acrylonitrile were added. The
reaction mixture was transferred into a Wilmad NMR tube
with a J. Young valve and stirred and monitored for 24 h. In
the 31P{1H} NMR spectra a signal assigned to the complex
[(diphos)Ni(κ1-N-acrylonitrile)2](OTf)2 was observed. 1H NMR
(300 MHz, CD2Cl2): δ 7.94 (m, 8H), 7.64 (m, 4H), 7.47 (m), 6.18
2. Experimental
2.1 General considerations
(dd, J = 17.8, 0.8 Hz), 6.04 (dd, J = 11.7, 0.8 Hz), 5.62 (dd, J =
2
17.8, 11.7 Hz), 2.10 (d, JPH
=
17.4 Hz, 4H). 31P{1H}
(121.5 MHz) δ 57.2 (s). 19F NMR (282.2 MHz): −77.6 (s).
Unless otherwise noted, all experiments were carried out using
standard Schlenk techniques in a double vacuum-argon mani-
fold or in a glovebox (MBraun Unilab) under high purity argon
(Praxair 99.998) and controlled concentrations of water and
oxygen (<1 ppm). Catalytic experiments were carried out in
Schlenk tubes or in stainless steel Parr (T315SS) reactors. All
purchased liquid reagents were of reagent grade and degassed
before use. Alkenes 1a–d, alkynes 1e–p, pyrrolidine and
[(COD)2Ni] (COD = 1,3-cyclooctadiene) were purchased from
Aldrich and stored in the glovebox for further use. Phosphine
dippe (1,2-bis(diisopropylphosphino)ethane) was prepared
from 1,2-bis(dichloro)ethane (Aldrich) and a solution of iso-
To this mixture were added 2 equiv. (9 μL, 7.8 mg,
0.11 mmol) of pyrrolidine and the tube containing the reaction
mixture was sealed and heated at 60 °C for 4 h. After this time
and according to the 1H NMR spectrum, full conversion of the
starting material was observed. 1H NMR (300 MHz, CD2Cl2):
3
δ 2.67 (t, JHH = 6.9 Hz, 4H), 2.48 (m, 4H), 1.72 (m, 4H)
(Scheme S1, ESI†).
2.3 Catalytic hydroamination of activated alkenes and
alkynes with the complex [(diphos)Ni](OTf)2 formed in situ
propylmagnesium chloride (2.0 M, Aldrich) in THF. Phos- In a typical experiment, a Schlenk tube was charged with 5 mg
phines PEt3, diphos (1,2-bis(diphenylphosphino)ethane), dippf of [(diphos)NiCl2] (0.010 mmol), 4.85 mg of AgOTf
(1,1′-bis(diisopropylphosphino)ferrocene), and dppf (1,1′-bis- (0.020 mmol), 0.2 mmol of alkene (10.6 mg, 13 μL in the case
(diphenylphosphino)ferrocene) were purchased from Aldrich of acrylonitrile) and 14 μL (14.2 mg, 0.2 mmol) of pyrrolidine
and used without further purification. Phosphites P(OEt)3 and in 5 mL of a solvent (benzonitrile, THF or pyrrolidine). The
P(OPh)3 were purchased from Strem Chemicals and stored in tube was sealed and heated in an oil bath at 100 °C for 4 h.
the glovebox for further use. Solvents were dried using stan- After this time, the reaction mixture was cooled down to
dard techniques and stored in the glovebox over 4 Å molecular ambient temperature, exposed to the air and passed through
sieves for 24 h prior to use. Deuterated solvents were a column of celite. The filtrate was diluted 1 : 1 in THF and
purchased from Cambridge Isotope Laboratories and stored analyzed by GC-MS.
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2.4 Catalytic hydroamination of alkynes with neutral Ni(II)
3. Results and discussion
In a typical experiment, following the above described pro-
cedure, a Schlenk tube and/or a Parr reactor was charged with
5 mg of [(dippe)NiCl2] (0.013 mmol), 0.255 mmol of alkyne
(26 mg for phenylacetylene) and 5 mL of pyrrolidine without
the addition of any other solvent. The tube and/or the reactor
was heated at the desired temperature (100 or 180 °C) with
constant stirring for 72 h. The reaction mixture was cooled
down to ambient temperature and filtered through celite. The
filtrate was diluted in THF and analyzed by GC-MS.
In a first assessment to test the catalytic activity of nickel(II)
compounds, complex [(diphos)Ni](OTf)2 (1) was used in stoi-
chiometric amounts to yield the complex [(diphos)Ni(κ1-acrylo-
nitrile)](OTf)2 followed by the addition of two equivalents of
pyrrolidine to afford the hydroamination of acrylonitrile. The
corresponding hydroamination product could be obtained
quantitatively (>99% yield in 4 h at 60 °C) in CD2Cl2
(Scheme S1, ESI†). After knowing the feasibility of the use of 1
in the hydroamination of acrylonitrile, the same reaction was
assayed in a catalytic fashion with acrylonitrile and other
closely related substrates as shown in Table 1.
As shown in Table 1, excellent conversions were obtained
with acrylonitrile (1a) regardless of the solvent (entries 1–3,
Schemes S2 and S3, ESI†). Also, there is no significant effect
on the yield when the reaction time was shortened from 72 h
in dioxane to 3–4 h in THF or benzonitrile. These observations
are comparable to similar yields obtained with closely related
systems16,26,36 and are a reflection of the highly activated
nature of acrylonitrile. Nevertheless, other substrates related to
acrylonitrile, such as alkenes 1b and 1c (entries 4 and 5),
showed a rather different reactivity due to a remarkable depen-
dence on the steric hindrance. By using 1d, which bears
the same functional groups of acrylonitrile, no conversion
was observed possibly because of the lack of conjugation
between the cyano group and the π C–C bond, thus inhibiting
the transfer of the Lewis acidity of the metal center.
2.5 Hydroamination of alkynes at 80 psi catalyzed by
complexes of the type [(P–P)Ni(COD)2] and [((PR3)2)Ni(COD)2]
formed in situ
In a typical experiment, Ni(COD)2 (2.4 mg, 0.0087 mmol) and
the phosphine (dippf: 0.0087 mmol, 3.6 mg) were dissolved
separately in 2.5 mL of pyrrolidine. After 20 min of constant
stirring, the solution containing the phosphine was added
slowly to the [Ni(COD)2] solution and the resulting mixture
was kept under constant stirring for 30 min yielding a brown-
yellowish solution; later, to this was added 1-phenyl-1-propyne
(21.5 mL, 0.1709 mmol). The resulting solution was trans-
ferred to a Parr® reactor and this was closed, taken out from
the glovebox and pressurized with argon at 80 psi. After this,
the reactor was heated in an oil bath at the desired tempera-
ture for 72 h. Once the time was over, the reactor was cooled
down to ambient temperature and depressurized. Finally, the
reaction mixture was exposed to air, filtered and analyzed by
GC-MS.
In the light of these results, the same reaction conditions
were tested for a group of activated alkynes as shown in
Table 2.
2.6 Hydroamination of alkynes at 80 psi catalyzed by
complexes of the type [(P–P)NiCl2]
Table 1 Catalytic hydroamination of acrylonitrile and related substrates
In a typical experiment, 0.0102 mmol of catalyst (5.0 mg for
[(dippf)NiCl2]) was dissolved in 5 mL of pyrrolidine forming a
yellow solution. To this was added 1-phenyl-1-propyne
(25.5 μL, 0.2039 mmol) with no apparent change in the color
of the solution. The reaction mixture was kept under stirring
for 5 min, transferred to a Parr® reactor, pressurized with
argon (80 psi) and heated at the desired temperature for 72 h.
After this time, the reaction mixture was treated as described
above.
Entry Alkene
1
Solvent
Time (h) Product
72
Yielda (%)
100
Dioxane
2
3
4
Benzonitrile
THF
3
3
4
99
98
9
2.7 Hydroamination of alkynes at 80 psi catalyzed by
complexes of the type [(PR3)2NiCl2] formed in situ
In a typical experiment, 3.2 mg of NiCl2·6H2O (0.0135 mmol)
were dissolved in a minimal amount of ethanol and further
were added 7 μL (0.027 mmol) of P(OPh)3 keeping the solution
under constant stirring for 30 min. Then 2.5 mL of pyrrolidine
and 33.5 μL (0.1871 mmol) of 1-phenyl-1-propyne were added
forming a yellow solution, which was transferred to a Parr®
reactor, pressurized with argon (80 psi), and heated at the
desired temperature for 72 h. After this time, the reaction
mixture was treated similarly to the above described
procedure.
THF
5
6
THF
THF
4
4
—
—
0
0
a Chromatographic yields.
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Table 2 Catalytic hydroamination of activated alkynes
Scheme 1 Intramolecular hydroamination of 2-ethynylaniline (1j) cata-
lyzed by dicationic Ni(II).
Entry
1
Alkyne
Product
Yielda (%)
64
any hydroamination product, in contrast with the high yields
for other competing reactions such as cyclotrimerization (8%)
and homocoupling (37%) possibly formed via a C(sp)–H acti-
vation, whenever 1j is very prone to oligomerize. Additionally,
with other terminal alkynes such as 3-phenyl-1-propyne (1k)
and 4-pentyn-1-ol (1l) no products were detected.
In search of better conditions for the hydroamination of 1j,
the dicationic catalyst was replaced for less acidic nickel
centers and in neat conditions using pyrrolidine both as a
reagent and a solvent (Table 3).
2
60
3
4
—
—
0
0
In the majority of the above-presented cases, the hydroami-
nation products were observed, although the conversions and
relative distribution of the products depended on the nature of
the catalyst (entries 1 to 3, Schemes S8 and S9, ESI†). In
general, the use of neutral nickel(II), an ancillary phosphine –
diphos or dippe – and pyrrolidine as a solvent afforded the
desired enamine 2j. Indeed, the yields and distribution of the
products are quite similar among the experiments made with
these phosphines. On the other hand, even though the conver-
sion using a catalyst without a ligand is high (entry 3), the
hydroamination product is formed in a very low yield, hence
indicating the strong importance of such an ancillary ligand in
the hydroamination of phenylacetylene. By diluting the
amount of pyrrolidine in a 1 : 10 pyrrolidine–THF solution
(entry 4), no hydroamination was observed showing the
imperative use of pyrrolidine or, eventually, a protic solvent,
perhaps to form the enamine in a previous step to the closing
of the cycle, which involves a [1,3] proton transfer.37
Other by-products observed in these experiments include 3j
and its isomers, derived from the above-described homo-
coupling of phenylacetylene. 3j is also hydroaminated to form
4j and this, in turn, undergoes a C–C cleavage to form 5j
(Scheme S10, ESI†), perhaps through a previous CvC transfer
hydrogenation by pyrroline31 followed by the C–C scission.
At this point we envisaged the addition of pyrrolidine to
unactivated alkynes such as 1-phenyl-1-propyne (1m),
diphenylacetylene (1n) and 2-hexyne (1o), yet these attempts
were unsuccessful. Even by testing other nickel-based catalysts
ranging from dicationic and neutral nickel(II) to nickel(0) pre-
cursors such as [(dippe)Ni(µ-H)]2 (5) and [(COD)2Ni] (6), it was
not possible to obtain the expected enamines at 100 °C and
72 h. Nevertheless, when 6 is used in catalytic amounts and at
a higher temperature (180 °C), the corresponding enamine was
obtained (2m, 4%) (Scheme 2). In addition, 1,3,5-triphenyl-
benzene (4m) was also observed as the cyclotrimerization
product of the starting material, which indeed is a common
product of the reaction of alkynes in the presence of zerovalent
nickel.38 Thereby, the obvious choice was to replace the catalyst
a Chromatographic yields.
With alkynes 1e and 1f, the corresponding hydroamination
products are obtained in moderate yields (entries 1 and 2,
Schemes S4 and S5, ESI†), although not as high as with acrylo-
nitrile, perhaps due to the lower activating effect of the ester
moiety compared to the cyano group. It is worth mentioning
that the possible steric effect caused by the extra methylene in
1f does not significantly affect the total conversion because of
the lower steric demand of the alkyne toward nucleophilic
attack by pyrrolidine compared to the above presented alkenes
(vide supra). Once again, the lack of reactivity of substrates 1g
and 1h, when compared with the same behavior of 1d,
suggests that the activating group necessarily must be conju-
gated to the C–C unsaturation in order to effectively coordinate
the substrate to the acidic metal center through a hard donor
and then transfer the Lewis acidity to the C–C unsaturation,
thus, facilitating the nucleophilic attack by the amine
(Fig. 1).16,27
In the same manner, successful conversions were obtained
for the intramolecular hydroamination of 2-ethynylaniline (1i)
in 36% yield to the corresponding indole (Scheme 1 and
Schemes S6, S7, ESI†), resulting in a comparable result to the
one obtained with a nickel(0) center.31 Nevertheless, when
these conditions were applied in the intermolecular hydroami-
nation of phenylacetylene (1j), even though there were
moderate conversion percentages (45%), we did not observe
Fig. 1 Proposed effect of the electronic conjugation on the hydro-
amination of activated alkenes catalyzed by nickel(II) complexes.
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Table 3 Hydroamination of phenylacetylene catalyzed by neutral Ni(II)
Entry
Cat.
Solvent
2ja (%)
3ja (%)
4ja (%)
5ja (%)
1
2
3
4
[(diphos)NiCl2] 2
[(dippe)NiCl2] 3
NiCl2·6H2O 4
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine–THF 1 : 10
22
25
6
12
18
11
57
38
28
37
0
28
27
46
0
[(dippe)NiCl2] 3
0
a Chromatographic yield.
Table 4 Catalytic hydroamination of 1-phenyl-1-propyne (1m) under
neat conditions and 80 psi of argon
Scheme 2 Catalytic hydroamination of 1-phenyl-1-propyne (1m).
T
2ma
5ma
3ma
4ma
Entry
Cat.
(°C)
(%)
(%)
(%)
(%)
1
2
3
4
5
6
7
8
9
[(dippf)Ni(COD)] 7
[(dppf)Ni(COD)] 8
[(dippf)NiCl2] 9
[(dppf)NiCl2] 10
[(P(OEt)3)2Ni(COD)] 11
[(PEt3)2NiCl2] 12
[(P(OPh)3)2Ni(COD)] 13
[(P(OPh)3)2Ni(COD)] 13
[(P(OPh)3)2NiCl2] 14
160
160
160
160
160
160
140
120
140
12
51
43
32
7
5
54
6
0
0
0
0
0
16
10
3
75
14
15
26
58
51
0
0
0
0
by a less basic metal center and, in this regard, the cyclo-
trimerization by-product was drastically diminished to 3%
and, at the same time, the desired enamine was obtained in a
considerably higher yield (29%, Schemes S11 and S12, ESI†) by
using 3 as a catalyst. These observations evidence, again, the
competition between the hydroamination of alkynes and other
side reactions.
0
8b
0
0c
0
2
0
42
16
0
a Chromatographic yield. b Additionally, 28% dimerization of 1m was
obtained. c 3% dimerization of 1m was obtained.
As depicted in Scheme 2, it was observed that 29% was the
best yield for the hydroamination of 1m. A presumable reason
for this was the limited mass transfer in the reaction media,
since the boiling point of 1m is only 5 °C above the tempera-
ture reached in these experiments. Therefore, we implemented
the use of argon pressure to enhance such a mass transfer by
avoiding the evaporation of the starting material. In addition,
some other nickel-based catalysts were tested under these
conditions. Pertinent results of these experiments are shown
in Table 4.
Table 5 Hydroamination of alkynes catalyzed by [((PhO)3P)2NiCl2]
According to what is shown in Table 4, with some catalysts,
particularly with 8–10, 13 and 14, better yields for the hydro-
amination product were obtained thus showing a remarkable
enhancement of the yield by raising the pressure with argon
and using other catalytic precursors. Once again, the selectivity
is highly affected with the use of low-valent nickel (entries 1
and 5) or σ-donor phosphines (entry 6), which eventually
afford a more basic metal center and, hence, the formation of
undesired hydrogenation or coupling products (3m–5m). In
this context, the hydrogenation products were diminished or
even inhibited by slightly lowering the temperature (entries 7
to 9, Scheme S13, ESI†) and the better conditions were found
to involve such lower temperatures and a π-acceptor phosphine
(entry 9). These optimized conditions were used to achieve the
hydroamination of a series of other alkynes as can be seen
in Table 5.
Entry
1
Alkyne
Product
Yielda (%)
29
2
3
4
20
78
91
a Chromatographic yield.
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characteristics of the “(P–P)Ni” fragment (dicationic versus
neutral) and this fact has given us a better insight aiming to
improve the activity and selectivity of this nickel catalyzed
process. Current studies are, in fact, underway to enhance
such selectivity with other phosphite and phosphonite ligands
and aiming to adapt this method for use under a non-inert
atmosphere.
Table 6 Catalytic hydroamination of diphenylacetylene (1n)
Entry
Cat.
T (°C)
t (h)
2na (%)
3na (%)
1
2
3
4
5
6
[(PEt3)2NiCl2] 12
140
140
140
140
140
160
72
72
72
72
216
216
22
39
16
27
36
16
11
3
0
6
3
[(P(OEt)3)2NiCl2] 15
[(PPh3)2NiCl2] 16
[(P(OPh)3)2NiCl2] 14
[(P(OEt)3)2NiCl2] 15
[(P(OEt)3)2NiCl2] 15
Acknowledgements
25
Financial support from CONACYT (178265) and UNAM-DGAPA
(IN-210613) is gratefully acknowledged. A. R.-S. thanks
CONACYT (254535) for a scholarship for graduate studies. We
also thank Dr Alma Arévalo for her technical assistance.
a Chromatographic yield.
The alkynes employed in Table 5 are more activated than
1-phenyl-1-propyne and therefore better yields and selectivities
could be successfully obtained (Schemes S14–S21, ESI†). In
fact, the hydrogenation of the starting material was completely
inhibited. In previous experiments without the additional
argon pressure and by using 1, 3 or 6, the hydroamination of
1n and 1g was not observed at all (vide supra). In sharp con-
trast, with the conditions shown in Table 5, the desired enam-
ines for such alkynes were successfully obtained in moderate
yields (entries 1 and 2). In the same way, the yield for the
hydroamination of 1e (entry 4) was dramatically higher (91%)
than that with the use of dicationic nickel (1) at a lower
pressure (Table 2, entry 1, 64%).
References
1 M. B. Smith and J. March, March’s Advanced Organic Chem-
istry, John Wiley and Sons, New York, 5th edn, 2001.
2 F. Alonso, I. P. Beletskaya and M. Yus, Chem. Rev., 2004,
104, 3079–3159.
3 T. E. Müller, K. C. Hultzsch, M. Yus, F. Foubelo and
M. Tada, Chem. Rev., 2008, 108, 3795–3892.
4 G. Zi, F. Zhang, X. Liu, L. Ai and H. Song, J. Organomet.
Chem., 2010, 695, 730–739.
5 L. Ackermann, R. Sandmann, A. Villar and L. T. Kaspar,
Tetrahedron, 2007, 64, 769–777.
6 S. Doye, Synlett, 2004, 1653–1672.
7 L. Ackermann, R. G. Bergman and R. N. Loy, J. Am. Chem.
Soc., 2003, 125, 11956–11963.
In order to improve the yield for the hydroamination of 1n,
several other catalysts and reaction conditions were assessed.
Representative results of such experiments are shown in
Table 6.
Once again, better yields were obtained with π-acidic phos-
phines (entry 2 and Scheme S22, ESI†) and, in contrast, the
use of not so acidic ligands (16) or even σ-donating ligands
(12) gave lower conversions and/or higher yields for the un-
desired hydrogenation by-products. Therefore, the best yields
for the hydroamination product (2n) were obtained with 15 as
a catalyst at 140 °C. Using this catalyst at longer reaction times
(entry 5) does not significantly improve the transformation to
2n and a higher temperature (entry 6) ultimately has a negative
effect by decreasing the hydroamination and favoring the
hydrogenation product (Scheme S23, ESI†).
8 A. E. Strom and J. F. Hartwig, J. Org. Chem., 2013, 78, 8909–
8914.
9 B. D. Stubbert and T. J. Marks, J. Am. Chem. Soc., 2007, 129,
4253–4271.
10 A. Motta, I. L. Fragala and T. J. Marks, Organometallics,
2006, 25, 5533–5539.
11 S. Hong and T. J. Marks, Acc. Chem. Res., 2004, 37, 673–686.
12 S. Hong, S. Tian, M. V. Metz and T. J. Marks, J. Am. Chem.
Soc., 2003, 125, 14768–14783.
13 E.-i. Negishi, Handbook of organopalladium chemistry for
organic synthesis, John Wiley and Sons Inc., New York,
2002.
14 A. M. Johns, M. Utsunomiya, C. D. Incarvito and
J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 1828–1839.
15 T. E. Müller, M. Grosche, E. Herdtweck, A.-K. Pleier,
E. Walter and Y.-K. Yan, Organometallics, 1999, 19, 170–183.
4. Conclusions
We have successfully developed a methodology for the hydro-
amination of both activated and unactivated organic unsatura- 16 C. Munro-Leighton, S. A. Delp, E. D. Blue and
tions catalyzed by affordable nickel complexes, which, along T. B. Gunnoe, Organometallics, 2007, 26, 1483–1493.
with other investigations derived from the use of nickel as a 17 S. Zhu, N. Niljianskul and S. L. Buchwald, J. Am. Chem.
catalyst, could contribute to finding cheaper and more bio- Soc., 2013, 135, 15746–15749.
compatible alternatives to palladium or other expensive 18 V. H. Wong, T. S. Hor and K. K. Hii, Chem. Commun., 2013,
metals. In this particular case, the conversions and selec- 49, 9272–9274.
tivities have been shown to be remarkably influenced by 19 Y. Liu, G. Wu and Y. Cui, Appl. Organomet. Chem., 2013, 27,
the nature of the ancillary ligands and the electronic
206–208.
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Dalton Transactions
20 J. Michaux, V. Terrasson, S. Marque, J. Wehbe, D. Prim and 30 L. Ackermann, W. Song and R. Sandmann, J. Organomet.
J.-M. Campagne, Eur. J. Org. Chem., 2007, 2601–2603. Chem., 2011, 696, 195–201.
21 K. Komeyama, T. Morimoto and K. Takaki, Angew. Chem., 31 A. Reyes-Sánchez, F. Cañavera-Buelvas, R. Barrios-
Int. Ed., 2006, 45, 2938–2941.
22 L. Fadini and A. Togni, Tetrahedron: Asymmetry, 2008, 19,
2555–2562.
23 L. Fadini and A. Togni, Helv. Chim. Acta, 2007, 90, 411–424.
24 L. Fadini and A. Togni, Chem. Commun., 2003, 30–31.
25 C. Dash, M. M. Shaikh, R. J. Butcher and P. Ghosh, Inorg.
Chem., 2010, 49, 4972–4983.
Francisco, O. L. Cifuentes-Vaca, M. Flores-Alamo and
J. J. García, Organometallics, 2011, 30, 3340–3345.
32 F. Scott, C. Krüger and P. Betz, J. Organomet. Chem., 1990,
387, 113–121.
33 D. A. Vicic and W. D. Jones, J. Am. Chem. Soc., 1997, 119,
10855.
34 P. Byabartta, Transition Met. Chem., 2007, 32, 576–583.
26 A. B. Salah, C. Offenstein and D. Zargarian, Organo- 35 N. M. Brunkan and M. R. Gagné, Organometallics, 2002, 21,
metallics, 2011, 30, 5352–5364.
27 A. Castonguay, D. M.
1576–1582.
Spasyuk,
N.
Madern, 36 C. Dash, M. M. Shaikh, R. J. Butcher and P. Ghosh, Dalton
A. L. Beauchamp and D. Zargarian, Organometallics, 2009,
28, 2134–2141.
Trans., 2010, 39, 2515–2524.
37 R. Q. Su and T. E. Müller, Tetrahedron, 2001, 57, 6027–
28 T. E. Muller and A.-K. Pleier, J. Am. Chem. Soc., 1999, 583–588.
6033.
29 J. Hu, L. Liu, X. Wang, Y. Hu, S. Yang and Y. Liang, Green 38 B. L. Edelbach, R. J. Lachicotte and W. D. Jones, Organo-
Sustain. Chem., 2011, 1, 165–169. metallics, 1999, 18, 4040–4049.
1768 | Dalton Trans., 2014, 43, 1762–1768
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