Cobalt-Catalyzed and Lewis Acid-Assisted Nitrile Hydrogenation to Primary Amines: A Combined Effort

Article abstract of DOI:10.1021/jacs.7b07368

The selective hydrogenation of nitriles to primary amines using a bench-stable cobalt precatalyst under 4 atm of H₂ is reported herein. The catalyst precursor was reduced in situ using NaHBEt₃, and the resulting Lewis acid formed, BEt₃, was found to be integral to the observed catalysis. Mechanistic insights gleaned from para-hydrogen induced polarization (PHIP) transfer NMR studies revealed that the pairwise hydrogenation of nitriles proceeded through a Co(I/III) redox process.

Full text of DOI:10.1021/jacs.7b07368

Article
pubs.acs.org/JACS
Cobalt-Catalyzed and Lewis Acid-Assisted Nitrile Hydrogenation to
Primary Amines: A Combined Effort
†
†
Kenan Tokmic, Bailey J. Jackson, Andrea Salazar, Toby J. Woods, and Alison R. Fout*
School of Chemical Sciences, University of Illinois at Urbana−Champaign, 600 S. Mathews Avenue, Urbana, Illinois 61801, United
States
*
S Supporting Information
ABSTRACT: The selective hydrogenation of nitriles to
primary amines using a bench-stable cobalt precatalyst under
4
atm of H is reported herein. The catalyst precursor was
2
reduced in situ using NaHBEt , and the resulting Lewis acid
3
formed, BEt , was found to be integral to the observed catalysis.
3
Mechanistic insights gleaned from para-hydrogen induced
polarization (PHIP) transfer NMR studies revealed that the
pairwise hydrogenation of nitriles proceeded through a Co(I/
III) redox process.
INTRODUCTION
relatively lower cost, late first-row transition metals present
■
themselves as promising alternatives to their second- and third-
Developments for the selective formation of primary amines
have continued to attract interest because of their importance
in the bulk and fine chemical industries. Reduction of nitriles to
primary amines is commonly accomplished using heteroge-
18,19
row congeners.
Recent work by Beller demonstrates the utility of
incorporating bifunctional motifs into manganese- and iron-
20−22
1
−3
based nitrile hydrogenation systems.
Iron and cobalt
neous hydrogenation processes;
however, stoichiometric
4,5
catalysts developed by the Milstein group also carry out this
transformation, citing metal-hydride intermediates for the
amounts of promiscuous metal-hydride sources can also be
employed. In these cases, the functional group tolerance is
limited due to the harsh conditions typically used, and the
selectivity toward the formation of primary amines decreases
due to side reactions (Scheme 1). Among the synthetic
methodologies for the formation of primary amines, the
23,24
observed reactivity.
Very recently, a cobalt catalyst solely
featuring phosphine ligands was reported to carry out this
transformation; however, the operative mechanism has not yet
1
25
been elucidated. Exclusively metal-centered nitrile hydro-
genation using first-row transition metals has remained elusive,
and experimental investigations into this approach would
selective and catalytic reduction of nitriles using H represents
the most atom-economical route.
2
further advance the potential of such strategies.
Mes
Our group reported the cobalt complex, ( CCC)Co(H )-
Scheme 1. Primary Amine and Secondary Imine Formation
during Nitrile Hydrogenation
2
Mes
PPh ( CCC = bis(mesityl-benzimidazol-2-ylidene)phenyl),
3
which was active for the hydrogenation of terminal olefins and
2
6,27
the E-selective semihydrogenation of internal alkynes.
1
Mechanistic insights from H NMR spectroscopy and para-
hydrogen (p-H ) induced polarization (PHIP) transfer NMR
2
studies revealed a metal-centered Co(I/III) redox process was
operative. Reasoning that the multielectron redox process is a
direct result of incorporating the strong-field bis(carbene)
ligand as part of the catalytic system, we set out to determine
the competency of these cobalt complexes in the hydrogenation
of nitriles.
Investigations using low-valent late first-row transition metal
complexes for catalytic transformations face a significant
limitation from their greater sensitivity to air and moisture
compared to their platinum group congeners. To overcome this
challenge, the in situ activation of stable precursors,
Homogeneous counterparts are often more selective for
primary amines and operate under milder conditions. Catalytic
6
7−15
16−17
systems based on rhenium, ruthenium,
and rhodium
complexes have been shown to effectively mediate the
hydrogenation of nitriles to primary amines. Although these
catalytic systems present good activity and selectivity, cost and
environmental implications have motivated investigations into
more sustainable systems. Due to the inherent abundance and
Received: July 24, 2017
©
XXXX American Chemical Society
A
DOI: 10.1021/jacs.7b07368
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Article
‡
Table 1. Nitrile Hydrogenation Substrate Scope
‡
a
t
Conversion (>99%) determined by GC−MS. Yields were of the isolated hydrochloride salts. Catalyst (4 mol %), NaHBEt (8 mol %), KO Bu (12
3
b
mol %). GC−MS conversion was not determined; yields were of the isolated hydrochloride salts.
generally higher oxidation state metal sources, is accomplished
by employing readily available Grignard or metal hydride
prevented the formation of the secondary imine, as has been
1
reported in other systems (Scheme 1). A variety of bases were
2
8−32
t
reagents,
or metal alkoxides, as recently demonstrated by
examined (Table S1), and KO Bu proved to furnish the best
33
Mes
Thomas and co-workers. Naturally, ( CCC)Co(H )PPh3
yield of the primary amine (97%). Lowering the H pressure,
2
2
oxidizes upon exposure to air, so we sought to determine the
feasibility of a bench-stable Co(III) analogue for the hydro-
temperature, or reaction time resulted in either diminished
yield of the primary amine or no conversion of the nitrile.
Furthermore, the ability of other cobalt sources to mediate this
transformation were examined. (PPh ) CoN(SiMe ) , which
34
genation of nitriles. Encouraged by our previous studies
demonstrating that lower oxidation states of cobalt can be
3
2
3 2
26
accessed using a hydride source, we sought to use a
catalyzes C−N bond formation and the hydroboration of
35,36
commercially available source, NaHBEt , as the in situ activator.
3
olefins,
(PPh ) CoCl, and Co(acac) were inactive for the
3 3 3
Herein the selective hydrogenation of nitriles to primary
hydrogenation of nitriles to primary amines (Table S1).
Mes
amines using a bench-stable catalyst precursor, ( CCC)-
Substrate Scope. The optimized reaction parameters
CoCl py (1, py = pyridine), under low H pressure (4 atm) is
2
2
(toluene, 115 °C, 8 h, 4 atm H ) were determined and the
2
described. Mechanistic insights stemming from PHIP transfer
NMR studies as well as stoichiometric reactions demonstrate
the dual role of NaHBEt3 in the observed catalysis: (1)
reduction of the Co(III) precursor to the Co(I) active catalyst
and (2) hydrogenation of the nitrile functionality induced by
scope of this system toward both aromatic and aliphatic nitriles
was investigated (Table 1). Aromatic substrates with electron-
donating groups including methoxy, methyl, and naphthyl were
hydrogenated in high yields (1b−1g, 1m). Sterically hindered
substrates featuring ortho-substitution were tolerated (1d,1g).
Electron-withdrawing groups including fluoro, chloro, and
trifluoromethyl proceeded with slightly lower yields (1j−1l).
Anilines (1h−1i) were also tolerated under reaction conditions,
but phenols resulted in decomposition of the catalyst (Table
S2). The use of 4-acetylbenzonitrile gave only starting material.
Nitriles featuring nitro and amide functionalities were not
amenable to hydrogenation (Table S2). Additionally, on the
basis of our previous work, carbon−carbon multiple bonds
the resulting Lewis acid, BEt3.
RESULTS AND DISCUSSION
■
Optimization of Reaction Conditions. Akin to previously
23,24
reported systems,
we set out to optimize the reaction
parameters (base, temperature, and time) using benzonitrile as
t
a model substrate (Table S1). The use of 1 (2 mol %), KO Bu
(
4
6 mol %), and NaHBEt (4 mol %) in toluene at 115 °C under
3
26,27
atm of H for 8 h resulted in complete conversion of the
would be reduced under these conditions.
Increased
2
nitrile with excellent selectivity to the primary amine product as
determined by GC−MS (Table S1). N-benzylidenebenzyl-
amine was the sole product when the reaction was carried out
without base (Table S1, Entry 2). Thus, the addition of a base
catalyst loading for 1c, 1d, 1k, and 1l corresponded to an
increase in yield.
Aliphatic substrates including phenylacetonitrile (1o) and 3-
phenylpropionitrile (1p) gave 78 and 88% yield, respectively,
B
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while cyclohexylnitrile (1q) yielded 85% product. Alkyl nitriles
(
1r−1v) gave good yields when isolated as the hydrochloride
salts. Two unprecedented examples of first-row homogeneous
nitrile hydrogenation include acetonitrile (1r) and t-butylnitrile
(1s). Ethylamine is widely employed in industry, and the
hydrogenation of acetonitrile presents an atom-economical
37
synthesis for this product. The low yield (39%) of ethylamine
hydrochloride from acetonitrile likely arises from product loss
during the workup procedure due to the volatility of ethylamine
(
bp = 16−20 °C).
These results, as well as the retention and selectivity upon
scaling up the hydrogenation of 4-methylbenzonitrile (200 mg,
9
7%), demonstrate the utility of this system in hydrogenating
nitriles under low hydrogen pressure and moderate temper-
atures using a bench-stable cobalt precatalyst. However, to fully
understand the nuances of our system, detailed mechanistic
studies examining the nature of H addition and the active
2
species were needed. Such studies would delineate the metal-
centered reactivity from bifunctional motifs and resemble the
multielectron catalytic processes observed in similar cobalt
26,27,38,39
bis(carbene) complexes.
Mechanistic Studies. In the interest of probing the
1
reaction mechanism, in situ H NMR studies of the catalytic
nitrile hydrogenation were investigated. We previously reported
2
1
a PHIP transfer NMR study of a related Co(η -H )
Figure 1. H NMR (C
7
D
8
, 600 MHz) spectrum of 1 (2 mol %),
2
t
NaHBEt (4 mol %), KO Bu (6 mol %), and 4-methoxybenzonitrile
under 4 atm of p-H at 85 °C collected using a 45° pulse (top) and
H-OPSY pulse (bottom).
bis(carbene) pincer catalyst for the pairwise hydrogenation of
3
26,27
carbon−carbon multiple bonds.
Accordingly, a PHIP
2
1
transfer NMR study of the hydrogenation of nitriles under
catalytic conditions with p-H2 was employed to provide
mechanistic insights (vide infra) due to the intrinsic properties
of PHIP.
53,54
PASADENA
(para-hydrogen and synthesis allow dramat-
ically enhanced nuclear alignment) effect was observed. In this
case, the transfer of p-H occurred inside (high-field) the NMR
spectrometer at 85 °C with retention of the spin−spin coupling
between the H−H atoms. The use of a double-quantum OPSY
pulse sequence further corroborated the pairwise hydro-
genation of the nitrile group (Figure 1, bottom). The
hyperpolarization resulting from the hydrogenation of a nitrile,
imine, or other polar functionalities with p-H has not been
demonstrated thus far, with only non-hydrogenative means
having been observed.
observed when using 4-(trifluoromethyl)benzonitrile (Figure
S12).
Although the formation of the primary amine product was
also observed in the H NMR spectrum, a PHIP effect was not
seen for the corresponding protons (R−CH −NH ), suggest-
ing a different mechanism may be operative for the hydro-
genation of the imine. One possible mechanism for imine
hydrogenation involves a non-pairwise transfer of H by an
inner-sphere hydride-transfer mechanism.
hydrogenation of the imine proceeds too slowly,
PHIP transfer NMR spectroscopy has been demonstrated as
2
4
0−44
an effective analytical method to study heterogeneous
and
4
5−49
homogeneous hydrogenation reactions, H reactivity with
metal complexes, and, in rare instances, metal-free com-
2
5
0,51
pounds.
By creating a non-Boltzmann distribution of
nuclear spin-states, PHIP transfer NMR spectroscopy has also
allowed for the detection of reaction intermediates that may not
otherwise be amenable toward characterization by conventional
2
1
55−61
spectroscopic techniques. Hyperpolarization of H NMR
The PASADENA effect was also
signals resulting from PHIP are an indication of the pairwise
addition of the H atoms of p-H to magnetically distinct
2
positions on a substrate. Moreover, the characteristic emission
1
1
and absorption signals are observed in situ via H NMR
spectroscopy when the addition of p-H occurs faster than the
2
2
2
relaxation rate of the corresponding nuclei, and the spin−spin
coupling of the added p-H in the hydrogenated product is
2
retained. In the studies presented herein, a 45° pulse and a
2
5
2
62,63
double quantum OPSY (only para-hydrogen spectroscopy)
However, if the
1
64,65
filter in the H NMR experiment were used following the
or the
addition of p-H (see Supporting Information (SI)).
protons of the amine readily exchange with protic function-
alities, then the PHIP effect would also be thwarted.
2
We chose 4-methoxybenzonitrile for the 1H NMR
mechanistic investigations since the methoxy group (R-
Intrigued by the PHIP data, we performed additional
mechanistic and stoichiometric studies to define the active
catalytic species. To this end, the reactivity between 1 and
1
OCH ) provides a discernible H NMR resonance in the
3
nitrile and hydrogenation products (imine and amine). The
addition of p-H to a toluene-d solution consisting of 4-
NaHBEt was explored. We hypothesized that the treatment of
2
8
3
methoxybenzonitrile, 1 (2 mol %), NaHBEt (4 mol %), and
KO Bu (6 mol %) did not result in the observation of
hyperpolarized resonances at 30 or 60 °C. Polarization of the
1 with NaHBEt would reduce the precatalyst to an active
3
3
t
Mes
cobalt(I) species proceeding through a ( CCC)Co−(H)
2
intermediate, followed by reductive coupling of H . Accord-
2
imine moiety (R-HCNH) was seen (Figure 1) when the
ingly, treatment of a solution of 1 in benzene-d with 2 equiv of
6
solution was heated to 85 °C. Although the p-H was added
NaHBEt in a J. Young NMR tube resulted in the formation of
2
3
1
outside the NMR spectrometer (low-field) and at room
a brown solution. Monitoring by H NMR spectroscopy
temperature before being inserted into the spectrometer, the
revealed broadened downfield resonances corresponding to the
C
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Scheme 2. Synthesis of Complexes 2-py, 2-NCArOCH , 3-NCPh, and 3-NCArOCH
3
3
Figure 2. Molecular structures of 2-py and 3-NCPh depicted with 50% probability ellipsoids and 3-NCArOCH shown at 30% probability. Solvent
3
and H atoms have been omitted for clarity. Table S2 contains bond lengths and angles.
aryl protons, while the retention of a C -symmetric complex
S1 and S8). A C -symmetric complex was present in solution,
2
2
was discerned by the corresponding mesityl−CH resonances
as indicated by the two mesityl−CH resonances of 2-py at 1.96
3
3
at 1.99 and 1.92 ppm (Figure S9). Examining the reduction,
solution IR spectroscopy revealed an intense absorption at
and 1.83 ppm. Integration of the corresponding resonances in
1
the H NMR spectrum revealed the retention of the pyridine
−
1
Mes
2
(
082 cm , tentatively assigned as a ( CCC)Co−N complex
ligand in the reduced species. In contrast, a ligand derivative
2
1
vide infra). The formation of H was not observed by H
featuring 2,6-diisopropylphenyl flanking groups loses pyridine
2
3
4
NMR spectroscopy.
upon reduction and yields a 16-electron Co(I)−N complex.
2
Despite the fact that H was not observed, the addition of
Examining 2-py by solution IR spectroscopy revealed the
absence of a Co−N moiety, further confirming the H NMR
2
1
styrene to the previous reaction resulted in the formation of
2
Mes
ethylbenzene, indicative of the formation of ( CCC)Co−
assignment of this complex. To unambiguously determine the
molecular structure of 2-py, single crystals suitable for X-ray
diffraction studies were grown from a saturated diethyl ether
solution. The four-coordinate cobalt center adopts a square
(
H) in situ. Alternatively, using Cp ZrHCl (Cp = cyclo-
2
2
pentadienyl) as the hydride source resulted in a new complex,
Mes
(
CCC)Co−py (2-py) (vide infra) with concomitant
formation of H (Figure S8). Furthermore, the IR spectrum
planar geometry, with the pyridine ligand trans to the Co−C
2
aryl
did not contain a dinitrogen stretch, indicating that a Co−N2
complex was not present. After unsuccessful attempts to isolate
the reduced species from the corresponding byproducts, an
alternative route was used for preparation of 2-py.
bond (Figure 2).
After successfully isolating 2-py, we were interested in
understanding the coordination of the nitrile to the metal
1
center to corroborate the PHIP H NMR studies, which
The reduction of 1 with 2 equiv of KC afforded 2-py in 80%
yield (Scheme 2). Characterization of 2-py by H NMR
spectroscopy displayed a diamagnetic species that matched the
suggest that this transpires during catalysis. Accordingly, 1
8
1
equiv of 4-methoxybenzonitrile was added to 2-py yielding
Mes
(
CCC)Co(p-NCC H −OCH ) (2-NCArOCH ) (see SI).
6
4
3
3
1
product formed from the addition of Cp ZrHCl to 1 (Figures
Characterization by H NMR spectroscopy revealed a similar
2
D
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coordination environment to that of 2-py with the integrations
suggesting the coordination of one nitrile ligand (Figure S3).
Furthermore, examining this species by IR spectroscopy
pyridine is not necessary for the catalysis to proceed (Table
2
, Entry 8).
−1
revealed an intense absorption at 2184 cm , which is red-
−
1
−1
shifted by 32 cm from the free nitrile (νCN = 2216 cm ) and
66
is consistent with an end-on coordination mode.
Attempts to grow single crystals of 2-NCArOCH suitable
3
for structural determination studies proved unsuccessful.
However, with the addition of 1 equiv of PPh3 to 2-
NCArOCH , single crystals of 3-NCArOCH were obtained.
3
3
Alternatively, the addition of benzonitrile to the previously
Mes
26
reported ( CCC)Co(N )(PPh ) complex furnishes 3-
2
3
NCPh (see SI). The cobalt center in 3-NCArOCH and 3-
3
NCPh adopts a square pyramidal geometry (τ = 0.25 and 0.19,
6
7
respectively) with the nitrile bound trans to the Co−C
aryl
Figure 3. Reaction profile of the hydrogenation of 4-methoxybenzoni-
bond. The C≡N bond distances in 3-NCArOCH and 3-NCPh
1.165(7) Å and 1.157(3) Å, respectively) are within error of
the free molecules (1.1516(16) Å and 1.16 Å, respectively
3
t
trile with 2−py (2 mol %), BEt (4 mol %), and NaO Bu (6 mol %) in
3
(
68,69
toluene-d under 4 atm of H .
8 2
)
(
Figure 2). Additionally, vibrational modes in the IR spectrum
corresponding to the bound nitriles are observed at 2202 and
191 cm− for 3-NCArOCH and 3-NCPh. These are red-
1
2
3
To gain further mechanistic insights into the observed Lewis
acid-assisted catalysis, we next monitored the reaction profile of
a catalytic run. Even though mixtures were not observed when
isolating each amine, the detection of side-products throughout
the catalytic process would provide insights into the observed
selectivity. Accordingly, the concentrations of the reaction
components of a catalytic run were monitored to probe the
reaction progress using GC−MS analysis (Table S1). During
these studies, the primary imine intermediate was not observed
due to its reactive nature. Instead, the reaction profile was
−1
shifted from the free nitriles by 14 and 41 cm , respectively,
and support the end-on coordination mode of the nitrile to the
cobalt center.
Having established that the nitrile coordinates to the reduced
cobalt species in an end-on fashion, we next explored the
competency of 2-py and 2-NCArOCH for nitrile hydro-
3
t
genation. Using 2-py (2 mol %), KO Bu (6 mol %), and 4 atm
of H , the hydrogenation of 4-methylbenzonitrile did not
2
proceed, and only starting material was recovered (Table 2,
1
monitored in situ using H NMR spectroscopy to obtain a
more accurate representation of the reaction components
Table 2. Lewis Acid Screen for Catalysis
(
Figures 3 and S15).
The plot shows the decrease of the nitrile and initial increase
of the primary imine concentration, followed by consumption
of the primary imine and the steady increase in the primary
amine product. Notably, the formation of the secondary imine
is limited, suggesting that the primary imine is favored over the
secondary imine throughout the course of catalysis. The
addition of 1 equiv of the corresponding amine (with respect to
the nitrile) did not change the time required for the reaction to
reach completion, indicating an increased amine concentration
does not inhibit catalytic activity.
a
entry
catalyst
additive
substrate
yield (%)
b
1
2
3
4
5
6
7
8
2-py
-
R = H
R = 4Me
R = 4Me
R = 4Me
R = 4Me
R = 4Me
R = 4OMe
R = 4OMe
-
1
NaHBEt3
BEt3
95
91
82
70
98
91
92
2-py
2-py
LiOTf
Ca(OTf)2
BPh3
2-py
We next questioned if the presence of a Lewis acid was
necessary for the hydrogenation of the imine to proceed. Use of
a primary imine surrogate, N-benzylidenebenzylamine, in the
absence of Lewis acid yielded 10% conversion of the starting
material to the secondary amine as observed by GC−MS. In
2-py
1
NaHBEt3
BEt3
2-NCArOCH3
a
b
Isolated yield of the hydrochloride salt. Starting material only.
contrast, the addition of BEt (4 mol %) resulted in 90%
3
conversion to the amine. Therefore, the Lewis acid also
facilitates this second hydrogenation step but is not necessary
for the reaction to occur.
In view of these findings, we next re-examined the
hydrogenation of 4-acetylbenzonitrile, a substrate that proved
unamenable toward hydrogenation using previous reaction
conditions (vide supra). We recognized that the Lewis acid is
necessary for catalysis, so it was postulated that an interaction
of the Lewis acid with the ketone functionality could inhibit
catalytic turnover. Accordingly, the addition of 1.04 equiv of
Entry 1). Under optimized catalytic conditions, 2 equiv of
NaHBEt activates the precatalyst, with subsequent formation
3
of BEt . To our surprise, the addition of 2 equiv of BEt (4 mol
3
3
%
) to the 2-py catalyzed reaction enabled the hydrogenation to
proceed (Table 2, entry 3). This result suggests the borane,
acting as a Lewis acid, is intimately involved in the catalysis. To
further evaluate the necessity of Lewis acids in the catalysis,
BPh , LiOTf, and Ca(OTf) were targeted. The addition of
3
2
each Lewis acid to the catalytic reaction resulted in the
hydrogenation of 4-methylbenzonitrile to the primary amine
BEt with respect to the substrate furnished the primary amine
3
(
Table 2, Entry 4−6). The addition of 2-NCArOCH (2 mol
in 95% yield (Scheme 3). Notably, the ketone functionality was
not reduced under these conditions, which is a distinct
3
t
%
) to 2 equiv of BEt (4 mol %) and KO Bu (6 mol %) resulted
3
21
70,71
72
in the hydrogenation of 4-methoxybenzonitrile, indicating
difference from iron, ruthenium,
and palladium systems.
E
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Scheme 3. Nitrile Hydrogenation with Ketone Functionality
increasing electron-donating ability of the ligands, and
therefore, the nitrile group becomes more negatively charged.
79
On the basis of these studies and those presented herein, the
most viable role of the Lewis acid in the observed catalysis is
depicted in Figure 4.
The increase in Lewis acid equivalents was applied to formyl
and thio functionalities but did not improve catalysis.
To further understand the role of the Lewis acid, the
stoichiometric reactivity between BEt3 and the cobalt
complexes, 2-py and 2-NCArOCH was studied. Upon the
3
addition of 1 equiv of BEt to a solution of 2-py in benzene-d ,
3
6
Mes
Figure 4. Proposed coordination of the Lewis acid to the cobalt-bound
nitrile.
the formation of a C -symmetric species, ( CCC)Co−N ,
2
2
1
was observed by H NMR spectroscopy, akin to the reaction
between 1 and 2 equiv of NaHBEt (Figure S9).
3
Computational modeling and experimental data have shown
that reactivity of Lewis acidic boranes (BF and B(C F ) ) with
3
6 5 3
nitriles results in an electrostatic interaction in the subsequent
73,74
CONCLUSION
adduct formation.
borane interaction was present, we treated a solution of 2-
Interested in understanding if a nitrile···
■
In conclusion, the catalytic activity of a cobalt bis(carbene)
pincer system was extended toward the hydrogenation of a
broad scope of nitriles with excellent selectivity toward the
primary amines. Through the course of our studies, it was
determined that the hydrogenation does not proceed without
the addition of catalytic amounts of a Lewis acid. On the basis
of the mechanistic studies herein and corroborating literature
precedents, the nature of the Lewis acid is proposed to facilitate
a side-on coordination of the nitrile to the cobalt center,
1
NCArOCH with BEt , and the mixture was monitored by H
3
3
NMR spectroscopy. Unfortunately, there was no change in the
1
H NMR spectrum in benzene-d at room temperature nor
6
when monitoring the reaction in toluene-d8 at 100 °C.
Likewise, examining the reaction by IR spectroscopy revealed
no change of the C≡N stretch, and coordination of N was not
2
observed. Alternatively, the addition of a nitrile−borane
7
5
adduct to 2-py yielded 2-NCArOCH with no indication of
3
an interaction with BPh3.
permitting a pairwise transfer of H through a Co(I/III) redox
2
We next re-examined the PHIP transfer NMR studies using
process. Furthermore, supplemented by insights gleaned from
the mechanistic studies, a nitrile featuring a ketone functionality
was amenable toward the selective hydrogenation of only the
nitrile, with the addition of superstoichiometric amounts of
Lewis acid. Finally, in our approach investigating a bench-stable
hydrogenation precatalyst accompanied by in situ activation by
2
-py and BEt to examine the importance of the Lewis acid in
3
the pairwise process. Upon the addition of p-H to a toluene-d8
2
solution containing 4-(trifluoromethyl)benzonitrile, 2-py (2
t
mol %), NaO Bu (6 mol %), and BEt (4 mol %) at 25 °C,
3
hyperpolarization was not observed. When the solution was
heated to 65 °C, the PASADENA effect of the primary imine
NaHBEt , the presumed innocence of the Lewis acid byproduct
3
1
group was observed in the H NMR spectrum using a 45° and
was contested, and it proved to hold a substantial role in the
observed catalysis.
OPSY pulse (Figure S14). These results are comparable with
the PHIP transfer NMR data using 1 and NaHBEt3,
demonstrating that the Co(I)-species along with BEt affords
ASSOCIATED CONTENT
3
■
the same PHIP effect, albeit at lower temperatures. Addition-
ally, similar effects were observed using 4-methoxybenzonitrile
as the substrate (Figure S13). On the basis of the PHIP transfer
NMR data, the first step in the hydrogenation of nitriles
*
S
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b07368.
Crystallographic details of 3-NCPh (CIF)
Crystallographic details of 3-NCArOCH (CIF)
conforms with the concerted nature of H addition, which is
2
consistent with our previous studies of the cobalt-catalyzed
3
hydrogenation of carbon−carbon multiple bonds using a
Crystallographic details of 2-py (CIF)
Experimental details of the catalytic reactions and
spectral details (PDF)
26,27
bis(carbene) pincer ligand platform.
Although the nitrile was found to coordinate to the cobalt
center end-on at ambient temperatures, under catalytic
conditions, the coordination mode changes to accommodate
AUTHOR INFORMATION
■
the pairwise addition of H onto the metal center as indicated
2
Corresponding Author
*E-mail: fout@illinois.edu
ORCID
Toby J. Woods: 0000-0002-1737-811X
Alison R. Fout: 0000-0002-4669-5835
Author Contributions
by the PHIP NMR data. One possibility involves a side-on
coordination mode of the nitrile through the C≡N π-orbital
proceeding through a three-center bonding environment. In the
side-on coordination mode, the C≡N bond would be more
amenable toward functionalization, and the nitrogen lone pair
would be available to interact with a Lewis acid in a similar
76−78
fashion as observed in bisphosphine nickel(0) complexes.
†
K.T. and B.J.J. contributed equally.
A computational study by Jiao and co-workers reported that the
energy difference decreases between end-on and side-on
coordination modes of acetonitrile in cobalt complexes with
Notes
The authors declare no competing financial interest.
F
DOI: 10.1021/jacs.7b07368
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
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28) Friedfeld, M. R.; Shevlin, M.; Hoyt, J. M.; Krska, S. W.; Tudge,
ACKNOWLEDGMENTS
■
M. T.; Chirik, P. J. Science 2013, 342, 1076−1080.
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30) Chen, C.; Hecht, M. B.; Kavara, A.; Brennessel, W. W.;
The authors thank the NSF for financial support with a
CAREER award (1351961) to A.R.F. A.R.F. is a Sloan Research
Fellow and a Camille Dreyfus Teacher-Scholar. The authors
thank Charles R. Markus and Prof. Benjamin J. McCall for use
(
1
(
Mercado, B. Q.; Weix, D. J.; Holland, P. L. J. Am. Chem. Soc. 2015,
137, 13244−13247.
of the p-H generator; Charles R. Markus has been supported in
2
part by an NSF award (CHE 12-13811) and a NASA award
NNX13AE62G) to PI Prof. Benjamin J. McCall. Finally, we
thank Dr. Lingyang Zhu for help with the PHIP NMR studies.
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DOI: 10.1021/jacs.7b07368
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