Dehydrogenative Coupling of Aldehydes with Alcohols Catalyzed by a Nickel Hydride Complex

Article abstract of DOI:10.1021/acs.organomet.8b00888

A nickel hydride complex, {2,6-(ⁱPr₂PO)₂C₆H₃}NiH, has been shown to catalyze the coupling of RCHO and R′OH to yield RCO₂R′ and RCH₂OH, where the aldehyde also acts as a hydrogen acceptor and the alcohol also serves as the solvent. Functional groups tolerated by this catalytic system include CF₃, NO₂, Cl, Br, NHCOMe, and NMe₂, whereas phenol-containing compounds are not viable substrates or solvents. The dehydrogenative coupling reaction can alternatively be catalyzed by an air-stable nickel chloride complex, {2,6-(ⁱPr₂PO)₂C₆H₃}NiCl, in conjunction with NaOMe. Acids in unpurified aldehydes react with the hydride to form nickel carboxylate complexes, which are catalytically inactive. Water, if present in a significant quantity, decreases the catalytic efficiency by forming {2,6-(ⁱPr₂PO)₂C₆H₃}NiOH, which causes catalyst degradation. On the other hand, in the presence of a drying agent, {2,6-(ⁱPr₂PO)₂C₆H₃}NiOH generated in situ from {2,6-(ⁱPr₂PO)₂C₆H₃}NiCl and NaOH can be converted to an alkoxide species, becoming catalytically competent. The proposed catalytic mechanism features aldehyde insertion into the nickel hydride as well as into a nickel alkoxide intermediate, both of which have been experimentally observed. Several mechanistically relevant nickel species including {2,6-(ⁱPr₂PO)₂C₆H₃}NiOC(O)Ph, {2,6-(ⁱPr₂PO)₂C₆H₃}NiOPh, and {2,6-(ⁱPr₂PO)₂C₆H₃}NiOPh·HOPh have been independently synthesized, crystallographically characterized, and tested for the catalytic reaction. While phenol-containing molecules cannot be used as substrates or solvents, both {2,6-(ⁱPr₂PO)₂C₆H₃}NiOPh and {2,6-(ⁱPr₂PO)₂C₆H₃}NiOPh·HOPh are efficient in catalyzing the dehydrogenative coupling of PhCHO with EtOH.

Full text of DOI:10.1021/acs.organomet.8b00888

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Dehydrogenative Coupling of Aldehydes with Alcohols Catalyzed by
a Nickel Hydride Complex
Nathan A. Eberhardt, Nadeesha P. N. Wellala, Yingze Li, Jeanette A. Krause, and Hairong Guan*
Department of Chemistry, University of Cincinnati, P.O. Box 210172, Cincinnati, Ohio 45221-0172, United States
S
* Supporting Information
ABSTRACT: A nickel hydride complex, {2,6-(iPr2PO)2C6H3}NiH, has
been shown to catalyze the coupling of RCHO and R′OH to yield
RCO2R′ and RCH2OH, where the aldehyde also acts as a hydrogen
acceptor and the alcohol also serves as the solvent. Functional groups
tolerated by this catalytic system include CF3, NO2, Cl, Br, NHCOMe,
and NMe2, whereas phenol-containing compounds are not viable
substrates or solvents. The dehydrogenative coupling reaction can
alternatively be catalyzed by an air-stable nickel chloride complex, {2,6-
(iPr2PO)2C6H3}NiCl, in conjunction with NaOMe. Acids in unpurified
aldehydes react with the hydride to form nickel carboxylate complexes,
which are catalytically inactive. Water, if present in a significant quantity,
decreases the catalytic efficiency by forming {2,6-(iPr2PO)2C6H3}NiOH,
which causes catalyst degradation. On the other hand, in the presence of
a drying agent, {2,6-(iPr2PO)2C6H3}NiOH generated in situ from {2,6-
(iPr2PO)2C6H3}NiCl and NaOH can be converted to an alkoxide species, becoming catalytically competent. The proposed
catalytic mechanism features aldehyde insertion into the nickel hydride as well as into a nickel alkoxide intermediate, both of
which have been experimentally observed. Several mechanistically relevant nickel species including {2,6-(iPr2PO)2C6H3}-
NiOC(O)Ph, {2,6-(iPr2PO)2C6H3}NiOPh, and {2,6-(iPr2PO)2C6H3}NiOPh·HOPh have been independently synthesized,
crystallographically characterized, and tested for the catalytic reaction. While phenol-containing molecules cannot be used as
substrates or solvents, both {2,6-(iPr2PO)2C6H3}NiOPh and {2,6-(iPr2PO)2C6H3}NiOPh·HOPh are efficient in catalyzing the
dehydrogenative coupling of PhCHO with EtOH.
(R′ ≠ CH2R) would require two different aldehydes6 or
INTRODUCTION
■
alcohols7 to construct the ester C−O bond. In these cases,
Catalytic disproportionation of aldehydes to esters, also known
selectivity for cross-coupling over homocoupling products is
as the Tishchenko reaction, provides a straightforward route to
esters with the general formula RCO2CH2R (Scheme 1A).1 An
generally poor, unless one substrate is added in large excess or
two electronically biased ones are employed.8 Beyond the
alternative synthetic method involves catalytic coupling of two
molecules of RCH2OH with the concomitant loss of four
traditional esterification strategies focused on the reaction
between RCO2H and R′OH, catalytic dehydrogenative
coupling of aldehydes with alcohols has been developed as a
greener method to synthesize esters with diverse structures.9
As inferred by the balanced equation (Scheme 1C), to form
one RCO2R′ molecule, two hydrogen atoms must be removed.
This can be accomplished in an acceptorless fashion,10 by
using a sacrificial hydrogen acceptor11 or an oxidant,12 or
under electrochemical conditions.13
hydrogen atoms (Scheme 1B), either in the form of H2 (i.e.,
acceptorless dehydrogenation)2,3 or assisted by a hydrogen
acceptor4 or an oxidant.5 Making esters of the type RCO2R′
Scheme 1. Synthesis of Esters from Aldehydes and/or
Alcohols
On what appeared to be a completely different research
path, we studied {2,6-(iPr2PO)2C6H3}NiH (1) as a catalyst for
14
the hydrosilylation of aldehydes with PhSiH3 as well as the
reduction of CO2 with HBcat (HBcat = catecholborane) to
yield CH3OBcat and catBOBcat.15 The latter reaction was
shown to proceed via hydroboration of HCHO as the last stage
of the catalytic process. In attempts to replace the silane and
Received: December 8, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
the borane with H2 as a cheaper source of reductant, we
explored the possibility of utilizing 1 to catalyze the
hydrogenation of benzaldehyde (Scheme 2). The reaction
Table 1. Catalytic Dehydrogenative Coupling of
Benzaldehyde with Methanol or Ethanol
a
Scheme 2. Attempted Hydrogenation of Benzaldehyde in
Different Solvents
conversion of
temperature
PhCHO
c
c
entry 1 (mol %)
R′OH
(°C)
(%)
2:3a/3b:4
1
2
3
4
5
6
7
8
10
10
10
10
1
1
0.1
0.1
MeOH
EtOH
MeOH
EtOH
MeOH
EtOH
MeOH
MeOH
80
80
23
23
80
80
80
60
100
100
65
20
100
99
50:50:0
50:50:0
54:46:0
75:25:0
50:50:trace
50:50:0
b
b
93
8
49:49:2
50:50:0
a
carried out in THF produced a small amount of PhCH2OH,
likely due to stoichiometric reduction of PhCHO by the nickel
hydride.14 In contrast, using CH3CN as the solvent resulted in
catalytic cyanomethylation of PhCHO, a process that does not
need H2.16 A significant amount of PhCH2OH was, however,
obtained when the solvent was switched to MeOH. The failure
to observe any H2 uptake hinted to us that the reaction was not
a hydrogenation process either. After a closer inspection,
PhCO2Me was identified as the second product in similar
quantity to PhCH2OH, implying that PhCHO itself acted as a
hydrogen acceptor for the dehydrogenative coupling of
PhCHO with MeOH.
Standard conditions: a mixture of PhCHO (0.20 or 2.0 mmol) and 1
b
(0.020 mmol) in 1.0 mL of R′OH stirred for 24 h. A mixture of
PhCHO (20 mmol), MeOH (10 mmol), and 1 (0.020 mmol) stirred
c
1
for 24 h. Determined by H NMR spectroscopy using mesitylene as
the internal standard.
limit. The amount of PhCH2OH generated is equal to the
amount of PhCO2R′ when the reaction goes to completion or
the catalyst loading is ≤1 mol %. However, at a high catalyst
loading, when the conversion of PhCHO is low (entries 3 and
4), there is an excess of PhCH2OH found in the product
mixture. The presence of surplus PhCH2OH is an indication
that PhCHO reduction occurs before ester formation.
To our knowledge, there is only one previous example of
homogeneous nickel-catalyzed dehydrogenative coupling of
aldehydes with alcohols, which uses an N-heterocyclic carbene
(NHC) ligated Ni(0) species as the catalyst and PhCOCF3 as
the hydrogen acceptor.11b The proposed mechanism involves
oxidative addition of the aldehyde C−H bond to nickel. Such a
step is highly unlikely to occur with our Ni(II) hydride,
suggesting that our reaction operates by a different mechanism.
Given that nickel-catalyzed dehydrogenative coupling reactions
in general are rare in the literature,11b,17 we decided to
investigate our catalytic system in greater detail, particularly
concerning the mechanism. The obtained mechanistic
information not only helps improve the dehydrogenative
coupling reaction but also uncovers many pitfalls associated
with the reactions of metal hydrides with aldehydes. With these
goals in mind, we examined the substrate scope for the
esterification of RCHO with R′OH catalyzed by 1,
characterized several nickel species relevant to the catalytic
cycles, and investigated the roles that impurities could play
during the dehydrogenative coupling process.
In the aforementioned reaction, MeOH or EtOH acts as
both substrate and solvent. Attempts were made to determine
if a nonalcoholic solvent could be used for the dehydrogenative
coupling process (Table 2). Unfortunately, changing the
Table 2. Catalytic Dehydrogenative Coupling of
Benzaldehyde with Ethanol in Different Solvents
a
c
c
entry
solvent
conversion of PhCHO (%)
2:3b:4
b
1
EtOH
THF
toluene
DMSO
DMF
100
44
10
8
24
17
10
50:50:0
56:42:2
74:26:0
91:6:3
61:36:3
53:47:0
92:8:0
2
3
4
5
6
7
glyme
diglyme
a
Standard conditions: a mixture of PhCHO (0.40 mmol), EtOH (2.0
mmol), and 1 (0.020 mmol) in 1.0 mL of solvent stirred at 80 °C for
RESULTS AND DISCUSSION
b
■
24 h. A mixture of PhCHO (0.40 mmol) and 1 (0.020 mmol) in 1.0
c
1
Reaction Optimization and Substrate Scope. The
nickel-catalyzed dehydrogenative coupling of PhCHO with
MeOH was further investigated by varying the temperature
and catalyst loading. A similar transformation of PhCHO and
EtOH to PhCH2OH and PhCO2Et was also examined in this
context. As shown in Table 1, the esterification reaction can
take place at room temperature although the rate is greatly
accelerated by mild heating (80 °C). The catalyst loading
(with respect to the total PhCHO) can be lowered to 1 mol %
(entries 5 and 6) or even 0.1 mol % under neat conditions
(entry 7), resulting in a turnover number of 456 for producing
PhCO2Me. In each experiment, the Tishchenko product
PhCO2CH2Ph is either negligible or below the NMR detection
mL of EtOH stirred at 80 °C for 24 h. Determined by H NMR
spectroscopy using mesitylene as the internal standard.
solvent to THF or toluene resulted in a low conversion of
PhCHO. To ensure that the diminished reactivity was not due
to a decrease in solvent polarity, polar solvents such as DMSO,
DMF, glyme, and diglyme were tested. These solvents all
turned out to be inferior media for carrying out the catalytic
dehydrogenative coupling of PhCHO with EtOH.
The scope of alcohols for the dehydrogenative reaction
(performed in the alcohol of interest) was explored using
benzaldehyde as the coupling partner with a catalyst loading of
5 mol %. As shown in Table 3, methanol and ethanol proceed
B
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
6). 4-Hydroxybenzaldehyde was shown to be a problematic
substrate for the catalytic reaction (entry 7), once again
demonstrating the incompatibility of the phenol group with
the nickel hydride. To understand the substituent effects on
the reaction rates, the catalytic reaction was stopped after 1 h
instead of 24 h. It became evident that aldehydes bearing an
electron-withdrawing group (e.g., CF3, NO2, Cl, or Br) reacted
faster than those containing an electron-donating group (e.g.,
NHCOMe or NMe2).
Mechanistic Studies. One limitation of our catalytic
system lies in the fact that 50% of the aldehydes are sacrificed
as hydrogen acceptors. To overcome this shortcoming, a
deeper understanding of the reaction mechanism is needed.
For dehydrogenative coupling of aldehydes with alcohols
catalyzed by Ni(COD)2/IPr (COD = 1,5-cyclooctadiene, IPr
= 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene),11b Whit-
taker and Dong have proposed an acyl nickel hydride
intermediate resulting from oxidative addition of the aldehyde
Csp2−H bond (Scheme 3). The subsequent carbonyl insertion
Table 3. Catalytic Dehydrogenative Coupling of
Benzaldehyde with Different Alcohols
a
conversion of PhCHO
2:3a−
d
d
entry
R′OH
MeOH
EtOH
nPrOH
PhCO2R′
(%)
3g:4
1
2
3
3a
3b
3c
3d
3e
3f
100
100
72
98
84
5
50:50:0
50:50:0
53:47:0
57:39:1
81:19:0
100:0:0
b
4
c
iPrOH
5
PhCH(OH)Me
tBuOH
6
7
PhOH
3g
0
a
Standard conditions: a mixture of PhCHO (0.40 mmol) and 1
b
(0.020 mmol) in 1.0 mL of R′OH stirred at 80 °C for 24 h. Acetone
c
observed from the product mixture. Acetophenone observed from
d
1
the product mixture. Determined by H NMR spectroscopy using
mesitylene as the internal standard.
Scheme 3. Mechanism Proposed for Ni(0)-NHC-Catalyzed
Dehydrogenative Coupling of Aldehydes with Alcohols11b
well, affording PhCH2OH and PhCO2R′ in a 50:50 ratio. With
n-propanol, the catalytic efficiency drops substantially (entry
3), suggesting that the reaction is most effective with short-
chain alcohols. The use of secondary alcohols is complicated
by the competing transfer hydrogenation of PhCHO, resulting
in a higher PhCH2OH-to-PhCO2R′ ratio and the formation of
a ketone byproduct (entries 4 and 5). A more bulky alcohol,
tBuOH, shuts down the catalytic process completely, providing
PhCH2OH in 5% yield as a result of stoichiometric reduction
of PhCHO (entry 6). The reaction carried out in phenol does
not even produce PhCH2OH, implying that phenol is
incompatible with the nickel hydride.
Functional group tolerance was probed by introducing
various substituents such as CF3, NO2, Cl, Br, NHCOMe,
NMe2, and OH to the para position of benzaldehyde (Table
4). Under the typical catalytic conditions (5 mol % catalyst
loading, 80 °C, 24 h), most of these substituted benzaldehydes
reacted smoothly with methanol to give an equimolar mixture
of ArCH2OH and ArCO2Me with a combined yield of 95−
99% (entries 1−5). In contrast, the reaction of 4-
(dimethylamino)benzaldehyde was sluggish, only achieving a
total yield of 41% for the alcohol and the methyl ester (entry
of PhCOCF3 provides an acyl nickel alkoxide species, which
undergoes alkoxide exchange with the alcohol to be coupled.
The catalytic cycle is closed by a reductive elimination step to
release the ester product.
Table 4. Catalytic Dehydrogenative Coupling of Different
a
Aldehydes with Methanol
Our system employs a well-defined nickel hydride complex
directly as the catalyst. Carbonyl insertion into the Ni−H
bond, as postulated above, can be readily observed here by
NMR spectroscopy. In C6D6, the insertion rate correlates well
with the electrophilicity of the carbonyl group (i.e., 4-
CF3C6H4CHO > C6H5CHO > 4-Me2NC6H4CHO). 2H
NMR studies of the reaction of the nickel deuteride (1-d1)
with 2 equiv of 4-XC6H4CHO (in C6H6) suggest that the
insertion is irreversible at room temperature but reversible at
50 °C (Scheme 4). Of the three substrates examined, the
insertion product originating from 1-d1 and 4-CF3C6H4CHO
undergoes H/D exchange with the surplus aldehyde to the
least extent (∼5% over 24 h). This is not due to an equilibrium
isotope effect but rather to a kinetic phenomenon.18 A stronger
Ni−O bond rendered by the electron-withdrawing CF3
group19 may provide a ground-state stabilization that disfavors
the β-hydride elimination. Attempts to isolate the insertion
products in a pure form failed, in part due to their high
5:6
yield after
5:6 (after
conversion
(after 1
bc
,
c
c
c
entry
X
24 h (%)
24 h)
after 1 h (%)
h)
1
2
3
4
5
6
7
CF3
NO2
Cl
99
96
98
95
97
41
5
50:50
52:48
50:50
51:49
50:50
52:48
100:0
93
57
40
58
22
9
50:50
55:45
58:42
56:44
56:44
70:30
0:0
Br
NHCOMe
NMe2
OH
0
a
Standard conditions: a mixture of ArCHO (0.40 mmol) and 1
b
(0.020 mmol) in 1.0 mL of MeOH stirred at 80 °C. Combined
c
NMR yield of 5 and 6. Determined by 1H NMR spectroscopy using
mesitylene as the internal standard.
C
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
fastest step within the cycle. On the basis of our previous
observation of a facile deinsertion of PhCHO from {2,6-
(iPr2PO)2C6H3}NiOCH(CH2CN)Ph (eq 1),16 we propose
Scheme 4. Reversibility of Aldehyde Insertion Probed by
Deuterium-Labeling Experiments
that the second insertion step converting 8 to 9 is reversible.
Although increasing the temperature would reduce the steady-
state concentration of 9 (due to entropic effect), it allows the
elimination of 10 to occur more rapidly.
In an alcoholic solvent, R′OH, the alcohol is likely to
intercept the insertion products like 8 to yield {2,6-
(iPr2PO)2C6H3}NiOR′, which in turn reacts with aldehydes
in a similar fashion as 8 (i.e., aldehyde insertion followed by β-
hydride elimination). It should be noted that 1 dissolved in
CD3OD was slowly converted to {2,6-(iPr2PO)2C6H3}-
NiOCD3 (12-d3) and HD (triplet at 4.52 ppm, JH‑D = 42.8
Hz) with a 71% conversion achieved in 48 h.22 However, this
process is much less competitive than aldehyde insertion into
1. For instance, mixing 1 with 10 equiv of PhCHO in CD3OD
provided 12-d3 and PhCH2OD almost instantaneously without
forming HD. The ester product PhCO2CD3 grew over time,
accompanied by an increase in the amount of PhCH2OD. The
reaction became more favorable when the temperature was
raised to 80 °C (see Supporting Information for details).
The protonation of 1 with CD3OD described above and the
reversibility of aldehyde insertion demonstrated in Scheme 4
imply that the nickel hydride may catalyze dehydrogenative
coupling of primary alcohols to esters (i.e., the reaction in
Scheme 1B). Unfortunately, heating a mixture of 1 (1 mol %
catalyst loading) and PhCH2OH at 80 °C for 24 h yielded only
a trace amount of PhCO2CH2Ph. Although β-hydride
elimination from {2,6-(iPr2PO)2C6H3}NiOCH2Ph is kineti-
cally accessible, it is thermodynamically too uphill to produce
enough PhCHO.
sensitivity toward adventitious water.14 In fact, treatment of the
insertion products with water was shown to yield free alcohols
along with {2,6-(iPr2PO)2C6H3}NiOH (7), which also
decomposed rapidly during workup.20,21
The reaction of 1 with ∼3 equiv of 4-CF3C6H4CHO in
C6D6 offered more mechanistic insights. In addition to the
expected insertion product 8 (Scheme 5) along with a trace
Scheme 5. Ester Formation via Consecutive Insertions of an
Aldehyde
A mechanism consistent with our experimental data is
outlined in Scheme 6. Both the dehydrogenative coupling cycle
and the Tishchenko cycle start with aldehyde insertion into the
nickel hydride and finish with β-hydride elimination following
aldehyde insertion into a nickel alkoxide species. The
difference arises from which alkoxide species participates in
the second insertion step. Thus, the equilibrium for the
alkoxide exchange on nickel and the relative reactivity of nickel
alkoxide species toward aldehydes determine the selectivity.
For the reaction performed in R′OH, the equilibrium is shifted
far to the {2,6-(iPr2PO)2C6H3}NiOR′ side, which initiates the
dehydrogenative coupling process unless its reaction with
aldehydes is unfavorable.
Our proposed mechanism differs significantly from that of
Whittaker and Dong (Scheme 3),11b particularly regarding the
change (or the lack thereof) in nickel oxidation state. Although
we cannot rigorously rule out the possibility of forming a Ni(0)
species via Cipso−H reductive elimination from 1,22 the facile
aldehyde insertion observed with the hydride makes us prefer
the Ni(II)-only pathway (Scheme 6). Our mechanism is more
analogous to the one proposed by Liu and Eisen for the
dehydrogenative coupling of aldehydes with alcohols catalyzed
by actinide alkoxides (in the presence of PhCOCF3 as a
hydrogen acceptor).11c The actinide system, however, invokes
amount of 7 due to hydrolysis, another nickel pincer complex 9
was detected as a minor product (∼30%). Its 1H NMR
spectrum features an AB quartet at 4.47 and 4.31 ppm (JAB
=
12.8 Hz) and a singlet at 5.65 ppm (integrated to a 2:1 ratio),
consistent with a nickel species formed by two consecutive
insertions of the aldehyde. Heating the solution to 80 °C
resulted in a gradual disappearance of 9 and the aldehyde with
concomitant appearance of ester 10, presumably through a β-
hydride elimination process. The steps illustrated in Scheme 5
essentially complete a catalytic cycle for generating the
Tishchenko product. After 24 h of heating, the reaction
mixture consisted of 8 (44%), 9 (0.5%), 10 (46%), 4-
CF3C6H4CH2OH (6%), 4-CF3C6H4CHO (1.5%), and other
unidentified species (2%). The nickel hydride was absent from
this mixture, suggesting that the first insertion event is the
D
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 6. Catalytic Cycles Proposed for Ester Formation Catalyzed by the Pincer Nickel Hydride Complex
a Meerwein−Ponndorf−Verley type reduction of the hydrogen
acceptor instead of the reduction by a metal hydride.
An alternative mechanism may involve a nickel-catalyzed
Tishchenko reaction followed by a transesterification process.
To discern this mechanistic scenario, a reaction profile for
catalytic dehydrogenative coupling of PhCHO with EtOH was
examined. As illustrated in Figure 1, the major pathway appears
curious to see if {2,6-(iPr2PO)2C6H3}NiCl (11) could serve as
a precatalyst. Such an experiment would indirectly support our
proposed mechanism (Scheme 6). Indeed, 11 in conjunction
with NaOMe (in a 1:1 ratio) proved to be efficient and
selective in converting PhCHO and EtOH to PhCH2OH and
PhCO2Et (Table 5, entry 1). When NaOMe was replaced with
Table 5. Dehydrogenative Coupling of Benzaldehyde with
a
Ethanol Using a Precatalyst
conversion of PhCHO
b
c
c
entry
base
drying agent
(%)
2:3b:4
1
2
3
4
NaOMe
NaOH
NaOH
NaOH
99
8
92
95
49:49:2
0:0:100
48:46:6
49:49:2
Na2SO4
4 Å molecular
sieves
a
Standard conditions: a mixture of PhCHO (10 mmol), 11 (0.10
mmol), base (0.10 mmol), and EtOH (1.0 mL, 17 mmol) stirred at
b
c
80 °C for 24 h. About 1 g of drying agent added. Determined by 1H
NMR spectroscopy using mesitylene as the internal standard.
Figure 1. Reaction profile for nickel-catalyzed dehydrogenative
coupling of PhCHO and EtOH (conditions: 0.40 mmol of PhCHO
and 0.020 mmol of 1 in 1.0 mL of EtOH stirred at 80 °C).
NaOH, the catalytic reaction became inefficient with only 8%
of PhCHO converted, and the selectivity favored the
Tishchenko product (entry 2). However, adding a drying
agent such as anhydrous Na2SO4 or 4 Å molecular sieves
drastically improved the reaction, resulting in up to 95%
conversion of PhCHO primarily to PhCH2OH and PhCO2Et.
The effects of base and drying agent can be rationalized by
considering a hydroxide/ethoxide exchange equilibrium, high-
lighted in Scheme 7. For a closely related system involving a
to be the direct formation of PhCO2Et, as evidenced by a very
small amount of PhCO2CH2Ph observed throughout the
catalytic reaction. A possibility is that the transesterification
process was too fast to allow a substantial accumulation of the
Tishchenko product. However, a control experiment con-
firmed that the nickel hydride hardly catalyzed the trans-
esterification of PhCO2CH2Ph in EtOH (eq 2). These results
́
bis(phosphine)-based pincer ligand, Campora and co-workers
have reported an equilibrium constant of 1.4(2) × 10−3
favoring {2,6-(iPr2PCH2)2C6H3}NiOH and EtOH.24 Thus,
combining 11 with NaOH, despite being carried out in EtOH,
would yield 7 as the major nickel pincer species. This nickel
hydroxide complex, generated in situ from {2,6-
(iPr2PO)2C6H3}NiOTf and NaOH, was shown to react with
PhCHO to yield PhCO2CH2Ph and numerous intractable
products. However, in the presence of a drying agent, the
equilibrium is shifted to 13, which enters into a productive
cycle to generate PhCH2OH and PhCO2Et catalytically.
indicate that while it is not impossible to form the Tishchenko
product first and then the transesterification product, such a
route is not a major pathway leading to PhCO2Et.
Using a Nickel Chloride Complex as a Precatalyst.
Because POCOP-pincer ligated nickel alkoxide complexes can
form in situ by mixing the corresponding nickel chloride
complexes with sodium or potassium alkoxides,20a,23 we were
E
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 7. Proposed Activation of the Precatalyst and the
Subsequent Reactions
Figure 2. ORTEP drawing of {2,6-(iPr2PO)2C6H3}NiOC(O)Ph (14)
at the 50% probability level (hydrogen atoms omitted for clarity).
Selected bond lengths (Å) and angles (deg): Ni−C(1) 1.8818(15),
Ni−O(3) 1.9096(11), Ni−P(1) 2.1609(3), Ni−P(1A) 2.1609(3),
C(19)−O(3) 1.2853(18), C(19A)−O(4) 1.2341(18); C(1)−Ni(1)−
O(3) 175.83(5), P(1)−Ni−P(1A) 163.574(17).
Deactivation of the Catalyst. Throughout our study, a
number of species including impurities present in aldehydes,
water, and phenols were shown to retard or negatively impact
the catalytic reaction. Aldehydes used in this work must be
distilled or recrystallized prior to use. The main impurities in
unpurified aldehydes are carboxylic acids originating from
oxidation of the aldehydes. These acids may protonate the
nickel hydride or nickel alkoxide intermediates, resulting in
nickel carboxylate complexes that could be catalytically
inactive. Water, though not necessarily intolerable, can be
detrimental to the catalytic process, especially when it is
present in a sufficient amount to shift the hydroxide/alkoxide
exchange equilibrium to 7 (Scheme 7). Phenols may also be
acidic enough to protonate the hydride to form catalytically
inactive phenoxide species.
When water (100 equiv with respect to PhCHO) was added
intentionally to the reaction mixture, the conversion of
PhCHO dropped to only 11% with some Tishchenko product
being observed (eq 3).
To further understand the roles that impurities can play and
the reason why phenol is an incompatible functional group,
independent syntheses of the postulated catalyst deactivation
products were pursued. When 1 was mixed with PhCO2H in
C6D6, the desired nickel carboxylate complex {2,6-
(iPr2PO)2C6H3}NiOC(O)Ph (14) formed along with some
decomposition products. Attempts to separate 14 from these
byproducts were fruitless, so attention was turned to
alternative routes. Analytically pure 14 was eventually obtained
in high yield (92%) from a salt metathesis reaction between 11
and PhCO2Ag, following a similar procedure developed for a
nickel acetate complex.25 The crystal structure of 14 (Figure 2)
shows a κ1-benzoate, which is perpendicular to the
coordination plane. In contrast, our previously reported
formate complex {2,6-(iPr2PO)2C6H3}NiOC(O)H adopts an
in-plane conformation for the κ1-formate.15b Otherwise, the
bond metrics for the two complexes are almost identical. A
control experiment using 14 as a catalyst (1 mol % loading)
under the typical conditions (80 °C, 24 h, in EtOH) showed
no conversion of PhCHO, confirming that protonation of 1 by
acid impurities shuts down the catalytic reaction.
Another catalyst deactivation pathway that has been
implicated is specifically for reactions involving phenol-type
molecules as either substrates or solvents. Considering the
propensity of 1 and closely related nickel hydride complexes to
undergo protonation by acids,15a,26 we speculated that PhOH
could protonate 1 to yield a nickel phenoxide complex along
with dihydrogen. This was indeed observed from an NMR
reaction carried out in C6D6 (eq 4). It was, however,
interesting to note that 2 equiv of PhOH was needed to
fully protonate the hydride. An X-ray crystallographic study of
the organometallic product revealed an adduct of {2,6-
(iPr2PO)2C6H3}NiOPh (15) and PhOH bound by a hydrogen
bond (Figure 3).
The nickel phenoxide complex free of phenol was obtained
from the reaction of 11 with NaOPh (eq 5). Adding 1 equiv of
PhOH to a solution of 15 in C6D6 reproduced the NMR
spectra for the protonation reaction shown in eq 4. Apart from
the lack of aromatic resonances attributed to the hydrogen
The observed hydrolysis of the insertion products to yield 7
(Scheme 4) and the unwanted reactions of 7 with PhCHO
(Scheme 7) imply that water is harmful to the catalytic
reaction. Alcohols used in this study were dried over CaH2,
distilled, and then further dried using 4 Å molecular sieves.
F
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 3. ORTEP drawing of {2,6-(iPr2PO)2C6H3}NiOPh·HOPh
(15·HOPh) at the 50% probability level (all hydrogen atoms except
the one involved in hydrogen bonding omitted for clarity). Selected
bond lengths (Å) and angles (deg): Ni−C(1) 1.8834(18), Ni−O(3)
1.9147(13), Ni−P(1) 2.1907(6), Ni−P(2) 2.1890(6), C(19)−O(3)
1.342(2), C(25)−O(4) 1.359(3), O(4)−H 0.80(2), O(3)···H
1.87(2), O(3)···O(4) 2.664(2); C(1)−Ni−O(3) 179.67(7), P(1)−
Ni−P(2) 163.02(2), O(4)−H···O(3) 168(3).
Figure 4. ORTEP drawing of {2,6-(iPr2PO)2C6H3}NiOPh (15) at
the 50% probability level (hydrogen atoms omitted for clarity; only
molecule A shown; only symmetry-unique carbon and oxygen atoms
labeled). Selected bond lengths (Å) and angles (deg): Ni(1)−C(1A)
1.881(2), Ni(1)−O(3A) 1.8929(16), Ni(1)−P(1A) 2.1652(4),
Ni(1)−P(1AA) 2.1653(4), C(19A)−O(3A) 1.322(3); C(1A)−
Ni(1)−O(3A) 172.70(8), P(1A)−Ni(1)−P(1AA) 163.30(3).
PhCO2Ph could generate the nickel hydride 1. However,
PhCO2Ph was not observed (by GC-MS) throughout the
catalytic reaction. Instead, free PhOH was detected, suggesting
that 15 may undergo a phenoxide-ethoxide exchange with
EtOH to yield the catalytically active {2,6-(iPr2PO)2C6H3}-
NiOEt. Although a control experiment carried out in C6D6
showed no phenoxide-ethoxide exchange between 15 and
EtOH (10 equiv), such a process might still be operative in
EtOH. With an excess of PhOH, 1 should be converted to 15·
HOPh, and the hydrogen bonded PhOH presumably will
block EtOH from approaching the nickel center for the
phenoxide−ethoxide exchange. To our surprise, the in situ
generated 15·HOPh (by mixing 15 with 1 equiv of PhOH) was
found to be catalytically more active than 15 but slightly less
active than 1 (eq 6). At the moment, we do not fully
understand the reasons behind the reactivity differences.
We propose that sterics (i.e., from the R′ group in {2,6-
(iPr2PO)2C6H3}NiOR′) play a critical role in determining the
insertion rate and ultimately the efficiency of the overall
process. The fact that the catalytic reaction in MeOH is faster
than that in EtOH, which is evident at room temperature
(Table 1, entry 3 vs entry 4), can be explained by a more facile
PhCHO insertion with {2,6-(iPr2PO)2C6H3}NiOMe (12).
Based on the same argument, nickel n-propoxide and t-
butoxide should be even less reactive than the ethoxide
complex. Consistent with this hypothesis, the dehydrogenative
bonded PhOH, proton resonances of 15 are remarkably similar
to those of 15·HOPh. The 31P resonance of 15 is shifted
downfield by 0.35 ppm upon conversion to 15·HOPh. As
expected, in the absence of PhOH, the nickel center is less
crowded (Figure 4). Consequently, going from 15·HOPh to
15, the Ni−P and Ni−O bonds are contracted by 0.02−0.03
and 0.02−0.04 Å, respectively. However, the Ni−Cipso bond
distance remains unchanged at 1.88 Å and is almost identical
to that in 14. In our previous studies of POCOP-pincer ligated
nickel thiolate,19 isothiocyanate,27 and azide complexes,27 we
have also shown that the Ni−Cipso bond distance is unaffected
by its trans ligand.
Interestingly, the phenoxide complex 15 remains an active
catalyst for the dehydrogenative coupling of PhCHO with
EtOH, although it is less effective than the hydride complex 1
(eq 6). At 80 °C with a 1 mol % catalyst loading, 77% of
n
coupling reaction is low yielding in PrOH (Table 3, entry 3)
t
while stopped in BuOH (Table 3, entry 6). For secondary
i
alcohols such as PrOH and PhCH(OH)Me, because of the
PhCHO was converted in 24 h, providing a 50:50 mixture of
PhCH2OH and PhCO2Et with a negligible amount of
PhCO2CH2Ph. This reaction catalyzed by 1 would have
completed under the same conditions. Insertion of PhCHO
into the Ni−OPh bond of 15 followed by the elimination of
steric crowding, one would also expect a less efficient
dehydrogenative coupling reaction. However, the conversion
of PhCHO in these alcohols (Table 3, entries 4 and 5) is
higher than the conversion in nPrOH. These results should not
be interpreted as a sign of a fast PhCHO insertion. The
G
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
General Procedure for Catalytic Dehydrogenative Coupling
of Aldehydes with Alcohols. To a flame-dried 5-dram scintillation
vial equipped with a stir bar was added an aldehyde (2.0 mmol) and 1
mL of alcohol. Nickel hydride complex 1 (8.0 mg, 0.020 mmol, 1 mol
% catalyst loading) was then added, and the vial was capped and
wrapped with Parafilm to ensure appropriate sealing. The vial was
placed in an 80 °C oil bath and heated at this temperature. After a
given period of time, the vial was removed from the oil bath and
cooled to room temperature in a water bath. Mesitylene (28 μL, 0.20
mmol) was then added as an internal standard. An aliquot of the
reaction mixture was withdrawn and diluted with CDCl3 for NMR
analysis. Conversions of the aldehyde and product ratios were
observation of acetone and acetophenone as the byproducts
suggests that the higher conversion of PhCHO is due to a
competing transfer hydrogenation process.
CONCLUSIONS
■
In this work, we have carried out an in-depth study of
dehydrogenative coupling of aldehydes with alcohols catalyzed
by a nickel hydride complex. This catalytic system displays a
moderate functional group tolerance and is compatible with
various short-chain alcohols for the synthesis of esters. In doing
so, one equivalent of aldehyde is consumed as a sacrificial
hydrogen acceptor. Our mechanistic investigation supports a
catalytic cycle composed of four steps: (1) aldehyde insertion
into the nickel hydride, (2) alkoxide exchange between the
resulting insertion product and the alcohol, (3) another
aldehyde insertion step but with the nickel alkoxide
intermediate, and (4) β-hydride elimination to release the
ester product and regenerate the hydride. The competing
Tishchenko reaction follows an analogous catalytic cycle,
although it is suppressed due to the alkoxide exchange step
mentioned above, which diverts the aldehyde to participate in
the dehydrogenative coupling cycle. Guided by this mecha-
nistic analysis, we have successfully replaced the air-sensitive
nickel hydride catalyst with a nickel chloride complex as an air-
stable precatalyst.
1
obtained from H NMR integrations.
{2,6-(iPr2PO)2C6H3}NiOH (7) Generated in Situ. Under an
argon atmosphere, freshly ground NaOH (12 mg, 0.30 mmol) was
added to a solution of {2,6-(iPr2PO)2C6H3}NiOTf (50 mg, 0.091
mmol) in 0.5 mL of C6D6. The resulting orange suspension was
vigorously stirred at room temperature for 30 min, during which time
it turned to a gel-like material. C6D6 (1.0 mL) was added, and the
mixture was then passed through a Titan3 PTFE syringe filter. The
collected solution was analyzed by NMR spectroscopy. Attempts to
isolate the product in a solid form through evaporation of the solvent
led to significant decomposition. 1H NMR (400 MHz, C6D6, δ): 6.85
(t, JH−H = 8.0 Hz, ArH, 1H), 6.56 (d, JH−H = 8.0 Hz, ArH, 2H), 2.17−
2.07 (m, PCH(CH3)2, 4H), 1.41−1.34 (m, PCH(CH3)2, 12H), 1.28−
1.22 (m, PCH(CH3)2, 12H), −2.45 (br, NiOH, 1H). 13C{1H} NMR
(101 MHz, C6D6, δ): 169.50 (t, JP−C = 10.4 Hz, ArCortho), 105.44 (t,
J
P−C = 6.0 Hz, ArCmeta), 27.78 (t, JP−C = 10.2 Hz, PCH(CH3)2), 17.25
(t, JP−C = 3.6 Hz, PCH(CH3)2), 16.83 (s, PCH(CH3)2). 31P{1H}
NMR (162 MHz, C6D6, δ): 178.49 (s).
We have also examined potential catalyst deactivation
pathways, which we believe have implications in other systems
involving metal hydrides and aldehydes. In particular, we have
shown that acid impurities in aldehydes can protonate the
nickel hydride or the intermediates to form catalytically
inactive nickel carboxylate complexes. Water, if present in a
substantial amount, can decrease the catalytic efficiency by
forming a nickel hydroxide complex leading to multiple
decomposition pathways. Improvement of the catalytic system
would require the development of new ligands that promote
aldehyde insertion into the nickel alkoxide intermediate and,
more importantly, bypass aldehyde insertion into the nickel
hydride as well as alkoxide exchange for an acceptorless
dehydrogenative coupling reaction. These are ongoing efforts
in our laboratory.
Reaction of {2,6-(iPr2PO)2C6H3}NiOH (7) with PhCHO. To the
in situ generated solution of 7 in C6D6 (as described above) was
added 2.0 μL of PhCHO (20 μmol). The NMR spectra of the
reaction mixture were recorded immediately. On the basis of
integration of the aromatic resonances for 7 and the PhCHO
resonance, the ratio between 7 and PhCHO was determined to be
1:0.9. The reaction was monitored at room temperature for 4 days by
both 1H and 31P{1H} NMR spectroscopy. The NMR spectra showed
the formation of PhCO2CH2Ph and at least 12 different phosphorus-
containing products.
Monitoring the Catalytic Reaction by NMR Spectroscopy.
Under an argon atmosphere, 1 (4.0 mg, 0.010 mmol) and PhCHO
(10 μL, 0.10 mmol) were mixed with ∼0.4 mL of CD3OD in a J.
Young NMR tube. The reaction was monitored first at 23 °C and
then at 80 °C by both 1H and 31P{1H} NMR spectroscopy. At 23 °C,
the reaction produced {2,6-(iPr2PO)2C6H3}NiOCD3 (12-d3) and
PhCH2OD first, followed by a slow formation of PhCO2CD3 (13% in
16 h). At 80 °C, the reaction was complete within 24 h, producing a
mixture of PhCH2OD and PhCO2CD3 along with 12-d3 as the resting
state of the catalyst. 12-d3 was generated slowly (>48 h) by dissolving
1 in CD3OD or rapidly by mixing {2,6-(iPr2PO)2C6H3}NiOTf with
NaOMe in CD3OD. 1H NMR of 12-d3 (400 MHz, CD3OD, δ): 6.88
(t, JH−H = 8.0 Hz, ArH, 1H), 6.29 (d, JH−H = 8.0 Hz, ArH, 2H), 2.46−
2.38 (m, PCH(CH3)2, 4H), 1.46−1.36 (m, PCH(CH3)2, 24H).
31P{1H} NMR of {2,6-(iPr2PO)2C6H3}NiOCD3 (162 MHz, CD3OD,
δ): 176.90 (s).
EXPERIMENTAL SECTION
■
General Methods. All compounds described in this paper were
prepared under an argon atmosphere using standard glovebox and
Schlenk techniques. Benzene-d6 was dried over Na-benzophenone and
distilled under an argon atmosphere. Alcohols were dried over CaH2,
distilled under argon, and then stored with 4 Å molecular sieves. All
other dry and oxygen-free solvents used for synthesis and workup
(THF, toluene, and pentane) were collected from an Innovative
Technology solvent purification system. Aldehydes were freshly
distilled or recrystallized prior to use. {2,6-(iPr2PO)2C6H3}NiH
(1),14 {2,6-(iPr2PO)2C6H3}NiCl (11),28 and {2,6-(iPr2PO)2C6H3}-
NiOTf28 were synthesized following literature procedures. {2,6-
(iPr2PO)2C6H3}NiD (1-d1) was prepared using the same procedure
for making 1 except that LiAlD4 was employed as the deuteride
Synthesis of {2,6-(iPr2PO)2C6H3}NiOC(O)Ph (14). Under an
argon atmosphere, a suspension of 11 (100 mg, 0.23 mmol) and silver
benzoate (62 mg, 0.27 mmol) in 25 mL of THF was stirred at room
temperature in the absence of light for 6 h. The volatiles were
removed under a vacuum, and the residue was suspended in 40 mL of
toluene, which was subsequently filtered through a short plug of
Celite. The collected colored solution was evaporated to dryness, and
the resulting semisolid was washed with pentane three times (2 mL
each). After drying under a vacuum, the desired product was isolated
as a yellow powder (110 mg, 92% yield). 1H NMR (400 MHz, C6D6,
δ): 8.41 (d, JH−H = 8.4 Hz, ArH, 2H), 7.25 (t, JH−H = 7.4 Hz, ArH,
2H), 7.18 (t, JH−H = 6.8 Hz, ArH, 1H), 6.88 (t, JH−H = 8.0 Hz, ArH,
1H), 6.57 (d, JH−H = 8.0 Hz, ArH, 2H), 2.34−2.24 (m, PCH(CH3)2,
4H), 1.38−1.32 (m, PCH(CH3)2, 12H), 1.24−1.19 (m, PCH(CH3)2,
1
source. H, 13C{1H}, and 31P{1H} NMR spectra were recorded on a
2
Bruker Avance 400 MHz NMR spectrometer. H NMR spectra were
recorded on a Bruker Avance NEO 400 MHz NMR spectrometer.
1
2
Chemical shift values in H, H, and 13C{1H} NMR spectra were
referenced internally to the residual solvent resonances. 31P{1H}
NMR spectra were referenced externally to 85% H3PO4 (0 ppm).
Infrared spectra were recorded on a PerkinElmer Spectrum Two FT-
IR spectrometer equipped with a smart orbit diamond attenuated
total reflectance (ATR) accessory.
H
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
12H). 13C{1H} NMR (101 MHz, C6D6, δ): 171.04 (s, NiOCOPh),
170.02 (t, JP−C = 10.2 Hz, ArCortho), 136.56 (s, ArC), 130.54 (s, ArC),
130.21 (s, ArC), 129.26 (s, ArC), 122.48 (t, JP−C = 22.7 Hz, ArCipso),
105.56 (t, JP−C = 5.8 Hz, ArCmeta), 28.93 (t, JP−C = 11.0 Hz,
PCH(CH3)2), 17.79 (t, JP−C = 3.3 Hz, PCH(CH3)2), 16.96 (s,
PCH(CH3)2). 31P{1H} NMR (162 MHz, C6D6, δ): 183.55 (s). ATR-
IR (solid): νOCO = 1611 (νasym), 1569 (νasym), and 1356 (νsym) cm−1.
Anal. Calcd for C25H36O4P2Ni: C, 57.61; H, 6.96. Found: C, 57.82;
H, 6.81.
(iPr2PO)2C6H3}NiD (1-d1) and PhCHO, NMR spectra
of the catalytic reaction, and X-ray crystallographic
information for {2,6-(iPr2PO)2C6H3}NiOC(O)Ph (14),
{2,6-(iPr2PO)2C6H3}NiOPh·HOPh (15·HOPh), and
{2,6-(iPr2PO)2C6H3}NiOPh (15) (PDF)
Optimized Cartesian coordinates for 14, 15·HOPh, and
15 (MOL)
Accession Codes
Synthesis of NaOPh. Under an argon atmosphere, NaH (480 mg,
20 mmol) was added slowly to a solution of phenol (941 mg, 10
mmol) in 10 mL of THF. The resulting suspension was stirred at
room temperature for 30 min and then filtered via a cannula. The
collected filtrate was concentrated under a vacuum to yield a white
solid (1.10 g, 95% yield), which was used directly for the subsequent
synthesis.
CCDC 1881636−1881638 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Synthesis of {2,6-(iPr2PO)2C6H3}NiOPh (15). Under an argon
atmosphere, 11 (174 mg, 0.40 mmol) and sodium phenoxide (56 mg,
0.48 mmol) were mixed in 10 mL of THF and stirred at room
temperature for 16 h. The volatiles were removed under a vacuum,
and the residue was suspended in 40 mL of toluene, which was
subsequently filtered through a short plug of Celite. The collected
colored solution was evaporated to dryness to yield the desired
AUTHOR INFORMATION
Corresponding Author
*E-mail: hairong.guan@uc.edu.
ORCID
■
Hairong Guan: 0000-0002-4858-3159
1
product as a yellow powder (180 mg, 91% yield). H NMR (400
Notes
MHz, C6D6, δ): 7.28 (t, JH−H = 7.6 Hz, ArH, 2H), 7.11 (d, JH−H = 7.6
Hz, ArH, 2H), 6.85 (t, JH−H = 7.6 Hz, ArH, 1H), 6.71 (t, JH−H = 7.6
Hz, ArH, 1H), 6.54 (d, JH−H = 7.6 Hz, ArH, 2H), 2.02−1.93 (m,
PCH(CH3)2, 4H), 1.28−1.22 (m, PCH(CH3)2, 12H), 1.20−1.15 (m,
PCH(CH3)2, 12H). 13C{1H} NMR (101 MHz, C6D6, δ): 170.35 (s,
ArC), 169.85 (t, JP−C = 10.2 Hz, ArCortho), 129.17 (s, ArC), 122.85 (t,
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation (CHE-1464734
and CHE-1800151) for support of this research. Crystallo-
graphic data were collected on a Bruker D8 Venture
diffractometer (funded by NSF-MRI grant CHE-1625737) or
through the SCrALS (Service Crystallography at Advanced
Light Source) Program at Beamline 11.3.1 at the Advanced
Light Source (ALS), Lawrence Berkeley National Laboratory
(funded by the U.S. Department of Energy, Office of Basic
Energy Sciences, under contract No. DE-AC02-05CH11231).
2H NMR experiments were performed on a Bruker AVANCE
NEO 400 MHz NMR spectrometer (funded by NSF-MRI
grant CHE-1726092).
J
J
P−C = 22.4 Hz, ArCipso), 120.61 (s, ArC), 113.82 (s, ArC), 105.65 (t,
P−C = 5.8 Hz, ArCmeta), 28.32 (t, JP−C = 10.2 Hz, PCH(CH3)2), 16.82
(t, JP−C = 3.2 Hz, PCH(CH3)2), 16.74 (s, PCH(CH3)2). 31P{1H}
NMR (162 MHz, C6D6, δ): 178.85 (s). Anal. Calcd for
C24H36O3P2Ni: C, 58.45; H, 7.36. Found: C, 58.71; H, 7.65.
X-ray Structure Determination. Crystal data collection and
refinement parameters are provided in the Supporting Information.
Single crystals of 2,6-(iPr2PO)2C6H3}NiOC(O)Ph (14), {2,6-
(i Pr2 PO)2 C6 H3 }NiOPh·HOPh (15·HOPh), and {2,6-
(iPr2PO)2C6H3}NiOPh (15) were grown from pentane, benzene,
and THF-pentane, respectively. Intensity data for 14 and 15 were
collected at 150 K on a Bruker dual microfocus source D8 Venture
Photon-II diffractometer with Mo Kα radiation, λ = 0.71073 Å.
Intensity data for 15·HOPh were collected at 150 K on a Bruker
PHOTON-II detector at Beamline 11.3.1 at the Advanced Light
Source (Lawrence Berkeley National Laboratory) using synchrotron
radiation tuned to λ = 0.7749 Å. The data frames were processed
using the program SAINT. The data were corrected for decay,
Lorentz, and polarization effects as well as absorption and beam
corrections based on the multiscan technique. The structures were
solved by a combination of direct methods in SHELXTL and the
difference Fourier technique and refined by full-matrix least-squares
on F2. Compound 15 was refined as a twin, 180° rotation about the a
axis (∼6), twin law applied: 1 0 0 0−1 0−0.376 0−1 (Cell_Now).
Non-hydrogen atoms were refined with anisotropic displacement
parameters. The phenol OH hydrogen in 15·HOPh was located
directly from the difference map, and the coordinates were refined.
Remaining hydrogen atoms were calculated and treated with a riding
model. The crystal structures for 14, 15·HOPh, and 15 have been
deposited at the Cambridge Crystallographic Data Centre (CCDC)
and allocated the deposition numbers CCDC 1881636−1881638.
REFERENCES
■
(1) Seki, T.; Nakajo, T.; Onaka, M. The Tishchenko Reaction: A
Classic and Practical Tool for Ester Synthesis. Chem. Lett. 2006, 35,
824−829.
(2) For representative systems based on Ru, Os, or Ir, see:
(a) Murahashi, S.; Ito, K.; Naota, T.; Maeda, Y. Ruthenium Catalyzed
Transformation of Alcohols to Esters and Lactones. Tetrahedron Lett.
1981, 22, 5327−5330. (b) Blum, Y.; Shvo, Y. Catalytically Reactive
(η4-tetracyclone)(CO)2(H)2Ru and Related Complexes in Dehydro-
genation of Alcohols to Esters. J. Organomet. Chem. 1985, 282, C7−
C10. (c) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. Facile
Conversion of Alcohols into Esters and Dihydrogen Catalyzed by
New Ruthenium Complexes. J. Am. Chem. Soc. 2005, 127, 10840−
10841. (d) Musa, S.; Shaposhnikov, I.; Cohen, S.; Gelman, D. Ligand-
Metal Cooperation in PCP Pincer Complexes: Rational Design and
Catalytic Activity in Acceptorless Dehydrogenation of Alcohols.
Angew. Chem., Int. Ed. 2011, 50, 3533−3537. (e) Spasyuk, D.; Smith,
S.; Gusev, D. G. From Esters to Alcohols and Back with Ruthenium
and Osmium Catalysts. Angew. Chem., Int. Ed. 2012, 51, 2772−2775.
(f) Nielsen, M.; Junge, H.; Kammer, A.; Beller, M. Towards a Green
Process for Bulk-Scale Synthesis of Ethyl Acetate: Efficient Accept-
orless Dehydrogenation of Ethanol. Angew. Chem., Int. Ed. 2012, 51,
5711−5713. (g) He, L.-P.; Chen, T.; Gong, D.; Lai, Z.; Huang, K.-W.
Enhanced Reactivities Toward Amines by Introducing an Imine Arm
to the Pincer Ligand: Direct Coupling of Two Amines to Form an
Imine Without Oxidant. Organometallics 2012, 31, 5208−5211.
(h) Zeng, G.; Chen, T.; He, L.; Pinnau, I.; Lai, Z.; Huang, K.-W. A
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00888.
■
S
NMR and IR spectra of the new nickel pincer
complexes, NMR spectra of the reaction between {2,6-
I
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Green Approach to Ethyl Acetate: Quantitative Conversion of
Ethanol through Direct Dehydrogenation in a Pd-Ag Membrane
Reactor. Chem. - Eur. J. 2012, 18, 15940−15943. (i) Spasyuk, D.;
Vicent, C.; Gusev, D. G. Chemoselective Hydrogenation of Carbonyl
Compounds and Acceptorless Dehydrogenative Coupling of Alcohols.
J. Am. Chem. Soc. 2015, 137, 3743−3746. (j) de Boer, S. Y.; Korstanje,
T. J.; La Rooij, S. R.; Kox, R.; Reek, J. N. H.; van der Vlugt, J. I.
Ruthenium PNN(O) Complexes: Cooperative Reactivity and
Application as Catalysts for Acceptorless Dehydrogenative Coupling
Reactions. Organometallics 2017, 36, 1541−1549. (k) Sahoo, A. R.;
Jiang, F.; Bruneau, C.; Sharma, G. V. M.; Suresh, S.; Roisnel, T.;
Dorcet, V.; Achard, M. Phosphine-Pyridonate Ligands Containing
Octahedral Ruthenium Complexes: Access to Esters and Formic Acid.
Catal. Sci. Technol. 2017, 7, 3492−3498. (l) Alabau, R. G.; Esteruelas,
Catalysed Synthesis of Esters from Aldehydes and Alcohols.
Tetrahedron 1981, 37, 4313−4319. (b) Whittaker, A. M.; Dong, V.
M. Nickel-Catalyzed Dehydrogenative Cross-Coupling: Direct Trans-
formation of Aldehydes into Esters and Amides. Angew. Chem., Int. Ed.
2015, 54, 1312−1315. (c) Liu, H.; Eisen, M. S. Selective Actinide-
Catalyzed Tandem Proton-Transfer Esterification of Aldehydes with
Alcohols for the Production of Asymmetric Esters. Organometallics
2017, 36, 1461−1464.
(12) (a) Gopinath, R.; Patel, B. K. A Catalytic Oxidative
Esterification of Aldehydes Using V2O5-H2O2. Org. Lett. 2000, 2,
577−579. (b) Maki, B. E.; Scheidt, K. A. N-Heterocyclic Carbene-
Catalyzed Oxidation of Unactivated Aldehydes to Esters. Org. Lett.
2008, 10, 4331−4334. (c) De Sarkar, S.; Grimme, S.; Studer, A. NHC
Catalyzed Oxidations of Aldehydes to Esters: Chemoselective
Acylation of Alcohols in Presence of Amines. J. Am. Chem. Soc.
2010, 132, 1190−1191. (d) Liu, C.; Tang, S.; Zheng, L.; Liu, D.;
Zhang, H.; Lei, A. Covalently Bound Benzyl Ligand Promotes
Selective Palladium-Catalyzed Oxidative Esterification of Aldehydes
with Alcohols. Angew. Chem., Int. Ed. 2012, 51, 5662−5666.
(13) Finney, E. E.; Ogawa, K. A.; Boydston, A. J. Organocatalyzed
Anodic Oxidation of Aldehydes. J. Am. Chem. Soc. 2012, 134, 12374−
12377.
́
M. A.; Martínez, A.; Olivan, M.; Onate, E. Base-Free and Acceptorless
̃
Dehydrogenation of Alcohols Catalyzed by an Iridium Complex
Stabilized by a N,N,N-Osmaligand. Organometallics 2018, 37, 2732−
2740.
(3) For catalytic systems based on Fe, Co, or Mn, see:
̈
(a) Chakraborty, S.; Lagaditis, P. O.; Forster, M.; Bielinski, E. A.;
Hazari, N.; Holthausen, M. C.; Jones, W. D.; Schneider, S. Well-
Defined Iron Catalysts for the Acceptorless Reversible Dehydrogen-
ation-Hydrogenation of Alcohols and Ketones. ACS Catal. 2014, 4,
3994−4003. (b) Nguyen, D. H.; Trivelli, X.; Capet, F.; Paul, J.-F.;
Dumeignil, F.; Gauvin, R. M. Manganese Pincer Complexes for the
Base-Free, Acceptorless Dehydrogenative Coupling of Alcohols to
Esters: Development, Scope, and Understanding. ACS Catal. 2017, 7,
2022−2032. (c) Paudel, K.; Pandey, B.; Xu, S.; Taylor, D. K.; Tyer, D.
L.; Torres, C. L.; Gallagher, S.; Kong, L.; Ding, K. Cobalt-Catalyzed
Acceptorless Dehydrogenative Coupling of Primary Alcohols to
Esters. Org. Lett. 2018, 20, 4478−4481.
(14) Chakraborty, S.; Krause, J. A.; Guan, H. Hydrosilylation of
Aldehydes and Ketones Catalyzed by Nickel PCP-Pincer Hydride
Complexes. Organometallics 2009, 28, 582−586.
(15) (a) Chakraborty, S.; Zhang, J.; Krause, J. A.; Guan, H. An
Efficient Nickel Catalyst for the Reduction of Carbon Dioxide with a
Borane. J. Am. Chem. Soc. 2010, 132, 8872−8873. (b) Chakraborty,
S.; Patel, Y. J.; Krause, J. A.; Guan, H. Catalytic Properties of Nickel
Bis(phosphinite) Pincer Complexes in the Reduction of CO2 to
Methanol Derivatives. Polyhedron 2012, 32, 30−34. (c) Chakraborty,
S.; Zhang, J.; Patel, Y. J.; Krause, J. A.; Guan, H. Pincer-Ligated Nickel
Hydridoborate Complexes: the Dormant Species in Catalytic
Reduction of Carbon Dioxide with Boranes. Inorg. Chem. 2013, 52,
37−47.
(4) (a) Suzuki, T.; Matsuo, T.; Watanabe, K.; Katoh, T. Iridium-
Catalyzed Oxidative Dimerization of Primary Alcohols to Esters Using
2-Butanone as an Oxidant. Synlett 2005, 1453−1455. (b) Bertoli, M.;
Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.; Gusev, D. G.
Osmium and Ruthenium Catalysts for Dehydrogenation of Alcohols.
Organometallics 2011, 30, 3479−3482.
(5) Liu, C.; Tang, S.; Lei, A. Oxidant Controlled Pd-Catalysed
Selective Oxidation of Primary Alcohol. Chem. Commun. 2013, 49,
1324−1326.
(6) Hoshimoto, Y.; Ohashi, M.; Ogoshi, S. Nickel-Catalyzed
Selective Conversion of Two Different Aldehydes to Cross-Coupled
Esters. J. Am. Chem. Soc. 2011, 133, 4668−4671.
(7) (a) Gowrisankar, S.; Neumann, H.; Beller, M. General and
Selective Palladium-Catalyzed Oxidative Esterification of Alcohols.
Angew. Chem., Int. Ed. 2011, 50, 5139−5143. (b) Liu, C.; Wang, J.;
Meng, L.; Deng, Y.; Li, Y.; Lei, A. Palladium-Catalyzed Aerobic
Oxidative Direct Esterification of Alcohols. Angew. Chem., Int. Ed.
2011, 50, 5144−5148. (c) Srimani, D.; Balaraman, E.;
Gnanaprakasam, B.; Ben-David, Y.; Milstein, D. Ruthenium Pincer-
Catalyzed Cross-Dehydrogenative Coupling of Primary Alcohols with
Secondary Alcohols under Neutral Conditions. Adv. Synth. Catal.
2012, 354, 2403−2406.
(8) Curran, S. P.; Connon, S. J. Selenide Ions as Catalysts for Homo-
and Crossed-Tishchenko Reactions of Expanded Scope. Org. Lett.
2012, 14, 1074−1077.
(9) (a) Ekoue-Kovi, K.; Wolf, C. One-Pot Oxidative Esterification
and Amidation of Aldehydes. Chem. - Eur. J. 2008, 14, 6302−6315.
(b) Tang, S.; Yuan, J.; Liu, C.; Lei, A. Direct Oxidative Esterification
of Alcohols. Dalton Trans. 2014, 43, 13460−13470.
(16) Chakraborty, S.; Patel, Y. J.; Krause, J. A.; Guan, H. A Robust
Nickel Catalyst for Cyanomethylation of Aldehydes: Activation of
Acetonitrile under Base-Free Conditions. Angew. Chem., Int. Ed. 2013,
52, 7523−7526.
(17) (a) Jin, L.-K.; Wan, L.; Feng, J.; Cai, C. Nickel-Catalyzed
Regioselective Cross-Dehydrogenative Coupling of Inactive C(sp3)−
H Bonds with Indole Derivatives. Org. Lett. 2015, 17, 4726−4729.
(b) Soni, V.; Khake, S. M.; Punji, B. Nickel-Catalyzed C(sp2)−H/
C(sp3)−H Oxidative Coupling of Indoles with Toluene Derivatives.
ACS Catal. 2017, 7, 4202−4208. (c) Li, Z.-L.; Sun, K.-K.; Cai, C.
Nickel-Catalyzed Cross-Dehydrogenative Coupling of α-C(sp3)−H
Bonds in N-Methylamides with C(sp3)−H Bonds in Cyclic Alkanes.
Org. Lett. 2018, 20, 6420−6424.
(18) When in equilibrium, deuterium prefers the strongest bond,
which in this case would be the acyl−hydrogen (Csp2−H) bond of the
aldehyde rather than the benzylic carbon−hydrogen (Csp3−H) bond
of the nickel alkoxide complex.
(19) Among complexes {2,6-(iPr2PO)2C6H3}NiSC6H4X (X = 4-
OCH3, 4-CH3, H, 4-Cl, and 4-CF3), the one with the CF3 substituent
has the highest Ni−S bond dissociation energy. For details, see:
Zhang, J.; Adhikary, A.; King, K. M.; Krause, J. A.; Guan, H.
Substituent Effects on Ni−S Bond Dissociation Energies and Kinetic
Stability of Nickel Arylthiolate Complexes Supported by a Bis-
(phosphinite)-based Pincer Ligand. Dalton Trans. 2012, 41, 7959−
7968.
(10) (a) Murahashi, S.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H.
Ruthenium-Catalyzed Oxidative Transformation of Alcohols and
Aldehydes to Esters and Lactones. J. Org. Chem. 1987, 52, 4319−
4327. (b) Cheng, J.; Zhu, M.; Wang, C.; Li, J.; Jiang, X.; Wei, Y.;
Tang, W.; Xue, D.; Xiao, J. Chemoselective Dehydrogenative
Esterification of Aldehydes and Alcohols with a Dimeric Rhodium(II)
Catalyst. Chem. Sci. 2016, 7, 4428−4434.
(20) Related pincer nickel hydroxide complexes also proved to be
too unstable for isolation. For examples, see: (a) Hao, J.; Mougang-
́
Soume, B.; Vabre, B.; Zargarian, D. On the Stability of a POCsp3OP-
Type Pincer Ligand in Nickel(II) Complexes. Angew. Chem., Int. Ed.
2014, 53, 3218−3222. (b) Wellala, N. P. N.; Luebking, J. D.; Krause,
J. A.; Guan, H. Roles of Hydrogen Bonding in Proton Transfer to
κP,κN,κP-N(CH2CH2PiPr2)2-Ligated Nickel Pincer Complexes. ACS
Omega 2018, 3, 4986−5001.
(11) (a) Grigg, R.; Mitchell, T. R. B.; Sutthivaiyakit, S. Oxidation of
Alcohols by Transition Metal Complexes − IV: The Rhodium
J
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(21) Several pincer nickel hydroxide complexes have been isolated,
although the pincer ligands often lack P−O bonds or contain sterically
́
protected P−O bonds. For details, see: (a) Campora, J.; Palma, P.; del
́
Río, D.; Alvarez, E. CO Insertion Reactions into the M−OH Bonds of
Monomeric Nickel and Palladium Hydroxides. Reversible Decarbon-
ylation of a Hydroxycarbonyl Palladium Complex. Organometallics
2004, 23, 1652−1655. (b) Castonguay, A.; Beauchamp, A. L.;
Zargarian, D. New Derivatives of PCP-Type Pincer Complexes of
Nickel. Inorg. Chem. 2009, 48, 3177−3184. (c) Adhikari, D.; Mossin,
S.; Basuli, F.; Dible, B. R.; Chipara, M.; Fan, H.; Huffman, J. C.;
Meyer, K.; Mindiola, D. J. A Dinuclear Ni(I) System Having a
Diradical Ni2N2 Diamond Core Resting State: Synthetic, Structural,
Spectroscopic Elucidation, and Reductive Bond Splitting Reactions.
Inorg. Chem. 2008, 47, 10479−10490. (d) Zargarian, D.; Salah, A.
[2,6-Bis(diphenylphosphanyloxy)phenyl-κ3P,C1,P′]hydroxidonickel-
(II). Acta Crystallogr., Sect. E: Struct. Rep. Online 2011, 67, m940.
(e) Jonasson, K. J.; Mousa, A. H.; Wendt, O. F. Synthesis and
Characterisation of POCsp3OP Supported Ni(II) Hydroxo, Hydrox-
ycarbonyl and Carbonate Complexes. Polyhedron 2018, 143, 132−
137. (f) Mousa, A. H.; Bendix, J.; Wendt, O. F. Synthesis,
Characterization, and Reactivity of PCN Pincer Nickel Complexes.
Organometallics 2018, 37, 2581−2593.
(22) A similar protonation reaction was observed between {2,6-
(iPr2PCH2)2C6H3}NiH and MeOH. For details, see: Martínez-Prieto,
́
́
́
L. M.; Avila, E.; Palma, P.; Alvarez, E.; Campora, J. β-Hydrogen
Elimination Reactions of Nickel and Palladium Methoxides Stabilised
by PCP Pincer Ligands. Chem. - Eur. J. 2015, 21, 9833−9849.
(23) (a) Hao, J.; Vabre, B.; Zargarian, D. POCOP-Ligated Nickel
Siloxide Complexes: Syntheses, Characterization, and Reactivities.
Organometallics 2014, 33, 6568−6576. (b) Adhikary, A.; Krause, J. A.;
Guan, H. Configurational Stability and Stereochemistry of P-
Stereogenic Nickel POCOP-Pincer Complexes. Organometallics
2015, 34, 3603−3610.
́
́
(24) Martínez-Prieto, L. M.; Palma, P.; Alvarez, E.; Campora, J.
Nickel Pincer Complexes with Frequent Aliphatic Alkoxo Ligands
[(iPrPCP)Ni-OR] (R = Et, nBu, iPr, 2-hydroxyethyl). An Assessment
of the Hydrolytic Stability of Nickel and Palladium Alkoxides. Inorg.
Chem. 2017, 56, 13086−13099.
(25) Jonasson, K. J.; Wendt, O. F. Synthesis and Characterization of
a Family of POCOP Pincer Complexes with Nickel: Reactivity
Towards CO2 and Phenylacetylene. Chem. - Eur. J. 2014, 20, 11894−
11902.
(26) (a) Enthaler, S.; Bru
̈
ck, A.; Kammer, A.; Junge, H.; Irran, E.;
Gulak, S. Exploring the Reactivity of Nickel Pincer Complexes in the
̈
Decomposition of Formic Acid to CO2/H2 and the Hydrogenation of
NaHCO3 to HCOONa. ChemCatChem 2015, 7, 65−69. (b) Ma, Q.-
Q.; Liu, T.; Adhikary, A.; Zhang, J.; Krause, J. A.; Guan, H. Using CS2
to Probe the Mechanistic Details of Decarboxylation of Bis-
(phosphinite)-Ligated Nickel Pincer Formate Complexes. Organo-
metallics 2016, 35, 4077−4082. (c) Osipova, E. S.; Belkova, N. V.;
Epstein, L. M.; Filippov, O. A.; Kirkina, V. A.; Titova, E. M.; Rossin,
A.; Peruzzini, M.; Shubina, E. S. Dihydrogen Bonding and Proton
Transfer from MH and OH Acids to Group 10 Metal Hydrides
[(tBuPCP)MH] [tBuPCP = κ3-2,6-(tBu2PCH2)2C6H3; M = Ni, Pd].
Eur. J. Inorg. Chem. 2016, 2016, 1415−1424.
(27) Li, H.; Meng, W.; Adhikary, A.; Li, S.; Ma, N.; Zhao, Q.; Yang,
Q.; Eberhardt, N. A.; Leahy, K. M.; Krause, J. A.; Zhang, J.; Chen, X.;
Guan, H. Metathesis Reactivity of Bis(phosphinite) Pincer Ligated
Nickel Chloride, Isothiocyanate and Azide Complexes. J. Organomet.
Chem. 2016, 804, 132−141.
(28) Pandarus, V.; Zargarian, D. New Pincer-Type Diphosphinito
(POCOP) Complexes of Nickel. Organometallics 2007, 26, 4321−
4334.
K
DOI: 10.1021/acs.organomet.8b00888
Organometallics XXXX, XXX, XXX−XXX