Convenient transfer semihydrogenation methodology for alkynes using a PdII-NHC precatalyst

Article abstract of DOI:10.1021/cs4011502

A convenient and easy-to-use protocol for the Z-selective transfer semihydrogenation of alkynes was developed, using ammonium formate as the hydrogen source and the easily prepared and commercially available, highly stable complex PdCl(η³-C₃H₅)(IMes) (1) as the (pre)catalyst. Combined with triphenyl posphine as an additional ligand, this system provides a robust catalytic synthetic method that shows little to no over-reduction or isomerization after full substrate conversion. The system allows the direct use of solvents and reagents, as received from the supplier without drying or purification, thus providing a practical method for semihydrogenation of a broad range of alkynes. The mechanism behind these high and enhanced selectivities was determined through a set of kinetic experiments.

Full text of DOI:10.1021/cs4011502

Research Article
pubs.acs.org/acscatalysis
Convenient Transfer Semihydrogenation Methodology for Alkynes
Using a PdII-NHC Precatalyst
Ruben M. Drost,† Tessel Bouwens,† Nicolaas P. van Leest,† Bas de Bruin,‡ and Cornelis J. Elsevier*,†
†Molecular Inorganic Chemistry, Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1090 GD
Amsterdam, The Netherlands
‡Homogeneous Catalysis, Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1090 GD
Amsterdam, The Netherlands
S
* Supporting Information
ABSTRACT: A convenient and easy-to-use protocol for the Z-selective transfer
semihydrogenation of alkynes was developed, using ammonium formate as the
hydrogen source and the easily prepared and commercially available, highly
stable complex PdCl(η3-C3H5)(IMes) (1) as the (pre)catalyst. Combined with
triphenyl posphine as an additional ligand, this system provides a robust catalytic
synthetic method that shows little to no over-reduction or isomerization after full
substrate conversion. The system allows the direct use of solvents and reagents,
as received from the supplier without drying or purification, thus providing a
practical method for semihydrogenation of a broad range of alkynes. The mechanism behind these high and enhanced
selectivities was determined through a set of kinetic experiments.
KEYWORDS: alkyne reduction, palladium, N-heterocyclic carbene, NHC, transfer-hydrogenation
the E-alkene, migration of the double bond, and over-reduction
of the substrate (see also Figure 1). Furthermore, leaching of
the poisonous metals and poor reproducibility between batches
of catalyst are additional issues in its application. When
considering laboratory applications, it has another disadvantage:
it uses molecular hydrogen as the reductant, which requires
specific conditions for safe handling.41 Yet, despite these
drawbacks, Lindlar’s catalyst is still widely applied because it is
practical, it is cheap, commercially available, and does not
require inert conditions.
The importance of the semihydrogenation reaction,
especially at the laboratory scale, and the disadvantages of the
benchmark catalyst system mentioned above have prompted
the development of improved methodologies. To circumvent
the use of molecular hydrogen and to develop a safer protocol
that is more straightforwardly applicable, the transfer semi-
hydrogenation reaction of alkynes has been developed. While
sodium methanolate,22 a combination of silanes and alkyl
alcohols,39 and Hantzsch ester 1,4-dihydropyridine42,43 have
also been applied as the hydrogen source, the majority of the
applied systems use ammonium formate,44−49 which may also
be generated in situ by the decomposition of DMF.34,50
Transfer hydrogenation, especially the protocols using
ammonium formate, has greatly improved the applicability of
alkyne semihydrogenation. Catalyst systems that tolerate a wide
variety of functional groups have been developed, and when
applying these, high selectivities are obtained for many
INTRODUCTION
■
Catalysis is a research area of considerable activity, in which,
frequently, new and improved catalysts are developed and
reported. However, whether these catalysts are actually applied
depends on more than their performance: generally, a
convenient method is just as important, making applicability
an integral aspect of catalyst design. Z-Alkenes are present in
many biologically and pharmaceutically active compounds and
are produced in several bulk and fine chemical processes.1−4
Therefore, convenient methods for the synthesis of these
compounds, especially at the laboratory scale, are intensively
studied. Several methods for the synthesis of alkenes have been
developed, such as the Wittig,5−7 the Peterson8 and Julia9
olefination, olefin metathesis,10,11 cross-coupling reactions,12
and elimination13 of halides from alkenyl halides. However,
these methods suffer from the disadvantage that any preference
for the formation of E- or Z-isomers is highly substrate
dependent.3 Another often applied route is the reduction of
alkynes, which is the generally preferred methodology for two
reasons: first, it is a reliable method to obtain Z-alkenes, and
second, alkynes are versatile synthetic building blocks for,
among others, Sonogashira,14,15 Glaser,16,17 and Cadiot−
Chodkiewicz13 reactions.2,18,19 The catalytic semihydrogenation
of alkynes has mainly focused on palladium as the active metal,
using both particle and molecular catalysts.3,20−30 However,
catalysts based on other transition metals, such as Rh,31
Ru,32−34 Ni,35,36 Nb,37 Cr,38 Cu,39 and V40 have also been
reported. Although many processes have been developed, the
improved Lindlar’s catalyst (Pd black on BaCO3 that is
poisoned with PbOAc and quinoline) is still the benchmark.3,20
However, this catalyst suffers from isomerization of the Z- to
Received: December 5, 2013
Revised: March 14, 2014
Published: March 20, 2014
© 2014 American Chemical Society
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Figure 1. Transfer semihydrogenation of 1-phenyl-1-propyne, the catalysts applied, and the (expected) products of the reaction: Z-1-phenyl-1-
propene (Z), E-1-phenyl-1-propene (E), 1-phenyl-propane (Alk), and 1-phenyl-2-propene (Iso).
substrates.3 Currently, the main challenges are the prevention
of over-reduction and isomerization at high degrees of
conversion, selective conversion of (skipped) diynes, and
RESULTS AND DISCUSSION
■
The first requirement for the development of a hands-on and
selective catalytic synthetic protocol is the availability of a
achieving enhanced activities toward electron deficient 1,2-
suitable precatalyst. The stable PdCl(η3-C3H5)(NHC) com-
diaryl alkynes.
plexes such as 1−3 were reasoned to be ideal precatalysts.
We earlier reported on a catalyst system that applies Pd0-
Besides their high stability, they are straightforwardly
complexes with a bis-mesityl-imidazole-2-ylidene (IMes) ligand
synthesized in high yields, and some of them are even
that is highly selective for some of the most challenging
commercially available.52−54 Another reason to choose this type
substrates reported.47,51 This catalyst does not lead to any over-
of catalyst precursors was that they may be transformed directly
reduction nor isomerization of the Z-alkene product after
into the required active Pd0-species under the conditions of the
consumption of the substrate. This feature, up to then,
transfer semihydrogenation, which was confirmed in initial
remained one of the main challenges in this research field, so
studies (Scheme 1).55,56 Complexes 1−3 and their Pd0-
alleviation of this serious problem renders this type of catalysts
analogues 4 and 5 were screened in the semihydrogenation
an ideal basis for the design of a convenient semihydrogenation
of 1-phenyl-1-propyne (Figure 1 and Table 1). Since we
protocol. However, a disadvantage of this system is that the
focused on the prevention of over-reduction and isomerization,
active catalyst cannot be isolated and that the corresponding
a 5-fold excess of triethylammonium formate was applied. This
precatalyst is not shelf-stable. Therefore, the precatalyst must
allowed the determination of the true selectivity of the catalyst
be generated shortly before using it, which requires specific
know-how, hands-on experience with inorganic laboratory
manipulations, and specialized equipment that allows synthetic
manipulations under strict anaerobic conditions. As a result,
Table 1. Results of the Transfer Semihydrogenation of 1-
Phenyl-1-propyne with Various Precatalysts
a
,
b
c
d
e
#
cat.; add.
Z-yield (%)
Z-sel (conv) (%) time to FC (h)
this catalytic system is not very practical for many general
synthetic applications. In order to improve the applicability of
this catalytic methodology, we set out to develop a catalyst
system that is based on a shelf-stable Pd(NHC) catalyst, and
readily available additives may be employed for the enhance-
ment of their selectivity and stability. The aim is to obtain a
system that provides excellent selectivities in the semi-
hydrogenation of several representative alkynes using commer-
cially available analytical reagent (AR) grade solvents and
reagents, as received from the suppliers. Such a methodology
would provide a novel, easy to perform and straightforward
synthetic protocol for the semihydrogenation of alkynes to Z-
alkenes employing triethylammonium formate as the reducing
agent. Since improvement of a method and optimization for
individual substrates should, preferably, be achieved in a
rational fashion, mechanistic research is an essential aspect in
the development of a catalytic synthetic protocol. Hence, the
mechanism of the precatalyst activation, the molecularity of the
active catalyst, and, most noteworthy, the kinetic analysis of the
product formation were elucidated. On the basis of these
studies, a mechanism was proposed.
f
1
1
2
3
4
5
91
84
88
76
43
61
93
98
17
62
78
93 (97)
95 (90)
92 (97)
98 (77)
99 (44)
94 (64)
98 (95)
99 (98)
99 (18)
99 (63)
93 (83)
1.2
f
f
2
3.1
3
5.6
4
>24
>24
>24
24
5
d
6
6
7
1+ 1 PPh3
1+ 2 PPh3
1+ 4 PPh3
Pd(PPh3)4
8
24
c
9
>24
>24
>24
10
11
g
Lindlar
a
1 mol % catalyst and 2.7 mmol 1-phenyl-1-propyne, 70 °C. Additives
in equivalents with respect to the catalyst. For a full table of tested
precatalysts and additives. See Table S1, Supporting Information. GC-
yields given for the Z-alkene. Selectivity toward the Z-alkene in %
([response factor corrected GC area of Z-alkene]/[response factor
corrected GC area of the total products total product]·100%) at the
corresponding conversion, given in brackets. Time to reach full
conversion of the substrate; experiments were stopped after 24 h.
Strong over-reduction and isomerization of the Z-alkene product was
observed after full substrate conversion. 3 mol % of the catalyst was
b
c
d
e
f
g
used.
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instead of a selectivity induced by the stoichiometry of the
formic acid.
In a second approach to obtain better catalytic results, we
investigated the influence of several additives. On the basis of
our previous research, we first chose to use MA as an additive
ligand (Table S1 (Supporting Information), entries 7 and 8).
One equivalent of MA with respect to the catalyst showed little
improvement, and two equivalents did improve the Z-selectivity
of the reaction substantially. However, still some over-reduction
of the product occurred after full conversion of the substrate.
As an alternative, we tested triphenyl phosphine as an additive
ligand because it is water-stable, easy to handle, and readily
available (Figure 2).
From the results shown in Table 1, it is clear that the ligand
bearing two mesityl groups on the wing tips gives the highest
activity. Furthermore, PdII-precatalysts 1 and 2 hydrogenate 1-
phenyl-1-propyne significantly faster than their Pd0 analogues 4
and 5. However, these show a high degree of isomerization and
over-reduction of the product after full conversion of the
substrate (1 in Figure 2A and B and 2 and 3 in Figure S2
As mentioned above, applying catalyst 1 without any
additives leads to fast reactions, but these reactions are
associated with considerable over-reduction to the alkane and
Z-alkene to E-alkene isomerization, especially when the
reaction reaches full conversion of the alkyne (Table 1, entry
1 and Figure 2A and B). These problems can be circumvented
by the addition of two equivalents of PPh3. This leads to an
increased selectivity of the catalyst throughout the reaction
(Figure 2A and B), and most importantly, it virtually stops the
alkene over-reduction and alkene isomerization reactions at full
substrate conversion. Stronger coordinating additives, such as
diphenylphosphinobutane (DPPB), are less beneficial (Figure
2A). Addition of one equivalent of DPPB reduces the activity
several orders of magnitude, making the reactions too slow for
practical application. The beneficial influence of the NHC-
ligand was demonstrated through a control reaction with
Pd(PPh3)4 (Table 1, entry 10). This complex is an order of
magnitude slower than complex 1 with 2 equivalents of PPh3.
From this observation, we conclude that the NHC ligand forms
a more active complex and is not substituted for a phosphine
ligand during the reaction. The added value of applying this
NHC ligand system was further demonstrated by testing
[Pd(η3-C3H5)Cl]2, a common PdII source, as a precatalyst.
This simple Pd salt was significantly less selective and gave a
strong over-reduction; applying this compound with two and
four equivalents of PPh3 led to severe deactivation of this
catalyst (Table S1 (Supporting Information) entries 20−22).
Among the above-described systems, complex 1 combined with
2 equivalents of PPh3 proved to be the most robust and
selective, without compromising the reaction rates too much.
This finding allowed a significant simplification of the catalytic-
synthetic protocol, where all commercial solvents and reagents
can be used without additional purification and/or drying steps,
in which all time-consuming preparative manipulations and
Schlenk techniques can be omitted. Briefly bubbling an inert
gas (Ar or N2) through the reaction mixture of the reagents
before introducing complex 1 and the PPh3 additive suffices to
obtain excellent catalytic results.
Figure 2. Effect of applying additives together with catalyst 1 in the
semihydrogenation of 1-phenyl-1-propyne. (A) The yield in Z-alkene
versus time is shown. (B) The influence of the phosphine additive on
the selectivity throughout the reaction is shown (further over-
reduction and isomerization by precatalyst 1 without additives is
omitted for clarity).
(Supporting Information)). In previous mechanistic studies of
the Pd0-NHC catalyst, we found that maleic anhydride (MA)
functions as a boomerang ligand that slows down the reaction
but also enhances the selectivity of the catalyst.51 As, under the
applied catalytic conditions (Table 1,entry 1 and 2), a Pd0-
NHC species is generated in absence of stabilizing ligands such
as MA, the formation of more reactive but less selective species
is actually an expected observation.
Two approaches to improve these catalytic systems were
investigated. First, complexes with hemilabile ligand function-
alities were applied, which may prevent isomerization and over-
reduction of the product through competition for the
coordination site between the Z-alkene and the secondary
donor group within the ligand. Complex 6, that bears two
hemilabile triazole moieties on its wingtips, was tested in the
reaction and is highly selective. However, its activity was greatly
diminished with respect to precatalyst 1 (and 4); it does not
reach full conversion in 24 h, presumably due to too strong an
interaction between Pd and the triazole groups.
The substrate scope of this simplified and robust catalytic
procedure was explored, using a range of alkynes with various
electronic and steric properties, and containing different
functional groups that can potentially interfere with the transfer
semihydrogenation reaction. The results are summarized in
Table 2.
The catalyst system performs well for a wide range of alkynes
and is compatible with a variety of functional groups. In the
presence of an additional equivalent of NEt3 (to ensure neutral
conditions), the reaction is compatible with carboxylate
functionalities generated in situ from substrates containing
carboxylic acids (entries 4 and 17). The yields and selectivities
are somewhat compromised when the carboxylate group is
directly attached to the alkyne moiety of the substrate (entry
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4). This may well be the result of simultaneous (chelate)
binding of the alkyne and the carboxylate moieties of
propargilic acid to the metal.4 This hypothesis is supported
by the smooth and selective conversion of the methyl esters
shown in entries 5 and 6. The reaction in entry 5 does reach full
conversion; however, after a prolonged reaction time (14 h), a
yield of 85% of the Z-alkene was obtained, but a mass balance
of 90% was found on GC. Presumably, hydrolysis of the ester
takes place. The transfer semihydrogenation reaction does not
seem compatible with aldehydes that are linked directly to the
alkyne (entry 3). The substrate is fully converted within 3 h,
but none of the expected products was observed on GC-MS.
The NMR-spectrum of the crude reaction mixture did also not
allow us to identify which species were formed. However, when
a spacer is present between the aldehyde and the alkyne
moieties, excellent yields and conversions are obtained, and the
aldehyde functionality remains intact (entry 16). Primary
alcohols (entry 2) and allylic alcohols (entries 7 and 8) are also
hydrogenated efficiently. The results with the challenging allylic
alcohols, that easily eliminate water to form ene-ynes, are
noteworthy. Partial dehydration may still be the reason for the
observed incomplete mass balance (74%) when using 3-hexyn-
2-ol (entry 8). The selectivity toward the Z-alkene of this
substrate is excellent since no isomerized or alkane compounds
were observed. Several terminal alkenes were investigated
(entries 10, 11, and 12). The alkyl substituted alkyne is
converted neatly. However, the styrene products that are
formed when phenyl acetylens (entries 11 and 12) are
hydrogenated give rise to subsequent coupling reactions to
another styrene or alkyne molecule, which are detected as side
products in GC and GC-MS. Furthermore, the mass balances
are low (66 and 77%) for these reactions. This may be caused
by a side reaction, in which the styrene-like species are oligo- or
polymerized. Diphenyl acetylene (entry 13) is known to be a
difficult substrate in semihydrogenation reactions, but none-
theless, Z-stilbene is formed with high Z-selectivity at 77%
conversion. After 24 h, the conversion is virtually halted.
Possibly, improved results may be obtained by application of
higher catalyst loadings. The nicotinitrile (entry 14) only
reaches a conversion of 21%, but the selectivity is excellent, and
most importantly, the nitrile functionality is not hydrogenated.
1-Phenyl-pentyn-4-ene (entry 15) is converted with a moderate
selectivity and yield, but the results seem promising for this
difficult type of substrate. The conversion continued after 24 h,
but the selectivity decreased, and the determination of the exact
conversion became difficult because a byproduct formed that
was not separable on GC. Excellent results were further
obtained for 5-(2-phenyleth-1-ynyl)thiophene-2-carbaldehyde
(entry 16). This substrate is converted quickly and very
selectively. This is noteworthy, considering the complex
structure of this molecule that consists of multiple function-
alities that are known to interact with Pd. The selective
conversion of furoic acid (entry 17) is another example
demonstrating the high functional group tolerance of the
catalytic system. Furthermore, it should be noted that this
procedure was optimized for the conversion of 1-phenyl-1-
propyne, but given this wide variety of functionalies that are
present in the tested substrates, improved results for several of
these challenging entries may be obtained by tuning the
reaction conditions and the concentration of the additive.
After the successful development of this convenient method-
ology and demonstrating that it has a broad substrate scope, we
focused on the reaction mechanism behind these selective
Table 2. Transfer Semihydrogenation for a Selection of
Substrates Using the Simplified and Robust Catalytic
Procedure Based on Complex 1 and 2 Equivalents of PPh3
a
All substrates were used as received; 1 mol % catalyst, 2 mol % PPh3,
2.7 mmol of the selected substrate, 13.5 mmol of HCOOH, and 13.5
b
mmol of NEt3 at 70 °C. GC-yield for the Z-alkene except for entries 5
c
and 17, which are determined by NMR. Selectivity toward the Z-
alkene in % ([GC area of Z-alkene]/[internal standard corrected initial
GC area of alkyne −GC area of alkyne]·100%) conversion within
d
parentheses. The time at which the sample was taken. The reaction
was stopped after 48 h for entries 4 and 14 and after 24 h for entries 1,
e
7, and 13. Addition of fresh substrate and formic acid shows that the
catalyst is still active at full conversion. It was found that the reaction
time is dependent on the grade of the formic acid while it does not
f
g
affect the selectivity. See text. An additional equivalent of NEt3 was
h
added to ensure neutral conditions. For entry 8, a mass balance of
74% was found. Entry 11 had a mass balance of 66%, and entry 12 had
a mass balance of 77%.
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transfer semihydrogenation reactions. First, the mechanism of
the in situ reduction of the precatalyst to the active Pd0-species
was studied. Mass analysis of the gas phase of the reaction was
performed, and the formation of CO2 and propene was
detected confirming similar findings as reported by Nolan et
al.52,55 The presence of a Pd0-IMes species was subsequently
corroborated by a trapping experiment with CS2, in which the
dinuclear CS2 bridged [(Pd(IMes))2-μ(κ-S,-η2-CS2)]2 complex,
8, was isolated and characterized. On the basis of these findings,
we propose the mechanism for catalyst activation shown in
Scheme 1.
equivalents of phosphine, we noted an increased Z-selectivity
throughout the entire reaction (Figure 2B) when two
equivalents of PPh3 were applied. Subsequently, the influence
of the phosphine concentration on the rate was measured using
a catalyst concentration of 1.5 mM and a triphenylphosphine
concentration ranging from 0 to 6.0 mM (Figure S4,
Supporting Information). A strong inhibiting effect by the
phosphine was observed; when 1 and PPh3 are applied in a 1:1
ratio, the activity of the catalyst system is reduced by 80%, thus
demonstrating that the phosphine-coordinated complex is
either significantly less active or perhaps even in a dormant
state.
Scheme 1. Generation of the Pd0 Species from Precatalyst 1
and Its Trapping with CS2 Forming 8
The phosphine additive functions as an inhibitor and
increases the selectivity of the reaction. Subsequently, a kinetic
pseudo-first-order analysis of the product formation was
performed that determined the mechanism behind these
effects. This method allowed for the estimation of the rates
of formation of the individual reaction products, through which
the effects of phosphine on the rate of formation of each
product were quantified (Figure S5 (Supporting Information)
and Table 3).59,60 The model of the reaction was simplified by
Table 3. Calculated Values of the Individual Rate Constants
Quantifying the Influence of the Phosphine Additive on the
Pathways to the Reaction Products
1
1 + 1 PPh3
1 + 2 PPh3
First, the chloride ligand of 1 is exchanged for a formate ion,
which upon liberation of CO2 forms a hydride complex.
Subsequent reductive elimination of propene gives the active
Pd0-catalyst 7, which is likely to have two coordinating solvent
and/or substrate molecules bound to the metal. The addition of
CS2 leads to the formation of the highly stable complex 8,
which was isolated. The structure of 8 was derived from mass
spectrometry and the characteristic IR-vibrations for this rare
type of palladium complexes as reported by Ferrar et al.57
Subsequently, the kinetic order in the precatalyst was
determined by measuring the dependence of the reaction rate
on the catalyst concentration, varying the concentration of the
precatalyst between 0.7 and 2.3 mM. Using the differential rate
method, an order of 0.98 in the precatalyst was found. This
clearly indicated first order kinetics in the concentration of the
catalyst, pointing to a mononuclear active species (Figure S3,
Supporting Information).58
Cazin et al. recently reported a system that also consists of a
Pd0-NHC species with a phosphine ligand. This species is also
highly active in the transfer semihydrogenation of alkynes using
formic acid as the hydrogen source but without NEt3.46 At first
glance, these systems seem similar. However, they operate via
different mechanisms. The Pd0(NHC)(PCy3) complex by
Cazin et al. was found to generate molecular hydrogen under
catalytic conditions and was proposed to involve a dihydride
intermediate. For the currently discussed system, no
dihydrogen was detected by mass spectrometry of the gas
phase of the reaction. Apparently, the formation of hydrogen
does not occur in the catalyst system presented here. Most
likely, the currently reported reaction proceeds via an anionic
Pd0(NHC)(hydride) intermediate similar to that reported by
Hauwert et al., which operates with two separate hydrogen
donors (triethylammonium and formate).51
a
k1
k2
k3
3 × 10−02
1 × 10−03
8 × 10−05
7 × 10−03
4 × 10−05
6 × 10−05
6 × 10−03
1 × 10−07
6 × 10−05
a
k-Values were determined in min−1 at 70 °C.
treating the formation of the byproducts as a single reaction
step (Scheme 2 and Scheme S2 (Supporting Information)).
This not only greatly reduced the number of reaction constants
that need to be calculated (which increases the accuracy of the
fits) but also was in line with the proposed mechanism for the
Pd0-(Ar)BIAN (bis(aryl)acenaphthenequinonediimine) cata-
lyzed semihydrogenation of 1-octyne, in which all byproduct
formation proceeds via one common [Pd(hydrido)(BIAN)(Z-
alkenyl)] intermediate.4 With this (simplified) kinetic analysis,
three rate constants were determined: (1) the rate of
semihydrogenation of the alkyne to the Z-alkene (k1), (2)
the rate of isomerization and hydrogenation of the Z-alkene to
the byproducts (k2), and (3) the rate of direct conversion of the
alkyne into the byproducts (k3) (Scheme 2 and Figure S5
(Supporting Information)). Fitting the data and integration of
the differential equations showed that for the catalyst without
additive a stepwise mechanism (k1 + k2) is responsible for the
formation of the byproducts (>90%), while the contribution of
the direct isomerization pathway (k3) is negligible. This was
also proposed by Hauwert et al. and Kluwer et al.4,51
Table 3 clearly shows the role of the additive: it decreases the
alkene isomerization and over-reduction rate of the Z-alkene, k2,
by 4 orders of magnitude, while affecting the alkyne
semihydrogenation rate only by a factor of 5. The direct
over-reduction and isomerization pathway k3 is hardly affected
by PPh3. In fact, in the presence of two equivalents of PPh3, the
k2 isomerization and over-reduction pathway gets blocked
kinetically, while the k1 alkyne semihydrogenation pathway
remains clearly competitive over the intrinsically slow direct
isomerization pathway k3 (k1 remaining 2 orders of magnitude
larger than k3). The additive effect is most likely a result of
Having determined the kinetic order of the catalyst system
and the mechanism for the generation of the active catalyst, the
role of the additive was investigated. Comparing the selectivity
against the conversion of the reactions with zero, one, or two
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equivalents of PPh3 allows selective transformation of a variety
alkynes, differing in electronic and steric properties and
containing various functional groups, without the need for
strict solvent or reagent purification or the use of time-
consuming glovebox or Schlenk techniques. The PPh3 additive
substantially slows down over-reduction and isomerization of
the obtained Z-alkenes at high conversions. The detailed kinetic
analysis of the catalytic system provided a plausible mechanistic
rationale for the enhanced selectivities induced by PPh3.
Scheme 2. Proposed Role of the Additive on the Reaction
Pathways in the Catalytic Cycle
EXPERIMENTAL SECTION
■
Complex synthesis was performed using Schlenk techniques
under dry nitrogen. Solvents were dried according to standard
procedures and distilled prior to use,61 unless stated otherwise.
Maleic anhydride was crystallized from hot DCM. [Pd(Cl(η3-
C3H5)]2, triethyl amine, formic acid, potassium tert-butoxide,
and triphenylphosphine were purchased from Sigma Aldrich. A
Pd-DVTMS (1,3-divinyl-1,1,3,3-tetramethyl-disiloxane palladi-
um0) solution was generously provided by Umicore. Com-
pounds 1,62 3,63 4,64 and [1-mesityl-3-propyl-imidazolium]
bromide65 were synthesized according to literature procedures.
NMR spectra were recorded on Bruker AV 400 MHz, Bruker
DRX 300 MHz, and Varian Mercury 300 MHz spectrometers.
HR mass spectrometry was performed on a Bruker MicrO-
TOF-Q machine using ESI, and elemental analyses were
performed by Mikroanalytisches Laboratorium Kolbe, Mulheim
̈
an der Ruhr, Germany.
((1-Mesityl)-3-(propyl)-imidazolylidene)palladium(η3-
allyl)chloride (2). The corresponding imidazolium salt (0.20
g, 0.65 mmol) was stripped three times with toluene and
suspended in 40 mL of THF. Subsequently, [PdCl(η3-C3H5)]2
(0.12 g, 0.32 mmol) was added, and the solution was cooled in
dry ice in EtOH solution to approximately −60 °C. Upon
addition of KOtBu, the suspension turned into a pale yellow
solution. The solution was allowed to warm to 20 °C and
stirred overnight. The solvent was removed in vacuo, and the
crude product was suspended in toluene, which was filtered in
air over Celite. The solvent was removed and stripped with
DCM three times yielding 0.23 g (84%) of an off-white powder.
1H NMR (300 MHz, CDCl3) δ 7.10 (d, J = 1.8 Hz, 1H, Im-bb),
6.95 (s, 1H, Im-bb), 6.90 (d, J = 1.8 Hz, 2H, Ar), 5.13−4.80
(m, 1H, allyl), 4.46 (ABX, J = 14.3, 6.9 Hz, 1H, ImCH2), 4.29
(ABX, J = 13.8, 6.8 Hz, 1H, ImCH2), 4.10 (dd, J = 7.5, 2.2 Hz,
1H, allyl), 3.39−3.25 (m, 1H, allyl), 3.03−2.84 (m, 1H, allyl),
2.31 (s, 3H, ArCH3), 2.20 (s, 3H, ArCH3), 2.03 (s, 3H,
ArCH3),1.90 (m, 3H, ImCH2CH2CH3+ allyl), 0.93 (t, J = 7.4
Hz, 3H, ImCH2CH2CH3). 13C NMR (125 MHz, CDCl3) δ
181.03 (NCN), 138.88 (Ar), 136.54 (Ar), 136.07 (Ar), 135.33
(Ar), 129.24 (Ar), 128.799 (Ar), 122.36 (Im-bb), 121.36 (Im-
bb), 114.25 (allyl), 71.81 (allyl), 52.96 (allyl), 51.53 (CH2),
24.33 (CH2), 21.21 (Mes-CH3), 18.81 (Mes-CH3), 18.22
(Mes-CH3), 11.20 (CH3). MS ESI-TOF calculated for
C18H25N2Pd (MH+-Cl) 375.1054; found, 375.1071.
competition between the phosphine, the alkyne, and the Z-
alkene for coordination to the complex, with the improved
selectivities being a direct result of the relative coordination
strengths to palladium. The phosphine binds much stronger
than the Z-alkene, and hence, the additive slows down the over-
reduction and isomerization steps (k2) by substituting the
alkene and preventing its recoordination. The semihydrogena-
tion steps (k1) are also slowed down but to a lesser extent
because the binding affinity of the alkyne and PPh3 are
competitive. This implies that the selectivity of the semi-
hydrogenation of alkynes to Z-alkenes may be optimized for
specific substrates by variation of the phosphine ligand and its
concentration.
The combined mechanistic data led to the proposed
mechanism in Scheme 2, where the active species has the
form of a Pd(IMes)L2 complex (Scheme 2, B) that forms the Z-
alkene with a high initial selectivity (k1, C). The phosphine
additive rapidly removes intermediate C, thus slowing down
over-reduction and isomerization, and provides an alternative
pathway via species D back to B, leading to enhanced
selectivities.
Palladium0((1-mesityl)-3-(propyl)-imidazolylidene)-
(maleic anhydride)2 (5). The synthesis was performed in
manner similar to that for 2 using Pd(DVTMS)2 in DVTMS
1
CONCLUSIONS
solution with a Pd content of 7.66 mass % by AES. H NMR
■
We have developed a convenient and easy-to-use catalytic-
synthetic protocol for selective transfer semihydrogenation of
alkynes into Z-alkenes using ammonium formate as the
hydrogen source and the easily prepared and commercially
available complex [PdCl(η3-C3H5)(IMes)] (1) as the precata-
lyst. Combining the robust and air-stable (pre)catalyst with two
(400 MHz, CD2Cl2) δ 7.39 (d, J = 1.8 Hz, 1H, Im-bb), 7.17 (d,
J = 1.8 Hz, 1H, Im-bb), 7.00 (s, 2H, CH-Ar), 4.69 (s, 2H, MA),
4.41 (s, 2H, MA), 3.98 (t, J = 7.3 Hz, 2H, ImCH2), 2.34 (s, 3H,
CH3−Ar), 2.07 (s, 6H, CH3−Ar), 1.85 (h, J = 7.4 Hz, 2H,
ImCH2CH2CH3), 0.94 (t, J = 7.4 Hz, 3H, CH3). 13C NMR
(125 MHz, CDCl2) δ 176.58 (NCN),167.29 (MA), 166.85
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Research Article
(MA), 139.51 (Ar), 135.29 (Ar), 134.87(ArCH), 129.19 (Ar),
125.27 (Im-bb), 122.35 (Im-bb), 66.29 (MA), 65.88 (MA),
24.07 (Im-CH2), 20.63 (ImCH2CH2), 17.32 (ArCH3), 17.24
(ArCH3) 10.53 (CH3). MS ESI-TOF calculated for
C19H22N2NaO3Pd (M-Na+-MA) 455.5065; observed,
455.5075; calculated for C18H22N2NaO2Pd (M-Na+-MA-CO)
427.0614; observed, 427.0643. Also observed: 471.06 (MH+-
CO2), 441.04 (MH+-2CO2).
mL). The solution was stirred for 3 min, and 0.25 mL (1.0
mmol) of a 5 M CS2 solution in THF was added. After another
10 min of stirring, the solvent was removed. The crude product
was purified by column chromatography (DCM with 1% 5 M
CS2 in THF, in air, nondry solvents) yielding 0.02 g of an
1
intensely yellow compound (45% yield). H NMR (300 MHz,
CD2Cl2) δ 7.11 (s, 2H, Im-bb), 7.01 (s, 4H, Ar), 2.37 (s, 6H, p-
CH3Ar), 2.14 (s, 12H, o-CH3Ar). 13C NMR (75 MHz, CDCl3)
δ (CS2 13C not observed), 188.19 (NCN), 139.57 (p-C(Ar)),
136.54 (i-C(Ar)), 135.77 (o-C(Ar)), 129.66 (m-C(Ar)),
123.51(Im-bb), 21.64 (p-CH3Ar), 18.33 (o-CH3(Ar)). IR:
1119 cm−1 CS (s), 716 (s). MS ESI-TOF calculated for
C44H48KN4Pd2S4 (M+K+) 1013.0473; found, 1013.0493.
Elemental Analysis calculated for C44H48N4Pd2S4: C, 54.26;
H, 4.97; N, 5.75; Pd, 21.85; S, 13.17. Elemental analysis
observed: % C 52.54, % H 4.80, % N 5.57, % S 13.51.
Catalytic Transfer Semihydrogenation of Alkynes.
General Procedure. A Radleys’ twelve-place reaction station
with integrated heating and cooling setup was used for all
catalytic experiments. Samples were taken at regular time
intervals by filtering aliquots of the reaction mixture over short
silica columns and eluting with DCM. Samples were analyzed
on a Thermo Scientific Trace GC Ultra equipped with a R-Rxi
5 ms column (30 m, ID 0.25 mm) and quantified using the
response factor corrected GC-area with respect to the internal
standard. Samples were further analyzed by NMR-spectroscopy
on a Bruker 400 MHz spectrometer.
[1,3-Di((4−2,6-diisopropylphenyl)-1H-1,2,3-triazolyl)-
methylene-imidazolium] Bromide. Bisethynyl imidazolium
bromide66 (1.00 g, 4.44 mmol) was dissolved in a solution of
150 mL of water and 100 mL of tBuOH. First, the DiPP azide11
(2.00 g, 9.3 mmol) was added, followed by sodium ascorbate
(0.35 g, 1.3 mmol), and finally CuSO4·5H2O (0.22 g, 0.88
mmol). The resulting suspension was heated to 60 °C and
stirred for seven days, during which time an orange suspension
formed. All solvents were removed in vacuo, and the solid was
dissolved in 100 mL of DCM and washed with a saturated
NH4Br solution (25 mL 3×). The organic layer was separated,
dried over MgSO4, filtered over a glass filter, and removed in
vacuo. The obtained oil was suspended in 25 mL of toluene,
filtered over Celite, and layered with pentane for recrystalliza-
tion. The solid was dissolved in a minimum of DCM and
precipitated with pentane. The obtained solid (1.85 g) was then
purified by column chromatography (40/45/5 acetone/DCM/
MeOH, nondry solvents, in air) to yield 0.99 g (62%) of a
1
white powder. H NMR (300 MHz, CDCl3) δ 10.75 (s, 1H,
Im-bb), 8.28 (s, 2H, Trz), 7.76 (s, 2H, Im-bb), 7.49 (t, J = 7.8
Hz, 2H, Ar), 7.27 (d, J = 7.8 Hz, 4H, Ar), 5.91 (s, 4H, CH2),
Standard Catalytic Experiment (Using 1-Phenyl-1-pro-
pyne). A stock solution was prepared adding in their respective
order acetonitrile (320 mL, 250.3 g,) 1-phenyl-1-propyne (6.4
g, 55 mmol), p-xylene (internal standard, 5.68 g, 54 mmol),
triethylamine (27.00 g, 267 mmol), and formic acid (11.48 g,
267 mmol), which was saturated with nitrogen gas by gently
bubbling N2 through the solution for 20 min. From the stock
solution, 20 mL was taken by a syringe and added to one of the
12 reaction vessels. The exact amount of added stock solution
was determined by weighing; for this reason, molar and weight
percentages were applied to determine quantities and further
calculations. The Radleys’ station was heated to 70 °C, after
which the appropriate amount of catalyst and additive was
added in aluminum weighing trays. Reaction rates were
determined by taking the first order derivative of the conversion
at 15%.
Catalytic Semihydrogenation Using All Components as
Received. A stock solution was prepared with AR-Grade
MeCN with a water content of >200 ppm, 99% formic acid,
and 99% triethyl amine and p-xylene. The stock solution was
degassed for 10 min with argon, and 20 mL was added to the
reaction station. Subsequently, 2.7 mmol of the corresponding
substrate was added (used as received), and the reaction was
heated to 70 °C, at which point (t = 0) 1 mol % catalyst and 2
mol % PPh3 were added. Reactions were monitored by GC and
GC-MS (Jeol Accutof 4G GCv with a HP-5 MS capillary
column (30 m, 0.25 mmID)). When the reaction products were
not commercially available or products that are incompatible
with GC were expected, NMR (128 scans, d1 = 20 s) was also
used to follow the reaction over time. After 48 h, the reactions
were worked up to allow for a more detailed NMR analysis. For
entries (Table 2) 2, 3, 4, 5, 6, 8, 16, and 17, the reaction mixture
was poured on a 200 mL 2 M NaHSO4 aqueous solution. For
the other entries, demi-water was used. If the substrate
contained alkylic moieties, pentane was used for the extraction,
and if aryl moieties were present in the molecule, Et2O was
i
2.10 (dt, J = 13.5, 6.8 Hz, 4H, Pr-CH), 1.10 (d, J = 6.6 Hz,
24H, Me).13C NMR (101 MHz, MeOD) δ 140.49, 136.40,
135.04, 128.66, 128.31, 127.94, 124.58, 122.65, 53.73, 43.89.
MS (FAB-TOF) calculated for C33H43N8 (M+-Br) 551.3611;
found, 551.3607.
Palladium(η3-allyl)chlorido(1,3-di-((4−2,6-diisopropyl-
phenyl)-1H-1,2,3-triazolyl)methylene-imidazol-ylidene)
(6). The ligand (see procedure above) (0.24 g, 0.36 mmol) was
stripped three times with toluene (3 mL) and dissolved in 7 mL
of THF. Allylpalladium chloride dimer (0.066 g 0.18 mmol)
and KOtBu (0.056 g, 0.47 mmol) were suspended in 5 mL of
THF. The solution containing the ligand was added dropwise
to the suspension over 10 min. The solution was stirred
overnight and filtered over Celite in air, and the solvent was
removed. The complex was purified by column chromatog-
raphy (in air, nondry solvents) using 40:45:5 acetone, DCM,
MeOH eluents yielding 0.182 g of a white powder (64% yield).
1H NMR (400 MHz, CD2Cl2) δ 7.98 (s, 2H, Trz), 7.53 (t, J =
7.8 Hz, 2H, Ar), 7.32 (d, J = 7.8 Hz, 4H, Ar), 7.28 (s, 2H, Im-
bb), 5.67 (d, J = 2.3 Hz, 4H, CH2), 5.50 − 5.38 (m, 1H,
allylC2), 4.31 (d, J = 9.1 Hz, 1H, allyl), 3.74 (d, J = 7.0 Hz, 1H,
allyl), 3.28 (d, J = 13.5 Hz, 1H, allyl), 2.63 (d, J = 11.6 Hz, 1H,
i
allyl), 2.17 (dt, J = 13.7, 7.0 Hz, 4H, Pr-CH), 1.13 (d, J = 6.8
i
i
Hz, 12H, Pr-CH3), 1.09 (d, J = 6.9 Hz, 12H, Pr-CH3). 13C
NMR (101 MHz, CD2Cl2) δ 180.32 (NCN), 145.82 (Ar),
142.90 (Ar), 132.90 (Ar), 130.74 (Ar), 126.44 (Im-bb), 123.70
(Im-bb), 121.54 (C-triazole), 115.06 (allyl), 71.45 (CH2),
51,22 (allyl), 46.26 (CH-trz), 28.25 (iPr-CH), 23.75 (iPr-CH3),
23.57(iPr-CH3). MS (FAB-TOF) calculated for C36H47N8Pd
(M+-Cl) 697.2972; found, 697.2969.
Bis-[palladium0(1,3-dimesityl-imidazolylidene)-μ(κ-
S,η2)-carbon Disulfide] (8). Compound 1 (0.050 g, 0.1
mmol) was added to a degassed solution of formic acid (21 μL,
0.5 mmol) and triethylamine (0.07 mL, 0.5 mmol) in MeCN (5
1355
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Research Article
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ASSOCIATED CONTENT
■
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S
* Supporting Information
Full results of the catalytic reactions, conversion versus
selectivity graphs, data and graphs obtained from kinetic
experiments, the derivation of the equations used for pseudo-
first-order kinetics to determine the relative reaction constants,
and the corresponding fitted data. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: C.J.Elsevier@uva.nl.
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Notes
The authors declare no competing financial interest.
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305−308.
ACKNOWLEDGMENTS
■
This research was funded by the National Research School
Combination Catalysis (project no. 2009-2013-UVA-Elsevier-
02/03). We thank Umicore for providing the Pd-DVTMS
solution, Elwin Janssen for assistance with mass measurements,
and Dr. Santiago Gomez-Quero for his help with pseudo-first-
order kinetic product analysis.
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