E-selective semi-hydrogenation of alkynes with dinuclear iridium complexes under atmospheric pressure of hydrogen

Article abstract of DOI:10.1246/cl.160410

Semi-hydrogenation of alkynes was catalyzed by halide-bridged dinuclear iridium complexes, yielding (E)-alkenes with high selectivity. Mechanistic studies conducted with monohydride dinuclear species, dihydride mononuclear species, and trihydride dinuclear species led us to propose a mechanism involving dual cycles.

Full text of DOI:10.1246/cl.160410

CL-160410
Received: April 23, 2016 | Accepted: May 10, 2016 | Web Released: August 5, 2016
E-Selective Semi-hydrogenation of Alkynes with Dinuclear Iridium Complexes
under Atmospheric Pressure of Hydrogen
Kosuke Higashida and Kazushi Mashima*
Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531
(E-mail: mashima@chem.es.osaka-u.ac.jp)
Semi-hydrogenation of alkynes was catalyzed by halide-
bridged dinuclear iridium complexes, yielding (E)-alkenes with
high selectivity. Mechanistic studies conducted with mono-
hydride dinuclear species, dihydride mononuclear species, and
trihydride dinuclear species led us to propose a mechanism
involving dual cycles.
+
Cl
Cl
H
H
P
P
P
P
1a
= (rac)-BINAP
Ir
Ir
Cl-
P
P
Cl
Figure 1. The structure of dinuclear iridium complexes.
Table 1. Scope and limitation
Keywords: Dinuclear iridium complex
|
Stereoselective semi-hydrogenation
|
Alkyne
1a (1 mol%)
H2 (1 bar)
R
R
Stereoselective semi-hydrogenation of alkynes is one of the
most straightforward and atom-economical synthetic protocols
for preparing configurationally defined alkenes,1 which are
often found in natural products2 as well as in various organic
materials,3 and a much advantageous synthetic protocol than
semi-transfer-hydrogenation4 and Birch-type reduction.5 Semi-
hydrogenation of alkynes by heterogeneous catalyst systems
such as the Lindlar catalyst produces (Z)-alkenes as the main
product.6,7 The unique combination of two heterogeneous
catalyst systems was recently reported to catalyze the semi-
hydrogenation of alkynes under atmospheric pressure of H2 to
(E)-alkenes, where Pd3Pb/SiO2 catalyzed the hydrogenation of
alkynes to (Z)-alkenes, and RhSb/SiO2 facilitated the isomer-
ization of (Z)-alkenes to (E)-alkenes.8 On the other hand, some
homogeneous catalyst systems effectively achieve (E)-selective
semi-hydrogenation as the best solution for (E)-selective semi-
hydrogenation of alkynes. Fürstner and his collaborators
reported that a cationic ruthenium complex bearing a Cp*
ligand serves as a catalyst for (E)-selective semi-hydrogenation
of alkynes with high selectivity and wide functional group
tolerance.9 Milstein et al. demonstrated that an iron complex
with a PNP tridentate ligand acts as a catalyst for highly
(E)-selective semi-hydrogenation,10 and, quite recently, Mankad
et al. demonstrated that a unique bimetallic catalyst of Ag and
Ru hydrogenates alkynes under atmospheric pressure to give
the corresponding (E)-alkenes, and proposed a mechanism
involving heterolytic cleavage of a H-H bond by Ag-Ru
complexes.11 Moreover, a boron system of HB(C6F5)2 combined
with vinylpentafluorobenzene was reported to act as a moder-
ately active catalyst for (E)-selective semi-hydrogenation of
alkynes.12
R
Ph
Ph
+
1,4-dioxane
80°C, 16 h
Ph
2
3
4
Entry
R
(E)-3/%a
(Z)-3/%a 4/%a
1
2
3
4
5
C6H5
2a
2b
2c
2d
2e
2f
2g
2h
2i
97
94
96
92
95
98
91
95
93
79
90
87
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
n.d.b
5
3
5
4
8
4
2
4
5
6
p-MeOC6H4
p-(CH2OH)C6H4
p-BrC6H4
p-BpinC6H4
p-AcNHC6H4
p-AcC6H4
p-NCC6H4
p-NO2C6H4
TMS
6
7c
8c
9d
10
11
12
2j
2k
2l
7
10
6
nBu
C(CH3)2OH
aYields were determined by 1H NMR analysis using phenanthrene
as an internal standard. bn.d.: not detected. cThe reaction was
performed at 65 °C. The reaction was performed at 50 °C.
d
We conducted catalyst screening to select 1a as the best
catalyst (see SI). Next, we examined the substrate scope of this
reaction (Table 1). 1-Methoxy-4-(phenylethynyl)benzene (2b)
was hydrogenated to give the corresponding (E)-alkene 3b in
94% yield along with the formation of alkane 4b in 5% yield.
Alkyne 2c with the other electron-donating substituent resulted
in a similarly high (E)-selectivity of 3c in 96% yield. Alkynes
containing bromo and boronic ester groups were applicable for
this semi-hydrogenation to give the corresponding (E)-alkenes
without the loss of these functional groups, making them
available for further coupling reactions. Amide, acetyl, nitrile,
and nitro groups in 2f-2i, which are functional groups capable of
being hydrogenated,14 were tolerated under the hydrogenation
conditions, although a lower reaction temperature was required
for 2g-2i to avoid generating the corresponding alkanes 4g-4i.
The semi-hydrogenation of trimethylsilyl derivative 2j and n-
butyl derivative 2k afforded the corresponding (E)-alkenes with
high selectivity and moderate yields, whereas hydrogenation of
2-methyl-4-phenylbut-3-yn-2-ol (2l) was contaminated with a
significant amount of (Z)-alkene (5%).
We recently found that triply-halide-bridged dinuclear
iridium complexes bearing suitable chiral and achiral diphos-
phine ligands 1 catalyzed the hydrogenation of imine, N-
heteroaromatic compounds, and others, and maintained the
carbonyl and olefinic groups (Figure 1 and SI).13 As part of our
continuing efforts to expand the catalytic scope of the iridium
system of 1, we applied 1 to the catalytic hydrogenation of
alkynes, which led to semi-hydrogenation of alkynes under
atmospheric pressure of H2 to give the corresponding alkenes
with high (E)-selectivity.
866 | Chem. Lett. 2016, 45, 866–868 | doi:10.1246/cl.160410
© 2016 The Chemical Society of Japan

(S)-5a(1 mol%)
1a
(1 mol%)
(Z)-3a
(Z)-3a
(Z)-3a
no reaction
H2 (1 bar)
1,4-dioxane
80 °C, 1 h
+
4a
2a
(E)-3a
1,4-dioxane
80 °C, 16 h
97% yield 3% yield
(S)-5a (1 mol%)
(E)-3a
+
1,4-dioxane
80 °C, 1 h
Cl
H
3% yield
P
H
Ir
Cl-
Ir
6 (2 mol%)
P
P
(E)-3a
+
4a
Cl
H
1,4-dioxane
80 °C, 1 h
P
>99% yield <1% yield
Ir trihydride species
1M HCl/Et2O
(25 mol%)
5
no reaction
(Z)-3a
1,4-dioxane
80 °C, 1 h
Scheme 1. Semi-hydrogenation with iridium trihydride species.
Scheme 3. Catalytic activity for the isomerization of (Z)-3a.
6 (2 mol%)
H2 (1 bar)
4a
2a
2a
(E)-3a
+
insertion of 2a into an Ir-H bond of 6 gave (E)-alkenyl-iridium
species, whose reductive elimination resulted in the formation of
(Z)-3a, and 6 also worked as a catalyst for the isomerization of
(Z)-3a to (E)-3a. With respect to the isomerization, we tested the
catalytic performance of various iridium precursors, 1a, (S)-5,
and 6 along with HCl, which was expected to be formed in situ
from precursor 1a. Among them, 6 exhibited high catalytic
activity, whereas 1a, (S)-5a, and HCl exhibited almost no
activity for the isomerization (Scheme 3), suggesting that a
dihydride species catalyzed the isomerization, while monohy-
dride species had very low activity.
1,4-dioxane
80 °C, 16 h
51% yield 48% yield
6 (1.0 equiv)
(E)-3a
1,4-dioxane
80 °C, 1 h
82% yield
H
IrH2Cl((S)-binap)(pic)
N
H
P
Ir
P
6
Cl
Based on these experimental results, the plausible mecha-
nism can be divided into two cycles that involve the hydro-
genation of alkyne to (Z)-alkene (cycle I) and isomerization of
the (Z)-isomer to an (E)-isomer (cycle II) (Scheme 4). Under
optimal conditions, the dinuclear iridium complex 1a dissociates
to a monohydride iridium complex A, which reacts with H2 to
give a dihydride iridium complex B with the elimination of HCl.
Dihydride complex B works as a catalyst for both reaction
cycles. In cycle I, alkyne inserts into the Ir-H bond of B
followed by a reductive elimination to afford (Z)-alkene and
mononuclear Ir(I) complex C, whose exposure to hydrogen gas
regenerates B, although we cannot exclude another possible
mechanism of σ-bond metathesis-type direct cleavage of the
Ir-C(alkenyl) bond by H2 to regenerate B,15 as well as direct
semi-hydrogenation of alkyne to give (E)-alkene.9,16 In cycle II,
in situ-generated (Z)-alkene inserts into the Ir-H bond of B,
followed by rotation of the C-C bond and β-hydride elimination
to give the corresponding (E)-alkene and regenerate B as a
consequence of faster β-hydride elimination than reductive
elimination. The Ir(I) precursor (Table S2, Entry 9) and the
mononuclear iridium dihydride species 6 (Scheme 2) produced
more of the over-reduced product 4, and therefore, we propose
the potent scenario that the dinuclear iridium(III) species 1a and
5 were dormant species in equilibrium with B, and consumption
of alkynes shifted the equilibrium to dominant 5 together with
1a because of the different coordination abilities of alkynes
and alkenes to B. In fact, we conducted a semi-hydrogenation
of alkynes using a catalyst system of 6 treated with HCl
(25 mol %), which spontaneously generated the dinuclear
iridium(III) complex 1a, to significantly suppress the formation
of alkane 4a (less than 1%) while maintaining (E)-selectivity.
Scheme 2. Control experiments by iridium dihydride complex 6.
We conducted a time-course experiment of hydrogenating
2a under the optimized conditions, and each yield of (E)-3a, (Z)-
3a, and 4a was plotted over the reaction time. At the beginning,
(Z)-3a was formed, and the amount of (E)-3a gradually
increased with a decrease of (Z)-3a, indicating the isomerization
of (Z)-3a to (E)-3a. During the reaction, the yield of 4a was
suppressed and, after 16 h, only 3% of 4a was detected.
Additionally, under the optimized conditions, (Z)-3a was fully
converted to (E)-3a (95%) and a small amount of 4a (5% yield).
Measurement of the 1H NMR spectrum of the crude reaction
mixture after the hydrogenation of 2a revealed an iridium
trihydride complex 5a.13b Thus, we alternatively prepared the
corresponding iridium trihydride complex of (S)-BINAP [(S)-
5a], and examined its catalytic performance for the hydro-
genation of 2a, giving (E)-3a (97%) and 4a (3%) in almost the
same distribution as that of 1a (Scheme 1). Because complex 5a
was a product of recombination between a mononuclear iridium
dihydride species and a mononuclear iridium monohydride
species, both the dihydride species and monohydride species
were expected to be candidate active species. To investigate the
reaction mechanism, we performed some controlled experiments
using an isolated dihydride complex 6, whose monomeric
structure was supported by the coordination of α-picoline
(Scheme 2).13f We carried out the catalytic semi-hydrogenation
of 2a using 6 to afford (E)-3a in 51% yield along with the
over-reduction product 4a in 48% yield, and performed the
stoichiometric reaction of 6 with 2a under the conditions without
hydrogen gas to produce (E)-3a in 82% yield, indicating that
Chem. Lett. 2016, 45, 866–868 | doi:10.1246/cl.160410
© 2016 The Chemical Society of Japan | 867

S
H
Ir
B
P
P
Cl
S
5
1a
-S
-B
Cl
S = Solvent, Substrate
Ph
A
H2
H
Ir
(Z)-3a
H2
H2
Ph
P
P
Cl
S
P
P
S
Ir
H
S
Cl
HCl
HCl
C
Ph
H
H
Ph
H
Ir
P
P
S
H
(Z)-3a
II
Ph
P
I
Ph
Ir
P
P
Ir
Ph
P
Cl
H
S
Cl
Cl
H
Ph
H
B
H
H
P
P
P
Ir
Ir
2a
Ph
Ph
P
H
(E)-3a
Cl
S
Cl
Scheme 4. Proposed mechanism including dual cycles by dihydride species.
In summary, we developed (E)-selective semi-hydrogena-
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Supporting Information is available on http://dx.doi.org/
10.1246/cl.160410.
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868 | Chem. Lett. 2016, 45, 866–868 | doi:10.1246/cl.160410
© 2016 The Chemical Society of Japan