E-Selective Semi-Hydrogenation of Alkynes by Heterobimetallic Catalysis

Article abstract of DOI:10.1021/jacs.5b10357

A unique cooperative H₂ activation reaction by heterobimetallic (NHC)M′-MCp(CO)₂ complexes (NHC = N-heterocyclic carbene, M′ = Cu or Ag, M = Fe or Ru) has been leveraged to develop a catalytic alkyne semi-hydrogenation transformation. The optimal Ag-Ru catalyst gives high selectivity for converting alkynes to E-alkenes, a rare selectivity mode for reduction reactions with H₂. The transformation is tolerant of many reducible functional groups. Computational analysis of H₂ activation thermodynamics guided rational catalyst development. Bimetallic alkyne hydrogenation and alkene isomerization mechanisms are proposed.

Full text of DOI:10.1021/jacs.5b10357

Communication
pubs.acs.org/JACS
E‑Selective Semi-Hydrogenation of Alkynes by Heterobimetallic
Catalysis
Malkanthi K. Karunananda and Neal P. Mankad*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, United States
S
* Supporting Information
Our interest in bimetallic H2 activation began through the
ABSTRACT: A unique cooperative H2 activation reaction
by heterobimetallic (NHC)M′-MCp(CO)2 complexes
(NHC = N-heterocyclic carbene, M′ = Cu or Ag, M =
Fe or Ru) has been leveraged to develop a catalytic alkyne
semi-hydrogenation transformation. The optimal Ag−Ru
catalyst gives high selectivity for converting alkynes to E-
alkenes, a rare selectivity mode for reduction reactions
with H2. The transformation is tolerant of many reducible
functional groups. Computational analysis of H2 activation
thermodynamics guided rational catalyst development.
Bimetallic alkyne hydrogenation and alkene isomerization
mechanisms are proposed.
study of a heterobimetallic catalyst for the dehydrogenative
borylation of arenes.24 The proposed mechanism for this
transformation includes a key turnover step involving bimetallic
reductive elimination from (NHC)CuH + FpH (NHC = N-
heterocyclic carbene; Fp = FeCp(CO)2) to regenerate the
(NHC)Cu-Fp catalyst through loss of H2. The calculated
pathway25 for this dehydrogenation event has a low-energy
transition state that could reasonably be approached from the
reverse direction, i.e., in a hypothetical H2 cleaving reaction. We
thus reasoned that a (NHC)Cu-Fp complex or one of its
(NHC)Cu-[M] analogues26 ([M] = metal carbonyl anion)
might be active for bimetallic H2 addition. To explore this
possibility, we calculated the thermodynamics of this hypo-
thetical H2 activation, as a function of [M], using DFT methods
with a truncated NHC model (IMe = N,N′-dimethylimidazol-2-
ylidene, Table 1). The relative trends that emerged (Table 1)
atalytic hydrogenation of unsaturated organic substrates
Cremains a crucial application of homogeneous catalysis, in
part due to the exquisite control of selectivity that is possible
through catalyst design. The classical approach to catalytic
hydrogenation involves single-site oxidative addition/reductive
elimination mechanisms. This approach is exemplified by well-
known examples such as Wilkinson’s catalyst,1 the Schrock−
Osborn catalyst,2 and Crabtree’s catalyst3 that all operate by
RhI/RhIII or IrI/IrIII cycles initiated through single-site oxidative
addition of H2. Exciting developments have emerged through
exploring non-classical approaches to H2 activation. Represen-
tative examples include catalysts that activate H2 using metal−
ligand cooperativity4−8 or non-metal frustrated Lewis acid−
base cooperativity.9−11
Another cooperative effect to potentially exploit is bimetallic
cooperativity, wherein two metal sites within a catalyst
cooperate to activate H2 and initiate catalytic reduction of a
substrate. Although bimetallic H2 cleavage reactions have been
long known,12 their use in catalytic transformations is
underdeveloped.13−15 Previous examples of bimetallic hydro-
genation catalysts often suffer from poor activity,16 and in some
cases faster rates can actually be achieved by using
monometallic analogues that omit one of the two metal
sites.17 In this Communication, we report a semi-hydrogenation
reaction of alkynes that requires bimetallic cooperativity to
proceed. Through optimizing the nature of the bimetallic
pairing within a tunable catalyst design, we have achieved
unusual E-selectivity in the alkyne reduction, a rare selectivity
mode in hydrogenation catalysis18,19 that complements the
famously Z-selective Lindlar catalyst20 and more modern
updates. Other methods for converting alkynes to E-alkenes,
including stoichiometric Birch reduction or various catalytic
methods,21,22 do not use H2 as the terminal reductant.
Table 1. Thermodynamics for H2 Activation by (NHC)Cu-
[M]
relative nucleophilicity of
ΔG298 K
a
b
entry
[M]
[M]−
(kcal/mol)
1
2
3
4
5
6
7
8
FeCp(CO)2
RuCp(CO)2
Re(CO)5
70,000,000
21.9
c
7,500,000
20.1/14.5
26.4
25,000
500
77
WCp(CO)3
Mn(CO)5
24.8
33.0
MoCp(CO)3
CrCp(CO)3
67
34.0
4
34.5
Co(CO)4
1
49.0
a
b
c
From ref 23. Calculated by DFT for H2 cleavage. For (IMes)Ag in
place of (IMe)Cu.
guided our experimental catalyst development, although the
energies would be more accurate by including NHC sterics,
solvation, and (NHC)CuH dimerization27 energies.
As expected on the basis of facile dehydrogenation reactivity
observed previously,24,25 the H2 activation is thermodynami-
cally unfavorable for all systems calculated. Two key
observations guided our experimental trials. First, the general
trend is for H2 activation to be less favorable with decreasing
Received: October 3, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/jacs.5b10357
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
[M]− nucleophilicity.23 Second, among the most promising
candidates, the (NHC)Cu-Rp system (Rp = RuCp(CO)2) has
an unusually low ΔG value for H2 addition (Table 1, entry 2)
considering the relative nucleophilicity of [Rp]−. Based on
these observations, we began experimental studies with
(NHC)Cu-Fp and (NHC)Cu-Rp complexes. In a related
study, Meyer recently observed stoichiometric H2 activation
based on cooperation between [Rp]− and a carbon Lewis
acid.28
As expected, no evidence for any reaction occurring was
obtained by NMR spectroscopy when different (NHC)Cu-Fp
and (NHC)Cu-Rp complexes were exposed to H2. However,
when the reactions were done in the presence of alkynes at
elevated temperatures, alkene products were observed,
indicating that H2 was indeed being activated by the catalyst.
Preliminary experimentation indicated that appropriate con-
ditions for catalytic hydrogenation would include 150 °C
reaction temperature in xylenes solvent at 1 atm of H2 pressure.
Rapid catalyst decomposition was observed when polar solvents
were used in place of xylenes or when higher H2 pressures were
employed. Catalysis was observed at lower temperatures, but
multiple days were required for reaction progress to reach
completion.
in trace amounts. To confirm that both metal sites are required
for catalysis, we note that neither (IPr)AgOAc nor Rp2 catalyze
hydrogenation of diphenylacetylene (entries 9 and 10).
Preliminary indications are that the reaction does involve
homogeneous catalysis: a drop of Hg did not significantly
poison catalysis (entry 11), and we believe that the modest
lowering of conversion and erosion of selectivity is due to a
slow background reaction between (IMes)Ag-Rp and Hg,
evident from a visible color change even prior to heating
(IMes)Ag-Rp + Hg with H2 and alkyne.
Quantitative conversions of both an electron-rich and an
electron-poor diarylalkyne were achieved under these catalytic
conditions, still with high E:Z selectivity (Table 3, entries 2 and
Table 3. Alkyne Semi-Hydrogenation by (IMes)Ag-Rp
conversion
a
a
entry
R
R′
(%)
1:2:3
b
b
1
2
3
4
5
Ph
Ph
95.7
>99
90.2:4.2:1.1
71:24:5
4-MeOC6H4
4-F3CC6H4
4-(n-H11C5)C6H4
Ph
4-MeOC6H4
4-F3CC6H4
H
When comparing diphenylacetylene hydrogenation results
for (NHC)Cu-Fp catalysts (Table 2, entries 1 and 2) with
>99
91
72:20:8
c
d
91 :n.d.
d
nBu
>99
n.d.
Table 2. Alkyne Semi-Hydrogenation Catalyst Optimization
a
b
1
From H NMR integration against an internal standard. Averaged
c
d
over two independent runs ( 0.2 error bars). Terminal alkene. Not
determined.
3). A terminal alkyne also underwent quantitative reduction
(entry 4). 1-phenyl-1-hexyne underwent efficient reduction, but
we were unable to identify the product(s) formed (entry 5).
A hypothetical hydrogenation mechanism is shown in Figure
1a. Reversible H2 activation by the (NHC)M′-[M] catalyst
a
a
entry
catalyst
(IPr)Cu-Fp
conversion (%)
1:2:3
1
32
64
60
61
29
32
84
8:23:1
12:50:2
40:18:3
42:17:2
17:12:1
21:11:0
54:24:5
90.2:4.2:1.2
N/A
2
(IMes)Cu-Fp
(IPr)Cu-Rp
(IMes)Cu-Rp
(IPr)Ag-Fp
3
4
5
6
(IMes)Ag-Fp
(IPr)Ag-Rp
7
b
b
8
(IMes)Ag-Rp
(IPr)AgOAc
95.7
9
0
7
c
10
11
Rp2
4:3:0
(IMes)Ag-Rp + Hg drop
89
67:18:4
a
b
1
From H NMR integration against an internal standard. Averaged
c
over two independent runs ( 0.2 error bars). Catalyst loading was
10%, i.e., 20% Ru.
Figure 1. (a) Hypothetical mechanism for alkyne semi-hydrogenation
by (NHC)M′-[M] catalysts (M = Fe or Ru, M′ = Cu or Ag, L = IPr or
IMes). (b) Transition state for H2 activation by (IMe)Cu-Rp
calculated by DFT.
those for (NHC)Cu-Rp catalysts (entries 3 and 4), we found
that selectivity for trans-stilbene increased significantly when
substituting Fe for Ru. In all cases, the total conversions of
diphenylacetylene were low to modest, and so we proceeded to
test (NHC)Ag-Fp (entries 5 and 6) and (NHC)Ag-Rp
analogues (entries 7 and 8), which were predicted by DFT to
activate H2 more readily (Table 1, entry 2). Only for the
(NHC)Ag-Rp catalysts were high conversions realized. The
optimal catalyst was (IMes)Ag-Rp (IMes = N,N′-bis(2,4,6-
trimethylphenyl)imidazol-2-ylidene), which gave 96% conver-
sion of diphenylacetylene and yielded trans-stilbene as 95% of
the product mixture (Table 2, entry 8). The cis-stilbene was the
main side product, while 1,2-diphenylethane was formed only
produces (NHC)M′-H + [M]-H. This H2 activation can be
viewed as a heterolysis, producing an equilibrium mixture of a
protic species and a hyridic species. The calculated transition
state for H2 activation by (IMe)Cu-Rp is shown in Figure 1b
(ΔH⧧ = 20.1 kcal/mol, ΔS⧧ = −29.8 eu, ΔG⧧
= 29.0 kcal/
298K
mol). As expected for a late transition state, the Cu−Ru and
H−H bonds are almost completely broken (2.74 and 1.28 Å,
respectively, vs 2.44 and 0.75 Å in reactants). As we have noted
previously for a related reaction,29 one of the CO ligands
bridges the two metals in the transition state (Cu···CO = 2.64
B
DOI: 10.1021/jacs.5b10357
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Å) to provide stability as the metals separate. As evidence for
this step occurring, we note that H NMR peaks (e.g., in
species should also be susceptible to protonolysis by [M]-H,
consistent with our observation of trace alkanes in most
product mixtures. According to our catalyst optimization results
(Table 2), the general trends are for the cycle in Figure 2 to be
faster for M′ = Ag, M = Ru, and NHC = IMes.
1
toluene-d8: δ = 4.52 and −12.04, 5:1 integration) assigned to
RpH were observed in typical product mixtures, along with
precipitation of the coinage metal consistent with known
decomposition of (NHC)M′-H complexes.27,30,31 Following H2
activation, alkyne insertion into (NHC)M′-H produces a σ-
alkenyl intermediate. This hydrometalation step is expected to
proceed with syn stereochemistry, based on the known
reactivity of the (IPr)CuH dimer.27 Less is known about the
insertion chemistry of analogous (NHC)Ag-H species.30,31
Finally, protonolysis of the σ-alkenyl ligand by [M]-H
regenerates the (NHC)M′-[M] catalyst through bimetallic
elimination of the Z-alkene.
Finally, we sought to explore the functional group tolerance
of the transformation using a modified version of Glorius’s
robustness screening method.32 The reduction of diphenylace-
tylene was conducted in the presence of various additives
containing potentially reactive functional groups. Product
mixtures were analyzed at both partial (6 h) and full (24 h)
conversion (Table 5). It is clear from the partial conversion
Table 5. Time-Dependent Robustness Screening Data
According to this proposal, the alkyne substrate is initially
reduced to the Z-alkene, which must then be isomerized under
the reaction conditions. To probe the validity of this proposal,
we exposed cis-stilbene to the catalytic conditions and, indeed,
observed isomerization to the trans isomer (Table 4, entry 1).
ab
,
ab
,
entry
additive
conversion (%)
1:2:3
1
2
3
4
5
6
7
8
9
none
55/96
36/96
74/90
55/94
58/>99
79/99
68/79
65/>99
54/99
49:4:1/90:4:1
8:22:5/15:81:1
61:12:1/71:16:2
37:17:2/78:16:2
43:13:2/92:0:8
69:8:2/84:11:4
62:5:1/66:11:2
48:15:2/96:1:3
Table 4. Alkene Isomerization Studies
heptaldehyde
6-undecanone
acetonitrile
ethyl acetate
1-butanol
a
entry
alkene
variation on conditions
1:2:3
pyridine
1-dodecene
neopentyl chloride
1
2
3
4
cis-stilbene
trans-stilbene
cis-stilbene
cis-stilbene
none
92:4:5
98:0:2
39:13:2/94:2:3
none
a
b
1
catalyst omitted
H2 omitted
<1:99:0
22:78:0
From H NMR integration against an internal standard. Listed as 6
h/24 h.
a
1
From H NMR integration against an internal standard.
data that the rate of catalysis is not slowed by any of the
functional group tested, other than by aldehydes (entry 2).
From the full conversion data, it is evident that the alkyne
reduction is tolerant of many reactive functional groups. The
E:Z selectivity was eroded slightly by the presence of a pyridine
or a ketone (entries 3 and 7), and was actually inverted by the
presence of an aldehyde (entry 2). As an illustrative example,
the aldehyde additive was detected at the end of the reaction,
indicating that (IMes)Ag-Rp is capable of catalyzing alkyne
hydrogenation but not aldehyde reduction. The selective
reduction of alkynes in the presence of other reducible
functional groups (e.g., aldehydes, ketones, alkenes, nitriles) is
quite remarkable.
On the other hand, exposing the trans-stilbene to the catalytic
conditions resulted in no isomerization (entry 2). The Z-to-E
isomerization was stopped when the catalyst was omitted
(entry 3) and slowed when H2 was omitted (entry 4). These
observations indicate that cis-stilbene is a viable reaction
intermediate that isomerizes to trans-stilbene under the reaction
conditions, and that the isomerization is catalyzed by a H2-
derived metal−hydride species.
A proposed mechanism for isomerization is shown in Figure
2. The mechanism involves Z-alkene insertion into the
(NHC)M′-H intermediate to generate a metal−alkyl species.
This metal−alkyl subsequently undergoes β-hydride elimina-
tion to extrude either the E or Z alkene, the former of which is
favored thermodynamically. The metal−alkyl intermediate
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.5b10357.
Experimental procedures and spectral data (PDF)
Computational output (ZIP)
Crystallographic data (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*npm@uic.edu
Figure 2. Hypothetical mechanism for alkene isomerization under
hydrogenation conditions by (NHC)M′-[M] catalysts (M = Fe or Ru,
M′ = Cu or Ag, L = IPr or IMes).
Notes
The authors declare no competing financial interest.
C
DOI: 10.1021/jacs.5b10357
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
ACKNOWLEDGMENTS
■
Funds were provided by the NSF (CHE-1362294) and by an
Alfred P. Sloan Research Fellowship (to N.P.M.). The authors
thank Thomas Mazzacano for testing the reproducibility of
selected catalytic results. Computations were performed at the
UIC Extreme Computing facility.
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DOI: 10.1021/jacs.5b10357
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX