Dynamically Bifurcating Hydride Transfer Mechanism and Origin of

Feb 7, 2019 - The mechanism and heterodinuclear cooperative effects for AgRu-catalyzed alkyne semihydrogenation were analyzed with density-functional ...
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Dynamically Bifurcating Hydride Transfer Mechanism and Origin of Inverse Isotope Effect for Heterodinuclear AgRu-Catalyzed Alkyne Semi-Hydrogenation Ying Zhang, Malkanthi K Karunananda, Hsien-Cheng Yu, Kyle J Clark, Wendy Williams, Neal P. Mankad, and Daniel H. Ess ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b04130 • Publication Date (Web): 07 Feb 2019 Downloaded from http://pubs.acs.org on February 8, 2019

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Dynamically Bifurcating Hydride Transfer Mechanism and Origin of Inverse Isotope Effect for Heterodinuclear AgRu-Catalyzed Alkyne Semi-Hydrogenation Ying Zhang,‡ Malkanthi K. Karunananda,† Hsien-Cheng Yu,† Kyle J. Clark,‡ Wendy Williams,‡ Neal P. Mankad,†* and Daniel H. Ess‡* ‡Department

of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States, †Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, United States KEYWORDS. Heterodinuclear, Heterobimetallic, Density Functional Theory, Kinetic Isotope Effect, Hydrogenation.

ABSTRACT: The mechanism and heterodinuclear cooperative effects for AgRu catalyzed alkyne semi-hydrogenation were analyzed with density-functional theory (DFT) and experiment. This combined effort revealed that: 1) AgRu-catalyzed diphenylacetylene hydrogenation initially gives a kinetic mixture of cis-stilbene and trans-stilbene by an ionic Ag-H hydride transfer transition state and post-transition state bifurcation, which was identified by quasiclassical direct dynamics simulations; 2) the hydrogenation reaction exhibits an unexpected inverse kinetic isotope effect (KIE < 1) resulting from an inverse equilibrium isotope effect (EIE) for heterodinuclear H2/D2 activation; 3) the Ag-Ru heterodinuclear cooperative effective is critical for both H2 activation and vinylsilver protonolysis reaction steps; 4) rate studies and a computational analysis show that electron-donating groups accelerate catalysis.

Introduction Use of heterodinuclear-transition-metal catalysts with direct metal-metal interactions has emerged as a promising strategy to tackle challenging chemical transformations,1,2,3 including C-H functionalization,4 C-C and C-X coupling,5 carbon dioxide hydrogenation,6 and N2 reduction.7 Exploring heterodinuclear catalysts for synthetic applications can be advantageous because cooperative dinuclear effects result in unique mechanisms, reactivity, and selectivity that complement those available to mononuclear catalysts.8 An example of a dinuclear catalytic effect was reported by Mankad,9 who discovered that (NHC)Ag-RuCp(CO)2 complexes catalyze chemoselective hydrogenation of diarylalkynes with rare stereoselectivity for formation of trans-alkene products.10 For example, (IMes)AgRuCp(CO)2 provided >95% conversion for hydrogenation of diphenylacetylene at just 1 atm H2 pressure, yielding stilbene with a 90:4 trans:cis ratio, and with only trace over-reduction to 1,2-diphenylethane (Scheme 1a). Importantly, the presence of a cooperative dinuclear effect was demonstrated by showing that mononuclear components such as (IPr)AgOAc, [RuCp(CO)2]2, and HRuCp(CO)2 did not provide significant conversion or useful trans:cis selectivity when employed as catalysts under these conditions.11

a) Ph

Ph

20 mol% AgRu catalyst H2 (1 atm)

Ph Ph

xylenes 150°C, 24 h

90%

b)

Ph

Ph

- H2

L Ag Ru

Ag Ru OC CO

(IMes)Ag-RuCp(CO)2

H Ru

H H

Ph

L Ag H

OC CO

N

1%

4%

+ H2

L = IMes

N

Ph

OC Ph

CO Ph

H Ph

Ph

L Ag

[AgRu] cat. H2

Ph H Ru

Ph

OC CO H

Ph

Ph H

Scheme 1. a) Previously reported trans-selective alkyne semihydrogenation by a heterodinuclear AgRu catalyst.9 b) (NHC)AgRuCp(CO)2 catalyst and previously proposed catalytic cycle.

A preliminary mechanistic scheme accounting for these observations was proposed and is shown in Scheme 1b. First, dihydrogen activation was proposed to give transient Ag-H and Ru-H species. While the sterochemical course of Ag-H addition to alkynes is not known definitively, Ag-H addition to

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diphenylacetylene was proposed to give a cis-vinylsilver intermediate based on related alkyne syn-hydrocupration previously reported.12,13 Subsequent reaction with the Ru-H species would then liberate cis-stilbene and regenerate the dinuclear catalyst. It was proposed that the initially formed cisstilbene is then isomerized to the thermodynamically more stable trans-stilbene under the catalytic conditions. Experiments also showed that under (IMes)Ag-RuCp(CO)2 catalytic conditions shown in Scheme 1a, cis-to-trans isomerization of stilbene readily occurs in the presence of H2 To uncover the mechanistic origins of this AgRu heterodinuclear catalytic effect, and to understand its control over product selectivity during alkyne hydrogenation, we have undertaken a combined density-functional theory (DFT), direct dynamics, and experimental study of this transformation. This combined effort has revealed that: 1) AgRu-catalyzed diphenylacetylene hydrogenation initially gives a kinetic mixture of cis- and trans-stilbene by an ionic Ag-H hydride transfer transition state; 2) the hydrogenation reaction exhibits an unexpected inverse kinetic isotope effect (KIE < 1), which results from an inverse equilibrium isotope effect (EIE < 1) for dinuclear H2/D2 cleavage; 3) based on quasiclassical direct molecular dynamics simulations, trans:cis stilbene stereoselectivity may be influenced by a post-transition state dynamical bifurcation; 4) rate studies, and computational analysis, show that electron-donating groups accelerate catalysis. These collected findings allow us to propose a unique dinuclear cooperative mechanism for heterodinuclear alkyne semi-hydrogenation. Results and Discussion While the optimized (IMes)Ag-RuCp(CO)2 catalytic conditions called for a reaction temperature of 150°C, catalytic reaction rates were monitored with 1H NMR at 90°C due to instrumental limitations. To our surprise, the data indicated formation of both the trans- and cis-isomers of stilbene in a 1:2 ratio from diphenylacetylene hydrogenation (Scheme 2a). This trans:cis ratio was the same across the temperature range of 7090°C and the ratio did not change as the reaction progressed at these temperatures. An independent experiment established that catalytic isomerization of cis-stilbene to trans-stilbene mediated by (IMes)Ag-RuCp(CO)2 under 1 atm H2, which occurs rapidly at 150°C, does not proceed to any measurable extent at 90°C over the time course of these experiments. These observations have provided us with two new pieces of information that were unavailable in the initial catalytic study. First, the initial hydrogenation of diphenylacetylene produces a kinetic mixture of both trans- and cis-stilbene, not exclusively the cis-isomer as originally proposed. Second, while cis-totrans isomerization is kinetically competent under the optimized catalytic conditions to account for the high observed trans-selectivity, this isomerization must have a higher activation barrier than the hydrogenation itself. In addition to determining kinetic product ratios, we also measured initial rates of consumption of the diarylalkyne substrate. The KIE for the transformation was obtained by comparing independently measured initial rates for hydrogenation of diphenylacetylene by H2 and D2, respectively. To our surprise, we found that this transformation has an inverse KIE of 0.6 (Scheme 2a). We also found that semihydrogenation is sensitive to the electronic properties of the alkyne substrate, as

a)

Page 2 of 7 H2 or D2 (1 atm) 20 mol% AgRu cat. toluene, 90°C

H/D

H/D

kH/kD = 0.6 Z/E = 2

b) MeO

OMe

MeO H2 (1 atm) 20 mol% AgRu cat.

toluene, 90°C

H

H

OMe

kOMe/kH = 7.4

Scheme 2. a) Experimentally measured KIE and Z/E ratio. b) Approximate initial rate dependence of alkyne aryl group substitution.

the presence of para-methoxy substituents on the diarylalkyne was found to accelerate the reaction compared to diphenylacetylene by a factor of 7.4 (Scheme 2b). To determine the origin of the cooperative Ag-Ru heterodinuclear effects, as well as understand the inverse KIE and kinetic mixture of trans- and cis-stilbene, we executed a comprehensive DFT mechanistic study for semi-hydrogenation of diphenylacetylene. (U)M06-L/6-311++G(2d,2p)[def2TZVP]//(U)M06-L/6-31+G(d,p)[LANL2DZ] calculations were performed in Gaussian 09.14 Vibrational frequencies confirmed stationary points as either minima or transition-state structures. Thermodynamic corrections were applied at either 25°C or 90°C. Only low-spin singlet structures and energies are reported because triplet-spin structures are significantly higher in energy. All calculations were carried out with the SMD continuum solvent model for xylenes to incorporate an estimate of ΔGsolv.15 In addition to static calculations, we also carried out quasiclassical direct molecular dynamics simulations. Trajectories were initiated at the transition-state structure using local mode (including zero-point energy (ZPE)) and thermal sampling at 90°C and were propagated for 1000 fs with 1 fs time steps. For the carbene ligand, the model IMe = N,N’dimethylimidazol-2-ylidene was used for examination of reaction mechanisms. The complete IMes ligand was also examined for select structures and energies. Stimulated by the unexpected inverse KIE and kinetic mixture of trans- and cis-stilbene, we began searching for initial catalytic steps significantly different than H2 addition to Ag and Ru metal centers proposed in Scheme 1b. This led to a variety of closed-shell and open-shell intermediates being dismissed based on unviable thermodynamics (Scheme 3a). For example, catalysis does not begin with homolysis or heterolysis of the Ag-Ru bond, which requires >50 kcal/mol to cleave. Also, as would generally be expected, generation of a low-coordinate Ru or Ag metal center by either CO or carbene ligand dissociation requires too large an energy penalty to be viable (see Supporting Information (SI)). While the thermodynamics for Ag-Ru addition to one of the diphenylacetylene π bonds is reasonable, we have dismissed catalysis beginning by reaction with the alkyne based on a relatively large transition-state free energy barrier estimate (see SI). All this evidence suggests that semihydrogenation is initiated by H2 activation. Our calculations suggest that H2 activation is not initiated by electron transfer or mononuclear oxidative addition pathways, but rather the previously proposed one-step mechanism where H2 adds across Ag and Ru metal centers via TS1 that shown in Scheme 3b.9

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b)

a)

L

Ag Ph

R N

RuCp(CO)2 R N

Ph L

Ph

Ag Ru

H

N R

CO

Ph

Ph

Ru

TS2

OC CO

R N

homolysis L

Ag Ru N R

Ag + Ru

H H L

Ag Ru

H2

Ph R N

H2

0.0

OC Ag Ru

N R

R 15.3 (14.9) [15.5] N Ag H N + R

CO

H + H Ag Ru OC CO

Ph TS3

cis-1

cis-2

TS4 -8.6 (-8.8) [-14.1]

AgL trans-2 Ph AgL

Ph

-12.0 (-12.1) [-15.4] Ph

-39.6 (-40.0)

H

L Ag

L Ag

Ph Cp(CO)2RuH

H Ru

OC CO

Ph

H R = Me @ 25 C (R = Me @ 90 C) [R = IMes @ 25 C]

18.1 (17.9)

C

-7.6 (-8.0) [-8.9]

OC CO

Ph LAg

trans-1

22.7 (22.3)

22.6 (22.4)

Ru H

OC CO

R N N R

+

OC CO

OC CO

H2

Ph

Dynamical Bifurcation

32.3 (32.0) [31.2]

TS1 24.5 (24.2) [22.7]

H

N R

H

Ag

+ CO

Ph Ag

Ph

Ph

Ph

Ph

Ph

Scheme 3. a) Examples of first catalytic steps that are not viable based on thermodynamic and kinetic DFT calculations. b) M06-L/6311++G(2d,2p)[def2-TZVP]|SMD//M06-L/6-31+G(d,p)[LANL2DZ]|SMD enthalpy landscape at 25 °C and 90 °C for H2 semihydrogenation of diphenylacetylene. (kcal/mol)

The result of TS1 is the pair of metal hydrides (IMe)AgH and Cp(CO)2RuH, and this transitions state requires H‡ = 24.5 kcal/mol with the model IMe ligand and 22.7 kcal/mol with the complete IMes ligand. Consistent with the experimental lack of observation of either Ag-H or Ru-H species during catalysis, this first reaction step is endothermic by 15.3 kcal/mol for the IMe system. We initially assumed that the Ag-Ru heterodinuclear complex is the catalytic resting state and H2 activation transition state TS1 would be turnover limiting; however, calculation of the H2/D2 KIE based only on zero-point energies (ZPEs, E‡ZPE) gave a primary KIE of 1.3 (Scheme 4a), which is inconsistent with experimental rate data. With catalysis commencing by generation of a pair of metal hydrides, we then examined pathways and barriers for Cp(CO)2RuH and (IMe)AgH reaction with diphenylacetylene. The concerted cis-1,2-addition of Cp(CO)2RuH to one of the π bonds of diphenylacetylene has H‡ = 54.7 kcal/mol, relative to the catalyst ground state. This large barrier is consistent with slipping of the Cp group to allow for diphenylacetylene coordination. We also calculated the thermodynamics of hydrogen atom, proton, and hydride transfer. The lowest of these possibilities is hydrogen atom transfer, but with a H‡ >40 kcal/mol suggests that Cp(CO)2RuH is not effective at initiating diphenylacetylene hydrogenation (see SI). Without a low energy pathway to form a Ru-vinyl intermediate, a subsequent Ru-carbene type intermediate is unlikely.16 This relatively large cis-1,2-addition and hydrogen atom transfer barriers, and unfavorable thermodynamics for proton and hydride transfer, is consistent with Mankad’s previous experiments showing low catalytic semi-hydrogenation yields using this Ru-H species.9 For the Ag-H species, we initially assumed there would be a relatively low energy barrier for concerted cis-1,2-addition, which occurs readily for related Cu-H chemistry. However, extensive mapping of the potential energy surface showed no first-order saddle point for a one-step addition process (see SI).

However, using a constrained geometry, we estimated a cis-1,2addition transition state to have a H‡ of ~40 kcal/mol (see SI for details). This relatively large barrier seemed to us to be too high, especially for the 90 °C catalytic temperature. This prompted us to explore the energy surface for multi-step 1,2addition mechanisms. Surprisingly, despite very little solvent stabilization, we located a polar hydride transfer transition state, TS2 (Schemes 3b, 4a), that has an ~10 kcal/mol lower activation barrier than our concerted cis-1,2-addition estimate. The TS2 calculated activation parameters are H‡ = 32.3 kcal/mol for the IMe ligand and 31.2 kcal/mol for the IMes ligand. While these calculated H‡ values are consistent with other activation enthalpies experimentally measured for multimetallic reactions at similar temperatures,17 our experimental Eyring plot of rate constant data over the 60-90°C temperature range allowed us to estimate an activation H‡ parameter of 21.4 kcal/mol (see SI). This indicates that M06-L, and other density functionals (e.g. B97X-D) typically accurate for first-row transition metal reactions, significantly overestimates the barrier height of TS2. The geometry of TS2 has a bent Ag-H-C angle of ~150°. The Ag-H bond is elongated to 1.76 Å, the forming C-H bond is at 1.64 Å, and the PhCC angles show significant bending. Charge analysis indicates that TS2 is a hydride, not a hydrogen atom, transfer transition state (see SI). Because intrinsic reaction coordinate (IRC) calculations were unsuccessful to link TS2 to intermediates, we used quasiclassical (with ZPE) molecular dynamics simulations (40 total trajectories each with a randomized vibrationally averaged velocity distribution) to follow the reaction pathway(s) emanating to and from TS2. Our molecular dynamics simulations at 90 °C demonstrated that the reaction pathway dynamically splits after TS2 (Scheme 3b) and gave a ratio of 3:1 for trans-1:trans-2. All connected reverse trajectories resulted in separated (IMe)AgH and diphenylacetylene.

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Figure 1. Quasiclassical trajectory snapshots of forward progression of a representative trajectory a) leading to trans-2, and b) leading to trans-1. Each trajectory was initiated at TS2 using ZPE and thermal local mode sampling at 90°C, and propagated for 1000 fs. M06-L/631+G(d,p)[LANL2DZ]|SMD. (fs = femtosecond)

Figure 1a shows a representative trajectory leading to trans2 where after 50 fs the Ag-H bond has been severed and the CH bond formed. From 50 fs to 300 fs the newly formed vinyl anion reorients to form the vinylsilver intermediate. In the trajectory shown in Figure 1b, again, the hydride is transferred within 50 fs, but after this time, and up to 1000 fs, the Ag cation only interacts with the phenyl group of the vinyl anion and leads to trans-1. Overall, in the majority of trajectories by ~500 fs the (IMe)Ag cation migrates to coordination with one of the anionic phenyl group carbons to a structure similar to trans-1 that has a trans vinyl geometry, which is likely the result of the bent PhCC angle in the transition state. Trans-1 is endothermic by 17.9 kcal/mol, and we propose that this ion-pair intermediate can lead to either the trans- or cis-vinylsilver intermediates, which are likely irreversibly formed, and this provides a qualitative explanation for the kinetic mixture of trans- and cis-stilbene. cis-2 can result from trans-1 through a 4.6 kcal/mol barrier for vinyl anion inversion through an allenic transition-state structure TS3 (Scheme 3b).

A similar pathway may be operative in the trans-addition of (NHC)AuH complexes to dimethylacetylene dicarboxylate,18 which is sufficiently electron-deficient to favor ionic hydrometallation. The catalytic cycle is completed by Cp(CO)2RuH inducing protonation of the vinylsilver intermediate trans-2 (or cis-2) through TS4, which liberates trans- (or cis-) stilbene from the corresponding intermediates. We were surprised to find that the protonlysis barrier is only 11.5 kcal/mol. However, this low barrier is consistent with the stoichiometric protonolysis of (IPr)Cu(CHPhCH2Bpin) with Cp(CO)2RuH that occurs at room temperature.11 This uniquely low protonolysis barrier is likely the result of the forming covalent Ru-Ag bond in addition to the Ru-H acidity. The pKa of Cp(CO)2RuH has been estimated to be ~25.19 Therefore, as a comparison, we located TS4 analogues using NH3 and MeOH. For NH3, the barrier for the protonolysis step increases to 26.7 kcal/mol and with MeOH the barrier increases to 15.8, which is 4.3 kcal/mol larger than for protonolysis with Cp(CO)2RuH.

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b)

R N

R N

Ag H

H

N R

N R

H

Ag

Ru OC CO

Ph Ag

OC

TS1 kH/kD = 1.30

R N

+

H

N R

Ru H CO

Ph

TS2 kH/kD = 0.44 kH/kD = 1.3 without Ru-H

KH/KD = 0.34

c) H2 stretch   1400 D2

KH < KD

sum of  >1400

+ bends

stretches d) Ru

H

OC CO

(CO)2CpRu

H

in-plane stretch   464

(CO)2CpRu

H

in-plane bend   127

(CO)2CpRu

H

in-plane bend   130

CONCLUSIONS

Me N Ag H N Me

and the primary KIE of 1.3 (for TS2 relative to intermediate), since the rate law for this kinetic scenario would have kobs proportional to KeqkTS2 (Scheme 4b). Notably, this prediction is qualitatively similar to the experimentally determined KIE in that it is significantly less than 1. Inspection of Cp(CO)2RuH and (IMe)AgH structures indicates that all M-H vibrational frequencies are smaller than H2. Therefore, an inverse EIE results from the sum of several low energy vibrational frequencies in the metal hydrides that creates an overall deuterium ZPE preference (Scheme 4b). For Ru-H and Ag-H, the difference between hydrogen and deuterium stretching vibrational frequencies () is 464 and 465 cm-1, which is not enough to overcome the  of ~1400 cm-1 for H2/D2. Therefore, similar to the cases of W(PMe3)4I2 and Vaska’s complex, the origin of the inverse EIE, and ultimately the inverse KIE, is the low-energy bending modes. Scheme 4c depicts the two key bending modes in Cp(CO)2RuH and three key bending modes in (IMe)AgH that together are responsible for the inverse EIE and KIE. Lastly, with TS2 proposed to limit catalytic turnover, we calculated the ground states and TS2 for the para-methoxy diarylalkyne substrate. Consistent with the experimentally determined kOMe/kH relative rate of 7.4, the methoxy-substituted TS2 has H‡ = 29.2 kcal/mol, which is 1.6 kcal/mol lower than the diphenylacetylene TS2.

L Ag H in-plane stretch   465

L Ag H in-plane bends   85   60

L Ag H out-of-plane bend   132

Scheme 4. a) 3D representations of TS1 and TS2. (Å) b) Calculated KIE and EIE values relative to (IMe)Ag-RuCp(CO)2 and H2/D2. c) Graphical explanation of how the combination of stretches and bends provide lower energy deuterium states and inverse EIE. d) Difference () in H/D vibrational frequencies (cm-1) responsible for inverse EIE, and vector displacements.

The catalytic mechanism outlined in Scheme 3b indicates that TS2 is turnover limiting. This was unexpected to us because TS2 involves significant Ag-H stretching and, thus, would not be expected exhibit an inverse KIE. Indeed, the calculated KIE for TS2 compared to the (IMe)AgH intermediate that precedes it is 1.3. However, by including the Ru-H(D) intermediate by comparing TS2 to reactants, based only on ZPEs, we calculated an inverse KIE of 0.44 (Scheme 4b). Intriguingly, then, an inverse rather than primary KIE for TS2 is induced by a Ru-H intermediate that is idle during this reaction step. The origin of this effect is actually an inverse equilibrium isotope effect (EIE) for transformation of (IMe)Ag-RuCp(CO)2 to the pair of metal hydrides that feed into TS2, because these intermediates are endothermic compared to the reactants. Calculation of the EIE for this pre-equilibrium based on EZPE gave a value of 0.34 (Scheme 4b). Similar inverse EIEs have previously been reported by Parkin20 for H2 oxidative addition to W(PMe3)4I2 and by Goldman21 for Vaska’s complex Ir(PPh3)2(CO)Cl; however, in both of these cases metal cis-dihydrides are formed rather than pairs of metal hydrides as occurs in this heterodinuclear reaction.22 While there are several components of an EIE, Parkin and Goldman/Krogh-Jespersen showed that for these W and Ir complexes the relative H2/D2 equilibriums are controlled by ZPE effects.23 The predicted isotope effect of 0.44 can be seen as being composed of the inverse EIE of 0.34

Our experimental and computational effort examining AgRu semi-hydrogenation of alkynes revealed that at 90°C there is a mixture of cis-stilbene and trans-stilbene that results from H2 activation followed by ionic Ag-H hydride transfer, and after this transition state there is a dynamical path bifurcation.24 While the hydride transfer transition state is turnover limiting, the measured inverse H2/D2 KIE results from an idle Ru-H species with low-energy bending modes and an inverse EIE. The Ag-Ru heterodinuclear cooperative effective is critical for both H2 activation and vinylsilver protonolysis reaction steps, and rate studies and transition-state calculation showed that unexpectedly an electron-donating group accelerated catalysis. Overall, our calculated reaction mechanism demonstrates the key dinuclear cooperative effects are the reactive Ag-H intermediate is generated only by cooperative H2 activation across both metal centers and protonation of the vinylsilver intermediate has a very low barrier due to the presence of AgRu interaction in the transition state.

ASSOCIATED CONTENT Supporting Information. Experimental details, xyz coordinate file, and energies. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Author *[email protected] *[email protected]

The authors declare no competing financial interests.

ACKNOWLEDGMENT D.H.E. thanks Brigham Young University (BYU) and the Fulton Supercomputing Lab (FSL). D.H.E. and N.P.M. thank the National

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Science Foundation Chemical Catalysis Program for support (CHE-1764194 and CHE-1664632, respectively). M.K.K. received fellowship support from the Benjamin B. Freud Award. W.W. thanks the BYU Chemistry and Biochemistry Department for an Undergraduate Research Award.

ABBREVIATIONS DFT, Density Functional Theory; KIE, Kinetic Isotope Effect; EIE, Equilibrium Isotope Effect.

REFERENCES

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Polymetallic Complexes Linked to A Single-Frame Ligand: Cooperative Effects in Catalysis. Dalton Trans. 2013, 42, 10664-10681. 4. For example: a) Mazzacano, T. J.; Mankad, N. P. Base Metal Catalysts for Photochemical C–H Borylation That Utilize Metal– Metal Cooperativity. J. Am. Chem. Soc. 2013, 135, 17258-17261. b) Powers, D. C.; Ritter, T. Bimetallic Pd(III) Complexes in Palladium-Catalysed Carbon–Heteroatom Bond Formation. Nat. Chem. 2009, 1, 302-309. 5. For a review: a) Pye, D. R.; Mankad, N. P. Bimetallic Catalysis for C–C and C–X Coupling Reactions. Chem. Sci. 2017, 8, 17051718. For selected examples: b) Dürr, A. B.; Fisher, H. C.; Kalvet, I.; Truong, K.-N.; Schoenebeck, F. Divergent Reactivity of a Dinuclear (NHC)Nickel(I) Catalyst versus Nickel(0) Enables Chemoselective Trifluoromethylselenolation. Angew. Chem. Int. Ed. 2017, 56, 13431-13435. c) Steiman, T. J.; Uyeda, C. Reversible Substrate Activation and Catalysis at an Intact Metal–Metal Bond Using a Redox-Active Supporting Ligand. J. Am. Chem. Soc. 2015, 137, 6104-6110. d) Pye, D. R.; Cheng, L.-J.; Mankad, N. P. Cu/Mn Bimetallic Catalysis Enables Carbonylative Suzuki–Miyaura Coupling with Unactivated Alkyl Electrophiles. Chem. Sci. 2017, 8, 4750-4755. e) Levin, M. D.; Toste, F. D. Gold‐Catalyzed Allylation of Aryl Boronic Acids: Accessing Cross‐Coupling Reactivity with Gold. Angew. Chem. Int. Ed. 2014, 53, 6211-6215. 6. Cammarota, R. C.; Vollmer, M. V.; Xie, J.; Ye, J.; Linehan, J. C.; Burgess, S. A.; Appel, A. M.; Gagliardi, L.; Lu, C. C. A Bimetallic Nickel–Gallium Complex Catalyzes CO2 Hydrogenation via the Intermediacy of an Anionic d10 Nickel Hydride. J. Am. Chem. Soc. 2017, 139, 14244-14250. 7. Siedschlag, R. B.; Bernales, V.; Vogiatzis, K. D.; Planas, N.; Clouston, L. J.; Bill, E.; Gagliardi, L.; Lu, C. C. Catalytic Silylation of Dinitrogen with a Dicobalt Complex. J. Am. Chem. Soc. 2015, 137, 4638-4641. 8. a) Sinfelt, J. H. Bimetallic Catalysts: Discoveries, Concepts and Applications; John Wiley and Sons: New York, 1983. b) Bullock, R. M.; Casey, C. P. Heterobimetallic Compounds Linked by Heterodifunctional Ligands. Acc. Chem. Res. 1987, 20, 167-173. c) Zanello, P.; Tamburini, S.; Alessandro Vigato, P.; Antonio Mazzocchin, G. Syntheses, Structure and Electrochemical Characterization of Homo- and Heterodinuclear Copper Complexes with Compartmental Ligands. Coord. Chem. Rev. 1987, 77, 165273. d) Stephan, D. W. Early-Late Heterobimetallics Coord. Chem. Rev. 1989, 95, 41-107. e) Beuken, E. K. van den; Feringa, B. L. Bimetallic Catalysis by Late Transition Metal Complexes. Tetrahedron 1998, 54, 12985-13011. f) Wheatley, N.; Kalck, P. Structure and Reactivit of Early-Late Heterobimetallic Complexes. Chem. Rev. 1999, 99, 3379-3419. g) Gade, L. H. Highly Polar Metal–Metal Bonds in “Early–Late” Heterodimetallic Complexes. Angew. Chem. Int. Ed. 2000, 39, 2658-2678. h) Oro, L. A.; Sola, E. Mechanistic Aspects of Dihydrogen Activation and Catalysis by Dinuclear Complexes in Recent Advances in Hydride Chemistry, Elsevier, 2001, 299-327. 9. Karunananda, M. K.; Mankad, N. P. E-Selective Semi-Hydrogenation of Alkynes by Heterobimetallic Catalysis. J. Am. Chem. Soc. 2015, 137, 14598-14601. 10. Other examples of trans-selective hydrogenation catalysis using H2 as the reductant: a) Tokmic, K.; Fout, A. R. Alkyne Semihydrogenation with a Well-Defined Nonclassical Co–H2 Catalyst: A H2 Spin on Isomerization and E-Selectivity. J. Am. Chem. Soc. 2016, 138, 13700-13705. b) Furukawa, S.; Komatsu, T. Selective Hydrogenation of Functionalized Alkynes to (E)-Alkenes, Using Ordered Alloys as Catalysts. ACS Catal. 2016, 6, 2121-2125. c) Liu, Y.; Hu, L.; Chen, H.; Du, H. An Alkene‐Promoted Borane‐Catalyzed Highly Stereoselective Hydrogenation of Alkynes to Give Z‐ and E‐Alkenes. Chem. Eur. J. 2015, 21, 3495-3501. d) Srimani, D.; Diskin-Posner, Y.; Ben-David, Y.; Milstein, D. Iron Pincer Complex Catalyzed, Environmentally Benign, E‐Selective

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Semi‐Hydrogenation of Alkynes. Angew. Chem. Int. Ed. 2013, 52, 14131-14134. e) Radkowski, K.; Sundararaju, B.; Fürstner, A. A Functional‐Group‐Tolerant Catalytic trans Hydrogenation of Alkynes*. Angew. Chem. Int. Ed. 2012, 52, 355-360. 11. Karunananda, M. K.; Mankad, N. P. Heterobimetallic H2 Addition and Alkene/Alkane Elimination Reactions Related to the Mechanism of E-Selective Alkyne Semihydrogenation. Organometallics 2017, 36, 220-227. 12. Mankad, N. P.; Laitar, D. S.; Sadighi, J. P. Synthesis, Structure, and Alkyne Reactivity of a Dimeric (Carbene)copper(I) Hydride. Organometallics 2004, 23, 3369-3371. 13. Jordan, A. J.; Lalic, G.; Sadighi, J. P. Coinage Metal Hydrides: Synthesis, Characterization, and Reactivity. Chem. Rev. 2016, 116, 8318-8372. 14. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J., Gaussian 09, Revision B.01. Wallingford CT, 2009. 15. Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J. Phys. Chem. B 2009, 113, 6378-6396. 16. a) Leutzsch, M.; Wolf, L. M.; Gupta, P.; Fuchs, M.; Thiel, W.; Farès, C.; Fürstner, A. Formation of Ruthenium Carbenes by gemHydrogen Transfer to Internal Alkynes: Implications for Alkyne trans-Hydrogenation. Angew. Chem., Int. Ed. 2015, 54, 1243112436. b) Guthertz, A.; Leutzsch, M.; Wolf, L. M.; Gupta, P.; Rummelt, S. M.; Goddard, R.; Farès, C.; Thiel, W.; Fürstner, A. HalfSandwich Ruthenium Carbene Complexes Link trans-Hydrogenation and gem-Hydrogenation of Internal Alkynes. J. Am. Chem. Soc. 2018, 140, 3156-3169. 17. Butler, M. J.; White, A. J. P.; Crimmin, M. R. Heterobimetallic Rebound: A Mechanism for Diene to Alkyne Isomerization with M---Zr Hydride Complexes (M = Al, Zn, and Mg) Organometallics 2018, 37, 949-956. 18. Tsui, E. Y.; Müller, P.; Sadighi, J. P. 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