Investigation of β-H Elimination and Hydrogenolysis of Linear (NHC)Cu-alkyls

Salt-metathesis reactions of (IPr*CPh₃)CuCl and 1.3 equiv. of RMgCl for 10 min cleanly produced alkyl complexes 1^iPr and 1^tBu as determined by ¹H NMR spectroscopy. Alternatively, trapping of in situ generated (IPr*CPh₃)CuH with 1-hexene or cyclopentene provided complexes 1^R (R = hexyl, ^cPent), respectively (see Supporting Information for details on the isolation of these complexes).^[45] To understand the general reactivity pattern of linear (NHC)Cu(I)-alkyl complexes previously reported,^{[32-34, 39]} we evaluated the linear primary, secondary, and tertiary alkyl complexes (IPr*CPh₃)CuR (1^R, R = hexyl, ⁱPr, ^cPent, ^tBu) toward β-H elimination and hydrogenolysis. The adequate solution stability (t_1/2 ∼ 12 h, C₆D₆, 25 °C) and known spectroscopic characterization of the resulting (IPr*CPh₃)CuH monomer^[45] (1^H) in these transformations represent a major advantage for mechanistic studies. ¹H NMR spectroscopic studies of isolated primary 1^Hex shows no β-H elimination in C₆D₆ at 25 °C for >4 days or 80 °C for 24 h, nor hydrogenolysis under 4 atm H₂ at 25–80 °C (Scheme 1). Additionally, no catalytic hydrogenations of 1-hexene or cyclopentene were observed in the presence of 10 mol% of 1^Hex or 1^cPent in C₆D₆ under 4 atm H₂ at 25–80 °C over 24 h. The persistent concentration of these linear copper alkyl complexes during attempted catalytic reactions indicates no reactivity other than their gradual decomposition (<5%).

Moreover, the minimal β-H elimination and absence of isomerization with unsubstituted secondary or tertiary alkyl complexes 1^iPr or 1^tBu contrasts with the proposed tandem β-H elimination/isomerization process in the conversion of (IPr)Cu─CH(Ph)CH₂Bpin to (IPr)Cu–CH(BPin)CH₂(Ph) at 70 °C for 24 h.^{[39, 40]} The potential role of the boron functionality on β-H elimination in this complex remains unclear. ¹H NMR analysis of 1^iPr or 1^tBu in C₆D₆ over 7.5 days at 25 °C showed trace formation of propylene and isobutylene, respectively (Figure S11). However, neither 1^H nor the primary isomerized 1^nPr or 1^iBu products were observed. The starting complexes of 1^iPr or 1^tBu decomposed by 4% and 2%, respectively, with trace detection of free IPr*CPh₃ ligand. These observations suggest decomposition follows β-H elimination instead of reinsertion of the eliminated olefin over these long reaction times at low concentrations of 1^H and olefin that are produced. Under more forcing conditions (C₆D₆, 80 °C, 17.5 h), 7.6% decomposition of 1^tBu was observed by ¹H NMR spectroscopy. Kinetic modeling of this process, assuming an irreversible first-order process (i.e., β-H elimination), yields a barrier of 30.4 kcal mol⁻¹, which is consistent with our DFT investigation (vide infra). The solution stabilities of 1^R complexes are consistent with those reported previously for unsubstituted, linear (NHC)Cu-alkyl complexes.^[32-34]

Observed β-H Elimination of Trigonal Planar Cu(I)-Alkyls

Salt-metathesis reactions of (NBC^CPh3)CuCl and corresponding organomagnesium reagents cleanly generated complexes (NBC^CPh3)CuR (2^R, R = Me, Et, ⁱPr, ^cPr, ^tBu—see Supporting Information for details). Single crystals of 2^R were obtained by vapor diffusion of pentane into benzene solution at room temperature. ¹H NMR spectroscopic and single crystal X-ray diffraction (SCXRD) analysis of the isolated single crystals revealed stark differences in the stabilities of the alkyl complexes.

Complex 2^Me, isolated in 75% yield and devoid of β-hydrogen atoms, is thermally stable as a solid and in solution, yet it is exceedingly sensitive to air and moisture. Single crystals and C₆D₆ solutions of 2^Et are stable under nitrogen at ambient temperature and pressure but decompose to intractable mixtures under vacuum. ¹H NMR spectroscopic analysis of 2^Et generated in situ at room temperature showed trace ethylene, implying an operative β-H elimination pathway. However, the anticipated hydride product of (NBC^CPh3)CuH (2^H) was not detected. The independent synthesis and spectroscopic characterization of 2^H is discussed in a later section. The minimal β-H elimination is attributed to favorable ethylene reinsertion into (NBC^CPh3)CuH in this equilibrium. Moreover, the dissolution of isolated crystalline 2^Et in C₆D₆ reveals no free ethylene over 24 h.

To provide definitive spectroscopic evidence for β-H elimination, we examined the reactions of secondary and tertiary alkyl complexes 2^iPr and 2^tBu, which can isomerize to the corresponding thermodynamic primary alkyl products (Figure 2).^[47-49] Previous kinetic studies indicate that the insertion of unactivated olefins into isolated (IPr*CPh₃)CuH monomer proceeds by rate-limiting hydride transfer under pseudo-first-order conditions.^[45] Therefore, the expectedly slow second-order reaction between the CuH monomer and reduced olefin concentration should enable the observation of all relevant species in a mechanism of β-H elimination and reinsertion on the ¹H NMR timescale.

The ¹H NMR spectrum obtained immediately after adding ⁱPrMgCl to (NBC^CPh3)CuCl indicates clean formation of (NBC^CPh3)CuⁱPr (2^iPr). Spectroscopic monitoring of 2^iPr generated in situ in C₆D₆ at 25 °C shows free propylene and isomerization to 2^nPr, with no 2^iPr remaining after 24 h (Figure 2). After 3 days, 2^nPr, 2^H (vide infra), and propylene are still detected. The presence of 2^H was identified from key NBC^CPh3 resonances, as overlapping residual solvent signals obscure the hydride resonance of 2^H. Modeling of the reaction kinetics using COPASI^[50] provided a free energy barrier of 23.2 kcal mol⁻¹ for the β-H elimination of 2^iPr at 25 °C (Supporting Information Pages S34–S39). Additionally, SCXRD of red-brown single crystals obtained from the reaction mixture confirmed the structure of the isomerized product 2^nPr (Figure 3a). These observations corroborate the complete isomerization of secondary alkyl complex 2^iPr to the thermodynamically favored primary alkyl product 2^nPr. Moreover, an equilibrium of β-H elimination/reinsertion from 2^nPr is supported by continuous spectroscopic detection of 2^H and propylene.

The isomerization of 2^tBu is much slower than that of 2^iPr (Figure 2b). Initial qualitative ¹H NMR spectroscopic analysis of isolated 2^tBu in C₆D₆ over 7 days at 22 °C showed gradual conversion to 2^iBu, as determined by the loss of the ^tBu signal and concomitant growth of other key ⁱBu resonances. In addition to these two species, isobutylene and a third minor set of ligand resonances for 2^H (∼5%) are detected. In contrast to 2^iPr, the isomerization of isolated 2^tBu allowed observation of the corresponding 2^H with a CuH singlet at 3.79 ppm (C₆D₆, 25 °C). After 13 days, only 2^iBu, 2^H, and isobutylene are observed, consistent with β-H elimination occurring from the isomerized alkyl species. The slow isomerization of 2^tBu to 2^iBu at 25 °C enabled the collection of time-course concentration data for all observable species (Figure 2b). Kinetic modeling of the reaction determined barriers of β-H elimination for both 2^tBu and 2^iBu at 24.5 and 24.1 kcal mol⁻¹, respectively, along with an anti-Markovnikov insertion barrier of isobutylene into 2^H at 17.6 kcal mol⁻¹ (Supporting Information Pages S28–S33).

The preferential formation of primary alkyl products aligns with the general observation that these complexes are thermodynamically favored based on steric effects, particularly at a congested metal center.^[51] Although the current data cannot fully elucidate the origin for the faster β-H elimination rate of 2^iPr compared to that of 2^tBu (hours vs. days), we propose that 2^tBu experiences greater conformational constraints for adopting a syn coplanar rearrangement for β-H elimination, compared to that of 2^iPr, leading to a decreased rate of isomerization. The detection of CuH monomer, propylene, and isobutylene in the isomerization of secondary and tertiary alkyl complexes of 2^iPr and 2^tBu to their corresponding primary alkyl complexes indicates a β-H elimination/reinsertion mechanism rather than a π-allyl complex pathway.^[51]

The solid-state structure of 2^tBu (Figure 3b), obtained from immediate crystallization after synthesis, shows that one of the three Cu─C_β distances is significantly shorter (2.849(3) vs. 3.030(2) and 3.006(3) Å) and exhibits a smaller ∠Cu─C_α─C_β (106.1(1)° vs. 115.8(1)° and 114.5(1)°), suggesting a potential interaction between Cu and this β-CH₃ at −173 °C (the temperature of SCXRD data collection). Cooling a toluene-d₈ solution of 2^tBu to −90 °C revealed no de-coalescence of the β-CH₃ resonances by ¹H NMR spectroscopy, indicating no observable interactions at this temperature in solution. Moreover, the isomerization of 2^tBu occurs at 25 °C, therefore, the structural features of solid-state 2^tBu determined at −173 °C by SCXRD are (unsurprisingly) not representative of the relevant reaction conditions. DFT calculations on the geometry optimized structure and complementary occupied-virtual pairs (COVP) analysis of 2^tBu do not show significantly shortened β-CH₃···Cu distances or significant stabilization/interaction between Cu(I) d-orbitals and β-CH₃ groups of the ^tBu ligand (Supporting Information, Page S115).

We employed a strained alkyl group to disfavor the syn coplanar arrangement for β-H elimination^[52] to isolate (NBC^CPh3)Cu-cyclopropyl (2^cPr) (78% yield) that is stable to β-H elimination between 25–60 °C (vide infra). In addition to strain, the high-energy formation of the cyclopropene product also likely contributes to the stability of this robust alkyl species. Spectroscopic and crystallographic analysis confirmed the formation of 2^cPr (Figure 3c), with the strained Cu-cyclopropyl functionality containing no apparent β-CH₃ interactions at Cu (Cu–C_β = 3.119(4) and 3.158(3) Å).

Generation of (NBC^CPh3)CuH Monomer by Hydrogenolysis

The generation of metal hydride products by metal alkyl hydrogenolysis is well documented,^{[7, 53-55]} yet hydrogenolysis of Cu-alkyls is uncommon compared to those of Cu-alkoxides.^{[17, 23, 25, 28, 56, 57]} Based on the accepted β-H elimination mechanism of alkyl complexes,^{[58, 59]} the formation of (NBC^CPh3)CuH (2^H) from (NBC^CPh3)Cu-alkyls implies C–H σ-coordination of alkyl ligands before C─H bond cleavage. Dihydrogen might access similar σ-coordination at Cu(I) to facilitate hydrogenolysis;^{[60, 61]} therefore, we investigated the reaction of (NBC^CPh3)Cu-alkyl with H₂ to generate 2^H.

The isolation of stable 2^cPr enables direct examination of hydrogenolysis, since competitive β-H elimination of 2^Et, 2^iPr, and 2^tBu and the extreme sensitivity of 2^Me to adventitious moisture complicate these studies. Exposure of 2^cPr to 4 atm H_2(g) in C₆D₆ at 22 °C produced monomeric 2^H as observed by ¹H NMR spectroscopy, requiring 11 days to reach 39% conversion of 2^cPr. The initial introduction of H₂ formed trace (NBC^CPh3)CuOH (2^OH) by protonolysis of 2^cPr by adventitious H₂O, in which the 2^OH concentration is depleted within the first 5 h of reaction. The identity of 2^OH was confirmed by independent synthesis (Supporting Information, Page S101).

Despite incomplete hydrogenolysis of 2^cPr over even longer reaction times (22 °C for 22 days), the resulting 1:1.6 2^cPr/2^H mixture provided clear spectroscopic evidence of monomeric 2^H from the integration of the hydride singlet at 3.79 ppm to a single proton relative to the corresponding NBC^CPh3 ligand resonances in the ¹H NMR spectrum. This hydride signal exhibits a doublet cross-peak (²J_C–H = 14.4 Hz) in the ¹H–¹³C HMBC NMR spectrum, with the carbene carbon singlet at 186.8 ppm in the ¹³C{¹H} spectrum. The carbene resonance splits into a doublet (²J_C–H = 14.0 Hz) in the proton-coupled ¹³C spectrum, providing unequivocal evidence of only one hydride in the monomeric 2^H (Figure S45–S48). We observed minor decomposition of 2^H at room temperature (6% mass-balance loss over 11 days). Monitoring the hydrogenolysis of 2^cPr at 60 °C in C₆D₆ over 4 half-lives in 24 h shows rate acceleration but also increased decomposition to 75%. At this elevated temperature, 2^OH is also fully consumed (Figure 4).

Motivated by the persistence of 2^H in solution, we generated a copper alkoxide synthon for isolating this monomeric CuH.^[19] Because of the steric constraints at the Cu center from the NBC^CPh3 ligand, the ethoxide ligand was targeted instead of the commonly employed tert-butoxide analogue. (NBC^CPh3)CuOEt (2^OEt) was cleanly isolated in 76% by treating (NBC^CPh3)CuCl with 10 equiv. of KOEt in THF over 60 h at room temperature. A lack of solubility of KOEt in THF and the sterically hindered pocket at the CuCl center likely both contribute to the sluggish reaction. The crystal structure of 2^OEt exhibits orientational disorder of the ethoxide fragment into two separately observed conformations (57:43 ratio)—additional structural analysis is provided in the Supporting Information (Figure S36).

Addition of HSi(OEt)₃ to benzene or toluene solutions of 2^OEt at 22 °C rapidly and cleanly converts the dark-orange solution to a dark-brown solution containing 2^H and Si(OEt)₄ as indicated by ¹H NMR analysis in C₆D₆. Immediate precipitation with pentane yields a dark-brown powder, which can be isolated and stored at −30 °C for months without significant deterioration. Extended application of vacuum to remove all residual solvent leads to varying levels of decomposition, but the spectroscopic characterization of this isolated 2^H is consistent with all signals observed when generated via 2^cPr + H₂. Dissolution of 2^H in C₆D₆ engendered more decomposition (∼20% over 50 h, vide infra) when not pressurized with H₂. Attempts to synthesize the Cu-D isotopologue using DSi(OEt)₃ only led to its partial formation, with deuterium washing into the -CHPh₂ arms of the NBC^CPh3 ligand while in solution (Figures S42 and S43, vide infra).

The hydride resonance of 2^H at 3.79 ppm appears distinctly downfield from those of the three known CuH monomers (1.50–2.14 ppm),^{[45, 62, 63]} all of which are linear complexes supported by monodentate NHC ligands. Notably, (IPr*CPh₃)CuH (1^H), containing identical flanking aryls to that of 2^H, features a hydride resonance at 1.89 ppm (C₆D₆) in the ¹H NMR spectrum. The ²J_CH coupling of 14 Hz measured for 2^H is smaller than the previously reported ²J_C-H coupling (40.0–41.6 Hz) for linear monomeric Cu–H complexes. These spectroscopic differences can be ascribed to the geometry of 2^H since a carbene donor trans to the hydride is absent, abating the trans influence that impacts the magnitude of coupling and shielding effects observed in previous reports.^[64]

Although 2^H is sufficiently stable in solution for spectroscopic characterization at room temperature, attempts at obtaining single crystals were unsuccessful. Rather, a crystal of an intermediate species (Int) was isolated; its structure is shown in Figure 5. Although we were unable to cleanly isolate this complex on a preparative scale, solid-state structural analysis indicates deprotonation of a methine position at one of the -CHPh₂ groups of the NBC^CPh3 ligand, yielding an anionic fragment, in which the negative charge appears delocalized over the resulting biphenyl unit that coordinates η² to the now cationic Cu(I) center. Presumably, in the absence of H₂ under crystallization conditions, the hydride ligand of 2^H undergoes intramolecular deprotonation of a -CHPh₂ group with accompanying loss of H₂. Although the bound arene formally carries a delocalized negative charge, the Cu─C_arene bond lengths observed in Int are similar to those found in [(IPr)Cu(I)(η²arene)]SbF₆ complexes.^{[65, 66]}

To provide evidence for the key H/D exchange at the -CHPh₂ groups of the NBC^CPh3 ligand in this mechanistic proposal, we examined the reaction of 2^cPr with D₂ (Scheme 2). The reaction of 2^cPr at 60 °C with 4 atm of D₂ predominantly extruded cyclopropane instead of cyclopropane-d₁. A sample of cyclopropane-d₁ was independently synthesized for verification (Supporting Information, Page S65). The ¹H NMR signal for the four equivalent -CHPh₂ groups of the NBC^CPh3 ligand, typically observed at 6.00 ppm (C₆D₆, 60 °C), is absent. A corresponding signal is observed by ²H NMR spectroscopy at the same chemical shift during the reaction. The accompanying loss of a Cu–H signal at 3.65 ppm is also confirmed, and the corresponding Cu–D signal was observed in the ²H NMR spectrum for 2^D as well as the detection of HD gas (Figures S54 and S55). These results imply an equilibrium between 2^H/D and Int, with the resting state favoring 2^H/D under pressurized H₂/D₂ (Scheme 2). Notably, similar H/D exchange in the -CHPh₂ group is observed for the minor quantities of 2^OH/OD, occurring rapidly before the consumption of this species during the initial stages of the reaction (vide infra).

The predominant formation of cyclopropane, instead of cyclopropane-d₁, eliminates the conventional σ-bond metathesis mechanism of D₂ cleavage across the Cu-cyclopropyl functionality. This evidence supports a mechanism involving intramolecular deprotonation of a -CHPh₂ group at NBC^CPh3 by Cu-cyclopropyl to release cyclopropane, followed by heterolytic D₂ cleavage at Int to generate a Cu-D and the first -CDPh₂ group. The complete conversion of all remaining -CHPh₂ groups to -CDPh₂ groups invokes an iterative process of intramolecular deprotonation of -CHPh₂ by the resulting CuD to release HD to generate Int followed by D₂ cleavage to reform CuD. This mechanism of H₂/D₂ cleavage mirrors metal–ligand cooperativity (MLC) pathways in metal-catalyzed hydrogenation,^[67-69] and has inspired an emerging strategy for heterolytic H₂ cleavage at Cu(I).^{[14, 26, 56, 70]}

Additional trapping experiments were performed to further our mechanistic insight into dihydrogen activation from 2^cPr (Figure 6). ¹H NMR spectroscopic analysis of a C₆D₆ solution of 2^cPr at 60 °C without H₂ showed consumption of 2^cPr with concomitant formation of cyclopropane and highly broadened ligand resonances observed for the zwitterionic Int (Figure S52). The formation of cyclopropane corroborates intramolecular deprotonation of 2^cPr and eliminates the possibility of competing β-H elimination of 2^cPr to generate 2^H and cyclopropene. Two sequential intermediates are observed over the course of the reaction kinetics that indicate Int converts to an unidentified species (2^Unk). Upon addition of 1 atm H₂ to the reaction mixture, the broad resonances attributed to Int rapidly convert to 2^H. Moreover, 2^Unk undergoes a slow decay due to its ceased production. The consumption of 2^cPr is independent of [H₂] since the first-order decay kinetic profile of 2^cPr remains undeterred with H₂ addition. Kinetic modeling of the data yields a 26.5 kcal mol⁻¹ barrier for the intramolecular deprotonation of 2^cPr at 60 °C.

Collectively, the hydrogenolysis of linear and trigonal planar Cu-alkyl complexes supported by IPr*CPh₃ and NBC^CPh3 ligands, respectively, do not appear to participate in conventional heterolytic H₂ cleavage by a σ-bond metathesis mechanism, consisting of a four-center transition state arising from the association of metal-alkyl and H₂, that is often invoked for early to middle transition metal alkyl complexes.^{[53, 55]} This lack of reactivity toward H₂ at a Cu-alkyl group likely reflects the different polarization of metal-carbon bonds of early and late metals,^[71] and contributes to the dearth of hydrogenation reactivity at Cu(I)-alkyl species despite their prevalence. The coordination geometry of Cu-alkyl species supported by the NBC^CPh3 ligand overcomes this limitation indirectly by accessing H₂ activation via MLC intramolecular deprotonation of the CHPh₂ arm by the alkyl ligand. These pathways are not favorable in the linear congener, an effect likely due to both the enforced proximity of these groups as well as increased reactivity of the Cu-alkyl fragment in the three-coordinate system.

Catalytic Hydrogenation of Unactivated Olefins and Mechanistic Study

The successful net hydrogenolysis of 2^cPr to 2^H motivated the investigation of Cu-catalyzed olefin hydrogenation. Using unoptimized conditions, we examined the hydrogenation of 1-hexene, 1-octene, cyclopentene, cyclohexene, and cis-cyclooctene in C₆D₆ at 60 °C under 4 atm of H₂ for 8–24 h with 5–10 mol% 2^cPr. The results are summarized in Table 1. The hydrogenation of cyclopentene and cyclohexene is sluggish and lower yielding compared to that of 1-hexene and 1-octene. The conversion of cyclopentene and cyclohexene to their cycloalkyl products was observed in 51% and 13%, respectively, after 24 h at 60 °C using undried H₂. The selected substrates eliminate complicated speciation from β-H elimination/isomerization, simplifying ¹H NMR spectroscopic identification of intermediates for mechanistic investigation.

Operando ¹H NMR kinetic studies show resting states of alkyl complexes of 2^Hex, 2^Oct, and 2^cPent for 1-hexene, 1-octene, and cyclopentene hydrogenation, respectively. In contrast, cyclohexene hydrogenation engenders a resting state of 2^H, indicating turnover-limiting olefin insertion. The different insertion barriers for cyclopentene versus cyclohexene are attributed to a kinetic rather than a thermodynamic effect. The heats of hydrogenation, a general descriptor of olefin stability, of cyclopentene and cyclohexene are −26.8 and −28.2 kcal mol⁻¹,^[72] respectively, indicating hydrogenation of cyclopentene is more difficult than that of cyclohexene. The sterically congested pocket at the CuH center, combined with the rapid interconversion of the dissymmetric, half-chair conformer of cyclohexene at room temperature, compared to the smaller, less dynamic, and puckered cyclopentene, provides a rationale for disfavored cyclohexene insertion into CuH.^{[73, 74]} Similar results have been reported for iridium-catalyzed hydrogenation of these two cyclic olefins, in which the effect of ring strain and structural conformations (chair vs. boat) are attributed to this observed trend.^[75] The hydrogenation of the bulkier cis-cyclooctene provided no conversion, reflecting both the anticipated kinetically unfavored binding to CuH for insertion and the heat of hydrogenation.

To circumvent substrate mass-balance and H₂ mass-transport issues observed with 1-hexene hydrogenation (see Supporting Information Pages S68–S74 for details), mechanistic studies were completed with higher boiling 1-octene as a model system, ensuring accurate measurement of substrate decay during catalysis. Kinetic analysis of 1-octene hydrogenation using undried H₂ shows rapid olefin insertion into 2^H with a resting-state species of 2^Oct and trace 2^OH throughout the reaction (Figure 8b). Upon complete consumption of 1-octene after 11 h, the resting state of 2^Oct converts to 2^H, which undergoes gradual decomposition in the absence of substrate. A copper alkyl resting state appears to offer improved stability, whereas a copper hydride resting state increases the rate of catalyst decomposition (Figure 8b, Figures S60 and S62).

To understand the influence of trace H₂O on catalysis, we performed a quantitative ¹H NMR kinetic analysis of 1-octene hydrogenation with 2^cPr using dried H₂. Drying the H₂ gas stream using a moisture trap before addition to the reaction mixture inhibits the formation of (NBC^CPh3)CuOH, but also significantly decreases the catalytic rate (Figure 8a). Using undried H₂, the significant acceleration of 2^cPr activation and 1-octene decay in the presence of trace 2^OH (Figure 8b), generated from adventitious H₂O, implied a divergent mechanism of turnover. Control experiments using exclusively 2^OH showed an increased rate of catalytic turnover to octane, with 2^OH observed as the only resting state. The observed dependence of rate on H₂ concentration (Figure S82) indicates that, contrary to 2^cPr, which undergoes net hydrogenolysis through preceding intramolecular deprotonation to form Int, 2^OH is instead capable of direct H₂ activation, likely via an internal electrophilic substitution (IES) mechanism.^[76-78] After the formation of 2^H, fast olefin insertion into the transient CuH monomer produces 2^R, followed by protonolysis to reform 2^OH and release the respective alkane to complete turnover. Similar studies to discern the H₂ dependence of on-cycle copper alkyl species (2^Oct, as compared to 2^cPr) using H₂ pressure drop experiments and dried H₂ show only a minor dependence that can be attributable to trace H₂O still entering the system despite these precautions (Supporting Information Page S78).

In the presence of additional H₂O, the ¹H NMR signal for the hydroxide of 2^OH is significantly shifted due to hydrogen bonding (Figure S83). Single-crystal X-ray diffraction analysis confirms the presence of a hydrogen-bonding H₂O molecule to a monomeric Cu-OH in the solid-state structure of 2^OH·H₂O (Figure 7) when grown from mixtures containing additional water. In fact, the isolation and characterization of reactive low-coordinate, monomeric late-metal hydroxide complexes is particularly scarce.^{[79, 80]} This presence of excess H₂O also significantly influences the rate of catalysis; using 2^OH versus 2^OH·H₂O for 1-octene hydrogenation decreases the initial TOF from 2.8 to 1.6 h⁻¹, respectively (Figure S84).

Furthermore, we have demonstrated that 2^OEt is robust, as it is recyclable for a second round of 1-octene hydrogenation. After complete hydrogenation of 1-octene in 15.8 h with the initial 10 mol% 2^OEt with 4 atm H₂ at 60 °C in C₆D₆, a larger second charge of 1-octene was then added. The reaction mixture, now containing 3 mol% catalyst loading with respect to 1-octene by ¹H NMR integration, provided 99% conversion of 1-octene after 16.6 h under 4 atm H₂ and 80 °C. Once catalysis was complete, prolonged heating at 80 °C indicates a persistent [2^OEt] over 31.5 h, demonstrating its excellent thermal stability (Figure S79).

Based on the combined results of stoichiometric and operando kinetic studies, proposed mechanistic pathways for CuH-catalyzed olefin hydrogenation are summarized in Figure 8e. In catalytic reactions that do not generate 2^OH from trace H₂O or employ 2^OEt, the primary mechanism involves turnover-limiting intramolecular deprotonation of the ligand -CHPh₂ of 2^R to release alkane and yields the zwitterionic Int (R = cyclopropyl from precatalyst 2^cPr, or the resulting alkyl from olefin insertion). Subsequent rapid heterolytic cleavage of H₂ by Int produces 2^H (Figure 8e, outer blue path) that inserts the respective olefin to regenerate 2^R to complete the catalytic cycle. The Cu-cyclopropyl precatalyst 2^cPr disfavors β-H elimination to promote exclusive intramolecular deprotonation, whereas the resulting on-cycle alkyl 2^R species can participate in competitive β-H elimination/olefin insertion and intramolecular deprotonation. These competing processes result in a sluggish overall turnover and poor catalyst activation (complete 2^cPr decay observed after >20 h, Figure 8a).

In contrast, the inclusion of 2^OR (R = H, OEt) enables direct H₂ activation in conjunction with the slower intramolecular deprotonation pathway (Figure 8e), inner red path). In addition to the more rapid formation of 2^H via hydrogenolysis by the IES pathway, the facile reverse reaction between 2^H (or 2^R) and the respective protic co-catalyst (H₂O or EtOH) produced under these conditions further increases the mechanistic complexity. When 2^OR is the sole resting-state, the turnover of 1-octene is significantly increased versus the MLC-only pathway (Figure 8a,c,d). It is tenable that eliminating the H₂ mass-transport limitations observed with 2^OEt would improve the catalytic performance of the ethoxide congener to be at least comparable and plausibly beyond that of 2^OH.

In an intermediate scenario, the presence of adventitious H₂O forms trace 2^OH from 2^cPr pre-catalyst, leading to all accessible mechanistic pathways previously described. Under these conditions, acceleration of both pre-catalyst activation and overall turnover is observed due to the reiterative reaction sequence of 2^cPr protonolysis to generate 2^OH, which undergoes hydrogenolysis to form 2^H and regenerate H₂O (complete 2^cPr decay is observed after ∼5 h, Figure 8b). The magnitude of the accelerated rate of catalysis is dictated by the competitive rates of insertion/β-H elimination (2^H + olefin) versus protonolysis of 2^H back to 2^OH (2^H + H₂O). Also considering the decreased stability for the catalyst resting state of 2^H versus 2^R, the barriers of olefin insertion/β-H elimination contribute significantly to turnover efficiency. Importantly, the low-barrier hydrogenolysis of 2^OH minimizes the need for exceedingly high H₂ pressures that have been previously used for homogeneously CuH-catalyzed hydrogenations.^{[10, 12]} Ultimately, mixtures of 2^R/2^OR can facilitate faster turnover by trapping of transient HOR by copper-alkyl species if olefin insertion barriers yield a 2^R resting state, and in some cases can offer comparable reactivity to exclusively 2^OR conditions (Figure 1, bottom right).

Evaluation of this proposed mechanism through kinetic modeling was carried out under specific conditions where excess H₂O would not be present to influence the 2^OH hydrogenolysis reaction. In an H₂ pressure drop experiment, the catalytic hydrogenation of 1-octene at 60 °C was first observed after charging the reaction with 4 atm of undried H₂ to yield an observable quantity of 2^OH. After monitoring for 6 h, the mixture was flash frozen, and the pressure was decreased to 1 atm. Immediate resumption of the catalytic reaction at 60 °C highlights an inflection in rate due to turnover-dependent hydrogenolysis of 2^OH, with slowed substrate consumption until reaction completion (Supporting Information, Page S83). Modeling this experiment provided barriers for 2^OH hydrogenolysis (20.7 kcal mol⁻¹), 2^OH intramolecular deprotonation (24.0 kcal mol⁻¹), and 1-octene insertion (17.9 kcal mol⁻¹) at 60 °C.

The formation of a basic Cu─OH moiety in 2^OH for heterolytic H₂ cleavage via an IES pathway circumvents the inability of Cu-alkyl and the less effective MLC pathway to cleave H₂. However, the formation of a Cu─OH species does not necessarily result in H₂ activation in all cases, as catalytic hydrogenation of 1-hexene with 10 mol% linear 1^Hex under 4 atm of undried H₂ at 80 °C for 24 h shows no turnover, despite the verified formation of trace 1^OH in the reaction mixture by ¹H NMR spectroscopy (Figure S13). These observations emphasize the importance of a trigonal planar geometry at a monomeric Cu─OH for effecting H₂ activation under these mild reaction conditions.

Computational Analysis of β-H Elimination of Cu(I) Alkyls and Heterolytic H₂ Cleavage at a Monomeric Cu─OH

We carried out computational studies to further understand the role of coordination geometry and supporting ligands on the β-H elimination of alkyl complexes and the activation of H₂ at a monomeric hydroxide complex 2^OH. The computed free energy barriers ΔG^‡ for the endergonic β-H eliminations of linear 1^tBu and trigonal 2^tBu at 25 °C corresponds to 34.1 and 28.9 kcal mol⁻¹ (Figure 9), respectively, based on gas-phase Q-Chem^[81] calculation using dispersion-corrected wB97X-D functional,^{[1, 83]} def2-SVP basis set and corresponding def2-ECP effective core potential^[84] for Cu. Similar β-H elimination energy barriers of 1^tBu and 2^tBu were obtained at the wB97X-D/def2-TZVP and wB97X-D4/def2-SVP levels of theory (Supporting Information, Page S112). Though the computed absolute ΔG^‡ value for the β-H elimination of 2^tBu differs from the modelled experimental kinetic data at 24.5 kcal mol⁻¹, the difference of ΔΔG^‡ = 5.2 kcal mol⁻¹ between 1^tBu and 2^tBu derived computationally supports the lack of β-H elimination for 1^tBu at room temperature. Kinetic analysis at 80 °C for 1^tBu infers a barrier of 30.4 kcal mol⁻¹, with a corresponding gas-phase calculated barrier of 34.2 kcal mol⁻¹ at 80 °C. In addition, the calculated metrical parameters for the β-H elimination of 1^tBu and 2^tBu show late transition states with considerable structural similarities at the Cu–^tBu fragments (Figures S88 and S89), constituting complete sp³ C─H cleavage to form a Cu(H)(η²-isobutylene) species. The transition state (TS) structure of 1^tBu and 2^tBu adopts a distorted T shaped and a distorted tetrahedral geometry, respectively, according to the different binding modes of either supporting ligand. A direct structural and molecular orbital comparison of the two TS structures is provided in the Supporting Information (Supporting Information, Pages S113 and S114). These computational results further suggest that the microscopic reverse of Markovnikov isobutylene insertion into the trigonal planar (NBC^CPh3)CuH monomer is 1.1 kcal mol⁻¹ more favorable than that linear (IPr*CPh₃)CuH monomer.

The favorable β-H elimination of 2^tBu versus 1^tBu was further analyzed by the activation-strain model^{[85, 86]} for the two constituent fragments of carbene ligand and Cu–^tBu. This method decomposes ΔE^‡ into strain energy (ΔE_str) and interaction energy (ΔE_int). ΔE_str captures the deformation-induced energy difference between the transition state and ground state (GS) structure whereas ΔE_int reflects the difference in stabilizing interactions between the Cu–^tBu fragment and the remaining complex. The results are summarized in Figure 10. Complex 2^tBu exhibits a larger stabilization from ΔE_int by −10.1 kcal mol⁻¹ and larger strain energy by 4.7 kcal mol⁻¹ compared to those of 1^tBu. The remaining difference of ΔE_str is attributed to distortion of carbene ligands/geometry change at Cu.

To probe the origin of ΔE_int on the energetics of β-H elimination for 1^tBu and 2^tBu, we performed second generation absolutely localized molecular orbital-energy decomposition analysis (ALMO-EDA).^[87-89] This method decomposes the binding energy between the carbene ligand and Cu-alkyl fragment (ΔE_int) into components consisting of “frozen” terms (electrostatics, dispersion, and Pauli repulsions) and orbital relaxation terms (polarization and charge transfer). Computational results reveal that, although the strain that is induced upon transition-state formation is slightly higher in 2^tBu, the overall lowering of the β-H elimination barrier of 2^tBu relative to linear 1^tBu is attributed to more stabilizing nonbonding (electrostatics, dispersion) and bonding (metal–ligand charge transfer) interactions that result from their difference in geometry.

The influence of orbital symmetry by substituting IPr*CPh₃ for NBC^CPh3 ligand is further corroborated by the charge-transfer analysis (ΔE_CT). The complementary occupied-virtual pairs (COVP)^{[90, 91]} of 2^tBu demonstrate increased π-symmetric accepting orbitals on the NBC^CPh3 ligand in both the ground and transition states (Figure S92), thus contributing to 3.9 kcal mol⁻¹ greater ΔE_CT stabilization compared to 1^tBu (Figure 10).^[92] The combined accepting ability of NBC^CPh3 is approximately twice that of IPr*CPh₃ in the Cu^tBu complexes, suggesting a summative effect of having two carbene donors in NBC^CPh3 (Table S11).^[93] Unexpectedly, in this context, there appears to be no synergistic contribution between the two carbene donors and the conjugated naphthyridine linking unit.

We also employed computations to delineate the mechanism of H₂ activation by the hydroxide complex 2^OH since this reaction is turnover-limiting for accelerated catalytic hydrogenation, based on our kinetic investigation with 1-octene. Computations indicate H₂ cleavage at 2^OH occurs with a TS energy barrier of 18.6 kcal mol⁻¹ (implicit benzene solvent, 60 °C) (Figure 11), which corroborates the experimental barrier of 20.7 kcal mol⁻¹ at 60 °C by the fitted kinetic model. A discrete intermediate from the coordination of H₂ at the Cu(I) center of 2^OH prior to the TS was not detected; however, an adduct containing the interaction of H₂ through the lone pair of the hydroxide ligand was endergonic by 5.6 kcal mol⁻¹ from the ground state of 2^OH and H₂. This atypical interaction has been documented in a comprehensive computational investigation for the IES mechanism of varied (pincer)PdOH complexes and H₂.^[77] This insight hints at yet another adverse effect of excess H₂O on the reduced catalytic turnover, since extensive hydrogen-bonding of 2^OH/H₂O can interfere with 2^OH/H₂ adduct formation en route to H₂ activation.

The computed TS structure, summarized in Figure 11, shows a distorted tetrahedral geometry at Cu (τ₄′ = 0.67) with a hydrogen atom from H₂ oriented directly towards a lone pair of the OH ligand. Bond distances of 1.80 and 1.78 Å of Cu─H1 and Cu─H2, respectively, are significantly longer than expected for a formal Cu─H group based on the Cu─H bond distance of 1.57 Å for geometry-optimized 2^H product. Additionally, an H1─H2 bond distance of 0.96 Å in the TS structure indicates a weakly interacting and intact H₂ at the Cu(I) center rather than an elongated dihydrogen or a dihydride species.^[94] Moreover, notable elongation of the Cu─OH bond by 0.35 Å was observed at the transition state. Taken together, this pathway resembles an early transition state for H₂ cleavage and its metrical parameters are consistent with those reported for computational TS structures of IES for Pd-OH and H₂.^[77]