Elementary Reactions at Organocopper (III): A Gas-Phase and

Article pubs.acs.org/Organometallics

Elementary Reactions at Organocopper(III): A Gas-Phase and Theoretical Study Krista L. Vikse and Peter Chen* Laboratorium für Organische Chemie, ETH Zürich, Zürich 8093, Switzerland S Supporting Information *

ABSTRACT: The role of copper(III) in copper-catalyzed coupling reactions is a topic of much debate in the literature, in large part due to the difficulty in isolating the typically reactive species. Advanced mass spectrometry experiments allow the isolation and interrogation of reactive species in the absence of any solvent, counterions, or competing species. Macrocyclic aryl-X-copper(III) complexes were isolated in the gas phase and subjected to collision-induced dissociation experiments to examine their unimolecular reactivity both qualitatively and quantitatively. When X = Cl or Br, the complexes fragment solely by deprotonation of nitrogen and concomitant loss of HX. The experimentally determined energies of activation are 33.4 ± 0.9 kcal mol−1 (X = Cl) and 35.8 ± 0.9 kcal mol−1 (X = Br). This process is analogous to nucleophile activation at a copper(III) center, and it is observed preferentially over C-X reductive elimination in the gas phase due to the strong ligating ability of the employed macrocyclic ligand. The measured activation energies for the observed nucleophile activation were used to test the performance of a range of popular DFT functionals for predicting reactivity at CuIII. Most dispersion-corrected functionals reproduced the experimental results with reasonable errors (D3bj-corrected TPSSh performed best), whereas the uncorrected values tended to significantly underestimate the activation energies. When X = I, a second fragmentation pathway becomes competitive, which involves loss of I• and reduction of copper from CuIII to CuII. The relative energetics of one-electron versus two-electron processes at CuIII are discussed.

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INTRODUCTION Organocopper(III) intermediates have recently gained considerable attention as potential intermediates in copper-catalyzed coupling reactions.1 The idea is not new: the involvement of CuIII in Ullmann−Goldberg couplings has been postulated since the 1970s,2 and more recently, carbon−heteroatom oxidative couplings have been proposed to proceed via an organocopper(III) intermediate.3 However, experimental evidence for the intermediacy of CuIII complexes has only recently appeared and only under special conditions. For example: rapid injection NMR has been used to trap complexes relevant to copper-catalyzed conjugate additions (Scheme 1A);4 mass spectrometry has allowed the investigation of tetraalkylcuprates related to classic Gillman reagents (Scheme 1B);5 and model complexes stabilized with macrocyclic ligands have been investigated in solution (Scheme 1C).6−8

Despite excellent progress in the area, there is still relatively little known about the inherent reactivity of catalytically competent organo-copper(III) intermediates and a number of recent reviews have summarized the outstanding issues specifically with respect to the Ullmann-type couplings.9−11 Two open questions are of particular interest to us: (1) C-X oxidative addition at CuI to give CuIII (eq 1) and nucleophile activation (eq 2) at CuIII have both been proposed as potentially key elementary steps in copper-catalyzed modified Ullmann-type reactions. RX + [Cu I] → [(R)(X)Cu III]

(1)

[(R)(X)(NuH)Cu III] + :B → [(R)(Nu)Cu III] + BHX (2)

What are the energetics associated with these two processes for an isolated and well-defined CuIII complex? (2) For Ullmann-type reactions, there is convincing evidence for the operation of both one- and two-electron-based mechanisms involving CuIII and/or CuII.2,12−14 What can be said about the propensity of CuIII to participate in one- and two-electron processes and what factors might favor one type of reactivity over the other?

Scheme 1. Reactive Organometallic Copper(III) Complexes

Received: January 15, 2015 Published: March 24, 2015 © 2015 American Chemical Society

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Organometallics Since most proposed CuIII intermediates have proven difficult to isolate, a great deal of emphasis has been placed on DFT analysis of potential reaction mechanisms, but so far, these analyses have led to conflicting results.12,15 This may not be so surprising considering the significant functional-dependent variability that is possible in DFT-calculated energies of a given organometallic system.17 Unfortunately, when it comes to large organometallic complexes in unusual oxidation states, there exists very limited experimental data against which the performance of DFT functionals can be compared. Here, we use mass spectrometry to isolate individual reactive species in the gas phase where their fundamental unimolecular chemistry can be observed experimentally. By this method, qualitative trends in reactivity can be extracted and, under carefully controlled conditions, accurate activation energies for elementary reactions can be experimentally determined. The specific aims of this work were to address the questions posed above and to provide some experiment-based guidelines for selecting an appropriate DFT method to predict the reactivity of organocopper(III) complexes. The stable, but still reactive, CuIII complexes reported by Stahl and co-workers6,17−21 (Scheme 1C, hereafter referred to as [(macro)CuX]+) offered an excellent system to probe the fundamental chemistry of organocopper(III) in the gas phase. The model complexes are inherently charged (a distinct advantage for MS studies), and they come fully equipped with aryl, halide, and neutral nitrogen-based ligands: the key players in modified Ullman-type coupling reactions. Furthermore, Stahl and Ribas have extensively characterized the solution-phase reactivity of these species, which provides us with a solid foundation for our gas-phase studies and calculations.6−21 While we were aware that the strong binding of the macrocyclic ligand in the gas phase may hamper C-X reductive elimination (the favored reactivity in solution, and the microscopic reverse of C-X oxidative addition to CuI), the fact that, unlike other reactive CuIII species, these complexes are very well-defined makes them attractive for this preliminary gas-phase study. Thus, here we report the gas-phase unimolecular reactivty of [(macro)CuX]+ (Scheme 1C), where X = Cl, Br, and I. The gas-phase reactivity is compared to known solution-phase chemistry from the work of Ribas and Stahl, and several popular DFT methods are tested for their ability to predict reactivity at organocopper(III).

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were extrapolated to give an approximation of the TCID curve at zero collision cell pressure (i.e., single-collision conditions), and this curve was fitted using the LCID program to determine E0.24 The activation energies reported herein were obtained by reciprocal-variance weighted averaging over three independent data sets. A detailed description of the TCID experiment and data processing is provided in the Supporting Information. DFT Calculations. All calculations were performed using Gaussian 0925 except for those involving the PW6B95 functional,26 which is not available in Gaussian and was calculated using the ORCA program package (version 3.0.1).27,28 Functional testing was performed by fully optimizing the relevant structures using the functional of choice and the Def2-TZVP basis set for all atoms with the associated Def2-ECP on iodine.29 For D3-corrected energies, Grimme’s D3 correction30 was added (using the new bj-damping31 in all cases except for M06 and M06L, for which it does not exist). Potential energy diagrams were constructed using the D3bj-corrected TPSSh functional32 and the Def2-TZVP basis set for all atoms with the associated Def2-ECP on iodine. Vibrational frequencies were calculated for all optimized structures to ensure that they corresponded to true ground-state or transition-state structures (having zero or one imaginary frequency, respectively). All electronic energies are corrected for the zero-point vibrational energy (Ereported = Eelectronic + Ezpve) using the harmonic approximation.

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RESULTS Micromolar acetonitrile solutions of [(macro)CuX]+ (X = Cl, Br, and I) were analyzed by ESI-MS, and the resulting full mass spectra are provided in the Supporting Information (Figure S1). The cations [(macro)CuX]+ were then isolated in the gas phase within the ion trap of the mass spectrometer and subjected to collision-induced dissociation (CID). At low normalized collision energies, a single fragmentation pathway is observed for both X = Cl and Br, while, when X = I, the complex remains intact (Figure 1). The fragmentation pathway corresponds to loss of HX and gives the product ion [(macroH)Cu]+ (m/z 308, Scheme 2, eq 4).

EXPERIMENTAL SECTION

Solvents and reagents were purchased from commercial sources and used without further purification. Synthesis of [(macro)Cu] 2+ (ClO4−)2 was achieved using a literature procedure.22 The halogenated complexes [(macro)CuX]+ClO4− (X = Cl, Br, I) could also be prepared in isolated form by the literature procedure;6 however, for the convenient preparation of MS samples, the halogenated complexes were prepared in situ by addition of excess NaX to a 1 mM acetonitrile solution of [(macro)Cu]2+(ClO4−)2, followed by a 10-fold dilution. Mass Spectrometry. Qualitative mass spectrometry experiments were performed on a Finnigan LCQ classic 3D-Ion Trap mass spectrometer with a standard ESI source. CID experiments were performed using standard isolation and excitation procedures (Q = 0.25, activation time: 30 ms). In cases where a very low mass cutoff was required, CID experiments were performed on a Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer. Quantitative TCID experiments were performed on a modified Finnigan MAT TSQ-700 fitted with an ESI source and a custom 24pole ion guide and thermalization chamber as described previously.23 One data set for a given reaction consists of five TCID curves, each measured with a different argon pressure in the collision cell (see Figure 3a for an example). The five experimentally determined curves

Figure 1. CID of [(macro)CuX]+ (X = Cl, Br, I) at a normalized collision energy of 10 (arbitrary units).

To determine the source of the proton in the fragment, HX labeling studies were performed. Upon addition of excess CH3OD to an acetonitrile sample of [(macro)CuX]+, the triply deuterated [(macro-d3)CuX]+ is immediately formed. This is observed in the mass spectrum as a clean 3 Da shift in the m/z value of the complexes and is consistent with deuterium exchange at the three amines of the macrocyclic ligand. CID of 1295

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Organometallics Scheme 2. Potential Unimolecular Reactions of [(macro)CuX]+

the triply deuterated complex leads solely to loss of XD, indicating that one of the amines in the macrocyclic ligand is deprotonated upon CID (see the Supporting Information, Figures S2 and S3). CID of the product ion [(macro-H)Cu]+ (m/z 308) gives a complicated spectrum with m/z 306 as the major product ion peak. (see the Supporting Information, Figure S4). At higher collision energies, [(macro)CuI]+ also fragments; however, in addition to the fragmentation pathway for loss of HX, a second reaction occurs with the same appearance energy: loss of I• (Figure 2). The branching ratios (i.e., yields) were

Figure 3. (a) Experimental signal intensities as a function of ion energy at a series of different collision cell pressures, and (b) zeroextrapolated reaction cross section (black circles) and 20 LCID fittings (lines) for the fragmentation of [(macro)CuBr]+ into HBr and [(macro-H)Cu]+.

transition state (vida inf ra). When X = Cl, the energy for HCl loss is 33.4 ± 0.9 kcal mol−1. The case where X = I is interesting since a one-electron and a two-electron process are competitive with each other. Unfortunately, it was not possible to obtain reliable TCID data for this system since the two operational fragmentation pathways give products separated by only 1 mass unit (or 2 if the deuterated system is measured) and they cannot be distinguished from one another in the TCID experiments without severely compromising the accuracy of the results. With accurate experimental thermochemical data for the unimolecular reactions of [(macro)CuX]+ (X = Cl, Br) in hand, we tested a series of DFT functionals to ascertain their predictive ability with respect to these systems. Nine popular functionals were tested: with and without Grimme’s D3 correction. A summary of the results is given in Table 1. Finally, using the most successful functional (D3bj-corrected TPSSh), the relative energies for C-X reductive elimination and subsequent dissociation from copper (eq 3), loss of HX (eq 4), and loss of X• (eq 5) from [(macro)CuX]+ were calculated when X = Cl, Br, and I (Figure 4). Ground-state structures were calculated based on the geometry of the reported crystal structures;6 however, only complexes in which the halide is on the same face of the complex as the nitrogen-bound protons were considered since this orientation is a requirement for subsequent HX elimination. Loss of HX in Figure 4 (far left) is shown to proceed via a loose transition state, and LCID fittings were calculated accordingly. This is based on the fact that DFT scans of the N−H bond length from reactant to product showed no evidence of a defined transition state structure;

Figure 2. CID of [(macro)CuI]+ at a normalized collision energy of 15 (arbitrary units).

measured for these two products at moderate collision energy. 60% of total product ion intensity is due to loss of HI, while 40% is due to loss of I• (Figure 2). When the deuterated complex [(macro-d3)CuI]+ was subjected to CID, 37% of the product intensity was due to DX loss and 63% was due to I• loss (see the Supporting Information, Figure S3). Absolute activation energies for loss of HX from [(macro)CuX]+ when X = Cl or Br were extracted by performing threshold-CID (TCID) experiments and subsequent fitting of the experimental data with the LCID program.24 An example of the data obtained when X = Br is shown in Figure 3 (see the Supporting Information, Figures S5−S7 for representative data where X = Cl and Table S1 for a summary of the LCID data). When X = Br, the energy required for loss of HBr is 35.8 ± 0.9 kcal mol−1, assuming the process does not involve a tight 1296

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[(macro)CuX]+ (X = Cl, Br, I) undergo reductive elimination (RE) to form a new C−X bond (eq 3 in Scheme 2).6,19 The activation energy of this RE process was of interest to us since it is the microscopic reverse of oxidative addition of an aryl halide to CuI. However, upon CID in the gas phase, no RE was observed; instead, the complexes all fragment primarily via loss of HX (Figures 1 and 2, eq 4 in Scheme 2). If RE did occur in the gas phase, the process would be detected as the formation of Cu+ (the other product, macroX, would be neutral and undetectable by MS). Since the low-mass cutoff of an ion trap MS is too high to detect Cu+ (m/z 63/65) under our experimental conditions, the CID experiments were repeated on a triple quadrupole instrument which has a low-mass cutoff of 50 m/z. No formation of Cu+ was observed (data not shown). The reason for this discrepancy between solutionphase and gas-phase reactivity is clear from the calculated energetics of these two processes. The right-hand side of Figure 4 shows the calculated energies for RE and subsequent ligand dissociation. While RE is calculated to be facile in the gas phase (13−20 kcal mol−1), the subsequent dissociation of the macrocyclic product is extremely unfavorable. (143−146 kcal mol−1 higher in energy than the ground-state complexes!) This is clearly due in large part to the dissociation of copper from the three ligated nitrogen groups of the macrocycle, but how much of the energy barrier can be attributed to this effect? There is no direct comparison in the literature; however, reported measurements of the dissociation energies of three subsequent imidazole ligands from copper(I) indicate that loss of three nitrogen-based ligands from copper could contribute in the range of 150 kcal mol−1 in binding energy.33 Thus, dissociation of the three nitrogen groups from the macrocyclic complexes discussed here could in theory account for the entire dissociation energy of the RE product (shown on the very right-hand side of Figure 4). It is plausible, then, that, for a related nonmacrocyclic complex, RE would be observed as the

Table 1. DFT Functionals Test Results functional

Cla

Bra

Ia

B3LYP B3LYPD3bj BP86 BP86D3bj M06 M06D3z M06L M06LD3z PBE PBED3bj PBE0 PBE0D3bj PW6B95 PW6B95D3bj TPSS TPSSD3bj TPSSh TPSShD3z TPSShD3bj experiment

20.33 28.46 20.84 29.34 25.46 26.55 27.40 27.82 22.66 27.59 24.25 29.02 24.27 27.54 22.61 29.09 23.16 28.37 33.77 33.4 ± 0.9

23.21 32.45 24.02 33.98 26.24 27.38 26.98 27.41 26.1 31.45 27.96 33.38 27.87 31.79 25.64 32.98 26.36 32.36 37.86 35.8 ± 0.9

23.09 33.78 24.74 36.69 25.79 26.97 26.91 27.34 27.02 33.20 28.69 35.04 29.39 34.28 25.78 34.31 26.46 33.15 39.16

Calculated activation energies (kcal mol−1) for loss of HX (X = Cl, Br, I) via a loose transition state. “D3” indicates that the energies were corrected with Grimme’s D3 correction using either bj or zero (z) damping.

a

instead, the reaction coordinate resembles a barrierless dissociation (i.e., a loose transition state; see the Supporting Information, Figures S8−S10).

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DISCUSSION Gas-Phase versus Solution-Phase Reactivity. In solution, Ribas and Stahl demonstrated that the complexes

Figure 4. DFT-calculated reaction pathways for loss of HX or loss of X• (left) and C-X reductive elimination, followed by ligand dissociation (right). Values are given in kcal mol−1. Optimized structures are shown for the case where X = Br. Analogous structures exist for the cases where X = Cl and I (see the Supporting Information, Figure S11). 1297

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that deprotonation of the amino ligands that are cis to the aryl moiety is favored by 8.7 kcal mol−1 (TPPShD3bj). On the basis of this significant energy difference, we assume that deprotonation during our TCID experiments occurs solely from the nitrogen atoms cis to the aryl ligand (Scheme 2, eq 4). Then, due to the symmetry of the molecule, there are two identical nitrogen groups that may be deprotonated. The doubly degenerate nature of this pathway was accounted for in the LCID fittings. Qualitatively, the energy required for nucleophile activation increases in the order Cl < Br < I (Figure 1). This fragmentation order is consistent with the halide acting as a base to deprotonate nitrogen: the most basic halide (Cl) requires the least amount of fragmentation energy. Interestingly, deprotonation of these types of macrocycle-copper complexes is not solely a gas-phase phenomenon. Deprotonation at nitrogen has also been observed by Ribas in solution in the presence of anionic phenolate nucleophiles and was found to enhance the rate of subsequent C-O reductive elimination.21 Experimental Activation Energies. With a qualitative understanding of their unimolecular reactivities, the compounds [(macro)CuX]+ (X = Cl, Br) were analyzed on a modified triple quadrupole mass spectrometer that is capable of extracting accurate thermochemical data. For X = I, it was not possible to obtain reliable absolute energetics by TCID since there were two competing product channels that differed by only 1 mass unit. The measurement of accurate TCID curves relies on having a parent ion population with a well-defined distribution of kinetic and internal energies. This is accomplished in part by selecting the parent ions with a very wide isolation window to avoid imparting extra energy to the ions. The required wide isolation results in an ion signal that spans up to 10 m/z units; thus, distinguishing between two product peaks that differ by only one mass unit is impossible. If, on the other hand, the parent peak was isolated with a sufficiently narrow window to resolve the two product ions, the energy of the parent ions would no longer be well-defined. Nevertheless, when X = Br or Cl, analysis is straightforward. The energy required for loss of HX is 35.8 ± 0.9 kcal mol−1 when X = Br, and 33.4 ± 0.9 kcal mol−1 when X = Cl. DFT Functionals Test. The absolute activation energies we obtained experimentally gave us the rare opportunity to assess how accurately the various DFT functionals can predict reactivity at CuIII. Here, the fact that we operate in the gas phase is an asset. Benchmarking studies that are conducted against solution-phase experimental results necessarily employ a solvent model to reconcile experiment to theory. As a consequence, the combined accuracy of the electronic structure calculation and the solvent model is assessed and the two cannot be deconvoluted. Conversely, in the gas phase, we are able to assess the accuracy of the electronic structure calculation alone.34 Nine common functionals were tested with and without Grimme’s D3 correctionand the results are listed in Table 1. Generally, the D3-corrected functionals performed reasonably well with errors less than ±6 kcal mol−1 compared to the experimentally determined values. They also all predicted that loss of HX would be energetically more favorable when X = Cl (except for M06L, which was unable to distinguish between the systems). The uncorrected functionals underestimated the energy required for HX loss by between 6 and 13 kcal mol−1. Furthermore, the results are relatively sensitive to the type of D3 correction performed (see the Results section for TPSShD3bj vs TPSShD3z). Overall, the

major fragmentation channel in the gas phase and activation energies for RE would be accessible. The investigation of such nonmacrocyclic systems, while much more complicated due to their greater instability, is the next aim of this work and will be the topic of a future report. In solution, solvation can begin to mitigate the highly endothermic nature of dissociation of the macrocyclic RE product, but, even in solution, RE and dissociation of the macrocyclic products is not observed unless the solution is acidic.6 It has been proposed that acid acts to protonate the macrocycleeffectively reducing the denticity of the ligand by oneand only then is product formation observed. This is consistent with our gas-phase results in which no acid (or solvent) is present to aid in dissociation of the macrocycle, and thus, no RE product is observed. RE is likely occurring reversibly under our experimental conditions, but the final product cannot dissociate from copper. Thus, the process is not observed in the MS experiments since there is no change in the m/z value of the ion. Instead, the higher energy, irreversible loss of HX is observed. Loss of HX from these complexes is interesting in itself since it corresponds to another potentially important elementary step in copper-catalyzed Ullmann-type reactions: nucleophile activation (i.e., deprotonation of coordinated NuH). In solution, this is proposed to occur with the help of an external base, but in the gas phase, the process is necessarily intramolecular. Thus, one of the neutral nitrogen ligands (NuH) is deprotonated by the coordinated halide. The result is loss of HX and formation of a copper complex with a new anionic nitrogen ligand. In the context of copper-catalyzed Ullmann-type reactions, this elementary step results in a copper complex that is set for reductive elimination of a new C−N bond (e.g., see the lowermost species in the cycle shown in Scheme 3). Scheme 3. Two Possible CuI/CuIII Catalytic Cycles for Modified Ullmann-Type Couplings

In the literature, nucleophile activation in modified Ullmanntype reactions has been proposed to occur either at CuI (before oxidative addition of the aryl halide, Scheme 3, Path I) or at CuIII (after oxidative addition of the aryl halide, Scheme 3, Path II).11 For these macrocyclic ligands, the latter is favored due to preorganization of the complex for oxidative addition of the aryl halide and stabilization of the resulting CuIII complex.6 Thus, using this system, we can directly examine nucleophile activation at CuIII. First, deuterium labeling studies (see the Supporting Information, Figures S2 and S3) confirm that the observed loss of HX is the result of one of the nitrogen atoms of the macrocyclic ligand being deprotonated. Of the two chemically distinct N−H bonds in the molecule, DFT calculations indicate 1298

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Organometallics D3bj-corrected TPSSh functional best predicts the experimental energies and reproduces the observed trends in reactivity. The success of TPSSh is consistent with a recent benchmarking study that used a test set containing various organometallic complexes including copper in the +1 oxidation state.16 On the basis of the results of our screen, the D3bj-corrected TPSSh functional was used to calculate all the geometries and energies reported herein. Two-Electron versus One-Electron Processes. At slightly higher collision energies, [(macro)CuI]+ fragments via two channels: (A) loss of HI, which results in nucleophile activation (analogous to the X = Cl and Br systems), and (B) loss of I•, which results in metal reduction (CuIII → CuII). As mentioned in the Results section, the relative product ion intensities were 60:40 for loss of HI and loss of I•, respectively, and this is entirely consistent with the calculated activation energies which predict loss of HI to be slightly energetically favored. For the triply deuterated complex, the ratio was 37:63 in favor of I• loss, consistent with a significant primary isotope effect. Taking a closer look at the DFT-calculated potential energy diagram, we gain some insight into the observed reactivity as X is varied from Cl to Br to I. The left-hand side of Figure 4 shows the energy required for loss of HX or loss of X• for each of the complexes [(macro)CuX]+. While the energy required for loss of HX increases from Cl to Br to I as the halide becomes less basic, the energy required to reduce copper and liberate X• increases in the opposite order (I < Br < Cl) as the resulting halide radical becomes more stable. When X = Cl, loss of HX (two-electron chemistry) is calculated to be favored by about 30 kcal mol−1, when X = Br, loss of HX is favored by around 18 kcal mol−1, but when X = I, the one-electron and two-electron processes are competitive and both fragmentation pathways are observed by CID.35 The fact that one-electron chemistry can be “turned on” simply by switching one ligand from bromide to iodide is revealing as it demonstrates explicitly the fickle nature of CuIII toward one- and two-electron processes. What causes this change in reactivity? Consider the two observed fragmentation pathways in detail. Both pathways occur through a loose transition state, so the measured activation energy is the difference in energy between the reactants and products (not the energy difference between the reactants and some transition state). Furthermore, due to the similar nature of the reactions, they likely have similar entropy terms; thus, we can safely compare the relative thermochemistry of the two processes. The fragmentation by loss of HX (Scheme 4A) can be broken up into four hypothetical steps: homolytic cleavage of the CuX bond, homolytic cleavage of an NH bond, formation of a nondative CuN bond, and homolytic formation of a new HX bond. The second fragmentation process which releases X• (Scheme 4B) is simply a homolytic cleavage of the CuX bond. Using the fragmentation pathways as defined above, we can say four things: (1) Both pathways A and B involve homolytic cleavage of the CuX bond; therefore, changes in the CuX bond strength cannot influence the preferred reaction pathway. (2) The newly formed CuN bond in pathway A is identical regardless of the identity of X; therefore, it cannot be the cause of the observed change in reactivity on going from X = Br to X = I. (3) The NH bond strength can also be expected to remain about the same regardless of the identity of X and thus cannot explain the observed change in reactivity. (4) Given points 1−3, the factor that is primarily responsible for the change in

Scheme 4. Bonds Broken and Formed upon (A) HX Formation and (B) X• Formation

reactivity as we change X is the homolytic bond energy of HX. In other words, the HBr bond strength (homolytic BDE = 87.55 ± 0.04 kcal mol−1) is high enough to favor formation of HBr over reduction of CuIII, whereas the HI bond strength (homolytic BDE = 71.32 ± 0.21 kcal mol−1) is not.36 Thus, the difference in observing solely two-electron chemistry and observing both one- and two-electron chemistry is only about 16 kcal mol−1. In light of these results, it is perhaps not surprising that reported mechanistic studies on copper-catalyzed Ullmann-type reactions often come to opposing conclusions about the importance of one-electron and two-electron processes. Furthermore, this result demonstrates the feasibility of controlling one-electron and two-electron chemistry at organo-Cu(III) with slight changes to ligand sphere, identity of the external base, or reaction conditions.

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CONCLUSIONS Gas-phase reactivity studies represent a valuable tool for organometallic chemists. Elementary reactions can be studied in isolation, and there is growing evidence (including the results of this work) that gas-phase reactivity can predict solutionphase reactivity as long as key experimental differences, such as solvation, are accounted for. The gas-phase unimolecular reactivity of the complexes [(macro)CuX]+ reported here is entirely consistent with known solution-phase reactivity. C-X reductive elimination is the favored pathway in both the gas phase and the solution phase; however, the macrocyclic substrate hinders release of product in both media (more so in the gas phase due to lack of solvation). Deprotonation of the coordinated macrocyle is also an accessible reaction in both the gas and the solution phases and is a model for nucleophile activation at a CuIII center. This observed elementary reaction was used to test the performance of nine popular DFT methods in predicting reactivity at CuIII. D3-corrected functionals generally performed well, whereas uncorrected methods significantly underestimated experimental gas-phase activation energies. Overall, D3bj-corrected TPSSh was found to be the most appropriate method. It is important to note that 1299

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(18) King, A. E.; Huffman, L. M.; Casitas, A.; Costas, M.; Ribas, X.; Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 12068−12073. (19) Casitas, A.; Poater, A.; Solà, M.; Stahl, S. S.; Costas, M.; Ribas, X. Dalton Trans. 2010, 39, 10458−10463. (20) Huffman, L. M.; Casitas, A.; Font, M.; Canta, M.; Coatas, M.; Ribas, X.; Stahl, S. S. Chem.Eur. J. 2011, 17, 10643−10650. (21) Casitas, A.; Ioannidis, N.; Mitrikas, G.; Costas, M.; Ribas, X. Dalton Trans. 2011, 40, 8796−8799. (22) Ribas, X.; et al. Chem.Eur. J. 2005, 11, 5146−5156. (23) Couzijn, E. P. A.; Zocher, E.; Bach, A.; Chen, P. Chem.Eur. J. 2010, 16, 5408−5415. (24) Narancic, S.; Bach, A.; Chen, P. J. Phys. Chem. A 2007, 111, 7006−7013. (25) Frisch, M. J.; et al. Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford, CT, 2009. See the Supporting Information for the complete citation. (26) Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2005, 109, 5656−5667. (27) Neese, F. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2012, 2, 73− 78. (28) Neese, F. ORCA − An ab initio, DFT and semiempirical SCF-MO package, Version 3.0.1; Max-Plank-Institute for Chemical Energy Conversion: Ruhr, Germany, 2013. (29) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297−3305. (30) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 154104. (31) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32, 1456−1465. (32) Tao, J. M.; Perdew, J. P.; Staroverov, V. N.; Scuseria, G. E. Phys. Rev. Lett. 2003, 91, 146401. (33) Rannulu, N. S.; Roders, M. T. Phys. Chem. Chem. Phys. 2005, 7, 1014−1025. (34) Kobylianskii, I. J.; Widner, F. J.; Kräutler, B.; Chen, P. J. Am. Chem. Soc. 2013, 135, 13648−13651. (35) In our experience, competitive fragmentation pathways have activation energies that differ by only 2 or 3 kcal mol−1. Thus, the fact that both channels are observed experimentally in the CID experiments suggests to us that the difference between the two channels is closer to 2 or 3 kcal mol−1 than the 6 kcal mol−1 suggested by DFT. (36) BDEs derived from: Chase, M. W. J. NIST-JANAF Thermochemical Tables, 4th ed.; Monograph No. 9; NIST: Gaithersburg, MD, 1998.

theoretical calculations were instrumental in reconciling the results from gas- and solution-phase experiments. Finally, we have demonstrated that small changes in the ligand sphere can significantly affect the likelihood of one- or two-electron chemistry at CuIII. Efforts are now underway to apply our validated DFT methods and our arsenal of gas-phase experiments to more reactive (nonmacrocyclic) CuIII complexes that are too short-lived to be characterized in the condensed phase.

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ASSOCIATED CONTENT

S Supporting Information *

Full reference citation for ref 25, supplementary mass spectra, description of TCID experiment and LCID fitting including representative data for [(macro)CuCl]+, a summary of LCID fitting parameters, DFT rationale for selecting the loose transition state model in LCID fittings, and DFT-calculated optimized structures. An MDL Molfile of all computed molecule Cartesian coordinates in a format for convenient visualization. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (P.C.). Notes

The authors declare no competing financial interests.

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ACKNOWLEDGMENTS K.L.V. thanks NSERC and ETH Zürich for postdoctoral fellowships.

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REFERENCES

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DOI: 10.1021/acs.organomet.5b00038 Organometallics 2015, 34, 1294−1300