Ir(III) Catalytic Cycle? - ACS Publications - American Chemical Society

May 30, 2017 - School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China. ‡. Gaussian Inc., 340 Quinnipiac Street,...
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Ir(III)/Ir(V) or Ir(I)/Ir(III) Catalytic Cycle? Steric-Effect-Controlled Mechanism for the para-C−H Borylation of Arenes Lei Zhu,† Xiaotian Qi,† Yingzi Li,† Meng Duan,† Lufeng Zou,‡ Ruopeng Bai,*,† and Yu Lan*,† †

School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China Gaussian Inc., 340 Quinnipiac Street, Building 40, Wallingford, Connecticut 06492, United States

‡

S Supporting Information *

ABSTRACT: Density functional theory method N12 was used to study the mechanism of the [Ir(cod)OH]2/Xyl−MeO−BIPHEP-catalyzed para-selective C−H borylation reaction. The results revealed that the use of a bulky diphosphine ligand such as Xyl−MeO−BIPHEP was unfavorable for the previously proposed iridium(III)/iridium(V) catalytic cycle because it resulted in considerable steric repulsion in the hepta-coordinated iridium(V) intermediate. Inspired by this steric effect, we have proposed a novel iridium(I)-/iridium(III)-based catalytic cycle for this transformation and shown that it can be used to account for the experimental results. The iridium(I)/iridium(III) catalytic cycle induced by this steric effect consists of several steps, including (i) the oxidative addition of the C−H bond of the substrate to an active iridium(I) boryl complex; (ii) the reductive elimination of a C−B bond; (iii) the oxidative addition of B2pin2 to an iridium(I) hydride complex; and (iv) the reductive elimination of a B−H bond. Notably, the computed regioselectivity of this reaction was consistent with the experimental observations. The high para-selectivity of this reaction was also explained using structural analysis and a 2D contour model, which revealed that the strong steric repulsion between the diphosphine ligand and the meta-substituents resulted in a higher energy barrier for metaC−H activation.

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INTRODUCTION Synthetic methods for the activation and functionalization of C−H bonds continue to attract considerable interest from the synthetic chemistry community as efficient strategies for the construction of complex molecules.1 Research toward the development of iridium-catalyzed aromatic C−H borylation reactions,2 in particular, has grown considerably because of the versatility and utility of the resulting arylboron compounds.3 These reactions typically involve the use of an iridium(I) catalyst precursor in combination with a 4,4′-di-tert-butyl-2,2′bipyridine (dtbpy)2d,4 or 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4phen) ligand5 with bis(pinacolato)diboron (B2pin2) or pinacolborane (HBpin) as a boron source. The mechanism of the iridium-catalyzed aromatic C−H borylation reaction was recently established following a series of theoretical and experimental studies, which indicated that a common iridium(III)/iridium(V) catalytic cycle could be favorable in some cases.6 As shown in Scheme 1, the use of a small ligand such as dtbpy or Me4phen in the iridium-catalyzed aromatic C−H borylation reaction would result in the formation of an iridium(III) triboryl complex, as previously demonstrated by Hartwig and co-workers.6b Furthermore, the subsequent oxidative addition of the C−H bond to the iridium(III) triboryl complex would give a hepta-coordinated iridium(V) hydride intermediate as the rate-determining step (RDS) in this catalytic cycle. Finally, the reductive elimination of the C−B bond would afford the aryl boronate ester product, © XXXX American Chemical Society

Scheme 1. Comparison of the Iridium(III)/Iridium(V) and Iridium(I)/Iridium(III) Catalytic Cycles

which would be accompanied by the regeneration of the active catalyst in the presence of B2pin2 or HBpin. These experimental Received: February 27, 2017

A

DOI: 10.1021/acs.organomet.7b00151 Organometallics XXXX, XXX, XXX−XXX

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Organometallics conclusions are consistent with the results of a theoretical study reported by Sakaki et al.,6a which confirmed the validity of an iridium(III)/iridium(V) catalytic cycle in the iridium-catalyzed C−H borylation reaction. Although this combination of theoretical and experimental studies has resulted in a plausible and elegant catalytic cycle, this mechanism only involves iridium(III) and iridium(V) species, and the key step, involving the generation of a hepta-coordinated iridium(V) hydride intermediate, looks congested. While this mechanistic cycle would be acceptable for a small ligand, the use of a large ligand could potentially prevent the formation of the heptacoordinated iridium(V) hydride intermediate through steric effects.7 The fact that this reaction does proceed in the presence of a large ligand suggests that an iridium(I)/iridium(III) catalytic cycle is possible, because the extent of the steric repulsion between the corresponding penta-coordinated aryliridium(III) boryl intermediate would be weaker than that of the hepta-coordinated iridium(V) intermediate. To assess the possibility of this alternative pathway, Itami and co-workers reported a highly para-selective aromatic C−H borylation of monosubstituted benzene derivatives (Figure 1).8

Figure 2. Optimized structures of iridium(III) triboryl complexes 5, 6, and 8 and iridium(I) boryl complex 7. The bond lengths are given in Å.

carbon. Given that the reactivity of a C−H bond is determined by a variety of different factors in addition to the stability of the resulting Ir−C bond, it is possible that electronic and steric effects could also play important roles in determining the regioselectivity of this reaction.7b,11 Notably, the use of monosubstituted arenes as substrates in this reaction resulted in preferential borylation at the meta and para positions with only negligible borylation at the ortho position because of the steric repulsion of substrates.4a,12 Recent efforts to afford exclusive para-selectivity are generally based on controlling electronic effects, with studies directed toward adjusting the steric interplay between the substituted arenes and the active catalyst to achieve para-C−H borylation being surprisingly rare. Itami’s borylation protocol represents a practical and efficient approach for the para-selective borylation of substituted arenes and heteroarenes, and could be used for the development of other para-C−H bond activation processes. The huge potential and high regioselectivity of this reaction therefore inspired us to study its mechanism in detail to determine the origin of its regioselectivity. The mechanism of this transformation is generally believed to involve a conventional iridium(III)/ iridium(V) catalytic cycle.6b However, we envisioned that an iridium(I)/iridium(III) catalytic cycle would be more appropriate for the [Ir(cod)OH]2/Xyl−MeO−BIPHEP system based on steric effects (Scheme 1). The optimized structure of Ir(Bpin)3/Xyl−MeO−BIPHEP 8 revealed that the metal center was tightly surrounded by the diphosphine ligand and boryl group. The oxidative addition of an aromatic C−H bond or B2pin2 (2) to iridium(III) complex 8 would presumably be restricted by considerable steric hindrance with the ligand, which would make it difficult to form the iridium(V) intermediate. With this in mind, we investigated the formation of an iridium(V) intermediate using DFT calculations. The results of this analysis confirmed our suspicion that this process operated via an iridium(I)/iridium(III) catalytic cycle. Moreover, to elucidate the true mechanism of this [Ir(cod)OH]2/ Xyl−MeO−BIPHEP-catalyzed para-selective C−H borylation

Figure 1. [Ir(cod)OH]2/Xyl−MeO−BIPHEP-catalyzed para-selective C−H borylation.

In this case, they developed a new catalytic system consisting of an [Ir(cod)OH]2 precatalyst with a bulky diphosphine ligand, Xyl−MeO−BIPHEP, to afford high levels of para-selectivity in high yield. In contrast to the flat structure formed by the dtbpy or Me4phen ligand following its coordination to the iridium catalyst, it was envisaged that the bulkiness of the diphosphine ligand would result in pronounced steric hindrance to the left side of the iridium center (as shown in Figure 2). This ingenious design would therefore suppress the activation of the meta-C−H bond through steric repulsion between the diphosphine ligand and the substituents on the benzene ring. In this way, the para-C−H bond would be distinguished as the most suitable site for borylation. Herein, we report the results of our theoretical study, where Itami’s reaction was selected as a suitable example to prove our hypothesis that an alternative iridium(I)/iridium(III) catalytic cycle is possible if a larger ligand is used. The regioselectivity of this C−H borylation reaction has also been evaluated in the current study as a critical piece of evidence to prove our hypothesis.9 Density functional theory (DFT) calculations were performed by Houk’s group to investigate the origins of the selectivity observed in the iridium-catalyzed borylation of substituted arenes and heteroarenes.6a,e,10 The results of distortion/interaction analysis revealed that the regioselectivity of this reaction was mainly controlled by differences in the interaction energies between the iridium catalyst and the arene B

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free energy of 8 was determined to be 2.2 kcal/mol lower than that of 7, the corresponding activation free energy of this step reached up to 34.9 kcal/mol. These data suggested that the formation of iridium(III) triboryl complex 8 would be difficult. The subsequent oxidative addition of another molecule of B2pin2 to 8 would result in the formation of iridium(V) complex 11 via transition state 10-ts. However, the activation free energy for this step was determined to be as high as 107.7 kcal/mol, whereas the relative free energy of 11 was 93.4 kcal/ mol, which clearly indicated that it would not be possible for iridium(V) complex 11 to be formed in this catalytic system. The optimized structure of 9-ts showed that the Ir−P1 and Ir− P2 bond lengths were 2.43 and 2.21 Å, respectively, which are longer than those observed in complex 7 (2.37 and 2.16 Å, respectively). Moreover, the Ir−P1 and Ir−P2 bond lengths in transition state 10-ts were even longer at 2.62 and 2.87 Å, respectively, highlighting the extent of the steric repulsion between the diphosphine ligand and the Bpin groups. The high activation free energies required for the generation of iridium(III) and iridium(V) complexes 8 and 11 can therefore be attributed to steric effects. We also considered the use of trimethyl(phenyl)silane (1) as a substrate in this reaction, which would result in the formation of aryliridium(V) complex 13 following the oxidative addition of its C−H bond to iridium(III) via transition state 12-ts (Figure 4). The activation free energy was determined to be 63.5 kcal/mol, whereas the relative free energy of 13 was found to be 54.4 kcal/mol. Structural analysis of 12-ts showed that the Ir−P1 and Ir−P2 bonds increased in length during the oxidative addition step to 2.58 and 2.50 Å, respectively. Furthermore, the length of the C−H bond in 12-ts was found to be 1.7 Å, which indicated that this transition state was occurring quite far along the reaction coordinate. The subsequent reductive elimination of the C−B bond via transition state 14-ts afforded iridium(III) hydride complex 15 with the concomitant release of borylation product 3. The corresponding activation free energy was determined to be 81.1 kcal/mol. The oxidative addition of B2pin2 (2) to complex 15 resulted in the formation of iridium(V) hydride complex 17 via transition state 16-ts. The formation of 17 was determined to be endergonic by 27.2 kcal/mol relative to iridium(I) boryl complex 7, with the overall activation free energy reaching 83.1 kcal/mol. Moreover, the meta−C-H oxidative addition of reactant 1 to iridium(III) complex 8 has also been calculated. The activation free energy of this process is determined to be 72.5 kcal/mol (see Figure S4 for details). These data led to the conclusion that it would not be possible for this transformation to proceed via the previously reported iridium(III)/iridium(V) catalytic cycle using this [Ir(cod)OH]2/Xyl−MeO−BIPHEP system because of steric hindrance from the diphosphine ligand.19 With regards to the iridium(I)/iridium(III) mechanism, we have evaluated three plausible reaction pathways in this study (Scheme 2). All three of these catalytic cycles start with the oxidative addition of the C−H bond of the substrate to an iridium(I) boryl complex, resulting in the formation of an aryliridium(III) intermediate. The subsequent reductive elimination of the C−B bond via Path A would afford the borylation product with the concomitant formation of an iridium(I) hydride complex. The oxidative addition of the B−B bond of B2pin2 (2) to the iridium(I) hydride complex followed by the reductive elimination of B−H would regenerate the iridium(I) boryl complex, thereby closing the catalytic cycle. Alternatively,

reaction and the source of its selectivity, we considered the iridium(III)/iridium(V) and iridium(I)/iridium(III) catalytic cycles in our calculations. Herein, we report the results of these calculations with particular emphasis on the discovery of a novel iridium(I)/iridium(III) mechanism for the C−H borylation of arenes using sterically hindered ligands.

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COMPUTATIONAL METHODS

All DFT calculations were carried out using the Gaussian09 series of programs.13 The geometries were optimized using the B3-LYP14 method with a standard 6-31G(d) basis set (LANL08(f)15 basis set for Ir). Harmonic vibrational frequency calculations were performed for all of the stationary points to confirm them as local minima or transition structures, as well as deriving the thermochemical corrections for the enthalpies and free energies. The N1216 functional was used with the 6-311++G(d,p) basis set (LANL08(f) basis set for Ir) to calculate the solvation single point energies to give more accurate energy information. The solvent effects were considered by single point calculations on the gas-phase stationary points using an SMD17 continuum solvation model. The energies reported in this study are the N12 calculated Gibbs free energies in hexane solvent, which is obtained by eq 1, where Esolv‑N12 is the single point energy calculated by N12 in hexane and Gcorr‑B3LYP is the thermal correction to Gibbs free energy calculated by B3LYP in gas phase. Moreover, the N12 calculated enthalpy HN12, which is obtained by eq 2, where Hcorr‑B3LYP is the thermal correction to enthalpy calculated by B3LYP in gas phase, is also given in free energy profiles. The optimized structures have been displayed using CYLview.18

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G N12 = Esolv‐N12 + Gcorr‐B3LYP

(1)

HN12 = Esolv‐N12 + Hcorr‐B3LYP

(2)

RESULTS AND DISCUSSION In this study, we initially calculated the free energy for the generally accepted iridium(III)/iridium(V) catalytic cycle. The free energy profile for the oxidative addition of the B−B bond in B2pin2 (2) to iridium(I) boryl complex 7, which would lead to the formation of iridium(III) triboryl complex 8 via transition state 9-ts, is shown in Figure 3. Although the relative

Figure 3. Free energy profile for the generation of iridium(III) and iridium(V) complexes 8 and 11. The diphosphine ligand used in this calculation was Xyl−MeO−BIPHEP. The bond lengths are given in Å. C

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Figure 4. Free energy profile for the iridium(III)/iridium(V) catalytic cycle for the para-selective C−H borylation of trimethyl(phenyl)silane (1). The diphosphine ligand used for this calculation was Xyl−MeO−BIPHEP. The bond lengths are given in Å.

complex 7. Given that the activation free energy of transition state 23-ts was determined to be 22.0 kcal/mol, the regeneration of the iridium(I) catalyst would most likely be the RDS in Path A. Notably, the low energy barrier for this step supports the idea that the iridium(I)/iridium(III) catalytic cycle in Path A is much more likely to occur compared with the iridium(III)/iridium(V) mechanism. In Path B, the reductive elimination of B−H would preferentially occur from intermediate 19, which would lead to the formation of aryliridium(I) complex 25 via transition state 24-ts with the concomitant release of HBpin. The activation free energy for this process was determined to be 27.9 kcal/mol, which is 13.6 kcal/mol higher than the relative free energy of 20-ts in Path A. The RDS for Path B was found to be the oxidative addition of the B−B bond of B2pin2 (2) which would proceed via transition state 26-ts to give iridium(III) complex 27 with an activation free energy of 42.8 kcal/mol. The subsequent reductive elimination of the C− B bond would proceed via transition state 28-ts to give borylation product 3 and regenerate complex 7. Overall, the activation free energies of each step in Path B were higher than those of Path A, especially the step involving the oxidative addition of the B−B bond. These results therefore suggest that the mechanism described by Path B would be kinetically unfavorable compared with the mechanism described by Path A and that the former of these two pathways could be safely ruled out. The σ-bond metathesis mechanism described by Path C, which proceeds via transition state 29-ts, was also excluded based on its exorbitant energy barrier (up to 74.8 kcal/mol). The mechanism of this iridium(I) catalyzed para-C−H Borylation was also studied in Musaev’s work.6i The iridium(I)/ iridium(III) catalytic cycle was excluded in their work because the DFT calculation results suggested that “the conversion of the initial monoboryl Ir(I) catalyst to a tris-boryl Ir(III) complex (1 + B2pin2 → 3) through B−B oxidative addition is still more likely to occur than C−H activation”. Thus, we recalculated these data using other methods. As Musaev and coworkers have tested B3LYP, M06,20 wB97x-D,21 and mPW1k22 for regioselectivity, these four methods and N12 are employed

Scheme 2. Plausible Iridium(I)/Iridium(III) Catalytic Cycle for the Borylation of Trimethyl(phenyl)silane (1)

this reaction could proceed via Path B, with sequential B−H reductive elimination, B−B oxidative addition and C−B reductive elimination steps. Lastly, this process could occur via a σ-bond metathesis mechanism, as shown in Path C. The reaction pathways described above were subjected to a computational analysis, and the results are summarized in Figure 5. The activation free energy for the para-selective oxidative addition of the C−H bond of the substrate to complex 7 via transition state 18-ts was found to be 14.7 kcal/ mol, which is 20.2 kcal/mol lower than the energy required for the formation of iridium(III) triboryl complex 8 (34.9 kcal/ mol). This result therefore indicated that the generation of aryliridium(III) intermediate 19 was kinetically more favorable than the formation of intermediate 13. According to Path A (the blue pathway), it would then be possible to obtain borylation product 3 via transition state 20-ts with an activation free energy of 14.3 kcal/mol. The oxidative addition of the B−B bond of B2pin2 (2) to resulting iridium(I) hydride complex 21 would then occur through transition state 22-ts, with an activation free energy of 20.4 kcal/mol. The subsequent reductive elimination of the B−H bond from iridium(III) hydride intermediate 15 would regenerate iridium(I) boryl D

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Figure 5. Free energy profile of the iridium(I)/iridium(III) catalytic cycle for the para-selective C−H borylation of trimethyl(phenyl)silane (1). The diphosphine ligand used for this calculation was Xyl−MeO−BIPHEP.

reaction will proceed along the iridium(I)/iridium(III) catalytic cycle and that the B−B oxidative addition could not take place. To provide further support for the above conclusion and exclude the effect of solvation calculation, we reoptimized all the structure in Figure 3 (ref 6i, Musaev’s papaer) using B3LYP/6-31G(d) (Lanl08(f) for Ir) in gas phase. Harmonic vibrational frequency calculations were performed for the stationary points to confirm them as local minima or transition structures, as well as deriving the thermal corrections for free energies. Comparison between B3LYP and B3LYP-D3 calculated free energy profile in gas phase is shown in Figure 6. These two sets of data are quite different. In B3LYPcalculated free energy profile, either the coordination of trimethyl(phenyl)silane or B2pin2 to iridium(I) complex 1 is endergonic by more than 10.0 kcal/mol. The activation free energy for B−B oxidative addition is 21.9 kcal/mol, which is 6.5 kcal/mol higher than that of TSCH. These results are in good accordance with the data shown in Table 1. A conclusion could be drawn that the B3LYP-D3 method would underestimate energy information, and the utilization of B3LYP-D3 for structure optimization in Musaev’s work afforded a series of

to recalculate the solvation single-point energy. All the solvation calculations were performed in hexane using 6-311+ +G(d,p) basis set (Lanl08(f) for Ir) based on B3LYP-D323/[631G(d,p) + Lanl2dz for (Ir)] optimized structures. The thermal correction to Gibbs free energy reported by Musaev and co-workers is also used to afford the new Gibbs free energy. Computational results are summarized in Table 1. Different from B3LYP-D3 calculated results, the coordination of B2pin2 calculated by B3LYP is endergonic by 29.4 kcal/mol, and the activation free energy for B−B bond oxidative addition reaches as high as 40.3 kcal/mol. These energy data are close to that obtained by N12. In fact, besides wB97x-D, the data calculated via other methods all have large deviation from that obtained by B3LYP-D3. Obviously, using B3LYP-D3 for geometry optimization would greatly underestimate the energy information. More importantly, Table 1 also reveals that all of these five methods calculated relative free energies of TSBB are much higher than that of TSCH. Consequently, on the basis of Musaev provided structures, the B−B oxidative addition to monoboryl iridium(I) should be more difficult to occur compared with C−H activation, which means that the whole E

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Organometallics Table 1. Computational Results for Different Methods Calculated B−B and C−H Bond Oxidative Addition to Monoboryl Iridium(I)

ΔGsolv(kcal/mol)

1M

2M

TSBB

3M

2′M

TSCH

B3LYP-D3a B3LYP M06 wB97xD mPW1K N12

0.0 0.0 0.0 0.0 0.0 0.0

−15.2 29.4 −7.5 −15.8 20.0 31.3

−8.6 40.3 1.3 −7.6 28.1 33.5

−44.3 −2.0 −31.9 −46.1 −15.4 −2.1

−6.2 21.5 −2.5 −6.5 14.9 22.2

−4.0 7.1 −12.6 −18.2 −0.8 3.9

a

Figure 7. Structural and activation free energy data for transition states (a) 18-ts, (b) 18-ts-m, (c) 30-ts-p-Et, and (d) 30-ts-m-Et. The bond lengths are given in Å. The free energies are given in kcal/mol.

The B3LYP-D3 calculated relative energies were reported in ref 6i.

the oxidative addition of the meta-C−H to complex 7 was defined as 18-ts-m (Figure 7b) with an activation free energy of 18.3 kcal/mol. A comparison of the structures of 18-ts-m with 18-ts suggested that the para-C−H activation of trimethyl(phenyl)silane (1) would be favored over the meta-C−H activation by 4.0 kcal/mol, which is consistent with the 88% para-selectivity obtained experimentally. Structural analysis showed that the lengths of the Ir−H, Ir−C, and C−H bonds in 18-ts (Figure 7a) were 1.68, 2.22, and 1.36 Å, respectively, which were similar to the corresponding bond lengths in 18-tsm (1.67, 2.23, and 1.37 Å, respectively). These data therefore implied that the core structures of the transition states for these two oxidative addition reactions were very similar to each other. The main difference between these two transition states was the distinct spatial repulsion observed in 18-ts-m, where the H3− H4 and H5−H6 distances were found to be 2.71 and 2.55 Å, respectively. In contrast, the closest distance observed between the diphosphine ligand and the para-substituent in 18-ts for the para-C−H activation of the substrate was determined to be 3.14 Å, indicating that this structure would experience less steric hindrance than 18-ts-m. It could therefore be concluded that greater steric repulsion between the diphosphine ligand and the meta-substituent in 18-ts-m leads to the higher energy barrier observed for meta-C−H activation compared with paraC−H activation. To provide further evidence to support this conclusion, we investigated the free energy profile for the C−H activation of ethylbenzene, which has a smaller steric bulk than trimethyl(phenyl)silane (1). Experimentally, the para-selectivity of this substrate was much less than that of trimethyl(phenyl)silane (1) at 31%. The theoretical evaluation of the C−H oxidative addition step for ethylbenzene revealed that the meta-C−H activation was kinetically favored over the para-C−H activation, with the activation free energy of 30-ts-p-Et (Figure 7c) being 0.7 kcal/mol higher than that of 30-ts-m-Et (Figure 7d). This result is contrary to that of trimethyl(phenyl)silane (1) and is consistent with the experiment. As shown in Figure 7d, the

Figure 6. Comparison between B3LYP and B3LYP-D3 calculated free energy profile of B−B and C−H bond oxidative addition in gas phase.

different results, thereby leading to a conclusion inconsistent with these reported herein using other different functionals. The C−H bond oxidative addition to monoboryl iridium(I) is proven to be easier to occur than that of B−B bond oxidative addition. Therefore, the reation will take place along the iridium(I)/iridium(III) pathway. Having established the iridium(I)/iridium(III) catalytic cycle described in Path A as the most plausible mechanism for the [Ir(cod)OH]2/Xyl−MeO−BIPHEP-catalyzed aromatic C−H borylation, we conducted a series of theoretical studies to rationalize the regioselectivity of this reaction based on this mechanism (Figure 7). For reactant 1, the transition state for F

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for the higher para-selectivity of bulky substrates in the [Ir(cod)OH]2/Xyl−MeO−BIPHEP system. Besides trimethylsilyl substituted benzene, other reactants bearing bulky substituents such as acetophenone ketal and tertbutylbenzene have also been tested in calculation. As shown in Figure 8a,b, para- and meta-C−H activation transition states of

H3−H4 and H4−H5 distances, which were selected to highlight the extent of the steric repulsion in 30-ts-m-Et, were found to be 4.02 and 3.94 Å, respectively. Furthermore, the closest distance between the diphosphine ligand and the para-substituent in 30-ts-p-Et was 4.04 Å (Figure 7c). These data indicated that there was very little spatial repulsion in 30ts-p-Et or 30-ts-m-Et; therefore, the steric effect does not play a dominant role in determining the para-selectivity for substrates bearing small substituents. The electron-donating nature of ethyl on benzene ring might be responsible for the higher meta-selectivity observed for ethylbenzene. The electronic effect of substituents is then studied to conclude the origin of regioselectivity. As shown in Table 2, Table 2. Calculated Activation Free Energies for Studying the Electronic Effect

substrate

borylation position

product ratio in experiment

ΔG⧧ (kcal/mol)

50 50 56 44

14.5 14.2 14.8 11.5 12.1 16.2 16.0 11.1 10.9 15.7 16.3

32 33 34 35 36 37

p m p m p m 4 5 4 5

Figure 8. Structural and activation free energy data for transition states (a) 38-ts-ketal-p, (b) 38-ts-ketal-m, (c) 39-ts-tBu-p, and (d) 39-tstBu-m. The bond lengths are given in Å. The free energies are given in kcal/mol.

acetophenone ketal are located as 38-ts-ketal-p and 38-tsketal-m, respectively. Activation free energy for meta-C−H activation is found to be 2.8 kcal/mol higher than that of paraC−H activation, which is consistent with the experimental data (para/meta ratio = 79:21). For tert-butylbenzene involved reaction, activation free energy for the para-C−H oxidative addition to iridium(I) boryl complex 7 via 39-ts-tBu-p is determined to be 15.5 kcal/mol (Figure 8c), which is 1.4 kcal/ mol lower than that of meta-C−H activation via 39-ts-tBu-m (Figure 8d), suggesting that para-C−H activation is more favored. Thus, computational results reach the same conclusion as that observed in experiment, and the energy barrier difference could be attributed to steric effect as well. Finally, a 2D contour model24 was used in this study to illustrate the differences in the steric repulsion across the different regions of the diphosphine ligand Xyl−MeO− BIPHEP. Figure 9 shows a 2D contour map along the z axis of the van der Waals surface of structural fragment 31-IrLBpin. The structural coordinates of 31-IrL-Bpin were derived from transition state 18-ts. The red regions of this 2D contour map represent areas where there was strong repulsion with the substrate, with the deeper red colors indicating stronger steric repulsion. The two dark red regions shown in Figure 9 were positioned in close proximity to the meta-substituents. Notably, the para-substituent was positioned much further away from these two areas of high steric hindrance, which is consistent with the low activation free energy for the para-selective oxidative addition of the C−H bond to the iridium ion.

activation free energy for the borylation of benzene (32) is 14.5 kcal/mol. When toluene (33) is used as the substrate, activation free energies for para- and meta-C−H activation are determined to be 14.2 and 14.8 kcal/mol, which are all very close to 14.5 kcal/mol. For CF3-substituted substrate 34, corresponding values for para- and meta-C−H activation are 11.5 and 12.1, respectively. The energy difference is merely 0.6 kcal/mol. While for electron-donating group substituted substrate 35, activation free energies for para- and meta-C−H activation are found to be 16.2 and 16.0 kcal/mol. These data imply that the electron-withdrawing group on benzene ring could facilitate the C−H activation process, while the electrondonating substituent would result in higher activation free energy. In addition, ortho-disubstituted benzene derivatives 36 and 37, which have been employed in experiment, were also calculated. No matter whether 36 or 37 is used in calculation, the activation free energies for C−H activation at 4- or 5position of benzene ring are very close to each other. Thus, the computational results are in good accordance with the experimental conclusion that the electronic effect does not make a difference on the regioselectivity. This result also indirectly verifies our conclusion that the steric effect accounts G

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Additional computational details and energies of all reported structures (PDF) Cartesian coordinates for all calculated structures (XYZ)

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Ruopeng Bai: 0000-0002-1097-8526 Yu Lan: 0000-0002-2328-0020 Author Contributions

Figure 9. 2D contour map of the van der Waals surface of the structural fragment 31-IrL-Bpin. Distances are given in Å. Ir was located at the origin of the coordinate system in the contour map. The contour line of zero was defined as being in the same plane as the Ir atom. Negative distances (blue) indicate that the ligand was farther away from the substrate; positive distances (red) indicate that the ligand was closer to the substrate.

L.Z. and X.Q. contributed equally to this work. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This project was supported by the National Science Foundation of China (Grant 51302327) and Fundamental Research Funds for the Central Universities (Chongqing University) (no. 106112017CDJXY220007). We are also grateful to Graduate Scientific Research and Innovation Foundation of Chongqing, China (no. CYB16034) for financial support.

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CONCLUSION The mechanism of the iridium-catalyzed aromatic C−H borylation of arenes has been studied using the newly reported N12 DFT method. Previous reports pertaining to this reaction have resulted in the proposal of an iridium(III)-/iridium(V)based catalytic cycle involving a hepta-coordinated iridium(V) intermediate based on various theoretical and experimental results. However, we found that the use of bulky diphosphine ligand Xyl−MeO−BIPHEP was unfavorable for this mechanism because of considerable steric repulsion in the iridium(V) intermediate. Instead, the theoretical calculations reported in this study are indicative of a novel iridium(I)-/iridium(III)based catalytic cycle. The iridium(I)/iridium(III) catalytic cycle induced by this steric effect consists of several steps, including (i) the oxidative addition of C−H to an active iridium(I) boryl complex; (ii) the reductive elimination of a C−B bond; (iii) the oxidative addition of B2pin2 to an iridium(I) hydride complex; and (iv) the reductive elimination of B−H. Notably, the computed regioselectivities were consistent with the experimental observations. The high para-selectivity observed in the [Ir(cod)OH]2/Xyl−MeO−BIPHEP system could also be explained by the steric effect. The results of structural analysis and 2D contour modeling experiments also revealed that the steric repulsion between the diphosphine ligand and the metasubstituents was greater than the repulsion with the parasubstituents, thereby leading to the higher energy barrier for meta-C−H activation. Given that this innovative iridium(I)/ iridium(III) catalytic cycle has been shown to be suitable for reactions involving sterically hindered ligands, we believe this work could provide a platform for understanding the mechanisms of other iridium-catalyzed reactions. Moreover, the steric repulsion experienced at different regions of the ligand was clearly described using 2D contour maps, which could also provide valuable guidance for the design of new iridium catalysts.

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DOI: 10.1021/acs.organomet.7b00151 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

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DOI: 10.1021/acs.organomet.7b00151 Organometallics XXXX, XXX, XXX−XXX