Mechanism and Origins of Regio- and Enantioselectivities of Iridium

Feb 13, 2018 - Institute of New Energy, Shenzhen, Guangdong 518031, P.R. China ... which afford the opposite enantiomers of product with the aryl grou...
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Article Cite This: J. Org. Chem. 2018, 83, 2937−2947

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Mechanism and Origins of Regio- and Enantioselectivities of IridiumCatalyzed Hydroarylation of Alkenyl Ethers Mei Zhang,† Lingfei Hu,† Yanmin Lang,† Yang Cao,‡ and Genping Huang*,†,§ †

Department of Chemistry, School of Science and Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Tianjin University, Tianjin 300072, P. R. China ‡ Institute of New Energy, Shenzhen, Guangdong 518031, P.R. China § National Demonstration Center for Experimental Chemistry and Chemical Engineering Education, National Virtual Simulation Experimental Teaching Center for Chemistry and Chemical Engineering Education, Tianjin University, Tianjin 300072, P. R. China S Supporting Information *

ABSTRACT: The iridium-catalyzed hydroarylation of alkenyl ethers developed by Nishimura and co-workers (Ebe, Y.; Onoda, M.; Nishimura, T.; Yorimitsu, H. Angew. Chem. Int. Ed. 2017, 56, 5607− 5611) represents a rare example of regio- and enantioselective hydroarylation of challenging internal alkenes. In the present study, density functional theory calculations were performed in order to investigate the detailed reaction mechanism and the origins of the experimentally observed regio- and enantioselectivities. The computations show that the initial C−H oxidative addition and the isomerization between the allylic ethers and the 1-alkenyl ethers via the migratory insertion into the Ir−H bond/β-hydride elimination are both feasible. The reaction was found to proceed through the modified Chalk−Harrod-type mechanism via the migratory insertion into the Ir−C bond/C−H reductive elimination. The migratory insertion into the Ir−C bond constitutes the rate- and selectivity-determining step of the overall reaction. The calculations reproduced quite well the experimentally observed regio- and enantioselectivities. The enantioselectivity of the reaction was found to arise from the reactions of the (E)- and (Z)-1-alkenyl ethers, which afford the opposite enantiomers of product with the aryl group installed at the α-position to the alkoxy group. It turns out that the strong electron-donating character of the alkoxy group plays an important role in determining the regioselectivity, since it can stabilize the developed positive charge of the α-insertion transition state, leading to the aryl group being selectively installed at the α-position.

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Although significant progress has been achieved, the development of enantioselective hydroarylations remains a key challenge in this field.9b,10 In this regards, Nishimura and co-workers very recently reported an intriguing work on the iridium-catalyzed hydroarylation of alkenyl ethers (Scheme 1).11 They found that with an iridium/chiral diphosphine complex, the reaction of 2-phenylpyridine 1 and alkenyl ether (E)-2 generated hydroarylation product (S)-3 with good enantioselectivity. The significance of the reaction goes beyond the construction of a new C−C bond with a chiral center. In fact, the reaction was proposed to involve an olefin isomerization of the alkenyl ethers into the corresponding 1-alkenyl ethers (Scheme 2), and the aryl group was selectively installed at the α-carbon atom to the alkoxy group. The reaction thus represents a rare example of regio- and enantioselective hydroarylation of challenging internal alkenes. As shown in Scheme 3, after an initial C−H oxidative addition to form Ir(III) hydride complex A, two related but fundamentally different mechanisms have been proposed for this type of transformation. Taking the formation of products 3

ransition-metal-catalyzed hydroarylations of alkenes provide one of the most efficient protocols for the construction of C−C bond.1,2 In this context, iridium complexes have recently attracted great research interest due to their unique features (e.g., reactivity and regioselectivity) compared to other transition-metal complexes,2 such as those of ruthenium, rhodium, platinum, nickel, and cobalt.3,4 In particular, ruthenium-, nickel-, and cobalt-catalyzed hydroarylation reactions with monosubstituted alkenes generally afford linear products, while branched products can only be generated with aryl-substituted alkenes.4 On the other hand, recent advances showed that branched-selective hydroarylations can be realized for both alkyl- and aryl-substituted alkenes using iridium complexes.5−11 For example, Shibata and co-workers developed in 2012 an iridium-catalyzed branched-selective hydroheteroarylation of indoles with both alkyl- and arylsubstituted alkenes.7 Bower et al. found that in the iridiumcatalyzed carbonyl-directed hydroarylation of monosubstituted alkenes, either linear or branched selectivity can be achieved by subtle modification of the diphosphine ligand.8 Additionally, Nishimura and co-workers developed a series of iridiumcatalyzed completely branched-selective hydroarylations of vinyl ethers.9 © 2018 American Chemical Society

Received: February 8, 2018 Published: February 13, 2018 2937

DOI: 10.1021/acs.joc.8b00377 J. Org. Chem. 2018, 83, 2937−2947

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The Journal of Organic Chemistry Scheme 1. Iridium-Catalyzed Hydroarylation of Alkenyl Ether (E)-2

C−C reductive elimination is the rate- and selectivitydetermining step. Very surprisingly, we have recently found that for the iridium-catalyzed hydroarylations of monosubstituted alkenes and vinyl ethers,16 the Chalk−Harrod-type mechanism is unfeasible due to the high-energy barrier required for the C−C reductive elimination, and moreover the experimentally observed regioselectivity could not be reproduced within this mechanistic scenario. Instead, the reactions were found to proceed through the modified Chalk−Harrodtype mechanism, with the regioselectivity of the reaction being determined by the migratory insertion into the Ir−C bond. It is noteworthy that, since the C−C reductive elimination from an Ir(III) center is rare or unknown, several experimental works proposed the modified Chalk−Harrod-type mechanism for the Ir-catalyzed hydroarylations, although no evidence was provided to prove the mechanism in these works.5g,10 Following our continuous research interest in this field,16,17 we decided to investigate computationally the title reaction by employing density functional theory (DFT) calculations. The calculations indeed show that after the C−H oxidative addition and the olefin isomerization, the reaction takes place through a modified Chalk−Harrod-type mechanism (the migratory

Scheme 2. Proposed Isomerization of Alkenyl Ether (E)-2

as an example, the widely accepted Chalk−Harrod-type mechanism12 involves a migratory insertion into the Ir−H bond to form intermediate C, followed by the C−C reductive elimination to give the hydroarylation products. Alternatively, a modified Chalk−Harrod-type mechanism13,14 through a migratory insertion into the Ir−C bond and C−H reductive elimination is also possible. To gain some insights into the reaction mechanism, Nishimura and co-workers conducted deuterium-labeling experiments,11 which showed that the migratory insertion into the Ir−H does occur and that this step and the C−H oxidative activation are both reversible. The detailed reaction mechanisms of the Ru-, Ni-, and Cocatalyzed hydroarylations have been investigated computationally,15 which showed that the reactions occur through the widely accepted Chalk−Harrod-type mechanism and that the Scheme 3. Possible Reaction Mechanisms

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The Journal of Organic Chemistry Scheme 4. C−H Oxidative Addition and Isomerization of Allylic Ether (E)-2

which in the experiments led to slightly lower enantioselectivity (88% ee). Experimentally, [Ir(cod)2]BARF with the (R)-binap was used as the precatalyst.11 The counterion BARF− was believed to be a spectator ligand, and in our calculations only the [Ir(cod)2]+ was considered. The ligand exchange process between the [Ir(cod)2]+ and (R)-binap to form active catalyst [Ir(cod)(R)-binap]+ (INT0) was calculated to be highly exergonic by 33.4 kcal/mol, and we thus set the sum of the free energies of the free reactants (1 and (E)-2) and INT0 to be the zero on the relative free energy scale. In what follows, the C−H oxidative addition of 2phenylpyridine 1 and the isomerization of allylic ether (E)-2 will be investigated first. Next, the detailed reaction mechanism for the formation of main product (S)-3 will be elucidated by considering all possible pathways. After the detailed reaction mechanism is established, the results for the formation of product (R)-3 will be presented, and the origins of the enantioselectivity will be discussed. Finally, the hydroarylation reactions, in which the aryl group is installed at the β- and γcarbon atom to the methoxy group leading to the formation of products 4 and 5, will be considered in order to shed light on the origins of the regioselectivity.

insertion into the Ir−C bond/C−H reductive elimination). More importantly, the experimentally observed regio- and enantioselectivities were well reproduced and rationalized by the calculations. The enantioselectivity of the reaction was found to arise from the reactions of the (E)- and (Z)-1-alkenyl ethers, which afford the opposite enantiomers of product with the aryl group installed at the α-position to the alkoxy group. The regioselectivity of the reaction is mainly caused by the electron-donating character of the alkoxy group, which can stabilize the developed positive charge on the α-insertion transition state. To the best of our knowledge, the current study also represents the first example of a computational study of the enantioselective hydroarylations.



COMPUTATIONAL DETAILS All calculations were performed at the B3LYP18 level of theory using the Gaussian 09 package.19 Geometry optimizations were carried out with a mixed basis set of LANL2DZ20 for Ir, and 631G(d) for other atoms. Vibrational frequencies were computed analytically at the same level of theory to confirm whether the structures are minima (no imaginary frequencies) or transition states (only one imaginary frequency). Key transition-state structures were confirmed to connect corresponding reactants and products by intrinsic reaction coordinate (IRC) calculations.21 Solvation effects (toluene, ε = 2.3741) were taken into account by performing single-point calculations using the SMD model.22 To obtain better accuracy, energies of the optimized geometries were calculated using single-point calculations with a larger basis set, which is SDD23 for Ir and 6-311+G(2d,2p) for other atoms. The final free energies reported in the article (ΔGsol) are the large basis set single-point energies with gas-phase Gibbs free energy correction (at 298.15 K), solvation correction, and dispersion correction obtained using the DFT-D3(BJ) method developed by Grimme and co-workers.24,25 In order to ensure that the lowest-energy conformation of intermediates and transition states was presented and discussed in the text, extensive conformational searches were conducted. The experiments showed that the highest enantioselectivity (92% ee) could be achieved using (R)-binap* as ligand. However, in order to reduce the computational cost, in current calculations we modeled the reaction with (R)-binap as ligand,



C−H OXIDATIVE ADDITION AND ISOMERIZATION OF THE ALLYLIC ETHER According to the proposed reaction mechanism (Scheme 3), the first step of the reaction is the C−H oxidative addition of 2phenylpyridine 1, which is the common initial step for both Chalk−Harrod and modified Chalk−Harrod-type pathways. As reported in Scheme 4, the calculations show that in order to affect the C−H oxidative addition step, active catalyst INT0 has first to undergo a ligand exchange process with 1 to release the cod ligand and generate intermediate INT1. This step is endergonic by 1.5 kcal/mol. From INT1, the C−H oxidative addition through transition state TS1 was found to be quite facile, requiring an energy barrier of only 5.3 kcal/mol relative to INT1 (i.e., 6.8 kcal/mol relative to INT0). The C−H oxidative addition was calculated to be exergonic, and the resulting five-coordinated Ir(III) hydride intermediate INT2 is 2.6 kcal/mol more stable than INT0. 2939

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Figure 1. Calculated energy profile of the formation of product (S)-3 through the migratory insertion into Ir−H/C−C reductive elimination.

accessible. Therefore, in order to draw definitive conclusions on the detailed reaction mechanism and the origins of the regio- and enantioselectivities, all possible hydroarylation reactions with 2 and 6 were considered in current calculations. In the following section, the results of the reactions with 1alkenyl ethers 6 leading to the formation of main product (S)-3 will be presented first, and the detailed reaction mechanism will be established by comparing the energies of the possible pathways.

After the C−H oxidative addition, the reaction of intermediate INT2 with allylic ether (E)-2 could take place, which would afford the possible hydroarylation products where the aryl group is installed at the β- and γ-carbon atom to the methoxy group (such as products 4 and 5, Scheme 2), rather than the experimentally observed main product (S)-3. Therefore, the isomerization of allylic ether (E)-2 to 1-alkenyl ethers 6 has to occur first (Scheme 3), from which the reaction with intermediate INT2 can generate main product (S)-3. Transition-metal-catalyzed olefin isomerization has been extensively investigated both experimentally and computationally.26 It has been widely proposed that with the aid of the M− H species, the isomerization can be realized through the migratory insertion of alkene into the M−H bond followed by the β-hydride elimination. We thus examined this pathway for the isomerization of allylic ether (E)-2 to 1-alkenyl ethers 6 promoted by Ir(III) hydride intermediate INT2 (Scheme 4). The isomerization begins with the coordination of the C−C double bond of (E)-2 to the Ir center of INT2 to form intermediate (E)-INT3,27 from which the γ-insertion of allylic ether (E)-2 into the Ir−H bond takes place through transition state (E)-TS2 to afford five-coordinated Ir(III) alkyl intermediate (E)-INT4. From (E)-INT4, the β-hydride elimination occurring with the Cα−H bonds via transition states (E)-TS3 and (Z)-TS3 leads to the formation of intermediates (E)-INT5 and (Z)-INT5, from which a ligand dissociation step can produce the 1-alkenyl ethers (E)-6 and (Z)-6, respectively. In addition, the isomerization of allylic ether (E)-2 to (Z)-2 was also considered, which was found to proceed through the β-hydride elimination transition state (Z)TS2. The results show that the energy barriers of the γ-insertion into the Ir−H bond and β-hydride elimination are relatively low, being around 17−19 kcal/mol with respect to INT2. As will be disclosed below, these energy barriers as well as the free energies of the corresponding transition states were calculated to be lower than those of the subsequent steps, which is thus in accordance with the deuterium-labeling experiments, showing that the C−H activation and migratory insertion into the Ir−H bond steps are reversible.11 Moreover, it was found that the energy differences between allylic ethers 2 and 1-alkenyl ethers 6 are rather small, being within 2 kcal/mol, which indicate that these species are both kinetically and thermodynamically



DETAILED PATHWAY LEADING TO THE FORMATION OF MAIN PRODUCT (S)-3 In principle, four possible hydroarylation products, in which the aryl group is installed at the α- and β-carbon atom to the methoxy group (i.e., products (S)-3, (R)-3, (S)-4, and (R)-4), can be obtained via the reactions of 1-alkenyl ethers (E)-6 and (Z)-6 with intermediate INT2. In this section, we will only focus on the formation of experimentally observed main product (S)-3. The other results will be presented in the appropriate sections below dealing with the origins of the selectivities. As mentioned in the Introduction (Scheme 3), the reactions can take place through two possible pathways, namely the Chalk−Harrod-type pathway (migratory insertion into the Ir− H bond/C−C reductive elimination) and modified Chalk− Harrod-type pathway (migratory insertion into the Ir−C bond/ C−H reductive elimination). Both possible pathways were thus considered in the calculations, and the energies will be compared to establish the reaction mechanism. The calculated energy profile for the formation of product (S)-3 via the migratory insertion into Ir−H/C−C reductive elimination is given in Figure 1. The calculations show that the coordination of the C−C double bond of 1-alkenyl ether (Z)-6 to the Ir center of intermediate INT2 leads to the formation of intermediate (Z)-INT6, which was calculated to be endergonic by 11.1 kcal/mol. Then, the β-insertion of 1-alkenyl ether (Z)-6 into the Ir−H bond takes place through transition state (Z)TS4 with an energy barrier of 17.6 kcal/mol relative to INT2 + (Z)-6, resulting in five-coordinated Ir(III) alkyl intermediate (Z)-INT7. Finally, the catalytic cycle is closed by the C−C reductive elimination via transition state (S)-TS5, leading to the formation of product-coordinated complex (S)-INT8, which through a ligand exchange process with the cod ligand releases 2940

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Figure 2. Calculated energy profile of the formation of product (S)-3 through the migratory insertion into Ir−C/C−H reductive elimination. Distances of the optimized geometric structures are given in Å.

previous studies.16 The overall energy barrier of the reaction with 1-alkenyl ether (E)-6 to form main product (S)-3 was calculated to be 24.4 kcal/mol relative to INT2 + (Z)-6. The reaction with 1-alkenyl ether (Z)-6 to form main product (S)-3 was found to be much less favorable than that with 1-alkenyl ether (E)-6. The transition state (Z)-TS6, which corresponds to the α-insertion of 1-alkenyl ether (Z)-6 into the Ir−C bond, was calculated to be 6.3 kcal/mol higher in energy than (E)-TS6. The origin of this energy difference is probably due to the different conformational arrangement of these octahedral transition states. The optimized geometric structures show that in transition state (E)-TS6, the phosphine ligand is trans to the aryl group, while in (Z)-TS6, the H ligand is trans to the aryl group (Figure 2). Considering that the trans effect of the H ligand is stronger than the phosphine ligand, the breaking Ir−C bond is longer in (Z)-TS6 than in (E)-TS6 by 0.14 Å. As a consequence, the disruption of aromaticity of the aryl group in (Z)-TS6 is greater than that in (E)-TS6, which thus results in the energy of (Z)-TS6 being much higher than that of (E)TS6.28 It should be pointed out here that there are a large number of conformational isomers for each mode of migratory insertion into the Ir−C bond and all of these were computed and compared in the calculations (see Supporting Information for details). Taking all results together, the calculations show that the energy barrier of the migratory insertion into Ir−H/C−C reductive elimination is higher than that of the migratory insertion into Ir−C/C−H reductive elimination by 4.3 kcal/ mol (25.8 kcal/mol of (S)-TS5 versus 21.5 kcal/mol of (E)TS6). Therefore, we concluded that the formation of main product (S)-3 should proceed through the reaction of 1-alkenyl ether (E)-6 with intermediate INT2 via the pathway of the migratory insertion into the Ir−C bond followed by C−H reductive elimination (modified Chalk−Harrod-type mecha-

main product (S)-3 and regenerates active catalyst INT0. The intermediate (Z)-INT7 can also be generated through the reaction of 1-alkenyl ether (E)-6 with intermediate INT2. Starting with intermediate (E)-INT6, the β-insertion of 1alkenyl ether (E)-6 into the Ir−H bond occurs via transition state (E)-TS4 with an energy barrier of 21.2 kcal/mol relative to INT2 + (Z)-6. The resulting intermediate (E)-INT7 then isomerizes to give a more stable intermediate (Z)-INT7. The results show that the C−C reductive elimination constitutes the rate-determining step of this pathway, with an overall energy barrier of 28.7 kcal/mol relative to INT2 + (Z)-6. We have previously shown that the Ir-catalyzed hydroarylation reactions may also proceed through the migratory insertion into the Ir−C bond followed by C−H reductive elimination.15 The calculated energy profile of this alternative pathway and the optimized geometric structures of key transition states are shown in Figure 2. The calculations show that the reaction with 1-alkenyl ether (E)-6 begins with the formation of intermediate (E)-INT9 by the coordination of C−C double bond of (E)-6 to the Ir center of INT2, which requires an energy cost of 5.2 kcal/mol relative to INT2 + (E)-6. Subsequently, the α-insertion into the Ir−C bond was found to occur via transition state (E)-TS6, which gives intermediate (E)-INT10. To close the catalytic cycle, intermediate (E)-INT10 undergoes the C−H reductive elimination via transition state (E)-TS7 to form productcoordinated intermediate (E)-INT11, which could give main product (S)-3 and regenerate active catalyst INT0 through a ligand exchange process with the cod ligand. The results show that the energy of C−H reductive elimination is lower than that of α-insertion into the Ir−C bond (21.5 kcal/mol of (E)-TS6 versus 18.9 kcal/mol of (E)-TS7), which indicates that the migratory insertion into the Ir−C bond is the rate-determining step of this mechanistic scenario, in agreement with our 2941

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Figure 3. Calculated energy profile of the formation of product (R)-3 through the migratory insertion into Ir−C/C−H reductive elimination. Distances of the optimized geometric structures are given in Å, respectively.

On the other hand, the formation of product (R)-3 via the αinsertion of 1-alkenyl ether (E)-6 into the Ir−C bond was found to take place via transition state (E)-TS8. For the same reason as discussed above, (E)-TS8 was calculated to be higher in energy than (Z)-TS8, by 4.5 kcal/mol. The results thus show that the reactions with 1-alkenyl ethers (E)-6 and (Z)-6 afford the opposite enantiomers of product with the aryl group installed at the α-position ((S)-3 and (R)3), and 1-alkenyl ether (E)-6 is more reactive than (Z)-6 (Figures 2 and 3). The energy difference between transition states (E)-TS6 and (Z)-TS8 was calculated to be 1.6 kcal/mol (21.5 kcal/mol of (E)-TS6 versus 23.1 kcal/mol of (Z)-TS8), corresponding to a calculated 82% ee at reaction temperature (80 °C), which is in good agreement with the experimentally observed 88% ee.11 The optimized geometric structures show that the distances of the forming and breaking bonds in both (E)-TS6 and (Z)-TS8 are quite similar, and the conformational arrangement of these transition states is the same except the different configuration of the Cα−Cβ double bond (Figures 2 and 3). Scheme 5 shows the Newman projections of (E)-TS6 and (Z)-TS8 viewing along the Cα−Cβ bond, in which the dihedral angle C−Cα−Cβ−Ir was found to be different. In (E)-

nism). In the next section, the results of forming product (R)-3 will be presented and compared with those of (S)-3 in order to rationalize the origins of the enantioselectivity.



ORIGINS OF ENANTIOSELECTIVITY The results show that the formation of product (R)-3 follows the same reaction mechanism as established above. The calculated energy profile together with the optimized geometric structures of key transition states is given in Figure 3, and the results of the alternative pathway via migratory insertion into Ir−H/C−C reductive elimination are provided in Supporting Information. The computations show that the formation of product (R)-3 via the reaction of 1-alkenyl ether (Z)-6 is more favorable than that with 1-alkenyl ether (E)-6. The opposite occurs in the formation of product (S)-3, with the reaction with 1-alkenyl ether (E)-6 being more favored than with 1-alkenyl ether (Z)-6. This difference also results in the experimentally observed enantioselectivity, as will be discussed below. The calculations show that the reaction of 1-alkenyl ether (Z)-6 with intermediate INT2 begins with the coordination of the C−C double bond to the Ir center to form intermediate (Z)-INT12, which is 3.0 kcal/mol less stable than INT2 + (Z)-6. (Z)INT12 then undergoes the α-insertion of 1-alkenyl ether (Z)-6 into the Ir−C bond via transition state (Z)-TS8, resulting in the formation of intermediate (Z)-INT13. Finally, the C−H reductive elimination occurs through transition state (Z)-TS9 and forms product-coordinated complex (Z)-INT14, which could release product (R)-3 through a ligand exchange step with the cod ligand. The overall energy barrier of forming product (R)-3 was calculated to be 26.0 kcal/mol relative to INT2 + (Z)-6.

Scheme 5. Newman Projections of (E)-TS6 and (Z)-TS8 Viewing Along the Cα−Cβ Bond

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Figure 4. Calculated energy profile of the formation of products (R)-4 and (S)-4. Distances and angles of the optimized geometric structures are given in Å and degrees, respectively.

Figure 5. Calculated energy profile of the formation of products (R)-5 and (S)-5. Distances and angles of the optimized geometric structures are given in Å and degrees, respectively. 2943

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The Journal of Organic Chemistry TS6, the dihedral angle C−Cα−Cβ−Ir is 2.1°, which is the nearly ideal square-planar geometry required in the migratory insertion. However, in (Z)-TS8, as a result of the steric repulsion between two hydrogen atoms (2.31 Å), the dihedral angle C−Cα−Cβ−Ir is distorted to −13.8°, which thus results in (Z)-TS8 being less favored than (E)-TS6, leading to the experimentally observed enantioselectivity. To be noted, the correlation between the dihedral angle and the selectivity has also been found previously in palladium-catalyzed Heck arylations.29

The calculated preference for the α-insertion into the Ir−C bond is in accordance with the previous studies on the Pdcatalyzed Heck reactions on vinyl ethers,30,31 and the origin of the regioselectivity is ascribed to the electronic effect of the alkoxy group. It has been previously argued that with a cationic metal center, the dominant character of the alkene migratory insertion transition state involves alkene acting as a Lewis base reacting with the electrophilic metal atom.32 In this sense, when the developed positive charge is more stabilized, the transition state is preferred. The optimized geometric structures of the migratory insertion transition states in current study are in good agreement with this hypothesis (Figures 2−5). In fact, the distance of the forming Ir−C bond is around 2.15 Å, very close to that in the resulting intermediates. In contrast, the forming C−C bond remains quite long (>1.95 Å). Therefore, in the current case, the developed positive charge at the Cα of (E)TS6 can be significantly stabilized by the strong electrondonating methoxy group, while no such stabilization is observed in (R)-TS10 and (S)-TS12, which thus results in the α-insertion into the Ir−C bond being favored compared to the β- and γ-insertion into the Ir−C bond. The NBO charge analysis further supports our conclusions (Scheme 6), showing



ORIGINS OF REGIOSELECTIVITY Having elucidated the detailed reaction mechanism and the origins of the enantioselectivity, in this section, we now turn our attention to the reactions leading to the formation of products 4 and 5, in which the aryl group is installed at the βand γ-carbon atom to the methoxy group, to explore the origins of the regioselectivity. For products (R)-4 and (S)-4, several possible pathways can be envisioned, since the reactions of intermediate INT2 with all allylic ethers 2 and 1-alkenyl ethers 6 could possibly afford these products. The calculations show that among these possibilities, the reactions of intermediate INT2 with allylic ethers (E)-2 and (Z)-2 are the most favorable ones for the formation of products (R)-4 and (S)-4, respectively (see Supporting Information for the results of the other possibilities). As shown in Figure 4, the formation of product (R)-4 was found to be slightly more favored than the formation of product (S)-4. The β-insertion of allylic ether (E)-2 into the Ir−C bond via transition state (R)-TS10 was calculated to be 0.9 kcal/mol lower in energy than the β-insertion of allylic ether (Z)-2 into the Ir−C bond via transition state (S)-TS10. This energy difference can be explained with the same reason given above. The dihedral angle C−Cβ−Cγ−Ir in transition state (R)-TS10 is −9.8°, while in transition state (S)-TS10 the dihedral angle C−Cβ−Cγ−Ir is 13.4° (Figure 4). Figure 5 shows the most favorable pathways leading to the formation of products (R)-5 and (S)-5 (see Supporting Information for the results of the other possibilities). The calculations show that both products (R)-5 and (S)-5 should be generated from the reactions of allylic ether (E)-2 with intermediate INT2. It was found that the γ-insertion of allylic ether (E)-2 into the Ir−C bond via transition state (S)-TS12, which can eventually lead to product (S)-5, is 1.3 kcal/mol lower than that through transition state (R)-TS12, leading to product (R)-5. To be noted, the dihedral angle C−Cγ−Cβ−Ir in transition state (S)-TS12 is −7.1°, while in transition state (R)-TS12, the dihedral angle C−Cβ−Cγ−Ir is 5.0°, which does not agree well with the explanation put forward above. However, in transition state (S)-TS12 a π−π interaction was found between the phenylpyridine moiety and the phenyl group of the (R)-binap ligand (3.78 Å, Figure 5), while no such interaction exists in transition state (R)-TS12, which may thus provide an additional stabilization to (S)-TS12. The results presented above show that the energy barriers of the formation of products 4 and 5 are higher than that for the formation of main product (S)-3, by at least 2.6 kcal/mol (Figures 2, 4, and 5). In addition, products 4 and 5 were calculated to be less stable than main product (S)-3, by at least 2.1 kcal/mol. These results indicate that the formation of main product (S)-3 is favored both kinetically and thermodynamically. Therefore, our calculations reproduce quite well the experimentally observed regioselectivity.11

Scheme 6. NBO Charge Analysis of Substrates 2 and 6

that in 1-alkenyl ethers 6, the strong electron-donating character of the methoxy group polarizes the C−C double bond, making the Cα positively charged and Cβ negatively charged with a considerable charge separation. On the other hand in allylic ethers 2, due to the presence of one carbon atom between the methoxy group and the C−C double bond, the methoxy group behaves as an electron-withdrawing group, with both Cβ and Cγ being negatively charged.



CONCLUSIONS To summarize, we have presented a comprehensive DFT study on the mechanism and origins of regio- and enantioselectivities of the iridium-catalyzed hydroarylation of alkenyl ethers. The results show that the reaction is initiated by a facile C−H oxidative addition to generate Ir(III) hydride intermediate, which can promote easily the isomerization between the allylic ethers and the 1-alkenyl ethers via the migratory insertion into the Ir−H bond/β-hydride elimination. Both Chalk−Harrodtype mechanism (migratory insertion into the Ir−H bond/C− C reductive elimination) and modified Chalk−Harrod-type mechanism (migratory insertion into the Ir−C bond/C−H reductive elimination) were considered, and the comparison of the energies shows that the reaction proceeds through the modified Chalk−Harrod-type mechanism. The migratory insertion into the Ir−C bond constitutes the rate- and selectivity-determining step of the overall reaction. The experimentally observed regio- and enantioselectivities were reproduced quite well by the calculations. The enantioselectivity of the reaction was found to arise from the reactions of the (E)- and (Z)-1-alkenyl ethers, which afford the opposite enantiomers of product with the aryl group installed at the α-position. The reaction of the (Z)-1-alkenyl ether is 2944

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(2) For selected reviews, see: (a) Nagamoto, M.; Nishimura, T. ACS Catal. 2017, 7, 833−847. (b) Pan, S.; Shibata, T. ACS Catal. 2013, 3, 704−712. (c) Crisenza, G. E. M.; Bower, J. F. Chem. Lett. 2016, 45, 2− 9. (3) For selected examples, see: (a) Lewis, J. C.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2007, 129, 5332−5333. (b) Bair, J. S.; Schramm, Y.; Sergeev, A. G.; Clot, E.; Eisenstein, O.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 13098−13101. (c) Fallon, B. J.; Derat, E.; Amatore, M.; Aubert, C.; Chemla, F.; Ferreira, F.; Perez-Luna, A.; Petit, M. J. Am. Chem. Soc. 2015, 137, 2448−2451. (d) Johnson, D. G.; Lynam, J. M.; Mistry, N. S.; Slattery, J. M.; Thatcher, R. J.; Whitwood, A. C. J. Am. Chem. Soc. 2013, 135, 2222−2234. (e) Yamamoto, S.; Saga, Y.; Andou, T.; Matsunaga, S.; Kanai, M. Adv. Synth. Catal. 2014, 356, 401−405. (f) Zhan, H.; Zhao, L.; Li, N.; Chen, L.; Liu, J.; Liao, J.; Cao, H. RSC Adv. 2014, 4, 32013−32016. (g) Andou, T.; Saga, Y.; Komai, H.; Matsunaga, S.; Kanai, M. Angew. Chem., Int. Ed. 2013, 52, 3213−3216. (h) Liu, C.; Han, X.; Wang, X.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126, 3700−3701. (i) Schinkel, M.; Wallbaum, J.; Kozhushkov, S. I.; Marek, I.; Ackermann, L. Org. Lett. 2013, 15, 4482− 4484. (j) Schinkel, M.; Marek, I.; Ackermann, L. Angew. Chem., Int. Ed. 2013, 52, 3977−3980. (k) Lim, S.-G.; Ahn, J.-A.; Jun, C.-H. Org. Lett. 2004, 6, 4687−4690. (l) Burgess, S. A.; Joslin, E. E.; Gunnoe, T. B.; Cundari, T. R.; Sabat, M.; Myers, W. H. Chem. Sci. 2014, 5, 4355− 4366. (m) McKeown, B. A.; Prince, B. M.; Ramiro, Z.; Gunnoe, T. B.; Cundari, T. R. ACS Catal. 2014, 4, 1607−1615. (n) Vaughan, B. A.; Webster-Gardiner, M. S.; Cundari, T. R.; Gunnoe, T. B. Science 2015, 348, 421−424. (o) Zell, D.; Bursch, M.; Müller, V.; Grimme, S.; Ackermann, L. Angew. Chem., Int. Ed. 2017, 56, 10378−10382. (4) For selected examples, see: (a) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993, 366, 529−531. (b) Okumura, S.; Tang, S.; Saito, T.; Semba, K.; Sakaki, S.; Nakao, Y. J. Am. Chem. Soc. 2016, 138, 14699−14704. (c) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. Angew. Chem., Int. Ed. 2010, 49, 4451−4454. (d) Nakao, Y.; Yamada, Y.; Kashihara, N.; Hiyama, T. J. Am. Chem. Soc. 2010, 132, 13666−13668. (e) Mukai, T.; Hirano, K.; Satoch, T.; Miura, M. J. Org. Chem. 2009, 74, 6410−6413. (f) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 16170−16171. (g) Chen, W.-C.; Lai, Y.-C.; Shih, W.-C.; Yu, M.S.; Yap, G. P. A.; Ong, T.-G. Chem. - Eur. J. 2014, 20, 8099−8105. (h) Lee, W.-C.; Wang, C.-H.; Lin, Y.-H.; Shih, W.-C.; Ong, T.-G. Org. Lett. 2013, 15, 5358−5361. (i) Shih, W.-C.; Chen, W.-C.; Lai, Y.-C.; Yu, M.-S.; Ho, J.-J.; Yap, G. P. A.; Ong, T.-G. Org. Lett. 2012, 14, 2046−2049. (j) Xu, W.; Yoshikai, N. Angew. Chem., Int. Ed. 2014, 53, 14166−14170. (k) Gao, K.; Yoshikai, N. J. Am. Chem. Soc. 2011, 133, 400−402. (l) Lee, P.-S.; Yoshikai, N. Angew. Chem., Int. Ed. 2013, 52, 1240−1244. (m) Lee, P.-S.; Yoshikai, N. Org. Lett. 2015, 17, 22−25. (n) Dong, J.; Lee, P.-S.; Yoshikai, N. Chem. Lett. 2013, 42, 1140−1142. (o) Xu, W.; Pek, J. H.; Yoshikai, N. Adv. Synth. Catal. 2016, 358, 2564−2568. (p) Xu, W.; Yoshikai, N. Angew. Chem., Int. Ed. 2016, 55, 12731−12735. (5) For selected examples, see: (a) Tsuchikama, K.; Kasagawa, M.; Hashimoto, Y.-K.; Endo, K.; Shibata, T. J. Organomet. Chem. 2008, 693, 3939−3942. (b) Dorta, R.; Togni, A. Chem. Commun. 2003, 760− 761. (c) Shibata, T.; Takano, H. Org. Chem. Front. 2015, 2, 383−387. (d) Takebayashi, S.; Shibata, T. Organometallics 2012, 31, 4114−4117. (e) Pan, S.; Ryu, N.; Shibata, T. Adv. Synth. Catal. 2014, 356, 929− 933. (f) Shibata, T.; Shizuno, T. Angew. Chem., Int. Ed. 2014, 53, 5410−5413. (g) Sevov, C. S.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 2116−2119. (h) Shibata, T.; Ryu, N.; Takano, H. Adv. Synth. Catal. 2015, 357, 1131−1135. (6) For related examples, see: (a) Xing, D.; Dong, G. J. Am. Chem. Soc. 2017, 139, 13664−13667. (b) Fernández, D. F.; Gulías, M.; Mascareñas, J. L.; López, F. Angew. Chem., Int. Ed. 2017, 56, 9541− 9545. (7) Pan, S.; Ryu, N.; Shibata, T. J. Am. Chem. Soc. 2012, 134, 17474− 17477. (8) (a) Crisenza, G. E. M.; McCreanor, N. G.; Bower, J. F. J. Am. Chem. Soc. 2014, 136, 10258−10261. For a related work, see:

disfavored due to the steric repulsion of the hydrogen atoms making the square-planar geometry of the migratory insertion distorted, while the insertion with the (E)-1-alkenyl ether is able to adopt the nearly ideal square-planar geometry, which thus results in the experimentally observed enantioselectivity. The regioselectivity of the reaction is mainly caused by the electronic effect of the alkoxy group. The strong electrondonating character of the alkoxy group can stabilize the developed positive charge of the α-insertion transition state, while in β- and γ-insertion transition states, no such effect is observed, thus favoring the α-insertion and leading to the aryl group being selectively installed at the α-position to the alkoxy group. The present results, together with our previous studies, may provide a general mechanistic scenario for iridium-catalyzed hydroarylations. The mechanistic insights and the origins of the regio- and enantioselectivities revealed by the DFT calculations should provide important implications for a better understanding of related olefin hydrofunctionalization reactions and the design of new catalytic systems. Computational studies on related olefin hydrofunctionalization reactions are currently ongoing in our laboratory.



ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00377. Additional computational results, computed energies, and Cartesian coordinates of all optimized structures (PDF)



AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Web: http://genpinghuang. weebly.com. ORCID

Genping Huang: 0000-0002-2249-1248 Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (No. 21503143) and the Natural Science Foundation of Tianjin (No. 16JCQNJC05600). Y.C. acknowledges the support from the Shenzhen Peacock Plan (No. 1208040050847074). We thank Prof. Stefano Santoro and Dr. Gang Lu for valuable discussions.



REFERENCES

(1) For selected reviews, see: (a) Catalytic Hydroarylation of CarbonCarbon Multiple Bonds; Ackermann, L.; Gunnoe, T. B.; Habgood, L. G., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, 2018. (b) Dong, Z.; Ren, Z.; Thompson, S. J.; Xu, Y.; Dong, G. Chem. Rev. 2017, 117, 9333−9403. (c) Yoshikai, N. Bull. Chem. Soc. Jpn. 2014, 87, 843−857. (d) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826− 834. (e) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731−1770. (f) Kitamura, T. Eur. J. Org. Chem. 2009, 2009, 1111− 1125. (g) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624−655. (h) Nakao, Y. Chem. Rec. 2011, 11, 242−251. (i) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879−5918. (j) Newton, C. G.; Wang, S.-G.; Oliveira, C. C.; Cramer, N. Chem. Rev. 2017, 117, 8908−8976. (k) Ping, L.; Chung, D. S.; Bouffard, J.; Lee, S.-g. Chem. Soc. Rev. 2017, 46, 4299−4328. 2945

DOI: 10.1021/acs.joc.8b00377 J. Org. Chem. 2018, 83, 2937−2947

Article

The Journal of Organic Chemistry

(24) (a) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32, 1456−1465. (b) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 154104−154119. (25) Adding the dispersion effects has been proven to significantly improve the performance of the B3LYP method. For selected examples, see: (a) Zheng, C.; Zhuo, C.-X.; You, S.-L. J. Am. Chem. Soc. 2014, 136, 16251−16259. (b) Xu, X.; Liu, P.; Lesser, A.; Sirois, L. E.; Wender, P. A.; Houk, K. N. J. Am. Chem. Soc. 2012, 134, 11012− 11025. (c) Yuan, R.; Lin, Z. ACS Catal. 2015, 5, 2866−2872. (e) Huang, G.; Kalek, M.; Himo, F. J. Am. Chem. Soc. 2013, 135, 7647−7659. (g) Huang, G.; Kalek, M.; Liao, R.-Z.; Himo, F. Chem. Sci. 2015, 6, 1735−1746. (h) Zhang, X.; Zou, H.; Huang, G. ChemCatChem 2016, 8, 2549−2556. (i) Wang, L.; Zou, H.; Zhang, X.; Huang, G. Org. Chem. Front. 2017, 4, 587−596. (j) Zou, H.; Wang, Z.-L.; Huang, G. Chem. - Eur. J. 2017, 23, 12593−12603. (k) Huang, G.; Diner, C.; Szabó, K. J.; Himo, F. Org. Lett. 2017, 19, 5904−5907. (l) Huang, G.; Xia, Y.; Sun, C.; Li, J.; Lee, D. J. Org. Chem. 2013, 78, 988−995. (m) Yu, S.; Liu, S.; Lan, Y.; Wan, B.; Li, X. J. Am. Chem. Soc. 2015, 137, 1623−1631. (n) Santoro, S.; Kalek, M.; Huang, G.; Himo, F. Acc. Chem. Res. 2016, 49, 1006−1018. (26) For selected examples, see: (a) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 5th ed.; Wiley: Hoboken, NJ, 2009; pp 229−231. (b) Werner, E. W.; Mei, T.-S.; Burckle, A. J.; Sigman, M. S. Science 2012, 338, 1455−1458. (c) Henriksen, S. T.; Tanner, D.; Cacchi, S.; Norrby, P.-O. Organometallics 2009, 28, 6201−6205. (d) Hamasaki, T.; Aoyama, Y.; Kawasaki, J.; Kakiuchi, F.; Kochi, T. J. Am. Chem. Soc. 2015, 137, 16163−16171. (e) Dang, Y.; Qu, S.; Wang, Z.-X.; Wang, X. J. Am. Chem. Soc. 2014, 136, 986−998. (27) As shown in below, the calculations show that the interconversion of INT2 to INT3 is feasible. Intermediate INT2 first isomerizes to INT2-a, which was calculated to be endergonic by 0.7 kcal/mol. Then INT2-a undergoes a ligand isomerization step to give intermediate INT2-b, from which the coordination of (E)-2 to the Ir center could give intermediate INT3. The overall energy barrier of this process is quite low, being 13.9 kcal/mol relative to INT2. We have also tried to locate the transition state connecting intermediates INT2-a and INT2-b, but the energy scan shows that there is no transition state existed between these intermediates.

(b) Crisenza, G. E. M.; Sokolova, O. O.; Bower, J. F. Angew. Chem., Int. Ed. 2015, 54, 14866−14870. (9) (a) Yamauchi, D.; Nishimura, T.; Yorimitsu, H. Chem. Commun. 2017, 53, 2760−2763. (b) Hatano, M.; Ebe, Y.; Nishimura, T.; Yorimitsu, H. J. Am. Chem. Soc. 2016, 138, 4010−4013. (c) Ebe, Y.; Nishimura, T. J. Am. Chem. Soc. 2015, 137, 5899−5902. (10) Shirai, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2015, 54, 9894− 9897. (11) Ebe, Y.; Onoda, M.; Nishimura, T.; Yorimitsu, H. Angew. Chem., Int. Ed. 2017, 56, 5607−5611. (12) Chalk, A. J.; Harrod, J. F. J. Am. Chem. Soc. 1965, 87, 16−21. (13) This alternative pathway that involves olefin migratory insertion into the M−C or M−X bond instead of M−H bond is referred to in the literature as the modified Chalk−Harrod mechanism. (a) Sakaki, S.; Sumimoto, M.; Fukuhara, M.; Sugimoto, M.; Fujimoto, H.; Matsuzaki, S. Organometallics 2002, 21, 3788−3802. (b) Sakaki, S.; Mizoe, N.; Sugimoto, M. Organometallics 1998, 17, 2510−2523. (14) For selected Ir(I)-catalyzed hydrofunctionalizations of alkenes, where the modified Chalk−Harrod mechanism was proposed, see: (a) Sevov, C. S.; Zhou, J.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 3200−3207. (b) Torigoe, T.; Ohmura, T.; Suginome, M. Angew. Chem., Int. Ed. 2017, 56, 14272−14276. (c) Sevov, C. S.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 9303−9306. (d) Sevov, C. S.; Zhou, J.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 11960−11963. (e) Zhou, J.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 12220−12221. (15) (a) Yang, Z.; Yu, H.; Fu, Y. Chem. - Eur. J. 2013, 19, 12093− 12103. (b) Jiang, Y.-Y.; Li, Z.; Shi, J. Organometallics 2012, 31, 4356− 4366. (c) Matsubara, T.; Koga, N.; Musaev, D. G.; Morokuma, K. Organometallics 2000, 19, 2318−2329. (d) Matsubara, T.; Koga, N.; Musaev, D. G.; Morokuma, K. J. Am. Chem. Soc. 1998, 120, 12692− 12693. (16) (a) Huang, G.; Liu, P. ACS Catal. 2016, 6, 809−820. (b) Zhang, M.; Huang, G. Dalton Trans. 2016, 45, 3552−3557. (17) For computational studies on transition metal-catalyzed C−H activations from our group, see: (a) Huang, G. Org. Lett. 2015, 17, 1994−1997. (b) Huang, G. J. Org. Chem. 2015, 80, 7564−7571. (c) Zhang, M.; Huang, G. Chem. - Eur. J. 2016, 22, 9356−9365. (d) Zou, H.; Wang, Z.-L.; Cao, Y.; Huang, G. Chin. Chem. Lett. 2017 DOI: 10.1016/j.cclet.2017.10.034. (18) (a) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785−789. (b) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett. 1989, 157, 200−206. (c) Becke, A. D. J. Chem. Phys. 1993, 98, 5648−5652. (19) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Nor-mand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford, CT, 2009. (20) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270−283. (21) (a) Fukui, K. J. Phys. Chem. 1970, 74, 4161−4163. (b) Fukui, K. Acc. Chem. Res. 1981, 14, 363−368. (22) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378−6396. (23) (a) Dolg, M.; Wedig, U.; Stoll, H.; Preuss, H. J. Chem. Phys. 1987, 86, 866−872. (b) Andrae, D.; Häußermann, U.; Dolg, M.; Stoll, H.; Preuß, H. Theor. Chem. Acc. 1990, 77, 123−141.

(28) Oxgaard, J.; Bhalla, G.; Periana, R. A.; Goddard, W. A., III Organometallics 2006, 25, 1618−1625. (29) Xu, L.; Hilton, M. J.; Zhang, X.; Norrby, P.-O.; Wu, Y.-D.; Sigman, M. S.; Wiest, O. J. Am. Chem. Soc. 2014, 136, 1960−1967. (30) (a) Datta, G. K.; von Schenck, H.; Hallberg, A.; Larhed, M. J. Org. Chem. 2006, 71, 3896−3903. (b) Gøgsig, T. M.; Kleimark, J.; Lill, S. O. N.; Korsager, S.; Lindhardt, A. T.; Norrby, P.-O.; Skrydstrup, T. J. Am. Chem. Soc. 2012, 134, 443−452. (c) von Schenck, H.; Strömberg, S.; Zetterberg, K.; Ludwig, M.; Åkermark, B.; Svensson, M. Organometallics 2001, 20, 2813−2819. (31) For selected computational studies of the regioselectivity in olefin migratory insertion into M−H and M−X bonds, see: (a) Dang, L.; Zhao, H.; Lin, Z.; Marder, T. B. Organometallics 2007, 26, 2824− 2832. (b) Yang, Y.; Liu, P. ACS Catal. 2015, 5, 2944−2951. (c) Fristrup, P.; Le Quement, S.; Tanner, D.; Norrby, P.-O. Organometallics 2004, 23, 6160−6165. (d) Guo, W.; Zhou, T.; Xia, Y. Organometallics 2015, 34, 3012−3020. (e) Hong, X.; Wang, J.; Yang, Y.-F.; He, L.; Ho, C.-Y.; Houk, K. N. ACS Catal. 2015, 5, 5545− 5555. (f) Nakamura, A.; Munakata, K.; Ito, S.; Kochi, T.; Chung, L. W.; Morokuma, K.; Nozaki, K. J. Am. Chem. Soc. 2011, 133, 6761− 6779. (g) Tye, J. W.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 14703−14712. (h) Liu, Y.; Tang, Y.; Jiang, Y.-Y.; Zhang, X.; Li, P.; Bi, S. ACS Catal. 2017, 7, 1886−1896. (i) Xu, Z.-Y.; Jiang, Y.-Y.; Su, W.; 2946

DOI: 10.1021/acs.joc.8b00377 J. Org. Chem. 2018, 83, 2937−2947

Article

The Journal of Organic Chemistry Yu, H.-Z.; Fu, Y. Chem. - Eur. J. 2016, 22, 14611−14617. (j) Lu, G.; Liu, R. Y.; Yang, Y.; Fang, C.; Lambrecht, D. S.; Buchwald, S. L.; Liu, P. J. Am. Chem. Soc. 2017, 139, 16548−16555. (k) Wu, J.; Xu, W.; Yu, Z.-X.; Wang, J. J. Am. Chem. Soc. 2015, 137, 9489−9496. (l) Edwards, A. J.; Macgregor, S. A.; Rae, A. D.; Wenger, E.; Willis, A. C. Organometallics 2001, 20, 2864−2877. (m) Macgregor, S. A.; Wenger, E. Organometallics 2002, 21, 1278−1289. (n) Yu, J.-L.; Zhang, S.-Q.; Hong, X. J. Am. Chem. Soc. 2017, 139, 7224−7243. (32) von Schenck, H.; Åkermark, B.; Svensson, M. J. Am. Chem. Soc. 2003, 125, 3503−3508.

2947

DOI: 10.1021/acs.joc.8b00377 J. Org. Chem. 2018, 83, 2937−2947