Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2020 Jun 15;5(25):15446–15453. doi: 10.1021/acsomega.0c01587

Density Functional Theory Study on the Mechanism of Iridium-Catalyzed Benzylamine ortho C–H Alkenylation with Ethyl Acrylate

Jiarong Wang 1, Baoping Ling 1,*, Peng Liu 1, Yuxia Liu 1, Yuan-Ye Jiang 1, Siwei Bi 1,*
PMCID: PMC7331057  PMID: 32637819

Abstract

graphic file with name ao0c01587_0009.jpg

Iridium-catalyzed oxidative o-alkenylation of benzylamines with acrylates was enabled by the directing group pentafluorobenzoyl (PFB). Density functional theory calculations were performed to explore the detailed reaction mechanism. The calculated results reveal that N-deprotonation prior to C–H activation is favored over direct C–H activation. Moreover, C–H activation is reversible and not the rate-determining step, which has been supported by the experimental observation. The regio- and stereoselectivity of ethyl acrylate insertion are controlled by the steric effect and the carbon atom with a larger orbital coefficient of the π* antibonding orbital in the nucleophilic attack, respectively. The migratory insertion of ethyl acrylate is computationally found to be rate-determining for the whole catalytic cycle. Finally, the seven-membered ring intermediate IM11 undergoes a sequential N-protonation and β-H elimination with the assistance of AcOH, rather than β-H elimination and reductive elimination proposed experimentally, to afford the o-alkenylated product. IM11 is unable to directly cyclize through C–N reductive elimination because both sp3-hybridized N and C atoms are unfavorable for N–C reductive elimination. The origin of the directing group PFB preventing the product and intermediates undergoing aza-Michael addition has been explained.

Introduction

Benzylamines, as a kind of cheap reactant, have been greatly developed in organic synthetic chemistry.1 In recent years, benzylamines have been used as units that are biologically active in the synthesis of drugs and chemical materials.2 In particular, they act as appropriate raw materials to make the ortho-substitution reaction possible in transition metal catalytic reactions.3 In previous studies, the ortho-alkenylation of a variety of arene compounds was achieved via direct C–H activation.4 However, the ortho-alkenylation of benzylamine substrates encounters great challenges, such as the oxidation of benzylamines,5 the limitation to the substrate benzylamine,6 the competition between C–H alkenylation and olefin hydroarylation,7 and the cyclization of alkenylation products via an intramolecular aza-Michael addition.8 For example, the Kim group9 reported a rhodium-catalyzed oxidative alkenylation of N-benzyltriflamides with olefins in 2014, but the product finally cyclized to afford the isoindolines. In 2015, Carretero and co-workers10 utilized the catalyst-controlled divergent heteroaryl/aryl functionalization of picolinamides to selectively yield isoquinoline or ortho-olefinated benzylamine derivatives. In 2016, Zhao and co-workers11 have reported rhodium(III)-catalyzed oxidative C–H/C–H cross-coupling of heteroarenes and masked benzylamines and presented a new synthesis approach of ortho-heteroarylated benzylamines under mild conditions. Therefore, the suitable directing group is needed to ensure the ortho-substitution and prevent further aza-Michael addition.

Recently, Fu and co-workers12 have developed a new approach to achieve the oxidative alkenylation of benzylamines (Scheme 1). In this reaction, pentafluorobenzoyl (PFB), a directing group which can efficiently prevent the product cyclization by aza-Michael addition, is required to control the ortho-alkenylation of benzylamines with ethyl acrylate. A possible mechanism proposed by the authors has been shown in Scheme 2. Amide nitrogen of benzylamine 1 coordinates to the active catalyst IrCp*(OAc)2 and then undergoes N–H deprotonation and C–H activation via concerted metalation–deprotonation (CMD) to afford the intermediate B. Next, the migratory insertion of ethyl acrylate 2a to the Ir–C bond gives the intermediate C. Sequential β-H elimination and reductive elimination processes take place to yield the alkenylated product 3 and an Ir(I) species. Finally the Ir(I) species is oxidized by AgOAc to regenerate the active catalyst Ir(III) species. In previous theoretical studies, the C–H alkenylation of anilines and tertiary benzylamines through direct β-H elimination and reductive elimination has been reported, in which either the sp2-hybridized N or C atom is favorable for N–C reductive elimination.13 Primary and secondary benzamides coupling with alkynes or alkenes to synthesize heterocycle compounds have been reported experimentally.14 In the current study, the actual sequence of β-H elimination and reductive elimination remains unclear and the role of the directing group PFB has not been explored. In addition, a kinetic isotope effect (KIE) value of 1.3 observed experimentally indicates that the ortho C–H activation is not involved in the rate-determining step, but the real rate-determining step is unclear. Moreover, the catalytic details of the alkenylation of secondary benzylamine bearing a special PFB directing group are still unclear. Therefore, a density functional theory (DFT) study has been conducted herein to reveal the detailed catalytic mechanism.

Scheme 1. Ir-Catalyzed ortho-Alkenylation of Benzylamine with Acrylate by Fu et al.12.

Scheme 1

Open in a new tab

Scheme 2. Possible Reaction Mechanism Proposed by Fu et al.12.

Scheme 2

Open in a new tab

Computational Details

All the DFT calculations were carried out with the Gaussian 09 program.15 Geometry optimizations and frequency calculations for all the intermediates and transition states were conducted at the M06 level of theory16 in conjugation with the ultrafine grid.17 The BS1 mixed basis set designates that the effective core potential of Hay and Wadt with a double-ζ basis set (LANL2DZ)18 is used for Ir (ζf = 0.938) and the 6-31G(d,p) basis set19 is used for C, O, N, F, Cl, and H atoms. Intrinsic reaction coordinate calculations were performed to trace the reaction pathway. Vibration frequency calculations were conducted at the same level to achieve the thermodynamic corrections. Each minima has zero imaginary frequency, while each transition state has only one imaginary frequency.

The solvent effect was treated with a self-consistent reaction field using the SMD model.20 Single-point calculations were performed using the larger basis set 6-311++G(d,p) for C, O, N, F, Cl, and H atoms and SDD for Ir, which is denoted as the BS2 mixed basis set. Chlorobenzene (PhCl) was used as the solvent with a dielectric constant value of 5.61. For comparison, other level calculations for the key intermediates and transition state, such as B3LYP,21 M06L,22 and B97XD,23 were included, in Table S1. The calculated results show that the M06 functional is more appropriate in comparison with other functionals. Thus, all the energies discussed in the current study are the relative Gibbs free energies in the PhCl solvent with thermodynamic corrections in the gas phase using the M06 functional.16 Atomic orbital analysis and noncovalent interaction (NCI) analysis are implemented using the Multiwfn program,24 and the NCI isosurfaces are generated using the VMD 1.9.3 program.25

Results and Discussion

In the catalytic reaction system, several species are added to control the reaction condition. Based on the experimental and calculated results, the Cp*Ir(OAc)2 species Cat is selected as the active catalyst and the zero energy reference (Supporting Information, Figure S1).26 According to the calculated results, the reaction mechanism can be divided into three stages: N–H deprotonation and C–H activation (stage I), migratory insertion of ethyl acrylate (stage II), and the ortho-alkenylation of benzylamine and catalyst regeneration (stage III).

Stage I: N–H Deprotonation and C–H Activation.

According to the proposed mechanism in Scheme 2, the energy profile for N–H deprotonation and C–H activation is given in Figure 1. First, the active catalyst Cat interacts with 1 to form the N-coordinated intermediate IM1, which then undergoes the N–H deprotonation process via a CMD pathway27 to give IM3. This step needs to overcome an overall energy barrier of 18.6 kcal/mol (TS2 relative to Cat). After dissociation of HOAc, the intermediate IM3-2O converts to IM5 via structural isomerization. Subsequently, C–H activation occurs to yield a five-membered iridacycle IM7 via TS6 with an overall barrier of 21.6 kcal/mol (TS6 relative to Cat), and release of the resulting HOAc molecule generates the more stable five-membered iridacycle IM8.

Figure 1.

Figure 1

Open in a new tab

Calculated energy profile for N–H deprotonation and C–H activation. The relative Gibbs energies and relative enthalpic energies (in parentheses) are given in kcal/mol.

Additionally, an alternative pathway for C–H activation was also considered (Figure S2), where the N–H keeps intact. However, this pathway is excluded because of a high overall energy barrier of 29.8 kcal/mol.

Stage II: Migratory Insertion of Ethyl Acrylate.

Theoretical explanations for selective alkene insertion into the TM–C bond have been previously reported,28 depending on the different electronic densities at the two carbon atoms of alkenes. The regio- and stereoselectivity for ethyl acrylate insertion are also considered, as shown in Figure 2. Starting from IM8, ethyl acrylate 2a inserts into the Ir(III)–C bond to achieve the possible seven-membered iridacycle intermediates. In path I, the carbon atom linking to the ester substituent of 2a takes a nucleophilic attack on the Ir(III) center to give the desired seven-membered intermediate IM11, and this pathway overcomes an overall energy barrier of 27.8 kcal/mol (TS10 relative to IM8). In path II, the terminal alkenyl carbon of 2a couples with the Ir(III) center to finish the insertion of 2a (step IM8 → IM11′), and this process requires an overall energy barrier of 36.8 kcal/mol, which is higher by 9.0 kcal/mol than that in path I. Thus, the insertion of 2a in path I is more favorable, and this can be understood by means of molecular orbital interactions. The carbon from Ir–C takes a nucleophilic attack at the alkenyl carbon of ethyl acrylate 2a, and the larger orbital coefficient of the π* antibonding orbital of 2a is more favorable for the insertion. According to the calculated results in Figure 3A, the coefficients of C1 and C4 are 36.8% and 20.8%, respectively. Clearly, the nucleophilic attack with the carbon from Ir–C at C1 of 2a is approved over that at C4 of 2a. Thus, the regioselectivity of 2a insertion is determined by the larger orbital coefficient of the π* antibonding orbital of 2a, and this result is consistent with that of previous theoretical investigations.13c,24c In addition, insertions of 2a with the ester group proximate to benzylamine (path III and IV) are unfavorable because of the steric effect, which is verified by the NCI analysis, in Figure 4. One can see that the steric repulsions between the ester group and the directing group PFB in TS10 and TS10′are obviously smaller than those in TS10-a and TS10-b, respectively, predicting that the stereoselectivity of 2a insertion is determined by the steric effect.

Figure 2.

Figure 2

Open in a new tab

Calculated energy profiles for the insertion of ethyl acrylate 2a. The relative Gibbs energies and relative enthalpic energies (in parentheses) are given in kcal/mol.

Figure 3.

Figure 3

Open in a new tab

Lowest unoccupied molecular orbitals of alkenes with spatial plots and atomic contributions (isovalue = 0.02). (A) Ethyl acrylate 2a and (B) methoxyethene 2b.

Figure 4.

Figure 4

Open in a new tab

Noncovalent interaction analyses for the transition states TS10 (A), TS10-a (B), TS10′ (C), and TS10-b (D). Blue, green, and red surfaces represent the strong attraction, weak interaction, and steric effect, respectively.

We have also considered the influence of the electron-donating group of methoxyethene 2b on its regioselectivity of insertion. The calculated free energy profiles, as shown in Figure S3, and the atomic contributions, in Figure 3B, show that the nucleophilic attack of the carbon from Ir–C on C4 of 2b with the larger orbital coefficient is favored, and this result further supported the abovementioned calculated regioselectivity of alkenyl insertion. Additionally, the influence of the directing group of benzylamine on the reactivity has also been considered. When the directing group PFB is replaced with 2,6-dimethylbenzoyl, the overall energy barrier of step IM8″ → IM11″ is calculated to be 31.4 kcal/mol (Figure S4), further indicating that the strong electron-withdrawing directing group is vital to improve the reactivity, which is in agreement with the experimental results.12

Taken together, starting from IM8, the insertion of 2a is favored by the nucleophilic attack of carbon from the Ir–C bond on the larger orbital coefficient of the π* antibonding orbital of 2a, and this process overcomes an energy barrier of 27.8 kcal/mol. The formation of IM8 via C–H activation (IM5 → IM8 via TS6 in Figure 1) requires an energy barrier of 21.6 kcal/mol, while the reverse reaction (IM8 → IM5) overcomes an overall energy barrier of 22.1 kcal/mol. Both data are lower than those of 2a insertion; thus, we predict that the C–H activation process is reversible, which has been demonstrated by the H/D exchange experiments.12

Stage III: Catalyst Regeneration and the ortho-Alkenylation of Benzylamine.

Starting from IM11, several plausible reaction pathways with the corresponding energy barrier have been proposed and examined, as shown in Scheme 3. In case I, the sequential β-hydride elimination and reductive elimination steps, as shown in Scheme 2 (C → Cp*Ir(I)), occur to afford the alkenylated product, and this case undergoes TS15-a to give IM16-a with an overall energy barrier of 37.8 kcal/mol. The detailed energy profiles of case I are given in Figure S5. In addition, starting from IM14-a, it first undergoes a dissociation isomerization of the double bond to give IM17-b, which is followed by reductive elimination to generate IM20-b via TS19-b. However, the overall energy barrier is calculated to be as high as 43.1 kcal/mol (Figure S5). Thus, case I is ruled out. In case II, the N–C bond formation via a direct reductive elimination starting from IM11 is explored. Clearly, case II is difficult to occur with an extremely high energy barrier of 70.5 kcal/mol (Figure S6) because both sp3-hybridized C and N atoms are unfavorable for N–C reductive elimination.13 In case III, 1,2-H migration assisted by the Ir center and C–N reductive elimination take place to generate the five-membered ring intermediate IM19-d. Starting from IM11, β-H elimination occurs to afford the intermediate IM14-a, as shown in Figure S5, which undergoes isomerization to achieve IM15-d (Figure S7). Then, H-migration to the ortho-carbon atom and C–N reductive elimination occur to deliver the five-membered ring intermediate IM19-d via TS18-d. Likewise, this pathway is also infeasible with an extremely high energy barrier of 60.1 kcal/mol (TS18-d relative to IM17-d) because both N and C atoms, for reductive elimination in TS18-d, are sp3-hybridized. In case IV, N-protonation and reductive elimination processes are finished with the assistance of acetic acid. This pathway overcomes an overall energy barrier (IM11 → IM14 via TS13) of 18.1 kcal/mol, and the detailed calculated results are given in Figure 5. Therefore, we concluded that case IV is the most favorable pathway starting from IM11.

Scheme 3. Plausible Pathways Proposed Starting from IM11.

Scheme 3

Open in a new tab

Figure 5.

Figure 5

Open in a new tab

Calculated energy profiles for the catalyst regeneration and o-alkenylation product of benzylamine. The relative Gibbs energies and relative enthalpic energies (in parentheses) are given in kcal/mol.

As shown in Figure 5, acetic acid coordinates with IM11 to afford IM12 in which the hydroxyl of acetic acid forms a hydrogen bond with the nitrogen atom of benzylamine. Then, the nitrogen atom is protonated by acetic acid to deliver IM14 via TS13 with a free energy barrier of 18.1 kcal/mol relative to IM11. IM14 isomerizes to the more stable IM15 through nitrogen atom dissociation, and then, β-H elimination takes place to yield IM17 via TS16. Subsequently, the hydride was transferred from the Ir(III) center to acetate via reductive elimination to generate acetic acid and the Ir(I) complex IM19, which overcomes an energy barrier of 11.9 kcal/mol (TS18 vs IM15). Finally, acetic acid dissociates from IM19 to afford the Cp*Ir(I) complex IM20 with the lower energy (Figure S8), which releases the desired o-alkenylation product of benzylamine, and Cp*Ir(I) is oxidized by the additive AgOAc to regenerate the catalyst. This process occurs easily with an overall energy barrier of 18.1 kcal/mol (IM11 → IM14 via TS13). Additionally, an alternative pathway starting from IM14 is also considered, as shown in Figure S9. IM14 first isomerizes to IM15′ through a κ1–κ2 transformation of acetate; then, IM15′ undergoes a sequential β-H elimination and hydride migration to yield the Z-configuration product. However, this pathway requires an overall energy barrier of 25.5 kcal/mol (TS18′ vs IM11), which is higher by 7.4 kcal/mol than that of the abovementioned pathway and thus it is ruled out. Comparing TS18′ (Figure S9) with TS18 (Figure 5), an energy difference of 9.0 kcal/mol results from the larger steric hindrance between the aromatic ring and ester group in the Z-configuration transition state TS18′.

Taken together, the formation of five- and six-membered ring intermediates in cases II and III needs to experience a direct C–N reductive elimination, but this process is infeasible because both sp3-hybridized N and C atoms are unfavorable for the direct reductive elimination. In contrast, the ortho-alkenylated product in case IV is formed with the assistance of AcOH without undergoing a cyclization process, which is more facile to occur. For the entire catalytic process, the migratory insertion of ethyl acrylate is the rate-determining step with an overall energy barrier of 27.8 kcal/mol, which is higher than that of the C–H activation by 6.2 kcal/mol. This result is supported by the KIE experiment, and a KIE value of 1.3 suggests that the ortho C–H bond activation is not involved in the rate-determining step.12

In addition, the role of the directing group PFB has been investigated, and the diverse plausible pathways for the aza-Michael addition of the product or intermediates, as shown in Figure S10, have been considered. First, product 3 undergoes a direct intramolecular aza-Michael addition to form 3′ in the absence of the catalyst (Figure S10A). However, this pathway is ruled out because of the ring strain presented in the four-membered transition state P′-ts with an overall free energy barrier of 61.0 kcal/mol. Then, aza-Michael addition has been taken into account in the presence of the catalyst (Figure S10B). Staring from IM15-d, C(sp2)-N reductive elimination occurs via TS16-e to give IM17-e, which is followed by hydride migration to obtain the aza-Michael addition product, but the relative free energy of TS16-e is calculated to be 38.9 kcal/mol, which is higher by 20.2 kcal/mol than that of IM14, in Figure 5 and thus it is also excluded. Additionally, aza-Michael addition reaction in the presence of the catalyst and the base acetate has also been considered, as shown in Figure S10C. IM20-c experiences N-deprotonation with the assistance of acetate via a barrierless process; then, C(sp2)-N reductive elimination takes place to afford IM21-AcO. This pathway is infeasible because of an overall free energy barrier of 48.4 kcal/mol. Therefore, the directing group PFB could effectively prevent the product or intermediates undergoing cyclization via an aza-Michael addition.

Conclusions

We herein report a detailed catalytic mechanism of iridium-catalyzed benzylamine ortho C–H alkenylation with ethyl acrylate through DFT calculations. This mechanism involves N-deprotonation, C–H activation, the insertion of ethyl acrylate, N-protonation with the assistance of acetate acid, β-H elimination, and reductive elimination processes. The N-deprotonation prior to C–H activation via the CMD process is favored over direct C–H activation, and the C–H activation process is reversible, which has been demonstrated by the H/D exchange experiment. The migratory insertion of ethyl acrylate is the rate-determining step with an overall energy barrier of 27.8 kcal/mol, which is higher than that of the C–H activation process by 6.2 kcal/mol and supported by the KIE experiment. Furthermore, the migratory insertion of ethyl acrylate is finished through a nucleophilic attack of the carbon from Ir–C on C1 with a larger atomic orbital coefficient of ethyl acrylate. In contrast to the plausible mechanism by the Fu group12 where the intermediate C was proposed to undergo sequential β-H elimination and reductive elimination steps to afford the alkenylation product, the calculated results reveal successive N-protonation, β-H elimination, and reductive elimination processes with the assistance of acetic acid, giving the ortho-alkenylation product benzylamine and Cp*Ir(I). Finally, Cp*Ir(I) is further oxidized by AgOAc to regenerate the catalyst. Six- and seven-membered ring intermediates are unable to directly cyclize to form cycloaddition products because N–C reductive elimination is difficult to occur for both sp3-hybridized N and C atoms, and the directing group PFB plays an essential role in preventing the product or intermediates from cyclizing via an aza-Michael addition.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (nos. 21873055 and 21702119), the Natural Science Foundation of Shandong Province (nos. ZR2019MB016 and ZR2017QB001), and the High Performance Computing Center of Qufu Normal University.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c01587.

  • Relative free energies and enthalpies calculated using different functionals, relative stabilities of various species in the reaction system, and calculated energy profiles of unfavored pathways (PDF)

  • Cartesian coordinates and calculated energies (in hartrees) of all structures presented herein (XYZ)

The authors declare no competing financial interest.

Supplementary Material

ao0c01587_si_001.pdf (839.5KB, pdf)
ao0c01587_si_002.xyz (382KB, xyz)

References

  1. a Madia V. N.; Messore A.; Pescatori L.; Saccoliti F.; Tudino V.; De Leo A.; Bortolami M.; Scipione L.; Costi R.; Rivara S.; Scalvini L.; Mor M.; Ferrara F. F.; Pavoni E.; Roscilli G.; Cassinelli G.; Milazzo F. M.; Battistuzzi G.; Di Santo R.; Giannini G. Novel benzazole derivatives endowed with potent antiheparanase activity. J. Med. Chem. 2018, 61, 6918–6936. 10.1021/acs.jmedchem.8b00908. [DOI] [PubMed] [Google Scholar]; b Abonia R.; Garay A.; Castillo J.; Insuasty B.; Quiroga J.; Nogueras M.; Cobo J.; Butassi E.; Zacchino S. Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents. Molecules 2018, 23, 520. 10.3390/molecules23030520. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Hirashima S.-i.; Narushima T.; Kawada M.; Nakashima K.; Hanai K.; Koseki Y.; Miura T. Asymmetric conjugate additions of carbonyl compounds to nitroalkenes under solvent-free conditions using fluorous diaminomethylenemalononitrile organocatalyst. Chem. Pharm. Bull. 2017, 65, 1185–1190. 10.1248/cpb.c17-00596. [DOI] [PubMed] [Google Scholar]; d Casimiro L.; Groppi J.; Baroncini M.; La Rosa M.; Credi A.; Silvi S. Photochemical investigation of cyanoazobenzene derivatives as components of artificial supramolecular pumps. Photochem. Photobiol. Sci. 2018, 17, 734–740. 10.1039/c8pp00062j. [DOI] [PubMed] [Google Scholar]
  2. a Yang S.; Cheng R.; Zhao T.; Luo A.; Lan J.; You J. Rhodium-catalyzed C–H/C–H cross coupling of benzylthioethers or benzylamines with thiophenes enabled by flexible directing groups. Org. Lett. 2019, 21, 5086–5090. 10.1021/acs.orglett.9b01679. [DOI] [PubMed] [Google Scholar]; b Purkait A.; Jana C. K. N-aminations of benzylamines and alicyclic amines with nitrosoarenes to hydrazones and hydrazides. Synthesis 2019, 51, 2687–2696. 10.1055/s-0037-1610701. [DOI] [Google Scholar]; c Liu Y.; Afanasenko A.; Elangovan S.; Sun Z.; Barta K. Primary benzylamines by efficient N-Alkylation of benzyl alcohols using commercial Ni catalysts and easy-to-handle ammonia sources. ACS Sustainable Chem. Eng. 2019, 7, 11267–11274. 10.1021/acssuschemeng.9b00619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. a Mulet C.; Escolano M.; Llopis S.; Sanz S.; Ramírez de Arellano C.; Sánchez-Roselló M.; Fustero S.; del Pozo C. Dual role of vinyl sulfonamides as N-nucleophiles and Michael acceptors in the enantioselective synthesis of bicyclic delta-sultams. Adv. Synth. Catal. 2018, 360, 2885–2893. 10.1002/adsc.201800548. [DOI] [Google Scholar]; b Hu Y.; Xie Y.; Shen Z.; Huang H. Palladium-catalyzed ring-forming aminoalkenylation of alkenes with aldehydes initiated by intramolecular aminopalladation. Angew. Chem., Int. Ed. 2017, 56, 2473–2477. 10.1002/anie.201611853. [DOI] [PubMed] [Google Scholar]; c Hu Y.; Shen Z.; Huang H. Palladium-catalyzed intramolecular hydroaminocarbonylation to lactams: additive-free protocol initiated by palladium hydride. ACS Catal. 2016, 6, 6785–6789. 10.1021/acscatal.6b01939. [DOI] [Google Scholar]; d Kapoor M.; Chand-Thakuri P.; Young M. C. Carbon dioxide-mediated C(sp2)–H arylation of primary and secondary benzylamines. J. Am. Chem. Soc. 2019, 141, 7980–7989. 10.1021/jacs.9b03375. [DOI] [PubMed] [Google Scholar]; e Ogiwara Y.; Tamura M.; Kochi T.; Matsuura Y.; Chatani N.; Kakiuchi F. Ruthinium-catalyzed ortho-selective C-H alkenylation of aromatic compounds with alkenyl esters and ethers. Organometallics 2014, 33, 402–420. 10.1021/om401204h. [DOI] [Google Scholar]; f Lin H.; Pan X.; Barsamian A. L.; Kamenecka T. M.; Bannister T. D. Native directed site-selective δ-C(sp3)-H and δ-C(sp2)-H arylation of primary amines. ACS Catal. 2019, 9, 4887–4891. 10.1021/acscatal.8b04927. [DOI] [Google Scholar]; g Pramanick P. K.; Zhou Z.; Hou Z.-L.; Yao B. Free amino group-directed γ-C(sp3)–H arylation of α-amino esters with diaryliodonium triflates by palladium catalysis. J. Org. Chem. 2019, 84, 5684–5694. 10.1021/acs.joc.9b00605. [DOI] [PubMed] [Google Scholar]
  4. a Wang S.-M.; Moku B.; Leng J.; Qin H.-L. Rh-catalyzed carboxylates directed C–H activation for the synthesis of ortho-carboxylic 2-arylethenesulfonyl fluorides: access to unique electrophiles for SuFEx click chemistry. Eur. J. Org. Chem. 2018, 4407–4410. 10.1002/ejoc.201800762. [DOI] [Google Scholar]; b Lv H.; Shi J.; Huang J.; Zhang C.; Yi W. Rhodium(III)-catalyzed and MeOH-involved regioselective monoalkenylation of N-aryureas with acrylates. Org. Biomol. Chem. 2017, 15, 7088–7092. 10.1039/c7ob01627a. [DOI] [PubMed] [Google Scholar]; c Patureau F. W.; Glorius F. Rh catalyzed olefination and vinylation of unactivated acetanilides. J. Am. Chem. Soc. 2010, 132, 9982–9983. 10.1021/ja103834b. [DOI] [PubMed] [Google Scholar]
  5. Deb A.; Hazra A.; Peng Q.; Paton R. S.; Maiti D. Detailed Mechanistic Studies on Palladium-catalyzed selective C–H olefination with aliphatic alkenes: a significant influence of proton shuttling. J. Am. Chem. Soc. 2017, 139, 763–775. 10.1021/jacs.6b10309. [DOI] [PubMed] [Google Scholar]
  6. Manikandan R.; Madasamy P.; Jeganmohan M. Ruthenium-catalyzed ortho alkenylation of aromatics with alkenes at room temperature with hydrogen evolution. ACS Catal. 2016, 6, 230–234. 10.1021/acscatal.5b02218. [DOI] [Google Scholar]
  7. a Ebe Y.; Onoda M.; Nishimura T.; Yorimitsu H. Iridium-catalyzed regio- and enantioselective hydroarylation of alkenyl ethers by olefin isomerization. Angew. Chem., Int. Ed. 2017, 56, 5607–5611. 10.1002/anie.201702286. [DOI] [PubMed] [Google Scholar]; b Grélaud S.; Cooper P.; Feron L. J.; Bower J. F. Branch-selective and enantioselective iridium-catalyzed alkene hydroarylation via anilide-directed C–H oxidative addition. J. Am. Chem. Soc. 2018, 140, 9351–9356. 10.1021/jacs.8b04627. [DOI] [PubMed] [Google Scholar]; c Huang G.; Liu P. Mechanism and origins of ligand-controlled linear versus branched selectivity of iridium-catalyzed hydroarylation of alkenes. ACS Catal. 2016, 6, 809–820. 10.1021/acscatal.5b02201. [DOI] [Google Scholar]
  8. Morita T.; Satoh T.; Miura M. Rhodium(III)-catalyzed ortho-alkenylation of anilines directed by a removable boc-protecting group. Org. Lett. 2017, 19, 1800–1803. 10.1021/acs.orglett.7b00569. [DOI] [PubMed] [Google Scholar]
  9. Mishra N. K.; Park J.; Sharma S.; Han S.; Kim M.; Shin Y.; Jang J.; Kwak J. H.; Jung Y. H.; Kim I. S. Direct access to isoindolines through tandem Rh(iii)-catalyzed alkenylation and cyclization of N-benzyltriflamides. Chem. Commun. 2014, 50, 2350–2352. 10.1039/c3cc49486a. [DOI] [PubMed] [Google Scholar]
  10. Martínez Á. M.; Echavarren J.; Alonso I.; Rodríguez N.; Gómez Arrayás R.; Carretero J. C. RhI/RhIII catalyst-controlled divergent aryl/heteroaryl C-H bond functionalization of piconamides with alkynes. Chem. Sci. 2015, 6, 5802–5814. 10.1039/c5sc01885d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hu J.; Li G.; Yuan C.; Huang Z.-B.; Shi D.-Q.; Zhao Y. Rhodium(III)-catalyzed oxidative C–H/C–H cross-coupling of heteroarenes and masked benzylamines. Org. Lett. 2016, 18, 5998–6001. 10.1021/acs.orglett.6b02773. [DOI] [PubMed] [Google Scholar]
  12. Yang X.; Sun R.; Zhang C.; Zheng X.; Yuan M.; Fu H.; Li R.; Chen H. Iridium-catalyzed benzylamine C–H alkenylation enabled by pentafluorobenzoyl as the directing group. Org. Lett. 2019, 21, 1002–1006. 10.1021/acs.orglett.8b04005. [DOI] [PubMed] [Google Scholar]
  13. a Chen W.-J.; Lin Z. Rhodium(III)-catalyzed hydrazine-directed C-H activation for indole synthesis: mechanism and role of internal oxidant probed by DFT studies. Organometallics 2015, 34, 309–318. 10.1021/om501130c. [DOI] [Google Scholar]; b Ajitha M. J.; Huang K.-W. Mechanism and regioselectivity of Rh(III)-catalyzed intermolecular annulation of aryl-substituted diazenecarboxylates and alkenes: DFT insights. Organometallics 2016, 35, 450–455. 10.1021/acs.organomet.5b00831. [DOI] [Google Scholar]; c Leitch J. A.; Wilson P. B.; McMullin C. L.; Mahon M. F.; Bhonoah Y.; Williams I. H.; Frost C. G. Ruthenium(II)-catalyzed C-H functionalization using the oxazolidinone heterocycle as a weakly coordinating directing group: experimental and computational insights. ACS Catal. 2016, 6, 5520–5529. 10.1021/acscatal.6b01370. [DOI] [Google Scholar]; d Tamizmani M.; Gouranga N.; Jeganmohan M. Rhodium(III)-catalyzed ortho-alkenylation ofanilides with maleimides. ChemistrySelect 2019, 4, 2976–2981. 10.1002/slct.201900522. [DOI] [Google Scholar]
  14. a Song G.; Chen D.; Pan C.-L.; Crabtree R. H.; Li X. Rh-catalyzed oxidative coupling between primary and secondary benzamides and alkynes: synthesis of polycyclic amides. J. Org. Chem. 2010, 75, 7487–7490. 10.1021/jo101596d. [DOI] [PubMed] [Google Scholar]; b Suzuki C.; Morimoto K.; Hirano K.; Satoh T.; Miura M. Ruthenium- and rhodium-catalyzed dehydrogenative ortho-alkenylation of benzulamines via free amino group directed C-H bond cleavage. Adv. Synth. Catal. 2014, 356, 1521–1526. 10.1002/adsc.201400088. [DOI] [Google Scholar]; c Manikandan R.; Jeganmohan M. Recent advances in the ruthenium(II)-catalyzed chelation-assisted C-H olefination of substituted aromatics, alkenes and heteroaromatics with alkynes via the deprotonation pathway. Chem. Commun. 2017, 53, 8931–8947. 10.1039/c7cc03213g. [DOI] [PubMed] [Google Scholar]
  15. 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.; Normand J.; Raghavachari K.; Rendell A.; Burant J. C.; Iyengar S. S.; Tomasi J.; Cossi M.; Rega N.; Millam J. M.; Klene M.; Knox J. E.; Cross J. B.; Bakken V.; Adamo C.; Jaramillo J.; Gomperts R.; Stratmann R. E.; Yazyev O.; Austin A. J.; Cammi R.; Pomelli C.; Ochterski J. W.; Martin R. L.; Morokuma K.; Zakrzewski V. G.; Voth G. A.; Salvador P.; Dannenberg J. J.; Dapprich S.; Daniels A. D.; Farkas O.; Foresman J. B.; Ortiz J. V.; Cioslowski J.; Fox D. J.. Gaussian 09; Gaussian, Inc.: Wallingford, CT, 2009.
  16. a Zhao Y.; Truhlar D. G. Density functionals with broad applicability in chemistry. Acc. Chem. Res. 2008, 41, 157–167. 10.1021/ar700111a. [DOI] [PubMed] [Google Scholar]; b Zhao Y.; Truhlar D. G. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor. Chem. Acc. 2008, 120, 215–241. 10.1007/s00214-007-0310-x. [DOI] [Google Scholar]; c Truhlar D. G. Molecular modeling of complex chemical systems. J. Am. Chem. Soc. 2008, 130, 16824–16827. 10.1021/ja808927h. [DOI] [PubMed] [Google Scholar]; d Zhao Y.; Truhlar D. G. Benchmark energetic data in a model system for grubbs II metathesis catalysis and their use for the development, assessment, and validation of electronic structure methods. J. Chem. Theory Comput. 2009, 5, 324–333. 10.1021/ct800386d. [DOI] [PubMed] [Google Scholar]
  17. For the comments on utilizing ultrafine grid in DFT calculations; a Gräfenstein J.; Izotov D.; Cremer D. Avoiding singularity problems associated with meta-GGA (generalized gradient approximation) exchange and correlation functionals containing the kinetic energy density. J. Chem. Phys. 2007, 127, 214103. 10.1063/1.2800011. [DOI] [PubMed] [Google Scholar]; b Johnson E. R.; Becke A. D.; Sherrill C. D.; DiLabio G. A. Oscillations in meta-generalized-gradient approximation potential energy surfaces for dispersion-bound complexes. J. Chem. Phys. 2009, 131, 034111. 10.1063/1.3177061. [DOI] [PubMed] [Google Scholar]; c Wheeler S. E.; Houk K. N. Integration grid errors for meta-GGA-predicted reaction energies: origin of grid errors for the M06 suite of functionals. J. Chem. Theory Comput. 2010, 6, 395–404. 10.1021/ct900639j. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Jiang Y.-Y.; Man X.; Bi S. Advances in theoretical study on transition-metal-catalyzed C-H activation. Sci. China: Chem. 2016, 59, 1448–1466. 10.1007/s11426-016-0330-3. [DOI] [Google Scholar]
  18. a Wadt W. R.; Hay P. J. Ab initio effective core potentials for molecular calculations. Potentials for main group elements Na to Bi. J. Chem. Phys. 1985, 82, 284–298. 10.1063/1.448800. [DOI] [Google Scholar]; b Hay P. J.; Wadt W. R. Ab initio effective core potentials for molecular calculations. Potentials for K to Au including the outermost core orbitals. J. Chem. Phys. 1985, 82, 299–310. 10.1063/1.448975. [DOI] [Google Scholar]
  19. Huzinaga S. Basis sets for molecular calculations. Comput. Phys. Rep. 1985, 2, 281–339. 10.1016/0167-7977(85)90003-6. [DOI] [Google Scholar]
  20. a Dolg M.; Wedig U.; Stoll H.; Preuss H. Energy-adjusted abinitio pseudopotentials for the first row transition elements. J. Chem. Phys. 1987, 86, 866–872. 10.1063/1.452288. [DOI] [Google Scholar]; b Andrae D.; Häußermann U.; Dolg M.; Stoll H.; Preuß H. Energy-adjusted abinitio pseudopotentials for the 2nd and 3rd row transition-elements. Theor. Chim. Acta 1990, 77, 123–141. 10.1007/bf01114537. [DOI] [Google Scholar]
  21. a Becke A. D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 1993, 98, 5648–5652. 10.1063/1.464913. [DOI] [Google Scholar]; b Lee C.; Yang W.; Parr R. G. Development of the colle-salvetti correlationenergy formula into a functional of the electron density. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785–789. 10.1103/physrevb.37.785. [DOI] [PubMed] [Google Scholar]
  22. Zhao Y.; Truhlar D. G. A new local density functional for main-group thermochemistry, transition metal bonding, thermochemical kinetics, and noncovalent interactions. J. Chem. Phys. 2006, 125, 194101. 10.1063/1.2370993. [DOI] [PubMed] [Google Scholar]
  23. Chai J.-D.; Head-Gordon M. Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections. Phys. Chem. Chem. Phys. 2008, 10, 6615–6620. 10.1039/b810189b. [DOI] [PubMed] [Google Scholar]
  24. a Lu T.; Chen F. Multiwfn: a multifunctional wavefunction analyzer. J. Comput. Chem. 2012, 33, 580–592. 10.1002/jcc.22885. [DOI] [PubMed] [Google Scholar]; b Deng X.; Dang Y.; Wang Z.-X.; Wang X. How does an earth-abundant copper-based catalyst achieve anti-markovnikov hydrobromination of alkynes? A DFT mechanistic study. Organometallics 2016, 35, 1923–1930. 10.1021/acs.organomet.6b00246. [DOI] [Google Scholar]; c Ling B.; Liu Y.; Jiang Y.-Y.; Liu P.; Bi S. Mechanistic insights into the ruthenium-catalyzed [4 + 1] annulation of enzamides and propargyl alcohols by DFT Studies. Organometallics 2019, 38, 1877–1886. 10.1021/acs.organomet.8b00769. [DOI] [Google Scholar]
  25. Humphrey W.; Dalke A.; Schulten K. VMD: Visual Molecular Dynamics. J. Mol.Graphics 1996, 14, 33–38. 10.1016/0263-7855(96)00018-5. [DOI] [PubMed] [Google Scholar]
  26. Yang X.; Sun R.; Zhang C.; Zheng X.; Yuan M.; Fu H.; Li R.; Chen H. Iridium-catalyzed benzylamine C–H alkenylation enabled by pentafluorobenzoyl as the directing group. Org. Lett. 2019, 21, 1002–1006. 10.1021/acs.orglett.8b04005. [DOI] [PubMed] [Google Scholar]
  27. a Gorelsky S. I.; Lapointe D.; Fagnou K. Analysis of the concerted metalation-deprotonation mechanism in palladium-catalyzed direct arylation across a broad range of aromatic substrates. J. Am. Chem. Soc. 2008, 130, 10848–10849. 10.1021/ja802533u. [DOI] [PubMed] [Google Scholar]; b Lapointe D.; Fagnou K. Overview of the Mechanistic Work on the concerted metallation–deprotonation pathway. Chem. Lett. 2010, 39, 1118–1126. 10.1246/cl.2010.1118. [DOI] [Google Scholar]; c Wu J.-Q.; Zhang S.-S.; Gao H.; Qi Z.; Zhou C.-J.; Ji W.-W.; Liu Y.; Chen Y.; Li Q.; Li X.; Wang H. Experimental and theoretical studies on rhodium-catalyzed coupling of benzamides with 2,2-difluorovinyl tosylate: diverse synthesis of fluorinated heterocycles. J. Am. Chem. Soc. 2017, 139, 3537–3545. 10.1021/jacs.7b00118. [DOI] [PubMed] [Google Scholar]; d Jiang Y.-Y.; Man X.; Bi S. Advances in theoretical study on transition-metal-catalyzed C-H activation. Sci. China: Chem. 2016, 59, 1448–1466. 10.1007/s11426-016-0330-3. [DOI] [Google Scholar]
  28. a Zhang S.; Chen Z.; Qin S.; Lou C.; Senan A. M.; Liao R.-Z.; Yin G. Non-redox metal ion promoted oxidative coupling of indoles with olefins by the palladium(II) acetate catalyst through dioxygen activation: experimental results with DFT calculations. Org. Biomol. Chem. 2016, 14, 4146–4157. 10.1039/c6ob00401f. [DOI] [PubMed] [Google Scholar]; b Deng J.; Wen X.; Qiu Z.; Li J. Mechanism of Rh(III)-catalyzed cyclopropanation using N-enoxyphthalimides and alkenes: insights from DFT calculations. Tetrahedron 2016, 72, 8456–8462. 10.1016/j.tet.2016.11.017. [DOI] [Google Scholar]; c Guo W.; Zhou T.; Xia Y. Mechanistic understanding of the aryl-dependent ring formations in Rh(III)-catalyzed C-H activation/cycloaddition of benzamides and methylenecyclopropanes by DFT calculations. Organometallics 2015, 34, 3012–3020. 10.1021/acs.organomet.5b00317. [DOI] [Google Scholar]; d Chafaa F.; Nacereddine A. K.; Djerourou A. Unravelling the mechanism and the origin of the selectivity of the [3+2] cycloaddition reaction between electrophilic nitrone and nucleophilic alkene. Theor. Chem. Acc. 2019, 138, 123. 10.1007/s00214-019-2510-6. [DOI] [Google Scholar]; e Sivasakthikumaran R.; Jambu S.; Jeganmohan M. Ruthenium(II)-catalyzed distal weak O-coordinating C-H alkylation of arylacetamides with alkenes: combined experimental and DFT studies. J. Org. Chem. 2019, 84, 3977–3989. 10.1021/acs.joc.8b03257. [DOI] [PubMed] [Google Scholar]; f Ling B.; Liu Y.; Jiang Y.-Y.; Liu P.; Bi S. Mechanistic insights into the ruthenium-catalyzed [4+1] annulation of benzamides and propargyl alcohols by DFT studies. Organometallics 2019, 38, 1877–1886. 10.1021/acs.organomet.8b00769. [DOI] [Google Scholar]; g Hu L.; Wu Z.; Huang G. Mechanism and origins of regio- and stereoselectivities in iridium-catalyzed isomerization of 1-alkenes to trans-2-alkenes. Org. Lett. 2018, 20, 5410–5413. 10.1021/acs.orglett.8b02319. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao0c01587_si_001.pdf (839.5KB, pdf)
ao0c01587_si_002.xyz (382KB, xyz)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES