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. 2020 Jun 15;5(25):15446-15453.
doi: 10.1021/acsomega.0c01587. eCollection 2020 Jun 30.

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
Affiliations

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

Jiarong Wang et al. ACS Omega. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Ir-Catalyzed ortho-Alkenylation of Benzylamine with Acrylate by Fu et al.
Scheme 2
Scheme 2. Possible Reaction Mechanism Proposed by Fu et al.
Figure 1
Figure 1
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.
Figure 2
Figure 2
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
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
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.
Figure 5
Figure 5
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.
Scheme 3
Scheme 3. Plausible Pathways Proposed Starting from IM11
See this image and copyright information in PMC

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