Understanding the Structure‐Activity Relationship of Ni‐Catalyzed Amide C−N Bond Activation using Distortion/Interaction Analysis

• Published in: ChemCatChem Vol. 13; no. 15; pp. 3536 - 3542
• Main Authors: Xie, Pei‐Pei, Qin, Zhi‐Xin, Zhang, Shuo‐Qing, Hong, Xin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 06.08.2021
• Subjects: Amide C−N activation; Amides; Chelation; Density functional theory; DFT calculations; Distortion; Distortion/interaction analysis; Ductile-brittle transition; Energy of dissociation; Free energy; Heat of formation; Mathematical analysis; Nickel catalysis; Reagents; Structure-activity relationship; Substrates; Transition metals
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.202100672

Transition metal‐catalyzed amide C−N bond activation has emerged as a powerful strategy to utilize amides in synthetic transformations. The key mechanistic basis for the rational design of amide reagents is the structure‐activity relationship of amide C−N bond activation. In this work, the controlling factors of Ni/PCy3‐catalyzed amide C−N bond activation barrier are elucidated with density functional theory (DFT) calculations and distortion/interaction analysis. We found that the substrate distortion is the key factor that differentiates the amide reactivity in the C−N bond activation. The substrate distortion of amide is associated with two distinctive structure‐activity relationships. The general planar amides undergo a classic three‐membered ring oxidative addition to cleave the C−N bond, in which the C−N heterolytic bond dissociation energy has a linear relationship with the activation barrier. The twisted amides have a chelation‐assisted transition state for the amide C−N bond cleavage, and the twisted angle τ can serve as a predictive parameter for the reactivity of the twisted amides. The understanding of the structure‐activity relationship of amide C−N bond activation provides a rational and predictive basis for future reaction designs involving transition metal‐catalyzed amide C−N bond activation. Computational catalysis: The structure‐activity relationship and the key controlling factors of amide activation barriers were elucidated by DFT calculation and distortion/interaction analysis.