Metal-Free α-C(sp3)–H Functionalized Oxidative Cyclization of Tertiary N,N-Diaryl Amino Alcohols: Theoretical Approach for Mechanistic Pathway

• Main Authors: Zakir Ullah, Mihyun Kim
• Format: Article
• Language: English
• Published: MDPI AG 2017-03-01
• Series: Molecules
• Subjects: α-C(sp3)–H functionalization; oxidative cyclization; tertiary amine; 6-exo-trig; metal-free C–H activation
• Online Access: http://www.mdpi.com/1420-3049/22/4/547

The mechanistic pathway of TEMPO/I2-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 was investigated. Based on direct empirical experiments, three key intermediates (aminium radical cation 3, α-aminoalkyl radical 4, and iminium 5), four types of reactive species (radical TEMPO, cationic TEMPO, TEMPO-I, and iodo radical), and three types of pathways ((1) SET/PCET mechanism; (2) HAT/1,6-H transfer mechanism; (3) ionic mechanism) were assumed. Under the assumption, nine free energy diagrams were acquired through density functional theory calculations. From the comparison of solution-phase free energy, some possible mechanisms were excluded, and then the chosen plausible mechanisms were concretized using the more stable intermediate 7.