Keteniminium Salts: Reactivity and Propensity toward Electrocyclization Reactions

Area of Science:

• Computational chemistry
• Organic synthesis
• Heterocyclic chemistry

Background:

• Keteniminium salts are versatile precursors for heterocyclic synthesis.
• Understanding the factors influencing their electrocyclization is crucial for efficient synthetic design.

Purpose of the Study:

• To computationally assess the efficiency of keteniminium salt electrocyclization reactions.
• To investigate the formation of various 3-amino heterocyclic systems, including 3-aminopyrroles, 3-aminoindoles, 3-aminobenzothiophenes, and 3-aminobenzofurans.
• To explore the impact of heteroatoms (NMe, O, S) and substituents on reaction outcomes.

Main Methods:

• Density Functional Theory (DFT) calculations were employed.
• Analysis included population analysis, Quantum Theory of Atoms in Molecules (QTAIM), Nucleus-Independent Chemical Shift (NICS), Atom-Centered Index of Diamagnetism (ACID), and local reactivity descriptors (Parr and Fukui functions).
• Frontier Molecular Orbital (FMO) theory was used to confirm the pericyclic nature of the reactions.

Main Results:

• The electrocyclization of enamines yielding 3-aminopyrroles was identified as the most kinetically and thermodynamically favorable pathway.
• The pericyclic mechanism of these electrocyclizations was confirmed through multiple theoretical analyses.
• Substituent effects were investigated, providing deeper insights into the reactivity of heteroatom-containing keteniminium systems.

Conclusions:

• The study successfully predicted the most efficient route for synthesizing various 3-amino heterocycles via keteniminium salt electrocyclization.
• Computational findings were validated through experimental confirmation for selected systems.
• This work offers a valuable predictive tool for designing synthetic strategies involving keteniminium electrocyclizations.