Curtin-Hammett-Driven Intramolecular Cyclization of Heteroenyne-Allenes to Phenanthridine-Fused Quinazoliniminiums

Intramolecular cyclization of the heteroenyne-allene 2-((biphenyl-2-ylimino)methyleneamino)benzonitrile 1 to phenanthridine-fused quinazoliniminium salt PQ in the presence of a Lewis acid at room temperature involves formation of two new bonds: a C-C bond and a C-N bond. In this article, density functional theory (B3LYP and M06-2X) was employed in conjunction with 6-311G* basis set to gain insights into the mechanism of this cyclization reaction. The solvent effects were considered using Polarizable Continuum Model with nitromethane as the solvent. Our calculations show that C-C bond formation precedes the C-N bond formation. Precisely, the mechanism involves initial protonation of 1 at N_α and N_β of the carbodiimide to form rapidly equilibrating conformers of the tautomers 2a,b and 3a,b. The Curtin-Hammett principle is invoked to determine the course of the reaction from these protonated species, which predicts that the intramolecular Friedel-Crafts type N-acylation (C-C bond formation) occurs between the protonated carbodiimide and biphenyl ring of the isomer 3b to form phenanthridinium cation 6b via transition state TS3_b6_b. Once 6b is formed, it converts to its most stable tautomers 8R and 9a. Once again, the Curtin-Hammett principle suggests that intramolecular nucleophilic attack is preferred from the tautomer 8R, where phenanthridine N-atom (N_β) attacks the protonated nitrile group (C-N bond formation) and results in the formation of intermediate 11 via TS8_R11. 11 then tautomerizes to the most stable cation 13. The coordination of the latter with the chloride anion yields the phenanthridine-fused heterocyclic salt PQ with overall release of energy. The pathways involving protonation at the nitrile (N_γ) of 1 were found to be energetically unfavorable and thus insignificant to the mechanism of cyclization.