Construction of six-membered nitrogen-heterocycles via intramolecular cyclization of iminyl radical: A theoretical perspective

In this study, we reported a potential method of constructing six-membered nitrogen-containing heterocycles via intramolecular cyclization of R2-substituted 4-penteniminyl radicals (R2 = –NO2, –SO2OH, –CF3, –SO2Ph, –CN, –CONMe2, –p-PhNO2, and –COOH). All of these investigated iminyl radicals exhibit strong preference for 6-endo cyclization products over 5-exo products. We further explored possible reasons to lead to the predominant 6-endo regioselectivity, including electronic density, stereoelectronic effect (intrinsic barrier), and thermodynamic contribution to reaction barrier. The computed results provided a potential synthetic strategy towards constructing six-membered N-heterocycles by intramolecular cyclization of substituted iminyl radicals.