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 R-2-substituted 4-penteniminyl radicals (R-2 = -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. (C) 2013 Elsevier B.V. All rights reserved.