Abstract
Novel 2-perfluoroalkylmethyl,4-arylamino substituted tetrahydroquinolines (THQ) were expeditiously synthesized from perfluoroalkyl iodides RF–I and monosubstituted anilines. First, radical bis-addition of vinylacetate on RF–I afforded gem-iodoacetoxy derivatives (newly characterized by NMR and MS) being actually masked/activated aldol synthons. Their reaction in 1:4 ratio with arylamines afforded title THQ under mild conditions in good yields (60–95%) and diastereoselectivities (65:35 – 95:5 cis/trans isomer ratio); m-substituted anilines regiospecifically lead to 7-substituted THQ. Mechanistic investigation suggested the THQ formation to proceed through Michael then imine addition of two aniline units on an RF-substituted crotonaldehyde intermediate; then through the cyclization of the resulting bis(arylamino/imino) intermediate through electrophillic aromatic substitution. Various RF (C6, C2, C4) and arylamine substitutions (p-,o-,m- alkyl, alkoxyl, halogen…) were thus exemplified.