Diastereoselective Synthesis of Perfluoroalkylmethyl‐Substituted 1,2,3,4‐Tetrahydroquinolines Derivatives through 1‐Iodo‐1,3‐bis(acetoxy) Synthons

Abstract

AbstractNovel 2‐perfluoroalkylmethyl,4‐arylamino substituted tetrahydroquinolines (THQ) were expeditiously synthesized from perfluoroalkyl iodides RF−I and monosubstituted anilines. First, radicalbis‐addition of vinyl acetate on RF−I affordedgem‐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 : 5cis/transisomer 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 resultingbis(arylamino/imino) intermediate through electrophilic aromatic substitution. Various RF(C6, C2, C4) and arylamine substitutions (p‐,o‐,m‐ alkyl, alkoxyl, halogen…) were thus exemplified.