Gold-Catalyzed Intramolecular Allylic Amination of 2-Tosylaminophenylprop-1-en-3-ols. A Concise Synthesis of (±)-Angustureine

An efficient synthetic route to 1,2-dihydroquinolines that relies oil AuCl3/AgSbF6-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols is described herein. Uniquely, the reactions were found to only proceed rapidly at room temperature in the presence of the gold and silver catalyst combination and produce the 1,2-dihydroquinoline products in yields of 4091 91%. The method was shown to be applicable to a broad range of 2-tosylaminophenylprop-1-en-3-ols containing electron-withdrawing, electron-donating, and sterically demanding substrate combinations. The mechanism is suggested to involve activation of the alcohol Substrate by the AuCl3/AgSbF6 catalyst. This is followed by ionization of the starting material, which causes intramolecular nucleophilic addition of the sulfonamide unit to the allylic cation moiety and construction of the 1, 2-dihydroquinoline. The utility of this N-heterocyclic ring forming Strategy as a synthetic tool that makes use Of alcohols as pro-electrophiles was exemplified by its application to the Synthesis of the bioactive tetrahydroquinoline alkaloid (+/-)-angustureine.