Synthesis of 8-Aminoquinolines by Using Carbamate Reagents: Facile Installation and Deprotection of Practical Amidating Groups

Abstract

Described herein is the development of practical routes to 8-aminoquinolines by using readily installable and easily deprotectable amidating reagents. Two scalable procedures were optimized under RhIII-catalyzed conditions: i) the use of pre-generated chlorocarbamates and ii) a two-step one-pot process that directly employs carbamates. Both approaches are highly convenient for the gram-scale synthesis of 8-aminoquinolines under mild conditions. Facile deprotection of the synthetically versatile amidating groups was achieved under the Pd-catalyzed transfer hydrogenation conditions with simultaneous deoxygenation of quinoline N-oxides, thus yielding 8-aminoquinolines in excellent overall efficiency.