ABSTRACT
Gold(III)-catalyzed annulation of electron-deficient alkynes and 2-amino-arylcarbonyls provides general modular one-step access to a broad scope of quinoline products. This highly selective reaction is a useful alternative to the classic Friedländer synthesis, which requires harsh reaction conditions. In contrast, the developed method works under relatively mild PicAuCl2-catalyzed conditions and exhibits a high functional group tolerance (40 examples; yields of ≤96%). Another feature of the developed approach is a versatility toward other electron-deficient alkynes. Alkynylsulfones, alkynylcarbonyls, alkynylphosphonates, propiolonitriles, and trifluoromethylated alkynes can be used as the starting materials for the preparation of quinolines diversely substituted at position 3. On the basis of experimental data, we proposed a reaction mechanism in which gold(III) functions as a strong electrophilic activator of the C≡C bond and the carbonyl group. The synthetic potential of the presented method is additionally illustrated by practical postmodifications of the obtained compounds, including a two-step synthesis of interpirdine, a potent drug candidate.
ABSTRACT
Gold(I)-catalyzed [4 + 2] cycloaddition of indolylynamides and cyanamides (aminonitriles) is an efficient redox-neutral and atom-economic route to diversely substituted 1,3-diamino-ß-carbolines. The protocol operates under mild conditions (Ph3PAuNTf2 5 mol %, DCE, 60 °C) with a good tolerance to functional groups (23 examples and yields up to 98%). The obtained ß-carboline systems represent a versatile synthetic platform with modifiable substituents for successive functionalizations. Control experiments indicate the crucial role of both the nature of reactants and the identity of employed catalysts in the developed cycloaddition.
