Gold(I)-Catalyzed Intramolecular Addition of Pyridines to Unactivated Alkenes: Synthesis of Indolizinium and Quinolinium Derivatives.

Nitrogen-containing heterocycles, such as indoliziniums and quinoliniums, are essential structural scaffolds in medicinal chemistry and include bioactive alkaloids of therapeutic interest. Herein, we report a regioselective gold(I)-catalyzed intramolecular cyclization enabling the addition of pyridine and quinoline motifs onto unactivated alkenes to form indolizinium and quinolinium derivatives in high yields, by using HFIP as the solvent and para-toluenesulfonic acid as an acidic additive. Over thirty derivatives were synthesized, with yields ranging from 43% to 97%, covering a wide diversity of substitutions on the pyridine ring, the alkene chain, and their linker. Extension of this strategy to an oxidant-free gold(I/III) redox cross-coupling further enabled direct aryl functionalization. Finally, the synthetic potential of these compounds was demonstrated through various post-functionalizations and a formal synthesis of gephyrotoxin, highlighting their value for drug discovery and natural product synthesis.