Dual Hard/Soft Gold Catalysis: Intermolecular Friedel-Crafts-Type α-Amidoalkylation/Alkyne Hydroarylation Sequences by N-Acyliminium Ion Chemistry

Gold catalysts have been applied in cascade-type reactions for the synthesis of different nitrogen-based compounds. The reactions likely proceed by a new gold-catalyzed cascade intermolecular alpha-amidoalkylation/intramolecular carbocyclization cascade process by unifying both the sigma- and pi-Lewis acid properties of the gold salts. In the first part of this report we show that the sigma-Lewis acidity of gold(I) and gold(III) could be exploited to efficiently catalyze the nucleophilic substitution of various alkoxy- and acetoxylactams. The reaction was found to be applicable to a wide range of cyclic N-acyliminium ion precursors and various nucleophiles, including allyltrimethylsilane, silyl enol ethers, arenes, and active methylene derivatives. As a logical progression of this study, a combined hard/soft binary catalytic gold system was then used to implement an unprecedented tandem intermolecular Friedel-Crafts amidoalkylation/intramolecular hydroarylation sequence allowing an expedient access to new, complex, fused polyheterocyclic structures from trivial materials.