Annulated N-Heterocycles by Tandem Gold(I)-catalyzed [3,3]-Rearrangement/Nazarov Reaction of Propargylic Ester Derivatives: an Experimental and Computational Study

The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of propargylic ester derivatives is a useful strategy for the synthesis of cyclopenta-fused N-heterocyclic structures present in many natural compounds. Readily available lactams are converted into the corresponding enol phosphates and triflates and coupled to propargyl alcohols under Sonogashira conditions. After acetylation, the gold-catalyzed rearrangement of the so formed enynyl acetates readily occurs when using 3-5 mol % of a gold(I) catalyst. The rearrangement generates a divinyl cation which undergoes a 4pi electrocyclization (Nazarov reaction) leading to the target compound in good to excellent yield. This process has been studied in details both experimentally and computationally, trying to understand the influence of both the reaction conditions and structural features of the substrate on the reaction rate and regioselectivity, as well as the torquoselectivity in the ring closure step. A series of examples illustrates at the end the scope of the reaction.