Counter Ion Effect in Au/Ag-Catalyzed Chemoselective 6-<i>endo</i>-<i>dig</i> N‑ and O‑Cyclizations of Enyne–Urea System: Diversity-Oriented Synthesis of Annulated Indoles

A two-step protocol for the diversity-oriented synthesis of annulated indoles following MCR-post MCR modification concept is described. The reaction initially proceeds through the annulation of 2-(2,2-dibromovinyl)­aniline, an isocyanate, and a terminal alkyne in a three-component tandem format via Cu/Pd-catalyzed cross coupling to afford N-1 and C-2 functionalized indole. In the subsequent step, the enyne–urea derivative undergoes chemo- and regioselective 6-endo cyclization to afford O-cyclized product in the presence of Au­(I)/AgNO3 and N-cyclized product in the presence of Au­(I)/AgOTf under a post-MCR modification step. A mechanistic investigation following a recent pioneering work on the silver effect in gold catalysis (Shi, X. J. Am. Chem. Soc. 2012, 134, 9012) explains the role of counterion on Au/Ag-catalyzed regiodivergent pathways.