Modeling Possible Biogenetic Pathways to the Isomeric Pyrano[2,3-g]indole and Pyrano[3,2-f]indole Cores of Certain Prenylated Indole Alkaloids Using Gold(I)-Catalyzed Intramolecular Hydroarylation Reactions

A significant subset of the so-called prenylated indole alkaloids (PIAs) contains an angularly fused pyrano[2,3-g]indole core, while a smaller number embody the isomeric and linearly fused pyrano[3,2-f]indole one. In an effort to probe the capacities of intramolecular hydroarylation (IMHA) reactions to allow for the selective formation of one or other of these motifs, a series of 6-((2-methylbut-3-yn-2-yl)oxy)-1H-indoles varying in the nature of the substituents at C1-C3 was prepared and subjected to reaction with a range of gold(I) catalysts. In every instance, preferential (but not exclusive) formation of the angularly fused pyrano[2,3-g]indole isomer was observed. This was so even as the C2 and C3 substituents increasingly resembled those associated with key members of the PIA family of natural products. These IMHA protocols have been deployed in the total syntheses of the natural products (±)-1, (±)-2, (±)-3, (±)-4, 25, and 26. The possible biosynthetic implications of these studies are discussed.