Investigations into Indole Formation: Base-mediated Formation of N-hydroxy- and N-alkoxyindoles, Ancillary Ligand Development for Watanabe-Cenini-Söderberg Cyclization, and Total Synthesis of Racemosin B

A novel, base-mediated cyclization was developed to form N-hydroxy- and N-alkoxyindoles from 2-(2-nitrophenyl)butenoates. Potassium tert-butoxide or sodium tert-pentoxide, with or without the in-situ addition of an electrophile, formed a multitude of N-hydroxy- and N-alkoxyindoles. The formation of these butanoate precursors was improved via a Barluenga coupling reaction. Novel 4,5,6,7-tetramethoxy-1,10-phenanthroline was utilized as an ancillary ligand within the Watanabe-Cenini-Söderberg reductive cyclization reaction conditions. These new reaction conditions produced high yields for sterically hindered 2-nitrostyrenes and the first synthesis of dilemmaone A using this reductive cyclization. Racemosin B was synthesized in a three-step process utilizing a Suzuki coupling reaction, followed by the improved WCS reductive cyclization conditions. Substitutions to the terphenyl precursor structure were made, allowing for possible substituted racemosin B analogs