Synthesis of Tetrahydro-β-carbolines via Cascade Sigmatropic Rearrangements

We have developed a synthesis for tetrahydro-β-carbolines involving cascade sigmatropic rearrangements. The substrates were conveniently prepared from parent anilines via a [2,3]-sigmatropic rearrangement and cyanomethylation. Silver-mediated decyanation afforded the corresponding iminium cation, which underwent a cascade consisting of an aza-Cope rearrangement, an aza-oxa-Cope rearrangement, an aromatization, and a Pictet–Spengler reaction, and tetrahydro-β-carbolines were obtained as the single product. The reaction involved seven bond scissions and four bond formations and was triggered by a single reagent.