An ion-pair as a superacidic precatalyst for the synthesis of indole alkaloids: a novel entry into the Fischer indole synthesis

Abstract

We report the first application of [Ph₃C]⁺[B(C₆F₅)₄]⁻ in ion-pair catalysis to the Fischer indole synthesis, enabling efficient construction of structurally diverse indole frameworks under mild conditions. Using the [Ph₃C]⁺[B(C₆F₅)₄]⁻ ion pair as a highly active and selective catalyst, a broad range of substrates, including sterically hindered and electronically diverse partners, were converted to indoles in good to excellent yields. The method delivers high regioselectivity even in structurally complex settings, as demonstrated in concise total syntheses of paullone, (±)-desbromoarborescidine A, tjipanazole D, and tjipanazole I. Scale-up synthesis was also achieved without loss of efficiency, highlighting the operational simplicity of the protocol. This work establishes ion-pair-catalysed Fischer indole synthesis as a versatile and scalable platform for rapid access to bioactive heterocyclic scaffolds.