Multi-hydroxyl POSS supported iridium complexes as a recyclable catalyst for selective synthesis of N-/C-substituted indoles and the total synthesis of HIV-1 fusion inhibitor

Abstract

A novel pyridyl-thiadiazole ligand has been designed, synthesized, and employed in the preparation of a heterogeneous iridium catalyst supported on multi-hydroxyl polyhedral oligomeric silsesquioxane. The as-prepared catalyst exhibits excellent catalytic activity in the one-pot cascade selective synthesis of N-/C-substituted indole derivatives from amino alcohols and alcohols via borrowing hydrogen strategy. Meanwhile, it was observed that this approach has a good functional group tolerance and broad substrate scope. Notably, by employing this catalytic system, an inhibitor against gp41-mediated HIV-1 fusion core structure could be conveniently synthesized from 2-aminophenethyl alcohol derivatives and benzyl alcohols in 41 % total yield for only four steps via “borrowing hydrogen” strategy. Mechanistic explorations showed that this transformation undergoes cascade processes, involving N/C-alkylation through borrowing hydrogen strategy, and oxidative cyclization. Recycling experiments disclosed that the catalyst could be easily recovered and reused for at least seven times with good TON.