Efficient Catalytic Condensation of Methyl Ketones with Indole to Form All‐Carbon Quaternary Center Bisindolylmethanes Mediated by Strong Dual Brønsted Acid

A dual Brønsted acid catalyst (1a) with perfluorobutylsulfonimide groups synthesizes bisindolylmethanes (BIMs) bearing all-carbon quaternary centers. Methanol enables 59%–99% yields (30 °C), with acetophenone showing >90% selectivity. Intensified conditions suppress BIMs from acetone (<16%), favoring tetrahydrocyclopenta[b]indole (4, 54%–77%). Solvent-driven hydrogen-bonding modulates 1a's acid strength (¹H NMR), highlighting that solvent-driven complementarity dictates selectivity via electronic alignment, guiding acid-tunable catalysis design.

Abstract

This study develops a protocol for synthesizing bisindolylmethanes (BIMs) with all-carbon quaternary centers using a dual Brønsted acid catalyst (1a) containing two meta-positioned perfluorobutylsulfonimide groups. The catalyst activates aliphatic and aromatic methyl ketones in methanol at 30 °C, yielding 59%–99% BIMs products, with acetophenone showing >90% selectivity. Under harsher conditions (e.g., high acetone concentration or catalyst loading), BIMs formation from acetone drops to <16%, while tetrahydrocyclopenta[b]indole (4) becomes dominant (54%–77% yield), indicating indole substituents’ electronic control over pathway selection. Solvent-dependent ¹H NMR studies demonstrate hydrogen-bond-driven modulation of 1a's acid strength, explaining solvent-dependent selectivity. These findings highlight substrate-catalyst electronic complementarity in governing product selectivity, providing a framework for designing acid strength-tunable systems for BIMs synthesis.

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