Substituted Catechols as H-Bonding Organocatalysts in Conjugated Addition Reactions of (Hetero-)Arenes to Nitroolefins
Year: 2026
Type: preprint
Abstract: Hydrogen-bond donor organocatalysts based on thioureas, silanols, amidines and diols have been studied in-depth. However, catechols – as prototypical diol catalysts – are comparatively underexplored despite their structural simplicity, straightforward accessibility, and tunability. Here, we systematically investigate substituted catechols as hydrogen-bond donor catalysts for the conjugate addition of indoles to nitroolefins. Screening of the catechol substitution pattern identified 4bromocatechol as the most active derivative. Comparison with related diols established the importance of the vicinal arrangement and phenolic nature of the hydroxy groups. The catechol catalyst exhibits broad functional group tolerance in diverse substrate combinations. Further, the reaction was performed on multigram scale under solvent-free conditions. Combined NMR spectroscopic studies, titrations, kinetic experiments, and DFT calculations suggest a concentration-dependent association of the catechol catalyst into dimers or higher aggregates. Remarkably, 4-bromocatechol outperformed established hydrogen-bond donor catalysts. These results establish catechol as a simple, readily tuneable, and highly effective hydrogen-bond donor motif and provide a fundamental understanding of their high activity.
Source: ChemRxiv
Authors: Tom H.R. Kuster, Louis Blum, Tobias Schnitzer
Institution: University of Freiburg
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: Evonik Stiftung, Vector Stiftung
OpenAlex ID: W7223189132