Urea Activation by an External Brønsted Acid: Breaking Self-Association and Tuning Catalytic Performance

Abstract

In this work, we hypothesize that Brønsted acids can activate urea-based catalysts by diminishing its self-assembly tendency. As a proof of concept, we used the asymmetric Friedel–Crafts alkylation of indoles with nitroalkenes as a benchmark reaction. The resulting 3-substituted indole derivatives were obtained with better results due to cooperative effects of the chiral urea and a Brønsted acid additive. Such synergy has been rationalized in terms of disassembly of the supramolecular catalyst aggregates, affording a more acidic and rigid catalytic complex.

Keywords

• Brønsted acids
• Friedel-Crafts
• organocatalysis
• self-association
• synergy
• urea