Tandem buildup of complexity of aromatic molecules through multiple successive electrophile generation in one pot, controlled by varying the reaction temperature?

Organic & Biomolecular Chemistry Pub Date: 2015-12-24 DOI: 10.1039/C5OB02240A

Abstract

While some sequential electrophilic aromatic substitution reactions, known as tandem/domino/cascade reactions, have been reported for the construction of aromatic single skeletons, one of the most interesting and challenging possibilities remains the one-pot build-up of a complex aromatic molecule from multiple starting components, i.e., ultimately multi-component electrophilic aromatic substitution reactions. In this work, we show how tuning of the leaving group ability of phenolate derivatives from carbamates and esters provides a way to successively generate multiple unmasked electrophiles in a controlled manner in one pot, simply by varying the temperature. Here, we demonstrate the autonomous formation of up to three bonds in one pot and formation of two bonds arising from a three-component electrophilic aromatic substitution reaction. This result provides a proof-of-concept of our strategy applicable for the self-directed construction of complex aromatic structures from multiple simple molecules, which can be a potential avenue to realize multi-component electrophilic aromatic substitution reactions.

Graphical abstract: Tandem buildup of complexity of aromatic molecules through multiple successive electrophile generation in one pot, controlled by varying the reaction temperature
Recommended Literature