Total Synthesis of (S)-Cularine via Nucleophilic Substitution on a Catechol

Catechols are part of many essential chemicals and are valuable, typically nucleophilic intermediates used in synthesis. Here we describe an unexpected transformation in which they play the role of the electrophile in a formal nucleophilic aromatic substitution. We made this discovery while studying a seven-membered dioxepin ring formation during a synthesis of the benzyltetrahydroisoquinoline (S)-cularine. We suggest a chain mechanism for this new transformation that is triggered by molecular oxygen and that propagates an electrophilic ortho-quinone.

Automated summary

This discovery reveals the unexpected role of catechols as electrophiles in a formal nucleophilic aromatic substitution reaction. The transformation is proposed to proceed through a chain mechanism triggered by molecular oxygen.