Related Experiment Video
Updated: Nov 25, 2025

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Total Synthesis of (S)-Cularine via Nucleophilic Substitution on a Catechol
Zheng Huang1, Xiang Ji1, Jean-Philip Lumb1
1Department of Chemistry, McGill University, Montreal, Quebec H3A 0B8, Canada.
Abstract:
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.
Related Concept Videos
Nucleophilic Acyl Substitution of Carboxylic Acid Derivatives
SN2 Reaction: Stereochemistry
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
Preparation of Alcohols via Substitution Reactions
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
Reactions of α-Halocarbonyl Compounds: Nucleophilic Substitution
SN1 Reaction: Stereochemistry
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...

