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Anodic Cyclization Reactions and the Mechanistic Strategies That Enable Optimization
Ruozhu Feng1, Jake A Smith1, Kevin D Moeller1
1Department of Chemistry, Washington University , St. Louis, Missouri 63130, United States.
Accounts of Chemical Research
|September 1, 2017
Summary
Anodic electrochemistry enables systematic study of oxidative cyclization mechanisms. This method helps identify and solve problems in radical cation generation, cyclization, and product formation for improved synthetic strategies.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Electrochemistry
Background:
- Oxidation reactions are vital in synthesis for functional group manipulation and creating reactive intermediates.
- Oxidative cyclization reactions, involving radical cation intermediates, are powerful but complex synthetic tools.
- Challenges in controlling radical cation stability and subsequent reaction steps hinder new transformations.
Purpose of the Study:
- To systematically probe the mechanism of oxidative cyclization reactions using anodic electrochemistry.
- To develop diagnostic tools and solutions for common problems encountered in oxidative cyclizations.
- To provide a mechanistic understanding for optimizing and expanding synthetic applications of oxidative cyclizations.
Main Methods:
- Utilizing anodic electrochemistry for controlled generation of radical cations under neutral conditions.
- Employing proton NMR spectroscopy to diagnose issues in the initial cyclization step (e.g., polymerization, trapping).
- Analyzing current efficiency and cyclic voltammetry to identify problems with the second oxidation step and final cation quenching.
Main Results:
- Electrochemical methods effectively prevent radical cation polymerization and allow mechanistic diagnosis.
- Proton NMR identifies specific issues like solvent trapping or elimination, guiding solutions like tuning radical cations or trapping groups.
- Optimized conditions, including substrate modification and electrolyte concentration, address issues in subsequent oxidation and cation quenching steps.
Conclusions:
- Anodic electrochemistry provides a powerful platform for dissecting oxidative cyclization mechanisms.
- A systematic approach using electrochemical and spectroscopic diagnostics allows for effective problem-solving in complex oxidations.
- This work facilitates the development of new, reliable, and efficient synthetic methodologies based on oxidative cyclizations.
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