Anodic Cyclization Reactions and the Mechanistic Strategies That Enable Optimization

• DOI: 10.1021/acs.accounts.7b00287
• Publication Date: 2017-08-31T19:16:55Z
• Authors: Ruozhu Feng; Jake A. Smith; Kevin D. Moeller
• Keywords: 01 natural sciences; 0104 chemical sciences

Oxidation reactions are powerful tools for synthesis because they allow us to reverse the polarity of electron-rich functional groups, generate highly reactive intermediates, and increase functionality molecules. For this reason, oxidation have been continue be subject intense study. Central these efforts is development mechanism-based strategies that think about intermediates frequently central success mechanistic pathways those trigger. example, consider oxidative cyclization triggered by removal an electron from olefin lead cyclic products functionalized further elaboration. successful, radical cation intermediate must first generated using conditions limit its polymerization then channeled down a productive desired pathway. Following cyclization, second step necessary product formation, after which resulting quenched in controlled fashion avoid undesired elimination reactions. Problems can arise at any one or all steps, fact complicates reaction optimization discourage new transformations. Fortunately, anodic electrochemistry offers outstanding opportunity systematically probe mechanism The use electrochemical methods allows generation cations under neutral environment helps prevent intermediate. Once generated, series "telltale indicators" used diagnose problematic less successful transformation. A set potential solutions address each type problem encountered has developed. problems with initial leading either cation, proton solvent trapping intermediate, identified NMR spectrum crude material. Such shows retention group. addressed tuning altering group, channeling Specific examples shown Account. poor current efficiency general decomposition spite voltammetry evidence rapid cyclization. Solutions involve improving addition properly placed electron-donating group substrate concentration electrolyte (a change stabilizes step). final typically overoxidation. require approach slows side changes so quickly trapped irreversible fashion. Again, Account highlights along specific experimental protocols utilized.