Aromatic Substitution in Synthesis: Friedel-Crafts Reactions and Benzylic Chemistry

Explore the intricacies of aromatic substitution reactions in organic chemistry through this 51-minute lecture from Yale University's Freshman Organic Chemistry II course. Delve into the Friedel-Crafts reaction, learning how it creates new alkyl- or acyl-aromatic bonds with or without cation rearrangement. Discover the challenges of synthetic organic chemistry by designing reaction sequences involving diazonium intermediates to access various substituted benzenes. Examine nucleophilic aromatic substitution in electron-withdrawing aromatic rings and its significance in biochemistry. Investigate the special properties of phenyl-substituted alkanes, focusing on benzylic reactivity and steric hindrance, and their historical importance in organic chemistry development. The lecture covers five chapters, including the discovery of Friedel-Crafts alkylation and acylation, strategies to avoid rearrangements, synthetic accessibility via aromatic substitution, and the contributions of Moses Gomberg to the field.