Chapter 23: Chemoselectivity and Protecting Groups

Free radicals form through homolytic bond cleavage initiated by heat, light, or radical initiators such as peroxides and AIBN, and their stability follows a hierarchy analogous to carbocation stability, with tertiary radicals more stable than secondary or primary species due to hyperconjugation and electron delocalization effects. The chapter systematizes radical reactions into three mechanistic stages: initiation, in which radical species are generated; propagation, where chain reactions proceed through sequential hydrogen abstraction and radical formation; and termination, which ends the chain cycle through radical recombination. These mechanisms are illustrated through halogenation reactions of alkanes, with bromination demonstrating superior selectivity at tertiary positions compared to chlorination, a difference explained by Hammond's postulate and the later transition state characteristics of the rate-determining step. Synthetic applications receive substantial attention, including allylic bromination using N-bromosuccinimide, radical-mediated cyclization for carbon ring construction, and the anti-Markovnikov addition of hydrogen bromide to alkenes in the presence of peroxides, reactions inaccessible through conventional ionic pathways. The chapter also covers radical polymerization processes, where monomer units sequentially add to a growing chain through radical propagation, controlled by initiators that regulate polymer chain length and properties. Comparative analysis with polar mechanisms clarifies why radical chemistry produces distinct regio- and stereochemical outcomes, enabling synthetic access to transformations otherwise difficult or impossible through ionic routes. Additionally, the text addresses the biological significance of free radicals in enzymatic catalysis, oxidative deoxyribonucleic acid damage, and cellular signaling, contextualizing radical chemistry within both synthetic and biochemical frameworks.