Mild Methods for Alkyl Radical Generation and Their Translation to Radiochemistry for Molecular Imaging Probe Development

This thesis describes the development of mild methodologies toward alkyl radical formation and their application to positron emission tomography (PET) imaging probe development. The first transition metal- and light-free auxiliary enabled remote functionalization of unactivated aliphatic alcohols was developed. This protocol enabled the selective activation of inert tertiary, secondary, and even primary CH bonds of primary, secondary, and tertiary alcohols toward β-, - and - diazenes. Subsequent hydrogenation afforded the corresponding aminoalcohols in good to excellent yields. Aerobic oxidation of secondary diazenes yielded sterically bulky 1,3- hydroxyketones in good yields. Next, the alkyl Heck-type reaction of activated and unactivated tertiary alkyl halides was developed, building on previous work on the photoinduced palladium- catalyzed exogenous photosensitizer- and oxidant-free alkyl Heck-type reaction of primary and secondary alkyl halides with vinyl arenes and heteroarenes. The method featured a broad functional group tolerance toward valuable synthons bearing quaternary centers at the allylic position in good to excellent yields. When phenyl vinyl ether was used as a coupling partner, the reaction proceeded by radical-polar crossover (RPC) pathway to afford double addition mixed acetal products. This protocol was integrated with rapid, Markovnikov selective iodofluorination of alkenes in the first one-pot formal alkenylfluorination of alkenes as a modular prosthetic group (PG) toolkit for PET imaging probe development. A new class of aliphatic prosthetic groups was synthesized en route to valuable organofluorine compounds. The methodology was translated to radiochemistry in generally good radiochemical yields, and an automated protocol for PG- synthesis was developed. The RPC mechanism was expanded to afford -fluoroethers, in the first photoinduced Pd(0/I/II)-catalyzed direct alkyl(radio)fluorination of electron rich alkenes.