Development of Acetal Radicals in Organic Synthesis

Project Summary/Abstract The foundation of the Kim Research Group at Temple University is built upon the development of new designer reagents and methods to access high-value carbonyl compounds from acetal-based radical precursors. To that end, this proposal strives to implement acetal radicals as a means to access a diverse array of medicinally relevant molecular platforms. To address these challenges, we have designed a set of novel reagents to overcome rapid decarbonylation side reactions of acyl radicals and developed a platform to synthesize carbonyl compounds of interest to those in the agrochemical, pharmaceutical, and material industries. Additionally, our fundamental research in acetal radicals has provided alternative opportunities to study them in fragment coupling reactions. This work will aid in the rapid construction of molecular complexity by combining C–H activation with C–C bond formations to construct a wide variety of molecular scaffolds. This research is well poised to tackle necessary synthetic challenges in order to build pharmaceutically relevant precursors, allowing it to be widely adopted within the synthetic medicinal community. We have devised two research programs to address these research aims. Research Program I will explore the use of acetal radicals to install high-value ketones that can serve as carboxylic acid bioisosteres. Research Program II will explore alternative C–C couplings of acetal radicals to install highly oxidized carbon fragments for complex molecular syntheses. This research will be essential in shaping the next generation of design principles for improved pharmaceuticals to tackle human diseases more effectively.