Recent synthetic methodology advancements towards all-carbon quaternary center formation and applications

Abstract

The synthesis of organic molecules through regioselective and enantioselective processes represents a significant challenge in organic chemistry, but constructing molecules with all-carbon quaternary centers poses even greater complexity. The importance of synthetic organic chemistry in daily life cannot be overstated, as organic molecules are fundamental to human existence - from the nutrients that sustain us to the pharmaceutical products that maintain our health. Fundamental knowledge on chemical reactivity, particularly that of carbon-carbon bond formation in sterically hindered substrates, is of great interest in developing and studying new chemical matter. Increases in precision medicine have also highlighted the importance of molecular selectivity towards biological targets and the need to access complex molecular scaffolds with unique stereochemistry features such as quaternary carbon centers. The scarcity of molecules containing all-carbon quaternary centers has constrained our ability to fully explore their properties. This report examines recent methodological advances since 2019 in their synthesis, focusing on three key synthetic approaches: single electron transfer (SET) mediated reactions, reactions mediated by chemical phenomena associated with charge separation (electrochemistry), Lewis acid and transition metal mediated cyclization/rearrangement reactions. These innovative synthetic strategies open new pathways for creating complex chemical structures, advancing our ability to develop both novel therapeutic candidates and new materials. The enhanced efficiency of these approaches enables the exploration of increasingly sophisticated molecular architectures, expanding opportunities for discovering compounds with unique biological activities and material properties.