Expanding the Synthetic Utility of β-Dicarbonyl Compounds in Stereoconvergent Reactions

The conversion of racemic starting materials to stereochemically complex products through stereoconvergent pathways is a powerful synthetic tool. As the prototypical case, hydrogenative enantioconvergent reactions of α-substituted β-oxo acid derivatives have been widely employed in the industrial production of enantiomerically enriched secondary alcohols. Despite the theoretical capacity of these intermediates to deliver enantiopure tertiary alcohols, non-hydrogenative enantioconvergent reactions of this class of compounds remain rare. Our efforts expanding the synthetic utility of β-oxo acid derivatives beyond hydrogenative chemistry are discussed. The high acidity of β-dicarbonyls was leveraged for the development of stereodivergentvergent copper-catalyzed borylative cyclization reactions of racemic β-keto esters, a doubly stereoconvergent crystallization enabled by asymmetric catalysis, and crystallization-enabled Henry reactions. These methods provide access to highly functionalized building blocks containing up to five contiguous stereogenic centers in a single synthetic operation.