LAUSR

The stereoselective synthesis of complex targets requires the precise orchestration of chemical transformations that simultaneously establish the connectivity and spatial orientation of desired bonds. In this work, we describe a complementary paradigm for the synthesis of chiral molecules and their isomers, which tunes the three-dimensional structure of a molecule at a late stage. Key to the success of this strategy is the development of a mild and highly general photocatalytic method composed of decatungstate polyanion and disulfide cocatalysts, which enable the interconversion of unactivated tertiary stereogenic centers that were previously configurationally fixed. We showcase the versatility of this method—and the implementation of stereoediting logic—by the rapid construction of chiral scaffolds that would be challenging to access using existing tools and by the late-stage stereoediting of complex targets. Description Light tweak to carbon–hydrogen configuration The relative configuration of chemical bonds in a molecule often has great influence over its pharmaceutical properties. It therefore complicates drug synthesis that many readily available precursors, as well as many common reactions, can deliver one possible mutual configuration of carbon centers but not another. Y. Zhang et al. report that a tungsten-based photocatalyst paired with a disulfide hydrogen transfer agent can efficiently modify the configuration of tertiary carbon–hydrogen bonds that are conventionally inert. This process, which generally, but not exclusively, favors the thermodynamic product, offers a convenient means of precisely toggling between diastereomers in complex molecules. —JSY Photocatalysis can efficiently and selectively modify the configuration of conventionally inert carbon–hydrogen bonds.