Alcohol group migration by proximity-enhanced H atom abstraction

Subtle changes in molecular structure can lead to profound changes in molecular function. However, even minor structural refinements can require the complete resynthesis of a target molecule, adding time and cost to molecular design campaigns¹. Recently, editing methods have emerged targeting subtle molecular perturbations, including atomic substitution, stereocentre inversion and functional group repositioning². These precision tools hold the potential to streamline the optimization of molecular function by fine-tuning molecular structure. Here we report an editing method that enables the migration of common alcohol functional groups to proximal sites with predictable stereo- and regiochemical outcomes. The reaction proceeds through a 1,2-acyloxy radical migration step under reversible H atom transfer catalysis conditions promoted by the excited-state decatungstate polyanion. Proximity effects arising from non-covalent interactions between substrate and reagent enable efficient radical formation at polarity-mismatched positions. Application of this tool at a late synthetic stage allows for the precise repositioning of alcohol functional groups, whereas integration with common alcohol group installation methods provides new synthetic strategies to access challenging oxygenation patterns.