Photocatalytic Radical‐Polar Crossover Enables Modular Access to Bicyclo2.m.nAlkane Alcohol Bioisosteres

ABSTRACT The strategic replacement of aromatic rings with saturated bioisosteres has become a pivotal strategy in medicinal chemistry, offering a proven path to improve the metabolic stability and safety profiles of drug candidates. Conventional access to these valuable saturated scaffolds, however, heavily relies on strain‐release strategies that mandate the use of highly strained, synthetically challenging precursors. Herein, we report a general platform based on a visible‐light‐induced radical–polar crossover (RPC) manifold. This method employs bench‐stable γ‐ and δ‐keto acids as radical precursors, which, upon activation, engage in cross‐coupling with a diverse array of π‐systems. This straightforward approach provides direct and efficient access to a wide range of synthetically elusive saturated bicyclic alcohol bioisosteres. By circumventing the need for pre‐strained intermediates, our strategy delivers the target architectures in high yields with excellent functional group tolerance. Furthermore, successful product derivatizations underscore the synthetic utility of this method, while mechanistic investigations corroborate the proposed RPC pathway. Together, these findings establish our platform as a practical and robust alternative to current paradigms.