Stereoselective synthesis through remote functionalization

Transition-metal-catalysed alkene isomerization is instrumental to remote functionalization processes, in which a chemical transformation is induced at a position remote from the initial reactive site. The dynamic nature of alkene isomerization, which is crucial for such transformations, often leads to substantial difficulties in controlling the stereochemistry of C(sp3) centres along the carbon skeleton. This review features synthetic methods that tackle this issue and strategically leverage alkene isomerization to control C(sp3) stereocentres in complex organic molecules. Stereocentres can be created at either the initiation or termination site of an isomerization process, retained during chain-walking across the molecular backbone or revealed through restructuring of the carbon skeleton by selective ring-opening of a strained ring. As each of these options imposes different mechanistic requirements, the different examples are divided according to the stage in the chain-walking process at which stereochemistry is established and the type of intermediates that lead to stereodefined products. Remote functionalization through alkene isomerization is a popular strategy in organic synthesis. The dynamic nature of alkene isomerization typically leads to difficulties in controlling the stereochemistry of C(sp3) centres along the carbon skeleton. This Review outlines synthetic methods that tackle this issue and leverage alkene isomerization to control C(sp3) stereocentres in complex organic molecules.