Molecules that can adopt distinct diastereomeric forms (e.g., cis or trans) are ubiquitous and can be found in pharmaceuticals, materials, and commodity chemicals. The differing physical properties of diastereomers, and the ability to control their interconversion, has enabled applications ranging from the control of cell wall function to the operation of molecular motors. To date, switchable diastereomers based on planar motifs such as olefins, azobenzenes, or imines have been used as building blocks for constructing complex molecular scaffolds (Figure ). By contrast, 3-dimensional (3D) motifs that isomerize substituents in perpendicular planes are comparably rare and remain underdeveloped. Synthetic routes to motifs with controlled 3D isomerization processes may enable novel applications that build on existing precedence with their 2D congeners or in unexplored reticular frameworks.