Dictating Thermodynamic Control through Tethering: Applications to Stereoselective Bis-Spiroketal Synthesis.

Approaches to stereocontrol that invoke thermodynamic control fail when two or more potential products are energetically similar, but rational structural perturbations can be employed to break the energetic degeneracy and provide selective transformations. This manuscript illustrates that tethering is an effective approach for the stereoselective construction of bis-spiroketals with thermodynamically similar stereoisomers, providing a new approach to set remote stereocenters and prepare complex structures that have not previously been accessed stereoselectively.