Determination of the relative stereochemistry of flexible ring systems by a cage-based crystalline sponge method

Abstract We present a cage-based crystalline sponge method as a practical strategy for the relative stereochemical determination of flexible saturated heterocycles that are not amenable to nuclear magnetic resonance analysis. Validated using a bis-tetrahydrofuran series and complex bioactives, this method offers a robust solution for resolving stereochemical ambiguities in conformationally flexible molecular systems.