Organocatalytic Desymmetrization Prompts Central-to-Planar Chirality Transfer to [2.2]Paracyclophanes

Planar chiral [2.2]paracyclophanes consist of two functionalized benzene rings connected by two ethylene bridges. These organic compounds have a wide range of applications in asymmetric synthesis, as both ligands and catalysts, and in materials science, as polymers, energy materials and dyes. However, these molecules can only be accessed by enantiomer separation via a) time-consuming chiral separations and b) kinetic resolution approaches, often with a limited substrate scope, yielding both enantiomers. Here, we report a simple, efficient, metal-free protocol for organocatalytic desymmetrization of centrosymmetric diformyl[2.2]paracyclophanes. Our detailed experimental mechanistic study highlighted differences in the origin of enantiocontrol of pseudo-para and pseudo-ipso diformyl derivatives in NHC catalysed desymmetrizations based on whether a key Breslow intermediate is irreversibly or reversibly formed in this process. This gram-scale reaction enables a wide range of follow-up derivatizations of carbonyl groups, producing various enantiomerically pure planar chiral [2.2]paracyclophane derivatives, thereby underscoring the potential of this method.