Synthesis of Planar Chiral [2.2]Paracyclophanes via Biocatalyzed Desymmetrization of Primary Alcohols

Planar chirality represents a distinct and underexplored form of molecular asymmetry that arises from restricted three-dimensional conformations. It holds significant potential for expanding chemical space and enabling the development of novel chiral reagents, catalysts, and functional materials. Among the most prominent scaffolds exhibiting planar chirality is the rigid and conformationally stable [2.2]paracyclophane (PCP), known for its exceptional photophysical and electronic properties. In this work, we present a simple, cost-effective, and scalable biocatalytic desymmetrization strategy for the efficient synthesis of two key disubstituted PCP intermediates, the pseudo-geminal and pseudo-para isomers, directly addressing the current lack of catalytic methods for inducing planar chirality on this scaffold. This practical approach enables access to structurally complex PCP frameworks and underscores the largely overlooked potential of biocatalysis as a powerful, sustainable route to planar chiral molecules.