Tri- and Tetra- <i>ortho</i> -Substituted Biaryls via Lithium Cuprate-Catalyzed Reductive Desymmetrization of Isophthaldehydes

Polyfunctionalized chiral biaryls, especially those with dense <i>ortho</i> substitution patterns, are important building blocks for catalysts, pharmaceuticals, and advanced materials. Stereoselective synthesis of these congested architectures while simultaneously introducing multiple sites for further modification is highly sought after. Here, we report that a combination of an aziridinyl methanol-derived tetradentate ligand and a lithium cuprate salt can differentiate between the pair of aldehydes in biaryl isophthaldehydes to enable a desymmetric hydrosilylation. The bimetallic synergy within the ligand pocket delivers excellent enantiocontrol not only for structurally diverse tri-<i>ortho</i>-substituted isophthaldehydes from axis-forming cross-coupling but also for polyaldehydes prepared via the "plane-to-axis" ozonolysis of pyrenes. This strategy further exploits the reactivity of the resulting primary alcohol and remaining aldehyde to accommodate divergent postreduction transformations. Notably, the bismethylene-biaryl product generated by desymmetrization, with its four readily modifiable <i>ortho</i> positions, offers modular access to biaryl frameworks bearing diverse functionalities and structural features for broad applications.