Adamantyl-BOX Ligand Enabling Stereoselective Synthesis of Axially Chiral Aldehydes Bearing Vicinal Stereogenic Centers.

Biaryl frameworks combining axial and multiple central chiralities are highly valuable in synthesis and drug discovery. However, simultaneous construction of axial and vicinal central chiralities faces severe matching/mismatching limitations. Herein, we describe a dual photoredox/nickel-catalytic system for desymmetrization of biaryl dialdehydes. By employing a bisoxazoline ligand bearing bulky adamantylphenyl side arms, its chiral cavity and distal substituent effects work synergistically to achieve high stereoselectivity, furnishing homoallylic alcohols with up to >20:1 dr and 99% ee. DFT calculations demonstrate that stereoselectivity is predominantly governed by a complex network of noncovalent interactions between the ligand and substrate.