Cobalt-catalyzed enantioselective [2+2+2] cycloaddition/electrocyclic ring opening cascade of aldehydes and diynes

Transition metal-catalyzed [2+2+2] cycloaddition represents a cornerstone methodology in organic synthesis. However, the cobalt-catalyzed asymmetric cycloaddition system remains underexplored despite its synthetic potential and advantages. This work describes a cobalt-catalyzed atroposelective [2+2+2] cycloaddition/electrocyclic ring-opening cascade between 1,6-diynes and axial pre-chiral biaryl dialdehydes, to generate axially chiral conjugated diene ketones. Notably, aldehydes serve as both oxygen and carbon donors, undergoing formal double bond cleavage to forge new C=O and C=C bonds in a single catalytic cycle. The cascade transformation operates under mild, redox-neutral conditions, achieving exceptional Z/E selectivity, high enantioselectivity, and broad functional group compatibility. Mechanistic investigations combining density functional theory calculations and experimental studies suggest the involvement of a cobalt-mediated [2+2+2] cycloaddition and ring-opening step in the cascade process. The deformation energy of the catalyst and substrate steric effects contributed to chiral induction.