Transient Directing Group-Enabled Palladium-Catalyzed Axially Chiral C–H Alkynylation

Efficient and modular approaches to accessing diverse atropisomers remain challenging. We reported a palladium-catalyzed enantioselective C-H alkynylation of styrene derivatives via a transient directing group (TDG) strategy, affording axially chiral styrenes under mild conditions with high enantioselectivity. Pyrrole-based transient chiral auxiliaries obtained by computationally assisted design played critical roles in both transient directing group formation and stereochemical control. Computational studies revealed that enhanced auxiliary rigidity and multiple noncovalent interactions enabled effective enantiodifferentiation. The resulting axially chiral aldehydes are versatile platforms, readily converting into valuable chiral molecules such as carboxylic acids and alcohols in one step. Notably, the derived chiral carboxylic acids act as competent ligands for asymmetric catalysis, highlighting the synthetic utility and broader potential of this strategy.