Pd-catalyzed enantioselective synthesis of axially chiral alkylidene cycloalkanes

Precise synthesis of axially chiral molecules is an important goal that organic chemists are actively pursuing because of their high value in pharmaceutics, fine chemicals, and materials science. The enantioselective synthesis of non-atropisomeric axially chiral alkylidene cycloalkanes, despite their utility, has been considered a great challenge and remains underexplored due to the remote distance between the chirality-related groups or atoms. We established a general efficient methodology to synthesize axially chiral alkylidene cycloalkanes via palladium-catalyzed asymmetric allylic alkylation, showing excellent enantioselectivities, high yields, and a wide substrate scope. The additive effect plays a pivotal role to improve the chem-and enantioselectivity in this reaction. Due to the value and structural diversity of the products, this method provides the opportunity to further tap into the applied potential of axially chiral olefins in related research fields.

Automated summary

The precise synthesis of axially chiral molecules is highly valuable in pharmaceutics, fine chemicals, and materials science. However, the enantioselective synthesis of non-atropisomeric axially chiral alkylidene cycloalkanes has been a great challenge due to the remote distance between chirality-related groups or atoms. We developed a general efficient methodology using palladium-catalyzed asymmetric allylic alkylation, which showed excellent enantioselectivities, high yields, and a wide substrate scope. The additive effect played a crucial role in improving the chem- and enantioselectivity of this reaction. Due to the value and structural diversity of the products, this method provides an opportunity for further exploration of the applied potential of axially chiral olefins in related research fields.