Chemists crack the code for building complex molecules with mirror-image precision
Researchers have developed a new palladium-catalyzed method that builds complex ring-shaped molecules with precise stereochemistry—a key requirement for pharmaceuticals and fine chemicals. The breakthrough uses a clever workaround to combine two notoriously difficult chemical operations in one step, potentially accelerating drug discovery timelines and reducing manufacturing costs.
Originaltitel: Enantioselective Palladium-Catalyzed Oxidative Carbocyclization-Borylation of Dienallenes
<p>Oxidation reactions are of fundamental importance in nature and often proceed in an enantioselective manner. Palladium-catalyzed oxidative cascade carbocyclizations are efficient protocols for C-C bond formation and cyclic scaffolds construction, thus attracting widespread attention. However, the development of enantioselective versions of these reactions is challenging because commonly used phosphine-based ligands are not tolerated under oxidative conditions. The use of chiral phosphoric acids (CPAs) that provide a chiral counterion to the metal is one solution to this problem. Herein, we report a palladium-catalyzed oxidative enantio-and diastereo-selective carbocyclization-borylation of dienallenes via desymmetrization, enabling the construction of a diverse set of cyclohexenes bearing two nonadjacent stereocenters (up to 99.5:0.5 er and >20:1 dr). The asymmetric induction was obtained by the use of a catalytic amount of chiral diphenyl-3,3'- biphenanthryl-4,4 '-diyl phosphate-phosphoric acid (VAPOL-PA) through significant ligand acceleration. Moreover, the reaction could be advanced into aerobic biomimetic oxidation, where molecular oxygen was used as the terminal oxidant. The introduction of a readily modifiable boronate group with a stereogenic center at the beta-position further demonstrated the synthetic utility of this methodology.</p>