Enantioselective Synthesis of Pillar[5]arenes by Dynamic Kinetic Resolution via Pd-Catalyzed Suzuki Cross-Coupling
A. Konter, Jaume Rostoll‐Berenguer, Céline Besnard, Baptiste Leforestier, Clément Mazet
Abstract
We report a dynamic kinetic resolution based on a Pd-catalyzed asymmetric Suzuki cross-coupling reaction to afford enantioenriched and configurationally stable pillar[5]arenes. When applied to A1/A2-ditriflate-pillar[5]arenes, the method displays a high level of catalytic efficiency and stereoselectivity across a broad substrate scope. The approach can be extended to the synthesis of nearly enantiopure rim-differentiated and tetra-arylated macrocycles. The enantioenriched macrostructures can be readily derivatized into mono- and dinuclear transition metal complexes. The intricate conformational dynamics of these systems can be captured using a neural network model approach, together with metadynamics simulations. Experimental and computational analyses are consistent, with the second cross-coupling being enantio-determining in the sequential double cross-coupling reaction. Additional computational studies indicate that stereodifferentiation involves a combination of repulsive steric factors and stabilizing secondary interactions.