Enantiodivergent Kinetic Resolution of 1,1′-Biaryl-2,2′-Diols and Amino Alcohols by Dipeptide-Phosphonium Salt Catalysis Inspired by the Atherton-Todd Reaction

A highly enantiodivergent organocatalytic method is disclosed for the synthesis of atropisomeric biaryls via kinetic resolution inspired by a dipeptide-phosphonium salt-catalyzed Atherton-Todd (A-T) reaction. This flexible approach led to both R- and S-enantiomers by fine-tuning of bifunctional phosphonium with excellent selectivity factors (s) of up to 1057 and 525, respectively. The potential of newly synthesized O-phosphorylated biaryl diols was illustrated by the synthesis of axially chiral organophosphorus compounds. Mechanistic investigations suggest that the bifunctional phosphonium halide catalyst differentiates between the in-situ-generated P-species in the A-T process, mainly involving phosphoryl chloride and phosphoric anhydride, thus leading to highly enantiodivergent O-phosphorylation reactions. Furthermore hydrogen bonding interactions between the catalysts and phosphorus molecules were crucial in asymmetric induction.

Automated summary

An innovative enantiodivergent organocatalytic method was developed for the synthesis of atropisomeric biaryls, inspired by a dipeptide-phosphonium salt-catalyzed Atherton-Todd reaction. The method allowed for the production of both R- and S-enantiomers with high selectivity factors, showcasing the potential of the newly synthesized O-phosphorylated biaryl diols. Mechanistic investigations revealed the crucial role of hydrogen bonding interactions between the catalysts and phosphorus molecules in asymmetric induction.