An Enantioselective Suzuki-Miyaura Coupling To Form Axially Chiral Biphenols

Axial chirality features prominently in molecules of biological interest as well as chiral catalyst designs, and atropisomeric 2,2'-biphenols are particularly prevalent. Atroposelective metal-catalyzed cross-coupling is an attractive and modular approach to access enantioenriched biphenols, and yet existing protocols cannot achieve this directly. We address this challenge through the use of enantiopure, sulfonated SPhos (sSPhos), an existing ligand that has until now been used only in racemic form and that derives its chirality from an atropisomeric axis that is introduced through sulfonation. We believe that attractive noncovalent interactions involving the ligand sulfonate group are responsible for the high levels of asymmetric induction that we obtain in the 2,2'-biphenol products of Suzuki-Miyaura coupling, and we have developed a highly practical resolution of sSPhos via diastereomeric salt recrystallization.

Automated summary

Axial chirality is important in molecules of biological interest and chiral catalyst designs. Atropisomeric 2,2'-biphenols are commonly found, and their synthesis with enantioenrichment is desirable. By using enantiopure, sulfonated SPhos (sSPhos), a ligand with an atropisomeric axis introduced through sulfonation, a practical separation method is developed to access enantioenriched biphenols. The high levels of asymmetric induction obtained in the Suzuki-Miyaura coupling reaction may be attributed to attractive noncovalent interactions involving the ligand sulfonate group.