Mechanistic study on the enantiodivergent kinetic resolution of axial chiral binaphthol via the peptide-phosphonium salt-catalyzed Atherton–Todd reaction†

Abstract

Density functional theory calculations were conducted to elucidate the mechanism and stereoselectivity of the Atherton–Todd reaction-guided enantiodivergent kinetic resolution of axial chiral binaphthol catalyzed by peptide-phosphonium salts. The reaction involved the formation of two reactive phosphorus species: diphenylphosphinic chloride and diphenylphosphinic anhydride . Subsequent nucleophilic acylation of the deprotonated diol anion with / yielded chiral O-phosphorylation products. The hydrolysis of was identified as the rate-determining step in the uncatalyzed reaction. Peptide-phosphonium salts accelerated the hydrolysis of , reducing the energy barriers for the → transformation, for the two phosphonium salts with diverse side chains ( and ). In the kinetic resolution process, the chiral peptide-phosphonium salt catalysts simultaneously activated the diol anion and / through ion-pairing and multiple hydrogen bonding interactions. preferentially interacted with and the R-diol anion via favorable π–π stacking, affording the R-product, while exhibited higher affinity for and the S-diol anion due to significant steric effects, leading to the formation of the S-atropisomer. Structural analysis of five representative catalysts revealed that silicon substituents, steric effects from Bn and Boc groups, and dipeptide skeletons collectively contributed to a well-defined chiral environment. These features enhanced the catalyst's rigidity and chiral recognition ability, enabling excellent enantioselectivity.