Metal-free oxidative cross-coupling enabled practical synthesis of atropisomeric QUINOL and its derivatives

Abstract

As an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis.

1-(Isoquinolin-1-yl)naphthalen-2-ol (QUINOL) is an atropisomeric heterobiaryl that serves as a platform for the synthesis of other biaryl ligands useful in asymmetric catalysis. Here, the authors report a straightforward oxidative cross-coupling reaction between isoquinolines and 2-naphthols to efficiently access the QUINOL scaffolds in a metal-free manner.