Copper(II)-Catalyzed Enantioselective Friedel-Crafts Alkylation Reactions of 1-Naphthols and Electron-Rich Phenols with Trifluoropyruvates

J Org Chem. 2025 Jul 3. doi: 10.1021/acs.joc.5c00112. Online ahead of print.

Abstract

By fine-tuning the electronic and steric properties of the chiral ligands, chiral Cu(II) complex-catalyzed enantioselective Friedel-Crafts alkylation/lactonization of 1-naphthols and electron-rich phenols with trifluoropyruvates provided the desired products with up to 99% ee and up to 99% yield. The reactions were carried out on a gram scale with low catalyst loading. Especially, the optically pure GABAB positive allosteric modulator (R)-BHFF was prepared using this protocol.