Copper-Catalyzed Enantioselective Interrupted Azide-Alkyne Cycloaddition to Access Axially Chiral Diaryl Ethers

Abstract

While transition metal-catalyzed enantioselective azide-alkyne cycloadditions are well-established for accessing 1,4-disubstituted triazoles, the direct enantioselective synthesis of chiral 1,4,5-trisubstituted triazoles from terminal alkynes via an interrupted process remains largely underdeveloped. Herein, we report a copper-catalyzed enantioselective interrupted azide-alkyne cycloadditions. This method enables the facile construction of enantioenriched axially chiral diaryl ethers bearing a 1,4,5-trisubstituted triazole moiety directly from terminal alkynes. Mechanistic studies reveal the absence of further kinetic resolution process of the product, underscoring the crucial role of our newly developed chiral ligand L5 in achieving excellent enantiocontrol and yield. The combination of Et3N and LiOtBu is essential to the inhibition of protonated byproduct. The orthogonal reactivity of the residual terminal alkyne and amine groups within the products provides versatile platforms for downstream chemistry, enriching the structural diversity of axially chiral diaryl ethers.