Kinetic resolution of 1-(1-alkynyl)cyclopropyl ketones via gold-catalyzed divergent (4 + 4) cycloadditions: stereoselective access to furan fused eight-membered heterocycles.

Abstract

Chiral eight-membered heterocycles comprise a diverse array of natural products and bioactive compounds, yet accessing them poses significant challenges. Here we report a gold-catalyzed stereoselective (4 + 4) cycloaddition as a reliable and divergent strategy, enabling readily accessible precursors (anthranils and ortho-quinone methides) to be intercepted by in situ generated gold-furyl 1,4-dipoles, delivering previously inaccessible chiral furan/pyrrole-containing eight-membered heterocycles with good results (56 examples, all >20 : 1 dr, up to 99% ee). Moreover, we achieve a remarkably efficient kinetic resolution (KR) process (s factor up to 747). The scale-up synthesis and diversified transformations of cycloadducts highlight the synthetic potential of this protocol. Computational calculations provide an in-depth understanding of the stereoselective cycloaddition process.