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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
26 Apr 2024
Accepted
14 May 2024
First published
22 May 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024, Advance Article

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

X. Wang, R. Lv and X. Li, Chem. Sci., 2024, Advance Article , DOI: 10.1039/D4SC02763A

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