Ruthenium-Catalyzed Diversified Kinetic Resolutions of Diaryl-Substituted Cyclobutenones via Asymmetric Transfer Hydrogenation

Abstract

1,2-Diaryl-3,4-dialkyl cyclobutanes (DA₂CBs) are important scaffolds in numerous bioactive substances. However, the concise asymmetric synthesis of this type of compound remains a formidable challenge, especially in a stereodivergent manner. In this work, we report for the first time the diversified kinetic resolutions of diaryl-substituted cyclobutenones through Ru-catalyzed asymmetric transfer hydrogenation (ATH). The protocol affords a range of diaryl-substituted four-membered rings with structural and stereochemical diversity, which facilitates the total synthesis of six representative natural products in a stereodivergent fashion. Detailed mechanistic studies have been conducted to reveal the origin of the three kinetic resolution modes, and the catalysts are found to play vital roles in determining the reaction pathways, a phenomenon that has been scarcely observed in the field of ATH.