Asymmetric Transfer Hydrogenation of Acyclic 1,4-Diketones for the Synthesis of Diversified Cyclic Products via Double Dynamic Kinetic Resolution

Abstract

Asymmetric transfer hydrogenation (ATH) serves as a powerful strategy to access enantioenriched substances; however, constructing diversified molecular skeletons and converting acyclic substrates into cyclic products via ATH remain challenging. In this full article, we report on the selective ATH of acyclic racemic 1,4-diketones. By modulating the electron-withdrawing groups (EWGs) on the substrates and tuning the reaction conditions, four types of cyclic products─including dihydrofurans, γ-lactones, tetrahydrofuranols, and tetrahydrofurans─are obtained through a double dynamic kinetic resolution (DKR) process. Moreover, the synthetic value of this method has been demonstrated by the synthesis of five bioactive compounds, i.e., megacerotonic acid, (7′E)-(7R,8R)-salvianolic acid V, prunellanate B, calyxolane A, and a magnosalicin-type neolignane, which fall into three categories of active molecular families. Mechanistic insights are further elucidated through combined experimental studies and density functional theory (DFT) calculations.