Catalytic Asymmetric Transfer Hydrogenation of β,γ-Unsaturated α-Diketones.

Abstract

Asymmetric transfer hydrogenation (ATH) has been recognized as a highly valuable strategy that allows access to enantioenriched substances and has been widely applied in the industrial production of drug molecules. However, despite the great success in ATH of ketones, highly efficient, regio- and stereoselective ATH on enones remains underdeveloped. Moreover, optically pure acyloins and 1,2-diols are both extremely useful building blocks in organic synthesis, medicinal chemistry, and materials science, but concise asymmetric approaches allowing access to different types of acyloins and 1,2-diols have scarcely been discovered. We report in this paper the first highly efficient ATH of readily accessible β,γ-unsaturated α-diketones. The protocol affords four types of enantioenriched acyloins and four types of optically pure 1,2-diols in highly regio- and stereoselective fashion. The synthetic value of this work has been showcased by the divergent synthesis of four related natural products. Moreover, systematic mechanistic studies and density functional theory (DFT) calculations have illustrated the origin of the reactivity divergence, revealed the different roles of aromatic and aliphatic substituents in the substrates, and provided a range of unique mechanistic rationales that have not been disclosed in ATH-related studies.