Bimetallic Ru/Ru‐Catalyzed Asymmetric One‐Pot Sequential Hydrogenations for the Stereodivergent Synthesis of Chiral Lactones.

Asymmetric sequential hydrogenations of α‐methylene γ‐ or δ‐keto carboxylic acids are established in one‐pot using a bimetallic Ru/Ru catalyst system, achieving the stereodivergent synthesis of all four stereoisomers of both chiral γ‐ and δ‐lactones with two non‐vicinal carbon stereocenters in high yields (up to 99%) and with excellent stereoselectivities (up to >99% ee and >20:1 dr). The compatibility of the two chiral Ru catalyst systems is investigated in detail, and it is found that the basicity of the reaction system plays a key role in the sequential hydrogenation processes. The protocol can be performed on a gram‐scale with a low catalyst loading (up to 11000 S/C) and the resulting products allow for many transformations, particularly for the synthesis of several key intermediates useful for the preparation of chiral drugs and natural products. [ABSTRACT FROM AUTHOR]