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

Abstract

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.

Concise synthesis of (25S)-Δ4-dafachronic acid and desulfated boophiline enabled by photoinduced decarboxylative allylation and asymmetric hydrogenation

“…These unfavorable results encouraged us to explore another strategy, involving decarboxylative allylation followed by asymmetric hydrogenation. Zhang's group has successfully developed a highly efficient catalytic system for enantioselective hydrogenation of α-substituted acrylic acids, 10 which has prompted our investigation into decarboxylative allylation. Although a similar reaction has been reported by the Chen group through a photoredox catalysis strategy, 12 we want to develop a photocatalyst-free transformation instead.…”

Iridium-Catalyzed Asymmetric Hydrogenation of Unfunctionalized Cycloalkenes to Access Chiral 2-Aryl Tetralins

“…In 2016, Andersson and co-workers reported a P,N-ligated iridium imidazole-based complex-catalyzed asymmetric hydrogenation of cyclohexene derivatives (Scheme b) . Considering the importance of chiral 2-aryl tetralin and to continue our research interests on the asymmetric hydrogenation, especially the application of our developed axis-unfixed biphenylphosphine-oxazoline (BiphPHOX) ligand in asymmetric hydrogenation reactions, herein, we report an iridium-catalyzed asymmetric hydrogenation of 3-aryl-1,2-dihydronaphalenes (Scheme c).…”