Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of β-Substituted α-Oxobutyrolactones

Abstract

A concise and effective ruthenium-catalyzed asymmetric transfer hydrogenation of β-substituted α-oxobutyrolactones has been developed, delivering a series of cis-β-substituted α-hydroxybutyrolactone derivatives with excellent yields, enantioselectivities, and diastereoselectivities. Two consecutive stereogenic centers were constructed in one step through dynamic kinetic resolution under basic conditions. The reaction could be conducted on a gram scale without loss of activity and enantioselectivity. The reductive products could be easily transformed into useful building blocks.

Hydrogen-Bonding Ability of Noyori–Ikariya Catalysts Enables Stereoselective Access to CF3-Substituted syn-1,2-Diols via Dynamic Kinetic Resolution

“…Efficient DKR relies on a fast dynamic interconversion of the starting material’s enantiomers and on a highly enantio-discriminating asymmetric transformation. , Noyori–Ikariya type ruthenium catalysts for asymmetric transfer hydrogenation (ATH), for example C1 – C8 (Figure a), − were used in efficient DKR of several classes of complex ketones. − Traditionally, the origin of enantioselectivity for the reduction of ketones with this type of catalyst has been associated with the CH/π interaction between an electron-deficient η 6 -arene ligand and π electrons of the ketone substrate . Configuration at the α-stereocenter during DKR-ATH was deemed to be controlled by the steric repulsion (Figure b), − although this assertion was rarely supported by computational analysis. , …”

“… 9 − 11 Traditionally, the origin of enantioselectivity for the reduction of ketones with this type of catalyst has been associated with the CH/π interaction between an electron-deficient η 6 -arene ligand and π electrons of the ketone substrate. 12 Configuration at the α-stereocenter during DKR-ATH was deemed to be controlled by the steric repulsion ( Figure 1 b), 13 − 20 although this assertion was rarely supported by computational analysis. 21 , 22 …”