Asymmetric Synthesis of Diverse Glycolic Acid Scaffolds via Dynamic Kinetic Resolution of α-Keto Esters

Abstract

The dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation has been developed as a technique for the highly stereoselective construction of structurally diverse β-substituted-α-hydroxy carboxylic acid derivatives. Through the development of a privileged m-terphenylsulfonamide for (arene)RuCl(monosulfonamide) complexes with a high affinity for selective α-keto ester reduction, excellent levels of chemo-, diastereo-, and enantiocontrol can be realized in the reduction of β-aryl- and β-chloro-α-keto esters.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…137,138,139,140,141,142 In 2009, Zhang and coworkers disclosed the asymmetric transfer hydrogenation DKR strategy for the reduction of cyclic and acyclic β-ketosulfones under mild conditions with a broad substrate scope (Scheme 24). 143 Along similar lines, β-formyl-sulfones can also be reduced efficiently to the corresponding primary alcohols.…”

Diametric Stereocontrol in Dynamic Catalytic Reduction of Racemic Acyl Phosphonates: Divergence from α-Keto Ester Congeners

“…Based on our group’s recent success in tuning the diastereoselectivity of the DKR-ATH of β-chloro-α-keto esters through the application of a bulky m -terphenylsulfonamide ligand, 6b aminosulfonamide L2 was employed in the reduction of 1b in DMF and delivered a marked increase in diastereoselectivity (entry 2). Changing the solvent to DMSO resulted in a boost in diastereoselection up to 20:1 (entry 3).…”

“…We recently documented a new Ru(II)-catalyzed DKR-ATH of β-aryl-α-keto esters B providing hydride delivery from the Si -face to afford α-hydroxy esters E with high levels of diastereo- and enantioselectivity (path c). 6 Extrapolating from precedent, the dynamic reduction of racemic α-aryl acyl phosphonate B was proposed to occur with analogous facial preference; however, in the event, the reduction occurred from the opposite diastereotopic face providing the quasidiastereomeric product F with excellent levels of selectivity (path d). 7 …”

Dynamic Kinetic Asymmetric Transformations of β‐Stereogenic α‐Ketoesters by Direct Aldolization

“…We postulated that the identity of the β‐substituent of the α‐ketoester would be important in promoting the desired reactivity owing to its direct impact on both the β‐CH acidity and the steric environment about the ketone. To this end, we selected β‐halo‐α‐ketoesters to investigate this potential reactivity profile owing to their successful previous use as substrates in DKR reactions 5b. 7…”