Kinetic Resolution, Dynamic Kinetic Resolution and Asymmetric Desymmetrization by N-Heterocyclic Carbene Catalysis

Abstract

N-Heterocyclic carbenes (NHCs) are now well-established organocatalysts for a large number of asymmetric and non-asymmetric transformations. In the last 15 years, there has been significant interest in using NHCs in kinetic resolution (KR), dynamic kinetic resolution (DKR) and asymmetric desymmetrization reactions for the stereoselective synthesis of enantioenriched compounds, with diverse substrates and activation modes being adopted to this end. This short review brings into focus the progress made on NHC-catalyzed KR, DKR, and asymmetric desymmetrization from 2004 until December 2018. The literature discussed in this article is classified on the basis of the type of reaction involving the NHC catalyst.1 Introduction2 Acylation Strategies2.1 O-Acylation2.2 N-Acylation2.3 C-Acylation3 Aldol-Acylation Processes4 Benzoin Reactions5 Stetter Reactions6 Miscellaneous Approaches7 Conclusion

Access to Optically Enriched α-Aryloxycarboxylic Esters via Carbene-Catalyzed Dynamic Kinetic Resolution and Transesterification

“…Mild conditions are involved, and the desired enantiomer can be obtained with over 90% yields (for most substrates) and up to 99:1 er values. Key mechanistic steps of our reaction include addition of a chiral NHC catalyst to the racemic ester substrate ( 1 ) to form two azolium ester intermediates [( S )- I and ( R )- I ] that can readily isomerize to each other. Selective reaction of the azolium ester intermediates with the alcohol substrate ( 2 ) constitutes a dynamic kinetic resolution process that leads to a stable ester product ( 3 ) with an excellent yield and optical purity.…”

Metal-Catalyzed Enantioconvergent Transformations

“…Iron-catalyzed enantioconvergent Kumada reaction of αchloro and α-bromo alkanoates 7 has been described by Nakamura and co-workers. 43 This cross-coupling is catalyzed by Fe(acac) 3 and the chiral phosphine (R,R)-BenzP (16) working in THF at 0 °C to give esters 9 in up to 92% yield and 82% ee (Scheme 4). Compounds 9 were readily transformed into the corresponding α-aryl alkanoic acids 17 with up to >98% ee by simple deprotection/recrystallization.…”

Stereodivergent Nucleophilic Additions to Racemic β-Oxo Acid Derivatives: Fast Addition Outcompetes Stereoconvergence in the Archetypal Configurationally Unstable Electrophile

“…The conversion of racemic starting materials to stereochemically complex products through stereoconvergent pathways is a powerful synthetic tool . As the prototypical case, hydrogenative stereoconvergent reactions of α-substituted β-oxo acid derivatives have been widely employed in the scalable production of enantiomerically enriched secondary alcohols .…”