Organocatalytic Enantioselective α-Hydroxymethylation of Aldehydes: Mechanistic Aspects and Optimization

• DOI: 10.1021/acs.joc.5b00380
• Publication Date: 2015-03-20T19:22:36Z
• Authors: Robert K. Boeckman; Kyle F. Biegasiewicz; Douglas J. Tusch; John R. Miller
• Keywords: Kinetic resolution; Reactivity

Further studies of the direct enantioselective α-hydroxymethylation aldehydes employing α,α-diarylprolinol trimethylsilyl ether class organocatalysts are described. This process has proven efficient for access to β-hydroxycarboxylic acids and δ-hydroxy-α,β-unsaturated esters from in generally good yields, excellent enantioselectivity, compatibility with a broad range functional groups aldehyde. The goal these was identify critical reaction variables that influence yield enantioselectivity such as catalyst structure, pH medium, purity reactants reagents particularly respect presence acidic impurities, nature buffer, along standard including solvent, time, temperature mixing efficiency. previously identified intermediate lactol been further characterized its reactivity examined. These have led identification most translating directly into improved substrate scope, reproducibility, yields.