Single-Flask Enantioselective Synthesis of α-Amino Acid Esters by Organocatalysis

An operationallysimple Knoevenagel condensation/asymmetricepoxidation/dominoring-opening esterification (DROE) approach has been disclosed tosuccessfully access a good variety of (R)- and (S)-& alpha;-arylglycine esters from commercially availablealdehydes, phenylsulfonyl acetonitrile, cumyl hydroperoxide, anilines,and readily available Cinchona alkaloid-based catalystsusing a single solvent and reaction vessel. DFT calculations performedon the key asymmetric epoxidation showed the importance of cooperativeH-bonding interactions in affecting the stereocontrol.

Automated summary

An operationally simple method, called the Knoevenagel condensation/asymmetric epoxidation/dominoring-opening esterification (DROE) approach, has been developed to access a wide range of (R) and (S)-α-arylglycine esters using a single solvent and reaction vessel. The method involves commercially available aldehydes, phenylsulfonyl acetonitrile, cumyl hydroperoxide, anilines, and readily available Cinchona alkaloid-based catalysts. Density functional theory calculations revealed the significance of cooperative H-bonding interactions in achieving stereocontrol.