Cinchona Organocatalyzed Enantioselective Amination for Quaternized Serines as Tertiary Amides

Herein, we describe a Cinchona-aminocatalyzed enantioselective α-hydrazination of an α-formyl amide for the production of protected quaternized serines as tertiary amides with ee’s of generally >98% and ≤99% yields. The proposed TS model supported by density functional theory calculations involves a quinuclidinium ion Brønsted acid-assisted delivery of DtBAD, which occurs from the Re face of an H-bonded enaminone when using a 9S-cinchonamine catalyst, resulting in a hydrazide with the R-configuration as determined by X-ray analysis.