Mechanistic Insights into the Organocatalytic Kinetic Resolution of Oxazinones through Alcoholysis

A complete computational study has been performed in order to rationalise the results of a new organocatalytic approach to the kinetic resolution of 4-substituted oxazinones which results in highly enantioenriched and orthogonally-protected β-amino acids. DFT-analysis elucidated the preferable binding orientation of the 4-oxazinone under study, predicted the formation of the observed major R product with a calculated ee in good agreement with the experimental data and allowed a complete mechanistic and stereochemical understanding of the catalysis. The alcoholytic kinetic resolution of a 7-memebered ring analogue to generate enantioenriched γ-amino acids was experimentally and computationally investigated for the first time.