Theoretical Mechanistic Investigation of the Dynamic Kinetic Resolution of N‑Protected Amino Acid Esters using Phase-Transfer Catalysts

A detailed theoretical mechanistic investigation on the
dynamic
kinetic resolution of N-protected amino acid esters using phase-transfer
catalysts is described. Semiautomatic exhaustive conformation search
of transition state (TS)-like structures were carried out using the
ConFinder program and the pseudo-TS conformational search (PTSCS)
method. This conformational search method successfully provided reasonable
TS structures for determining the stereoselectivity in the asymmetric
base hydrolysis of hexafluoroisopropyl (HFIP) esters as well as the
racemization mechanism. Furthermore, the independent gradient model
(IGM) analysis of the TS structures suggested that the H-bonding interactions
with the oxyanion hole and π-stacking interactions are the common
important features of the proposed TS structures that determine the
stereoselectivity.