Solvent and TMEDA effects on the configurational stability of chiral lithiated aryloxiranes

Abstract

The employment of hexane/N,N,N',N'-tetramethylethylenediamine (TMEDA) dramatically hinders the racemization of those lithiated styrene oxides (trifluoromethyl-, chloro-, and phenylthio-substituted) that have been proven to be configurationally unstable in THF on the timescale of their reactions. The barriers to inversion and the activation parameters, calculated (Eyring equation) for reactions performed in THF, THF/TMEDA, and hexane/TMEDA, suggest the intervention of particular enantiomerization mechanisms for each case. The role of TMEDA in both coordinating and noncoordinating solvents has also been questioned and discussed in light of the kinetic data gathered and a model for deprotonation in hexane/TMEDA has also been proposed. The synthetic benefits of our results became apparent on establishing an asymmetric synthesis of an industrially important antifungal agent.