Dynamic kinetic resolution of 1-substituted-3-methyl-3-phospholene oxides via the formation of diastereomeric alkoxyphospholenium salts

Abstract

A dynamic kinetic resolution method based on the formation of covalent diastereomeric intermediates was elaborated for the preparation of enantiomerically enriched 1-substituted-3-methyl-3-phospholene oxides. The 3-phospholene oxides were first converted to the corresponding chloro-3-phospholenium chlorides. The dynamic interconversion between the enantiomers of the chlorophospholenium salts was verified experimentally, as it is the key step for a dynamic resolution. The cyclic chlorophospholenium salts were reacted with a chiral auxiliary bearing a hydroxy function to form the corresponding diastereomeric alkoxyphospholenium salts in unequal amounts. The diastereomeric species then rearranged into the corresponding optically active 3-phospholene oxides upon heating. After a screening of chiral auxiliaries and the optimization of the reaction conditions, several scalemic 1-aryl- or 1-alkyl-3-methyl-3-phospholene oxides were prepared in excellent yields and with ee-s up to 35%. The key steps of this resolution were investigated by quantum chemical calculations to get some insights into the factors responsible for the stereoselection.