Resolution of aryl-H-phosphinates applied in the synthesis of P-stereogenic compounds including a Brønsted acid NMR solvating agent

Abstract

A library of racemic H-phosphinates incorporating a variety of alkoxy groups or substituted aryl groups was prepared. Starting with resolving agent screening, an efficient enantioseparation method was developed and optimized using (R,R)-(1-naphthyl)-spiro-TADDOL as the resolving agent. This method gave 12 out of 16 H-phosphinates with an ee of above 91%, and 9 of these derivatives were practically enantiopure (ee > 98%). Moreover, this resolution could be used on a gram-scale. The structures of the diastereomeric intermediates and the secondary interactions between them were investigated by single-crystal XRD, and the most important factors of enantiomeric recognition were established. (R)-1-Adamantyl phenyl-H-phosphinate was stereospecifically transformed into a few secondary and tertiary phosphine oxides. Moreover, two P-stereogenic Brønsted acids were prepared, and their applicability as chiral NMR solvating agents was assessed.