Synthesis and Desymmetrization of meso-2,3-Diphenylpiperazine for Application in Asymmetric Transformations

Abstract

The meso-2,3-diphenylpiperazine was prepared in 86 % yield with 99:1 dr from the readily accessible 5,6-diphenyl-2,3-dihydropyrazine by NaBH4/MeOH reduction. The corresponding diastereomeric amides prepared using (R)-(-)-menthyl chloroformate, after separation, benzylation and hydrolysis gave both isomers of optically active N-benzyl-2,3-diphenylpiperazine samples in up to 94 % ee which after further enrichment using the simple achiral oxalic acid afforded samples of both enatiomers in 99 % ee. Reaction of the chiral optically active N-benzyl-2,3-diphenylpiperazine with terminal alkynes and aldehydes in the presence of ZnCl2 gave the corresponding propargylamines with very high diasterioselectivities (up to 99:1 dr) from which both enantiomers of chiral allenes were obtained in up to 82–86 % ee by reaction with ZnBr2 in toluene at 120 °C.