Efficient synthesis and resolution of meta-substituted inherently chiral aminocalix[4]arene derivatives

Abstract

Efficient synthesis and resolution of a series of meta-substituted inherently chiral aminocalix[4]arene derivatives have been described. Consequently, the meta-nitro, bromo and chloro substituted inherently chiral calix[4]arenes could be directly synthesized by the nitration, bromination, and chlorination of the acylating product of aminocalix[4]arene. meta-Cyano and phenyl substituted inherently chiral aminocalix[4]arenes were readily obtained by the nucleophilic substitution reaction or Suzuki coupling reaction from the meta-bromo substituted one under the Pd-catalyzed conditions. For kinetic resolution of the racemic inherently chiral aminocalix[4]arenes, it was found that the electron-withdrawing ability of substituent was helpful to improving the resolution efficiency of the acylation process, and the kinetic resolution could be efficiently applied to the resolution of meta-nitro substituted inherently chiral aminocalix[4]arene, providing (cS)- or (cR)-isomer in up to 95% or 99.9% ee value, respectively, with the corresponding chiral acylating reagent. Moreover, by introduction of the chiral auxiliary, enantiopure antipodes of meta-cyano and phenyl substituted inherently chiral aminocalix[4]arenes could also be readily obtained. These enantiopure aminocalix[4]arenes are potential building blocks for constructing novel chiral receptors and asymmetric catalysts.