Oleksandr A. Yesypenko

This review summarized and systematized the currently known methods of substituting phenolic fragments of calix[4]arenes in the para-position, mainly focusing on the conditions of regioselective carrying out such processes. The reactions of the further transformation of the inserted functional groups, which allows the expansion of the family of para-substituted calixarenes, are also considered. These reactions can be used in the synthesis of inherently chiral calix[4]arenes with asymmetric substitution on the upper rim.

A practical method of selective alkylation of the third hydroxyl group of disubstituted tert-butyl-calix[4]arenes using anhydrous barium hydroxide as a base was developed in this study. The use of this method in the synthesis of inherently chiral derivatives is shown herein.

A preparative method for the synthesis of optically pure N‐(1‐phenylethyl)amides of inherently chiral (cR)‐ and (cS)‐dibenzoyloxy‐calix[4]arene acetic acids has been developed. Their absolute stereochemical configuration was determined by X‐ray diffraction analysis.

Inherently chiral dialkyloxy-calix[4]arene acetic acids with asymmetric placement of substituents on the lower rim of the macrocycle were first studied as enantiodiscriminating additives to the mobile phase MeCN/H₂O/HCOOH (75/25/0.02 by volume) in the high-performance liquid chromatography (HPLC) separation of d,l-alanine and d,l-valine on the achiral stationary phase ZORBAX Original CN. The dependence of enantio-binding properties on the position of alkyl groups is demonstrated. The highest resolution (1.65) and enantioselectivity (1.80) were obtained for the 1,2-dipropyloxy-calix[4]arene acetic acid.

The enantiodiscrimination properties of stereomerically pure inherently chiral calix[4]arene acetic acids, as well as their esters and amides in relation to 1‐phenylethylamine stereoisomers in liquid and gaseous phases were studied by means of proton magnetic resonance spectroscopy (¹H NMR) and quartz crystal microbalance (QCM) techniques. Series of QCM sensors with thin films of inherently chiral calix[4]arenes, immobilized on the quartz resonator surfaces by spin‐coating and spreading drop methods have been fabricated. It was shown that sensors based on calix[4]arene acetic acids are able to recognize R‐ and S‐forms of 1‐phenylethylamine in gaseous phase under concentration level of 10–400 ppm.

This paper shows that 25‐propyloxy‐26,27‐dibenzoyloxy‐calix[4]arene can be a convenient precursor for the formation of inherently chiral configuration on the calixarene platform. The methods for sequential regioselective debenzoylation and electrophilic substitution on the upper rim were developed. The inherently chiral calix[4]renes with two and three different functional groups on the upper rim were synthesized.