Calixarenes With Combined Axial Chirality And Inherent Chirality:Synthesis And Chiral Recognition

In calixarene chemistry, inherently chiral calixarenes have been extensively studied and frequently used in molecular recognition, asymmetric catalysis, molecular self-assembly and functional materials. Synthesis of novel, functionalized, and optically pure inherently chiral calixarenes in an efficient and concise manner is an ongoing theme of related study. In our group, we designed to introduce a crown ether containing an axial chiral BINOL moiety on the lower rim of the calixarene to obtain calixarene diastereomers with combined axial chirality and inherent chirality via monoalkylation. The resultant diastereomers were readily separated by column chromatography. The reaction showed high generality and distinct diastereoselectivity.We also studied the chiral recognition of these calixarenes by fluorescence titration and 1H NMR titration.This paper consists of two parts, the first part introduces calix[5]arenes with combined axial chirality and inherent chirality: synthesis and chiral recognition; the second part introduces calix[4]arenes with combined axial chirality and inherent chirality: synthesis and chiral recognition.Part I: Calix[5]arenes with combined axial chirality and inherent chirality:synthesis and chiral recognitionCalix[5]arene diastereomeric pairs with combined axial chirality and inherent chirality were synthesized via monoalkylation of 1,3-substituted calix[5]crown-6incorporating an axially chiral BINOL moiety, with ethyl bromoacetate. The resultant diastereomers I-(S)-4a and I-(S)-4b, which possess both axial chirality and inherent chirality, were readily separated by column chromatography. Respective hydrolysis afforded diastereomeric acids I-(S)-5a and I-(S)-5b.By fluorescence titration, amino alcohol-induced fluorescence quenching was observed for I-(S)-5a and I-(S)-5b. The highest enantioselectivity, based on the ratio of Stern–Volmer constants KSV(S)/KSV(R), reached 1.90 in the case of I-(S)-5a with2-amino-1-phenylethanol, and I-(S)-5b with phenylalaninol. The highest diastereoselectivity of 1.83, measured by KSV(5a)/KSV(5b), occurs in the case of I-(S)-5a/I-(S)-5b with(R)-phenylalaninol.Part II: Calix[4]arenes with combined axial chirality and inherent chirality:synthesis and chiral recognitionCalix[4]arene diastereomeric pairs with combined axial chirality and inherent chirality were synthesized via monoalkylation of calix[4]arene 1,2-BINOL crown-4with different electrophiles. The resultant diastereomers were readily separated by column chromatography and we obtained trisubstituted diastereomeric pairs4a-7a/4b-7b. The reaction showed high generality and distinct diastereoselectivity.Further derivatization afforded trisubstituted diastereomeric pairs 8a-9a/8b-9b and tetrasubstituted compounds 10a-11a/10b-11 b.Based on the X-ray crystal structure, II-(S)-7a was assigned as the(S,c S)-configurational isomer. We also successfully cultivated single crystals of tetrasubstituted compounds II-(S)-10 a and II-(S)-11 a, which verified their partial cone conformation and(S, c S)-configuration.By fluorescence titration and 1H NMR titration, II-(S)-8a/II-(S)-8b and II-(S)-11a/II-(S)-11 b showed poor enantioselectivity of the chiral recognition to?-aminoalcohols. II-(S)-9a showed insignificant enantioselectivity of the chiral recognition to 2-chloromandelic acid by 1H NMR titration, the maximal guest-induced chemical shift difference(??) being 0.019 ppm.