Synthetic strategies to inherently chiral calix[4]arenes with mixed ligating functionalities at the lower rim

Abstract

The syntheses of 19 atropisomeric inherently chiral calix[4] arenes derived from syn-proximal (1,2)-bis[(2-pyridylmethyl)oxy]calix[4]arene 2 and mixed syn-distal (1,3)-[(2-pyridylmethyl)oxy] [(2-quinolylmethyl)oxy]calix[4]arene 6 are described. Treatment of 2 with 1 equiv of electrophile RX in DMF in the presence of Cs 2 CO 3 afforded racemic tri-O-alkylated cone conformers 3a-k (A α A α B α C α type), while with an excess of alkylating agent under analogous conditions the chiral tetra-O-alkylated partial cone conformers 4a-d (A α A α B α B β type) were formed. Similarly, exhaustive alkylation of 6 with either PicCl.HCl or QuinCl.HCl gave the chiral partial cone derivatives 7a,b (A α A α A α B β type), respectively. Further alkylation of 3i (R=benzyl) with PicCl.HCl and Cs 2 CO 3 provided partial cone derivative 7c (A α A α A β B α type), while with PrBr and NaH cone tetraether 8 (A α A α B α C α type) was obtained. Proton and carbon NMR spectral features of these compounds are discussed. Atropisomerism in tri-O-alkylated calix[4]arenes was demonstrated by dynamic NMR studies on the less encumbered allyl derivative 3a, which showed no hint for conformational inversion up to 375 K. 2D COSY spectra clearly show that in partial cone structures 4d and 7a-c the N-heteroaryl pendant group of the totated aryl moiety lies in, and effectively fills, the calix cavity produced by the remaining three aryl rings. The structure of the trisubstituted racemic calix[4]arene 3i has been determined by X-ray crystallography. The molecule adopts a distorted cone conformation with the two pendant pyridinyl groups in th syn-proximal arrangement on one side of the pendant benzyl moiety. There is an intramolecular O-H...O hydrogen bond between the phenolic oxygen OD and the proximal etheral oxygen OA (to which is bonded the benzyl residue) with O...O 2.85 A˙