SYNTHETIC STRATEGIES TO INHERENTLY CHIRAL CALIX[4]ARENES WITH MIXED LIGATING FUNCTIONALITIES AT THE LOWER RIM

The syntheses of 19 atropisomeric inherently chiral calix[4]arenes der ived from syn-proximal (1,2)-bis[(2-pyridylmethyl)oxy]calix[4]arene 2 and mixed syn-distal -pyridylmethyl)oxy][(2-quinolylmethyl)oxy]calix[4 ] arene 6 are described. Treatment of 2 with 1 equiv of electrophile R X in DMF in the presence of Cs2CO3 afforded racemic tri-O-alkylated co ne conformers 3a-k (A(alpha)A(alpha)B(alpha)C(alpha) type), while with an excess of alkylating agent under analogous conditions the chiral t etra-O-alkylated partial cone conformers 4a-d (A(alpha)A(alpha)B(alpha )B(beta) type) were formed. Similarly, exhaustive alkylation of 6 with either PicCl.HCl or QuinCl.HCl gave the chiral partial cone derivativ es 7a,b (A(alpha)A(alpha)A(beta)B(alpha) type), respectively. Further alkylation of 3i (R=benzyl) with PicCl.HCl and Cs2CO3 provided partial cone derivative 7c (A(alpha)A(alpha)A(beta)B(alpha) type), while with PrBr and NaH cone tetraether 8 (A(alpha)A(alpha)B(alpha)C(alpha) type ) was obtained. Proton and carbon NMR spectral features of these compo unds are discussed. Atropisomerism in tri-O-alkylated calix[U arenes w as demonstrated by dynamic NMR studies on the less encumbered allyl de rivative 3a, which showed no hint for conformational inversion up to 3 75 K. 2D COSY spectra clearly show that in partial cone structures 4d and 7a-c the N-heteroaryl pendant group of the rotated aryl moiety lie s in, and effectively fills, the calix cavity produced by the remainin g 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 gr oups in the 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 ethereal oxygen OA (to which is bo nded the benzyl residue) with O...O 2.85 Angstrom.