CHIRAL RECOGNITION OF CINCHONA ALKALOIDS AT THE MINOR AND MAJOR GROOVES OF 1,1'-BINAPHTHYL RECEPTORS

A variety of chiral 1,1'-binaphthyl derivatives with one or two hydrox yl groups at either the 2,2'-(minor groove) or the 7,7'-positions (maj or groove) were prepared for enantioselective recognition of the cinch ona alkaloids quinine and quinidine. The study was initiated when it w as found that 7,7'-bis(benzyloxy)-2,2'-dihydroxy-1,1'-binaphthyl ((+/- )-1a) was readily resolved through simple clathrate formation with qui nine and quinidine. Optical resolution of (+/-)-1a was also achieved b y fractional crystallization of its cyclic phosphate ester with quinid ine. The absolute configuration of the optically pure binaphthyl deriv atives was established by transformation of (-)-1a into a binaphthyl d erivative of known absolute configuration (R) through reactions of def ined stereochemistry. The X-ray crystal structure analysis of the (S)- (+)-1a.quinidine complex showed that ion pairing is the major interact ion between the two components. Complexation of quinine and quinidine at both major and minor grooves of the 1,1'-binaphthyl derivatives occ urred in CDCl3 with a significant degree of chiral recognition, and di fferences in stability between diastereomeric complexes were as large as Delta(Delta G degrees) approximate to 1 kcal mol(-1) (293 K). Quini ne is consistently better bound by the (R)-receptors whereas quinidine always prefers the (S)-enantiomers. The structures of the complexes, which are stabilized by hydrogen-bonding and aromatic-aromatic interac tions, were analyzed on the basis of the complexation-induced changes in H-1 NMR chemical shifts of the binding partners at saturation bindi ng Delta delta(sat), H-1{H-1} nuclear Overhauser effects (NOEs), and m olecular modeling.