Chiral Pyridine-Based Macrobicyclic Clefts: Synthesis and Enantiomeric Recognition of Ammonium Salts

An achiral (3) and two chiral pyridine-based macrobicyclic clefts (4 and 5) have been prepared by treating 2,6-bis[[2',6'-bis(bromomethyl)-4'-methylphenoxy]methyl]pyridine (2) with the appropriate achiral and chiral glycols. Starting 2 was prepared by first treating 2,6-bis(hydroxymethyl)-4-methylphenol with 2,6-[(tosyloxy)methyl]pyridine followed by phosphorus tribromide. Achiral macrobicyclic cleft 3 formed a complex at 25 degrees C in 50% CH(3)OH/50% CHCl(3) (v/v) with a primary ammonium salt (log K = 3.15) as evidenced by a significant change in the (1)H NMR spectrum. Highly organized (S,S,S,S)-4, prepared by treating 2 with (1S,5S)-3-oxapentane-1,5-diol, exhibited recognition at 25 degrees C in 20% C(2)H(5)OH/80% 1,2-C(2)H(4)Cl(2) (v/v) for the (S)-enantiomer of alpha-(1-naphthyl)ethylammonium perchlorate (NapEt) over its (R)-form (Delta log K = 0.85). This high recognition factor probably reflects an increase in molecular rigidity by the introduction of a second macro ring on the monocyclic pyridinocrown ligand.