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]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% CH3OH/50% CHCl3 (v/v) with a primary ammonium salt (log K=3.15) as evidenced by a significant change in the (1)HNMR 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% C2H5OH/80% 1,2-C2H4Cl2 (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.