A series of chiral bridged macrocyclic 1,4-dihydropyridines has been prepared, and the potential of these compounds for enantioselective reductions has been examined. A typical synthesis begins with pyridine-3-5-dicarboxylic acid (9, W = OH), which is coupled with (S)-valine to produce ultimately the bis-coupled product 10 (X = OH). This is converted to the bis(cesium carboxylate) and is allowed to react in dimethylformamide (DMF) solution at 10-2 to 5 × 10-3 M concentration with 1,5-dibromo-3-oxapentane. The macrocycle 11a (R = CH(CH3)2) is obtained in 48% yield. Subsequent methylation with CH3I/Mg(ClO4)2·1.5H2O leads to the pyridinium perchlorate, which is reduced to 1,4-dihydropyridine with Na2S2O4. In this manner, 28 different chiral bridged macrocyclic 1,4-dihydropyridines (7) have been synthesized by starting from valine, alanine, phenylglycine, phenylalanine, and proline. Various bridges of different compositions, lengths, and shapes have been incorporated. All these bridged compounds in a nonprotic solvent like CH3CN in the presence of a stoichiometric amount of Mg(ClO4)2·1.5H2O reduce activated carbonyl compounds to the corresponding alcohols; the corresponding pyridinium salt is formed. The most studied example is the reduction of ethyl phenylglyoxylate to ethyl mandelate. If the amino acids have the S configuration, the ethyl mandelate produced will have the S configuration. The enantiomeric excesses vary between 36% and 90% and decrease with increasing bridge length of the macrocycle from a maximum for a bridge with a length of five atoms (either pentamethylene or 3-oxapentyl). An explanation for these results is offered. It is assumed that the reactive species is a complex of bridged 1,4-dihydropyridine, Mg2+, and carbonyl component. Although Mg2+ does not bind strongly to the macrocycles (log Ks 2-3 depending on the compound), this cation apparently has the ability to organize the macrocycles, even when they can assume several conformations of widely differing shape, into a common geometry which leads to reduction. The cation has the ability in fact to redistribute the conformational populations. These conclusions are supported by 13C NMR studies of complexation as well as circular dichroism (CD) studies, which are reported separately.