Approaches to combinatorial synthesis of heterocycles: A solid-phase synthesis of 1,4-dihydropyridines

N-Immobilized enamino esters 2 derived from amine-functionalized PAL or Rink polystyrene resins react with preformed 2-arylidene beta-keto esters or directly with beta-keto esters and aldehydes to afford, upon trifluoroacetic acid cleavage, 1,4-dihydropyridine (DHP) derivatives in good yields. The mechanism of this transformation on solid support has been studied using C-13 NMR and IR spectroscopies. This new solid-phase synthesis has been applied to the preparation of several bioactive DHPs and is designed to be amenable to the ''split and pool'' protocol for combinatorial library synthesis.