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 β-keto esters or directly with β-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 13C 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.