APPROACHES TO COMBINATORIAL SYNTHESIS OF HETEROCYCLES - A SOLID-PHASESYNTHESIS OF 1,4-DIHYDROPYRIDINES

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