Demonstration of the feasibility of a direct solid-phase split-pool Biginelli synthesis of 3,4-dihydropyrimidinones

Article abstract of DOI:10.1021/ol048946r

(Chemical Equation Presented) A direct, Lewis acid-catalyzed Biginelli synthesis of 3,4-dihydropyrimidinones has been performed on high-capacity polystyrene macrobeads with a polymer O-silyl-attached N-(3-hydroxypropyl)urea. Resin-urea was first reacted separately with either 4-bromo- or 4-chlorobenzaldehyde and LiOTf in MeCN at 80°C. After washing, the beads were pooled and reacted with ethyl acetoacetate and LiOTf in MeCN at 80°C. Formation of only one kind of Biginelli product per bead demonstrated the feasibility of a solid-phase non-Atwal two-step split-and-pool synthesis of 3,4-dihydropyrimidinones.