A Novel Concept in Combinatorial Chemistry in Solution with the Advantages of Solid-Phase Synthesis: Formation of N-Betaines by Multicomponent Domino Reactions

Advantages of solid‐phase and liquid‐phase synthesis are combined in a new concept of combinatorial chemistry: a domino sequence comprising Knoevenagel and hetero‐Diels–Alder reactions with subsequent hydrogenation starting from protected aminoaldehydes, 1,3‐dicarbonyl compounds, and enol ethers leads to N‐heterocycles of high diversity with a betaine structure, which are isolated in highly pure form by precipitation with diethyl ether (see scheme). Cbz=benzyloxycarbonyl, Bn=benzyl.