A solid-phase traceless synthesis of tetrahydroquinoxalines

A solid-phase traceless synthesis of tetrahydroquinoxalines with three combinatorial steps is reported. An aldehyde functionalized polystyrene resin was reductively aminated by amino alcohols, and then the resin bound secondary amines were reacted with o-fluoronitrobenzenes. The hydroxy group was mesylated and the nitro group was reduced by tin(II) chloride to the anilines, which spontaneously cyclized. The secondary aniline nitrogen of the resulting tetrahydroquinoxalines was further derivatized with acyl chlorides and isocyanates. After acidolytic cleavage from the resin, tetrahydroquinoxalines with three points of diversity were obtained.