Resin-bound 4-phenyl-1,2-dihydroquinoline (DHQ): a new safety-catch linker for solid-phase organic synthesis (SPOS)

A new safety-catch linker has been developed for combinatorial solid-phase chemistry. Azidomethyl-polystyrene, obtained by nucleophilic substitution of chloromethyl-polystyrene, undergoes an acid promoted Schmidt rearrangement. The resulting polymer-bound iminium participates in an aza Diels–Alder cycloaddition, which leads to a supported dihydroquinoline (DHQ resin). The acylated form of the DHQ resin is stable under basic, acidic and mild reducing agents. The cleavage proceeds in two steps (i) oxidative aromatization leading to an activated quinolinium and (ii) nucleophilic displacement of the quinoline resin. The overall process is high yielding and efficient.