Synthesis of a new class of highly functionalised benzamides by threefold sequential nucleophilic substitution at a resin-bound polyelectrophile

We have developed a solid-phase synthesis of a new class of highly substitu ted and functionalised benzamides, This synthesis is based an the sequentia l introduction of three different nucleophiles at a resin-bound 4,5-difluor o-2-nitrobenzamide. After displacement of one fluorine atom by a thiol and oxidation to a sulfone, the remaining fluorine atom and the nitro group cou ld be substituted sequentially by two different, aliphatic amines. In each of the three nucleophilic substitutions it was possible to use unprotected functionalised nucleophiles, giving fast and easy access to libraries of sm all organic molecules featuring polar functional groups such as hydroxy, am ino, and ester groups and various heterocycles.