Use of a convertible isocyanide for generation of Ugi reaction derivatives on solid support: Synthesis of alpha-acylaminoesters and pyrroles

The Ugi four component condensation employing 1-isocyanocyclohexene as a convertible isocyanide has been adapted to solid supported synthesis. Using Wang or Rink resin and a linker derived from succinic anhydride, Ugi reactions proceeded smoothly. The products were then converted under acidic alcohol conditions to esters, acids, and to pyrroles via 1,3-dipolar cycloadditions to an acetylene. The intermediate in both transformations is a 1,3-oxazolinium-5-one arising from cycloelimination of the cyclohexenamide from the Ugi product.