A Solid-Phase Synthesis of N,N‘-Disubstituted Ureas and Perhydroimidazo[1,5-a]pyrazines via the Curtius Rearrangement

Abstract
An efficient method for trapping isocyanates, generated from the Curtius rearrangement, with resin-bound amines is reported. A commercially available carboxylic acid is treated with diphenylphosphoryl azide, followed by thermal rearrangement, cooling, and trapping in one pot. Cleavage from the resin gives an N, N'-disubstituted urea in excellent purity, as demonstrated with several heterocyclic and aliphatic carboxylic acids. Further utility is shown by preparing several novel perhydroimidazo[1,5-a]pyrazines.