The synthesis of biologically relevant 4(5)‐phosphono‐5(4)‐aminoimidazoles using a Pd‐catalyzed coupling reaction

Regiochemically defined 1‐benzyl‐4‐phosphono‐5‐carboalkoxyimidazoles were synthesized from the corresponding 4‐bromoimidazoles using a tetrakis(triphenylphosphine)palladium(0)‐catalyzed coupling reaction with diethyl phosphite. The corresponding Michaelis‐Arbusov reaction failed to give a phospho‐nylated product. The carbomethoxy moiety was converted to an amino group using a Curtius rearrangement to afford 1‐benzyl‐4‐phosphono‐5‐amino‐imidazoles. Following deprotection and hydrolysis, phos‐phonic acid‐linked aminoimidazoles were accessed that resemble intermediates formed during purine biosynthesis.