Nef/Perkow Cascade towards Imidazo Phosphate Derivatives

We report an efficient synthesis of imidazolyl vinyl phosphate and imidazolyl phosphate derivatives via a one-pot sequential four-component reaction. The addition of isocyanides to acyl chlorides (Nef reaction) leads to imidoyl chlorides which can later be treated with trialkylphosphites in a Perkow-type reaction [1]. The outcome of this reaction step depends of the nature of the starting acyl chloride. For acyl chlorides possessing chloride atoms at the 2 position, the vinyl phosphate derivatives are obtained. However for acyl chlorides substituted by esters, the Perkow step leads to the formation of ketenimines phosphates [2]. Vinyl phosphate imidoyl chlorides and ketenimine phosphates obtained in Nef/Perkow sequence may be easily converted to imidazolyl vinyl phosphate and imidazolyl phosphate derivatives under addition of propargyl amine in basic condition and in the presence of silver carbonate as a C [3]. We are currently exploring the potential addition of other nucleophiles to these Nef- Perkow phosphate intermediates.