Diethyl 2,4-Dioxoimidazolidine-5-phosphonates: Horner-Wadsworth-Emmons Reagents for the Mild and Efficient Preparation of C-5 Unsaturated Hydantoin Derivatives

Article abstract of DOI:10.1021/jo00024a036

The phosphonates 19 and 20 were prepared from hydantoin and 1-methylhydantoin, respectively, by way of bromination at C-5 and a subsequent Michaelis-Arbuzov reaction with triethyl phosphite.The Horner-Wadsworth-Emmons-type reagents 19 and 20 were found to react readily with aromatic and aliphatic aldehydes, in the presence of a base, to produce C-5 unsaturated hydantoin derivatives 22 and 26, generally in high yield.The products 22 and 26 were frequently isolated as mixtures of E and Z isomers depending upon the identity of the aldehyde and phosphonate.The isomeric configuration of the products was determined from analysis of NMR spectral data.Long-range (13)C-(1)H coupling constants between the C-4 carbonyl of the hydantoin ring and the olefinic proton were found to be diagnostic of isomer geometry.Conditions were also developed that allowed coupling of 19 and 20 with cyclic and acyclic ketones and α-dicarbonyl compounds to afford the corresponding olefinic products.C-5 unsaturated hydantoin derivatives are of synthetic utility as precursors to α-amino acid derivatives, pyruvates, and the imidazo<4,5-b>quinolin-2-one heterocyclic ring system, a class of potent inhibitors of low Km cAMP phosphodiesterase and the chromophore present in the siderophore azotobactin.