Synthesis of 2-Substituted-5-halo-2,3-dihydro-4(H)-pyrimidin-4-ones and Their Derivatization Utilizing the Sonogashira Coupling Reaction in the Enantioselective Synthesis of α-Substituted β-Amino Acids

摘要

A convenient, one-pot procedure for the synthesis of 1-benzoyl-2(S)-substituted-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones by tandem decarboxylation/β-iodination of the corresponding 6-carboxy-perhydropy-rimidin-4-ones was developed. In addition, several 1-benzoyl-2(S)-substituted-5-bromo-2,3-dihydro-4(H)-pyrimidin-4-ones were readily prepared by bromination of 1-benzoyl-2(S)-substituted-2,3-dihydro-4(H)-pyrimidin-4-ones. Subsequently, Sonogashira coupling of the halogenated heterocyclic enones with various terminal alkynes produced 1-benzoyl-2(S)-isopropyl-5-ahcynyl-2,3-dihydro-4(H)-pyrimidin-4-ones in good yields. Hydrogenation of the unsaturated C—C moieties in the Sonogashira products followed by acid hydrolysis afforded highly enantioenriched α-substituted β-amino acids.