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 alpha-substituted beta-amino acids.
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/beta-iodination of the corresponding 6-carboxy-perhydropyrimidin-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-alkynyl-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 alpha-substituted beta-amino acids.
Díaz-Sánchez
Blanca R
BR
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000 México, D.F., Mexico.
Iglesias-Arteaga
Martín A
MA
Melgar-Fernández
Roberto
R
Juaristi
Eusebio
E
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D006219:Halogens / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D006868:Hydrolysis; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D014498:Uracil / Q000737:chemistry
D000596:Amino Acids; D006219:Halogens; D011725:Pyridines; D011744:Pyrimidinones; D014498:Uracil; D006859:Hydrogen