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DOI: 10.1055/s-0028-1087794
Synthesis of Chiral 4-Trifluoromethyl-3,4-dihydroazin-2-ones
V. A. Sukach, N. M. Golovach, N. V. Melnichenko, I. F. Tsymbal, M. V. Vovk*
National Academy of Sciences of Ukraine, Kyiv, Ukraine
Publication History
Publication Date:
19 February 2009 (online)
Significance
Reported is the synthesis of chiral CF3-substituted dihydroazinones 2, 3 and 4. The reaction involves the condensation of chiral β-CF3-β-aminoketones 1 with isocyanates giving intermediary ureas which undergo cyclization to afford 3,4-dihydropyrimidin-2-(1H)-ones 2 (60-91% yield, 70-80% ee, no erosion of chirality). On the other hand, treatment of 1 with potassium isocyanate and potassium rhodanide in boiling AcOH gives dihydropyrimidinones 3 and dihydropyrimidin-2(1H)-thiones 4 in 71-96% yields, respectively. The heterocyclic thiones 4 were obtained by condensation of 1 with aroyl isothiocyanates followed by cyclization in acetic acid. Depending on conditions, reaction of 1 with triphosgene can lead to the formation of isocyanates 6 or dihydrooxazinones 5 (48-69% yield, 75-80% ee, no erosion of chirality). Condensation of isocyanates 6 with aliphatic amines affords a mixture of 2 and 5.