Heterocyclization of N-(1-chloro-2,2,2-trifluoroethylidene)carbamates with β-enaminoesters—a novel synthetic strategy to functionalized trifluoromethylated pyrimidines

Control of Regio‐ and Enantioselectivity in the Asymmetric Organocatalytic Addition of Acetone to 4‐(Trifluoromethyl)pyrimidin‐2(1H)‐ones

“…First, we studied the organocatalytic reaction of ketones with 6‐substituted pyrimidones 1 , which, owing to the very different electrophilicity of the two reaction centers, were assumed to react only at the more‐active 4‐position of the pyrimidine ring. Initial experiments were conducted by using four types of starting pyrimidones, with substituents of various nature in the 1,5,6‐positions (Table 1);6a acetone was chosen as a nucleophilic reagent, L ‐proline was used as a catalyst, and DMSO was the solvent.…”

“…4‐(Trifluoromethyl)pyrimidin‐2(1 H )‐ones I represent fluorinated nucleobase analogues derived from the substitution of the amino group of cytidine or the hydroxy group of uracil and thymine (in one of their tautomeric forms) by the trifluoromethyl group. Their synthesis has been described in a series of papers,6 including our own method,6a but chemical and biological properties still remain insufficiently explored7 and are of great promise for synthetic applications and bioactivity studies. It is quite evident that the introduction of the electron‐withdrawing trifluoromethyl group at the 4‐position of the pyrimidone nucleus induces electron deficiency at this site, and thus an attractive electrophilic center is created.…”

Development of an efficient route to CF3-substituted pyrrolopyrimidines through understanding the competition between Michael and aza-Henry reactions

“…3f,5 The organocatalytic enantioselective addition of β-cyclopropylnitroethane to 4-trifluoromethyl-2 (1H)-quinazolinones is of particular interest as an efficient approach to the promising anti-HIV drug DPC083. 3f 4-(Trifluoromethyl)-1,2-dihydropyrimidin-2-ones recently prepared by us 6 are an interesting object for the aza-Henry reaction. Moreover, a pyrimidine unit is a privileged building block for drug discovery and some fluorinated pyrimidines have found important applications in this field.…”

“…Hz, 3 J HH = 3 6. Hz, CH 2 ), 4.65 (dd, 1H, 2 J HH = 11.6 Hz, 3 J HH = 4.8 Hz, CH 2 ), 5.36-5.40 (m, 1H, CH), 7.35-7.55 (m, 5H), 7.73 (bs, 1H, NH).13 C NMR (125 MHz, CDCl 3 ): 52.9, 59.6, 75.0, 101.8, 118.9 (q, 1 J CF = 275.0 Hz, CF 3 ), 127.4, 128.6, 129.9, 137.01 (q, 2 J CF = 37.5 Hz, C-6), 138.3, 149.7, 162.5.…”

Synthesis and Cation Recognition Study of Novel Benzo Crown Ether Functionalized Enamine Derivatives

“…Amongst them β-enaminones represent a useful moiety for the synthesis of heterocyclic scaffolds such as pyrrole, dihydropyridine, piperidine, pyrimidine etc. [21][22][23][24][25] .…”