Cousins DL,
Fricero P,
Kopf KP. M,
McColl EJ,
Czechtizky W,
Lim YH,
Harrity JP.
*
University of Sheffield, UK
Pyrimidin-6-yl Trifluoroborate Salts as Versatile Templates for Heterocycle Synthesis.
Angew. Chem. Int. Ed. 2021;
60: 9412-9415
DOI:
10.1002/anie.202101297
Key words
trifluoropyrimidinylborates - cross-coupling - chemoselectivity - thiobenzofurans
Significance
Reported is a new method for synthesizing trifluoro(pyrimidin-4-yl)borate salts 3 in high yields by the condensation of ynone trifluoroborates 1 with amidines 2. Products 3 contain a trifluoroborate group at the C4 position, and this chemistry is highlighted by the unique ability of the trifluoroborate group to undergo chemo- and regioselective reactions at other positions on the pyrimidine scaffolds. Compounds 1 (R1 = EDG, EWG) were well tolerated, affording the corresponding products 3. Pyrazole- and alkyl-substituted ynone trifluoroborates also underwent smooth condensations with amidines 2 to afford products 3. The reaction of the ynone salts 1a with amidines 2a gave the 2-aminopyrimidines 4a, whereas the N-substituted guanidines 2b gave a range of N-substituted analogues 5–9. These compounds were isolated as single regioisomers, and the regioselectivity was assigned by X-ray crystallographic analysis in the case of 6 (R3 = Bn).
Comment
Pyrimidines are present in nucleic acids and many biologically active compounds, including numerous pharmaceutical and agrochemical products whose syntheses are known (R. Abderrahim, E. Leclerc, J.-M. Campagne
Eur. J. Org. Chem. 2017, 2856). The synthesized C4 borylated pyrimidines are stable toward strongly nucleophilic amidines and guanidines, as well as alkylating agents, and even bromine. A reaction route for elaboration of a suitably activated C–B bond was also demonstrated. The potential of the products to undergo further reaction was demonstrated by transformations of 4a into products 10–13 under various reaction conditions.
