Synthesis of Heterocycles from Potassium Trifluoro(pyrimidin-4-yl)borate Salts

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.

Publication History

Article published online:
20 April 2021