ABSTRACT
Non-catalysed addition of trifluoroacetonitrile imines to enol ethers provided fully regioselectively (3 + 2)-cycloadducts, which either spontaneously or via Brønsted acid-induced elimination of ROH molecules led to the formation of 3-trifluoromethylated pyrazoles. In the case of 2,3-dihydrofuran, the respective bicyclic intermediate was isolated and its structure was confirmed by X-ray analysis. Using the developed protocol the synthesis of a known antitumor compound SC-560 was performed in 45% yield. Subsequent functionalisations of selected 4-(ω-hydroxyalkyl)pyrazoles at C(5) through lithiation/addition, cross-coupling reactions or via intramolecular Pd-catalysed C-H arylations opened up an access to polysubstituted pyrazoles including unusual tricyclic systems comprising 7-membered rings (oxepane, thiepane and azepane) as the central unit.
ABSTRACT
Transformations of functional groups OCOPh, OCH2Ph, I, NO2, and CO2Me in Blatter's radical derivatives 1-5 were investigated in order to develop synthetic tools for incorporation of the benzo[1,2,4]triazinyl system into complex molecular architectures. Thus, basic hydrolysis of OCOPh or Pd-catalyzed debenzylation of OCH2Ph gave phenol functionality, which was acylated and alkylated. Pd-catalyzed Suzuki, Negishi, Sonogashira, and Heck C-C cross-coupling reactions of iodo derivatives 1c, 1d, and 2d were also successful and efficient. Reduction of NO2 in 1e led to aniline derivative 1t, which was reductively alkylated with hexanal and coupled to l-proline. Selected benzo[1,2,4]triazinyl radicals were characterized by EPR and electronic absorption spectroscopy, and the results were analyzed in tandem with DFT computational methods. Lastly, the mechanism for formation of the 1,4-dihydrobenzo[1,2,4]triazine ring was investigated using the B3LYP/6-31G(2d,p) method.
