Reactions of 3-cyclopropyl-3-oxopropionitrile anion generated by electroreduction of 5-cyclopropylisoxazole

Abstract

3 Cyclopropyl 3 oxopropionitrile anion obtained by cathodic reduction of 5 cyclopropyl isoxazole in an aprotic medium was used as an example to demonstrate that cyano ketone anions show a dual reactivity. The reaction of acetyl chloride with the electrogenerated tetrabutylammonium salt of 3 cyclopropyl 3 oxopropionitrile gave O acylation products, whereas the reaction with its sodium salt gives C acylation products. The reactions of these salts with hydroxylamine hydrochloride follow a different route: in the case of the tetra butylammonium salt, resinification takes place, while in the case of the sodium salt, 5 amino 3 cyclopropylisoxazole is formed. The condensation of this product with 4,4,4 trifluoro 1 (2 thienyl)butane 1,3 dione in glacial AcOH affords 3 cyclopropyl 6 (2 thienyl) 4 (trifluoro methyl)isoxazolo[5,4 b]pyridine in 85% yield.Previously, 1 we described for the first time reductive electrolysis of 5 substituted isoxazoles and studied regu larities of this process in nonaqueous media on cathodes with high (graphite) and low (ordinary steel) hydrogen overvoltage. Irrespective of the nature of the electrode, the reduction of isoxazoles 1а,b is accompanied by proton removal from position 3 of the isoxazole ring to give carb anions 2, which are readily isomerized to linear enolate anions 3 (Scheme 1). Acidification of the final reaction mixture during the standard workup results in β cyano ketone 4 as the major electrolysis products. Scheme 1 R = cyclo C 3 H 5 (a), Ph (b)Compounds 4 were prepared by both direct cathodic deprotonation of isoxazoles 1 and by the alternative indi rect cathodic deprotonation of these isoxazoles using methoxide and tert butoxide anions as electrogenerated bases. 1 As a development of these studies, here we obtained the first information on the reactivity of enolate anions of type 3 generated by cathodic reduction (steel cathode, MeCN) of 5 cyclopropylisoxazole (1а), which was cho sen as the model compound.

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…[313] Petrosyan et al carried out condensation of 5-aminoisoxazole 590 with 4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dione 1 in acetic acid to form isoxazolo [5,4-b]pyridine 591 regioselectively (Scheme 208). [314] Kotljarov et al reported the synthesis of polyfluoroalkylcontaining fused pyridines 594-596 and chromanones 593 by treating 3-(polyfluoroacyl)-4H-chromen-4-ones 80 with aminoheterocycles 592 (Scheme 209). [315] Authors mentioned that the ratio of the products is dependent on the structure of aminoheterocycle, and solvent employed.…”

“…carried out condensation of 5‐aminoisoxazole 590 with 4,4,4‐trifluoro‐1‐(2‐thienyl)butane‐1,3‐dione 1 in acetic acid to form isoxazolo[5,4‐ b ]pyridine 591 regioselectively (Scheme 208). [314] …”