T. S. Kuznetsova

Rearrangements and cyclizations—XVI: Ring-opening reactions of 1,1-diacetylcyclopropane with hydrazine and hydroxylamine derivatives as the novel synthesis of β-X-ethyl substituted pyrazoles and isoxazoles

Abstract The reactions of 1,1-diacetylcyclopropane ( 1 ) with a number of hydrazine and hydroxylamine derivatives proceed via cyclopropane ring opening with incorporation of external nucleophile (solvent) to give the 4-β-X-ethyl derivatives of 3,5-dimethylpyrazoles and -isoxazoles, a novel route to these heterocycles. This ring cleavage occurs especially smoothly in water as a solvent. A rationale for this unusually mild nucleophilic cyclopropane ring opening is discussed.

Unexpected Heterocyclization of Electrophilic Alkenes by Tetranitromethane in the Presence of Triethylamine. Synthesis of 3-Nitroisoxazoles

Novel reaction of tetranitromethane (TNM) with electrophilic alkenes in the presence of triethylamine yielding substituted 3-nitroisoxazoles was found and studied. Triethylamine increases the reactivity of TNM toward electrophilic alkenes promoting their heterocyclization, and the reactions proceed in an unusual way. A variety of alpha,beta-unsaturated aldehydes, ketones, esters, amides, phosphonates, and nitro and sulfur compounds was involved in the heterocyclization reaction, and a wide range of functionalized 3-nitroisoxazoles was obtained in good to high yields. The scope and limitations of the reaction and the mechanistic aspects are discussed.

Three-Component Heterocyclization of gem-Bromofluorocyclopropanes with NOBF4: Access to 4-Fluoropyrimidine N-Oxides

Novel three-component heterocyclization involving gem-bromofluorocyclopropanes, nitrosyl tetrafluoroborate, and a molecule of the solvent (nitrile) yielding previously unknown fluorinated pyrimidine N-oxides is described. A two-step synthetic approach to 4-fluoropyrimidine N-oxides from alkenes under mild conditions is developed using this reaction. Mechanistic aspects of the heterocyclization are discussed.

Rearrangements and cyclization-XVII : Mechanism of the formation of 1,2-azoles in reactions of 1,1-diacyclopropanes with hydrazine and hydroxylamine derivatives

Abstract The mechanism of recently discovered ring-opening reactions of 1,1-diacyclopropanes with hydrazine and hydroxylamine derivatives is investigated using the 1H-NMR flow (and stopped-flow) method and transient formation of spiro-activated intermediates of type 4 and 19 is proved. The mechanistic and synthetic sequences of these findings are discussed.

Synthesis of amino acids of cyclopropylglycine series

The review covers methods of synthesis of amino acids of the cyclopropylglycine series published in the past decade. Main methods of synthesis of cyclopropylglycines are based on the carbene and ylide addition to alkenes, enzymatic reactions, the Kulinkovich cyclopropanation of esters and amides, MIRC reactions, the modification of cyclopropanecarbaldehydes by the Strecker reaction, and other transformations of functional groups of cyclopropanes. Particular attention is given to 2-carboxycyclopropylglycines and 3,4-methanoprolines. These compounds have attracted interest as conformationally rigid cyclopropane-containing analogs of glutamic acid and proline and also as components of physiologically active peptides. The physiological properties of cyclopropylglycines are briefly characterized.

Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents

A versatile synthesis of novel 5-hydroxylaminoisoxazoles bearing adamantane moieties has been accomplished using the heterocyclization reactions of readily available unsaturated esters by the treatment with tetranitromethane in the presence of triethylamine and subsequent reduction of resulting 5-nitroisoxazoles by SnCl2 with the participation of THF. A number of obtained isoxazole derivatives were evaluated for their antioxidative activity, inhibition of lipoxygenases and impact on the rat liver mitochondria. The majority of tested compounds demonstrated moderate antiradical activity in DPPH test (up to EC50 16μM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4μM) and Fe(2+)- and Fe(3+)-induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3μM). All tested isoxazole derivatives promoted the phosphorylating respiratory activity simultaneously with maximal stimulated respiratory activity of mitochondria and do not reveal any toxicity towards the primary culture of rat cortex neurons.

Synthesis of New 3,4-Disubstituted Furazans

A series of new 3,4-substituted furazans was synthesized on the basis of the mutual transformations of the functional groups in halogenomethyl and bisacyl derivatives of furazan.

Carbenoid rearrangement in the series of substituted gem-dibromospiropentanes

A series of new substituted gem-dibromospiropentanes was studied in a reaction with methyllithium at −55...−50°C. This reaction is a carbenoid rearrangement that leads to the formation of monomeric and dimeric bromocyclobutenes and also to the products of cyclobutylidene insertion into a C-H bond of the solvent depending on the character of substituents in the dibromospiropentane fragment.

Synthesis of nitrosubstituted triangulanes

The [1+2] cycloaddition of ethyl nitrodiazoacetate to various methylenecyclopropanes afforded 1-ethoxycarbonyl-1-nitropolyspirocyclopropanes. These compounds were used in the synthesis of first representatives of nitrosubstituted triangulanes. Nitrospiropentane was prepared also by dehydrohalogenation of 1-bromomethyl-1-(nitromethyl)cyclopropane.

Synthesis of β-Aminoethyl-substituted Pyrazoles

Methods have been developed for the synthesis of 3,5-dimethyl-4-(2-N-mono- and -disubstituted and also unsubstituted aminoethyl)pyrazoles from 1,1-diacetylcyclopropane.