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Reaction of nitronates with arynes affords tricyclic nitroso acetals, which serve as precursors of valuable aminodiols bearing up to four contiguous stereocenters.

A facile synthesis of [5,5]-annulated N-fused heterocycles – pyrrolo[2,1-b]thiazoles and pyrrolo[1,2-b]indazoles via Cu(II)-mediated oxidative [3+2]-annulation between nitroalkenes and azolium ylides was developed. The reaction proceeds in mild conditions with copper (II) trifluoroacetate/2,6-lutidine system as a promoter. The method is applicable to a broad range of nitroalkenes and azolium salts, providing target N-fused heterocycles in moderate to good yields. In the case of α-fluoronitroalkenes unique fluorinated derivatives were accessed via this methodology.

An efficient route for the synthesis of multifunctionalized pyrrolidines based on copper-catalyzed diastereoselective [3 + 2]-cycloaddition of nitroalkenes with azomethine ylides was developed. Novel fluorinated heterocycles - β-fluoro-β-nitropyrrolidines - were accessed via this method. The products can be prepared in good to excellent yields and with high diastereoselectivity. Subsequent transformations of pyrrolidines including oxidative aromatization into fluorinated pyrrolines and medicinally attractive β-fluoro-NH-pyrroles as well as chemoselective reduction reactions were demonstrated. Application of the developed procedures for the non-fluorinated analogues was demonstrated to lead to various β-substituted pyrrole derivatives.

Chlorination of conjugated nitroalkenes with iodobenzene dichloride or sulfuryl chloride to give target α-chloronitroalkenes in good yields is described. Details of the procedure depend on the donating ability of the nitroalkene substituents. The activity of the described chlorinating agents increases in order ‘PhICl2/Py’ < ‘SO2Cl2’ < ‘SO2Cl2/HCl’ with the former producing the best yields for highly donating substrates and the latter for non-activated groups. An autocatalytic role of hydrogen chloride and the chemoselectivity of chlorination were also demonstrated.

Currently, the chemistry of organofluorine compounds is a leading and rapidly developing area of organic chemistry. Fluorine present in a molecule largely determines its specific chemical and biological properties. This thematic issue covers the trends of organofluorine chemistry that have been actively developed in Russia the last 15 – 20 years. The review describes nucleophilic substitution and heterocyclization reactions involving fluorinated arenes and quinones and skeletal cationoid rearrangements in the polyfluoroarene series. The transformations involving CF3-substituted carbocations and radical cations are considered. Heterocyclization and oxidative addition reactions of trifluoroacetamide derivatives and transformations of the organic moiety in polyfluorinated organoboranes and borates with retention of the carbon – boron bond are discussed. Particular attention is devoted to catalytic olefination using freons as an efficient synthetic route to fluorinated compounds. The application of unsymmetrical fluorine-containing N-heterocyclic carbene ligands as catalysts for olefin metathesis is demonstrated. A variety of classes of organofluorine compounds are considered, in particular, polyfluorinated arenes and 1,2-diaminobenzenes, 1-halo-2-trifluoroacetylacetylenes, α-fluoronitro compounds, fluorinated heterocycles, 2-hydrazinylidene-1,3-dicarbonyl derivatives, imines and silanes. The potential practical applications of organofluorine compounds in fundamental organic chemistry, materials science and biomedicine are outlined. The bibliography includes 1019 references.

A new tandem double acylation/rearrangement reaction of nitro compounds is described. It has a broad substrate scope allowing the mild and efficient synthesis of α-acyloxy oxime esters in high yields and regioselectivity. According to the obtained data, the mechanism for transformation was proposed. The utility of the obtained α-hydroxy oxime esters was demonstrated.

Acylation of nitronates affords α-acyloxyoxime derivatives via an umpolung functionalization of the α-position. This transformation involves generation of hitherto unknown N-acyloxy, N-oxyenamines and their fast [3,3]-sigmatropic rearrangement driven by the cleavage of the weak N-O bond. The reaction has a broad scope, and it is regioselective in the case of nitronates possessing nonsymmetrically substituted α-positions. Application to the formal total synthesis of clausenamide and cis-clausenamide is presented.

A convenient method for arylation of mono- and disubstituted 1,2,3-triazoles by copper-catalyzed Chan-Lam coupling was developed. The method is applicable for the regioselective synthesis of fluorescent 4-halogen-substituted (Hal = F, Cl, Br) 2,5-diaryl-1,2,3-triazoles in high yields. Comparative study of their fluorescent properties revealed that 4-fluorosubstituted triazoles possess the highest quantum yield (up to 0.69) among halogenated triazoles possessing Cl and Br in the position 4.

A one-pot three-component route towards fluorinated five/five-annulated nitroso acetals bearing two fused isoxazolidine rings is described. Target nitroso acetals were obtained with complete regioselectivity and high stereoselectivity. The mechanism of this tandem [4 + 1]/[3 + 2] cycloaddition was proposed to include the intermediate formation of elusive 3-fluoro-isoxazoline-N-oxides as key intermediates. This method is applicable for the synthesis of a broad scope of nitroso acetals starting from various fluoronitroalkenes, halogenated dicarbonyl compounds and dipolarophiles of different electronic nature.

New efficient synthesis of 4-fluoro-5-aryl-1,2,3-NH-triazoles was elaborated. The reaction of NaN3 with arylsubstituted α fluoronitroalkenes resulted in domino construction of target fluorinated triazoles. Sulfamic acid was found to be an effective promoter for this heterocyclization. It was demonstrated that subsequent functionalization of obtained triazoles proceeds highly regioselectively at the N-2 position. The observed regioselectivity was supported by DFT calculations.

Due to their availability and versatile reactivity, nitronates have become important building blocks in the stereoselective synthesis of bioactive molecules. This short review provides a summary of recent developments on the synthesis, chemistry and applications of O-alkyl and O-silyl nitronates.1 Introduction2 Approaches to the Synthesis of Nitronates2.1 Synthesis of Six-Membered Cyclic Nitronates2.1.1 Formal [4+2] Approaches2.1.2 Formal [3+3] Approaches2.1.3 Other Approaches2.2 Synthesis of Five-Membered Cyclic Nitronates2.2.1 Formal [3+2] Approaches2.2.2 Formal [4+1] Approaches2.2.3 Oxidation Approaches3 Chemistry of Nitronates3.1 Nitronates as α-C-Nucleophiles3.2 Nitronates as α-C-Electrophiles3.3 Nitronates in [3+n]-Annulation Reactions3.4 Reactions Involving the β-Carbon Atom of Nitronates3.5 Miscellaneous Transformations4 Conclusion

In this article, comprehensive studies on the nucleophilic chlorination and bromination of readily available six-membered cyclic nitronates (1,2-oxazine-N-oxides) are reported. Under optimized conditions (POCl3 or (COBr)2 with Hunig’s base), 3-halo-substituted 1,2-oxazines, which are difficult to access by other routes, were obtained in good to high yields. The latter were shown to be convenient precursors to other 3-substituted 1,2-oxazine derivatives using Lewis/Bronsted acid-assisted substitution of the halide atom for C-, S-, and N-nucleophiles.

A new method was developed for the synthesis of fully substituted 3-haloisoxazoles. This process includes the synthesis of isoxazoline N-oxides from α-halonitroalkenes and subsequent dehydration mediated by the silyl triflate/triethylamine system.

Silyl nitronates undergo rhodium-catalyzed formal [3+3]-cycloaddition with enol diazoacetates to form N-silyloxy-3,6-dihydro-2H-1,2-oxazines. The scope of the reaction and the extent of the major side process were evaluated. A mechanistic scheme was proposed. The nitrogen inversion barrier in the obtained nitroso acetals was estimated based on both quantum calculations and kinetic measurements.

A synthesis of hitherto unknown bicyclic nitroso acetals possessing two annulated six-membered rings is accomplished. The synthesis comprises formal [3+3] cycloaddition of six-membered cyclic nitronates with donor-acceptor cyclopropanes. Some chemical transformations and conformational preferability of the obtained nitroso acetals are discussed.

A general method for the synthesis of substituted indolizines by copper(II) acetate-promoted oxidative [3 + 2]-annulation of α-fluoronitroalkenes with in situ generated pyridinium ylides was developed. Application of the copper(II) acetate–2,6-lutidine system provides efficient access to various 1-fluoroindolizines in up to 81% yield. Both electron-rich and electron-deficient nitroalkenes as well as different pyridinium and isoquinolinium salts can be involved in the reaction. Moreover, it was found that copper-mediated annulation is applicable for other α-substituted (alkyl, chloro, and ester) nitroalkenes giving rise to the corresponding indolizines. First synthesis of monofluorinated [3,2,2]cyclazines was demonstrated via oxidative annulation of 3-unsubstituted fluoroindolizines with diethyl acetylene dicarboxylate.

The [3+3]-cycloaddition of cyclopropane dicarboxylates with 3-methyl-5,6-dihydro-4H-1,2-oxazine-N-oxides promoted by Yb(OTf)3 under hyperbaric conditions is described. The substrates scope and reaction mechanism are discussed.

Chemistry of covalent nitronates regarding nucleophilic addition to C=N bond is described. Various types of electrophilic activation of nitronates and stability of formed products are discussed with main attention paid to authors' work in the area.

A new highly efficient method for the synthesis of 2-fluoro-2-nitrostyrenes was described. Radical nitration of readily available 2-bromo-2-fluorostyrenes with Fe(NO3)3·9H2O resulted in the formation of the corresponding α-fluoro-nitroalkenes in isolated yields up to 92%. The reaction proceeded as a nitration-debromination sequence to highly stereoselectively give α-fluoro-nitroalkenes as Z-isomers only. The broad scope of this method was demonstrated. Prepared monofluorinated alkenes were shown to be versatile building blocks for the synthesis of various fluorinated products.

Silyl nitronates obtained in situ from the corresponding aliphatic nitro compounds react with dimethylformamide dimethyl acetal giving 2-nitroenamines in moderate to good yields. The reaction pathway is discussed.

1,1-Cyclopropane diesters with donor substituents undergo formal [3+3] cycloaddition with various silyl nitronates under Yb(OTf)3 catalysis in the presence of a proton scavenger to give target N-silyloxy tetrahydro-1,2-oxazines in 56–98% yield. The reasons determining the reaction diastereoselectivity are discussed. The resulting tetrahydro-1,2-oxazines are transformed into pyrroline-N-oxides via a novel TfOH-promoted silanol elimination reaction.

The first formal [3 + 3]-cycloaddition of nitronates with donor-acceptor cyclopropanes is reported. The reaction is catalyzed by ytterbium trifluoromethanesulfonate and leads to hitherto unknown bicyclic nitrosoacetals, possessing two annelated six-membered rings.

The first successful synthesis of 1H-2,3-benzoxazine 3-oxides has been described. The efficiency of the approach is provided by the C–C-coupling of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitroalkanes catalyzed by Pd(dba)2/JohnPhos system followed by in situ recyclization of the intermediates. Several representative transformations allowing selective modification of the nitronate as well as malonate functionalities in the resulting compounds are demonstrated.

A new strategy for the synthesis of 2-(1-hydroxy­alkyl)pyrrolidines and 2-amino-1,5-diols is suggested. The target compounds can be obtained in high yields from available precursors through the intermediacy of six-membered cyclic nitronates and their rearrangement products. Successive reduction of the latter led to the target products with moderate to high diastereoselectivity.

The total stereoselective synthesis of two highly potent phosphodiesterase IVb inhibitors from nitroethane, isovanillin, and ethyl vinyl ether was developed. The compounds obtained are the derivatives of hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one and tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one. The strategy proposed involves silylation of six-membered cyclic nitronates as a key step leading to 5,6-dihydro-4H-1,2-oxazines with the group CH2FG (FG = N3 or OH) at the C(3) atom.

The nucleophile-induced rearrangement of cyclic N-alkoxy- N-(silyloxy)enamines was investigated.As a result, a new strategy for the synthesis of β-pyranoneand β-furanone derivatives from nitro compounds is suggested.

The reactions of N,N-dioxyenamines with carboxylic and sulfonic acid anhydrides were investigated. A new method for the synthesis of α-hydroxyoxime derivatives via the reaction of N,N-dioxyenamines with trifluoroacetic anhydride is described.

A new approach toward the synthesis of 3-α-hydroxyalkyl-5,6-dihydro-4H-1,2-oxazines 1 from available 5,6-dihydro-4H-1,2-oxazine N-oxides 2 has been described. The key step of the process—the rearrangement of 3-alkiliden-2-siloxy-tetrahydro-1,2-oxazines 3 (ASENA)—was thoroughly investigated. Optimal experimental conditions were developed. A possible pathway of the ASENA rearrangement was proposed.