Nitrosation of β′-hydroxylamino-α,β-unsaturated oximes: synthesis of 1,7-dioxa-2,6-diaza-spiro[4,4]nona-2,8-diene ring system

Nitrosation of bis arylidene acetone oximes with nitrous acid in glacial acetic acid gives 3-vinyl pyrazolone-N,N′-dioxides in 32-37% yield. Similar reactions of 2-arylidene-6-(hydroxylamino-aryl-methyl)-cyclohexanone oximes give tricyclic compounds with dioxa-2,6-diaza-spiro[4,4]nona-2,8-diene ring systems in 77-84% yield.     

Diprotonated hydrazones and oximes as reactive intermediates in electrochemical reductions

The shape of plots of limiting currents of some hydrazones and oximes as a function of pH, the slopes of E_1/2-pH plots (particularly for benzaldehyde N,N,N-trimethylhydrazonium ion) and the presence of separate two or three waves in reductions of some oximes bearing electron withdrawing groups represent a proof of formation of diprotonated forms of hydrazones and oximes as reaction intermediates. They are formed at the surface of the electrode in an equilibrium preceding the uptake of the first electron.     

General and efficient synthetic approach to novel tricyclic spiroketones

A general and efficient synthetic approach to tricyclic spiroketones of interest as useful scaffolds in drug discovery was developed. Starting from commercially available benzyl 4-oxo-1-piperidinecarboxylate (5), spirocyclic tetralone 4, spirocyclic indanone 14, and spirocyclic benzocycloheptanone 15 were synthesized via six reaction steps in excellent overall yield.     

Reaction of substituted spiro[1,2,3,4-tetrahydronaphthalene-2,3′-(1′-pyrazolines)] with chlorinating reagents

In reaction of 4′-arylspiro[1,2,3,4-tetrahydronaphthalene-2,3′-(1′-pyrazolin)]-1-ones with N-chlorosuccinimide formed spirocyclic substituted 3-chloro-1-pyrazolines that lost nitrogen at heating transforming into spirocyclic chlorocyclopropanes. The reaction of the same pyrazolines with chlorine led to the formation of spirocyclic gem-dichlorocyclopropanes.     

A mild system for synthesis of aldoximes and ketoximes in the presence of N-hydroxyphthalimide in aqueous system

An efficient method for synthesis of oximes from aldehydes or ketones with N-hydroxyphthalimide or N-hydroxysuccinimide in water has been described. It is the first time to utilize NHPI as an oximation reagent to synthesize aldoximes and ketoximes from the corresponding organic carbonyl compounds without other reagents. The reaction tolerates various functional groups and affords the corresponding oximes in 76%–98% yields. The by-product phthalic acid can be recycled from the system. In addition, this method has been successfully applied to the synthesis of the precursor of some pharmacologically active amide molecules.     

Efficient one-pot synthesis of 2-azetidinones from acetic acid derivatives and imines using methoxymethylene-N,N-dimethyliminium salt

A cheap, versatile and convenient method for synthesis of β-lactams using methoxymethylene-N,N-dimethyliminium salt as an acid activator in Staudinger reaction is reported. This method is used for the preparation of monocyclic, spirocyclic, N-alkyl and three-electron-withdrawing group β-lactams. The products are obtained in good to excellent yields.     

Combining α-amidoalkylation reactions of N-acyliminium ions with ring-closing metathesis: access to versatile novel isoindolones spirocyclic compounds

A novel approach to diversely spirocyclic isoindoles has been developed by using N-acyliminium/ring-closing metathesis strategy. Spirocyclization precursors, diolefinic, and enyne spiro-fused-isoindole derivatives have been obtained by a regioselective reduction of the spiro-imide compounds, followed by the allylation of the N-acyliminium intermediates (generated from the acetoxylactam compounds). Ruthenium catalyzed ring-closing metathesis of the above unsaturated derivatives provided novel spiroisoindoles.     

Stereoselective approach to conjugated enone oximes from aliphatic nitro compounds and sulfur ylides

A novel approach to conjugated enone oximes from aliphatic nitro compounds deals with double silylation of N,N-bis(silyloxy) enamines followed by a stereoselective reaction with an ester-stabilized sulfur ylide. The proposed mechanism involves the generation of labile nitrosoalkenes as intermediates, which react with the sulfur ylide to give target enone oximes.     

The Vilsmeier reagent: a useful and versatile reagent for the synthesis of 2-azetidinones

(Chloromethylene)dimethylammonium chloride (Vilsmeier reagent), prepared easily from N,N-dimethylformamide and oxalyl chloride or thionyl chloride, works as a versatile acid activator reagent for the direct [2+2] ketene-imine cycloaddition of substituted acetic acid and imines in one-pot synthesis under mild conditions. Monocyclic, spirocyclic and 3-electron-withdrawing group β-lactams were synthesized by this method and optimization of conditions were performed.     

Diversity-Oriented Synthesis of Bioactive Azaspirocycles

A collection of novel azaspirocyclic β-arylethylamines was prepared in good yield and excellent diastereoselectivity by an expedient strategy that features condensation of a cyclic ketone with an amino allylsilane and a tandem aza-Sakurai cyclization to generate several different spirocyclic N-heterocycles. Subsequent elaboration of the spirocyclic scaffold was achieved via Pictet-Spengler cyclizations, Suzuki cross-coupling reactions, N-functionalizations, and olefin refunctionalization reactions to create a diverse library of compounds, several of which have nanomolar affinity for the sigma 1 receptor and transmembrane protein 97 (TMEM97).     

Microwave promoted oxazole synthesis: cyclocondensation cascade of oximes and acyl chlorides

Microwave irradiation promotes the rapid O,N-acylation-cyclodehydration cascade reaction of oximes and acid chlorides to give oxazoles.     

Stereocontrolled intramolecular nitrile oxide cycloaddition reaction using a gauche-gauche interaction

A gauche-gauche interaction is proposed as a powerful controlling factor for the stereochemistry in the intramolecular nitrile oxide cycloaddition reaction derived from N-protected 3-(N-allylamino)propionaldehyde and 2-(N-homoallylamino)acetaldehyde oximes. High levels of stereoselectivity (76% de to perfect) were obtained from the reaction involving nitrile oxides with substituents at the adjacent carbon atom to the tether nitrogen.     

[3+2] Cycloaddition of metal-containing azomethine ylides for highly efficient synthesis of mitosene skeleton

Efficient synthesis of tricyclic indole derivatives bearing a substituent at the 3-position of the indole nucleus was achieved by the [3+2] cycloaddition reaction of transition metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines with vinyl ethers. Third-row transition metal complexes, especially PtCl₂, turned out to be highly efficient for the reaction of internal alkynes and imidate substrates with wide generality. Moreover, as strong support for the reaction mechanism, the intermediate Pt-carbene complex was found to undergo intramolecular C-H bond insertion reaction to give tetracyclic indoline derivatives when benzyl vinyl ether was employed as a dipolarophile. This protocol provided a facile synthesis of highly functionalized tricyclic indole derivatives found as the basic skeleton of the mitosene family, such as mitomycin C.     

Comparison of preparation methods of N-arylsulfinyl-1,4-benzoquinone monoimines

Advantages and shortcomings were discussed of three procedures for preparation N-arylsulfinyl-1,4-benzoquinone imines: the reaction of arenesulfenyl chlorides with 1,4-benzoquinone oximes, the oxidation of N-arylthio-1,4-benzoquinone imines, and the reaction of arylsulfinyl chlorides with p-aminophenols followed by oxidation. A series of new N-arylsulfinyl-1,4-benzoquinone imines was obtained.     

Catalytic enantioselective alkene epoxidation using novel spirocyclic N-carbethoxy-azabicyclo[3.2.1]octanones

A general synthetic route allowing access to several spirocyclic N-carbethoxy-azabicyclo[3.2.1]octanones is developed. These novel ketones efficiently catalyse alkene epoxidation using Oxone^® with up to 91.5% ee.     

Reaction of difluorocarbene with anions from amides and oximes: Synthesis of N-difluoromethyl substituted amides, O-difluoromethylimidates or O-difluoromethyl substituted oximes under phase-transfer catalysis conditions

N-Aryl substituted amides react with chlorodifluoromethane in the presence of concentrated aqueous sodium hydroxide and benzyltriethylammonium chloride (TEBAC) as a catalyst in benzene (phase-transfer catalysis, PTC), affording mixtures of N- and O-difluoromethyl substituted derivatives. Amide anions are involved in this process. The reaction carried out with oximes gives O-difluoromethyl oxime ethers.     

Double nucleophilic N-alkylation of α-oxime-esters with Grignard reagents

Double nucleophilic N-alkylation of α-oxime-esters, affording N,N-dialkyl-α-amino acids is herein described. Grignard reagents accomplished double N-alkylations via umpolung and various N,N-dialkylated α-amino acids were successfully synthesized in 15 min. Both electron-withdrawing sulfonyl groups and electron-donating silyl and methyl groups on oximes were available. Alkylmagnesium species and (E)-configuration of α-oxime-ester were essential to this cascade reaction.     

Reaction of acetyl- and 1,1′-diacetylferrocene with isatin (Pfitzinger reaction)

An efficient method for the synthesis of 2-ferrocenyl-substituted quinoline-4-carboxylic acids via the reaction of acetyl- and 1,1′-diacetylferrocene with isatin under the conditions of the Pfitzinger reaction was developed. Starting from the obtained acids methyl esters, amides, N-methyl-N-methoxyamides, and oximes (at one of the free acetyl groups) of some of these compounds were synthesized.     

α-Hydroxy- and (α-acyloxyimino)benzylphosphonates

N-Hydroxyfluorobenzimidoylphosphonates and their O-acyl derivatives are synthesized. Reaction of phosphorylated oximes with sulfinyl chloride proceeds with rearrangement and leads to synthetically prospective N-sulfonylimidoylphosphonates. By the method of ¹⁹F NMR are revealed values of σ-constants of N-hydroxy- and N-acyloxy substituted imidoylphosphonate groups.     

Novel synthesis of 1,4-thiazin-2-one O-(tert-butyl) oximes and benzo[b][1,4]thiazin-2-one O-(tert-butyl) oximes in the presence of K2CO3/SiO2

A simple and efficient method was developed for the synthesis of 1,4-thiazin-2-one O-(tert-butyl) oximes and benzo[b][1,4]thiazin-2-one O-(tert-butyl) oximes from N-tert-butoxy acyl imidoyl bromides and 2-aminothiols in the presence of K₂CO₃/SiO₂. Twenty five novel compounds were readily synthesized in excellent yields using this procedure. The products possessed Z-stereochemistry with regard to the CN double bond. The reaction proceeded with initial substitution of bromine in the N-tert-butoxy acyl imidoyl bromides by mercapto groups in the presence of K₂CO₃/SiO₂, and subsequent intramolecular Schiff base formation.