Triazenolysis of alkenes as an aza version of ozonolysis.

Alkenes are broadly used in synthetic applications, thanks to their abundance and versatility. Ozonolysis is one of the most canonical transformations that converts alkenes into molecules bearing carbon-oxygen motifs via C=C bond cleavage. Despite its extensive use in both industrial and laboratory settings, the aza version-cleavage of alkenes to form carbon-nitrogen bonds-remains elusive.

Stable 2-Azaallyl Salts as a Bridge between 2-Azirines and Densely Functionalized 2-Pyrroles.

An efficient protocol for the synthesis of stable 2-azaallyl anion salts by the reaction of alkyl 2-bromo-2-azirine-2-carboxylates with trimethylsilyl cyanide/BuNF has been developed. The domino reaction proceeds in four steps via the cleavage of the azirine C-C bond to provide the tetrabutylammonium salts of stereochemically pure 2-azaallyl anions having U-configuration relative to the cyano groups. The anions with an -substituted aryl group or styryl group exist as a mixture of two geometrical isomers across the N2-C3 bond.

Triethylamine-Promoted Oxidative Cyclodimerization of 2-Azirine-2-carboxylates to Pyrimidine-4,6-dicarboxylates: Experimental and DFT Study.

An unprecedented oxidative cyclodimerization reaction of 2-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study and DFT calculations, the key steps of the reaction mechanism include nucleophilic addition of ,-diethylhydroxylamine to an azirine to form an (aminooxy)aziridine, generation of an azomethine ylide, and its 1,3-dipolar cycloaddition to the second azirine molecule.

Copper(II)-Catalyzed (3+2) Cycloaddition of 2-Azirines to Six-Membered Cyclic Enols as a Route to Pyrrolo[3,2-]quinolone, Chromeno[3,4-]pyrrole, and Naphtho[1,8-]indole Scaffolds.

A method for the [2+3] pyrroline annulation to the six-membered non-aromatic enols using 3-aryl-2-azirines as annulation agents is developed in the current study. The reaction proceeds as a formal (3+2) cycloaddition via the N1-C2 azirine bond cleavage and is catalyzed by both Cu(II) and Cu(I) compounds. The new annulation method can be applied to prepare pyrrolo[3,2-]quinoline, chromeno[3,4-]pyrrole, and naphtho[1,8-]indole derivatives in good to excellent yields from enols of the quinolin-2-one, 2-chromen-2-one, and 1-phenalen-1-one series.

Blue Light-Promoted Cross-Coupling of α-Diazo Esters with Isocyanides: Synthesis of Ester-Functionalized Ketenimines.

A metal-free scalable synthesis of functionalized ketenimines from alkyl α-(aryl/heteroaryl)-α-diazoacetates and alkyl isocyanides induced by blue light irradiation has been developed. The reaction proceeds at room temperature without any photocatalyst and provides ketenimines in moderate to good yields. Density functional theory (DFT) calculations and the experimental study showed that aryl(alkoxycarbonyl)carbenes in both singlet and triplet states can react with isocyanides but only the reaction of the former leads to the smooth formation of ketenimines.

ATP-Independent Initiation during Cap-Independent Translation of mA-Modified mRNA.

The methylation of adenosine in the N position (mA) is a widely used modification of eukaryotic mRNAs. Its importance for the regulation of mRNA translation was put forward recently, essentially due to the ability of methylated mRNA to be translated in conditions of inhibited cap-dependent translation initiation, e.g.

Azirine-containing dipeptides and depsipeptides: synthesis, transformations and antibacterial activity.

Azirine-containing dipeptides and depsipeptides with a wide range of substituents have been synthesized in high yields via the Passerini and Ugi multicomponent reactions (MCRs) using 2H-azirine-2-carboxylic acids as the acid component. The obtained MCR adducts have been transformed to lactam-fused aziridines, as well as pyrrole, imidazole, aziridine, and other derivatives, containing the dipeptide or depsipeptide moiety. The azirine-containing depsipeptides exhibit antibacterial activity against the ESKAPE pathogens, especially Gram-positive bacterial strains (E.

Regiodivergent Synthesis of Butenolide-Based α- and β-Amino Acid Derivatives via Base-Controlled Azirine Ring Expansion.

A method for the preparation of 5-aminobutenolides from 2-bromo-2-azirine-2-carboxylic esters/amides with arylacetic acids has been developed. The reaction regioselectivity can be switched by a change of the basic catalyst, making it possible to prepare both butenolide-based α- and β-amino acid derivatives. The change in the regioselectivity is interpreted in terms of the stability and reactivity of the enolates formed during the S2' substitution of the bromine in the azirine by the carboxylate ion.

Non-natural 2-azirine-2-carboxylic acids: an expedient synthesis and antimicrobial activity.

Non-natural 2-azirine-2-carboxylic acids were obtained in high yields by FeCl-catalyzed isomerization of 5-chloroisoxazoles to azirine-2-carbonyl chlorides followed by their hydrolysis. The 3-aryl- and 3-heteroaryl-substituted acids are stable during prolonged storage, exhibit antibacterial activity against ESKAPE pathogens and show a low level of cytotoxicity.

Selective Cu-Catalyzed Intramolecular Annulation of 3-Aryl/Heteryl-2-(diazoacetyl)-1-pyrroles: Synthesis of Benzo/Furo/Thieno[]-Fused 1-Indol-7-oles and Their Transformations.

The Co(III)-catalyzed reaction of 1,3-dicarbonyl compounds with 2-(diazoacetyl)-2-azirines, prepared by a simplified procedure from 2-azirin-2-carbonyl chlorides, led in high yields to the formation of 2-(diazoacetyl)pyrroles, while leaving the diazoacetyl function intact. The intramolecular aromatic substitution reaction of 2-(diazoacetyl)pyrroles, catalyzed by Cu(OTf), provided selectively previously unknown benzo[]- and hetero[]-fused indol-7-oles in good yields. Formylation of benzo[]indol-4-ol led selectively to the 5-formyl derivative, which is a good precursor for an unusual salen ligand and its Ni-complex.

2 H-Azirines as C-C Annulation Reagents in Cu-Catalyzed Synthesis of Furo[3,2- c]quinolone Derivatives.

A method of furo-annulation of 4-hydroxy-2-oxoquinoline-3-carboxylates with 3-arylazirines under Cu(II) catalysis was developed to synthesize a variety of 2,3-dihydrofuro[3,2- c]quinolones bearing a carbamate group at the C2 position. The reaction involves an azirine ring opening across the N-C2 bond and formation of a dihydrofuran ring with the inclusion of two azirine carbon atoms, accompanied by a shift of the ester group to the nitrogen. The discovered reaction is the first example of the use of 2 H-azirines for furo-annulation.

2-Diazoacetyl-2 H-azirines: Source of a Variety of 2 H-Azirine Building Blocks with Orthogonal and Domino Reactivity.

A synthesis of 2-diazoacetyl-2 H-azirines was developed starting from 2 H-azirine-2-carbonyl chlorides, generated by Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-Diazoacetyl-2 H-azirines easily undergo reactions characteristic of α-diazo ketones with preservation of the azirine ring. Reactions with hydrohalogenic, carboxylic, and p-toluenesulfonic acids provide novel 1-(3-aryl-2 H-azirin-2-yl)-2-halo- and 2-(R-oxy)ethan-1-ones in good yields.

Facile access to 2-acyloxy-, aryloxy- and alkenyloxy-2H-azirines via an S2'-S2' cascade in 2-halo-2H-azirines.

Various 2-oxygen-substituted 2H-azirine-2-carboxylic acid derivatives were synthesized in high yields under mild conditions from readily available precursors, 2-halo-2H-azirines and OH-reagents having pKa values in the range of 3-10. This reaction is the first example of substitution at the azirine carbon atom for which an unusual SN2'-SN2' cascade mechanism was revealed.

Cu(I)-NHC-Catalyzed (2 + 3)-Annulation of Tetramic Acids with 2H-Azirines: Stereoselective Synthesis of Functionalized Hexahydropyrrolo[3,4-b]pyrroles.

A stereoselective and high-yield synthesis of hexahydropyrrolo[3,4-b]pyrroles from tetramic acids and 2H-azirines under Cu(I)-NHC catalysis is developed. An unusual N-C2 azirine bond cleavage, initiated by a copper enolate, was rationalized in terms of a free radical reaction mechanism.

Internal translation initiation and eIF4F/ATP-independent scanning of mRNA by eukaryotic ribosomal particles.

The recombinant mRNAs with 5'-untranslated region, called omega leader, of tobacco mosaic virus RNA are known to be well translated in eukaryotic cell-free systems, even if deprived of cap structure. Using the method of primer extension inhibition (toe-printing), the ribosomal particles were shown to initiate translation at uncapped omega leader when its 5'-end was blocked by a stable RNA-DNA double helix, thus providing evidence for internal initiation. The scanning of the leader sequence and the formation of ribosomal 48S initiation complexes at the initiation AUG codon occurred in the absence of ATP-dependent initiation factor eIF4F, as well as without ATP.