Stereoselective allylation of azirines with allylindium reagents

Allylindium reagents allylated azirines to give allylaziridines in good yields. The delivery of the allyl group was well regulated by the substituents at the C³-carbon of azirines. The cis-allylation with respect to the substituent was realized with azirines bearing a hydroxylmethyl or an acetoxymethyl group due to the chelation with allylindium reagents, whereas the trans-allylation was achieved with azirines substituted by a methyl, phenyl, or ester group owing to the steric repulsion.     

Photochemistry of Fluorinated Phenyl Nitrenes: Matrix Isolation of Fluorinated Azirines

2,6-Difluorophenylnitrene and pentafluorophenylnitrene were generated in solid argon at 10 K by irradiation of the corresponding phenyl azides and characterized by IR and UV spectroscopy. Selective irradiation with lambda = 444 nm results in the formation of the corresponding azirines, while ketene imines are not produced. On lambda = 366 nm irradiation the azirines rearrange back to the nitrenes. The assignment of the azirines is confirmed by ab-initio calculations.     

Copper‐Catalyzed Trifluoromethylazidation of Alkynes: Efficient Access to CF3‐Substituted Azirines and Aziridines

A novel method for convenient access to CF₃‐containing azirines has been developed, and involves a copper‐catalyzed trifluoromethylazidation of alkynes and a photocatalyzed rearrangement. Both terminal and internal alkynes are compatible with the mild reaction conditions, thus delivering the CF₃‐containing azirines in moderate to good yields. The azirines can be converted into various CF₃‐substituted aziridines.     

Enantioselective Reaction of 2H‐Azirines with Phosphite Using Chiral Bis(imidazoline)/Zinc(II) Catalysts

The first highly enantioselective nucleophilic addition reaction of phosphites with 2H ‐azirines has been developed. The reaction was applied to various 3‐substituted 2H ‐azirines using novel chiral bis(imidazoline)/Zn^II catalysts to afford products in good yield with high enantioselectivity. The transformation of the obtained optically active aziridines showed that 2H ‐azirines act as either α,β‐ or β,β‐dicarbocationic amine synthons.     

Advances in 2H-azirine chemistry: A seven-year update

2H-Azirines are versatile building blocks for the preparation of various nitrogen-containing heterocycles. Seven years ago the comprehensive review on azirine chemistry was published in Tetrahedron. Since then, there had been an explosion of research activities in the field of these strained molecules. This renaissance is primarily associated with the discovery of new reactivity of azirines and in particular new catalytic and light-induced reactions, which made possible unusual transformations of this three-membered N-heterocycle into azole and azine derivatives as well as polyheterocyclic systems. The second reason for the progress of azirine chemistry is the development of methods for the preparation of new azirine derivatives. The third reason is the discovery of new synthetic equivalents of azirines, which permitted avoiding the use of unstable azirines in some modern catalytic procedures. In the present comprehensive review, we have placed particular emphasis on discussing the new developments in the synthesis and reactivity of azirines for the period from 2012 until the end of 2018.     

Ruthenium‐Catalyzed C−C Bond Cleavage of 2H‐Azirines: A Formal [3+2+2] Cycloaddition to Fused Azepine Skeletons

2H‐azirines can serve as three‐atom synthons by C?C bond cleavage, however, it involves a high energy barrier under thermal conditions (>50.0 kcal mol^?1). Reported is a ruthenium‐catalyzed [3+2+2] cycloaddition reaction of 2H‐azirines with diynes, thus leading to the formation of fused azepine skeletons. This approach features an unprecedented metal‐catalyzed C?C bond cleavage of 2H‐azirines at room temperature, and the challenging construction of aza‐seven‐membered rings from diynes. The results of this study provide a new reaction pattern for constructing nitrogen‐containing seven‐membered rings and may find applications in the synthesis of other complex heterocycles.     

Enantioselective Reaction of 2H‐Azirines

2H‐Azirines are useful precursors for the synthesis of a variety of chiral aziridine and amine derivatives with a range of biological activities. Owing to the ring strain and the presence of a C=N double bond, 2H‐azirines are more reactive than other types of ketimine, and undergo a range of enantioselective reactions, including reduction and Diels–Alder reactions, as well as nucleophilic addition to the C=N double bond. Therefore, the enantioselective reactions of 2H‐azirines has become a hot topic, in particular within the last few years. In this Minireview, we focus on the enantioselective reactions of 2H‐azirines by using catalytic or stoichiometric amounts of chiral additives, the reaction mechanisms, and the applications of these reactions of 2H‐azirines and related compounds in organic synthesis.     

Synthesis of 2H‐Azirines by Iridium‐Catalyzed Decarboxylative Ring Contraction of Isoxazol‐5(4H)‐ones

A phosphine‐free iridium‐catalyzed reaction of isoxazol‐5(4H)‐ones (isoxazolones) has been developed, and affords 2H‐azirines through decarboxylation and ring contraction. This method provides an efficient and environmentally benign protocol which could replace the conventional approaches used to synthesize 2H‐azirines.     

Facile construction of trifluoromethyl-azirines via one-pot metal-free Neber reaction

A Et₃N-mediated Neber reaction of aryl/alkyl-2,2,2-trifluoroethylketoximes has been developed. This one-pot metal-free protocol enables the facile construction of an array of trifluoromethyl-substituted azirines in moderate to high yields under mild reaction conditions. Further transformations of azirines to CF₃-containing pyrrole and amino-alcohol derivatives are also demonstrated.     

Allylation of N-heterocycles with allylic alcohols employing self-assembling palladium phosphane catalysts

The first palladium catalyst system that allows the direct allylation of indoles with allylic alcohols as substrates with water being the only byproduct is presented. The application of self-assembling ligands based on complementary hydrogen bonding was the key to success.     

Azirines in reactions involving the formation of a pyrrole ring (review)

The literature data on the synthesis of pyrroles from azirines are correlated in this review. The following processes are examined: the thermolysis and photolysis of azirines with aromatic radicals and double bonds, the rearrangement of aryl- and vinylazirines under the influence of metal complexes, the cycloaddition of olefins, the cycloaddition of acetylenes, and reactions with CH acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1299–1312, October, 1986.     

Sulfur substituted Small-ring Heterocycles

The synthesis of epoxy sulfines and sulfonyl azirines is described     

The rearrangements of naphthylnitrenes: UV/Vis and IR spectra of azirines, cyclic ketenimines, and cyclic nitrile ylides

Ar matrix photolysis of 1- and 2-naphthyl azides 3 and 4 at 313 nm initially affords the singlet naphthyl nitrenes, (1)()1 and (1)()2. Relaxation to the corresponding lower energy, persistent triplet nitrenes (3)()1 and (3)()2 competes with cyclization to the azirines 15 and 18, which can also be formed photochemically from the triplet nitrenes. On prolonged irradiation, the azirines can be converted to the seven-membered cyclic ketenimines 10 and 13, respectively, as described earlier by Dunkin and Thomson. However, instead of the o-quinoid ketenimines 16 and 19, which are the expected primary ring-opening products of azirines 15 and 18, respectively, we observed their novel bond-shift isomers 17 and 20, which may be formally regarded as cyclic nitrile ylides. The existence of such ylidic heterocumulenes has been predicted previously, but this work provides the first experimental observation of such species. The factors which are responsible for the special stability of the ylidic species 17 and 20 are discussed.     

Synthese d'aza-1 bicyclobutanes tri ou tetrasubstitues a substituant vinylique

Aza-1 bicyclobutanes 1 are readily prepared by reaction of azirines with gem-chloro(alkyl)allyllithium reagents.     

Reaction of difluorocarbene with 2H-azirines: generation and transformations of strained azomethine ylides -- aziriniodifluoromethanides

The reaction of difluorocarbene with azirines affords a new type of azomethine ylides, viz., strained aziriniodifluoromethanides. 1,3-Dipolar cycloadditions of ylides derived from 2-unsubstituted 3-arylazirines to dimethyl acetylenedicarboxylate and aldehydes give derivatives of 2,2-difluoro-1-azabicyclo[3.1.0]hex-3-ene-3,4-dicarboxylic acids and 1,4-oxazin-3(4H)-ones, respectively. Ylides derived from 2-mono- and 2,2-disubstituted azirines undergo isomerization to 2-aza-1,3-diene derivatives. 2,2-Difluoro-1-azabicyclo[3.1.0]hex-3-enes are transformed into 2-fluoropyridine derivatives in high yields and react with amines to give 2,4-diamino-1-azabicyclo[3.1.0]hex-2-ene derivatives.     

A simple approach to azirines containing an aldehyde functionality and their stabilization as palladium(II) complexes

A simple and useful method for the synthesis of azirines containing an aldehyde functionality, from open chain bromo/chloro-aldehydes at room temperature and their stabilization as palladium(II) complexes are reported.     

Synthesis of highly substituted indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes

Ynamides react with conjugated enynes in intramolecular [4 + 2] cycloadditions to afford substituted indolines that undergo oxidation with o-chloranil to furnish the corresponding indoles. The cycloaddition substrates are easily assembled from derivatives of 3-butynylamine by Sonogashira coupling with alkenyl halides followed by copper-catalyzed N-alkynylation with acetylenic bromides. Diynamides participate as particularly reactive 2pi components in the cycloaddition, providing access to indolines with carbon substituents at the C-7 position. Enynamides serve as 4pi components in a complementary version of the cycloaddition strategy which provides access to indoles and indolines substituted with carbon substituents at C-4. These enyne cycloadditions take place upon heating the substrates at 110-210 degrees C in toluene or 2,2,2-trifluoroethanol and in some cases can be achieved at 0 degrees C to room temperature in the presence of Lewis acids such as Me2AlCl.     

Kinetic Resolution of 2H‐Azirines by Asymmetric Imine Amidation

Highly efficient kinetic resolution of 2H‐azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N′‐dioxide/Sc^III complex, thus providing a promising method to obtain the enantioenriched 2H‐azirine derivatives and protecting‐group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H‐azirines were stereospecifically transformed into an unprotected aziridine and α‐amino ketone.     

Annulation of internal alkynes through a hydroamination/aza-Heck reaction sequence for the regioselective synthesis of indoles

Highly regioselective annulation reactions of unsymmetrically substituted alkynes by primary 2-bromo or 2-chloroanilines are achieved with an efficient one-pot protocol, which relies on a regioselective TiCl₄-catalyzed intermolecular hydroamination and a subsequent palladium-catalyzed intramolecular aza-Heck reaction. The use of unsymmetrically substituted alkynes in this strategy enables the synthesis of diversely functionalized indoles, with a regioselectivity that is complementary to the one obtained when employing Larock's annulation reaction.     

Photochemical and Thermal Reactions of Azido‐oligopyridines: Diazepinones,a New Class of Metal‐Complex Ligands

Azido‐oligopyridines were prepared, and their photochemical reactions resulted in diazepinones linked to pyridine moieties. The thermal reactions of azido‐oligopyridines with triple bonds yielded 2H‐azirines directly attached to oligopyridines.