3-Arylaziridine-2-carboxylic Acid Derivatives and (3-Arylaziridin-2-yl)ketones: The Aziridination Approaches

Aziridination reactions represent a powerful tool in aziridine synthesis. Significant progress has been achieved in this field in the last decades, whereas highly functionalized aziridines including 3-arylated aziridine-2-carbonyl compounds play an important role in both medical and synthetic chemistry. For the reasons listed, in the current review we have focused on the ways to obtain 3-arylated aziridines and on the recent advances (mainly since the year 2000) in the methodology of the synthesis of these compounds via aziridination.


Introduction
The finding of new potential anti-cancer and antiviral drugs, as well as the development of efficient methods for synthesizing them and their appropriate building blocks, is one of the most important problems in medical chemistry. Due to the electrophilic nature of the aziridine ring, derivatives of aziridine-2-carboxylic acid react with various nucleophiles, therefore becoming interesting synthetic substrates in order to create different amino acids, alkanolamines, and heterocyclic compounds [1]. Some derivatives of aziridine-2-carboxylic acid, namely, imexon, azimexon [2], and leakadine [3] were developed as anti-tumour agents and have shown anti-cancer immunomodulatory activity.
It is also known that derivatives of aromatic α,β-unsaturated carboxylic acids, such as caffeic acid [4] and its esters [5] have demonstrated cytotoxic effects and promotion of apoptosis in lung carcinoma cells. Its analogue, p-coumaric acid, has shown an anti-angiogenic effect [6], which is important to stop tumor development. In this light, 3-arylated derivatives of aziridine-2-carboxylic acid 1a,b (Scheme 1) and similar compounds containing an aziridine ring in phenylpropionic acid side chain could be predicted to have anti-cancer properties.
Authors of previous reviews have summarized the recent advances in the synthesis of aziridine-2-carbonyl compounds (Zalubovskis and Ivanova [7]) and in the overall aziridine chemistry and synthesis (Singh [8] and Luisi [9]). The generally known methods to obtain these compounds include aziridination, Gabriel-Cromwell cyclization of aminoalcohols, Diels-Alder cycloaddition to azirines, Baldwin rearrangement, and others. This review is focused on synthesizing 3-aryl substituted aziridines 1a-c (Scheme 1) via aziridination since aziridination has a wide perspective, especially in stereoselective synthesis; it is tolerant towards various functional groups and can be realized in mild conditions which are important for construction of more complex molecules. The structures 1a-c (Scheme 1) have two asymmetric carbons in 2(α-) and 3(β-) positions of aziridine ring, and therefore stereoselectivity of synthetic methods is important. Aziridination has two variations: carbon addition to the imine double bond via carbene sources (Scheme 1A) and nitrogen addition to the olefin double bond via nitrene sources (Scheme 1B).
variations: carbon addition to the imine double bond via carbene sources (Scheme 1, A) and nitrogen addition to the olefin double bond via nitrene sources (Scheme 1, B). Scheme 1. The general pathways of aziridination.

Aziridination of Imines (Path A)
This aziridination approach includes:

Aziridination of Imines with a Diazo Carbene Source (Wulff's AZ Reaction)
Catalytic asymmetric aziridination (AZ reaction) of imines using a carbene source represents the best explored and most popular group of synthetic methods of 3-arylated aziridines 1a-c (Scheme 1). The most common carbene sources are diazo compounds, e.g., ethyl diazoacetate (EDA) and its analogues.

Aziridination of Imines with a Diazo Carbene Source (Wulff's AZ Reaction)
Catalytic asymmetric aziridination (AZ reaction) of imines using a carbene source represents the best explored and most popular group of synthetic methods of 3-arylated aziridines 1a-c (Scheme 1). The most common carbene sources are diazo compounds, e.g., ethyl diazoacetate (EDA) and its analogues.
Structure of the self-assembled boroxinate-imine complex 8 (Scheme 4) has been characterized by X-ray diffraction in case of two "chemzyme"-substrate complexes [22]. A practical gram-scale methodology of boroxinate Brønsted acid-catalyzed AZ reaction has been developed [24]. The further steps in developing this asymmetric aziridination tool were experiments with double stereodifferentiation using imines 2 (Scheme 2) obtained from chiral amines (chiral PG) [25] and one-pot five-component reaction protocol: Base-induced formation of boroxinate catalyst 8 (Scheme 4) followed with subsequent addition of diazo compound 3 was replaced with simultaneous addition of all reagents [26].
The further increase of AZ reaction enantioselectivity was realized through insertion of substituents in 7, 7′ positions of biaryl ligand 5b as depicted in the Scheme 3 [27]. Improving of catalyst ligand included developing of iso-VAPOL ligand 4b illustrated in the Scheme 3 [28]. This ligand was an isomer of VAPOL 4a (Scheme 3) but had a chiral pocket of VANOL 5a (Scheme 3) and was available from much cheaper starting materials. Scheme 4. Boroxinate catalyst [15,17,21].
In the subsequent study [16], the active site of the aziridination catalyst "chemzyme" was explored using different N-substituents in the imine 2a (Scheme 2), and authors found that 3.5-dimethyldianisilmethyl (MEDAM) and 3.5-di-tert-butyldianisilmethyl (BUDAM) groups resulted in the best asymmetric inductions in AZ reaction. Further, evidence of cyclic self-assembled boroxinate Brønsted acid ion pair 8 (Scheme 4) acting as an active catalyst in the asymmetric AZ reaction has been reported [17].
Structure of the self-assembled boroxinate-imine complex 8 (Scheme 4) has been characterized by X-ray diffraction in case of two "chemzyme"-substrate complexes [22]. A practical gram-scale methodology of boroxinate Brønsted acid-catalyzed AZ reaction has been developed [24]. The further steps in developing this asymmetric aziridination tool were experiments with double stereodifferentiation using imines 2 (Scheme 2) obtained from chiral amines (chiral PG) [25] and one-pot five-component reaction protocol: Baseinduced formation of boroxinate catalyst 8 (Scheme 4) followed with subsequent addition of diazo compound 3 was replaced with simultaneous addition of all reagents [26].
The further increase of AZ reaction enantioselectivity was realized through insertion of substituents in 7, 7 positions of biaryl ligand 5b as depicted in the Scheme 3 [27]. Improving of catalyst ligand included developing of iso-VAPOL ligand 4b illustrated in the Scheme 3 [28]. This ligand was an isomer of VAPOL 4a (Scheme 3) but had a chiral pocket of VANOL 5a (Scheme 3) and was available from much cheaper starting materials.
A series (12 examples) of esters cis-1a1 (Scheme 2) were obtained by Thurston's group using BINOL-derived Brønsted acid catalyst 10a (Scheme 5) [30]. Multi-component variation of AZ reaction was carried out employing aromatic and heteroaromatic aldehydes. Other examples of multi-component AZ reaction approach involving the above mentioned VAPOL and BOROX catalysts are also known [31,32]. Optimal reaction protocol for aromatic aldehydes in synthesis of aziridines trans-1b (Scheme 2) was found [32].
A series (12 examples) of esters cis-1a1 (Scheme 2) were obtained by Thurston's group using BINOL-derived Brønsted acid catalyst 10a (Scheme 5) [30]. Multi-component variation of AZ reaction was carried out employing aromatic and heteroaromatic aldehydes. Other examples of multi-component AZ reaction approach involving the above mentioned VAPOL and BOROX catalysts are also known [31,32]. Optimal reaction protocol for aromatic aldehydes in synthesis of aziridines trans-1b (Scheme 2) was found [32].
Diazoacetates 3e are useful substrates for synthesis of highly functionalized β-aryl aziridine ketoesters cis-1a3 as shown in the Scheme 9 [44]. Six successful examples with different arylimines were presented. Unfortunately, if Ar = p-NO2Ph, or 2-pyridyl, no reaction was observed. On the other hand, some examples of products cis-1a3 with another ester groups and 2.2-diesters instead of ketoester were demonstrated. Scheme 9. Synthesis of 3-arylaziridine ketoesters [44].
Ionic liquids have been successfully tested for cis-selective AZ reactions [45,46]. Reactions of aromatic aldimines were carried out in bmim PF6 at room temperature [45] and in the same liquids in multi-component variation with 2 mol% of Bi(OTf)3 or 5 mol% of Sc(OTf)3 catalyst [46] addition. The yields of aziridines cis-1a in both studies exceeded 80%. Ten [45] and twelve [46] examples were demonstrated, respectively.
Sugar-derived imine also was successfully aziridinated under BF3*OEt2 catalysis [48]. The montmorillonite K-10 catalysis in imine-EDA aziridine-forming reaction is characterised by high cis-selectivity and good yields (15 examples). The demonstrated procedure is very simple, namely, reactions were performed at room temperature with EDA as solvent [49]. A similar method with LiClO4 catalysis allows to obtain broad spectrum (18 examples) of 3-aryl aziridine esters cis-1a at room temperature in acetonitrile over 4.5-7.5 h at >75% chemical yields and good stereoselectivity [50].
Diazoacetates 3e are useful substrates for synthesis of highly functionalized β-aryl aziridine ketoesters cis-1a3 as shown in the Scheme 9 [44] Diazoacetates 3e are useful substrates for synthesis of highly functionalized β-aryl aziridine ketoesters cis-1a3 as shown in the Scheme 9 [44]. Six successful examples with different arylimines were presented. Unfortunately, if Ar = p-NO2Ph, or 2-pyridyl, no reaction was observed. On the other hand, some examples of products cis-1a3 with another ester groups and 2.2-diesters instead of ketoester were demonstrated. Scheme 9. Synthesis of 3-arylaziridine ketoesters [44].
Ionic liquids have been successfully tested for cis-selective AZ reactions [45,46]. Reactions of aromatic aldimines were carried out in bmim PF6 at room temperature [45] and in the same liquids in multi-component variation with 2 mol% of Bi(OTf)3 or 5 mol% of Sc(OTf)3 catalyst [46] addition. The yields of aziridines cis-1a in both studies exceeded 80%. Ten [45] and twelve [46] examples were demonstrated, respectively.
Sugar-derived imine also was successfully aziridinated under BF3*OEt2 catalysis [48]. The montmorillonite K-10 catalysis in imine-EDA aziridine-forming reaction is characterised by high cis-selectivity and good yields (15 examples). The demonstrated procedure is very simple, namely, reactions were performed at room temperature with EDA as solvent [49]. A similar method with LiClO4 catalysis allows to obtain broad spectrum (18 examples) of 3-aryl aziridine esters cis-1a at room temperature in acetonitrile over 4.5-7.5 h at >75% chemical yields and good stereoselectivity [50].
Ionic liquids have been successfully tested for cis-selective AZ reactions [45,46]. Reactions of aromatic aldimines were carried out in bmim PF 6 at room temperature [45] and in the same liquids in multi-component variation with 2 mol% of Bi(OTf) 3 or 5 mol% of Sc(OTf) 3 catalyst [46] addition. The yields of aziridines cis-1a in both studies exceeded 80%. Ten [45] and twelve [46] examples were demonstrated, respectively.
Ionic liquids have been successfully tested for cis-selective AZ reactions [45,46]. Reactions of aromatic aldimines were carried out in bmim PF6 at room temperature [45] and in the same liquids in multi-component variation with 2 mol% of Bi(OTf)3 or 5 mol% of Sc(OTf)3 catalyst [46] addition. The yields of aziridines cis-1a in both studies exceeded 80%. Ten [45] and twelve [46] examples were demonstrated, respectively.
Sugar-derived imine also was successfully aziridinated under BF3*OEt2 catalysis [48]. The montmorillonite K-10 catalysis in imine-EDA aziridine-forming reaction is characterised by high cis-selectivity and good yields (15 examples). The demonstrated procedure is very simple, namely, reactions were performed at room temperature with EDA as solvent [49]. A similar method with LiClO4 catalysis allows to obtain broad spectrum (18 examples) of 3-aryl aziridine esters cis-1a at room temperature in acetonitrile over 4.5-7.5 h at >75% chemical yields and good stereoselectivity [50].
Sugar-derived imine also was successfully aziridinated under BF 3 *OEt 2 catalysis [48]. The montmorillonite K-10 catalysis in imine-EDA aziridine-forming reaction is characterised by high cis-selectivity and good yields (15 examples). The demonstrated procedure is very simple, namely, reactions were performed at room temperature with EDA as solvent [49]. A similar method with LiClO 4 catalysis allows to obtain broad spectrum (18 examples) of 3-aryl aziridine esters cis-1a at room temperature in acetonitrile over 4.5-7.5 h at >75% chemical yields and good stereoselectivity [50].

Aziridination of Imines with Other Carbene Precursors
Other carbene precursors or carbene-like species can be added to imines. These species include:

Variations of aza-Darzen Reaction
The most frequently used method is the addition of enolates derived from α-bromoesters to various imines (aza-Darzen reaction variations).

Variations of aza-Darzen Reaction
The most frequently used method is the addition of enolates derived from α-bromoesters to various imines (aza-Darzen reaction variations).
Another approach to chiral 3-aryl aziridine-2-carboxylic acid derivatives by asymmetric aza-Darzen type reaction is the use of chiral moiety in the imine component.
Chemical yields are good (57-78%) and stereoselectivity excellent, >95% dr in 14 demonstrated examples [58]. However, in some cases depending of the imine aryl substituent structure (using imines 2e2) inversion of stereochemistry has been observed and aziridines trans-1b5 obtained [59]. The mechanism of reaction and transition states were elucidated.
Another approach to chiral 3-aryl aziridine-2-carboxylic acid derivatives by asymmetric aza-Darzen type reaction is the use of chiral moiety in the imine component.
Another approach to chiral 3-aryl aziridine-2-carboxylic acid derivatives by asymmetric aza-Darzen type reaction is the use of chiral moiety in the imine component.
More complicated cascade reactions (Scheme 17) which allowed stereoselective obtaining of 3-arylated 2-chloro aziridines was demonstrated by Xu and co-authors [71]. This cascade coupling included nucleophilic addition of anion generated from silyldichloromethane 20 and nitriles 19 in presence of LDA and subsequent [1,3] -aza-Brooke rearrangement to give α-N-silyl imines in equilibrium with 1-azaenolate equivalents. These species were then trapped by imines 2g in an aza-Darzen type reaction to give aziridines 1c5 in good (up to 50%) yields and up to 10:1 selectivity demonstrated in 19 cases for each method. Remarkably, stereoselectivity strictly depends on the silyl group and the order of addition of 2g and HMPA (method A or B).
Yields up to 60% (determined by 19 FNMR) and up to 80% syn products were obtained in ten examples.
More complicated cascade reactions (Scheme 17) which allowed stereoselective obtaining of 3-arylated 2-chloro aziridines was demonstrated by Xu and co-authors [71]. This cascade coupling included nucleophilic addition of anion generated from silyldichloromethane 20 and nitriles 19 in presence of LDA and subsequent [1,3] -aza-Brooke rearrangement to give α-N-silyl imines in equilibrium with 1-azaenolate equivalents. These species were then trapped by imines 2g in an aza-Darzen type reaction to give aziridines 1c5 in good (up to 50%) yields and up to 10:1 selectivity demonstrated in 19 cases for each method. Remarkably, stereoselectivity strictly depends on the silyl group and the order of addition of 2g and HMPA (method A or B).

Ylides as Carbon Sources
An interesting variation of C=N double-bond aziridination are aziridinations of ylides. The first remarkable reports were made by Ishikava's group on reactions of guanidinium ylides with aryl aldehydes as a practical route for obtaining of inactivated 3-arylated aziridine-2-carboxylates 1a1 [72][73][74][75][76]. The initial study [72] for the first time reported the formation of guanidinium ylides 21b from guanidinium salts 21a in the presence of base (NaH or tetramethylguanidine) and their reactions with aryl aldehydes to form trans aziridines 1a1 (Scheme 18). In the subsequent publication [73], the potential reaction mechanism and role of the p-substituents in aldehyde aryl ring were explored. The authors concluded that in the case of EDG p-substituted benzaldehydes SNi-like mechanism and in case of EWG substituents SN2-type mechanism took place. Not only trans aziridines

Ylides as Carbon Sources
An interesting variation of C=N double-bond aziridination are aziridinations of ylides. The first remarkable reports were made by Ishikava's group on reactions of guanidinium ylides with aryl aldehydes as a practical route for obtaining of inactivated 3-arylated aziridine-2-carboxylates 1a1 [72][73][74][75][76]. The initial study [72] for the first time reported the formation of guanidinium ylides 21b from guanidinium salts 21a in the presence of base (NaH or tetramethylguanidine) and their reactions with aryl aldehydes to form trans aziridines 1a1 (Scheme 18). In the subsequent publication [73], the potential reaction mechanism and role of the p-substituents in aldehyde aryl ring were explored. The authors concluded that in the case of EDG p-substituted benzaldehydes S N i-like mechanism and in case of EWG substituents S N 2-type mechanism took place. Not only trans aziridines 1a1 are available with this method. Procedure of epimerization in β-(C3) position was described [74] using indium chloride catalyst. Aziridinomitosene skeleton synthesis [74], formal synthesis of (-)-podophyllotoxin [75] and synthesis of cyclic dipeptide (-)-benzolactam-V8 [76] has been demonstrated.

Ylides as Carbon Sources
An interesting variation of C=N double-bond aziridination are aziridinations of ylides. The first remarkable reports were made by Ishikava's group on reactions of guanidinium ylides with aryl aldehydes as a practical route for obtaining of inactivated 3-arylated aziridine-2-carboxylates 1a1 [72][73][74][75][76]. The initial study [72] for the first time reported the formation of guanidinium ylides 21b from guanidinium salts 21a in the presence of base (NaH or tetramethylguanidine) and their reactions with aryl aldehydes to form trans aziridines 1a1 (Scheme 18). In the subsequent publication [73], the potential reaction mechanism and role of the p-substituents in aldehyde aryl ring were explored. The authors concluded that in the case of EDG p-substituted benzaldehydes SNi-like mechanism and in case of EWG substituents SN2-type mechanism took place. Not only trans aziridines 1a1 are available with this method. Procedure of epimerization in β-(C3) position was described [74] using indium chloride catalyst. Aziridinomitosene skeleton synthesis [74], formal synthesis of (-)-podophyllotoxin [75] and synthesis of cyclic dipeptide (-)-benzolactam-V8 [76] has been demonstrated.
Simple trimethylammonium salts work similarly via amide-stabilized ammonium ylides (forming from salts 22a; Scheme 20) which react with aromatic aldimines 2a3 to form 3-arylated trans-aziridine carboxamides trans-1b [79]. Moderate to good yields and trans-selectivity has been demonstrated in eight examples. Remarkable feature is that ammonium salts 22b do not react with aldimines 2a2 in similar way. However, the classic aza-Darzen process-reaction of imines 2a2 with phenacyl bromide 15g-gives cis-aziridinyl ketones cis-1c6 in high yields.

Scheme 19. DABCO-promoted aziridination [78].
This one-pot aziridination process include quaternization of DABCO, then in situ formation of ammonium ylide in the presence of base and aziridination of imine 2a2 to obtain 3-arylated trans-aziridinyl ketones trans-1c6 in good yields (nine examples) and trans-selectivity. Enantioselective aziridination using chiral DABCO analogue also was demonstrated.
Simple trimethylammonium salts work similarly via amide-stabilized ammonium ylides (forming from salts 22a; Scheme 20) which react with aromatic aldimines 2a3 to form 3-arylated trans-aziridine carboxamides trans-1b [79]. Moderate to good yields and transselectivity has been demonstrated in eight examples. Remarkable feature is that ammonium salts 22b do not react with aldimines 2a2 in similar way. However, the classic aza-Darzen process-reaction of imines 2a2 with phenacyl bromide 15g-gives cis-aziridinyl ketones cis-1c6 in high yields.
Ester and amide-stabilized sulfur ylides generated form sulfonium salts were explored [82] as sources of aziridines (Scheme 23). It was established that ester and amidestabilized sulfur ylides 25 react with activated aryl aldimines 2a2 reversibly to form betaines 26 and the stereocontrolling step is represented by the base-controlled aziridine ring closure leading to aziridines 1a6, 1b6.
An interesting variation of aziridine synthesis from imines is the benzyne-promoted Darzen-type reaction of tertiary amine 27 as shown in the Scheme 25 [85]. This process was performed in mild conditions (no strong bases, room temperature) in the presence of 2-(trimethylsilyl)phenyl triflate 28, KF and a crown ether. Five different 3-arylated aziridine-2-carboxylates trans-1a1 were obtained in moderate to good yields (40-80%) and good trans-selectivity > 98:2 dr.

Aziridination of Olefins (Path B)
This pathway of aziridination includes:

Evans Aziridination
The reaction of olefins with active nitrene species generated from various nitrene precursors represents another well-known and reliably explored method to synthesize aziridine structures 1. The first approach, notable for 3-aryl aziridine-2-carboxylic acid derivative synthesis, is the classical Evans aziridination using PhI=NTs as nitrene precur-Scheme 25. Benzyne-promoted Darzen-type aziridination [85].

Aziridination of Olefins (Path B)
This pathway of aziridination includes:

Aziridination of Olefins (Path B)
This pathway of aziridination includes:

Evans Aziridination
The reaction of olefins with active nitrene species generated from various nitrene precursors represents another well-known and reliably explored method to synthesize aziridine structures 1. The first approach, notable for 3-aryl aziridine-2-carboxylic acid derivative synthesis, is the classical Evans aziridination using PhI=NTs as nitrene precursor, cinnamate type substrates 29 as olefins in the presence of Cu salts as catalysts (Scheme 26) [86,87].
The comparison of BOX 30a, AnBOX 30b and cHBOX 30c ligands in Evans-type chalcone substrate 29c aziridination and the exploration of π-stacking between chalcone and ligand aromatic systems were performed [99]. The results showed that π-interaction between chalcone substrates 29c and the AnBOX ligand's 30b anthracene backbone was important in order to improve the enantioselectivity of aziridination.
The comparison of BOX 30a, AnBOX 30b and cHBOX 30c ligands in Evans-type chalcone substrate 29c aziridination and the exploration of π-stacking between chalcone and ligand aromatic systems were performed [99]. The results showed that π-interaction between chalcone substrates 29c and the AnBOX ligand's 30b anthracene backbone was important in order to improve the enantioselectivity of aziridination.
The further improvements of Evans chalcone 29c and cinnamate 29a aziridination included use of Cu(2) and poly/perfluorinated alkoxyaluminate type anion complexes [100], alumina-supported [101] and immobilized magnetic Cu containing nanoparticles [102]. Use of gold instead of copper catalyst has also been reported [103].

Oxidative Aziridination
Another important method for asymmetric aziridination of alkenes is the reaction with N-aminophthalimide in the oxidative conditions (Pb(OAc) 4 or another oxidant) as a nitrene source. The asymmetric induction can be conducted with chiral moiety in the substrate and with chiral ligand. Thus, use of chiral auxiliary can be illustrated by aziridination of chiral camphor N-enoylpirazolidinone 29b1 to obtain aziridine-2-hydrazide trans-1b9 (Scheme 29) in good yield [104]. Another chiral camphor-based auxiliary-directed aziridination of aziridine esters was demonstrated [105] but this study was focused on only a single example of cinnamate 29a.  [100], alumina-supported [101] and immobilized magnetic Cu containing nanoparticles [102]. Use of gold instead of copper catalyst has also been reported [103].

Oxidative Aziridination
Another important method for asymmetric aziridination of alkenes is the reaction with N-aminophthalimide in the oxidative conditions (Pb(OAc)4 or another oxidant) as a nitrene source. The asymmetric induction can be conducted with chiral moiety in the substrate and with chiral ligand. Thus, use of chiral auxiliary can be illustrated by aziridination of chiral camphor N-enoylpirazolidinone 29b1 to obtain aziridine-2-hydrazide trans-1b9 (Scheme 29) in good yield [104]. Another chiral camphor-based auxiliary-directed aziridination of aziridine esters was demonstrated [105] but this study was focused on only a single example of cinnamate 29a. Scheme 29. Oxidative aziridination of a chiral substrate [104]. Chiral ligand-mediated variation of this aziridination was studied by the same authors [106]. Reaction of N-enoyl oxazolidinones 29b2 in similar conditions and in presence of ligand 35 lead to aziridine-carboxamides trans-1b10 in good yields and >80% ee (Scheme 30).

Scheme 29.
Oxidative aziridination of a chiral substrate [104]. Chiral ligand-mediated variation of this aziridination was studied by the same authors [106]. Reaction of N-enoyl oxazolidinones 29b2 in similar conditions and in presence of ligand 35 lead to aziridine-carboxamides trans-1b10 in good yields and >80% ee (Scheme 30).

Scheme 29.
Oxidative aziridination of a chiral substrate [104]. Chiral ligand-mediated variation of this aziridination was studied by the same authors [106]. Reaction of N-enoyl oxazolidinones 29b2 in similar conditions and in presence of ligand 35 lead to aziridine-carboxamides trans-1b10 in good yields and >80% ee (Scheme 30).
Oxaziridine 39 can be used simultaneously as oxidant and nitrogen source for oxidative nitrogen transfer alkene aziridinations in synthesis of 3-arylaziridine-2-carboxylates 1a1, and diesters 1a8 as shown in the Scheme 40 [124]. The reaction was carried out under mild conditions in presence of MgI2.
Similar asymmetric organocatalytic aziridination of enones with carbamate reagent TsONHCbz in the presence of catalyst salt 42 (Scheme 45) has been reported [134]. Aziridinyl ketones trans-1c12 were obtained in good yields and ee. Similar asymmetric organocatalytic aziridination of enones with carbamate reagent TsONHCbz in the presence of catalyst salt 42 (Scheme 45) has been reported [134]. Aziridinyl ketones trans-1c12 were obtained in good yields and ee. Scheme 45. Asymmetric organocatalytic aziridination of enones with carbamate reagent [134].

Conclusions
Aziridination has a great synthetic potential in synthesis of 3-arylated aziridine-2carboxylates, carboxamides and 2-aziridinylketones. The most important, well-explored, and practical in terms of imine C=N bond aziridination are Wulff's catalytic AZ reaction employing diazo compounds as carbene sources and various catalytic systems.
This method demonstrates a high stereoselectivity in a broad series of examples and allow obtaining both cis and trans aziridine products including nitriles and aldehydes selectively. In C=C bond aziridination, the main approaches include Evans olefin aziridination using PhI=NTs type nitrene sources under Cu catalysis, as well as oxidative aziridination variations.
Notably, Evans aziridination is suitable for aziridination of chalcone and cinnamate type substrates and oxidative methods allows to obtain also 3-arylaziridine-2-carboxamides. Remarkable are several methods which allow to directly access NH aziridines, such as Armstrong's aziridination.