Introduction

Amino groups, amino alcohols, vicinal diamines, and saturated nitrogen-containing heterocycles are widely found in drug molecules and their synthetic intermediates. The synthesis of these structures requires not only the introduction of nitrogen atoms, but also control over the position of nitrogen attachment, the arrangement of adjacent substituents, and the configurations of newly generated stereocenters.

Aziridine is a saturated three-membered nitrogen-containing heterocycle composed of two carbon atoms and one nitrogen atom. Because of the bond-angle and conformational constraints of the three-membered ring, its C—C and C—N bonds are present in relatively high-energy states. Ring-opening reactions can release part of the ring strain while retaining the amino group and introducing oxygen-, nitrogen-, sulfur-, halogen-, or carbon-based substituents. Ring expansion and strained-ring reorganization can further convert aziridines into azetidines and bridged nitrogen-containing scaffolds.

The reaction outcomes of aziridines are not determined solely by ring strain. The substituent on the nitrogen atom affects the electrophilicity of the ring carbons, the degree of C—N bond polarization, and the subsequent deprotection method; the substitution patterns of the two ring carbons affect the site of bond cleavage; and nucleophiles, acids, Lewis acids, radical conditions, and transition-metal catalytic systems control the type of newly formed bond, regioselectivity, and stereochemistry. Accordingly, the same aziridine scaffold can be converted into amino alcohols, vicinal diamines, β-substituted amines, azetidines, or bridged amines under different reaction conditions.

Aziridines mainly serve two roles in drug synthesis. In one role, they function as synthetic intermediates that undergo selective ring opening, ring expansion, or coupling to organize adjacent carbon centers, transfer stereochemical information, and construct various nitrogen-containing scaffolds. In the other, they are retained in a limited number of drugs or natural products as structural units capable of participating in covalent reactions with biological macromolecules.

This article focuses on aziridine structure and ring strain, N-substituent effects, methods for constructing the three-membered ring, selective ring opening, representative scaffold transformations, and applications in pharmaceutical process chemistry, illustrating how a highly strained small ring can be converted into a controllable intermediate for drug synthesis.

Keywords: aziridine; ring strain; N-substituent effects; regioselectivity; stereospecificity; enantioconvergence; cross-electrophile coupling; azetidine; β-substituted amines; drug synthesis

1 Structural and Reactivity Fundamentals of Aziridines

1.1 Bond Angles and Conformational Constraints of the Three-Membered Ring

The ideal bond angle of a saturated carbon atom is close to 109.5°, whereas the internal angles of an aziridine three-membered ring are close to 60°. The carbon and nitrogen atoms within the ring must deviate from their respective more stable bonding geometries, and the C—C and C—N bonds also exhibit some bent-bond character.

The ring strain of aziridines mainly includes:

① Angle strain: the internal bond angles deviate substantially from the ideal bond angle of a saturated carbon atom;

② Torsional strain: the bonds in the three-membered ring approach an eclipsed conformation and cannot form a stable staggered arrangement;

③ Substituent repulsion: substituents on the ring carbons and nitrogen atom may further increase steric congestion.

After a C—N bond is cleaved and a new chemical bond is formed, the geometric constraints of the three-membered ring are relieved. Ring-opening reactions therefore generally have a favorable thermodynamic driving force.

1.2 Ring Strain Provides the Driving Force, While Substrate Structure Determines the Reaction Pathway

The ring strain of an aziridine primarily affects the energy difference between the structures before and after ring opening. The actual reaction rate, site of bond cleavage, and product type also depend on the following factors:

① the substituent on the nitrogen atom and its electron-withdrawing ability;

② the degree of substitution and electronic environment of the two ring carbons;

③ the properties of the nucleophile;

④ the activation mode of the Brønsted acid or Lewis acid;

⑤ the stability of radical or transition-metal intermediates;

⑥ the conformation and ring size required for an intramolecular reaction.

Accordingly, the same class of aziridines may exhibit different regioselectivities under neutral nucleophilic, acidic, and metal-catalyzed conditions.

2 How N-Substituents Regulate Aziridine Reactivity

The nitrogen atom is not only part of the three-membered ring scaffold but may also be bonded to hydrogen, alkyl, aryl, sulfonyl, carbamate, or pyridinium groups. N-Substituents alter the electron density on nitrogen, the degree of C—N bond polarization, the electrophilicity of the ring carbons, and the subsequent deprotection method, making them key variables in aziridine route design.[1]

2.1 N-Sulfonyl Aziridines

The p-toluenesulfonyl group, o-nitrobenzenesulfonyl group, and other sulfonyl groups exert strong electron-withdrawing effects. They reduce electron donation from the nitrogen atom into the three-membered ring and increase the electrophilicity of the ring carbons.

These substrates generally have the following characteristics:

① they can undergo ring opening with oxygen, nitrogen, sulfur, halogen, and carbon nucleophiles;

② they exhibit relatively well-defined stereochemistry under bimolecular nucleophilic substitution conditions;

③ the sulfonyl group continues to protect the amino group after ring opening;

④ subsequent steps require suitable desulfonylation conditions.

Different sulfonyl groups do not behave identically. The p-toluenesulfonyl group generally has relatively high stability, whereas the o-nitrobenzenesulfonyl group is more readily removed by nucleophilic cleavage. Selection must therefore balance ring-opening activity, compatibility with preceding and subsequent steps, and deprotection conditions.

2.2 N-Carbamate Aziridines

tert-Butoxycarbonyl (Boc), benzyloxycarbonyl, and other carbamate groups provide moderate electronic regulation of aziridines while offering well-established deprotection methods.

The practical value of these substrates is mainly reflected in the following:

① they maintain the amino group in a protected state over multiple steps;

② they can participate in nucleophilic ring opening, Lewis acid activation, and certain ring-expansion reactions;

③ the deprotection method can be matched to the functional groups required in subsequent steps.

Their ring-opening activity is strongly influenced by the substitution pattern of the substrate and the reaction conditions and generally needs to be evaluated with the specific nucleophile and activating reagent.

2.3 Unprotected, N-Alkyl, and N-Aryl Aziridines

Unprotected aziridines and N-alkyl or N-aryl aziridines generally retain relatively strong electron-donating ability at nitrogen. Under neutral conditions, their ring carbons are often less electrophilic than those of N-sulfonyl aziridines.

Common activation methods include:

① protonation to form an aziridinium ion;

② coordination of a Lewis acid to the nitrogen atom;

③ quaternization to enhance C—N bond polarization;

④ conversion into activated derivatives containing a cleavable N—N bond.

After ring opening, these aziridines can directly retain the desired N-alkyl or N-aryl structure, helping to reduce subsequent deprotection steps.

2.4 N-Pyridinium Aziridines

N-Pyridinium aziridines contain both electrophilic ring-carbon sites and a reductively cleavable N—N bond. Their reactivity is not limited to conventional nucleophilic ring opening; they can also serve as latent dual electrophiles or precursors to N-aziridinyl radicals.

Under bromide-promoted conditions, the aryl-substituted N-pyridinium aziridines examined in the study can undergo ring opening to form β-brominated pyridinium amines. The newly formed benzylic C—Br bond can participate in nickel-catalyzed coupling, followed by reductive N—N bond cleavage to furnish β-functionalized phenethylamines.[8]

3 Main Methods for Constructing the Aziridine Three-Membered Ring

Aziridines can be constructed from alkenes, imines, or vicinal bifunctional precursors. These three routes follow different bond-forming logics and are suitable for different types of starting materials and stereochemical requirements.

3.1 Nitrogen-Group Transfer to Alkenes

Alkene aziridination forms one C—N bond at each end of a carbon—carbon double bond:

Alkene + nitrogen-transfer reagent → aziridine

Traditional methods often use a metal catalyst to generate a metal nitrene or nitrene-like intermediate, which then transfers the nitrogen-containing fragment to the alkene. Selectivity is jointly influenced by the electronic properties and substitution pattern of the alkene, the catalyst structure, and the nitrogen-containing reagent.

Asymmetric aziridination additionally requires the establishment of a chiral reaction environment. A 2023 study used noncovalent interactions among an achiral dirhodium catalytic center, a quinine-derived chiral cation, and an alkenyl alcohol substrate to achieve enantioselective aziridination of various disubstituted and trisubstituted alkenes.[3]

Electrochemical methods can first oxidatively activate an alkene and then form an aziridine with a primary amine. The electrochemical reaction reported by Holst et al. used primary amines and alkenes directly as starting materials and controlled the oxidation process through the electrodes, thereby expanding the synthetic approaches available for N-alkyl aziridines.[2]

3.2 Cyclization of Imines with Carbon-Based Reagents

Imines can react with halogenated carbanions, sulfur ylides, or other one-carbon reagents to close a C—N bond while forming a C—C bond.

Representative reactions include:

① the aza-Darzens reaction;

② addition–cyclization of sulfur ylides with imines;

③ three-membered-ring construction involving carbene or carbene-like reagents.

This route facilitates modification of the substituents on the two ring carbons. The relative configuration and enantioselectivity of the products are affected by the imine configuration, carbon-reagent structure, metal coordination, and chiral catalyst.

Imine + one-carbon nucleophile or ylide → substituted aziridine

3.3 Intramolecular Cyclization of Vicinal Bifunctional Precursors

1,2-Amino alcohols, haloamines, or amine precursors containing sulfonate leaving groups can form aziridines through intramolecular nucleophilic substitution.

The basic process includes:

① conversion of the hydroxy group into a sulfonate, sulfate, or another leaving group;

② base treatment to generate a nucleophilic nitrogen center;

③ intramolecular attack by nitrogen at the adjacent carbon to close the three-membered ring.

Vicinal amino leaving-group precursor → intramolecular substitution → aziridine

The Wenker reaction is representative of this route and generally converts a 1,2-amino alcohol into an aziridine through sulfation followed by base-promoted ring closure. In the manufacturing process for GDC-9545 (giredestrant), Wenker aziridine synthesis was used to prepare a key tryptamine-type starting material, demonstrating that classical intramolecular cyclization methods remain applicable to process routes for complex drugs.[4]

4 Factors Controlling Selective Ring Opening

Aziridine ring opening requires simultaneous determination of two issues: which C—N bond is cleaved and how the configuration of the attacked ring carbon changes. Different activation modes correspond to different intermediate structures and sources of selectivity.

4.1 Bimolecular Nucleophilic Substitution-Type Ring Opening

In a bimolecular nucleophilic substitution (S_N2)-type reaction, the nucleophile attacks the ring carbon from the backside of the C—N bond while simultaneously promoting C—N bond cleavage.

This pathway generally exhibits the following features:

① the less sterically hindered ring carbon is more readily attacked;

② the attacked carbon undergoes inversion of configuration;

③ the bond between the other ring carbon and the nitrogen atom is retained;

④ a chiral aziridine can transfer configurational information to the ring-opened product.

The general reaction can be represented as:

N-activated aziridine + Nu⁻ → β-substituted amine

Here, Nu⁻ may represent an oxygen, nitrogen, sulfur, halogen, or carbon nucleophile.

4.2 Acid- and Lewis-Acid-Activated Ring Opening

Coordination of a Brønsted acid or Lewis acid to the nitrogen atom can increase C—N bond polarization. If one ring carbon is bonded to an aryl, alkenyl, or other substituent capable of stabilizing positive charge, the reaction may proceed through a transition state or intermediate with pronounced carbocationic character.

In unsymmetrical 2,3-disubstituted N-activated aziridines capable of neighboring-group participation by an aryl group, titanium tetrachloride can promote the formation of a bridged phenonium ion, followed by selective ring opening with chloride to generate complex β-phenethylamine derivatives. This study demonstrates that Lewis acid activation, neighboring-group participation by the aryl group, and the structure of the bridged intermediate can jointly determine the reaction site.[6]

4.3 Intramolecular Attack and Coordination Control

When an aziridine side chain contains a hydroxy, sulfamate, carbonyl, or another coordinating functional group, the intramolecular geometry can affect the site of ring opening.

The main controlling factors include:

① the spatial distance between the nucleophilic group and the two ring carbons;

② the ring size that can be formed in the reaction;

③ chelation between a metal or Lewis acid and a side-chain functional group;

④ conformational strain in the transition state;

⑤ stability of the ring-opened product.

Intramolecular ring opening of aziridines by pendant sulfamates can convert cis- or trans-disubstituted aziridines into the corresponding vicinal-diamine precursors. Within the substrate scope examined in the study, the reaction exhibited clear regioselectivity and stereospecificity.[5]

4.4 Radical- and Transition-Metal-Catalyzed Ring Opening

When radicals or transition metals participate, selectivity is no longer determined primarily by the steric effects governing conventional nucleophilic substitution.

Possible steps include:

① preliminary ring opening by a halide ion to form a β-haloamine;

② single-electron transfer to generate a carbon radical;

③ capture of the radical or organohalide intermediate by nickel or another metal;

④ organozinc coupling systems may undergo transmetalation, whereas cross-electrophile coupling systems rely on an external reductant to maintain the nickel catalytic cycle and form a new C—C bond;

⑤ a chiral metal complex re-establishes the product configuration.

These reactions can form alkyl-, aryl-, alkenyl-, or carbonyl-related C—C bonds at the original ring carbon of the aziridine, thereby expanding the product range beyond that accessible through conventional nucleophilic ring opening.

4.5 Stereospecificity and Enantioconvergence

Stereospecificity describes the relationship between the configuration of the starting substrate and that of the product. In a typical S_N2-type ring opening, the attacked carbon undergoes inversion of configuration. An enantiopure aziridine can therefore be converted into a ring-opened product with a predictable configuration.

Enantioconvergence refers to the conversion of both enantiomers of a racemic substrate into the same major enantiomer of the product. This process generally requires a chiral catalyst and is accompanied by erasure or reorganization of the original substrate configuration.

5 Representative Transformations of Aziridines into Medicinal Chemistry Scaffolds

5.1 Nucleophilic Ring Opening to Construct Adjacent Difunctional Groups

Ring opening with oxygen, nitrogen, and sulfur nucleophiles can furnish amino alcohols, vicinal diamines, and amino sulfides, respectively. β-Haloamines formed by halide-induced ring opening can further participate in substitution, elimination, coupling, or heterocyclization reactions.

In these reactions, the aziridine performs three functions simultaneously:

① it fixes the spatial relationship between two adjacent carbon atoms;

② it retains an amino group;

③ it introduces a second functional group at the selected ring carbon.

The cyclic products obtained through ring opening by pendant sulfamates can undergo further reactions with different nucleophiles to prepare structurally diverse vicinal-diamine derivatives.[5]

5.2 Nickel-Catalyzed Enantioconvergent Alkylation

A reaction reported in 2024 used racemic N-sulfonyl styrenyl aziridines and primary alkyl bromides as starting materials. Catalysis by a chiral nickel–pyridine–imidazoline complex furnished enantioenriched β-alkyl phenethylamines.[7]

The reaction process supported by the study includes:

① regioselective opening of the aziridine by iodide to form a β-amino benzyl iodide;

② entry of the benzyl iodide and alkyl bromide into the nickel catalytic cycle;

③ control of the formation of the new C(sp³)—C(sp³) bond by the chiral nickel complex;

④ convergence of the two enantiomers of the racemic aziridine into the same major product configuration.

This method integrates C—N bond cleavage, C—C bond formation, and enantioselective control within a single reaction system.

5.3 Sequential Dual-Electrophile Reactions of N-Pyridinium Aziridines

N-Pyridinium aziridines can sequentially utilize the three-membered-ring carbon, the benzylic halide site, and the N—N bond.

A representative sequence is as follows:

① bromide opens the three-membered ring to form a β-brominated pyridinium amine;

② the benzylic C—Br bond undergoes nickel-catalyzed C—C coupling with an organozinc reagent;

③ reductive cleavage of the N—N bond releases a β-functionalized phenethylamine.

This route allows separate adjustment of the carbon substituent and nitrogen-substitution state of the phenethylamine scaffold and can be used for late-stage transformation of relatively complex molecules.[8]

5.4 One-Carbon Ring Expansion to Construct Azetidines

Aziridines can be converted into four-membered azetidines through insertion of one carbon atom. Ning et al. reported a rhodium-catalyzed one-carbon ring-expansion reaction of aziridines with vinyl N-[2-(trifluoromethyl)benzenesulfonyl]hydrazones to generate 2-vinylazetidines.[10]

The reaction process includes:

① in situ generation of a vinyl diazo compound from the hydrazone;

② dirhodium-catalyzed nitrogen extrusion to form a vinyl rhodium carbene;

③ interaction of the aziridine nitrogen atom with the carbene to form a vinyl aziridinium ylide;

④ rearrangement of the ylide through a diradical-related pathway and expansion into a four-membered ring.

This reaction retains the nitrogen-containing ring while adding one ring carbon, providing a route to the azetidine scaffold that differs from cyclization of open-chain precursors.

5.5 Reorganization with Bicyclo[1.1.0]butanes to Construct Bridged Amines

Aziridines can undergo a stereospecific formal [2σ+2σ] cycloaddition with bicyclo[1.1.0]butanes. In the presence of tris(pentafluorophenyl)borane, B(C₆F₅)₃, the two strained rings undergo scaffold reorganization to form 2-azabicyclo[3.1.1]heptane derivatives.[11]

When an enantioenriched aziridine is used, the reaction can transfer its stereochemical information to the bridged product. This method converts a relatively planar three-membered-ring starting material into a conformationally constrained, three-dimensional, saturated nitrogen-containing scaffold.

5.6 Radical Transfer of an Intact Aziridine Group

After single-electron reduction, an N-pyridinium aziridine can undergo N—N bond cleavage to generate a transient N-aziridinyl radical. This radical has been directly characterized by spin-trapping electron paramagnetic resonance (EPR) experiments.[9]

In the presence of oxygen, the N-aziridinyl radical can add to styrenyl alkenes and form 1,2-hydroxyaziridination products.

Traditional methods generally close the three-membered ring in situ on the target substrate, whereas aziridine-group radical transfer connects a preformed, intact aziridine unit to a new carbon scaffold.

6 Two Roles of Aziridines in Drug Synthesis

6.1 As Consumed Synthetic Intermediates

Most drug-synthesis routes use aziridines to control the connectivity between adjacent carbon centers and an amino group, after which the three-membered ring is consumed through ring opening, ring expansion, or scaffold reorganization.

This application offers the following advantages:

1. Transfer of Pre-Existing Stereochemical Information

Aziridines prepared from chiral amino alcohols or chiral alkenes can transfer the configuration of the starting material into the configurations of amino alcohols, vicinal diamines, or β-substituted amines through stereospecific ring opening.

2. Preparation of Multiple Analogues from a Common Intermediate

The same aziridine can react separately with oxygen, nitrogen, sulfur, and carbon reagents to construct a series of compounds containing the same amine scaffold but different β-substituents.

3. Conversion of Alkenes into Carbon Centers Suitable for Directed Functionalization

After alkene aziridination, the two ends of the original double bond are converted into two ring carbons with different steric and electronic environments. The N-substituent and catalytic system can further differentiate these two positions and control new bond formation.

The manufacturing process for GDC-9545 used Wenker aziridine synthesis to prepare a key tryptamine-type starting material. In this route, the aziridine ring functions as an intermediate and is not retained in the corresponding tryptamine fragment of the final product.[4]

6.2 As Reactive Structures Retained in the Final Molecule

Some natural products and drugs retain the aziridine ring in their final structures. In such cases, the electrophilicity of the three-membered ring may directly participate in covalent modification of biological macromolecules.

Mitomycin C is a representative example. Its quinone structure first undergoes reductive activation, followed by a series of elimination, rearrangement, and alkylation processes that generate reactive intermediates capable of forming monoadducts and interstrand cross-links with DNA. The aziridine structure participates in this activation cascade, but its DNA reactivity depends on reduction and structural transformation of the entire mitomycin scaffold.[12]

7 Selection of Aziridine Routes and Process Control

7.1 Selecting the Transformation Mode According to the Target Structure

7.2 N-Substituents Must Be Matched to the Complete Synthetic Route

Selection of the N-substituent should simultaneously consider the following stages:

① whether the aziridine can be formed with high selectivity;

② whether the intermediate has suitable stability;

③ whether the desired ring-opening conditions are compatible with other functional groups;

④ whether the N-substituent can be removed or retained at an appropriate stage;

⑤ whether deprotection by-products can be readily removed;

⑥ whether the N-substituent affects crystallization, extraction, or purification.

The N-substituent is therefore not only an electronic regulatory group but also part of the protecting-group strategy and process-purification strategy for the complete route.

7.3 Whether to Isolate the Aziridine Intermediate

Aziridine intermediates can be handled in the following ways:

① isolation and purification before the next step;

② in situ generation followed by direct ring opening;

③ one-pot cyclization–ring opening;

④ generation and immediate consumption in a continuous-flow system.

The choice depends on the thermal stability of the intermediate, concentration effects, potential polymerization, side reactions, crystallization behavior, and the effects of residual reagents from the preceding step on the subsequent reaction. Substituted aziridines with good stability and crystallinity facilitate accurate dosing and quality control. More reactive intermediates or intermediates with a greater accumulation risk can instead be converted in situ to reduce their instantaneous inventory in the reaction system.

7.4 Reactive Impurities and Purge Capability

Aziridine intermediates or related by-products with alkylating activity must be evaluated according to their specific structures and process exposure conditions. Risk assessment generally includes:

① whether the impurity contains a structural alert for DNA reactivity;

② whether it is consumed in subsequent reactions;

③ the purge capability of extraction, crystallization, and washing steps;

④ the actual or predicted residual level in the final active pharmaceutical ingredient;

⑤ the detection and quantification capabilities of the analytical method.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7(R2) guideline provides a framework for the identification, classification, risk characterization, and control of DNA-reactive mutagenic impurities. The specific control strategy should be established on the basis of the actual impurity structure, expected exposure, process purge capability, and experimental data.[13]

8 Classification and Research Applications of Representative Chemicals Related to Aziridine Three-Membered-Ring Construction, N-Substituent Effects, Selective Ring Opening, Scaffold Expansion, and Drug Applications

Table 1. Core Aziridines, Transformed Product Scaffolds, and Drug Structure Comparators

Table 2. Amino Alcohol and Haloamine Precursors, Nitrogen-Protecting Reagents, and Intramolecular Cyclization Reagents

Table 3. Nitrogen-Transfer Reagents, Oxidants, and Catalysts for Alkene Aziridination

Table 4. Nucleophiles and Lewis Acid Activators for Selective Ring Opening

Table 5. Reagents Related to Nickel-Catalyzed Cross-Electrophile Coupling, Carbene-Mediated Ring Expansion, and Strained-Ring Reorganization

References

[1] Ju X, Lee M, Leung J C, Lee J. Synthesis and Functionalization of Aziridines: A Perspective View from Pharmaceutical Industries. European Journal of Organic Chemistry, 2025, 28(15): e202401414. DOI: 10.1002/ejoc.202401414.

[2] Holst D E, Wang D J, Kim M J, Guzei I A, Wickens Z K. Aziridine Synthesis by Coupling Amines and Alkenes via an Electrogenerated Dication. Nature, 2021, 596(7870): 74–79. DOI: 10.1038/s41586-021-03717-7.

[3] Fanourakis A, Hodson N J, Lit A R, Phipps R J. Substrate-Directed Enantioselective Aziridination of Alkenyl Alcohols Controlled by a Chiral Cation. Journal of the American Chemical Society, 2023, 145(13): 7516–7527. DOI: 10.1021/jacs.3c00693.

[4] Xu J, Chung C K, McClory A, Mack K A, Dalziel M E, Fettes A, Clagg K, Lim N K, Wuitschik G, Jenny C, Finet L, Kammerer M, Zhang H, Angelaud R, Gosselin F. Efficient Manufacturing Process for the Selective Estrogen Receptor Degrader GDC-9545 (Giredestrant) via a Crystallization-Driven Diastereoselective Pictet–Spengler Condensation. Organic Process Research & Development, 2022, 26(3): 568–582. DOI: 10.1021/acs.oprd.1c00263.

[5] Nagamalla S, Thomas A A, Nirpal A K, Mague J T, Sathyamoorthi S. Ring Opening of Aziridines by Pendant Sulfamates Allows for Regioselective and Stereospecific Preparation of Vicinal Diamines. The Journal of Organic Chemistry, 2023, 88(22): 15989–16006. DOI: 10.1021/acs.joc.3c01731.

[6] Holst H M, Floreancig J T, Ritts C B, Race N J. Aziridine Opening via a Phenonium Ion Enables Synthesis of Complex Phenethylamine Derivatives. Organic Letters, 2022, 24(2): 501–505. DOI: 10.1021/acs.orglett.1c03857.

[7] Lan Y, Han Q, Liao P, Chen R, Fan F, Zhao X, Liu W. Nickel-Catalyzed Enantioselective C(sp³)–C(sp³) Cross-Electrophile Coupling of N-Sulfonyl Styrenyl Aziridines with Alkyl Bromides. Journal of the American Chemical Society, 2024, 146(37): 25426–25432. DOI: 10.1021/jacs.4c08435.

[8] Samanta S, Biswas P, O’Bannon B C, Powers D C. β-Phenethylamine Synthesis: N-Pyridinium Aziridines as Latent Dual Electrophiles. Angewandte Chemie International Edition, 2024, 63(31): e202406335. DOI: 10.1002/anie.202406335.

[9] Biswas P, Maity A, Figgins M T, Powers D C. Aziridine Group Transfer via Transient N-Aziridinyl Radicals. Journal of the American Chemical Society, 2024, 146(45): 30796–30801. DOI: 10.1021/jacs.4c14169.

[10] Ning Y Q, Chen H Z, Ning Y Y, Zhang J, Bi X. Rhodium-Catalyzed One-Carbon Ring Expansion of Aziridines with Vinyl-N-Triftosylhydrazones for the Synthesis of 2-Vinyl Azetidines. Angewandte Chemie International Edition, 2024, 63(12): e202318072. DOI: 10.1002/anie.202318072.

[11] Dutta S, Daniliuc C G, Mück-Lichtenfeld C, Studer A. Formal [2σ + 2σ]-Cycloaddition of Aziridines with Bicyclo[1.1.0]butanes: Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives. Journal of the American Chemical Society, 2024, 146(39): 27204–27212. DOI: 10.1021/jacs.4c11296.

[12] Cera C, Egbertson M, Teng S P, Crothers D M, Danishefsky S J. DNA Cross-Linking by Intermediates in the Mitomycin Activation Cascade. Biochemistry, 1989, 28(13): 5665–5669. DOI: 10.1021/bi00439a049.

[13] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH M7(R2): Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. Final Version, adopted on 3 April 2023.

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