A Straightforward Synthesis of 2‐[1‐Alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic Acid Derivatives via Domino Michael Addition?Cyclization Reaction

A new and efficient synthesis of 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives by a one‐pot three‐component reaction between primary amine, dialkyl acetylenedicarboxylate, and itaconic anhydride (=3,4‐dihydro‐3‐methylidenefuran‐2,5‐dione) is reported. The reaction was performed without catalyst and under solvent‐free conditions with excellent yields. Notably, the ready availability of the starting materials, and the high level of practicability of the reaction and workup make this approach an attractive complementary method to access to unknown 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of domino Michael addition? cyclization reaction is proposed (Scheme 2).     

Electron ionization mass spectra of 8‐aryl‐3,4‐dioxo‐2H,8H‐6,7‐dihydroimidazo[2,1‐c][1,2,4]triazines. Do they exhibit tautomerism in the gas phase?

The electron ionization mass spectra of the title compounds (1: a R = H, b 2-CH(3), c 4-CH(3), d 2,3-diMe, e 2-OCH(3), f 4-OCH(3), g 2-Cl, h 3-Cl, i 4-Cl, j 3,4-diCl) were recorded at 70 eV to determine the effects of substituents and the possible keto-enol tautomerism. The compounds showed several common fragment ions but also fragment ions which divided them into three classes, namely 1a-1d (parent compound and Me-substituted derivatives), 1e and 1f (MeO-substituted derivatives), and 1g-1j (Cl-substituted derivatives). The presence of the HOCN(+.) ion as well as the exponential dependence of its total ion current in the case of p- and also 3-Cl-substituted compounds (1a, c, f, h-j) on the Hammett sigma constants and the loss of CHO or one or two HOCN moieties can be somewhat easier explained by the presence of the enol form but as a whole the results support the predominance of the keto form, in parallel to the situation in solution.     

Mixed (PS/PO)‐Stabilized Geminal Dianion: Facile Diastereoselective Intramolecular C?H Activations by a Related Ruthenium–Carbene Complex

A new unsymmetrical geminal dianion that contained both a phosphine oxide moiety and a phosphine sulfide moiety has been synthesized. Its reactivity towards Ru^II was explored, which led to the formation of a highly reactive carbene complex that evolved at room temperature to yield a kinetic orthometalated Ru^II complex through C? H activation of the phenyl group of the phosphine oxide moiety. This insertion was found to be thermally reversible and a second C? H insertion occurred at a phenyl group of the phosphine sulfide moiety to form the thermodynamic orthometalated Ru^II complex in a diastereospecific manner. DFT calculations fully rationalized the experimental findings in terms of the relative energies of the kinetic and thermodynamic products and allowed the mechanism of this process to be fully understood.     

Methylidene Rare‐Earth‐Metal Complex Mediated Transformations of CN,NN and N?H Bonds: New Routes to Imido Rare‐Earth‐Metal Clusters

Three new patterns of reactivity of rare‐earth metal methylidene complexes have been established and thus have resulted in access to a wide variety of imido rare‐earth metal complexes [L₃Ln₃(μ₂‐Me)₃(μ₃‐Me)(μ ‐ NR)] (L=[PhC(NC₆H₃iPr₂‐2,6)₂]^?; R=Ph, Ln=Y ( 2 a ), Lu ( 2 b ); R=2,6‐Me₂C₆H₃, Ln=Y ( 3 a ), Lu ( 3 b ); R=p‐ClC₆H₄, Ln=Y ( 4 a ), Lu ( 4 b ); R=p‐MeOC₆H₄, Ln=Y ( 5 a ), Lu ( 5 b ); R=Me₂CHCH₂CH₂, Ln=Y ( 6 a ), Lu ( 6 b )) and [{L₃Lu₃(μ₂‐Me)₃(μ₃‐Me)}₂(μ ‐ NR′N)] (R′=(CH₂)₆ ( 7 b ), (C₆H₄)₂ ( 8 b )). Complex 2 b was treated with an excess of CO₂ to give the corresponding carboxylate complex [L₃Lu₃(μ‐η¹:η¹‐O₂CCH₃)₃(μ‐η¹:η²‐O₂C‐CH₃)(μ‐η¹:η¹:η²‐O₂CNPh)] ( 9 b ) easily. Complex 2 a could undergo the selective μ₃‐Me abstraction reaction with phenyl acetylene to give the mixed imido/alkynide complex [L₃Y₃(μ₂‐Me)₃(μ₃‐η¹:η¹:η³‐NPh)(μ₃‐C?CPh)] ( 10 a ) in high yield. Treatment of 2 with one equivalent of thiophenol gave the selective μ₃‐methyl‐abstracted products [L₃Ln₃(μ₂‐Me)₃(μ₃‐η¹:η¹:η³‐NPh)(μ₃‐SPh)] (Ln=Y ( 11 a ); Lu ( 11 b ). All new complexes have been characterized by elemental analysis, NMR spectroscopy, and most of the structures confirmed by X‐ray diffraction.     

Why are reactions of 2‐ and 8‐thioquinoline derivatives with iodine different?

The crystal structures of 1,2‐dihydro‐1,1′‐bi[thiazolo[3,2‐a]quinoline]‐10a,10a′‐diium diiodide hemihydrate, C₂₂H₁₆N₂S₂²⁺·2I⁻·0.5H₂O, and 1,2‐dihydro‐1,1′‐bi[thiazolo[3,2‐a]quinoline]‐10a,10a′‐diium iodide triiodide, C₂₂H₁₆N₂S₂²⁺·I⁻·I₃⁻, obtained during the reaction of 1,4‐bis(quinolin‐2‐ylsulfanyl)but‐2‐yne (2TQB) with iodine, have been determined at 120 K. The crystalline products contain the dication as a result of the reaction proceeding along the iodocyclization pathway. This is fundamentally different from the previously observed reaction of 1,4‐bis(quinolin‐8‐ylsulfanyl)but‐2‐yne (8TQB) with iodine under similar conditions. A comparative analysis of the possible conformational states indicates differences in the relative stabilities and free rotation for the 2‐ and 8‐thioquinoline derivatives which lead to a disparity in the convergence of the potential reaction centres for 2TQB and 8TQB.     

C?H/π‐Interaction‐Guided Self‐Assembly in π‐Conjugated Oligomers

We report CH/π hydrogen‐bond‐driven self‐assembly in π‐conjugated skeletons based on oligophenylenevinylenes (OPVs) and trace the origin of interactions at the molecular level by using single‐crystal structures. OPVs were designed with appropriate pendants in the aromatic core and varied by hydrocarbon or fluorocarbon tails along the molecular axis. The roles of aromatic π‐stack, van der Waals forces, fluorophobic effect and CH/π interactions were investigated on the theromotropic liquid crystallinity of OPV molecules. Single‐crystal structures of hydrocarbon OPVs provided direct evidence for the existence of CH/π interactions between the π‐ring (H‐bond acceptor) and alkyl C? H (H‐bond donor). The four important crystallographic parameters, d_c?x=3.79 Å, θ=21.49°, φ=150.25° and d_Hp?x=0.73 Å, matched in accordance with typical CH/π interactions. The CH/π interactions facilitate the close‐packing of mesogens in x–y planes, which were further protruded along the c axis producing a lamellar structure. In the absence of CH/π interactions, van der Waals interactions drove the assembly towards a Schlieren nematic texture. Fluorocarbon OPVs exhibited smectic liquid‐crystalline textures that further underwent Smectic A (SmA) to Smectic C (SmC) phase transitions with shrinkage up to 11 %. The orientation and translational ordering of mesogens in the liquid‐crystalline (LC) phases induced H‐ and J‐type molecular arrangements in fluorocarbon and hydrocarbon OPVs, respectively. Upon photoexcitation, the H‐ and J‐type molecular arrangements were found to emit a blue or yellowish/green colour. Time‐resolved fluorescence decay measurements confirmed longer lifetimes for H‐type smectic OPVs relative to that of loosely packed one‐dimensional nematic hydrocarbon‐tailed OPVs.     

Does a Stabilising Interaction Favouring the Z,Z Configuration of ?S‐NSN‐S? Systems Exist?

The existence of the orbital interaction presented in the literature as being the cause for the stabilisation of the Z,Z configuration of Ph-S-N=S=N-S-Ph (1) and its derivatives in the crystal phase, has been investigated. The results of theoretical calculations at the DFT/B3LYP/6-311+G* level of theory suggest that such a stabilising interaction might not exist or be extremely weak and that packing forces must be the main cause of the observed Z,Z configuration in the solid. To reach this conclusion structural and energetic parameters were combined to study the bonding in these -S-N=S=N-S- systems. For the analogous Ph-Se-N=S=N-Se-Ph (2) in particular the isomeric equilibrium in solution found in the variable-temperature 77Se NMR spectrum indicates that, in the gas phase or in solution, the observed Z,Z configuration is not stabilised to a greater extent than the Z,E configuration.     

Investigation on the individual contributions of N?H···OC and C?H···OC interactions to the binding energies of β‐sheet models

In this article, the binding energies of 16 antiparallel and parallel β‐sheet models are estimated using the analytic potential energy function we proposed recently and the results are compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparisons indicate that the analytic potential energy function can produce reasonable binding energies for β‐sheet models. Further comparisons suggest that the binding energy of the β‐sheet models might come mainly from dipole–dipole attractive and repulsive interactions and VDW interactions between the two strands. The dipole–dipole attractive and repulsive interactions are further obtained in this article. The total of N? H···H? N and C?O···O?C dipole–dipole repulsive interaction (the secondary electrostatic repulsive interaction) in the small ring of the antiparallel β‐sheet models is estimated to be about 6.0 kcal/mol. The individual N? H···O?C dipole–dipole attractive interaction is predicted to be ?6.2 ± 0.2 kcal/mol in the antiparallel β‐sheet models and ?5.2 ± 0.6 kcal/mol in the parallel β‐sheet models. The individual C^α? H···O?C attractive interaction is ?1.2 ± 0.2 kcal/mol in the antiparallel β‐sheet models and ?1.5 ± 0.2 kcal/mol in the parallel β‐sheet models. These values are important in understanding the interactions at protein–protein interfaces and developing a more accurate force field for peptides and proteins. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

2‐Halogeno‐1,3,2‐diazaarsolenes and 2‐halogeno‐1,3,2‐diazastibolenes: Examples for spontaneous E?X bond heterolysis or not?

2‐X‐1,3,2‐diazaarsolenes and 2‐X‐1,3,2‐ stibolenes (X = Cl, Br) were prepared from appropriate α‐amino‐aldimine precursors via transamination with ClSb(NMe₂)₂ or via base‐induced dehydrohalogenation with EX₃ (E = As, Sb). The products were further converted into 2‐iodo‐derivatives via halide exchange with Me₃SiI, or into 1,3,2‐diazaarsolenium or 1,3,2‐stibolenium salts via halide abstraction using E′X₃ (E′ = Al, Ga, Sb) or Me₃SiOTf. All compounds synthesized were characterized by spectroscopic data and several of them by single‐crystal X‐ray diffraction studies. The results of these investigations confirmed that diazaarsolenium or stibolenium cations are stabilized by similar π‐delocalization effects as the corresponding diazaphospholenium cations. 2‐Halogeno‐1,3,2‐diazaarsolenes and 2‐halogeno‐132‐stibolenes are best addressed as molecular species whose covalent E X bonds are as in 2‐chloro‐diazaphospholenes weakened by intramolecular π(C₂N₂) → σ*(E X) and, in the case of the Sb‐containing heterocycles, inter‐ molecular n(X′) → σ*(E X) hyperconjugation between the σ* (E X) orbital and a lone‐pair of electrons on the halogen atom of a neighboring molecule. Correlation of structural and spectroscopic data and the evaluation of halide transfer reactions allowed to conclude that the extent of E X bond weakening in the 2‐X‐substituted heterocycles decreases and thus the Lewis acidity of the cations increases, with increasing atomic number of the pnicogen atom. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:327–338, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20098     

Synthesis of Perfluoroalkyl‐Substituted γ‐Lactones and 4,5‐Dihydropyridazin‐3(2H)‐ones via Donor?Acceptor Cyclopropanes

Rh₂(OAc)₄‐Catalyzed decomposition of diazo esters in the presence of perfluoroalkyl‐ or perfluoroaryl‐substituted silyl enol ethers smoothly provided the corresponding alkyl 2‐siloxycyclopropanecarboxylates in very good yields. The generated donor? acceptor cyclopropanes are equivalents of γ‐oxo esters, which we demonstrated by their one‐pot transformations to yield fluorine‐containing heterocycles. A reductive procedure selectively afforded perfluoroalkyl‐substituted γ‐hydroxy esters or γ‐lactones. The treatment of the donor? acceptor cyclopropanes with hydrazine or phenylhydrazine afforded a series of perfluoroalkyl‐ and perfluoroaryl‐substituted 4,5‐dihydropyridazin‐3(2H)‐ones.     

Is the μ‐Oxo‐μ‐Peroxodiiron Intermediate of a Ribonucleotide Reductase Biomimetic a Possible Oxidant of Epoxidation Reactions?

Density functional calculations on a mu-oxo-mu-peroxodiiron complex (1) with a tetrapodal ligand BPP (BPP=N,N-bis(2-pyridylmethyl)-3-aminopropionate) are presented that is a biomimetic of the active site region of ribonucleotide reductase (RNR). We have studied all low-lying electronic states and show that it has close-lying broken-shell singlet and undecaplet (S=0, 5) ground states with essentially two sextet spin iron atoms. In strongly distorted electronic systems in which the two iron atoms have different spin states, the peroxo group moves considerably out of the plane of the mu-oxodiiron group due to orbital rearrangements. The calculated absorption spectra of (1,11)1 are in good agreement with experimental studies on biomimetics and RNR enzyme systems. Moreover, vibrational shifts in the spectrum due to (18)O(2) substitution of the oxygen atoms in the peroxo group follow similar trends as experimental observations. To identify whether the mu-oxo-mu-1,2-peroxodiiron or the mu-oxo-mu-1,1-peroxodiiron complexes are able to epoxidize substrates, we studied the reactivity patterns versus propene. Generally, the reactions are stepwise via radical intermediates and proceed by two-state reactivity patterns on competing singlet and undecaplet spin state surfaces. However, both the mu-oxo-mu-1,2-peroxodiiron and mu-oxo-mu-1,1-peroxodiiron complex are sluggish oxidants with high epoxidation barriers. The epoxidation barriers for the mu-oxo-mu-1,1-peroxodiiron complex are significantly lower than the ones for the mu-oxo-mu-1,2-peroxodiiron complex but still are too high to be considered for catalytic properties. Thus, theory has ruled out two possible peroxodiiron catalysts as oxidants in RNR enzymes and biomimetics and the quest to find the actual oxidant in the enzyme mechanism continues.     

Enantioselective Palladium‐Catalyzed Insertion of α‐Aryl‐α‐diazoacetates into the O?H Bonds of Phenols

A palladium‐catalyzed asymmetric O H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α‐aryl‐α‐diazoacetates into the O H bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium‐catalyzed asymmetric O H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α‐aryl‐α‐aryloxyacetates.     

Mechanistic Insight into the NN Bond‐Cleavage of Azo‐Compounds that was Induced by an Al?Al‐bonded Compound [L2−AlII?AlIIL2−]

An α‐diimine‐stabilized Al? Al‐bonded compound [L^2?Al^II? Al^IIL^2?] (L=[{(2,6‐iPr₂C₆H₃)NC(Me)}₂]; 1 ) consists of dianionic α‐diimine ligands and sub‐valent Al²⁺ ions and thus could potentially behave as a multielectron reductant. The reactions of compound 1 with azo‐compounds afforded phenylimido‐bridged products [L^?Al^III(μ₂‐NPh)(μ₂‐NAr)Al^IIIL^?] ( 2 – 4 ). During the reaction, the dianionic ligands and Al²⁺ ions were oxidized into monoanions and Al³⁺, respectively, whilst the [NAr]^2? imides were produced by the four‐electron reductive cleavage of the N?N double bond. Upon further reduction by Na, the monoanionic ligands in compound 2 were reduced to the dianion to give [(L^2?)₂Al^III₂(μ₂‐NPh)₂Na₂(thf)₄] ( 5 ). Interestingly, when asymmetric azo‐compounds were used, the asymmetric adducts were isolated as the only products (compounds 3 and 4 ). DFT calculations indicated that the reaction was quite feasible in the singlet electronic state, but the final product with the triplet‐state monoanionic ligands could result from an exothermic singlet‐to‐triplet conversion during the reaction process.     

Acid?Base Properties of Adenosine 5′‐Monophosphate,Guanosine 5′‐Monophosphate,and Inosine 5′‐Monophosphate in Aqueous Solutions of Methanol

The protonation constants of adenosine 5′‐monophosphate, guanosine 5′‐monophosphate, and inosine 5′‐monophosphate were determined in binary mixtures of H₂O containing 0, 10, 15, 20, 25, 30, 35, 40, 45, and 50% MeOH, using a combination of potentiometric and spectrophotometric methods at a constant temperature (25°) and constant ionic strength (0.1 mol?dm^?3 NaClO₄). The protonation constants were analyzed using the normalized polarity parameter (E ), and Kamlet, Abboud, and Taft (KAT) parameters. A linear correlation of log K vs. the normalized polarity parameter was obtained. Dual‐parameter correlation of log K vs. π* (dipolarity/polarizability) and α (H‐bond‐donor acidity), as well as π* and β (H‐bond‐acceptor basicity) also gives good results in various aqueous organic solvent mixtures. Finally, the results are discussed in terms of the effect of solvent on the protonation equilibria.     

C?C Cross‐Coupling Reactions of O6‐Alkyl‐2‐Haloinosine Derivatives and a One‐Pot Cross‐Coupling/O6‐Deprotection Procedure

Reaction conditions for the C? C cross‐coupling of O⁶‐alkyl‐2‐bromo‐ and 2‐chloroinosine derivatives with aryl‐, hetaryl‐, and alkylboronic acids were studied. Optimization experiments with silyl‐protected 2‐bromo‐O⁶‐methylinosine led to the identification of [PdCl₂(dcpf)]/K₃PO₄ in 1,4‐dioxane as the best conditions for these reactions (dcpf=1,1′‐bis(dicyclohexylphosphino)ferrocene). Attempted O⁶‐demethylation, as well as the replacement of the C‐6 methoxy group by amines, was unsuccessful, which led to the consideration of Pd‐cleavable groups such that C? C cross‐coupling and O⁶‐deprotection could be accomplished in a single step. Thus, inosine 2‐chloro‐O⁶‐allylinosine was chosen as the substrate and, after re‐evaluation of the cross‐coupling conditions with 2‐chloro‐O⁶‐methylinosine as a model substrate, one‐step C? C cross‐coupling/deprotection reactions were performed with the O⁶‐allyl analogue. These reactions are the first such examples of a one‐pot procedure for the modification and deprotection of purine nucleosides under C? C cross‐coupling conditions.     

6‐Chloroisocytosine and 5‐bromo‐6‐methylisocytosine: again,one or two tautomers present in the same crystal?

It is well known that pyrimidin‐4‐one derivatives are able to adopt either the 1H‐ or the 3H‐tautomeric form in (co)crystals, depending on the coformer. As part of ongoing research to investigate the preferred hydrogen‐bonding patterns of active pharmaceutical ingredients and their model systems, 2‐amino‐6‐chloropyrimidin‐4‐one and 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4‐one have been cocrystallized with several coformers and with each other. Since Cl and Br atoms both have versatile possibilities to interact with the coformers, such as via hydrogen or halogen bonds, their behaviour within the crystal packing was also of interest. The experiments yielded five crystal structures, namely 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (1/3), C₅H₇N₂⁺·C₄H₃ClN₃O⁻·3C₄H₄ClN₃O, (Ia), 2‐aminopyridin‐1‐ium 2‐amino‐6‐chloro‐4‐oxo‐4H‐pyrimidin‐3‐ide–2‐amino‐6‐chloropyrimidin‐4(3H)‐one–2‐aminopyridine (2/10/1), 2C₅H₇N₂⁺·2C₄H₃ClN₃O⁻·10C₄H₄ClN₃O·C₅H₆N₂, (Ib), the solvent‐free cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one (1/1), C₅H₆BrN₃O·C₅H₆BrN₃O, (II), the solvate 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–N‐methylpyrrolidin‐2‐one (1/1/1), C₅H₆BrN₃O·C₅H₆BrN₃O·C₅H₉NO, (III), and the partial cocrystal 2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐5‐bromo‐6‐methylpyrimidin‐4(1H)‐one–2‐amino‐6‐chloropyrimidin‐4(3H)‐one (0.635/1/0.365), C₅H₆BrN₃O·C₅H₆BrN₃O·C₄H₄ClN₃O, (IV). All five structures show R₂²(8) hydrogen‐bond‐based patterns, either by synthon 2 or by synthon 3, which are related to the Watson–Crick base pairs.     

Mechanistic Study on the Cleavage and Reorganization of C(sp3)?H and CN Bonds in Carbodiimides: Synthesis of 1,2‐Dihydrothiopyrimidines and 2,3‐Dihydropyrimidinthiones through Four‐Component Coupling

This study sheds light on the cleavage and reorganization of C(sp³)? H and C?N bonds of carbodiimides in a three‐component reaction of terminal alkynes, sulfur, and carbodiimides by a combination of methods including 1) isolation and X‐ray analysis of six‐membered‐ring lithium species 2‐S , 2) trapping of the oxygen‐analogues ( B‐O and D‐O ) of both four‐membered‐ring intermediate B‐S and ring‐opening intermediate D‐S , 3) deuterium labeling studies, and 4) theoretical studies. These results show that 1) the reaction rate‐determining step is [2+2] cycloaddition, 2) the C?N bond cleavage takes place before C(sp³)? H bond cleavage, 3) the hydrogen attached to C6 in 2‐S originates from the carbodiimide, and 4) three types of new aza‐heterocycles, such as 1,2‐dihydrothiopyrimidines, N‐acyl 2,3‐dihydropyrimidinthiones, and 1,2‐dihydropyrimidinamino acids are constructed efficiently based on 2‐S . All results strongly support the idea that the reaction proceeds through [2+2] cycloaddition/4π electrocyclic ring‐opening/1,5‐H shift/6π electrocyclic ring‐closing as key steps. The research strategy on the synthesis, isolation, and reactivity investigation of important intermediates in metal‐mediated reactions not only helps achieve an in‐depth understanding of reaction mechanisms but also leads to the discovery of new synthetically useful reactions based on the important intermediates.     

Transition‐metal‐catalyzed aminations and aziridinations of C?H and CC bonds with iminoiodinanes

Catalytic insertion or addition of a metal‐imido/nitrene species, generated from reaction of a transition‐metal catalyst with iminoiodanes, to C? H and C?C bonds offers a convenient and atom economical method for the synthesis of nitrogen‐containing compounds. Following this groundbreaking discovery during the second half of the last century, the field has received an immense amount of attention with a myriad of impressive metal‐mediated methods for the synthesis of amines and aziridines having been developed. This review will cover the significant progress made in improving the efficiency, versatility and stereocontrol of this important reaction. This will include the various iminoiodanes, their in situ formation, and metal catalysts that could be employed and new ligands, both chiral and non‐chiral, which have been designed, as well as the application of this functional group transformation to natural product synthesis and the preparation of bioactive compounds of current therapeutic interest. DOI 10.1002/tcr.201100018