We report a hypervalent iodine-mediated C-N cross-coupling between phenols or anilines and azoles. A catalytic variant based on in situ oxidation of an aryl iodide was also developed. The reaction proceeds at room temperature in an HFIP/CH3NO2 solvent system and avoids the use of prefunctionalized aryl halides as coupling partners. Under optimized conditions, triazoles, pyrazoles, and other azoles couple in up to 90% isolated yield with broad functional-group tolerance. The HFIP/CH3NO2 mixture (3:1) suppresses competitive O-N coupling and promotes selective C-N bond formation. A catalytic variant using an aryl iodide (10 mol %) with mCPBA and CF3COOH as the terminal oxidant-acid pair delivers comparable efficiency. This operationally simple protocol complements palladium- or copper-catalyzed methods by eliminating aryl-halide preactivation and transition metals.

Over the past three decades, hypervalent halogen catalysis has demonstrated significant versatility in facilitating various organic transformations. This review categorizes these catalytic reactions into two main classifications: oxidation catalysis and halogen-bond catalysis. Oxidation catalysis involves the utilization of hypervalent iodine compounds with co-oxidants to promote catalytic oxidation processes. Conversely, halogen-bond catalysis encompasses reactions promoted by the Lewis acidity of iodonium or bromonium salts. The chapter presents selected examples from each category, elucidating the applicable substrates, reaction limitations, and detailed experimental protocols.

In this study, we developed a metal-free, intermolecular C(sp2)-H imidation of anilines and phenols using sulfonimides, yielding isolable aryl sulfonimides under facile conditions. MesI(OAc)2 and HNTs2 combine to produce an O-bridged I(III)-NTs2 adduct, which is stabilized via π-π stacking and aids efficient sulfonimide transfer. The necessary mild conditions and broad functional group tolerance of this transformation establish a sustainable C─N bond formation approach to synthesizing various aryl sulfonimides via hypervalent iodine-mediated C─H imidation.

Abstract Halogenation-driven skeletal transformations play an important role in the biosynthesis of natural products, where halogenation can promote C–C bond cleavage under mild conditions. Drawing inspiration from these biosynthetic processes, the halogenative skeletal reconstruction of hydroxycoumarins is reported, which unexpectedly facilitates carbonyl deletion to yield valuable heterocyclic scaffolds. Notably, cleavage of both the C–C and C–O bonds occurs under the mildest nonenzymatic conditions reported to date (low reaction temperature and near-neutral reaction media), while also demonstrating broad substrate scope. This transformation converts readily accessible hydroxycoumarins into biologically relevant coumaranone scaffolds via a halogen-identity-dependent decarbonylative reconstruction. This work establishes halogenation-enabled carbonyl deletion as a useful strategy for skeletal transformation and provides an efficient approach to molecular scaffold editing relevant to medicinal chemistry.

Transition metal complexes have become increasingly important as catalysts in organic synthesis. Iron has emerged as an exceptionally versatile, cost-effective, and sustainable catalyst in contemporary organic synthesis owing to its competitive reactivity and selectivity. It efficiently overcomes the limitations of noble metal catalysts and substitutes for precious transition metals. Selective reduction of olefins, alkynes, and carboxylic derivatives as well as cross-coupling reactions involving C-O cleavage have been facilitated the use of iron as a catalyst, enhancing the catalyst scope in addition to the asymmetric synthesis employing chiral iron catalysts.Currently, heterogeneous iron catalysts showcase superior performance and have vast applications in industries, notably as iron-oxide-hybridized support systems such as clay, aluminosilicates, metal oxides, or polymeric matrices, which carbonize metals to perform various catalytic reactions. Among numerous applications, iron-catalyzed nucleophilic substitution processes are particularly significant, as they provide convenient access to C-C, C-N, C-O, and C-S bond formation in an efficient manner under mild and operationally friendly conditions. This review outlines the progress in iron-catalyzed nucleophilic substitutions with a focus on mechanistic insights, substrates involving benzylic, allylic, and propargylic, and the compatibility of functional groups such as alcohols, amine, amide, ketone, keto acids, etc., in supporting synthetic utility.

Haloketoesters are synthetic intermediates in various cyclization reactions that facilitate the production of biologically active compounds. Nonetheless, the selective synthesis of dihaloketoesters and trihaloketoesters, which are expected to be highly versatile, presents significant challenges. In this study, we designed a new synthetic approach that selectively and efficiently produces haloketoesters through the halogenative C-C bond cleavage and ring-opening reactions of cyclic 1,3-diketones. This convenient method enables the direct synthesis of di- and trichloro-functionalized ketoesters from 1,3-cyclohexadiones under mild conditions. Na2HPO4, employed as a buffer salt, proved to be effective in facilitating the alcoholytic ring-opening reaction of 2,2-dichloro-1,3-cyclohexadiones, which were generated as synthetic intermediates.

We developed an efficient method for aromatic chlorination by utilizing in situ generated hypervalent iodine(III) species formed from iodoarene and peracetic acid (PAA). This protocol facilitates electrophilic chlorination under mild conditions without strong acid additives and employs inexpensive inorganic chloride salts as the chlorine source, thereby eliminating the need for transition-metal catalysis or hazardous reagents. A series of aromatic and heteroaromatic arenes, including nucleobases and acid-sensitive functionalities, were successfully chlorinated in good-to-excellent yields (41-94%). This study expands the utility of PAA as an oxidant in hypervalent iodine(III) synthesis and offers a practical platform for the chlorination of aromatic rings and other nucleophiles.

A series of new triazole-substituted aryl iodides 1a-d were synthesized by Cu(I)-mediated [3+2] cycloaddition between 2-iodo-1,3-bis(prop-2-yn-1-yloxy)benzene (4) and aryl azides 5a-d. The structures of the synthesized compounds were confirmed by FT-IR, 1H NMR, 1 3C NMR, and HRMS analyses. The catalytic potential of iodoarenes 1a-d was evaluated toward the oxidation of sulfides. Furthermore, iodoarene 1c exhibited remarkable catalytic activity in the alpha-oxytosylation of acetophenones, affording the corresponding alpha-oxytosylated products in excellent yields (67%-94%).

In this study, a metal-free approach was developed for the synthesis of isocoumarin frameworks by exploiting the reactivity between ortho-carboxylate-ester-substituted diaryliodonium salts and acetoacetates. This transformation involved the sequential C-arylation of an activated methylene substrate, followed by in situ enolization and intramolecular lactonization to construct an isocoumarin core. Under operationally simple conditions, a range of diaryliodonium salts and acetoacetate esters were employed to afford structurally diverse isocoumarins. The resulting products contained synthetically valuable functional groups, including halogen, nitro, carboxylate ester, and azide substituents, which facilitated further derivatization and extension toward complex architectures and potential applications. Subsequent transformation of the selected isocoumarin products enabled the synthesis of furo[3,4-c]isochromene-1,5-dione motifs, which are observed in several natural products.

Diaryliodonium(III) salts with N-reactive amides are proposed as new attractive synthetic tools for the construction of benzo-fused nitrogen heterocycles. In this study, we have developed an efficient preparation method for ortho-functionalized diaryliodonium salts bearing N-phthalimide (N-NPhth) groups. Unlike strategies requiring ortho-leaving groups, these salts demonstrated their application in both transition metal-free and transition metal-catalyzed sequential coupling reactions, leading to the construction of five- and seven-membered heterocyclic compounds.

Constructing chemical bonds under green sustainable conditions has drawn attention from environmental and economic perspectives. The dissociation of (hetero)aryl-halide bonds is a crucial step of most arylations affording (hetero)arene derivatives. Herein, we summarize the (hetero)aryl halides activation enabling the direct (hetero)arylation of trapping reagents and construction of highly functionalized (hetero)arenes under benign conditions. The strategies for the activation of aryl iodides are classified into (a) hypervalent iodoarene activation followed by functionalization under thermal/photochemical conditions, (b) aryl-I bond dissociation in the presence of bases with/without organic catalysts and promoters, (c) photoinduced aryl-I bond dissociation in the presence/absence of organophotocatalysts, (d) electrochemical activation of aryl iodides by direct/indirect electrolysis mediated by organocatalysts and mediators acting as electron shuttles, and (e) electrophotochemical activation of aryl iodides mediated by redox-active organocatalysts. These activation modes result in aryl iodides exhibiting diverse reactivity as formal aryl cations/radicals/anions and aryne precursors. The coupling of these reactive intermediates with trapping reagents leads to the facile and selective formation of C-C and C-heteroatom bonds. These ecofriendly, inexpensive, and functional group-tolerant activation strategies offer green alternatives to transition metal-based catalysis.

Nitrogen-containing heterocycles are of particular research interest as they are commonly found in naturally occurring bioactive molecules. However, traditional synthetic approaches to these compounds have various drawbacks, including slow reaction rates, harsh reaction conditions (e.g., high temperatures or strong acids), and low product yields. In recent years, non-conventional synthetic methods, such as microwave irradiation, sonochemical synthesis, and mechanochemical approaches, have emerged as efficient and sustainable alternatives. These techniques provide multiple benefits in synthetic chemistry, enabling faster reactions, enhanced product yields, and superior reaction selectivities. Moreover, they reduce the reliance on toxic solvents and lower the overall energy requirements, ultimately leading to more sustainable processes. Furthermore, the application of green chemistry principles in the synthesis of N-heterocycles has enhanced their environmental compatibility. This review focuses on recent advancements in non-conventional synthetic strategies for constructing N-heterocyclic compounds. Key scaffolds discussed include pyridines, pyrrolidines, pyrroles, imidazoles, pyrazolines, indoles, pyrazoles and 1,2,3-triazoles, along with their fused analogs. These alternative approaches are noted for their synthetic efficiency and environmentally benign nature. Furthermore, the resulting heterocycles exhibit significant potential as biologically active molecules, particularly in the context of their antimicrobial, anticancer, and antioxidant activities.

Oxidation reactions are vital tools in synthetic organic chemistry. Oxidation of organic species such as alcohols, phenols, aldehydes and ketones provides synthetically valuable organic compounds, especially synthetic intermediates for several biologically active compounds. Some of these synthetic intermediates have shown their synthetic utility in the total synthesis of natural products. Several classical and modern synthetic approaches have been used to achieve these oxidation reactions. In this review article, various oxidation reactions achieved by metal catalysis are highlighted.

The divergent synthesis of 4-amino-1,2,3-triazoles was accomplished through the Cu-catalyzed cycloaddition of organic azides with alkynyliodonium(III) salts, followed by Cu-catalyzed triazole-amine coupling involving treatment with amines and amides. The in situ formation of 1,2,3-triazole iodonium salts is crucial to this approach, and the utilization of a Cu-catalyst facilitates cycloaddition and C-N bond formation. The synthesis of 1,2,3-triazolyliodonium(III) salts proposed in this study offers advantages, including mild reaction conditions, a broad substrate scope, and operational simplicity, while also providing efficient access to a complex and diverse range of 4-amino-1,2,3-triazole derivatives.

The amide functionalities are a crucial functional group in organic synthesis, playing a vital role in many processes that are essential for the efficient synthesis of important pharmaceutical and industrial compounds. Despite being one of the most commonly conducted reactions by researchers in both academia and industry, the synthesis of amides remains a staple in chemical research and development. Transamidation reactions enable the one-pot conversion of one type of amide into another. Additionally, this process is crucial in the complete synthesis of specific naturally-occurring compounds. However, these methods have certain limitations such as using toxic and corrosive starting materials, usage of strong acid or base, and metal mediated reaction, which can lead to excessive hydrolysis of the desired amide product. To overcome these challenges, more practical and efficient approaches have been developed. Metal-free transamidation reactions have emerged as a powerful and versatile synthetic methodology in organic chemistry, allowing for the direct conversion of amides into new amide products without relying on metal catalysts. In the review article, we have focused on various metal-free transamidation protocols of unactivated amides.

We have developed transition-metal-free synthetic methodologies for dibenzoxazepinones utilizing salicylamides as starting materials and employing two distinct types of successive hypervalent iodine-mediated arylocyclizations. This synthetic protocol encompasses selective phenol O-arylation of salicylamides with diaryliodonium salts, followed by electrophilic aromatic amination utilizing chemically or electronically generated hypervalent iodine reagents in the second stage of the process.

Benzimidazolinones exhibit unique biological activities and serve as building blocks in synthesizing pharmaceutical compounds. Although multiple synthetic approaches involving intermolecular cyclization reactions have been reported, intramolecular cyclization reactions are scarce, and more rational synthetic methods are required. Hypervalent iodine-catalyzed oxidative C–N coupling is a potentially effective approach for synthesizing benzimidazolinones under metal-free conditions. In this study, we present a method utilizing hypervalent iodine catalysis for the oxidative cyclization of N’-aryl urea compounds, resulting in the first metal-free synthesis of various benzimidazolinones.

Background: An efficient method for synthesizing cyclic arylsulfonium salts has been developed by selective aryl transfer to the sulfur atom from aryl(mesityl)iodonium triflates, a recyclable series of diaryliodonium salts. Methods: The utilization of sulfonium salts as valuable intermediates is well-established, as they exhibit high reactivity under conditions of heating or UV irradiation. However, their synthesis typically involves the reaction of diarysulfoxide with acid anhydride, which requires the oxidation of sulfur(II) to sulfoxide(IV) and thus limits the scope of synthesis. Hence, in this study, we employed recyclable mesityliodonium(III) salts and copper catalysis. Results: The method was used to synthesize cyclic arylsulfonium salts without the need for preoxidation of the sulfur atom, resulting in a facile and high-yield synthesis. Conclusion: The desired cyclic arylsulfonium salts were synthesized through selective transfer of the aryl group from mesityliodonium salts, demonstrating the effectiveness of the new approach.