Silver-Catalyzed Coupling of Unreactive Carboxylates: Synthesis of α-Fluorinated O-Aryl Esters.

α-Fluorinated aryl esters pose a challenge in synthesis via O-arylation of α-fluorinated carboxylates owing to their low reactivities. This limitation has been addressed by combining a silver catalyst with aryl(trimethoxyphenyl)iodonium tosylates to access α-fluorinated aryl esters. We envision that the catalytic system involves high-valent aryl silver species generated via the oxidation of silver(I) salt. The present method provided a synthetic protocol for various α-fluorinated aryl esters including fluorinated analogs of drug derivatives.

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions.

Diaryliodonium(III) salts are versatile reagents that exhibit a range of reactions, both in the presence and absence of metal catalysts. In this study, we developed efficient synthetic methods for the preparation of aryl(TMP)iodonium(III) carboxylates, by reaction of (diacetoxyiodo)arenes or iodosoarenes with 1,3,5-trimethoxybenzene in the presence of a diverse range of organocarboxylic acids. These reactions were conducted under mild conditions using the trimethoxyphenyl (TMP) group as an auxiliary, without the need for additives, excess reagents, or counterion exchange in further steps. These protocols are compatible with a wide range of substituents on (hetero)aryl iodine(III) compounds, including electron-rich, electron-poor, sterically congested, and acid-labile groups, as well as a broad range of aliphatic and aromatic carboxylic acids for the synthesis of diverse aryl(TMP)iodonium(III) carboxylates in high yields. This method allows for the hybridization of complex bioactive and fluorescent-labeled carboxylic acids with diaryliodonium(III) salts.

Organohypervalent heterocycles.

This review summarizes the structural and synthetic aspects of heterocyclic molecules incorporating an atom of a hypervalent main-group element. The term "hypervalent" has been suggested for derivatives of main-group elements with more than eight valence electrons, and the concept of hypervalency is commonly used despite some criticism from theoretical chemists. The significantly higher thermal stability of hypervalent heterocycles compared to their acyclic analogs adds special features to their chemistry, particularly for bromine and iodine. Heterocyclic compounds of elements with double bonds are not categorized as hypervalent molecules owing to the zwitterionic nature of these bonds, resulting in the conventional 8-electron species. This review is focused on hypervalent heterocyclic derivatives of nonmetal main-group elements, such as boron, silicon, nitrogen, carbon, phosphorus, sulfur, selenium, bromine, chlorine, iodine(III) and iodine(V).

Recent progress in metal assisted multicomponent reactions in organic synthesis.

To prepare complicated organic molecules, straightforward, sustainable, and clean methodologies are urgently required. Thus, researchers are attempting to develop imaginative approaches. Metal-catalyzed multicomponent reactions (MCRs) offer optimal molecular diversity, high atomic efficiency, and energy savings in a single reaction step. These versatile protocols are often used to synthesize numerous natural compounds, heterocyclic molecules, and medications. Thus far, the majority of metal-catalyzed MCRs under investigation are based on metal catalysts such as copper and palladium; however, current research is focused on developing novel, environmentally friendly catalytic systems. In this regard, this study demonstrates the effectiveness of metal catalysts in MCRs. The aim of this study is to provide an overview of metal catalysts for safe application in MCRs.

Iodine(V)-Based Oxidants in Oxidation Reactions.

The chemistry of hypervalent iodine reagents has now become quite valuable due to the reactivity of these compounds under mild reaction conditions and their resemblance in chemical properties to transition metals. The environmentally friendly nature of these reagents makes them suitable for Green Chemistry. Reagents with a dual nature, such as iodine(III) reagents, are capable electrophiles, while iodine(V) reagents are known for their strong oxidant behavior. Various iodine(V) reagents including IBX and DMP have been used as oxidants in organic synthesis either in stoichiometric or in catalytic amounts. In this review article, we describe various oxidation reactions induced by iodine(V) reagents reported in the past decade.

1,3-Dipolar Cycloaddition of 3-Chromonyl-Substituted Glycine Imino Esters with Arylidenes and in†situ Diastereodivergent via Retrocycloaddition.

1,3-Dipolar cycloaddition through in situ generation of azomethine ylide provides a straightforward and critically important sustainable approach for access to diverse pyrrolidine chemical space. Herein, we developed a metal-free AcOH-activated 1,3-dipolar cycloaddition protocol that permits the synthesis of uncommon pyrrolidine cycloadducts with excellent diastereoselectivity. The challenging substrates of 3-formylchromone, glycine ester.HCl and arylidene dipolarophile were reacted in the presence of AcONa, which played a dual role as a base and AcOH source, to deliver firstly endo-cycloadduct. Under prolonged reaction time at room temperature or heating; the endo-adduct underwent diastereodivergent via a sequence of retro-cycloaddition, stereomutation of the generated syn-dipole into anti-dipole and recycloaddition; to furnish the scarcely known exo'-cycloadduct with high diastereodivergency. The reaction worked well with a broad range of substrates and the stereochemistry of the obtained cycloadducts was determined without ambiguity using NMR- and X-ray analysis. Experimental and theoretical DFT calculation studies were performed to support the proposed reaction mechanism and elucidate the key role of AcOH in the process which seems more beneficial than other transition metal-catalyzed processes.

Cyclic Hypervalent Iodine-Induced Oxidative Phenol and Aniline Couplings with Phenothiazines.

C-H/N-H bond functionalization for direct intermolecular aryl C-N couplings is a useful synthetic process. In this study, we achieved metal-free cross-dehydrogenative coupling of phenols and anilines with phenothiazines using hypervalent iodine reagents. This method affords selective amination products under mild conditions. Electron-rich phenols and anilines could be employed, affording moderate-to-high yields of N-arylphenothiazines. Aniline amination proceeded efficiently at 20 °C, a previously unreported phenomenon.

Non-Palladium-Catalyzed Oxidative Coupling Reactions Using Hypervalent Iodine Reagents.

Transition metal-catalyzed direct oxidative coupling reactions via C-H bond activation have emerged as a straightforward strategy for the construction of complex molecules in organic synthesis. The direct transformation of C-H bonds into carbon-carbon and carbon-heteroatom bonds renders the requirement of prefunctionalization of starting materials and, therefore, represents a more efficient alternative to the traditional cross-coupling reactions. The key to the unprecedented progress made in this area has been the identification of an appropriate oxidant that facilitates oxidation and provides heteroatom ligands at the metal center. In this context, hypervalent iodine compounds have evolved as mainstream reagents particularly because of their excellent oxidizing nature, high electrophilicity, and versatile reactivity. They are environmentally benign reagents, stable, non-toxic, and relatively cheaper than inorganic oxidants. For many years, palladium catalysis has dominated these oxidative coupling reactions, but eventually, other transition metal catalysts such as gold, copper, platinum, iron, etc. were found to be promising alternate catalysts for facilitating such reactions. This review article critically summarizes the recent developments in non-palladium-catalyzed oxidative coupling reactions mediated by hypervalent iodine (III) reagents with significant emphasis on understanding the mechanistic aspects in detail.

Palladium-Catalyzed Organic Reactions Involving Hypervalent Iodine Reagents.

The chemistry of polyvalent iodine compounds has piqued the interest of researchers due to their role as important and flexible reagents in synthetic organic chemistry, resulting in a broad variety of useful organic molecules. These chemicals have potential uses in various functionalization procedures due to their non-toxic and environmentally friendly properties. As they are also strong electrophiles and potent oxidizing agents, the use of hypervalent iodine reagents in palladium-catalyzed transformations has received a lot of attention in recent years. Extensive research has been conducted on the subject of C-H bond functionalization by Pd catalysis with hypervalent iodine reagents as oxidants. Furthermore, the iodine(III) reagent is now often used as an arylating agent in Pd-catalyzed C-H arylation or Heck-type cross-coupling processes. In this article, the recent advances in palladium-catalyzed oxidative cross-coupling reactions employing hypervalent iodine reagents are reviewed in detail.

Iodine(III) reagents for oxidative aromatic halogenation.

Iodine(III) reagents have attracted chemical relvance in organic synthesis by their use as safe, non-toxic, green and easy to handle reagents in different transformations. These characteristics make them important alternatives to procedures involving hazardous and harsh reaction conditions. Their versatility as oxidants has been exploited in the functionalization of different aromatic cores, which allow the introduction of several groups. Metal-free arylation using iodine(III) reagents is by far one of the most described topics in the literature; however, other highly relevant non-aromatic groups have been also introduced. Herein, we summarize the most representative developed procedures for the functionalization of aryls and heteroaryls by introducing halogens, using different iodine(III) reagents.

Ligand- and Counterion-Assisted Phenol O-Arylation with TMP-Iodonium(III) Acetates.

High reactivity of trimethoxyphenyl (TMP)-iodonium(III) acetate for phenol O-arylation was achieved. It was first determined that the TMP ligand and acetate anion cooperatively enhance the electrophilic reactivity toward phenol oxygen atoms. The proposed method provides access to various diaryl ethers in significantly higher yields than the previously reported techniques. Various functional groups, including aliphatic alcohol, boronic ester, and sterically hindered groups, were tolerated during O-arylation, verifying the applicability of this ligand- and counterion-assisted strategy.

Diaryliodonium(III) salts in one-pot double functionalization of C-IIII and ortho C-H bonds.

Since the 1950s, diaryliodonium(III) salts have been demonstrated to participate in various arylation reactions, forming aryl-heteroatom and aryl-carbon bonds. Incorporating the arylation step into sequential transformations would provide access to complex molecules in short steps. This focus review summarizes the double functionalization of carbon-iodine(III) and ortho carbon-hydrogen bonds using diaryliodonium(III) salts. This involves arylation/intramolecular rearrangement, arylation followed by electrophilic aromatic substitution, three-component [2 + 2 + 2] cascade annulation, sequential metal-catalyzed arylations, and double functionalization via aryne formation.

µ-Oxo-Hypervalent-Iodine-Catalyzed Oxidative C-H Amination for Synthesis of Benzolactam Derivatives.

Benzolactams have unique biological activity and high utility in the synthesis of valuable compounds with direct applicability to oxindole alkaloids and antibacterial agents. Despite recent advances in organic chemistry and the growing number of reported methods for synthesizing benzolactams, their preparation still requires a multistep process. C-H amination reactions can convert aromatic C(sp2)-H bonds directly to C(sp2)-N bonds, and this direct approach to C-N bond formation offers effective access to benzolactams. Hypervalent iodine reagents are promising tools for achieving oxidative C-H amination. Motivated by our ongoing research efforts toward the development of useful hypervalent-iodine-mediated oxidative transformations, we herein describe an effective intramolecular oxidative C-H amination reaction based on µ-oxo hypervalent iodine catalysis for the synthesis of benzolactams bearing various functional groups.

Asymmetric Direct/Stepwise Dearomatization Reactions Involving Hypervalent Iodine Reagents.

A remarkable growth in hypervalent iodine-mediated oxidative transformations as stoichiometric reagents as well as catalysts has been well-documented due to their excellent properties, such as mildness, easy handling, high selectivity, environmentally friendly nature, and high stability. This review aims at highlighting the asymmetric oxidative dearomatization reactions involving hypervalent iodine compounds. The present article summarizes asymmetric intra- and intermolecular dearomatization reactions using chiral hypervalent iodine reagents/catalysts as well as hypervalent iodine-mediated dearomatization reactions followed by desymmetrization.

[3 + 2] Coupling of Quinone Monoacetals with Vinyl Ethers Effected by Tetrabutylammonium Triflate: Regiocontrolled Synthesis of 2-Oxygenated Dihydrobenzofurans.

The synthesis of 2-oxygenated dihydrobenzofurans involving the [3 + 2] coupling of quinone monoacetals with vinyl ethers has been realized by tetrabutylammonium triflate catalysis. The reaction involves a new activation method of the acetal moiety in quinone monoacetals under acid-free conditions affording the highly oxygenated dihydrobenzofurans. This new activation mode was achieved by using the triflate anion catalyst for stabilization of the highly reactive cationic intermediate.

Triflimide-Promoted Nucleophilic C-Arylation of Halopurines to Access N7-Substituted Purine Biaryls.

Functionalized nucleobases are utilized in a wide range of fields; therefore, the development of new synthesis methods is essential for their continued application. With respect to the C6-arylation of halopurines, which possess a substituent at the N7-position, only a small number of successful cases have been reported, which is predominately a result of large steric hinderance effects. Herein, we report efficient and metal-free C6-arylations and SNAr reactions of N7-substituted chloropurines in aromatic and heteroatom nucleophiles promoted by triflimide (Tf2NH) in fluoroalcohol.

Nucleophilic Aromatic Substitution of Polyfluoroarene to Access Highly Functionalized 10-Phenylphenothiazine Derivatives.

Nucleophilic aromatic substitution (SNAr) reactions can provide metal-free access to synthesize monosubstituted aromatic compounds. We developed efficient SNAr conditions for p-selective substitution of polyfluoroarenes with phenothiazine in the presence of a mild base to afford the corresponding 10-phenylphenothiazine (PTH) derivatives. The resulting polyfluoroarene-bearing PTH derivatives were subjected to a second SNAr reaction to generate highly functionalized PTH derivatives with potential applicability as photocatalysts for the reduction of carbon-halogen bonds.