Continuous‐Flow Electrochemical Generator of Hypervalent Iodine Reagents: Synthetic Applications

An efficient and reliable electrochemical generator of hypervalent iodine reagents has been developed. In the anodic oxidation of iodoarenes to hypervalent iodine reagents under flow conditions, the use of electricity replaces hazardous and costly chemical oxidants. Unstable hypervalent iodine reagents can be prepared easily and coupled with different substrates to achieve oxidative transformations in high yields. The unstable, electrochemically generated reagents can also easily be transformed into classic bench‐stable hypervalent iodine reagents through ligand exchange. The combination of electrochemical and flow‐chemistry advantages largely improves the ecological footprint of the overall process compared to conventional approaches.     

Preparation of Heteroaromatic (Aryl)iodonium Imides as I−N Bond‐Containing Hypervalent Iodine

Hypervalent iodine(III) compounds containing iodine–nitrogen bonds are very attractive amination reagents in organic synthesis. Heteroaromatic (aryl)iodonium imides containing a iodine–nitrogen bond and a hypervalent iodine(III) atom were prepared from heteroarenes, bis(sulfon)imides and (diacetoxyiodo)arenes under mild conditions. These compounds were stable under air and in organic solvents, and could be easily purified by precipitation. X‐ray crystal structure analysis indicated that the structure of N‐pivaloyl indolyl(phenyl)iodonium bis(tosyl)imides and N‐pivaloyl indolyl(2‐butoxyphenyl)iodonium bis(tosyl)imides was a dimer with a T‐shaped geometry at the iodine atom linked to an indole group and a bis(tosyl)imide by a monomer unit. Moreover, the use of substituted iodoarenes facilitated the purification of some of the heteroaromatic (aryl)iodonium imides.     

Hypervalent‐Iodine(III)‐Mediated Oxidative Methodology for the Synthesis of Fused Triazoles

The organic chemistry of hypervalent organoiodine compounds has been an area of unprecedented development. This surge in interest in the use of hypervalent iodine compounds has mainly been owing to their highly selective oxidizing properties, environmentally benign character and commercial availability. Hypervalent iodine reagents have also been used as an alternative to toxic heavy metals, owing to their low toxicity and ease of handling. Hypervalent organoiodine(III) reagents are versatile oxidants that have been successfully employed to extend the scope of selective oxidative transformations of complex organic molecules in synthetic chemistry. This Focus Review concerns the tandem in situ generation and 1,5‐electrocyclization of N‐heteroaryl nitrilimines into fused triazoles. We describe the importance of recently developed hypervalent‐organoiodine(III)‐catalyzed oxidative cyclization reactions, building towards the conclusion that hypervalent iodine chemistry is a promising frontier for oxidative cyclization, in particular of hydrazones, for the synthesis of fused triazoles.     

有机高价碘化学简介及其应用

近几十年来,有机高价碘化学蓬勃发展,有机高价碘试剂也受到化学合成工作者的广泛关注,关于有机高价碘试剂的反应性研究也获得了迅猛发展。有机高价碘试剂作为绿色、高效、多功能化的氧化剂,通常容易制备且操作简单,与已有的合成方法相比,该类试剂参与的反应表现出了许多独特的优点,并且具有与汞、铬、铅、铊等重金属试剂类似的反应性,但却没有这些试剂所带来的毒性和环境污染问题。本文介绍了有机高价碘化学的起源与发展,高价碘试剂的结构特点与分类,高价碘试剂在有机合成、材料化学及工业合成中的应用。     

Diastereoselective Radical Hydroacylation of Alkylidenemalonates with Aliphatic Aldehydes Initiated by Photolysis of Hypervalent Iodine(III) Reagents

Diastereoselective radical hydroacylation of chiral alkylidenemalonates with aliphatic aldehydes is realized by the combination of a hypervalent iodine(III) reagent and UV‐light irradiation. The reaction is initiated by the photolysis of hypervalent iodine(III) reagents under mild, metal‐free conditions, and is the first example of diastereoselective addition of acyl radicals to olefins to afford chiral ketones in a highly stereoselective fashion. The obtained optically active ketones are useful chiral synthons, as exemplified by the short formal synthesis of (?)‐methyleneolactocin.     

Structure and Reactivity of N-Heterocyclic Alkynyl Hypervalent Iodine Reagents

Ethynylbenziodoxol(on)e (EBX) cyclic hypervalent iodine reagents have become popular reagents for the alkynylation of radicals and nucleophiles, but only offer limited possibilities for further structure and reactivity fine-tuning. Herein, the synthesis of new N-heterocyclic hypervalent iodine reagents with increased structural flexibility based on amide, amidine and sulfoximine scaffolds is reported. Solid-state structures of the reagents are reported and the analysis of the I−C_alkyne bond lengths allowed assessing the trans-effect of the different substituents. Molecular electrostatic potential (MEP) maps of the reagents, derived from DFT computations, revealed less pronounced σ-hole regions for sulfonamide-based compounds. Most reagents reacted well in the alkynylation of β-ketoesters. The alkynylation of thiols afforded more variable yields, with compounds with a stronger σ-hole reacting better. In metal-mediated transformations, the N-heterocyclic hypervalent iodine reagents gave inferior results when compared to the O-based EBX reagents.     

有机合成中的高价碘应用

高价碘化物作为一种性能温和、选择性强及环境友好的氧化试剂在有机合成中得到了广泛的应用。近年来,各种不同结构的高价碘试剂和各种新的反应及应用大量涌现出来,使它们的应用领域从传统的醇类氧化扩展到一些结构复杂化合物的合成领域当中。本文以最常用和研究较多的几个高价碘化合物为例,对它们用于有机合成反应,如氧化、加成、取代和重排的最新进展进行了概述,对本研究小组重点研究的五价碘化合物邻羟基苯碘酰与酮类化合物的取代反应和烯烃化合物的加成反应也作了介绍。     

One‐Pot C−H Functionalization of Arenes by Diaryliodonium Salts

A transition‐metal‐free, mild, and highly regioselective synthesis of nitroarenes from arenes has been developed. The products are obtained in a sequential one‐pot reaction by nitration of iodine(III) reagents with two carbon ligands, which are formed in situ from iodine(I). This novel concept has been extended to formation of aryl azides, and constitutes an important step towards catalytic reactions with these hypervalent iodine reagents. An efficient nitration of isolated diaryliodonium salts has also been developed, and the mechanism is proposed to proceed by a [2,2] ligand coupling pathway.     

原位生成的高价碘试剂在有机合成中的应用进展

原位生成的高价碘试剂具有原子经济性、性能温和和绿色环保等优点,在诸多合成和不对称催化等反应中表现活跃.详细介绍了原位生成高价碘的概念以及反应机理,根据不同的反应类型分别对原位生成的三价碘、五价碘以及手性高价碘试剂在有机合成反应中的应用进行了归纳总结,分析了原位生成的高价碘试剂目前面临的问题,并对今后的发展趋势作了展望.     

Chiral Hypervalent Iodine Reagents: Synthesis and Reactivity

Chiral hypervalent iodine chemistry has been steadily increasing in importance in recent years. This review catalogues enantioselective transformations triggered by chiral hypervalent iodine(III/V) reagents, in stoichiometric or catalytic quantities, highlighting the different reactivities in terms of yield and enantioselectivity. Moreover, the synthesis of the most remarkable and successful catalysts has been illustrated in detail.     

Pioneering Metal‐Free Oxidative Coupling Strategy of Aromatic Compounds Using Hypervalent Iodine Reagents

We started our hypervalent iodine research about 30 years ago in the mid‐1980s. We soon successfully developed the single‐electron‐transfer oxidation ability of a hypervalent iodine reagent, specifically, phenyliodine(III) bis(trifluoroacetate) (PIFA), toward aromatic rings of phenyl ethers for forming aromatic cation radicals. This was one of the exciting and unexpected events in our research studies so far, and the discovery was reported in 1991. It also led to the next challenge, developing the metal‐free oxidative couplings for C–H functionalizations and direct couplings between the C–H bonds of valuable aromatic compounds in organic synthesis. In order to realize the effective oxidative coupling, pioneering new aromatic ring activations was essential and several useful methodologies have been found for oxidizable arenes. The achievements regarding this objective obtained in our continuous research are herein summarized with classification of the aromatic ring activation strategies.     

Synthesis of Sulfoximidoyl‐Containing Hypervalent Iodine(III) Reagents and Their Use in Transition‐Metal‐Free Sulfoximidations of Alkynes

Well‐defined hypervalent iodine(III) reagents incorporating transferable sulfoximidoyl groups were obtained through ligand exchange reactions of methoxy(tosyloxy)iodobenzene (MTIB) with NH sulfoximines in good to excellent yields. The solid‐state structure of a representative product was characterized by X‐ray crystallography. Utilizing these reagents in synthesis provides a new, transition‐metal‐free approach towards N‐alkynylated sulfoximines.     

Reactions between Diazo Compounds and Hypervalent Iodine(III) Reagents

Site‐selective “cut and sew” transformations employing diazo compounds and hypervalent iodine(III) compounds involve the departure of leaving groups, a “cut” process, followed by a reorganization of the fragments by bond formation, a “sew” process. Bearing controllable cleavage sites, diazo compounds and hypervalent iodine(III) compounds play a critical role as versatile reagents in a wide range of organic transformations because their excellent nucleofugality allows for a large number of unusual reactions to occur. In recent years, the combination of diazo compounds and hypervalent iodine(III) reagents has emerged as a promising tool for developing new and valuable approaches, and has met considerable success. In this Minireview, this combination is systematically illustrated with recent advances in the field, with the aim of elaborating the synthetic utility and potential of this concept as a powerful strategy in organic synthesis.     

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.     

Solvent‐Free One Pot Synthesis of 2‐aryl/Heteroarylbenzothiazoles Using Hypervalent Iodine (III) Reagents

In this article, an efficient, environmentally benign, one‐pot and simple synthesis of 2‐aryl/heteroarylbenzothiazoles by the reaction of 2‐aminothiophenol and aryl/heteroaryl aldehydes mediated by hypervalent iodine (III) reagents under solvent‐free condition at room temperature is demonstrated. All the reactions were carried out by grinding the reactants (2‐aminothiophenol and aryl/heteroaryl aldehydes) with hypervalent iodine (III) reagents in a mortar with pestle. Phenyliodine bistrifluoroacetate act as an efficient oxidizing reagent in comparison to iodobenzene diacetate in term of reaction time but yields are comparative. The advantages of this protocol are the one‐step procedure, mild reaction conditions, high yields of the products, and no side reactions.     

Vicinal Difunctionalization of Alkenes with Iodine(III) Reagents and Catalysts

Hypervalent iodine(III) reagents have been known for over a century, and their reaction profile is still actively investigated. Recent years have seen impressive improvements in the area of alkene difunctionalization reactions, where new methodologies have become available. Especially chiral non‐racemic hypervalent iodine(III) reagents and catalysts have emerged as versatile tools for the realization of important enantioselective transformations.     

Bench‐Stable Electrophilic Indole and Pyrrole Reagents: Serendipitous Discovery and Use in C–H Functionalization

The development of reagents allowing the reversal of the standard reactivity (Umpolung) of small building blocks is an important field of research in chemistry, as it allows increasing the flexibility of organic synthesis. Indoles and pyrroles are ubiquitous heterocycles in natural products and drugs. They are usually functionalized making use of their high nucleophilicity. In contrast, only few methods are based on the use of electrophilic indole and pyrrole synthons, as the needed reagents are highly unstable or can be used only with a very narrow scope. Herein, we report the serendipitous discovery and first use in the C–H functionalization of arenes of IndoleBX and PyrroleBX, new thermally highly stable benziodoxol(on)e hypervalent iodine reagents. IndoleBX and PyrroleBX could be obtained in one step from the corresponding heterocycles and acetoxy benziodoxolone using a Lewis acid catalyst. The mild reactions conditions allowed the introduction of a broad range of functional groups, including ethers, halogens and boronic esters. The new reagents could then be used in the rhodium‐ and ruthenium‐catalyzed C–H heteroarylation of arene rings bearing heterocyclic or benzamide directing groups. Such transformations could not be realized using previously reported C–H functionalization procedures.     

Facile Oxidative Rearrangements Using Hypervalent Iodine Reagents

Aromatic substituents migrate in a novel oxidative cyclization mediated by iodine(III) reagents. 4-Arylbut-3-enoic acids are cyclized and rearranged to 4-arylfuran-2(5H)-ones by hypervalent iodine compounds in good to excellent yields under mild reaction conditions. Other ring sizes are also accessible. The mechanism of the reaction is described in detail, and calculations highlight the cationic nature of the intermediates in the rearrangement. The fast access to heavily substituted furanones is used for the synthesis of biologically active derivatives.     

Metal‐Free CH Bond Activation of Branched Aldehydes with a Hypervalent Iodine(III) Catalyst under Visible‐Light Photolysis: Successful Trapping with Electron‐Deficient Olefins

Direct acyl radical formation of linear aldehydes (RCH₂‐CHO) and subsequent hydroacylation with electron‐deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.     

Structurally Defined Molecular Hypervalent Iodine Catalysts for Intermolecular Enantioselective Reactions

Molecular structures of the most prominent chiral non‐racemic hypervalent iodine(III) reagents to date have been elucidated for the first time. The formation of a chirally induced supramolecular scaffold based on a selective hydrogen‐bonding arrangement provides an explanation for the consistently high asymmetric induction with these reagents. As an exploratory example, their scope as chiral catalysts was extended to the enantioselective dioxygenation of alkenes. A series of terminal styrenes are converted into the corresponding vicinal diacetoxylation products under mild conditions and provide the proof of principle for a truly intermolecular asymmetric alkene oxidation under iodine(I/III) catalysis.