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。     

Hypervalent Iodine‐Catalyzed Oxidative Functionalizations Including Stereoselective Reactions

Hypervalent iodine chemistry is now a well‐established area of organic chemistry. Novel hypervalent iodine reagents have been introduced in many different transformations owing to their mild reaction conditions and environmentally friendly nature. Recently, these reagents have received particular attention because of their applications in catalysis. Numerous hypervalent iodine‐catalyzed oxidative functionalizations such as oxidations of various alcohols and phenols, α‐functionalizations of carbonyl compounds, cyclizations, and rearrangements have been developed successfully. In these catalytic reactions stoichiometric oxidants such as mCPBA or oxone play a crucial role to generate the iodine(III) or iodine(V) species in situ. In this Focus Review, recent developments of hypervalent iodine‐catalyzed reactions are described including some asymmetric variants. Catalytic reactions using recyclable hypervalent iodine catalysts are also covered.     

Hypervalent iodine chemistry in synthesis: scope and new directions

The impressive development of hypervalent iodine chemistry in recent years is reflected by the number of publications in this area. Although the synthesis of the first hypervalent iodine compound dates back more than 100 years, the investigation of the reactivities of these compounds and their efficient use as metal-free reagents in organic synthesis is still ongoing. This contribution summarizes recent achievements and highlights key findings and developments that will influence future research and lead to novel applications of hypervalent iodine reagents in synthesis.     

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.     

Reactions of hypervalent iodine reagents with palladium: mechanisms and applications in organic synthesis

The unique reactivity of hypervalent iodine reagents with Pd0 and PdII complexes has been exploited for a variety of synthetically useful organic transformations. For example, IIII reagents have been used in place of aryl halides for diverse Pd-catalyzed C-C and C-heteroatom bond-forming cross-coupling reactions. In addition, these reagents have found application in Pd-catalyzed oxidation reactions, including the oxidative functionalization of C-H bonds and the 1,2-aminooxygenation of olefinic substrates. This review discusses both the synthetic utility and the interesting mechanistic features of these transformations.     

Recent advancements in palladium-catalyzed reactions involving molecular oxygen

Oxidation reactions have significant value in organic chemistry, having been in focus continuously due to the high efficiency in building up molecular complexity. In the past few decades, transition metal-catalyzed oxidation reactions have been significantly explored and have played important roles in organic synthesis. Compared to the widely-used oxidants, such as inorganic salts, peroxides, hypervalent iodine reagents and quinones, molecular oxygen (O₂), which is natural, inexpensive, and environmentally friendly, is a highly appealing oxidant in academic and industry area for green and sustainable chemistry. Recently, significant advances have been made in palladium-catalyzed reactions using O₂ as the oxidant. This critical review highlights some of the recent developments in molecular oxygen-involved Pd-catalyzed oxidation reactions with a focus on mechanistic strategies and new reaction developments.     

Tyrosine bioconjugation with hypervalent iodine

Hypervalent iodine reagents have recently emerged as powerful tools for late-stage peptide and protein functionalization. Herein we report a tyrosine bioconjugation methodology for the introduction of hypervalent iodine onto biomolecules under physiological conditions. Tyrosine residues were engaged in a selective addition onto the alkynyl bond of ethynylbenziodoxolones (EBX), resulting in stable vinylbenziodoxolones (VBX) bioconjugates. The methodology was successfully applied to peptides and proteins and tolerated all other nucleophilic residues, with the exception of cysteine. The generated VBX were further functionalized by palladium-catalyzed cross-coupling and azide–alkyne cycloaddition reactions. The method could be successfully used to modify bioactive natural products and native streptavidin to enable thiol-mediated cellular uptake.

A tyrosine bioconjugation for the introduction of hypervalent iodine onto biomolecules is described. The transformation was applied to peptides and proteins and was used to modify native streptavidin to enable thiol-mediated cellular uptake.     

Synthetic application of water-soluble hypervalent iodine reagents in aqueous media

Along with the vigorous development of hypervalent iodine chemistry, water-soluble hypervalent iodine reagents have received considerable attentions in recent years. In order to obtain water-soluble hypervalent iodine reagents, two strategies have been employed including introduction of hydrophilic functional groups onto the phenyl ring and formation of complex of iodosylbenzene with crown ether. And, it is observed that four kinds of hypervalent iodine reagents exhibit more or less solubility in water including hypervalent iodine reagents containing hydrophilic ligands, diaryliodonium salts, oligomeric iodosylbenzene sulfate, and iodylbenzene and its derivatives. In this review, we summarize these water-soluble hypervalent iodine reagents and their broad synthetic applications in aqueous media.     

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.     

Strategies to Control Hypervalent Iodine – Primary Amine Reactions

The field of hypervalent iodine chemistry has been prevalent since 1886. Its journey from obscurity to coming into the limelight has witnessed many effective transformations which have benefited the synthetic community at large. The reactivity of primary amines with hypervalent iodine reagents causes difficulty in synthetic outcome or not feasible due to high exothermicity of amine iodine which is an acid base reaction. This minireview highlights the worthwhile reactivity of hypervalent iodine reagents with aromatic and aliphatic primary amines. Some recent literature has been discussed to make a clear understanding on how such high reactivity of primary amine is controlled by introducing modulation in either substrate or reaction conditions, most of which are carried out under ambient reaction conditions.     

Recent Advances in Rapid Synthesis of Non-proteinogenic Amino Acids from Proteinogenic Amino Acids Derivatives via Direct Photo-Mediated C–H Functionalization

Non-proteinogenic amino acids have attracted tremendous interest for their essential applications in the realm of biology and chemistry. Recently, rising C–H functionalization has been considered an alternative powerful method for the direct synthesis of non-proteinogenic amino acids. Meanwhile, photochemistry has become popular for its predominant advantages of mild conditions and conservation of energy. Therefore, C–H functionalization and photochemistry have been merged to synthesize diverse non-proteinogenic amino acids in a mild and environmentally friendly way. In this review, the recent developments in the photo-mediated C–H functionalization of proteinogenic amino acids derivatives for the rapid synthesis of versatile non-proteinogenic amino acids are presented. Moreover, postulated mechanisms are also described wherever needed.     

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。     

Organoiodine(V) reagents in organic synthesis

Organohypervalent iodine reagents have attracted significant recent interest as versatile and environmentally benign oxidants with numerous applications in organic synthesis. This Perspective summarizes synthetic applications of hypervalent iodine(V) reagents: 2-iodoxybenzoic acid (IBX), Dess-Martin periodinane (DMP), pseudocyclic iodylarenes, and their recyclable polymer-supported analogues. Recent advances in the development of new catalytic systems based on the generation of hypervalent iodine species in situ are also overviewed.     

Iodine(III) mediators in electrochemical batch and flow reactions

The anodic oxidation of aryl iodides is a powerful method for synthesis of hypervalent iodine compounds, which have matured to frequently used reagents in organic synthesis. The electrochemical route eliminates the use of expensive or hazardous oxidants for their synthesis. Hypervalent iodine reagents generated at the anode are successfully used as either in-cell or ex-cell mediators for many valuable chemical transformations including fluorinations and oxidative cyclisations. The recent advances in the area of flow electrochemistry are providing additional benefits and allow new synthetic applications. Mechanistic insights and novel technologies enable the development of new concepts for sustainable chemistry.     

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.     

Platinum‐Catalyzed Domino Reaction with Benziodoxole Reagents for Accessing Benzene‐Alkynylated Indoles

Indoles are omnipresent in natural products, bioactive molecules, and organic materials. Consequently, their synthesis or functionalization are important fields of research in organic chemistry. Most works focus on installation or modification of the pyrrole ring. To access benzene‐ring‐functionalized indoles with an unsubstituted pyrrole ring remains more challenging. Reported herein is a platinum‐catalyzed cyclization/alkynylation domino process to selectively obtain C5‐ or C6‐functionalized indoles starting from easily available pyrroles. The work combines, for the first time, a platinum catalyst with ethynylbenziodoxole hypervalent iodine reagents in a domino process for the synthesis of polyfunctionalized arene rings and gives access to important building blocks for the synthesis of bioactive compounds and organic materials.     

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.     

芳香化合物在碘或碘化铵催化作用下的单溴代反应

研究了芳香化合物在碘或碘化铵催化作用下的单溴代选择性反应, 该反应是经过有机高价碘中间体进行的. 通过该反应, 富电子芳香化合物在碘或碘化铵催化作用下很容易与溴化钾、 间氯过氧苯甲酸、 对甲苯磺酸和少量苯的混合物发生反应, 常温下短时间内得到产率良好并具有区域选择性的单溴代芳香化合物. 考察了反应条件的影响, 提出了可能的反应机理, 为简单快速合成单溴代芳香化合物提供了新方法.     

Benzylic C–H isocyanation/amine coupling sequence enabling high-throughput synthesis of pharmaceutically relevant ureas

C(sp³)–H functionalization methods provide an ideal synthetic platform for medicinal chemistry; however, such methods are often constrained by practical limitations. The present study outlines a C(sp³)–H isocyanation protocol that enables the synthesis of diverse, pharmaceutically relevant benzylic ureas in high-throughput format. The operationally simple C–H isocyanation method shows high site selectivity and good functional group tolerance, and uses commercially available catalyst components and reagents [CuOAc, 2,2′-bis(oxazoline) ligand, (trimethylsilyl)isocyanate, and N-fluorobenzenesulfonimide]. The isocyanate products may be used without isolation or purification in a subsequent coupling step with primary and secondary amines to afford hundreds of diverse ureas. These results provide a template for implementation of C–H functionalization/cross-coupling in drug discovery.

A copper-based catalyst system composed of commercially available reagents enables C–H isocyanation with exquisite (hetero)benzylic site selectivity, enabling high-throughput access to pharmaceutically relevant ureas via coupling with amines.     

Sequential Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols

Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors. The method has been further extended to the synthesis of deuterated benzylic alcohols. The iron-catalyzed Kumada cross-coupling exploits the high stability of benzamide bonds, enabling challenging C(sp²)–C(sp³) cross-coupling with alkyl Grignard reagents that are prone to dimerization and β-hydride elimination. The subsequent sodium dispersion promoted reduction of carboxamides proceeds with full chemoselectivity for the C–N bond cleavage of the carbinolamine intermediate. The method provides access to valuable benzylic alcohols, including deuterium-labelled benzylic alcohols, which are widely used as synthetic intermediates and pharmacokinetic probes in organic synthesis and medicinal chemistry. The combination of two benign metals by complementary reaction mechanisms enables to exploit underexplored avenues for organic synthesis.