Iodonium Ylides Research Articles

Triflyl [18F]Fluoride as a Solution for Base-sensitive Late-stage Nucleophilic Aromatic 18F-Fluorination Reactions.

Fluorine-18 is the predominant radionuclide used to label Positron Emission Tomography (PET) tracers. One outstanding challenge in nucleophilic aromatic radiofluorination reactions is the sensitivity of precursors and catalysts for basic reaction conditions, which are necessary for the work-up of [18F]fluoride, resulting in limited reproducibility. Triflyl [18F]fluoride is a new [18F]fluoride source that allows freedom in choice of type and amounts of base and cryptand. The aim of the current work is to explore the scope and limitations of triflyl [18F]fluoride in the late-stage nucleophilic aromatic 18F-fluorination of various functionalized precursors, exploring reduced amounts of base and cryptand. The assessment allowed for the application of this new nucleophilic [18F]fluoride reagent to the successful radiosynthesis of boron, stannane, hypervalent iodonium ylide and phenol substrates bearing electron-deficient, -neutral and -rich functional groups as well as the clinically relevant PET tracers [18F]FPEB, [18F]mFBG and [18F]SynVesT-1.

Recent Progress in Synthetic Applications of Hypervalent Iodine(III) Reagents.

Hypervalent iodine(III) compounds have found wide application in modern organic chemistry as environmentally friendly reagents and catalysts. Hypervalent iodine reagents are commonly used in synthetically important halogenations, oxidations, aminations, heterocyclizations, and various oxidative functionalizations of organic substrates. Iodonium salts are important arylating reagents, while iodonium ylides and imides are excellent carbene and nitrene precursors. Various derivatives of benziodoxoles, such as azidobenziodoxoles, trifluoromethylbenziodoxoles, alkynylbenziodoxoles, and alkenylbenziodoxoles have found wide application as group transfer reagents in the presence of transition metal catalysts, under metal-free conditions, or using photocatalysts under photoirradiation conditions. Development of hypervalent iodine catalytic systems and discovery of highly enantioselective reactions using chiral hypervalent iodine compounds represent a particularly important recent achievement in the field of hypervalent iodine chemistry. Chemical transformations promoted by hypervalent iodine in many cases are unique and cannot be performed by using any other common, non-iodine-based reagent. This review covers literature published mainly in the last 7-8 years, between 2016 and 2024.

Microwave‐Assisted Rhodium (III)‐Catalyzed [3+3] Annulation of 2‐Benzyl‐2H‐indazole‐6‐carboxylic Acids with Iodonium Ylides: A Regioselective Synthesis of Indazole‐Fused Chromenes

Abstract: A Rh (III)‐catalyzed redox‐neutral C‐H activation/ [3+3] cyclization of 2‐benzyl‐2H‐indazole‐6‐carboxylic acids with iodonium ylides under microwave irradiation for the synthesis of indazole‐fused chromenes has been reported. The critical feature of this method is that the C‐H activation of the C7‐H bond of 2‐benzyl‐2H‐indazole‐6‐carboxylic acid proceeds with regioselectivity in the presence of the proximate C5‐H bond without the need for external oxidant. Microwave irradiation reduced the reaction time as compared to conventional heating. The detailed mechanistic study disclosed the mechanistic pathway of the reaction.

Rhodium(III)-Catalyzed C-H Activation/[5 + 2] Cascade Annulation of Aroyl Hydrazides with Iodonium Ylides for the Synthesis of Seven-Membered Dibenzodiazepinediones.

A novel Rh(III)-catalyzed C-H activation/[5 + 2] cascade annulation of aroyl hydrazides with iodonium ylides is accomplished, in which diverse seven-membered dibenzodiazepinediones were afforded in moderate to excellent yields. This annulation reaction features an ideal functional group tolerance and a wide substrate scope. Large-scale and derivatization reactions were conducted to demonstrate the potential utility of this transformation.

Transition-Metal-Catalyzed Directed C-H Bond Functionalization with Iodonium Ylides: A Review of the Last 5 Years.

Transition-metal-catalyzed directed C-H functionalization with various carbene precursors has been widely employed for constructing a wide range of complex and diverse active molecules through metal carbene migratory insertion processes. Among various carbene precursors, iodonium ylides serve as a novel and emerging carbene precursor with features including easy accessibility, thermal stability and high activity, which have attracted great attention from organic chemists and have achieved tremendous success in organic transformation. In this review, recent progress on the application of iodonium ylides with multifunctional coupling characteristics in C-H bond activation reactions is summarized, and the potential of iodonium ylides is discussed.

Synthesis of Oxaspirocyclohexadienones via Lewis‐Acid Catalyzed [2+3]‐Annulations of p‐Quinone Methides and Iodonium Ylides

AbstractHerein, we report a mild method for the synthesis of oxaspirocyclohexadienones by using a combination of Lewis acid‐HFIP mediated [2+3]‐annulation of p‐quinone methides (p‐QMs) and iodonium ylides. The proposed mechanism proceeds through a one‐pot sequence of carbonyl activation/cyclopropyl formation/Cloke‐Wilson rearrangement to provide a broad range of oxaspirocyclohexadienones in moderate to high yields. Interestingly, the spiro‐annulated products were further converted to tetrahydroxanthane derivatives via BF3.OEt2 mediated dienone‐phenol rearrangement pathway. Moreover, the spiro‐annulated derivatives also showed a moderate anti‐tuberculosis activity against Mycobacterium tuberculosis H37Ra ATCC25177.

Photocatalyst-Free Visible Light-Induced C(sp2)-H Arylation of Quinoxalin-2(1H)-ones and Coumarins.

Herein, we describe a visible light-induced C(sp2)-H arylation method for quinoxalin-2(1H)-ones and coumarins using iodonium ylides without the need for external photocatalysts. The protocol demonstrates a broad substrate scope, enabling the arylation of diverse heterocycles through a simple and mild procedure. Furthermore, the photochemical reaction showcases its applicability in the efficient synthesis of biologically active molecules. Computational investigations at the CASPT2//CASSCF/PCM level of theory revealed that the excited state of quinoxalin-2(1H)-one facilitates electron transfer from its π bond to the antibonding orbital of the C-I bond in the iodonium ylide, ultimately leading to the formation of an aryl radical, which subsequently participates in the C-H arylation process. In addition, our calculations reveal that during the single-electron transfer (SET) process, the C-I bond cleavage in iodonium ylide and new C-C bond formation between resultant aryl radical and cationic quinoxaline species take place in a concerned manner. This enables the arylation reaction to efficiently proceed along an energy-efficient route.

Synthesis of 1,4-oxathiins via [3+3] annulation of pyridinium 1,4-zwitterionic thiolates with iodonium ylides

A straightforward and valuable approach for the synthesis of 1,4-oxathiins has been developed via [3 ​+ ​3] annulation of pyridinium 1,4-zwitterionic thiolates with iodonium ylides. C–S and C–O bonds were formed in one pot manner in this transformation, which features with readily available substrates, excellent tolerance of functional groups and mild reaction conditions. It would be of great value for the construction of 1,4-oxathiins with biological and pharmacological activity.

Rhodium-Catalyzed Synthesis of Phenanthrenes from Biarylboronic Acids and Sulfoxonium or Iodonium Ylides

Rhodium-Catalyzed Synthesis of Phenanthrenes from Biarylboronic Acids and Sulfoxonium or Iodonium Ylides

Accessing 7,8-Dihydroquinoline-2,5-diones via Rh-Catalyzed Olefinic C-H Activation/[4+2] Cyclization.

Herein, we report a rhodium-catalyzed C-H activation/[4+2] cyclization reaction between α,β-unsaturated amides and iodonium ylides for the synthesis of novel 7,8-dihydroquinoline-2,5-diones and analogues. This protocol provides a series of pyridones fused with saturated cycles with good functional group compatibility, good water and air tolerance, and good to excellent yields under mild and green reaction conditions. Additionally, scale-up synthesis can be smoothly performed with as low as 0.25 mol % catalyst loading. Recycling experiments and different transformation experiments were also carried out to demonstrate the potential synthetic utility of this protocol.

Iron-Catalyzed Annulation of 2-Aminobenzaldehydes with Iodonium Ylides: A Mild and General Route for the Synthesis of Acridinone Derivatives

Iron-Catalyzed Annulation of 2-Aminobenzaldehydes with Iodonium Ylides: A Mild and General Route for the Synthesis of Acridinone Derivatives

Light Induced Cobalt(III) Carbene Radical Formation from Dimethyl Malonate As Carbene Precursor.

Radical-type carbene transfer catalysis is an efficient method for the direct functionalization of C-H and C=C bonds. However, carbene radical complexes are currently formed via high-energy carbene precursors, such as diazo compounds or iodonium ylides. Many of these carbene precursors require additional synthetic steps, have an explosive nature, or generate halogenated waste. Consequently, the utilization of carbene radical catalysis is limited by specific carbene precursors that access the carbene radical intermediate. In this study, we generate a cobalt(III) carbene radical complex from dimethyl malonate, which is commercially available and bench-stable. EPR and NMR spectroscopy were used to identify the intermediates and showed that the cobalt(III) carbene radical complex is formed upon light irradiation. In the presence of styrene, carbene transfer occurred, forming cyclopropane as the product. With this photochemical method, we demonstrate that dimethyl malonate can be used as an alternative carbene precursor in the formation of a cobalt(III) carbene radical complex.

Rh-Catalyzed α-Arylation of Cyclic 1,3-Dicarbonyls with Benzocyclobutenols Enabled by a Cyclic Iodonium Ylide Strategy.

To date, the general and catalytic α-arylation of cyclic 1,3-dicarbonyls remains elusive. We now report the first Rh-catalyzed α-arylation of cyclic 1,3-dicarbonyls with benzocyclobutenols through a cyclic iodonium ylide strategy. Our strategy represents a good solution for the previously challenging α-arylation of cyclic 1,3-dicarbonyls with sterically demanding aryl partners, which is especially appropriate for structurally unique heteroaromatic 1,3-dicarbonyls. Our approach features mild conditions, readily available starting materials, high yields, excellent functional group-tolerance, and simple operation, providing expedient access toward medically important 2-aryl (hetero)cyclic 1,3-dicarbonyls. The practicality of this approach is demonstrated by the gram-scale synthesis, one-pot synthesis, and numerous downstream transformations.

Metal-Free Selective para-Tosyloxylation of N-Arylbenzamides using [Hydroxy(tosyloxy)iodo]benzene

Abstract: An efficient approach for the tosyloxyl group transfer in several N-arylbenzamides has been achieved using HTIB (Koser’s reagent) under mild reaction conditions. Its simplicity, efficiency, and reduced reliance on hazardous reagents make it an attractive choice for chemists seeking sustainable alternatives. The proposed methodology offered single-step para-selective tosyloxylation, ensuring the prevention of the synthesis of mixtures of ortho and meta-isomers. The corresponding products were obtained with moderate to excellent efficiency. The current approach eliminated the need for harsh, acidic, and toxic metals, ensuring safer handling and minimizing environmental impact. A plausible mechanism for tosyloxylation of N-arylbenzamides involving iodonium ylide has been proposed.

Highly Stereoselective Synthesis of Multisubstituted Olefins from Alkynyl Tetracoordinate Borons and Iodonium Ylides via a Cyclic Intermediate.

We developed an intriguing and practical strategy for highly stereoselective assembly of multisubstituted olefins from alkynyl tetracoordinate boron species via a cyclic intermediate with 1,2-phenyl migration. We also developed a general method for the construction of deuterated trisubstituted alkenes from a cheap deuteration source, D2O, and the corresponding deuterated trisubstituted alkenes were obtained with excellent deuteration rates. This transformation features a novel reaction mechanism, exclusive stereoselectivity, and deuterated trisubstituted alkenes with excellent deuteration ratios.

Catalytic and Base-free Suzuki-type α-Arylation of Cyclic 1,3-Dicarbonyls via a Cyclic Iodonium Ylide Strategy.

To date, it remains challenging to achieve a general and catalytic α-arylation of cyclic 1,3-dicarbonyls, particularly ubiquitous heteroaromatic ones. In most cases, the preparation of their medically significant arylated derivatives requires multistep synthetic sequences. Herein, we introduce a new, convenient strategy involving the conversion of cyclic 1,3-dicarbonyls to cyclic iodonium ylides (CIYs), followed by rhodium-catalyzed α-arylation with arylboronic reagents via carbene coupling. This approach is mild, operationally simple, base-free, biocompatible, and exhibits broad substrate scope (>100 examples), especially with respect to various heteroaromatic 1,3-dicarbonyls and ortho-substituted or base-sensitive arylboronic acids. Importantly, owing to the excellent compatibility with various arylboronic acids or boronate esters (ArBpin, ArBneop, or ArBF3K), this method allows the late-stage installation of heterocyclic 1,3-dicarbonyl motifs in highly complex settings. The utility of this transformation is further demonstrated through significantly simplifying the synthesis of several bioactive molecules and natural products.

Catalytic and Base‐free Suzuki‐type α‐Arylation of Cyclic 1,3‐Dicarbonyls via a Cyclic Iodonium Ylide Strategy

AbstractTo date, it remains challenging to achieve a general and catalytic α‐arylation of cyclic 1,3‐dicarbonyls, particularly ubiquitous heteroaromatic ones. In most cases, the preparation of their medically significant arylated derivatives requires multistep synthetic sequences. Herein, we introduce a new, convenient strategy involving the conversion of cyclic 1,3‐dicarbonyls to cyclic iodonium ylides (CIYs), followed by rhodium‐catalyzed α‐arylation with arylboronic reagents via carbene coupling. This approach is mild, operationally simple, base‐free, biocompatible, and exhibits broad substrate scope (>100 examples), especially with respect to various heteroaromatic 1,3‐dicarbonyls and ortho‐substituted or base‐sensitive arylboronic acids. Importantly, owing to the excellent compatibility with various arylboronic acids or boronate esters (ArBpin, ArBneop, or ArBF3K), this method allows the late‐stage installation of heterocyclic 1,3‐dicarbonyl motifs in highly complex settings. The utility of this transformation is further demonstrated through significantly simplifying the synthesis of several bioactive molecules and natural products.

Application of Sulfoxonium Ylides or Iodonium Ylides in Rhodium‐Catalyzed Synthesis of Phenanthrenes

AbstractThe transmetalation triggered rhodium‐catalyzed C−H bond activation and tandem annulation of 2‐biphenylboronic acids with sulfoxonium ylides or iodonium ylides has been developed. Various products of phenanthrenes were constructed under redox‐neutral conditions in 34–86% yields. Several mechanism exploration experiments and derivatization reactions were conducted in sequence to gain a deeper understanding of the process and the potential of this transformation. It offers an alternative approach for the synthesis of phenanthrene derivatives.

Rhodium-Catalyzed Difunctionalization of Alkenes Using Cyclic 1,3-Dicarbonyl-Derived Iodonium Ylides.

Herein, we introduce an iodonium ylide strategy to achieve novel α-alkylation of cyclic 1,3-dicarbonyls through harnessing C(sp3)-Rh species generated from 5-exo-trig cyclization to provide rapid access to molecular hybridization of medically important isoindolin-1-ones and cyclic 1,3-dicarbonyls from readily available substrates. This approach features mild conditions, good yield, excellent functional group tolerance, and the simultaneous formation of two new chemical bonds and one stereogenic center. Moreover, the hydroxyl group of resulting product provides a good handle for downstream transformations. Importantly, we also demonstrate this strategy can be achieved in a one-pot manner. A C(sp3)-Rh complex was prepared and proved to be the key intermediate.

Rh(III)-catalyzed selective mono- and dual-functionalization/cyclization of 1-aryl-5-aminopyrazoles with iodonium ylides.

An efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as a single coupling partner was demonstrated, in which fused benzodiazepine skeletons were obtained in excellent yields. This method greatly improved an effective approach to dual C-H unsymmetrical functionalization.