Reaction Of Ylides Research Articles

Iridium-Catalyzed Asymmetric Cascade Allylation/Pictet-Spengler Cyclization Reaction for the Enantioselective Synthesis of 1,3,4-Trisubstituted Tetrahydroisoquinolines.

An iridium-catalyzed trifluoroacetic acid-promoted asymmetric cascade allylation/Pictet-Spengler cyclization reaction of azomethine ylides with aromatic allylic alcohols is reported. This protocol provides a facile and scalable method for the construction of 1,3,4-trisubstituted tetrahydroisoquinolines containing two stereogenic centers in good yields (up to 96%) with generally excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). Furthermore, a series of aromatic heterocycle-fused piperidines were also obtained with excellent enantiocontrol by this methodology.

β-Substituted Alkenyl Heteroarenes as Dipolarophiles in the Cu(I)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides Empowered by a Dual Activation Strategy: Stereoselectivity and Mechanistic Insight.

The catalytic asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides with various electron-deficient alkenes provide the most straightforward protocol for the preparation of enantioenriched pyrrolidines in organic synthesis. However, the employment of conjugated alkenyl heteroarenes as dipolarophiles in such protocols to afford a class of particularly important molecules in medicinal chemistry is still a great challenge. Herein, we report that various β-substituted alkenyl heteroarenes, challenging internal alkene substrates without a strong electron-withdrawing substituent, were successfully employed as dipolarophiles for the first time in the Cu(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides. This reaction furnishes a large array of multistereogenic heterocycles incorporating both the biologically important pyrrolidine and heteroarene skeletons in good yields with exclusive diastereoselectivity and excellent enantioselectivity. Our extensive density functional theory (DFT) calculations proposed a working model to explain the origin of the stereochemical outcome and elucidated uncommon dual activation/coordination of both the dipole and dipolarophile substrates by the metal, in which a sterically bulky, rigid, and monodentate phosphoramidite ligand with triple-homoaxial chirality plays a pivotal role in providing an effective chiral pocket around the metal center, resulting in high enantioselectivity. The additional coordination of the heteroatom in the dipolarophile substrate to Cu is also critical for the exclusive diastereoselectivity and enhanced reactivity. Our calculations also predicted the reverse and high enantioinduction for the corresponding substrates with monocyclic heteroarenes as well as regiospecific cycloaddition to the less reactive internal C═C bond of one related dipolarophile diene substrate. Such unique steric effect-directed enantioswitching and coordination-directed regioselectivity were verified experimentally.

Sequential N‐Arylation and Intramolecular Imine Addition Reaction of Indoloazomethine Ylides with Arynes for the Synthesis of Thiadiazepine Derivatives

AbstractMetal‐free reaction of indoloazomethine ylides with 2‐(trimethylsilyl)aryl triflates in the presence of TMAF and MeOH provided 1,4‐thiadiazepines through sequential N‐arylation and intramolecular imine addition reaction, which is fully oxidized with p‐chloranil. These compounds are smoothly isomerized to indoloindolizines in quantitative yield. Moreover, formation of indoloindolizine was accessed from indoloazomethine ylide and 2‐(trimethylsilyl)aryl triflate in semi‐one‐pot.magnified image

A cascade deprotonation/intramolecular aldol reaction of α-carbonyl sulfonium ylides with 2-mercaptoindole-3-carbaldehydes and 2-mercaptobenzaldehydes to access thieno[2,3-b]indoles and benzothiophenes.

The first catalyst-free cascade deprotonation/intramolecular aldol reaction of α-carbonyl sulfonium ylides with 2-mercaptoindole-3-carbaldehydes and 2-mercaptobenzaldehydes was developed. A series of thieno[2,3-b]indoles and benzothiophenes were smoothly obtained in high to excellent yields. The salient features of the protocol include catalyst-free conditions, an environment-friendly solvent, broad substrate scope, and large-scale synthesis.

Organocatalytic asymmetric synthesis of α-amino esters from sulfoxonium ylides.

Described here is the first organocatalytic asymmetric N–H insertion reaction of α-carbonyl sulfoxonium ylides. Without a metal catalyst, this reaction represents an attractive complement to the well-established carbene insertion reactions. As a stable surrogate of diazocarbonyl compounds, sulfoxonium ylides reacted with a range of aryl amines to provide efficient access to α-aryl glycines with excellent enantiocontrol in the presence of a suitable chiral phosphoric acid catalyst. The high stability and weak basicity of sulfoxonium ylides not only enable this protocol to be user-friendly and practically useful, but also preclude catalyst decomposition, which is crucial to the excellent amenability to electron-poor amine nucleophiles. Detailed mechanistic studies indicated that the initial protonation is reversible and the C–N bond formation is rate-determining.

Unprecedented access to functionalized pyrrolo[2,1-a]isoquinolines from the domino reaction of isoquinolinium ylides and electrophilic benzannulated heterocycles.

We have come across an unexpected reaction between electrophilic indoles and isoquinolinium methylides for accessing functionalized pyrrolo[2,1-a]isoquinolines. The reaction was found in general to yield the products in good yields. We also observed the formation of S-S-bridged bis-pyrrolo[2,1-a]isoquinolines from the reaction of 3-nitro benzothiophene and isoquinolinium methylides.

Ultrasound assisted synthesis of hybrid quinoline-imidazole derivatives: a green synthetic approach.

A green, straightforward and efficient study for obtaining hybrid quinoline-imidazole derivatives under ultrasound (US) irradiation as well as under conventional thermal heating (TH) has been presented. The reaction pathway involves only two steps: the N-alkylation of imidazole ring and a Huisgen [3 + 2] dipolar cycloaddition reaction of ylides to dimethyl acetylenedicarboxylate (DMAD). For both types of reactions, a green workup procedure under US irradiation has been presented. Under US irradiation, the N-alkylation of nitrogen atoms from the imidazole nucleus has outstanding benefits in terms of reaction time, energy consumption and yields, and can thereby be considered an environmentally friendly method. Forty new hybrid quinoline-imidazole compounds have been synthesized: 18 salts, 8 dihydro-benzopyrrolo imidazolo quinoline, 9 benzopyrrolo-imidazolo quinoline and 5 dihydro-pyrroloquinoxaline quinoline cycloadducts.

Diastereoselective Synthesis of γ‐Lactones through Reaction of Sulfoxonium Ylides, Aldehydes, and Ketenes: Substrate Scope and Mechanistic Studies

AbstractIn this article, we describe the synthesis of γ‐lactones through the reaction of sulfoxonium ylides, aldehydes, and disubstituted ketenes. The one‐pot sequential method provides access to γ‐lactones from disubstituted ketenes, in moderate to excellent yields, and with good diastereoselectivity favoring the trans‐diastereomer (dr up to 92 : 8). The reaction mechanism was investigated by performing labeling, crossover, and various control experiments. The results of those experiments support the reaction mechanism involving betaine formation, reaction of the betaine with a ketene to form an enolate intermediate, [3,3]‐sigmatropic rearrangement of an enolate intermediate, and finally, 5‐exo‐tet cyclization to afford the γ‐lactone product.

Straightforward Synthesis of Succinimide-Fused Pyrrolizidines by A Three-Component Reaction of α-Diketone, Amino Acid, and Maleimide

AbstractAn efficient, one-pot, three-component [3+2] cycloaddition reaction of azomethine ylide obtained from α-dicarbonyl compounds (cyclic and acyclic diketone or keto ester) and amino acids with maleimides under catalyst-free conditions has been developed. This cascade protocol shows high efficiency and remarkable functional group tolerance, and the ubiquitous succinimide-fused pyrrolizidines with a highly compact and strained scaffold were obtained with high yield and excellent diastereoselectivity. Furthermore, this novel and atom-economical strategy could be performed on a gram scale with comparable reaction efficiency.

1,3-Dipolar cycloaddition reactions of azomethine ylides with seven-membered cyclic N-sulfony imines access to polycyclic sulfonamides

Abstract A straightforward and efficient strategy for the synthesis of novel functionalized polycyclic sulfonamides containing e-sultams motif under metal-free catalysis via [3 + 2] 1,3-dipolar cycloaddition reactions of azomethine ylides generated in situ with seven-membered cyclic N-sulfony imines has been achieved. The present process was carried out under mild reaction conditions to give polycyclic sulfonamides in high yield (up to 95%). Additionally, the conversion of the cycloadduct to other useful structure has also been developed. The structure of the typical product was clearly established by X-ray crystallography.

Domino Annulation Reaction of Sulfur Ylides and Morita-Baylis-Hillman Carbonates of Isatins: Synthesis of Oxospiro[bicyclo[3.1.0]hexane-6,3'-indolin] Scaffolds.

A sequential [3 + 2]/[2 + 1] annulation domino reaction of crotonate-derived sulfur ylides and Morita-Baylis-Hillman carbonates of isatins for the construction of oxospiro[bicyclo[3.1.0]hexane-6,3'-indolin] scaffolds in moderate to good yields with almost 1:1 diastereoselectivity has been developed. Mild reaction conditions and readily accessible starting materials as well as excellent functional group compatibility render this transformation a powerful tool for the synthesis of spirocyclopropyloxindoles. A gram-scale synthetic procedure was also successfully carried out and a plausible reaction mechanism could be proposed.

Chemoselective Rearrangement Reactions of Sulfur Ylide Derived from Diazoquinones and Allyl/Propargyl Sulfides.

Here, we describe three types of rearrangement reactions of sulfur ylide derived from diazoquinones and allyl/propargyl sulfides. With Rh2(esp)2 as the catalyst, diazoquinones react with allyl/propargyl sulfides to form a sulfur ylide, which undergoes a chemoselective tautomerization/[2,3]-sigmatropic rearrangement reaction, a Doyle-Kirmse rearrangement/Cope rearrangement cascade reaction, or a Doyle-Kirmse rearrangement/elimination reaction, depending on the substituent of the sulfides. The protocol provides alkenyl and allenyl sulfides and multisubstituted phenols with moderate and high yields.

Recent Perspectives on Rearrangement Reactions of Ylides via Carbene Transfer Reactions.

Among the available methods to increase the molecular complexity, sigmatropic rearrangements occupy a distinct position in organic synthesis. Despite being known for over a century sigmatropic rearrangement reactions of ylides via carbene transfer reaction have only recently come of age. Most of the ylide mediated rearrangement processes involve rupture of a σ‐bond and formation of a new bond between π‐bond and negatively charged atom followed by simultaneous redistribution of π‐electrons. This minireview describes the advances in this research area made in recent years, which now opens up metal‐catalyzed enantioselective sigmatropic rearrangement reactions, metal‐free photochemical rearrangement reactions and novel reaction pathways that can be accessed via ylide intermediates.

Transition-metal-free [3+3] annulation reaction of sulfoxonium ylides with cyclopropenones for the synthesis of 2-pyrones

An efficient and practical synthetic approach was developed for the tandem synthesis of trisubstituted 2-pyrone derivatives from sulfoxonium ylides and cyclopropenones. This [3+3] annulation reaction was carried out under transition-metal-free conditions. A broad range of functional groups were tolerant under mild conditions, and a variety of 2-pyrones were obtained in moderate to good yields.

A total and convergent synthesis of (7Z,11Z,13E)-7,11,13-Hexadecatrienal, the major sex pheromone component of the citrus leafminer, Phyllocnistis citrella

• Successful multistep synthesis of (7Z,11Z,13E)-7,11,13-Hexadecatrienal. • The GC purity of (7Z,11Z,13E)-7,11,13-Hexadecatrienal achieved 89.75%. • A new concept in the green chemistry principles for the multistep synthesis of (7Z,11Z,13E)-7,11,13-Hexadecatrienal is shown by presenting green metrics calculation. (Z, Z, E)-7, 11, 13-Hexadecatrienal, the major component of the sex pheromone of the citrus leaf miner Phyllocnistis citrella is efficiently and stereoselectively synthesized starting from the commercially available 6-Bromo-1-hexanol and described hereby. The synthesis of (Z, Z, E)-7, 11, 13-Hexadecatrienal was carried out by using the key step being Wittig reaction of the protected ylide using potassium tertiary butoxide a base to furnish 11Z double bond ( Z )-isomer as the major product. The stereoselective formation of the 7Z double bond is formed by the stereospecific reduction of internal alkyne with sodium borohydride (PIINi). The synthetic methodology is inexpensive with its operational simplicity and it will be attractive for academic and industrial research.

Facile Synthesis of (E)-5-Styrylpyrimidines via Wittig Reaction Using So-dium Tripolyphosphate in Water

Abstract: An inexpensive and eco-friendly Wittig olefination protocol has been developed to prepare novel (E)-5-styrylpy-rimidines. The reaction of pyrimidine phosphonium ylide with different aryl/hetero-aryl aldehydes underwent smoothly in the presence of sodium tripolyphosphate (STPP) in aqueous condition giving (E)-5-styrylpyrimidines (10a-t) in very high yields (77-96 %).

Huisgen [3 + 2] Dipolar Cycloadditions of Phthalazinium Ylides to Activated Symmetric and Non-Symmetric Alkynes.

We present herein a straightforward and efficient pathway for the synthesis of pyrrolophthalazine cycloadducts via Huisgen [3 + 2] dipolar cycloaddition reactions of phthalazinium ylides to methyl propiolate or dimethyl acetylenedicarboxylate (DMAD). A thoroughly comparative study concerning the efficiency of synthesis, conventional thermal heating (TH) versus microwave (MW) and ultrasound (US) irradiation, has been performed. The cycloaddition reactions of phthalazinium ylides to methyl propiolate occur regiospecific, with a single regioisomer being obtained. Under conventional TH, the cycloaddition reaction of phthalazinium ylides with DMAD occurs to a mixture of inseparable partial and fully aromatized pyrrolophthalazine cycloadducts, while MW or US irradiation are leading only to fully aromatized compounds, with the reactions becoming selective. A feasible mechanism for formation of fully aromatized compounds is presented. Besides selectivity, it has to be noticed that the reaction setup under MW or US irradiation offer a number of other certain advantages: higher yields, decreasing of the amount of used solvent comparative with TH, decreasing of the reaction time from hours to minutes and decreasing of the consumed energy; consequently, these reactions could be considered environmentally friendly.

Unveiling the Reactivity of Cyclic Azomethine Ylides in [3+2] Cycloaddition Reactions within the Molecular Electron Density Theory

The [3+2] cycloaddition (32CA) reactions of cyclic azomethine ylides with a series of acetylene derivatives have been studied within the Molecular Electron Density Theory (MEDT). Analysis of the Conceptual DFT indices allows the characterisation of the ambiphilic character of these cyclic AYs, thus participating as strong electrophiles and strong nucleophiles in polar 32CA reactions. The activation enthalpies associated with the 32CA reactions of these cyclic AYs are found in reasonable agreement with the experimental outcomes. These reactions proceed through a one‐step mechanism. The 32CA reactions with 1‐dimethylamino‐1‐propyne and dimethyl acetylenedicarboxylate take place through highly asynchronous polar transition states (TSs). On the other hand, the strain present in cyclooctyne allows explaining its participation in a non‐polar 32CA reaction via a synchronous TS. The present MEDT study allows establishing that the substitution in these cyclic AYs changes their parent pseudodiradical‐type reactivity to the zwitterionic‐type one.

Diastereoselective Synthesis of Spiro[indoline‐3,7′‐pyrrolo[1,2‐a]azepines] via Sequential [3+2] Cycloaddition and Ring Expansion Reaction

AbstractSpiro[indoline‐3,7′‐pyrrolo[1,2‐a]azepines] were conveniently synthesized in satisfactory yields and with high diastereoselectivity from three‐component reaction of L‐proline, isatins and chalcones and sequential reaction with dimethyl but‐2‐ynedioate or methyl propiolate in refluxing methanol. The ferrocenyl‐chalcones and dibenzylideneacetones were also successfully used in this one‐pot two‐step reaction to give novel ferrocenyl and styryl‐substituted spiro compounds. The reaction mechanism included domino [3+2] cycloadddtition reaction of azomethine ylide with chalcone and ring‐expansion reaction of in situ generated spiro[indoline‐3,3′‐pyrrolizine] with electron‐deficient alkynes.

Gold-Catalyzed Sigmatropic Rearrangement Reactions via Carbene Transfer Reactions.

Sigmatropic rearrangements are an important fundamental toolbox in organic synthesis to access complex molecular fragments. Yet, the rearrangement reactions of onium ylides via gold catalyzed carbene transfer reactions are relatively unexplored. Herein, we describe a gold-catalyzed sigmatropic rearrangement of sulfonium and selenium ylides (39 examples, up to 99% yield). Furthermore, we report on the limitations of sigmatropic rearrangement reactions of aryl allyl anilines, which deliver exclusively C-H functionalized products.