Sulfur Ylides Research Articles

Transition-metal-free C-S bond cleavage and transformation of organosulfur compounds.

The activation and transformation of organic chemical bonds is a fundamental scientific problem. In the past several decades, C-S bond cleavage for the construction of C-C and C-heteroatom bonds has received tremendous attention in organic chemistry. Although significant progress has been made in the field of transition metal strategies, a variety of novel transition-metal-free strategies have also been developed using halogenated reagents, oxidants, acids, and bases. Moreover, organic photochemical and electrochemical methods have also been developed to achieve transition-metal-free C-S bond cleavage of organosulfur compounds. To date, however, no comprehensive review of transition-metal-free strategies has been reported. Therefore, we herein provide a comprehensive review of the major advances in the field of the transition-metal-free C-S bond cleavage and transformation of organosulfur compounds, including thioethers, sulfoxides, sulfones, thioacetals, sulfonium salts, and sulfur ylides.

Transition metal-free [2,3]-sigmatropic rearrangement in the reaction of sulfur ylides with allenoates.

An unprecedented transition metal free [2,3]-sigmatropic rearrangement involving stabilized sulfur ylides and allenoates has been thoroughly established. The scope and utility of this reaction have been extensively studied resulting in C-C bond formation under mild conditions with greater than 20 examples reported. A highlight of the work is the simple and fully operational process that does not involve the use of carbenes or the associated hazardous and sensitive reagents. The reaction can be performed at room temperature and using an open flask. Interestingly, the new C-C bond formation reaction is gram scalable, and the obtained isomers are readily separable, affording interesting building blocks that can be used in the preparation of complex molecules.

Synthesis of α-pyrones via gold-catalyzed cycloisomerization/[2 + 1] cycloaddition/rearrangement of enyne-amides and sulfur ylides

A novel gold-catalyzed cycloisomerization/[2 + 1]cycloaddition/rearrangement of enyne-amides and sulfur ylides is reported. This strategy enables rapid and efficient construction of a series of α-pyrone derivatives.

Photoinduced carbene transfer for copper-catalyzed asymmetric [4 + 1] cycloadditions: an entry to chiral indolines bearing quaternary stereocenters

A copper-catalyzed asymmetric [4 + 1] cycloaddition of ethynylbenzoxazinones with sulfur ylides formed in situ by photoinduced carbene transfer is reported to afford chiral indolines with good efficiency, enantio- and diastereoselectivities.

Access to thiazoline and spiro[indoline-3,3'-thiophene] scaffolds via a formal [3 + 2] annulation reaction of crotonate-derived sulfur ylides and β-ketothioamides.

A formal [3 + 2] annulation reaction of crotonate-derived sulfur ylides and β-ketothioamides (KTAs) was successfully developed to produce good-to-excellent yields of thiazoline and spiro[indoline-3,3'-thiophene] scaffolds. This transformation is a powerful tool for the synthesis of thiazoline and spiro[indoline-3,3'-thiophene] scaffolds due to its mild reaction conditions, easily accessible starting materials, and broad substrate scope. A large-scale reaction was carried out to ensure the practical applicability of this methodology. Finally, the plausible mechanistic pathway of the developed methodology was investigated.

An interrupted Corey-Chaykovsky reaction of designed azaarenium salts: synthesis of complex polycyclic spiro- and fused cyclopropanoids.

Simultaneous dearomatizing spirannulation of pyridinium salts is still in its infancy. Here, we present an organized skeletal remodeling of designed pyridinium salts by utilizing an interrupted Corey-Chaykovsky reaction to access unprecedented and structurally intriguing molecular architectures such as the vicinal bis-spirocyclic indanones and spirannulated benzocycloheptanones. This hybrid strategy rationally merges the nucleophilic features of sulfur ylides with the electrophilic pyridinium salts to achieve the regio- and stereoselective synthesis of new classes of cyclopropanoids. The plausible mechanistic pathways were derived from experimental results and control experiments.

Highly efficient construction of 2,3-disubstituted indoline derivatives by [4 + 1] annulation of sulfur ylides and o-sulfonamido aldimines

A highly efficient [4 + 1] annulation of sulfur ylide salts and o-sulfonamido aldimines for construction of valuable 2,3-disubstituted indolines is reported. It is worth noting that indoles could also be synthesized by this cascade reaction.

(Thiolan-2-yl)diphenylmethanol Benzyl Ether-Catalyzed Asymmetric Cyclopropanation of Chalcones.

We devised a new method for asymmetric cyclopropanation by employing (S)-(thiolan-2-yl)diphenylmethanol benzyl ether as an organocatalyst. Under optimal conditions, an in situ generated sulfur ylide reacts with (E)-chalcones via a Johnson-Corey-Chaykovsky reaction to afford a variety of cyclopropanes in excellent yields and stereoselectivities. This strategy employs low-environmental-risk reaction conditions and reusable catalysts. Hence, it is a green and efficient method for constructing cyclopropane scaffolds.

Theoretical Photoelectron Spectroscopy of Low-Valent Carbon Species: A ∼6 eV Range of Ionization Potentials among Carbenes, Ylides, and Carbodiphosphoranes.

High-quality density functional theory calculations underscore a nearly 6 eV range for the ionization potentials (IPs) of neutral, low-valent carbon compounds, including carbenes, ylides, and zero-valent carbon compounds (carbones) such as carbodiphosphoranes (CDPs) and carbodicarbenes. Thus, adiabatic IPs as low as 5.5 ± 0.1 eV are predicted for CDPs, which are about 0.7-1.2 eV lower than those of simple phosphorus and sulfur ylides. In contrast, the corresponding values for N-heterocyclic carbenes are about 8.0 eV while those for simple singlet carbenes such as dichlorocarbene and difluorocarbene range from about 9.0 eV to well over 11.0 eV.

Water‐assisted, Highly‐selective and Rapid Synthesis of Cyclopropane Derivatives by a [2+1] Annulation Reaction

AbstractThe [2+1] annulation reaction of α‐keto sulfur ylides and β, γ‐unsaturated‐α‐ketoesters was studied in detail. A series of 1,2,3‐trisubstituted cyclopropane derivatives were acquired in moderate to good yields with excellent diastereoselectivities through this rapid and effective reaction in only 10 minutes. The reaction condition is simple and mild without any alkali, catalyst or additive. The corresponding experiments revealed that single cyclopropane product could be obtained in the assistance of water in this reaction.

Synthesis of Spiro-Epoxy oxindole derivatives via unexpected oxidation/consecutive Corey-Chaykovsky reaction

Unexpected oxidation/consecutive Corey-Chaykovsky reaction of N-2,2,2-trifluoroethylisatin ketimines is conducted via a one-pot process using sulfur ylide to form spiro-epoxy oxindole derivatives. This unprecedented reaction proceeds smoothly under mild conditions, is operationally simple, and tolerates various functional groups. Notably, while the general Corey-Chaykovsky reaction of imines affords aziridines, this work describes the first oxidation step to produce isatins as intermediates followed by the Corey-Chaykovsky reaction.

Synthesis of a Thiazole Library via an Iridium-Catalyzed Sulfur Ylide Insertion Reaction.

A library of thiazoles and selenothiazoles were synthesized via Ir-catalyzed ylide insertion chemistry. This process is a functional group, particularly heterocycle-substituent tolerant. This was applied to the synthesis of fanetizole, an anti-inflammatory drug, and a thiazole-containing drug fragment that binds to the peptidyl-tRNA hydrolase (Pth) in Neisseria gonorrheae bacteria.

Synthesis of Benzofurans from Sulfur Ylides and ortho‐Hydroxy‐Functionalized Alkynes

AbstractThe synthesis of benzofurans from readily accessible sulfur ylides and ortho‐hydroxy aryl alkynes is reported. The transformation proceeds through an isomerization/nucleophilic addition/cyclization/aromatization cascade. The substrate scope is very general with respect to both reactants and the products are afforded in 43–94% yield under conditions which are catalyst‐free and additive‐free.magnified image

Distinction between the reactivity of phosphorus ylide vs sulfur ylide with the carbonyl compounds : Simplicity and logic

Distinction between the reactivity of phosphorus ylide vs sulfur ylide with the carbonyl compounds : Simplicity and logic

Metal-Free [5 + 1] Cycloaddition-Aromatization of Benzotriazoles and Sulfur Ylides to Construct 1,2,4-Benzotriazines.

Reported herein is a novel [5 + 1] cycloaddition-aromatization of benzotriazoles and sulfur ylides to efficiently construct 1,2,4-benzotriazine derivates with good yield. This new protocol does not employ any transition metal reagent and enables the cycloaddition by cleavage of the N-N single bond. The use of inexpensive and readily available starting materials, a broad substrate scope, mild reaction conditions, metal-free, and versatile functionalization of the 1,2,4-benzotriazines make this strategy more attractive.

Direct Stereodivergent Olefination of Carbonyl Compounds with Sulfur Ylides.

The reactivity of phosphorus and sulfur ylides toward carbonyl compounds constitutes a well-known dichotomy that is a common educational device in organic chemistry—the former gives olefins, while the latter gives epoxides. Herein, we report a stereodivergent carbonyl olefination that challenges this dichotomy, showcasing thiouronium ylides as valuable olefination reagents. With this method, aldehydes are converted to Z-alkenes with high stereoselectivity and broad substrate scope, while N-tosylimines provide a similarly proficient entry to E-alkenes. In-depth computational and experimental studies clarified the mechanistic details of this unusual reactivity.

1,1-Difunctionalization of α‑Carbonyl Sulfur Ylides with Thiosulfonates: Synthesis of β-Keto Thiosulfones

Abstract1,1-Difunctionalization of α‑carbonyl sulfur ylides and thiosulfonates under simple conditions is disclosed. In this protocol, two new C–S bonds are constructed in a one-step reaction. A series of aliphatic and aromatic β-keto thiosulfones were obtained in moderate to good yields. This reaction probably proceeds through sulfur ylide-involved­ nucleophilic substitution of an ion pair within a solvent cage.

Photoredox-Catalyzed and Copper(II) Salt-Assisted Radical Addition/Hydroxylation Reaction of Alkenes, Sulfur Ylides, and Water

A visible light-driven photoredox-catalyzed and copper(II)-assisted three-component radical addition/hydroxylation reaction of alkenes, sulfur ylides, and water is reported. This process shows broad substrate scope and high functional group tolerance, with respect to both readily available sulfur ylides and alkenes, providing high-yielding and practical access to valuable γ-hydroxy carbonyl compounds. Key to the success of the reaction is the controlled generation of α-carbonyl carbon radicals from sulfur ylides via sulfonium salts by a visible-light-driven proton-coupled electron transfer (PCET) strategy in a mixture of 2,2,2-trifluoroethanol/CH2Cl2. Addition of Cu(TFA)2·H2O helps to accelerate the radical-cation crossover to improve the reaction efficiency. Mechanistic studies suggest that the hydroxy moiety in the products stems from water. This study also builds up a platform for further investigation into the radical synthetic chemistry of sulfur ylides.

Generation of Dimethyl Sulfoxide Coordinated Thermally Stable Halogen Cation Pools for C−H Halogenation

AbstractA method to generate halogen cation pools from the reaction of 1,2‐dihaloethanes (hal=Br, I) and dimethyl sulfoxide (DMSO) for C−H halogenation of arenes and heteroarenes was reported. The initial reaction of DMSO and 1,2‐dihaloethane generates the sulfur ylide, which undergoes pyrolytic elimination of ethylene by affording halonium ions. These ions were accumulated and stabilized by DMSO through coordination by forming halogen cation pools for the halogenation reaction. This protocol was selective for electrophilic monohalogenation of arenes at room temperature; however, polyhalogenated products were formed by raising the reaction temperature. Late‐stage halogenation of heteroarenes and some commonly marketed drugs signifies the synthetic utility of this protocol in pharmaceutical chemistry. Unlike the classical methods, the in‐situ generated electrophilic bromonium ion was further exploited for the direct synthesis of α‐diketones from the alkenes under base‐free conditions.magnified image

Total Syntheses of Scabrolide A and Nominal Scabrolide B.

The marine natural product scabrolide A was obtained by isomerization of the vinylogous 1,4-diketone entity of nominal scabrolide B as the purported pivot point of the biosynthesis of these polycyclic norcembranoids. Despite the success of this maneuver, the latter compound itself turned out not to be identical with the natural product of that name. The key steps en route to the carbocyclic core of these targets were a [2,3]-sigmatropic rearrangement of an allylic sulfur ylide to forge the overcrowded C12–C13 bond, an RCM reaction to close the congested central six-membered ring, and a hydroxy-directed epoxidation/epoxide opening/isomerization sequence to set the “umpoled” 1,4-dicarbonyl motif and the correct angular configuration at C12.