Sulfonium Ylides Research Articles

Difluorocarbene Generation via a Spin-Forbidden Excitation under Visible Light Irradiation.

The generation of difluorocarbene from difluoromethane bis(sulfonium ylide) 1 through spin-forbidden excitation under irradiation with 450 nm blue light was reported. The formation of difluorocarbene was confirmed by its reaction with styrene derivatives for the generation of difluorocyclopropanation and insertion into RX-H bonds (X = O, S) for the generation of RXCF2H. The spin-forbidden excitation mechanism for the formation of difluorocarbene from difluoromethane bis(sulfonium ylide) was supported by spectroscopic and kinetic studies as well as computational chemistry. The homolytic cleavage of two S-C bonds in compound 1 under irradiation was confirmed by time-resolved EPR spectroscopic studies of the precursor's free-radical-capturing reaction, as well as the isolation of the dimer of dimethyl (phenylthiol)malonyl radical. Further studies showed that the homolytic cleavage process occurred asynchronously in the solvent cage based on the isotope-labeled scrambling experiments and DFT calculations.

Design of Stable Chiral Aminosulfonium Ylides and Their Catalytic Asymmetric Synthesis

AbstractThe isolation and catalytic enantioselective synthesis of configurationally stable S‐stereogenic sulfonium ylides have been significant challenges in the field of asymmetric synthesis. These reactive intermediates are crucial for a variety of synthetic transformations, yet their inherent tendency towards rapid inversion at the sulfur stereocenter has hindered their practical utilization. Conventional approaches have focused on strategies that incorporate a C=S bond‐containing cyclic framework to help mitigate this stereochemical lability. In this work, we present an alternative tactic that leverages the stabilizing influence of an adjacent N‐atom and cyclic sulfide moiety. Exploiting a copper catalyzed enantioselective intermolecular carbene transfer reaction, structurally diverse S‐stereogenic aminosulfonium ylides have been achieved in excellent yields and enantioselectivities. Experimental results indicate that the careful selection of 2‐diazo‐1,3‐diketone precursors is crucial for achieving optimal stereoinduction in this transformation. The resulting highly enantioenriched aminosulfonium ylides allow for further stereospecific elaborations to furnish aminosulfonium ylide oxides and sulfinamide. This work expands the boundaries of chiral sulfonium ylide chemistry, providing access to a broad range of previously elusive S‐stereogenic aminosulfonium ylide scaffolds.

Phase-transfer-shuttle generated in situ enables novel SN1-type fluorination of sulfonium ylide with hydrofluoric acid

Phase-transfer-shuttle generated in situ enables novel SN1-type fluorination of sulfonium ylide with hydrofluoric acid

Design of Stable Chiral Aminosulfonium Ylides and Their Catalytic Asymmetric Synthesis.

The isolation and catalytic enantioselective synthesis of configurationally stable S-stereogenic sulfonium ylides has been a significant challenge in the field of asymmetric synthesis. These reactive intermediates are crucial for a variety of synthetic transformations, yet their inherent tendency towards rapid inversion at the sulfur stereocenter has hindered their practical utilization. Conventional approaches have focused on strategies that incorporate a C=S bond-containing cyclic framework to help mitigate this stereochemical lability. In this work, we present an alternative tactic that leverages the stabilizing influence of an adjacent N-atom and cyclic sulfide moiety. Exploiting a copper catalyzed enantioselective intermolecular carbene transfer reaction, structurally diverse S-stereogenic aminosulfonium ylides have been achieved in excellent yields and enantioselectivities. Experimental results indicate that the careful selection of 2-diazo-1,3-diketone precursors is crucial for achieving optimal stereoinduction in this transformation. The resulting highly enantioenriched aminosulfonium ylides allow for further stereospecific elaborations to furnish aminosulfonium ylide oxides and sulfinamide. This work expands the boundaries of chiral sulfonium ylide chemistry, providing access to a broad range of previously elusive S-stereogenic aminosulfonium ylide scaffolds.

Visible-Light-Mediated gem-Difunctionalization of Diazo Compounds with Vinyl Sulfoxonium Ylides and Thiols

AbstractA visible-light-induced multicomponent reaction of vinyl sulfoxonium ylide, thiol, and diazo ester to generate tertiary sulfide is described. The present diastereoselective gem-difunctionalization of the diazo ester can be achieved under mild conditions, as it does not require any additives, catalysts, or transition metals and is tolerant of air and moisture. Due to more nucleophilicity, vinyl sulfoxonium ylide undergoes S–H insertion with thiols to generate an allyl sulfide intermediate. Simultaneously, diazo ester undergoes photolysis to generate a carbene intermediate. Subsequently, the coupling of carbene and allyl sulfide intermediates generates sulfonium ylide, which undergoes Doyle–Kirmse rearrangement to generate tertiary sulfide scaffolds.

One-Carbon Homologation of Knoevenagel Adducts: Enantioselective Access to Benzhydryl Derivatives.

A one-carbon homologation of Knoevenagel adducts enabling the insertion of a CHAr fragment is reported. The strategy involves a sulfur ylide mediated cyclopropanation followed by the rearrangement of cyclopropanes and enables the synthesis of a series of benzhydryl derivatives. Mechanistic studies reveal that the cyclopropane rearrangement involves a Lewis acid catalyzed ring-opening followed by the 1,2-migration of an aryl group. The possibility of controlling the absolute stereochemistry of the generated stereogenic allylic carbon center using a chiral sulfonium ylide is demonstrated.

3+3] Annulation of Diazoenals and α-Mercapto Ketones via Protic Sulfonium Ylides: Direct Synthesis of 2H-Thiopyrans, Innovative Progenitors for Unstudied 2H-Thiopyran-2-ones and 4H-Thiopyran-4-ones.

Herein, we report a new Rh(II)/Sc(III)-catalyzed [3+3] annulation between diazoenals and α-mercapto ketones for the direct synthesis of 4-formyl-2H-thiopyrans. The reaction proceeds via protic sulfonium ylides derived from highly electrophilic Rh-enalcarbenoids, followed by regioselective intramolecular aldol condensation. Further studies revealed that 4-formyl-2H-thiopyrans are novel precursors for unstudied 2H-thiopyran-2-ones and 4H-thiopyran-4-ones. The 4H-thiopyran-4-ones were obtained via a novel O2/Et3N-mediated oxidative deformylation. This methodology was applied to the short synthesis of structurally complex pyrimidine-fused 2H-thiopyran via cascade Schmidt, Ritter, and intramolecular cyclization reactions.

Diastereoselective synthesis of trans-2,3-dihydroindoles via formal [4 + 1] annulation reactions of a sulfonium ylide.

We have established an in situ generated sulfonium-ylide mediated annulation to construct 2,3-disubstituted-2,3-dihydroindoles. The [4 + 1] annulation approach relied on Michael addition/substitution reactions. These reactions were carried out at ambient temperature to deliver dihydroindoles with excellent yields and diastereoselectivities. Moreover, the versatility of this approach allows for the introduction of various functional groups, enabling further diversification of the dihydroindoles. Also, the cascade approach was broadened to synthesize dihydrobenzofurans.

·YlideFluor-CF2Cl: a shelf-stable, versatile electrophilic or radical chlorodifluoromethylating reagent

An easily available chlorodifluoromethylating reagent YlideFluor-CF2Cl based on the sulfonium ylide skeleton was developed.

Ring expansion of spirocyclopropanes with stabilized sulfonium ylides: highly diastereoselective synthesis of cyclobutanes.

A novel method was devised for regioselective ring expansion of Meldrum's acid-derived spirocyclopropanes to spirocyclobutanes with stabilized sulfonium ylides, affording 1,2-trans-disubstituted 6,8-dioxaspiro[3.5]nonane-5,9-diones in up to 87% yields without the formation of any isomers. The aforementioned reaction was also applied to the barbituric acid-derived spirocyclopropane, resulting in the formation of the corresponding cyclobutanes.

DNA-Conjugated Cyclopropane Derivatives Constructed from Sulfonium Ylides with α,β-Unsaturated Ketones.

Here, we report a DNA-compatible reaction for the generation of cyclopropane derivatives using thiolides with α,β-unsaturated ketones in the absence of transition metal and N2 protection, which is convenient for DNA encoded library (DEL) construction. This approach allows the rapid and efficient production of a series of DEL libraries of potentially biologically active cyclopropanes and spirocyclopropyl oxindole derivatives.

Recent Advances in the Asymmetric Doyle–Kirmse Reaction

AbstractThe asymmetric Doyle–Kirmse reaction has become increasingly important in the construction of chiral sulfides, especially for those with quaternary carbon stereocenters. Over the few past decades, a series of catalytic asymmetric approaches have been developed promoted by copper, rhodium, nickel, and other chiral catalysts. Apart from the frequently investigated sulfonium ylides, the enantioselective [2,3]-sigmatropic rearrangement of selenium ylides and iodonium ylides has also been discovered recently. This review summarizes recent advances in the asymmetric Doyle–Kirmse reaction according to the patterns of chirality induction. The synthetic methods for rearranged products, reaction mechanisms and applications are discussed in this review.1 Introduction2 Asymmetric Doyle–Kirmse Reaction Controlled by Chiral Free Ylides3 Asymmetric Doyle–Kirmse Reaction Controlled by Chiral Metal-Bound Ylides4 Conclusion and Outlook

The trialkylsulfonium cation holds promise to capture carbon dioxide: In-silico evidence toward a novel scavenger

The concentration of carbon dioxide (CO2) in the Earth’s atmosphere is linked to the acute problem of global warming. For the first time, we herein introduce trialkylsulfonium aprotic ionic liquids (ILs) as a group of seemingly highly capacitive CO2 scavengers. We advocate the viability of the new sorbents by the reaction profiles recorded by means of hybrid density functional theory. All stages constituting CO2 chemisorption, such as the ethyldimethylsulfonium [S211] cation deprotonation, [S211]-ylide carboxylation at the α-methylene group, and aprotic anion carboxamidation have been explored. The [S211]-ylide formation reaction is thermochemically forbidden but its cost is affordable. The energetic cost ranges from a tiny number of +14 kJ/mol for [S211] indazolide to a mediocre value of +50 kJ/mol for [S211] 1,2,4–triazolide. The barriers corresponding to the sulfonium-based cation deprotonation range from +39 kJ/mol for benzimidazolide to +60 kJ/mol for 1,2,4-triazolide. The energy loss during the ylide intermediate formation is strongly compensated for by the subsequent sulfonium ylide carboxylation. The energetic gain is weakly dependent on the nature of the heterocyclic aprotic anion (AHA) being –99 to –110 kJ/mol for different ionic species studied. The AHAs additionally participate in CO2 capture following the route of carboxamidation thanks to their nitrogen sites. The most thermochemically favorable carbamate forms out of [S211] indazolide, –68 kJ/mol. The steric and covalent barriers associated with these reactions are of the order of thermal motion energy, whereas a specific chemical structure of AHA engenders marginal differences. The rationalization of the energy reaction profiles is given in terms of partial atomic charges, geometrical peculiarities, steric barriers, imaginary vibrational frequencies, and related descriptors. The reported computational results favor trials of the sulfonium-based ILs for CO2 chemisorption both thermochemically and kinetically.

Rh-Catalyzed [2,3]-Sigmatropic Rearrangement of Alkynyl Carbenes with Allyl Sulfides to Access Sulfide-Substituted 1,5-Enynes.

This study describes the development of Rh-catalyzed [2,3]-sigmatropic rearrangement of alkynyl carbenes with allyl sulfides. The protocol exhibits equitable functional group tolerance and allows the formation of a variety of synthetically valuable sulfide-substituted 1,5-enyne products. To the best of our knowledge, this is the first example of [2,3]-sigmatropic rearrangement of alkynyl carbenes. DFT analysis supports the involvement of rhodium carbene generation, sulfonium ylides formation, and [2,3]-sigmatropic rearrangement pathway.

Stereoselective Synthesis of trans-Stilbenes through Silver-Catalyzed Self-Coupling of N-Triftosylhydrazones: An Experimental and Theoretical Study.

A silver-mediated homocoupling of N-triftosylhydrazones for the construction of trans-stilbenes has been presented. This protocol is characterized by its suitability for both inter- and intramolecular reactions, operational simplicity, high efficiency with excellent stereoselectivity, broad substrate scope, and good functional group tolerance. A plausible mechanism involving nucleophilic attack of in situ generated sulfonium ylides on silver carbene was proposed on the basis of experimental results and DFT calculations, which further indicates that π-π stacking interactions play a dominant role in stereoselectivity control.

New Insight into the Reactivity of S,S-Bis-ylide.

The present work focuses on the reactivity of S,S-bis-ylide 2, which presents a strong nucleophilic character, as evidenced by reactions with methyl iodide and CO2, affording C-methylated salts 3 and betaine 4, respectively. The derivatization of betaine 4 affords the corresponding ester derivative 6, which is fully characterized by using NMR spectroscopy and X-ray diffraction analysis. Furthermore, an original reaction with phosphenium ions leads to the formation of a transient push-pull phosphino(sulfonio)carbene 8, which rearranges to give stabilized sulfonium ylide derivative 7.

Synthesis of Indole-Substituted Trifluoromethyl Sulfonium Ylides by Cp*Rh(III)-Catalyzed Diazo-carbenoid Addition to Trifluoromethylthioether.

The indole-substituted trifluoromethyl sulfonium ylide has been developed via Cp*Rh(III)-catalyzed diazo-carbenoid addition to trifluoromethylthioether and is the first example of an Rh(III)-catalyzed diazo-carbenoid addition reaction with trifluoromethylthioether. Several kinds of indole-substituted trifluoromethyl sulfonium ylide were constructed under mild reaction conditions. The reported method exhibited high functional group compatibility and broad substrate scope. In addition, the protocol was found to be complementary to the method disclosed by a Rh(II) catalyst.

Copper‐Catalyzed Enantioselective Doyle–Kirmse Reaction of Azide‐Ynamides via α‐Imino Copper Carbenes

Abstract[2,3]‐Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle–Kirmse reaction) generated from metal carbenes represents one of the powerful methods for the construction of C(sp3)−S and C−C bonds. Although significant advances have been achieved, the asymmetric versions via the generation of sulfonium ylides from metal carbenes have been rarely reported to date, and they have so far been limited to diazo compounds as metal carbene precursors. Here, we describe a copper‐catalyzed enantioselective Doyle–Kirmse reaction via azide‐ynamide cyclization, leading to the practical and divergent assembly of an array of chiral [1,4]thiazino[3,2‐b]indoles bearing a quaternary carbon stereocenter in generally moderate to excellent yields and excellent enantioselectivities. Importantly, this protocol represents a unique catalytic asymmetric Doyle–Kirmse reaction via a non‐diazo approach and an unprecedented asymmetric [2,3]‐sigmatropic rearrangement via α‐imino metal carbenes.

Copper-Catalyzed Enantioselective Doyle-Kirmse Reaction of Azide-Ynamides via α-Imino Copper Carbenes.

[2,3]-Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle-Kirmse reaction) generated from metal carbenes represents one of the powerful methods for the construction of C(sp3 )-S and C-C bonds. Although significant advances have been achieved, the asymmetric versions via the generation of sulfonium ylides from metal carbenes have been rarely reported to date, and they have so far been limited to diazo compounds as metal carbene precursors. Here, we describe a copper-catalyzed enantioselective Doyle-Kirmse reaction via azide-ynamide cyclization, leading to the practical and divergent assembly of an array of chiral [1,4]thiazino[3,2-b]indoles bearing a quaternary carbon stereocenter in generally moderate to excellent yields and excellent enantioselectivities. Importantly, this protocol represents a unique catalytic asymmetric Doyle-Kirmse reaction via a non-diazo approach and an unprecedented asymmetric [2,3]-sigmatropic rearrangement via α-imino metal carbenes.

Application of sulfonium and sulfoxonium ylides in organocatalyzed asymmetric reaction

Sulfur-based ylides are very important and valuable reagents in organic synthesis and have been widely applied in the preparation of cyclic compounds and the formation of C-X (X = C, N, O, S, B, P) bond. Since the early 2000s, asymmetric organocatalysis has become a powerful strategy in organic synthesis (even highlighted by the 2021 Nobel Prize in Chemistry) and has attracted widespread research interest among synthetic organic chemists. In this area, a large number of outstanding achievements have been registered in the novel chiral catalysts design, new compounds synthesis, various reagents application, and versatile reaction discovery. Given the extensive application of sulfonium and sulfoxonium ylides in organic synthesis, in this review, we mainly summarize the organocatalyzed asymmetric reactions involving these ylide reagents as one of the reactants. Detailed reaction mechanisms, transition states and some synthetic applications are highlighted. The challenges and opportunities of this field are also discussed in the outlook.