Sulfur Ylides Research Articles

Merging the Reactivity of (Pseudo)cyclic Hypervalent Iodine Reagents and Carbenes or Carbenoids

AbstractIn this short review, we present applications merging the reactivity of cyclic hypervalent iodine reagents with carbenes and carbenoids developed in the period 2014–2024. The use of more stable cyclic hypervalent iodine reagents has led to major advances in this area. The combination of iodine(III) chemistry with carbenes or carbenoids enables new disconnections that are not possible using classical reactivity. Both the use of hypervalent iodine compounds as partners in reactions with metal carbenes and as reagents combining the reactivity of iodine(III) and carbenes in a single molecule to give carbyne equivalents are discussed in this review.1 Introduction2 Transfer of Fluorinated Groups (F, CF3)3 Oxy- and Aminoalkyn(en)ylation3.1 Oxy- and Aminoalkynylation with Acceptor-Substituted Diazo Compounds3.2 Oxyalkenylation with Acceptor-Substituted Diazo Compounds3.3 Oxyalkynylation with Acceptor-Acceptor-Substituted Diazo Compounds4 Carbyne Equivalents4.1 Diazo-Based Reagents4.2 Sulfur Ylide Based Reagents5 Conclusion

Site-Selective Direct γ-Difunctionalization of Diazoenals: Application to the Synthesis of Enal-Functionalized Allenes and Furans.

A new approach for the synthetically important γ-functionalized enals has been developed. The strategy involves rhodium-catalyzed direct C-C & C-S bond forming site-selective γ-difunctionalization of diazoenals with aryl propargyl sulfides via sulfur ylide [2,3] sigmatropic rearrangement, resulting in the highly functionalized γ-allenyl(sulfanyl)enals in excellent yield at ambient temperature. This highly versatile approach constitutes a viable alternative to the remote carbonyl-directed γ-functionalization of unmodified enals which suffer from competitive side reactions. The synthetic utility of the γ-allenyl(sulfanyl)enals was demonstrated by the InCl3-catalyzed cycloisomerization to the trisubstituted furanyl-enals via an unusual 1,4-sulfanyl migration. In addition, an operationally simple and efficient one-pot [3+2] annulation of diazoenals and propargyl sulfides, involving combined γ-difunctionalization and cycloisomerization was successfully developed for the diverse enal-functionalized furans.

Umpolung Approach to Aldol Products via Isoxazoline N-Oxides as Intermediates.

A two-step umpolung approach to the diastereoselective synthesis of aldols was developed, in which a conjugated nitroalkene is used as the synthetic equivalent of the enolonium cation, while a sulfur ylide acts as the equivalent of the α-carbinol anion. The resulting isoxazoline N-oxides undergo catalytic reductive cleavage to aldols under mild conditions at room temperature and under 1 atm hydrogen pressure. The efficiency of the method was demonstrated by the synthesis of a series of polysubstituted β-hydroxyketones that are difficult to synthesize using the classical aldol reaction. The developed approach allows for the regiodivergent assembly of aldols by selecting a nitroalkene isomer with the appropriate position of the C,C double bond.

Converting Strain Release into Aromaticity Loss for Activation of Donor-Acceptor Cyclopropanes: Generation of Quinone Methide Traps for C-Nucleophiles.

Here, we present a new approach for the activation of donor-acceptor cyclopropanes in ring-opening reactions, which does not require the use of a Lewis or Brønsted acid as a catalyst. Donor-acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and isomerization to form the corresponding quinone methides. This innovative strategy was applied to achieve (4 + 1)-annulation of cyclopropanes with sulfur ylides, affording functionalized dihydrobenzofurans. Additionally, the generated ortho- and para-(aza)quinone methides can be trapped by various CH-acids.

Generation and Application of Sulfur Ylides in Light‐Mediated Transformations

Sulfur ylides are essential reagents in various organic reactions like epoxidation and cyclopropanation. While traditionally employed in ionic chemistry, recent advancements in visible‐light‐driven photocatalysis reveal their potential as sources of radicals or free carbenes. The photochemical or photocatalytic generation of reactive intermediates using sulfur ylides expands the utility of these reagents in modern organic synthesis, offering sustainable solutions to emerging challenges. Despite early demonstrations in the 1960s, the past years have witnessed a surge in photochemical methods utilizing sulfur ylides as precursors. The use of redox‐active photocatalysts has facilitated numerous radical reactions. This review consolidates key findings in sulfur ylide chemistry, particularly focusing on photo‐mediated reactions, to stimulate further research interest in this dynamic field.

Synthesis of 1,1,3-Polyfunctionalized Cyclobutane Derivatives from the Reaction of Sulfur Ylides with Bicyclo[1.1.0]butanes.

1,1,3-Polyfunctionalized cyclobutane derivatives have been synthesized from sulfur ylides and bicyclo[1.1.0]butanes (BCBs). This protocol operates under mild reaction conditions without the need for catalysts, generally producing moderate to good yields of syn-addition derivatives with structural diversity. An unexpected intramolecular rearrangement mechanism has also been proposed.

Concise and Stereospecific Total Synthesis of Arenastatin A and Its Segment B Analogs.

A novel and concise synthetic method for arenastatin A, a cytotoxic cyclic depsipeptide of marine origin, was developed in this study. The convergent assembly of the four segments, including the cross-metathesis reaction, gave a cyclization precursor, and Fmoc deprotection caused simultaneous macrocyclization. The Corey-Chaykovsky reaction using a chiral sulfur ylide afforded arenastatin A with complete stereoselectivity in the longest linear sequence of seven reaction steps from the known compound. Using this synthetic method, some analogs of segment B were prepared through a late-stage diversification strategy. The simple SN2 reaction of the thiolate toward the tosylate precursor, prepared using almost the same synthetic method as described above, provided the desired sulfide analogs.

Catalyst-Free Domino Cross-Olefinations and Intramolecular Cyclizations of Morita-Baylis-Hillman Carbonates with Sulfur Ylides.

A novel strategy for the catalyst-free domino cross-olefination and intramolecular cyclization of Morita-Baylis-Hillman carbonates with sulfur ylides has been established, resulting in the synthesis of 1,2-dihydroquinolines with a broad scope, excellent chemoselectivity, and high efficiency. Mechanistic experiments revealed the process of 1,1-dipole cross-olefination and highlighted the assistance of the amino group in achieving successful transformations.

Photochemical Reactions of Sulfur Ylides

Abstract: Photochemical reactions offer unparalleled opportunities to access elusive chemical pathways and develop innovative strategies for constructing complex molecules. Within organic synthesis, photochemical reactions have become indispensable tools for accessing complex molecular structures, such as pharmaceuticals and natural products. The ability of sulfur ylides to participate in these diverse processes has made them indispensable tools in the synthetic chemist's toolbox. The use of sulfur ylides in photochemical transformations has garnered significant attention in the synthetic organic chemistry community, and they serve as powerful intermediates in several chemical transformations. This review article presents a comprehensive overview of the photochemical reactions mediated by sulfur ylides. Herein, we describe the key aspects of the reactivity of sulfur ylides in the presence of light. The reactivity of these compounds can be classified into three categories: sulfur ylides as energy acceptors, as electron donors, and as trapping reagents.

Palladium-Catalyzed (4 + 1) Annulation of 4-Vinylbenzodioxinones with Sulfur Ylides: Diastereoselective Synthesis of Dihydrobenzofuran Derivatives.

Palladium-catalyzed (4 + 1) annulation of 4-vinylbenzodioxinones with sulfur ylides has been developed to afford various dihydrobenzofuran derivatives in moderate to high yields with excellent diastereoselectivities. The scale-up reaction and further derivations of the product worked well, demonstrating the application potential of the current reaction in organic synthesis.

Direct Synthesis of α-Ketothioamide Derivatives through a One-Pot Reaction of Sulfur Ylides, Nitrosobenzenes, and Thioacetic Acid.

A one-pot approach has been developed for the synthesis of α-ketothioamide derivatives from sulfur ylides, nitrosobenzenes, and thioacetic acid. This protocol is carried out under mild reaction conditions in generally moderate to excellent yields without any precious catalysts, affording the derivatives with structural diversity. Additionally, a possible mechanism for this chemical transformation is proposed.

Synthesis of Sulfo(xo)nium Diacylmethylides

AbstractSulfo(xo)nium diacylmethylides (sulfur ylides) are simple, stable, readily prepared, and versatile synthons. Compared with the sulfo(xo)nium monoacylmethylides, they can be compatible with more rigorous reaction conditions and showcase unique characteristics due to their excellent stability. This concept article provides an account for the syntheses of sulfo(xo)nium diacylmethylides, including the utilization of active methylene compounds, carbene precursors, sulfo(xo)nium monoacylmethylides, and electron‐deficient alkynes as substrates, with discussions on substrate scopes, proposed mechanisms, selected product examples, and applications. Challenges for further exploration and prospect on sulfo(xo)nium diacylmethylides in the future are also suggested.

Interrupted Corey-Chaykovsky Reaction of Tethered Bis-Enones to Access 2,3-Epoxy-hexahydrofluoren-9-ones.

The Corey-Chaykovsky reaction is usually employed to synthesize cyclopropanes from activated olefins. We intercepted the intermediates prevailing during this transformation and diverted the process for the creation of intricate molecular motifs. We describe an unusual skeletal remodelling of tethered bis-enones to 2,3-epoxy-hexahydrofluoren-9-ones via an "interrupted Corey-Chaykovsky reaction". The strategy rationally merges the nucleophilic features of sulfur ylides with electronically biased olefins to achieve the regio- and stereoselective synthesis of several new classes of hydrofluorenones. We have demonstrated the synthetic utility of the products in accessing several highly functionalized molecules.

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.

Two-fold enhancement of equatorial bis-PCBM-C60 adducts using a supramolecular mask

ABSTRACT Regioselective poly-functionalization of fullerenes is highly desired to boost the applicability of pure-isomer poly-adducts. Here, we show how the supramolecular nanocapsule 1·(BArF)8 acts as a supramolecular mask and provides a two-fold enhancement up to 56% of equatorial e,e-bis-PCBM-C60 adducts using semi-stabilised sulfur ylides as reagents. This strategy conforms to a rapid and straightforward methodology in comparison to the reported tedious multi-stage and multicolumn HPLC process in peak-recycling mode.

Pd-Catalyzed [4 + 1] Annulation Strategy to Functionalized 4-Methyleneproline Derivatives.

A Pd-catalyzed formal [4 + 1] cycloaddition reaction of sulfur ylides and in situ-generated Pd-stabilized zwitterions offers a convenient route to a series of functionalized proline derivatives. The utility of this method is demonstrated by a gram-scale synthesis and chemoselective functionalization of a proline-based derivative.

Palladium/copper-cocatalyzed three-component tandem cyclization of o-alkenyl arylisocyanides and sulfur ylides with alcohols: direct synthesis of spiro 3,3′-cyclopropyl oxindoles

A novel palladium/copper-cocatalyzed tandem cyclization of o-alkenyl arylisocyanides and sulfur ylides with alcohols has been developed, providing a simple and efficient method for the synthesis of spiro 3,3′-cyclopropyl oxindoles in a single step.

Shining light on sulfonium salts and sulfur ylides: recent advances in alkylation under photoredox catalysis

Recent advancements in photoredox alkylation with sulfur ylides, sulfonium salts and related analogues are summarized in this review.

Substrate-directed divergent annulations of sulfur ylides: synthesis of functionalized bispirocyclopentane and bispirocyclopropane derivatives.

Herein, an efficient, substrate-directed divergent [2 + 3]/[2 + 1] annulation of tetra-substituted oxa-dienes and allylic sulfur ylides has been successfully developed. Under precise annulation regulation, a series of functionalized bispirocyclopentane and bispirocyclopropane derivatives were synthesized in a highly stereoselective and economical manner (up to 95% yield, >20 : 1 dr or >20 : 1 E/Z). This protocol offers the advantages of mild conditions, high chemo-, regio- and diastereoselectivity and broad substrate compatibility. In addition, the synthetic practicality of this protocol was evaluated through a scale-up preparation and a series of three-component reactions utilizing in situ generated sulfur ylides.

Enantioselective Synthesis of Unsymmetrical α,α-Diarylacetates via Organocatalyzed Formal C-H Insertion Reactions of Sulfoxonium Ylides with Indoles and Pyrroles

The chiral unsymmetrical α,α-diarylmethine skeleton is widely found in natural products and synthetic pharmaceuticals. The catalytic asymmetric C-H insertion reaction of simple, unprotected indoles and pyrroles with α-aryl sulfur ylides...