Α-carbonyl Sulfoxonium Ylides Research Articles

Ru(II)-Catalyzed Carboamination of Olefins with α-Carbonyl Sulfoxonium Ylides.

The first ruthenium-catalyzed carboamination of olefins with α-carbonyl sulfoxonium ylides is reported. The utilization of an inexpensive ruthenium catalyst enables the concise synthesis of pharmaceutically important isoindolin-1-ones, which possess both a stereogenic center and β-carbonyl side chain. This method is mild, efficient, and scalable and allows for the coupling of a wide range of aryl-, heteroaryl-, alkenyl-, and alkyl-substituted sulfoxonium ylides. Moreover, the carbonyl side chain in the resulting product provides a good handle for downstream transformations. For mechanistic studies, a ruthacyle complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions.

Unveiling a Strategy for Ring Opening of Epoxides: Synthesis of 2-Hydroxyindolinylidenes Using α-Ester Sulfoxonium Ylides.

The untapped potential of α-carbonyl sulfoxonium ylides in epoxide ring-opening reactions has been a notable gap in current research, with such reactivity predominantly associated with the highly reactive dimethylsulfoxonium methylide. This study introduces an innovative approach wherein an epoxide indole, formed in situ from 2-hydroxyindoline-3-triethylammonium bromide, undergoes reaction with α-ester sulfoxonium ylides. The outcome is the efficient synthesis of a range of 2-hydroxyindolin-3-ylidenes, demonstrating favorable yields (41-81%) and Z/E ratios from 4:1 to those of exclusive Z isomers. Additionally, the photophysical properties of the synthesized indolinylidenes are explored, along with their derivatization using various nucleophiles under acid catalysis.

α-Carbonyl sulfoxonium ylides in transition metal-catalyzed C-H activation: a safe carbene precursor and a weak directing group.

Transition metal-catalyzed cross-coupling of sp2 C-H bonds with diazo compounds via carbene migratory insertion represents an efficient strategy for the construction of C-C and C-heteroatom bonds in organic synthesis. Despite the popularity of diazo compounds as coupling partners in C-H activation, they pose serious safety and stability issues due to potential exothermic reactions linked with the release of N2 gas. However, compared with diazo compounds, sulfoxonium ylides are generally crystalline solids, more stable, widely used in industrial scales, and easier/safer to prepare. Therefore, recent years have witnessed an upsurge in employing α-carbonyl sulfoxonium ylides as an alternative carbene surrogate in transition metal-catalyzed C-H activation. Unlike diazo compounds, α-carbonyl sulfoxonium ylides contain inherent potential to serve as a coupling partner as well as a weak directing group. This review will summarize the progress made in both categories of reactions.

Enantioselective Intramolecular Iridium-Catalyzed Cyclopropanation of α-Carbonyl Sulfoxonium Ylides.

Enantioselective cyclopropanation of α-carbonyl sulfoxonium ylides (SY) has so far been limited to addition/ring closure reactions on electron-poor olefins. Herein, we report the iridium-catalyzed intramolecular cyclopropanation of SY in the presence of a chiral diene in up to 96% yield and 98% enantioselectivity. Moreover, density functional theory calculations suggest that the re face of the olefin preferably attacks an iridium carbene intermediate in an asynchronous concerted step that is independent of the geometry of the olefin.

Organocatalytic asymmetric azidation of sulfoxonium ylides: mild synthesis of enantioenriched α-azido ketones bearing a labile tertiary stereocenter.

Disclosed here is a catalytic asymmetric azidation reaction for the efficient synthesis of α-azido ketones bearing a labile tertiary stereocenter. With a superb chiral squaramide catalyst, a mild asymmetric formal H-N3 insertion of α-carbonyl sulfoxonium ylides proceeded with excellent efficiency and enantioselectivity. This organocatalytic process not only complements the previous α-azidation approaches for the formation of quaternary stereocenters and mostly for 1,3-dicarbonyl compounds, but also has advantages over the well-known metal-catalyzed asymmetric carbene insertion chemistry using α-diazocarbonyl compounds. Detailed mechanistic studies via control reactions and NMR studies provided important insights into the reaction pathway, which features reversible protonation and dynamic kinetic resolution. The curiosity in mechanism also led to the development of a simplified alternative protocol with a cheaper HN3 source.

Enantioselective Indole Insertion Reactions of α-Carbonyl Sulfoxonium Ylides.

The first example of organocatalytic enantioselective C-H insertion reactions of indoles and sulfoxonium ylides is reported. Under the influence of phosphoric acid catalysis, levels of enantiocontrol in the range of 20-93% ee and moderate yields (up to 50%) were achieved for 29 examples in formal C-H insertion reactions of free indoles and α-carbonyl sulfoxonium ylides. No nitrogen protection on the indole is necessary.

Hydroxyl-Directed Ruthenium-Catalyzed peri-Selective C–H Acylmethylation and Annulation of Naphthols with Sulfoxonium Ylides

Herein, we report a highly efficient ruthenium-catalyzed peri-selective C(sp2)-H acylmethylation of 1-naphthols with α-carbonyl sulfoxonium ylides by utilizing hydroxyl as a weakly coordinating directing group. This new method imparts good reactivity, excellent chemo- and regioselectivity, and broad functional group tolerance and involves mild reaction conditions. The C-H acylmethylated products can be readily cyclized into fluorescent annulated pyrans by a one-pot process.

Efficient Synthesis of Sulfur-Stereogenic Sulfoximines via Ru(II)-Catalyzed Enantioselective C-H Functionalization Enabled by Chiral Carboxylic Acid.

Ru(II)-catalyzed enantioselective C-H functionalization involving an enantiodetermining C-H cleavage step remains undeveloped. Here we describe a Ru(II)-catalyzed enantioselective C-H activation/annulation of sulfoximines with α-carbonyl sulfoxonium ylides using a novel class of chiral binaphthyl monocarboxylic acids as chiral ligands, which can be easily and modularly prepared from 1,1'-binaphthyl-2,2'-dicarboxylic acid. A broad range of sulfur-stereogenic sulfoximines were prepared in high yields with excellent enantioselectivities (up to 99% yield and 99% ee) via desymmetrization, kinetic resolution, and parallel kinetic resolution. Furthermore, the resolution products can be easily transformed to chiral sulfoxides and key intermediates for kinase inhibitors.

Metal-catalyzed B-H acylmethylation of pyridylcarboranes: access to carborane-fused indoliziniums and quinoliziniums.

Metal-catalyzed mono-acylmethylation of pyridylcarboranes has been realized using α-carbonyl sulfoxonium ylides as a coupling partner. The reaction features high efficiency, excellent site-selectivity and good functional group tolerance. In the presence of pyridyl and enolizable acylmethyl groups, a post-coordination mode has been proposed and validated by in situ high resolution mass spectroscopy (HRMS) to rationalize the unique mono-substitution. Post-functionalization at the newly incorporated alkyl site provides additional utility of this method, including the construction of carborane-fused indoliziniums and quinoliziniums. We believe that these mono-alkylated carboranes, together with their post-functionalized derivatives, may find applications in luminescent materials and drug discovery in the near future.

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.

Access to multi-functionalized oxazolines via silver-catalyzed heteroannulation of enamides with sulfoxonium ylides

Disclosed herein is an efficient Ag-catalyzed [4 + 1] heteroannulation reaction of enamides with α-carbonyl sulfoxonium ylides. The diastereoselective transformation provides a practical access to a diverse range of multi-functionalized oxazoline derivatives. The synthetic utility of the resultant tetra-substituted oxazolines is further demonstrated by a series of useful manipulations into valuable building blocks of pharmaceutical relevance.

Ruthenium(II)-Catalyzed Homocoupling of α-Carbonyl Sulfoxonium Ylides Under Mild Conditions: Methodology Development and Mechanistic DFT Study.

A mild ruthenium(II)-catalyzed homocoupling of α-carbonyl sulfoxonium ylides was developed and the detailed mechanism was understood based on DFT calculations in the current report. The catalytic system utilizes the α-carbonyl sulfoxonium ylide as both the directing group for ortho-sp2 C-H activation and the acylmethylating reagent for C-C coupling. Various substituents are compatible in the transformation and a variety of isocoumarin derivatives were synthesized at room temperature without any protection. The theoretical results disclosed that the full catalytic cycle contains eight elementary steps, and in all the cationic Ru(II) monomer is involved as the catalytic active species. The acid additive is responsible for protonation of the ylide carbon prior to the intramolecular nucleophilic addition and C-C bond cleavage. Interestingly, the intermediacy of free acylmethylation intermediate or its enol isomer is not necessary for the transformation.

Thiourea Catalyst Governs Novel Enantioselective S–H Insertion of α-Carbonyl Sulfoxonium Ylides to Arylthiols

Thiourea Catalyst Governs Novel Enantioselective S–H Insertion of α-Carbonyl Sulfoxonium Ylides to Arylthiols

Regioselective Synthesis of α-Phosphinoylnaphthols through Rhodium-Catalyzed Annulation of 1-Alkynylphosphine Oxides with Sulfoxonium Ylides

α-Phosphinoylnaphthols were obtained by redox-neutral annulation­ of 1-alkynylphosphine oxides with α-carbonyl sulfoxonium ylides under rhodium(III) catalysis. This protocol shows good regio­selectivity and broad functional-group tolerance.

Thioether-Directed C4-Selective C-H Acylmethylation of Indoles Using α-Carbonyl Sulfoxonium Ylides.

Site-selective direct functionalization of an indole benzenoid core has been a great challenge due to its inherently poor reactivity. We herein demonstrate an iridium-catalyzed C4-selective acylmethylation of indoles using α-carbonyl sulfoxonium ylides as carbene precursors. This method exhibits high efficiency and broad functional group compatibility. The directing group was easily removed or converted to other functionalities after the catalysis. The potential synthetic utility of the coupling products was highlighted by constructing medium-sized polycyclic indoles.

Copper-catalyzed N–H insertion reactions from sulfoxonium ylides

Abstract The first use of copper(II) as an efficient catalyst for N–H insertion reactions between anilines and α-carbonyl sulfoxonium ylides is described. Products, 39 arylglycine derivatives, were obtained in yields up to 97% employing a simple and fast experimental procedure.

Enantioselective S-H Insertion Reactions of α-Carbonyl Sulfoxonium Ylides.

The first example of enantioselective S−H insertion reactions of sulfoxonium ylides is reported. Under the influence of thiourea catalysis, excellent levels of enantiocontrol (up to 95 % ee) and yields (up to 97 %) are achieved for 31 examples in S−H insertion reactions of aryl thiols and α‐carbonyl sulfoxonium ylides.

Ruthenium-Catalyzed Synthesis of Pyrrolo[1,2-a]quinoxaline Derivatives from 1-(2-Aminophenyl)pyrroles and Sulfoxonium Ylides

A ruthenium-catalyzed [5+1] annulation of 1-(2-aminophenyl)pyrroles with α-carbonyl sulfoxonium ylides is reported. This reaction provides a one-step method for synthesizing pyrrolo[1,2-a]quinoxaline derivatives under ambient conditions. The system proceeds with a short reaction time and a high functional-group tolerance. Notably, this divergent protocol tolerates β-keto sulfoxonium ylides and can be applied to α-ester sulfoxonium ylides. A preliminary study was made of the mechanism of the reaction, and a reaction pathway is proposed.

Pd/C-Catalyzed Carbonylative Synthesis of α-Carbonyl-α'-Amide Sulfoxonium Ylides from Azides.

The synthesis of α-carbonyl-α'-amide sulfoxonium ylides by Pd/C-catalyzed carbonylative transformation of azides with α-carbonyl sulfoxonium ylides has been studied. This method offers a direct approach to produce synthetically useful α-carbonyl-α'-amide sulfoxonium ylides in high efficiency. By using readily available substrates, 39 examples of products were prepared in good yields with outstanding functional group compatibility. An example of converting the obtained ylide into the corresponding 1,3-dicarbonyl compound has been given as well.

Rh(III)-Catalyzed Reaction of α-Carbonyl Sulfoxonium Ylides and Alkenes: Synthesis of Indanones via [4 + 1] Cycloaddition.

The synthesis of indanone derivatives by the Rh(III)-catalyzed reaction of α-carbonyl sulfoxonium ylides with activated alkenes is reported. The reaction shows a high tolerance for functional groups and furnishes a variety of substituted indanone derivatives via a formal [4 + 1] cycloaddition. Highly stable sulfoxonium ylides were used as substrates in this C-H functionalization, and their bifunctional character could be effectively exploited using Rh(III) catalysis via sequential double C-C bond formation. Based on mechanistic studies including deuterium-labeling experiments, the reaction is proposed to proceed as follows: Rh(III)-catalyzed C-H oxidative alkenylation via β-hydride elimination, readdition of H-Rh species, a 1,2-carbon shift with the elimination of DMSO, and protonation.